bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic Paroxysmal Hemicrania-Tic Syndrome
Authors: Caminero AB , Pareja JA , Dobato JL
Published: March 2003

We report the coexistence of both chronic paroxysmal hemicrania (CPH) and trigeminal neuralgia (tic douloureux) in a female patient. The clinical features combined to make a configuration of CPH-tic syndrome. The two components of the syndrome appeared synchronously in the same orbital region—first branch of the trigeminal nerve—with a latency of several years after the onset of isolated tic attacks of the second and third trigeminal divisions. The concurrence of both types of pain in the same symptomatic area may have some significance for pathogenic, clinical, and pharmacological aspects of such a syndrome. We discuss all these and postulate a provisional distinction between CPH-V2,3 tic and CPH-V1 tic.
Flow Cytometric Analysis of Lymphocyte Subsets in Migraine Patients During and Outside of an Acute Headache Attack
Authors: Mosnaim AD , Kulaga H , Adams AJ , Wolf ME , Puente J , Freitag F , Diamond S
Published: March 2003

We have conducted flow cytometric studies of two subsets of lymphocyte markers in groups of migraineurs during ( n = 12; group B) and outside ( n = 10; group C) of a migraine without aura attack (total n = 22; group A), including a group of patients tested in both of these phases ( n = 5; group D), and compared these results with those obtained from a population of age-comparable, sex- and race-matched healthy volunteers ( n = 12; group E). Comparison of the first set of lymphocytes (CD3+CD16+56+, CD3-CD16+56+, CD3-CD19+, CD3+CD19+, and CD3+HLA-DR+) between the patients in group A and the controls (group E) showed differences, reflecting greater group A percentages of CD3+CD16+CD56+ and CD3-CD19+ lymphocytes. Furthermore, these differences reached statistical significance only for the CD3+CD16+CD56+ lymphocytes, and then solely for the patients in group C (Scheffe's test, p< 0.05). Paired analysis of the above lymphocyte markers for subjects in group D failed to show significant differences between patients when they were having and not having a migraine attack, raising the possibility that results from a larger study could show meaningful increases in percentages of CD3+CD16+CD56+ lymphocytes as one of the immune parameters useful for differentiating migraineurs from controls. Comparison of a second set of lymphocyte markers (CD19+CD5+, CD20+CD72-, CD20-CD72+, CD20+CD72+) among either the different groups of patients or between the patients and controls failed, however, to show statistically significant differences, emphasizing the apparent specificity of the findings described above for CD3+CD16+CD56+ lymphocytes. Our results, albeit of a preliminary nature, suggest the occurrence of significant, differential changes in lymphocyte subset immunophenotyping between groups of pain-free migraineurs and patients during an acute migraine episode or controls. Corroboration of these findings may prove useful in clinical laboratory practice to identify changes in immunological parameters specifically associated with migraineurs, and help towards a better understanding of the etiology and pathophysiology of this condition.
Peripheral Autonomic Potentials in Primary Headache and Drug-Induced Headache
Authors: Evers S , Voss H , Bauer B , Sörös P , Husstedt I-W
Published: March 2003

Autonomic functions of different primary headache types have been investigated in several studies, most of them analyzing cardiovascular reflex mechanisms or biochemical changes. The results are contradictory; only in tension-type headache and in cluster headache has a sympathetic hypofunction been shown in a preponderance of studies. We analyzed the peripheral autonomous potentials (PAPs) in different primary headache types and in drug-induced headache and compared the results with those of healthy subjects and of patients with low back pain. Latencies of PAPs were significantly increased in all headache types but not in low back pain; amplitudes of PAPs did not show significant differences compared to healthy subjects. Patients with a long duration of drug abuse had increased PAP latencies, whereas patients with a high number of migraine attacks per year had decreased latencies. Our data suggest that sympathetic hypo-function as measured by PAP latencies is a general phenomenon in headache but not in all pain syndromes. Drug abuse leads to an increase of this hypofunction. While measuring PAPs is not an appropriate method by which to differentiate between headache disorders, it allows assessment of autonomic disturbances in primary and drug-induced headache.
Differential Effects of Migraine Drugs on Cerebral Blood Flow Autoregulation
Authors: Vraamark T , Waldemar G , Paulson OB
Published: March 2003

The effect of the migraine drugs ergotamine and sumatriptan on the cerebral blood flow (CBF) autoregulation was studied in halothane/nitrous oxide-anesthetized normotensive Wistar Kyoto rats. Ergotamine, an ergot alkaloid affecting 5HT, norepinephrine, and dopamine receptors, was administered intravenously as a single dose of 25 μg/kg. Sumatriptan, a selective 5HT1-like receptor agonist, was administered by intravenous infusion of 300 μg/kg/h. CBF was measured with the intracarotid 133Xe-injection method. The blood pressure limits of CBF autoregulation were determined by computerized least sum of square analysis. CBF autoregulation was preserved after both ergotamine and sumatriptan. Ergotamine shifted the lower blood pressure limit of CBF autoregulation towards higher blood pressures from 60 ± 3 mmHg to 82 ± 4 mmHg ( p<0.01), but did not significantly affect the upper blood pressure limit of CBF autoregulation. Sumatriptan had no significant effects on the blood pressure limits of CBF autoregulation.
No Effect of Prophylactic Treatment with Metoprolol on Cerebrovascular Co2 Reactivity in Migraineurs
Authors: Kastrup A , Thomas C , Hartmann C , Schabet M
Published: March 2003

The prophylactic effect of metoprolol in the treatment of migraine is well known, but its mode of action is still unclear. In the past, increased CO2 reactivity has been reported as one pathognomic finding in interictal migraineurs. Using transcranial Doppler we assessed CO2 reactivity in 20 migraineurs before and 3 h after the first intake of 50 mg metoprolol, and subsequently twice after 1 and 8 weeks of continuous therapy with 150 mg metoprolol/d. Before initiation of therapy, migraineurs as a group had increased CO2 reactivity ( p=0.07) compared to 20 age- and sex-matched volunteers. While treatment with metoprolol has been reported to affect amplitudes of increased contingent negative variation or visual evoked potentials in interictal migraineurs, it had no influence on enhanced CO2 reactivity in the present study. Moreover, the pretreatment value of CO2 reactivity did not correlate with the clinical efficacy of metoprolol after a 2-month treatment period.
Reliability of Cephalic Thermal Thresholds in Healthy Subjects
Authors: Becser N , Sand T , Zwart J-A
Published: March 2003

Reproducibility and normal variation of cephalic warm and cold detection thresholds were investigated in three healthy subject groups. The face, the mastoid process, and the hands were studied. No significant intra-observer test-retest difference ( n=20) was found. Good reliability (intra-class correlation coefficient [ICC] > 0.4) was found for 13 of 14 measurements. A small significant inter-observer difference ( n=20) was found for cold thresholds. Good reliability (ICC > 0.4) was observed for both cold and warm thresholds in most of the test locations (6 of 8). In general, the largest variability was found in the mastoid and frontal lateral regions. Thermal thresholds varied with investigation site in 56 controls (ANOVA, p<0.0005). No significant gender differences were found for cephalic warm and cold thresholds. Most cold thresholds (4 of 5) but also some warm thresholds (2 of 5) increased with age at the cephalic sites. Our results reveal the frontal medial, the maxillar medial, and lateral regions as the most reliable cephalic test locations. The mastoid region may also be useful for investigating the upper cervical small-fiber function.
High-Density Assessment of the Ihs Classification Criteria for Migraine Without Aura: A Prospective Study
Authors: Honkoop PC , Sorbi MJ , Godaert GLR , Spierings ELH
Published: March 2003

Fifty-six adult female patients with the clinical diagnosis of MwoA kept a diary 6 times per day for 10 consecutive weeks to record the occurrence, pain characteristics, and accompanying symptoms of headache. In order to avoid bias due to retrospection or expectancy the diary was programmed into palmtop computers which signaled the patients with a beep to enter the diary with a random-fixed time schedule: two signals occurred in, respectively, the morning, the afternoon, and the evening, but at different times for each day. The palmtop computers also warranted flawless data storage and automatic computations of response delay and missing values. Of the 339 attacks, 75% had a duration of 4-72 h and 94% confirmed the International Headache Society classification criteria for MwoA concerning pain characteristics and accompanying symptoms. Our results obtained for attacks in treated patients are highly comparable with the results of Rasmussen, Jensen, and Olesen (1991) obtained in the general population with unknown treatment of headache. Together, both studies support the IHS classification criteria for MwoA. The electronic Experience Sampling Method also allowed for an unbiased description of the course of treated MwoA attacks: 67% subsided in the first day. In the 16 attacks the characteristics and accompanying symptoms were present in 60-80% of the attacks at the first assessment (9.30 a.m.) with the exception of moderate to severe pain intensity (37%) and nausea or vomiting (31%). A waxing and waning of characteristics and symptoms over the day remained in about 30-40% of the attacks with a tendency towards increases in the evening (7.30 p.m. and 10 p.m.). The method is there for a replication of this study in untreated MwoA patients.
Transcranial Doppler Evaluation of Cerebral Hemodynamics in Migraineurs During Prophylactic Treatment with Flunarizine
Authors: Fiermonte G , Annulli A , Pierelli F
Published: March 2003

Transcranial Doppler (TCD) recording was used to evaluate the mean flow velocity (MFV) and cerebrovascular reactivity to CO2 in 21 migraineurs during the interictal phase. Nine were affected by migraine with aura (MwA) and 12 by migraine without aura (MwoA). During each session the middle cerebral artery (MCA) flow velocity was examined in basal conditions, in hypocapnia after a 3-min period of hyperventilation, in basal conditions a second time, and in hypercapnia after breath-holding. The same procedure was followed in a group of 21 age-and sex-matched volunteers. Recordings were performed before (T1), during (T2), and after (T3) prophylactic treatment with flunarizine (10 mg/day for 2 months) to assess the possible effect of this drug on cerebral hemodynamics. In basal condition, increased MFV values were found in both MwA and MwoA patients. In MwA patients the reactivity index (RI) to hypocapnia was significantly increased in T1 ( p < 0.05). This abnormal cerebrovascular reactivity disappeared during flunarizine treatment (T2) and in the post-therapy period (T3).
Validation of a Migraine Work and Productivity Loss Questionnaire for use in Migraine Studies
Authors: Davies GM , Santanello N , Gerth W , Lerner D , Block GA
Published: March 2003

Migraine symptoms and therapy side effects cause significant functional disability that can result in work and productivity losses. Effective, well-tolerated migraine therapy with rapid onset of relief could decrease work and productivity losses. The Migraine Work and Productivity Loss Questionnaire (MWPLQ) evaluates the impact of migraine and migraine therapy on paid work. Data from a randomized, open-label extension study were collected over 3 months. Migraineurs were randomized to either rizatriptan (5HT1B/1D receptor agonist) or their usual migraine therapy. Data were analyzed from 164 patients who experienced at least one work-related migraine. Internal consistency (Cronbach's α) for the work difficulty domains ranged from 0.80 to 0.95. Work loss and work difficulty were moderately correlated ( r=0.39-0.58) with migraine severity and functional ability. Differences were found favoring rizatriptan for absenteeism (1.3 vs 2.4 h), effectiveness at work (62% vs 49%), and difficulty with work-related tasks ( p < 0.01). The MWPLQ demonstrated favorable measurement characteristics in this study and could be an important research tool for future evaluations of migraine-related work disability.
Primary Headache Care Delivery by Nonspecialists in Brazil
Authors: Vincent MB , de Carvalho JJ Freitas
Published: March 2003

Headaches are common disorders usually examined by nonneurologists. In order to assess how primary headache patients (IHS groups 1, 2, and 3) are generally managed by nonspecialists, 414 patients were asked about their previous headache care. Correct diagnosis had previously been made in only 44.9%, 6.7%, and 26.7% of the migraine, tension-type headache, and cluster headache patients, respectively. The patients underwent 501 investigative procedures motivated by the headache, averaging 1.21 examinations per patient, mostly EEGs. Preventive treatment was largely overlooked irrespective of the headache type. It is concluded that scientific improvements in headache care may be ineffective unless educational programs improve headache knowledge in general.
Interictal and Postictal Cognitive Changes in Migraine
Authors: Mulder EJCM , Linssen WHJP , Passchier J , Orlebeke JF , de Geus EJC
Published: March 2003

The question whether symptom-free migraine patients show cognitive impairments compared to matched control subjects is addressed, and also whether migraine patients show transient cognitive impairments induced by an attack. The Neuropsychological Evaluation System (NES2) was administered once in an interictal period and twice within 30 h after different migraine attacks. Since cognitive impairments could be related to attack duration or severity, cognitive performance was compared during a postictal period after sumatriptan use and during a postictal period after habitual nonvasoactive medication use. Twenty migraineurs without aura, 10 migraineurs with aura, and 30 matched headache-free controls participated in the study. During a headache-free period, migraineurs without aura responded as quickly as controls, while migraineurs with aura were slower than controls during all tasks specifically requiring selective attention. These effects were not aggravated by a preceding migraine attack, irrespective of medication use and attack duration.
Personality Traits and Psychological Reactions To Mental Stress of Female Migraine Patients
Authors: Stronks DL , Tulen JHM , Pepplinkhuizen L , Verheij R , Mantel GWH , Spinhoven P , Passchier J
Published: March 2003

The purpose of this study was (i) to compare a range of stress-related personality traits, including defense and coping mechanisms, of migraine patients ( n = 23) with those of tension headache patients ( n = 18) and dermatologically afflicted, but otherwise healthy, controls ( n = 22), and (ii) to compare their state anxiety and other moods before, during, and after the presentation of a psychological stressor (mental arithmetic). For all three groups, mental arithmetic induced a significant increase in state anxiety and mood disturbance, followed by a subsequent decrease during recovery. Migraine patients were not found to have a higher disposition for anxiety, depression, or rigidity than tension headache patients or controls. Between the headache groups no differences in the use of defense and coping mechanisms were found. Compared to the control group, however, both migraine patients and tension headache patients were more inclined to use internally focused defense mechanisms and less inclined to seek social support when confronted with a problem. The psychological reaction of migraine patients to mental stress hardly differed from tension headache and control subjects. Compared to the control subjects, however, both groups of headache patients exhibited a diminished recovery from feelings of vigour, depression, and fatigue due to the stress induced. It is suggested that this distinct psychological reaction to stress of headache patients versus healthy control subjects is related to the more internally focused defense style of the headache sufferers. Thus, in contrast to previous results, this study does not present evidence of a migraine personality. It suggests the development of specific personality characteristics as a consequence of suffering from episodic headache.
Baclofen for Prevention of Migraine
Authors: Hering-Hanit R
Published: March 2003

Baclofen, an analog of the putative inhibitory neurotransmitter γ-aminobutyric acid is capable of crossing the blood-brain barrier. The drug has been shown to have an antinociceptive action and is used effectively in the management of spasticity. Baclofen was first used in the treatment of trigeminal neuralgia in 1980 and is currently used in the management of various types of neuropathic pain. The effect of baclofen on migraine has not been previously studied. The aim of the present open pilot study was to evaluate the efficacy of baclofen in patients with migraine. Fifty-four patients with migraine with and without aura who experienced 4-8 migraine attacks during a 4-week baseline were included. Baclofen, 15-40 mgs, was given in three divided doses for 12 weeks. Headache frequency and severity were recorded. Fifty-one patients completed the trial. Baclofen was found to be effective in 86.2% with >50% headache reduction from baseline. Three patients could not tolerate the drug due to adverse events. In this open study, baclofen was found to be effective for prophylactic treatment of migraine.
Serotonin Infusions Inhibit Sensory Input From the Dural Vasculature
Authors: Lambert GA , Shimomura T , Boers PM , Gordon V , Donaldson C , Zagami AS
Published: March 2003

Intravenous infusions of serotonin (5-hydroxtryptamine creatinine sulphate, 5HT, 50-300 μg/kg/min) in cats reversibly inhibited the responses of cervical spinal cord neurons to electrical stimulation of the superior sagittal sinus. Inhibition developed over 20-30 min and resolved over the same time course, suggesting a dependence on accumulation of 5HT in the central nervous system. Inhibition was suppressed by prior intravenous injection of the 5HT antagonists methysergide (1 mg/kg) and methiothepin (1 mg/ kg). Infusions of 5HT (50 μg/kg/min) caused a rise in whole blood levels of 5HT by a factor of 1.5 of control values. 5HT levels in platelet-free plasma rose by a factor of 50. Levels of 5HT and 5 hydroxyindole acetic acid released into the cerebrospinal fluid rose significantly. The results suggest that earlier clinical observations that 5HT infusions can ameliorate the pain of migraine may not have been due to cranial vasoconstriction alone, but could have involved a central action of 5HT.
Human Isolated Coronary Artery Contraction To Sumatriptan: A Post Hoc Analysis
Authors: Van Den Brink A. Maassen , Bax WA , Ramrattan NN , Ferrari MD , Saxena PR
Published: March 2003

A post hoc analysis was performed on concentration response curves to sumatriptan in 62 human isolated coronary arteries. We determined whether donor-related clinical characteristics (age, sex, cause of death) and properties of the coronary artery (functional endothelial integrity, muscle mass) were related to the potency and efficacy of sumatriptan in contracting the human isolated coronary artery. The efficacy of sumatriptan was inversely related to the functional integrity of the vessel endothelium. Thus, contrary to expectation, coronary artery constriction to sumatriptan seems to be more pronounced in patients with nondiseased coronary arteries where the endothelium is intact. Nevertheless, in view of the high coronary reserve in these patients, myocardial ischemia after the use of sumatriptan is unlikely to occur, whereas in patients with coronary artery disease even a small contraction may be deleterious.
Perfusion Weighted Imaging During Migraine: Spontaneous Visual Aura and Headache
Authors: del Rio M. Sanchez , Bakker D , Wu O , Agosti R , Mitsikostas DD , Østergaard L , Wells WA , Rosen BR , Sorensen G , Moskowitz MA , Cutrer FM
Published: March 2003

Using perfusion weighted imaging, we studied 28 spontaneous migraine episodes; 7 during visual aura ( n=6), 7 during the headache phase following visual aura ( n = 3), and 14 cases of migraine without aura ( n=13). The data were analyzed using a region-of-interest-based approach. During aura, relative cerebral blood flow (rCBF) was significantly decreased (27% ± 0.07) in occipital cortex contralateral to the affected hemifield. rCBV was decreased (15% ± 0.12) and mean transit time increased (32% ± 0.3), persisting up to 2.5 h into the headache phase. Other brain regions did not show significant perfusion changes. During migraine without aura, no significant hemodynamic changes were observed. In one patient who experienced both migraine with and without aura, perfusion deficits were observed only during migraine with aura. These findings suggest that decremental blood flow changes in occipital lobe are most characteristic of migraine with aura.
Interobserver Reliability of Diagnostic Criteria for Cervicogenic Headache
Authors: van Suijlekom JA , de Vet HCW , van den Berg SGM , Weber WEJ
Published: March 2003

To assess the interobserver reliability in distinguishing cervicogenic headache (CEH) from migraine without aura and tension-type headache we conducted a study keeping as closely as possible to daily clinical practice. In contrast to other reliability studies, which use data from clinical patient records or semistructured interviews recorded on videotape ('in vitro' design), we examined ‘live’ patients (‘in vivo’ design). Twenty-four headache patients participated in our ‘in vivo’ design experiment. During a session, each physician performed a physical examination and queried six patients in succession using a semistructured interview. Diagnosis was carried out in accordance with the International Headache Society (IHS) criteria and the criteria from Sjaastad and co-workers. Kappa statistics were used: 0.83 between the expert headache neurologists; 0.74/0.73 between the expert anesthesiologist in (head) pain treatment and both expert neurologists respectively; kappa ranged from 0.43 to 0.62 between the other physicians. The results of our ‘in vivo’ design study show that the reliability in diagnosing CEH, when strictly applying the criteria from Sjaastad and co-workers, is similar to the reliability in diagnosing migraine and tension-type headache according the IHS criteria.
Auditory Evoked Potentials in the Assessment of Central Nervous System Effects of Antimigraine Drugs
Authors: Roon KI , Sándor PS , Schoonman GG , Lamers FPL , Schoenen J , Ferrari MD , van Dijk JG
Published: March 2003

Because the “intensity dependence” of cortical auditory evoked potentials (IDAP) is under serotonergic control, it can be used to assess central antimigraine effects of 5HT1B/1D agonists. We measured IDAP before and 2 h after naratriptan (5 mg, n = 19) and zolmitriptan (5 mg, n = 19) in healthy volunteers. IDAP was expressed as the amplitude-stimulus intensity function (“ASF slope”). Naratriptan tended to increase ASF slope (mean difference 0.23 ± 0.62 μV/10 dB, p = 0.06) while zolmitriptan (0.08 ± 0.95 μV/10 dB, p = 0.35) did not. We assessed the suitability of IDAP for measuring central antimigraine drug effects using repeatability data (see companion paper). We calculated the trade-off between the size of the expected drug effects (ASF slope difference) and the necessary sample size. Because of poor repeatability 36 to 80 subjects are required to detect ASF slope changes in the 0.25–0.5 μV/10 dB range. These data can be used to design trials using IDAP.
SB-220453, A Potential Novel Antimigraine Agent, Inhibits Nitric Oxide Release Following Induction of Cortical Spreading Depression in the Anaesthetized Cat
Authors: Read SJ , Smith MI , Hunter AJ , Upton N , Parsons AA
Published: March 2003

Profound nitric oxide release associated with cortical spreading depression (SD), has been implicated in stroke, traumatic brain injury and migraine pathophysiology. SB-220453 represents a mechanistically novel, well-tolerated class of compounds which may have therapeutic potential in the treatment of conditions associated with neuronal hyperexcitability and inflammation. The aim of the present study was to investigate the effects of SB-220453 on the nitric oxide (NO) release associated with SD in the anaesthetized cat. In vehicle treated animals, KCl application for 6 min to the cortical suface produced repeated changes in extracellular direct current field potential with associated NO release. This activity was sustained for a median duration of 55 min (25–75% range, 32–59 min) and 59 min (25–75% range, 34–59 min), respectively. SB-220453 (1, 3 and 10 mg/kg i.p.) produced a dose-related inhibition of this activity and at the highest dose tested, the median duration of changes in extracellular field potential and NO release were reduced to 4 min (25–75% range, 4–5min) and 5 min (25–75% range, 5–5min), respectively. No effect was observed on basal systemic haemodynamic parameters or resting cerebral laser Doppler blood flux at any of the doses of SB-220453 tested. SB-220453 therefore represents a novel compound to assess the potential benefit of inhibiting SD associated nitric oxide release in neurological disease.
Physiology of the Menstrual Cycle
Authors: Silberstein S D , Merriam G R
Published: March 2003

The normal female life cycle is associated with a number of hormonal milestones: menarche, pregnancy, contraceptive use, menopause, and the use of replacement sex hormones. All these events and interventions alter the levels and cycling of sex hormones and may cause a change in the prevalence or intensity of headache. The menstrual cycle is the result of a carefully orchestrated sequence of interactions among the hypothalamus, pituitary, ovary, and endometrium, with the sex hormones acting as modulators and effectors at each level. Oestrogen and progestins have potent effects on central serotonergic and opioid neurons, modulating both neuronal activity and receptor density. The primary trigger of menstrual migraine appears to be the withdrawal of oestrogen rather than the maintenance of sustained high or low oestrogen levels. However, changes in the sustained oestrogen levels with pregnancy (increased) and menopause (decreased) appear to affect headaches. Headaches that occur with premenstrual syndrome appear to be centrally generated, involving the inherent rhythm of CNS neurons, including perhaps the serotonergic pain-modulating systems.
Risks and Benefits of Hormone Replacement Therapy
Authors: de Lignières B , MacGregor E A
Published: March 2003

Menopause, the permanent cessation of menstruation, is due to ovarian failure, which may lead to oestrogen deficiency diseases, particularly osteoporosis, cardiovascular disease and cerebrovascular disease. Mortality and morbidity caused by these conditions can be modified by using hormone replacement therapy, but the benefits of this therapy must be weighed against the increased risk of breast cancer and the symptomatic side-effects the treatment may cause. The combination of transdermal oestrogen and natural progesterone offers the most favourable risk-to-benefit profile.
Association Between Helicobacter Pylori Cytotoxic Type I Caga-Positive Strains and Migraine with Aura
Authors: Gasbarrini A , Gabrielli M , Fiore G , Candelli M , Bartolozzi F , De Luca A , Cremonini F , Franceschi F , Di Campli C , Armuzzi A , Ojetti V , Serricchio M , Pola R , Gasbarrini G , Giacovazzo M , Pola P
Published: March 2003

Recent studies have suggested an association between Helicobacter pylori infection and migraine. However, various strains of the bacterium are present, some endowed with greater pathogenicity. In particular, H. pylori type I CagA-positive strains induce a higher release of proinflammatory substances by the gastric mucosa that could trigger systemic vasospasms. The aim of the present study was to assess the prevalence of H. pylori CagA-positive strains in subjects with migraine. One hundred and seventy-five patients affected by migraine (49 with aura, 126 without aura) were consecutively enrolled and matched for sex, age, social background and geographical origin with 152 controls. Helicobacter pylori infection was assessed through 13C-urea breath test. Specific serological IgG against CagA were detected through ELISA. The prevalence of H. pylori infection was similar in migraine patients and in controls (40% vs. 39%, respectively). Among migraine patients, prevalence of infection was not related to presence or absence of aura (45% vs. 37%, respectively). However, among infected subjects, a significantly higher prevalence of CagA-positive strains was observed in patients affected by migraine with aura when compared with those affected by migraine without aura (41% vs. 19%, P < 0.01) and with controls (41% vs. 17%, P < 0.01). CagA-positive H. pylori strains were found to be strongly associated with migraine with aura. A higher inflammatory response of the gastric mucosa to more virulent strains could release substances that may act as triggers of vasospasm in peculiar cerebral arterial districts, probably implicated in the ‘aura’ phenomenon.
Rizatriptan Wafer–Sublingual vs. Placebo at the Onset of Acute Migraine
Authors: Klapper JA , O’Connor S
Published: March 2003

Rizatriptan wafer is a 5HT1B/1D agonist for use in the acute treatment of migraine. It is a freeze-fried formulation, approved for oral administration, which dissolves on the tongue and is swallowed with saliva. In this study the efficacy of sublingually administered rizatriptan 10-mg wafer was evaluated in a randomized, double-blind, placebo-controlled, out-patient study involving 39 migraineurs. Patients were instructed to treat a migraine at the onset of pain in order to evaluate time of onset of pain relief and pain relief at 1 h. The average time to onset of relief was 25 min for patients treated with rizatriptan wafer and 27 min for patients treated with placebo. At 1 h, 50% of the patients receiving rizatriptan wafer and 50% of the patients receiving placebo experienced significant relief. Implications and potential reasons for a high placebo response are discussed.
Different Effects of Gabaergic Anticonvulsants on 4-Aminopyridine-Induced Spontaneous Gabaergic Hyperpolarizations of Hippocampal Pyramidal Cells—Implication for their Potency in Migraine Therapy
Authors: Leniger T , Wiemann M , Bingmann D , Hufnagel A , Bonnet U
Published: March 2003

Clinical studies indicate anti-migraneous efficacy of the probably GABAergic anti-convulsants valproate and gabapentin. For the GABAergic anticonvulsants vigabatrin and tiagabine, studies about antimigraneous efficacy are missing. The aim of this study was to test the GABAergic potency of these drugs in vitro before further clinical studies. Intracellular recordings were obtained from hippocampal pyramidal cells. Spontaneous GABAergic hyperpolarizations (SGH) elicited by 75 μ m 4-aminopyridine were used to test the effect of these drugs on GABA-dependent potentials. Tiagabine (0.1 m m) prolonged the duration of SGH. Furthermore, monophasic SGH turned over into triphasic typical GABAergic membrane potential fluctuations within 20 min. In contrast, valproate, gabapentin, and vigabatrin failed to affect SGH up to 60 min of application. The reason for the fast action of tiagabine on SGH may be caused by a faster increase of synaptic GABA levels compared with other drugs. As migraine therapy benefits from an augmentation of GABA activity, we recommend clinical studies of tiagabine as a fast-acting agent in migraine attacks.
Work and Productivity Loss in the Rizatriptan Multiple Attack Study
Authors: Dasbach EJ , Carides GW , Gerth WC , Santanello NC , Pigeon JG , Kramer MS
Published: March 2003

The objective of this study was to measure the self-reported effect of acute migraine and its treatment on paid work and productivity loss. Patients self-administered a questionnaire in which the impact of a recent migraine on paid work and productivity activities was assessed. We included the questionnaire in a randomized, double-blind, placebo-controlled, crossover, out-patient study designed to examine the safety and efficacy of rizatriptan (5-HT1B/1D receptor agonist) 10 mg p.o. in patients treating four separate migraine attacks. A total of 407 patients, aged 18–65 years, suffering from moderate to severe migrainous headaches was studied. Patients receiving rizatriptan compared with placebo reported 0.7 fewer hours ( P < 0.01) of paid worked missed due to absenteeism, 0.4 fewer hours ( P < 0.05) of productive time lost on the job, and 1.1 fewer total hours ( P < 0.01) of work loss per migraine attack. Rizatriptan compared with placebo significantly reduced migraine-related work loss associated with absenteeism and decreased effectiveness on the job.
The Principles of Evidence-Based Medicine
Authors: Wiebe S
Published: March 2003

Evidence-based medicine (EBM) integrates individual clinical expertise with the best available external evidence in the care of individual patients. By enabling clinicians to directly appraise and apply current clinical research, EBM deals with the problems of deterioration in clinical performance, information overload, and lag in application of research findings to clinical practice. Thus, EBM is a useful tool to address the problems faced by clinicians attempting to provide optimum, current care for their patients. The rationale for EBM, its principles and application, as well as some limitations, are described here.
Acute Migraine Treatment Outcome Measures: A Clinician's View
Authors: Sheftell FD , Fox AW
Published: March 2003

The efficacy of acute therapies for migraine can be measured in many ways. Traditional endpoints (such as reduction in pain from moderate or severe to mild or absent) are used for regulatory purposes, but do not reflect all components of the migraine syndrome, nor, necessarily, what is most valued by patients and clinicians. There is also a pharmacokinetic–pharmacodynamic disconnection for these traditional types of endpoint, suggesting that they teach us little about how these drugs work. More rigorous, but nonetheless pain-score based, endpoints are reviewed. The biases that can attach to measures such as therapeutic gain and number needed to treat, in the context of migraine therapy, and the limitations of these measures for use in meta-analysis, are discussed. The clinical subtleties of these endpoints are numerous: understanding patients' ability to distinguish between multiple headache types, the best timing of treatment relative to the start of an attack, and measuring clinical outcome may be statistically difficult, but yet may also provide more clinical utility than pain-score analyses. The three therapeutic strategies ( Step, Stepped-within-attack, and Stratified care) are reviewed and the place of 5HT1B/1D agonists within them, based on the currently best available evidence, is identified. Consideration should be given to more real-life studies, to measuring drug efficacy after early administration during onset of headache, and to greater sophistication in our approach to the necessarily gestalt measures of patient satisfaction and treatment preference.
Drug Comparisons: Why are They so Difficult?
Authors: Salonen R
Published: March 2003

Comparing therapeutic agents in a drug class can be difficult. This article examines the ways in which the triptans can be and have been compared and evaluates the advantages and disadvantages of the approaches. Direct comparative trials are clearly the best method for evaluating the triptans, however, there is a scarcity of this type of data on the currently available compounds. Indirect comparison such as meta-analysis is a second method of comparing these agents but only serves as an estimate of relative efficacy or safety based on a comparison of pooled data derived from a number of different trials for each agent. Comparison of the data found in the regulatory documents represents another type of indirect comparison that can be done so long as the data is presented in a consistent format across products.
Analysis of Internet Sites for Headache
Authors: Peroutka SJ
Published: March 2003

The Internet is capable of providing an unprecedented amount of information to both physicians and patients interested in headache. To assess the status of headache information on the Internet (as of January 2000), a search for ‘headache’ was performed using 10 leading Internet search engines. The number of web pages identified ranged from 4419 (WebCrawler) to 506 426 (Northern Light). The ‘average’ search yielded nearly 150 000 web page listings for ‘headache’. The content was then reviewed of the top 10 listed web pages for each search (i.e. a total of 100 page listings). The results demonstrate that, at the present time, Internet-based information on headache is extensive but poorly organized. Editorial review of this potential valuable resource is required in order to maximize its utility in headache education and management.
Frequency and Predictors of Physician Consultations for Headache
Authors: Wang S-J , Fuh J-L , Young Y-H , Lu S-R , Shia B-C
Published: March 2003

We conducted a population-based headache questionnaire survey including questions on physician consultation for headache in Taipei, Taiwan from August 1997 to June 1998. The participants comprised 3377 subjects aged ≥ 15 years, of whom 328 (9.7%) had a diagnosis of migraine and 1754 (52%) had a diagnosis of non-migraine headache. Migraineurs had a higher physician consultation rate (once or more in the past year) than the subjects with non-migraine headache (54% vs. 31%, P < 0.0001). When frequency ≥ 10 times was taken as 10 times, the analysis showed that migraineurs consulted physicians more often than non-migraine headache subjects (2.36 vs. 0.96, P = 0.04). A small proportion of the subjects with either migraine (12%) or non-migraine headache (6%) accounted for 50% of total consultations within their groups. In addition to old age, low education levels, living in a rural area, migrainous features (nausea and photophobia), and work day loss, predictors of physician consultations also included ‘having been troubled with headache’ (odds ratio (OR) = 1.7) and co-morbidity with hypertension (OR = 1.8) or heart disease (OR = 2.2). Low copayment and unrestricted access to medical care, as well as cultural factors played an important role in the high consultation rates in our headache subjects. Moreover, this study found self-perception of headache impact and co-morbid illnesses were important factors affecting the decision to consult physicians about headache.
Personality Traits in Childhood and Adolescent Headache
Authors: Lanzi G , Zambrino CA , Ferrari-Ginevra O , Termine C , D'Arrigo S , Vercelli P , De Silvestri A , Guglielmino CR
Published: March 2003

We evaluate personality traits, anxiety and depression in a population of paediatric and adolescent patients, correlating personality characteristics with headache and sociodemographic variables. The clinical features of headache include specific personality traits. We report a clinical study of 57 patients (age 8–18 years), divided up as follows: 12 migraine with aura, 29 migraine without aura and 16 tension-type headache. One of Cattel's tests was administered to every patient; the Children's Depression Inventory test was administered to 53 patients and the Test Anxiety Inventory test to 43 subjects. The scores obtained by every patient in each test were correlated with the characteristics of headache and with sociodemographic data. We found that patients affected by idiopathic headache share some personality traits, mainly emotional rigidity and tendency to repress anger and aggression. These traits do not seem to be correlated with sociodemographic data and the duration of headache: we considered these as characteristic of migrainous patients.
Ophthalmoplegic Migraine: A Recurrent Demyelinating Neuropathy?
Authors: Lance JW , Zagami AS
Published: March 2003

The demonstration by magnetic resonance imaging (MRI) scanning of thickening and enhancement of the cisternal part of the oculomotor nerve in patients diagnosed as ‘ophthalmoplegic migraine’ prompts reconsideration of this uncommon disorder. The case histories of five patients, three male and two female, varying in age from 6 to 30 years, are presented here. Recurrent painful ophthalmoplegia started in infancy in two cases, childhood in two instances and adult life in one. One child had his first attacks at 3, 5 and 12 months of age, on each occasion 10 days after an injection of triple vaccine. The possibility of this condition being a recurrent demyelinating neuropathy is considered and its possible relationship to migraine explored.
Meta-Analysis of Rizatriptan Efficacy in Randomized Controlled Clinical Trials
Authors: Ferrari MD , Loder E , McCarroll KA , Lines CR
Published: March 2003

Data from seven randomized, placebo-controlled, double-blind phase III clinical trials were analysed to further evaluate the efficacy of rizatriptan 10 mg ( n = 2068) in comparison with placebo ( n = 1260) and rizatriptan 5 mg ( n = 1486) for the acute treatment of a migraine attack. Migraine was diagnosed according to International Headache Society criteria. Headache severity, associated migraine symptoms and functional disability were measured immediately before dosing and at 0.5, 1, 1.5 and 2 h. Headache recurrence (return of moderate or severe headache after an initial response) was also recorded. In addition to conventional pain relief (reduction of moderate or severe headache to mild or none) and pain free measures, the analysis looked at the elimination of associated migraine symptoms and disability in patients who had symptoms or disability at baseline. Maintenance of pain relief or pain-free status over 24 h was also analysed. At 2 h, rizatriptan 10 mg was significantly more effective than placebo for pain relief (71% vs. 38%, P < 0.001), and for elimination of pain, nausea, photophobia, phonophobia and functional disability. The benefit was maintained over 24 h; 37% of patients on rizatriptan 10 mg had sustained pain relief vs. 18% for placebo ( P < 0.001). Rizatriptan 10 mg was also more effective than rizatriptan 5 mg, with a significant superiority at 2 h on all measures except for elimination of nausea. The benefit was maintained over 24 h; 38% of patients on rizatriptan 10 mg had sustained pain relief vs. 32% for rizatriptan 5 mg ( P = 0.001).
Pain Thresholds and Tenderness in Neck and Head Following Acute Whiplash Injury: A Prospective Study
Authors: Kasch H , Stengaard-Pedersen K , Arendt-Nielsen L , Staehelin Jensen T
Published: March 2003

Objective of the investigation: In a 6-month prospective study of 141 consecutive acute whiplash-injured participants, and 40 acute, ankle-injured controls, pain and tenderness in the neck/head, and at a distant control site, were measured.

Basic procedures: Muscle palpation and pressure algometry in five head/neck muscle-pairs were performed after 1 week and 1, 3 and 6 months after injury. Algometry was performed at a distant control site.

Main findings: Whiplash-injured patients had lowered pressure-pain-detection thresholds and higher palpation-score initially in the neck/head, but the groups were similar after 6 months, and the control site was not sensitized.

Principal conclusion: Focal, but not generalized, sensitization to musculoskeletal structure is present until 3 months, but not 6 months, after whiplash injury, and probably does not play a major role in the development of late whiplash syndrome. Pressure algometry and palpation are useful clinical tools in the evaluation of neck and jaw pain in acute whiplash injury.
Quality of Life in Adolescents with Chronic Pain in the Head or at Other Locations
Authors: Hunfeld JAM , Passchier J , Perquin CW , Hazebroek-Kampschreur AAJM , van Suijlekom-Smit LWA , van der Wouden JC
Published: March 2003

The differences in quality of life and school absence were studied in one hundred adolescents from the open population who had reported chronic headache or chronic, physically unexplained, pain at other locations.

The adolescents kept a 3-week diary about their pain and completed a quality of life questionnaire. Of all chronic pain sufferers in this study, it was the adolescents with headache who showed the least frequent pain, but they reported the poorest quality of life and the largest school absence due to their pain.

Adolescents with headache or adolescents with back pain showed the highest negative correlations between pain parameters and quality of life. Headache sufferers showed highly negative relationships between pain parameters and most quality of life domains (median r = -0.46), and only in headache sufferers did this involve both intensity and frequency of pain.

Qualitative studies are needed to reveal the background to these differences.
Clinical Presentation of Transformed Migraine: Possible Differences Among Male and Female Patients
Authors: Krymchantowski AV , Moreira PF
Published: March 2003

Chronic daily headache (CDH) represents a group of non-paroxysmal headache disorders that occur on a daily or near-daily basis, for longer than 6 months. Even though it is a common problem, affecting 30–70% of the patients attending specialized headache clinics, it is not a well-defined and classified disorder, resulting in controversies regarding its description and approach. The aim of this study was to evaluate the clinical presentation of CDH due to transformed migraine and possibly compare the differences among male and female patients. Two hundred and seventy-one patients, 217 women and 54 men, ages 16–83 (mean 37.5 years for women and 41.4 for men), fulfilling the proposed criteria for transformed migraine and selected from a group of 300 consecutive CDH patients attending a subspecialty headache centre, were studied retrospectively. The most observed clinical presentation was pressure or tightening, bilateral fronto-temporal, moderate non-continuous headache, with a progressive onset. The association with nausea and phonophobia was demonstrated in 60% and 32% of the patients, respectively. The association with photophobia (29.6% male, 44.2% female, P = 0.05) sleep (77.7% male, 49.8% female, P = 0.0002) and emotional (87% male, 64.1% female, P = 0.001) disturbances, as well as the occurrence of intermittent full-blown migraine attacks (81.5% male, 95.4% female, P = 0.001) was significantly different among male and female patients. Overuse of symptomatic medications (SM) was observed in 87% of the male and in 83.8% of the female patients, with a significant difference concerning the use of more than one type of SM (male 68% compared with female 91.7%; P = 0.006). We concluded that TM patients have a clinical presentation compatible with previous descriptions but suggesting, even though limited by the restricted number of male patients, different aspects among male and female patients.