bluuebunny/crossref_metadata_2025 huggingface dataset:
Cosinor Analysis of Heart Rate Variability in Ambulatory Migraineurs
Authors: Tabata Masako , Takeshima Takao , Burioka Naoto , Nomura Takashi , Ishizaki Kumiko , Mori Nozomi , Kowa Hisanori , Nakashima Kenji
Published: March 2003

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.
Prevalence of Migraine, Tension‐type Headache, and Other Headaches in Hong Kong
Authors: Cheung Raymond T.F.
Published: March 2003

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.
Effectiveness of Amitriptyline in the Prophylactic Management of Childhood Headaches
Authors: Hershey Andrew D. , Powers Scott W. , Bentti Anna‐Liisa , DeGrauw Ton J.
Published: March 2003

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.
Intravenous Valproate Sodium (Depacon) Aborts Migraine Rapidly: A Preliminary Report
Authors: Mathew Ninan T. , Kailasam Jayasree , Meadors Lori , Chernyschev Oleg , Gentry Paula
Published: March 2003

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.
Oral Almotriptan in the Treatment of Migraine: Safety and Tolerability
Authors: Dodick David W.
Published: March 2003

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.
Effects of Aspirin During Exercise on the Incidence of High‐Altitude Headache: A Randomized, Double‐Blind, Placebo‐Controlled Trial
Authors: Burtscher Martin , Likar Rudolf , Nachbauer Werner , Philadelphy Michael , Pühringer Reinhard , Lämmle Thomas
Published: March 2003

Objective.—To evaluate the efficacy of aspirin for headache when exercising during acute high‐altitude exposure.

Background.—Aspirin effectively prevents headache when mostly resting during acute high‐altitude exposure. However, the majority of individuals exposed to high altitude perform mountaineering activities, which might trigger headache.

Design.—Randomized, double‐blind, placebo‐controlled trial.

Methods.—Thirty‐one healthy volunteers (20 men, 11 women; aged 22 to 59 years) were transported to an altitude of about 3000 meters and climbed up to 3800 meters. They then descended to a mountain hut at 3480 meters and spent 2 nights there. Tablets (placebo or 320 mg aspirin) were administered three times at 4‐hour intervals, beginning 2 hours before arrival at high altitude. Headache scoring and measurements of heart rate, blood pressure, and arterial oxygen saturation were performed.

Results.—Ninety‐three percent (14 of 15) of the placebo group and 56% (9 of 16) of the aspirin group developed headache when mountaineering activities were performed during acute exposure to high altitude (P<.05). Five hours after arrival at high altitude, mean resting oxygen saturation was 86.1% ±  2.1% with aspirin and 85.7 % ±  2.8% with placebo (P = .66). However, subjects in the aspirin group developed headache at saturation values less than or equal to 86%, while those in the placebo group developed headache at saturation values less than 90%.

Conclusions.—Although the prophylactic intake of about 1 gram of aspirin reduced the headache incidence when exercising during acute high‐altitude exposure, the incidence of headache was higher than previously shown for resting conditions. Aspirin resulted in tolerance to lower arterial oxygen saturation without development of headache; exercise had the opposite effect.
Effect of Botulinum Toxin A Injections in the Treatment of Chronic Tension‐type Headache: A Double‐Blind, Placebo‐Controlled Trial
Authors: Schmitt Wolfgang J. , Slowey Eva , Fravi Nina , Weber Sabine , Burgunder Jean‐Marc
Published: March 2003

In addition to vascular and supraspinal influences, contraction of craniofacial muscles or central sensitization processes following continuous nociceptive input of craniofacial muscles may play an important role in the pathogenesis of tension‐type headache. Chemodenervation induced by botulinum toxin injection is successfully used to decrease muscle tension. If muscle tension is important in this type of headache, then botulinum toxin could be helpful in its treatment. We conducted a randomized, placebo‐controlled study to examine the effect of 20 U botulinum toxin injected into frontal and temporal muscles in patients with chronic tension‐type headache. During a baseline of 4 weeks and a posttreatment period of 8 weeks, the effect was evaluated with daily records and the West Haven‐Yale Multidimensional Pain Inventory. Some improvement in affective variables were demonstrated in the botulinum group, but important outcome variables, such as pain intensity, the number of pain‐free days, and consumption of analgesics, were not statistically different between the groups. Reasons for these moderate effects may include the injection sites, dose of botulinum toxin, and duration of treatment.
The Outcome of Treating Patients With Suspected Rebound Headache
Authors: Warner John S.
Published: March 2003

Objective.—To prospectively document the outcome of patients suspected of having rebound headache.

Background.—Previous publications on rebound headache have, for the most part, implied that the patients improve, but have failed to specify the percent who improved, the pattern of improvement, or the end point that is achieved.

Methods.—This was a prospective study of 50 consecutive patients presenting with chronic daily headache of over 2 months' duration who were suspected of having rebound headache from the medications that they were using for pain relief, and who were eligible to follow our usual treatment protocol, ie, abrupt termination of the offending medications and use of subcutaneous injections of dihydroergotamine for excruciating headache.

Results.—One year after the initial patient was enrolled and 8 months after the last patient was enrolled, 29 patients (58%) achieved the goal of 6 or more consecutive headache‐free days; the mean time to achieve this goal was 84 days. Another 9 patients showed varying degrees of improvement; 1 continued to improve and achieved 5 consecutive headache‐free days after having omitted her medications for 10 months. Eleven patients failed to stop their medications or stopped their medications for only a brief interval. One patient continued to have daily headaches after having essentially omitted all pain relief medications for 12 months and was the only true treatment failure in the group.

Conclusions.—Most patients suspected of having rebound headache comply with the instructions to omit the offending agents and can be helped. This information might help other physicians who are treating patients suspected of having rebound headache.
Clusterlike Headache as First Manifestation of a Prolactinoma
Authors: Porta‐Etessam Jesús , Ramos‐Carrasco Araceli , Berbel‐García Ángel , Martínez‐Salio Antonio , Benito‐León Julian
Published: March 2003

We report a case of cluster headache in a patient with a macroprolactinoma. Symptomatic cluster headache was suspected because of an unsatisfactory response to medications that are usually effective in idiopathic cluster headache. The neurological examination was normal. However, magnetic resonance imaging demonstrated a large pituitary tumor. One year after starting treatment with cabergoline, the patient remains asymptomatic. Symptomatic cluster headache should be suspected when the clinical features of the headache are atypical. By inducing vascular mechanisms, the parasellar lesion may have played a role in initiating the cluster headache.
Self‐reported Photophobic Symptoms in Migraineurs and Controls Are Reliable and Predict Diagnostic Category Accurately
Authors: Mulleners W.M. , Aurora S.K. , Chronicle E.P. , Stewart R. , Gopal S. , Koehler P.J.
Published: March 2003

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.
Efficacy of Intravenous Magnesium Sulfate in the Treatment of Acute Migraine Attacks
Authors: Demirkaya Şeref , Vural Okay , Dora Babür , Topçuoğlu Mehmet Akif
Published: March 2003

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.
Divalproex in the Long‐term Treatment of Chronic Daily Headache
Authors: Freitag Frederick G. , Diamond Seymour , Diamond Merle L. , Urban George J.
Published: March 2003

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.
Delivery Outcome in Women Who Used Drugs for Migraine During Pregnancy With Special Reference to Sumatriptan
Authors: Källén Bengt , Lygner Per Erik
Published: March 2003

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.
Impaired Circadian Rhythmicity of Nociceptive Reflex Threshold in Cluster Headache
Authors: Nappi G. , Sandrini G. , Alfonsi E. , Cecchini A. Proietti , Micieli G. , Moglia A.
Published: March 2003

Background.—Alteration of circadian rhythmicity involving several endocrinologic and autonomic parameters has been observed in cluster headache.

Objectives.—To explore whether circadian failure of the pain control system may exist in cluster headache.

Methods.—The nociceptive flexion reflex threshold was studied in 25 patients with episodic cluster headache (14 active, 11 in remission) and 6 patients with chronic cluster headache, along with 10 normal volunteers throughout a 24‐hour period. The reflex response was evoked at the level of the biceps femoris by stimulating the sural nerve at the ankle. Single and population mean cosinor methods were used to detect the circadian rhythmicity.

Results.—In the patients with episodic cluster headache, a significant reduction in the nociceptive flexion reflex threshold was observed in both the active subgroup and the subgroup in remission (P<.05). In these patients, persistence of a significant 24‐hour rhythm during both the active period and remission was observed, but a shift of the phase was observed during clinical activity when compared with the remission period. A lack of circadian nociceptive flexion reflex threshold rhythmicity was found in the patients with chronic cluster headache.

Conclusions.—Our findings suggest that in cluster headache there may be impairment of the pain control system that is associated with periodic failure of the mechanisms involved in the organization of biological rhythms.
Primary Headaches: A Convergence Hypothesis
Authors: Cady Roger , Schreiber Curtis , Farmer Kathleen , Sheftell Fred
Published: March 2003

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.
Prevalences of Migraine and Tension‐type Headache in Adolescent Girls of Shiraz (Southern Iran)
Authors: Ayatollahi S.M.T. , Moradi F. , Ayatollahi S.A.R.
Published: March 2003

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.
A Polymorphism in the Interleukin‐1α Gene Influences the Clinical Features of Migraine
Authors: Rainero Innocenzo , Pinessi Lorenzo , Salani Giuliana , Valfrè Walter , Rivoiro Chiara , Savi Lidia , Gentile Salvatore , Giudice Rossana Lo , Grimaldi Luigi M.E.
Published: March 2003

Objective.—To evaluate whether a particular genotype of the interleukin‐1α (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.
Dopamine Receptor Genes and Migraine With and Without Aura: An Association Study
Authors: Shepherd A. Graeme , Lea Rod A. , Hutchins Colin , Jordan Kathryn L. , Brimage Peter J. , Griffiths Lyn R.
Published: March 2003

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 (χ2  =  0.1, P  =  .74 for DRD1; χ2  =  1.8, P  =  .18 for DRD3; and χ2  =  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.
Effects of Fluoxetine on Habituation of Pattern Reversal Visually Evoked Potentials in Migraine Prophylaxis
Authors: Ozkul Yasar , Bozlar Senay
Published: March 2003

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.
Prevalence of Migraines in NCAA Division I Male and Female Basketball Players
Authors: Kinart Chad M. , Cuppett Marchell M. , Berg Kris
Published: March 2003

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 (χ2 = 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 (χ2 = 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.
Triptans for Migraine Management in Adolescents
Authors: Winner Paul
Published: March 2003

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.
Migraine Medication Attributes Important for Patient Compliance: Concerns About Side Effects May Delay Treatment
Authors: Gallagher R. Michael , Kunkel Robert
Published: March 2003

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.
Disability and Chronic Posttraumatic Headache
Authors: Marcus Dawn A.
Published: March 2003

Objective.—To test the hypothesis that chronic posttraumatic headache is associated with greater severity and psychological distress than headache of nontraumatic origin.

Methods.—Two hundred eighty‐nine consecutive patients with chronic headache attending a university headache clinic were evaluated. Questionnaires about headache symptoms, quality of life (Medical Outcome Survey SF‐36 Health Survey), and psychological distress were completed.

Results.—Frequent headache (>4 days per week) occurred more often with traumatic (84%) than nontraumatic headache (60%). Traumatic headache resulted in greater reduced activity (3.31  ±  1.06 days per week versus 2.62  ±  1.11 days per week with nontraumatic headache; P  <  .001) and complete disability (2.89  ±  1.17 days per week versus 2.25  ±  1.17 days per week with nontraumatic headache; P  <  .001). Physical function was also rated significantly lower in patients with traumatic headache (SF‐36 score: 59.8  ±  27.7 versus 71.6  ±  26.4 with nontraumatic headache; P  <  .01). These differences were not attributable to differences in headache frequency or gender between patients with traumatic and nontraumatic headache. Psychological symptoms were similar between patients with traumatic and nontraumatic chronic headache.

Conclusions.—Chronic traumatic headache is associated with increased headache frequency and disability compared with nontraumatic headache. Headache evaluation should include an investigation for origin of headache and consideration for more aggressive treatment in patients with traumatic headache.
Clinical Pharmacokinetics of Frovatriptan
Authors: Buchan P. , Keywood C. , Wade A. , Ward C.
Published: March 2003

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.
The Short‐Term Impact of Adjunctive Tiagabine on Health‐Related Quality of Life
Authors: Cramer Joyce , Ryan Joan , Chang Joanne , Sommerville Kenneth ,   the M92‐825 Study Group
Published: March 2003

Summary: Combinations of tiagabine (TGB), carbamazepine (CBZ), and phenytoin (PHT) were compared for their impact on health‐related quality of life (HRQOL) and adverse effects related to treatment efficacy for people with frequent complex partial seizures. Two independent, randomized, double‐blind clinical trials for efficacy and safety were conducted simultaneously with treatment groups: CBZ+PHT versus CBZ+TGB, and PHT+CBZ versus PHT+TGB. Treatment was initiated at week 0 and continued through week 16. HRQOL was evaluated with the QOLIE‐89. Treatment success was defined as ≥50% reduction in complex partial seizures. Among patients who achieved a ≥50% reduction in seizures, addition of TGB to baseline PHT enhanced patient perceptions of attention/concentration (13%; p = 0.002), memory (17%; p = 0.042), and language subscales (22%; p = 0.004). Addition of CBZ to PHT led to positive change in the work/driving/social relations subscale (14%; p = 0.004). These improvements were significantly different only between visits, not between the two treatment groups. Seizure worry subscale scores showed improvement among all treatment groups and was probably related to participation in the clinical trial. These exploratory analyses suggest a possible early positive effect of TGB on patient‐perceived cognitive domains using the QOLIE‐89. These findings are limited by the small sample size and could be related to reduction in seizures.
Time Course of Postoperative Recovery of N‐Acetyl‐Aspartate in Temporal Lobe Epilepsy
Authors: Serles W. , Li L. M. , Antel S. B. , Cendes F. , Gotman J. , Olivier A. , Andermann F. , Dubeau F. , Arnold D. L.
Published: March 2003

Summary:  Purpose: To assess the time course of increases in N‐acetyl‐aspartate/creatine (NAA/Cr), which can be measured using proton MR spectroscopic imaging (1H‐MRSI), in patients with intractable nonlesional temporal lobe epilepsy (TLE) after successful epilepsy surgery.

Methods: We performed pre‐ and postoperative 1H‐MRSI in 16 seizure‐free (SF) patients and 16 not seizure‐free (NSF) TLE patients. We calculated a mixed‐design analysis of variance (ANOVA) between SF and NSF groups, ipsi‐ and contralateral to the side of operation, and pre‐ and postoperative NAA/Cr measurements. We applied nonlinear regression between pre‐ and postoperative NAA/Cr differences and the time interval between 1H‐MRSI scans to fit a negative exponential model to NAA recovery.

Results: Mixed‐design ANOVA revealed that (a) postoperative NAA/Cr was significantly higher in SF than in NSF patients (p = 0.02) and that (b) in the SF group, postoperative NAA/Cr values were significantly higher than preoperative values (p < 0.05) and returned to the normal range in most patients. According to our nonlinear regression model, in SF patients, there was a 50% increase relative to preoperative NAA/Cr values after 5.8 months, whereas an improvement of 95% was reached after 25 months.

Conclusions: Our results extend preliminary observations of postoperative NAA recovery of SF patients by characterizing the time course of recovery as an exponential function with a half‐time of ∼6 months. The reversal of neuronal metabolic dysfunction remote from the epileptic focus may underlie the clinical observation of improvement of cognitive dysfunction after successful epilepsy surgery.