bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
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.
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.