bluuebunny/crossref_metadata_2025 huggingface dataset:
Event‐Related Potentials in Posttraumatic Headache
Authors: Alberti Andrea , Sarchielli Paola , Mazzotta Giovanni , Gallai Virgilio
Published: March 2003

Objectives.—To assess impairment of cognitive functions occurring in patients with posttraumatic headache as a consequence of a minor cranial trauma in the absence of organic damage involving the central nervous system.

Background.—The term posttraumatic syndrome defines a stereotypic set of symptoms following traumatic brain injury that are subjective and varied. A deficit of cognitive function and impairment of the rapid processes of learning, attention, and short‐term memory have frequently been identified. Moreover, headache is the most frequent symptom reported by the patients.

Due to the nature of the symptoms, a great limitation in defining the posttraumatic syndrome is represented by the lack of methods and diagnostic tools that allow quantification of the subjective disturbances and evidence of the signs indicative of central nervous system involvement in this pathological condition.

Methods.—Twenty‐five subjects (16 women, 9 men; mean age, 28 ± 9 years) were examined between 3 and 6 months after the traumatic event. The P300 event‐related potential was recorded by an odd‐ball paradigm with an acoustic modality. The patients underwent electroencephalography and brain stem auditory evoked potentials; magnetic resonance imaging was performed to exclude the presence of cerebral lesions.

Results.—The mean latency of P300 was increased in both central electrodes (Cz and Pz) in patients with posttraumatic syndrome compared with controls (P<.001); assuming the value of mean ± 2 SD was the cutoff point between normal and abnormal results, the P300 latency results were altered in 13 patients (52%).

In the patient group, a significant correlation was demonstrated between Zung Depression Scale score and P3 and N2 wave latencies (r = 0.54, P <.004; r = 0.56, P<.003) and between Zung Anxiety Scale scores and P3 wave latencies (r = 0.46, P<.02).

Conclusions.—These data suggest the usefulness of the P300 event‐related potential in evaluating cognitive disturbances in patients affected by posttraumatic syndrome. Alteration of cognitive potential in such patients, even in the absence of lesions detectable by neuroimaging, indicate the functional impairment of specific cerebral areas that can occur after a traumatic event.
Remitting Form of Hemicrania Continua With Seasonal Pattern
Authors: Peres Mario F. P. , Stiles Marlind Alan , Oshinsky Michael , Rozen Todd D.
Published: March 2003

Hemicrania continua is a primary headache syndrome characterized by a continuous, unilateral headache that is completely responsive to indomethacin. Hemicrania continua exists in continuous and remitting forms. Ten cases of the remitting form have been reported, none of which have had a seasonal pattern. We report a patient with remitting hemicrania continua with a clear seasonal predilection.
Childhood Headache, Stress in Adolescence, and Primary Headache in Young Adulthood: A Longitudinal Cohort Study
Authors: Waldie Karen E.
Published: March 2003

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.
Long‐term Efficacy and Safety of Oral Almotriptan: Interim Analysis of a 1‐Year Open Study
Authors: Cabarrocas Xavier , Esbri Ramon , Peris Francesc , Ferrer Pau
Published: March 2003

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.
Interictal and Postictal Contingent Negative Variation in Migraine Without Aura
Authors: Mulder E.J.C.M. , Linssen W.H.J.P. , Passchier J. , De Geus E.J.C.
Published: March 2003

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.
Deficiency of Tumor Necrosis Factor α in a Subclass of Menstrual Migraineurs
Authors: Mueller Loretta , Gupta Adarsh K. , Stein T. Peter
Published: March 2003

Objective.—The objective of this study was to determine whether differences in urinary proinflammatory cytokines, interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6), and tumor necrosis factor α (TNF‐α), 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‐1β, IL‐6, and TNF‐α, 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‐1β levels between samples.

Interestingly, marked differences were found in TNF‐α values in menstrual migraineurs. Twelve (63%) of 19 migraineurs had at least one urine sample with undetectable TNF‐α 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‐α levels in women with migraine may signal a disordered neuroimmune communication network and predisposition to migraine.
Efficacy and Tolerability of Rizatriptan 10 mg in Migraine: Experience With 70 527 Patient Episodes
Authors: Göbel Hartmut , Heinze Axel , Heinze‐Kuhn Katja , Lindner Volker
Published: March 2003

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.
An Open‐Label Dose‐Titration Study of the Efficacy and Tolerability of Tizanidine Hydrochloride Tablets in the Prophylaxis of Chronic Daily Headache
Authors: Saper Joel R. , Winner Paul K. , Lake Alvin E.
Published: March 2003

Objective.—To assess effectiveness and safety of tizanidine hydrochloride tablets for the prophylaxis of chronic daily headache.

Background.—Tizanidine hydrochloride is an α2‐adrenergic agonist that inhibits the release and effectiveness of norepinephrine at both central sites (eg, the locus ceruleus) and the spinal cord. It acts as a central muscle relaxant and has antinociceptive effects. Preliminary research and retrospective analyses have suggested efficacy in treatment of both chronic tension‐type headache and chronic daily headache with migrainous features.

Design.—Thirty‐nine patients with more than 15 headache days per month (33 with migraine, 5 migrainous, 1 chronic tension‐type) completed a 4‐week baseline, with 31 completing a planned 12 weeks of treatment with tizanidine. Dosing was titrated from 2 mg at bedtime to a median daily dose of 14 mg (mean, 13.5; SD, 4.3; range, 4 to 20, divided over three doses per day) by treatment week 4.

Results.—The overall headache index through week 12 (headache frequency × average intensity × duration) declined significantly (P<.00000002), with a corresponding increase in mean percentage improvement from 49% for weeks 1 through 4, to 65% for weeks 5 through 8, and 64% for weeks 9 through 12 (P<.0182). During weeks 9 through 12, 67% had improved more than 50% compared to baseline. Overall headache frequency declined from 22.83 to 15.83 days per month (P<.00001), with frequency of severe headaches dropping from 7.52 to 3.58 days per month (P<.000035). Average headache intensity dropped from 1.83 to 1.07 (1‐to‐5 scale), peak intensity declined from 2.37 to 1.40, and mean duration was reduced from 6.96 to 4.00 hours per headache (P<.00001). Improvement also occurred on visual analog scales of overall headache status, mood, sleep, quality of life (P<.00001), and sexual function (P<.0075); as well as the Beck Depression Inventory‐II (P<.00073).

Mild‐to‐moderate adverse events reported by more than 10% of the patients included somnolence, asthenia, and dry mouth. Only 3 patients discontinued treatment due to adverse events: somnolence and dry mouth alone (n = 1), or in combination with either hyperkinesis (n = 1) or constipation (n = 1). One patient had elevated liver enzymes that returned to normal after the drug was discontinued.

Conclusions.—The results provide preliminary support for the efficacy, safety, and tolerability of tizanidine in the prophylaxis of chronic daily headache.
Serum Ionized Magnesium Levels and Serum Ionized Calcium/Ionized Magnesium Ratios in Women With Menstrual Migraine
Authors: Mauskop Alexander , Altura Bella T. , Altura Burton M.
Published: March 2003

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.
Headache Associated With Postpartum Cerebral Angiopathy: Monitoring With Transcranial Color‐Coded Sonography
Authors: Kubo Shigeki , Nakata Hiroyuki , Tatsumi Toshiaki , Yoshimine Toshiki
Published: March 2003

We report a case of postpartum cerebral angiopathy with headache; a rare entity that affects women within the early postpartum period. Cerebral angiography revealed multiple segmental narrowings of major cerebral arteries. The patient was monitored with transcranial color‐coded sonography of the middle cerebral artery. Abnormally increased flow velocity within the middle cerebral artery decreased following initiation of steroid therapy, and the patient's headache improved dramatically.
Migraine Without Aura and Migraine With Aura Are Distinct Disorders. A Population‐Based Twin Survey
Authors: Russell Michael Bjørn , Ulrich Vibeke , Gervil Morten , Olesen Jes
Published: March 2003

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.
5‐HT2A Receptor Activation and Nitric Oxide Synthesis: A Possible Mechanism Determining Migraine Attacks
Authors: Srikiatkhachorn Anan , Suwattanasophon Chalalai , Ruangpattanatawee Unchalee , Phansuwan‐Pujito Pansiri
Published: March 2003

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.
Platelet Serotonin Measures in Migraine
Authors: Jernej Branimir , Vladić Anton , Čičin‐Šain Lipa , Hranilović Dubravka , Banović Miroslav , Balija Melita , Bilić Ervina , Sučić Zvonimir , Vukadin Stjepan , Grgiêeviae Damir
Published: March 2003

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°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/109 platelets for PSL, 139 ± 25 vs. 142 ± 25 pmol 5HT/108 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/108 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.
Comparison of Therapeutic Gain With Therapeutic Ratio for the Assessment of Selective 5HT1B/1D Agonist Efficacy in Migraine
Authors: Fox Anthony W. , Keywood Charlotte , Sheftell Fred D. , Spierings Egilius L. H. , Winner Paul
Published: March 2003

Objective.—Comparison of use of therapeutic gain (TG) and therapeutic ratio (TR) for relative assessments of selective 5HT1B/1D agonist efficacy in the acute treatment of migraine.

Background.—Comparison of selective 5HT1B/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.
Refining the Clinical Spectrum of Chronic Paroxysmal Hemicrania: A Review of 74 Patients
Authors: Boes Christopher J. , Dodick David W.
Published: March 2003

Objective.—To refine the clinical spectrum of chronic paroxysmal hemicrania (CPH).

Methods.—From 1976 to 1996, 74 patients were diagnosed with CPH by Mayo Clinic neurologists. Data were collected on those cases.

Results.—Of the 74 patients, 62% were women. Most (93%; 69/74) had strictly unilateral pain, 78% (53/68) had daily attacks, and 4% (2/47) had no autonomic features. The mean usual attack duration was 26 minutes, whereas the mean usual attack frequency was six per day. Three‐quarters (30/40) had a consistent response to indomethacin, whereas 25% did not. In 34 patients, there were incomplete data concerning indomethacin response. Some (9/13) were able to stop indomethacin without headache recurrence. Few (2/25) stopped indomethacin because of side effects. Two patients had initial responses to indomethacin that did not persist. Oxygen was beneficial in three patients. Three surgically treatable cases of secondary CPH were identified.

Conclusions.—Attack duration is the clinical feature that best distinguishes CPH from other trigeminal autonomic cephalgias. Although long‐term therapy with indomethacin is generally well‐tolerated, some patients who clinically appear to have CPH do not respond to indomethacin, and tachyphylaxis may develop in some cases. Some patients are able to stop indomethacin without headache recurrence, highlighting the importance of a trial of discontinuation. A consistent clinical profile and treatment response do not exclude the possibility of intracranial pathology.
Psychosocial Impact of Headache and Comorbidity with Other Pains among Swedish School Adolescents
Authors: Fichtel Åsa , Larsson Bo
Published: March 2003

Background.—The psychosocial impact of headache combined with other pains has previously been insufficiently investigated.

Objective.— The present study examined the prevalence of headache, its comorbidity with other pains and psychosocial impact among adolescents.

Methods.— 793 adolescents in a sample recruited from 8 schools in the middle of Sweden were assessed.

Results.—Forty‐five percent of the adolescents reported ongoing pain during assessment and more than half of the adolescents reported at least one frequent pain during the previous 6 months. The most common pain among girls was headache (42%), but for boys muscle pain (32%) was most prevalent. Number of pains and perceived pain disability were also higher among girls than boys. One‐third of the headache sufferers had headache only, while one‐third reported one other frequent pain and the others had at least two other frequent pains. Overall, adolescents with frequent headaches had higher levels of anxiety or depressive symptoms, in addition to functional disability and usage of analgesic medication. Frequent headache sufferers reported more problems in everyday life areas than those with infrequent headaches.

Conclusions.—It is recommended that adolescents suffering from recurrent headaches routinely should be asked about the presence of other pains, anxiety and depressive symptoms, medication usage, in addition to psychosocial consequences in their everyday life activities. Longitudinal research is also needed to delineate causal relationships between psychosocial factors and recurrent pains, in particular regarding possible sex differences.
Sodium Valproate Prophylaxis in Childhood Migraine
Authors: Serdaroglu Gul , Erhan Elvan , Tekgul Hasan , Oksel Figen , Erermis Serpil , Uyar Meltem , Tutuncuoglu Sarenur
Published: March 2003

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.
Acupuncture in the Prophylactic Treatment of Migraine Without Aura: A Comparison with Flunarizine
Authors: Allais Gianni , De Lorenzo Cristina , Quirico Piero E. , Airola Gisella , Tolardo Giampiero , Mana Ornella , Benedetto Chiara
Published: March 2003

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.
Transient Visual Disturbances During Migraine Without Aura Attacks
Authors: Cologno Daniela , Torelli Paola , Manzoni Gian C.
Published: March 2003

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.
Almotriptan Reduces the Incidence of Migraine‐Associated Symptoms: A Pooled Analysis
Authors: Cady Roger
Published: March 2003

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.
Hormonal Factors in Migraine: A Population‐Based Study of Women Aged 40 to 74 Years
Authors: Mattsson Peter
Published: March 2003

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.
The Association Between Migraine and Juvenile Stroke: A Case‐Control Study
Authors: Schwaag Sonja , Nabavi Darius G. , Frese Achim , Husstedt Ingo‐W. , Evers Stefan
Published: March 2003

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.

Conclusions.—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.
Headache and Hemodialysis: A Prospective Study
Authors: Antoniazzi Ana L. , Bigal Marcelo E. , Bordini Carlos A. , Tepper Stewart J. , Speciali José G.
Published: March 2003

Objective.—To determine the prevalence and clinical characteristics of headache in patients undergoing hemodialysis and to compare the prevalence of headache prior to and following the beginning of a hemodialysis program.

Background.—About 70% of patients receiving hemodialysis complain of headache. Despite this, headaches have not been well studied in this group of patients.

Methods.—We evaluated a series of patients with chronic renal failure who attended 3 hemodialysis services in a Brazilian town from January of 1998 to December of 1999. Patients with headache were prospectively followed and classified according to the International Headache Society criteria. The headaches were also categorized according to their temporal profile relative to hemodialysis.

Results.—Headache was reported by 87 (70.7%) of the 123 patients studied. Prior to beginning dialysis, 48% had migraine, 19% had episodic tension‐type headache, and 8% had both. Headache related to arterial hypertension was the second most frequent headache diagnosis in these patients (25.4%). Fifty patients (57.5%) experienced headache during the session of hemodialysis. Thirty‐four were classified as dialysis headache, 7 were classified as migraine, 7 as episodic tension‐type headache, and 2 were unclassified. Twenty‐four patients (27.6%) reported dramatic improvement of their headaches after the beginning of the dialysis program.

Conclusions.—Headache is common in patients undergoing hemodialysis. Classification of such headaches according to the International Headache society criteria may be difficult.
Dose Range‐Finding Studies With Frovatriptan in the Acute Treatment of Migraine
Authors: Rapoport Alan , Ryan Robert , Goldstein Jerome , Keywood Charlotte
Published: March 2003

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‐HT1B/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.
Cortical Dysplasia: Electroclinical, Imaging, and Neuropathologic Study of 13 Patients
Authors: Tassi Laura , Pasquier Basile , Minotti Lorella , Garbelli Rita , Kahane Philippe , Benabid Alim Louis , Battaglia Giorgio , Munari Claudio , Spreafico Roberto
Published: March 2003

Summary:  Purpose: The aim of this study was to correlate the electroclinical and radiologic data with the neuropathologic findings and surgical outcome in epileptic patients with epilepsy and Taylor's focal cortical dysplasia (TFCD) and to characterize further the abnormal intermediate filaments expression in the balloon cell present in the peculiar dysplasia.

Methods: We retrospectively selected 13 TFCD patients who underwent surgery for intractable epilepsy with the aim of removing the magnetic resonance (MR)‐detectable lesion and/or the epileptogenic zone defined by stereoelectroencephalographic recordings. The surgical specimens were analyzed by means of routine neuropathologic and immunocytochemical studies. Antisera against different intermediate filaments also were used in serial adjacent sections to evaluate their coexpression in balloon cells.

Results: Histopathologic abnormalities typical of TFCD were found not only within the MR‐visible lesions but also in most of the epileptogenic zones with no MR signal alterations. Furthermore, the MR‐visible lesions contained a high proportion of cells with an abnormal expression of intermediate filament proteins. After a long follow‐up, 10 of the patients are now seizure free.

Conclusions: Our findings indicate that highly epileptogenic zones may correspond to tissue alterations not revealed by neuroimaging. Furthermore, the immunocytochemical data show that the dysplastic tissue detected by MR contained high concentrations of cells filled with abnormal intermediate filaments. The detected colocalization of neuronal and glial markers in balloon cells indicates a failure of cellular commitment during development.
Seizure Outcome after Temporal Lobectomy: Current Research Practice and Findings
Authors: McIntosh A. M. , Wilson S. J. , Berkovic S. F.
Published: March 2003

Summary:  Purpose: The literature regarding seizure outcome and prognostic factors for outcome after temporal lobectomy is often contradictory. This is problematic, as these data are the basis on which surgical decisions and counseling are founded. We sought to clarify inconsistencies in the literature by critically examining the methods and findings of recent research.

Methods: A systematic review of the 126 articles concerning temporal lobectomy outcome published from 1991 was conducted.

Results: Major methodologic issues in the literature were heterogeneous definitions of seizure outcome, a predominance of cross‐sectional analyses (83% of studies), and relatively short follow‐up in many studies. The range of seizure freedom was wide (33–93%; median, 70%); there was a tendency for better outcome in more recent studies. Of 63 factors analyzed, good outcome appeared to be associated with several factors including preoperative hippocampal sclerosis, anterior temporal localization of interictal epileptiform activity, absence of preoperative generalized seizures, and absence of seizures in the first postoperative week. A number of factors had no association with outcome (e.g., age at onset, preoperative seizure frequency, and extent of lateral resection).

Conclusions: Apparently conflicting results in the literature may be explained by the methodologic issues identified here (e.g., sample size, selection criteria and method of analysis). To obtain a better understanding of patterns of long‐term outcome, increased emphasis on longitudinal analytic methods is required. The systematic review of possible risk factors for seizure recurrence provides a basis for planning further research.