bluuebunny/crossref_metadata_2025 huggingface dataset:
Migraine and Cluster Headache-Their Management with Sumatriptan: A Critical Review of The Current Clinical Experience
Authors: Wilkinson M , Pfaffenrath V , Schoenen J , Diener H-C , Steiner TJ
Published: March 2003

Sumatriptan is a potent and selective agonist at the vascular 5HT1 receptor which mediates constriction of certain large cranial blood vessels and/or inhibits the release of vasoactive neuropeptides from perivascular trigeminal axons in the dura mater following activation of the trigeminovascular system. The mode of action of this drug in migraine and cluster headache is discussed. On the basis of a detailed review of all published trials and available data from post-marketing studies, the efficacy, safety, tolerability and the place of oral and subcutaneous sumatriptan in the treatment of both conditions are assessed. A number of double-blind clinical trials have demonstrated that sumatriptan 100 mg administered orally is clearly superior to placebo in the acute treatment of migraine headache and achieves significantly greater response rates than ergotamine or aspirin. In other studies, 70 to 80% of patients receiving sumatriptan 6 mg sc experienced relief of migraine headaches by 1 or 2 h after administration, and patients consistently required less rescue medication for unresolved symptoms. Sumatriptan was also effective in relieving associated migraine symptoms like nausea and vomiting. Sumatriptan was equally effective regardless of migraine type or duration of migraine symptoms. Overall, approximately 40% of patients who initially responded to oral or subcutaneous sumatriptan experienced recurrence of their headache usually within 24 h, effectively treated by a further dose of this drug.

In 75% of patients with cluster headache treated with sumatriptan 6 mg sc, relief was achieved within 15 min. Based on pooled study data, sumatriptan is generally well tolerated and most adverse events are transient. Adverse events following oral administration include nausea, vomiting, malaise, fatigue and dizziness. With the subcutaneous injection, injection site reactions occur in approximately 30%. Chest symptoms are reported in 3 to 5% but have been associated with myocardial ischaemia only in rare isolated cases. The recommended dosage of sumatriptan at the onset of migraine symptoms is 100 mg orally or 6 mg subcutaneously. The recommended dosage for cluster headache is 6 mg sumatriptan sc. Sumatriptan must not be given together with vascoconstrictive substances, e.g. ergotamines, or with migraine prophylactics with similar properties, e.g. methysergide. Sumatriptan should not be given during the migraine aura. It is contraindicated in patients with ischaemic heart disease, previous myocardial infarction, Prinzmetal (variant) angina and uncontrolled hypertension.
Influence of a Selective 5HT1-Receptor Agonist GR43175 on Platelet Responsiveness
Authors: Tozzi-Ciancarelli MG , Massimo C Di , Tozzi E , Mascioli A , Matteis G De , Carolei A
Published: March 2003

The possible interaction of sumatriptan, a selective 5HT1-receptor agonist, with platelet responsiveness has been investigated. Stimulation of platelet rich plasma with sumatriptan (1–100 μM) did not induce shape change, aggregation or modification of intraplatelet cytosolic calcium levels. Total inhibition of aggregation induced by 20 μM 5HT was observed in platelets preincubated for 20 min with 100 μM sumatriptan. In the same model, platelet stimulation with 4 μM adenosine 5'-diphosphate (ADP), concentration known to induce an irreversible single-phase curve, determined a decrease of aggregatory response. Concentrations from I μM to 50 μM of sumatriptan did not influence the aggregatory response induced by 5HT and ADP. These effects appear not to be determined by modifications of platelet calcium homeostasis. The possibility to modulate platelet responsiveness by sumatriptan offers a further approach for evaluating the probable link between platelet behaviour and pathophysiology of migraine.
Cerebrospinal Fluid Analyses in Migraine Patients and Controls
Authors: Rothrock JF , Mar KR , Yaksh TL , Golbeck A , Moore AC
Published: March 2003

To investigate the role of central neurotransmitters in the pathogenesis of migraine, we measured cerebrospinal fluid (CSF) levels of certain amino acids (glycine, taurine, glutamine) and metabolites of biogenic amines (5-hydroxyindoleacetic acid and homovanillic acid) in 38 migraine patients and compared them with the levels from 10 headache-free controls. The levels of taurine, glycine and glutamine were significantly higher in the migraine patients (p < 0.0001 for taurine and glycine; p < 0.0009 for glutamine); there were no significant differences among the three migraine subgroups (infrequent migraine, frequent migraine and transformed migraine). In seven patients subsequently treated with divalproex sodium, CSF taurine levels decreased significantly from pretreatment baseline values. These data support the concept that migraine is at least in part a disorder of central neurotransmission.
Pain Pressure Threshold in Cluster Headache Patients
Authors: Bono G , Antonaci F , Sandrini G , Pucci E , Nappi G , Rossi F
Published: March 2003

Pain perception threshold (PFT) in the head was assessed with a pressure algometer in 58 cluster headache (CH) patients (52M, 6F; 41 episodic and 17 chronic). Fourteen patients in cluster period were retested in remission. Thresholds were assessed at 10 symmetrical points on each side of the head and at the deltoid. Compared with controls ( n = 80), CH patients had lower PPT in the head and in the deltoid. PPT was lower on the symptomatic side than on the non-symptomatic side in patients with episodic CH during a cluster period ( p<0.001) and in patients with chronic CH ( p<0.05). This pattern was more evident during a cluster period than during remission ( p<0.05). A reduced PPT did not correlate with illness duration and pain side. The lowest PPT mean values were found at the anterior and intermediate levels of the temporal muscle on the symptomatic side. These results imply a central mechanism underlying the pathogenesis of CH.
Cerebrospinal Fluid Tyrosine and 3,4-Dihydroxyphenylacetic Acid Levels in Migraine Patients
Authors: Castillo J , Martínez F , Suárez C , Naveiro J , Lema M , Noya M
Published: March 2003

We studied biochemical parameters related with central dopaminergic neurotransmission in migraine patients during crisis. We determined tyrosine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels in cerebrospinal fluid (CSF) of 47 patients, 29 suffering migraine without aura and 18 suffering migraine with aura, comparing them with 27 control subjects. Tyrosine levels did not differ significantly between patients and controls. The CSF concentration of DOPAC was 0.73±0.55 ng/ml in the control population, 3.84±2.08 ng/ml in patients with migraine without aura and 3.30±l.49ng/ml in patients suffering migraine with aura. The concentration of DOPAC correlated positively with the intensity of headache. These results suggest that patients with migraine have a central dopaminergic hyperfunction, probably related to a coexisting central dysfunction of noradrenergic neurotransmision.
Inhalational Anesthetics Inhibit Spreading Depression: Relevance to Migraine
Authors: Piper RD , Lambert GA
Published: March 2003

Cortical spreading depression (SD) has not been shown in the human neocortex by direct cortical recordings. However, animal studies suggest that cortical injury, such as that occurring during neurosurgical procedures, should result in the initiation of SD. It is possible that inhibition of SD by volatile anesthetic agents may partially explain the failure to observe SD in the human neocortex during surgery. This study examines the effect of the anesthetic agents α-chloralose, halothane, nitrous oxide and isoflurane on the initiation of cortical SD in the cat neocortex. SD was seen in 100% of cats anesthetized with α-chloralose ( n = 15), in 3 of 7 (42%) animals anesthetized with isoflurane ( p < 0.05, χ2 with Yates correction) and none of the animals ( n = 4, 6 hemispheric preparations) anesthetized with halothane ( p < 0.005, χ2 with Yates correction, halothane vs α-chloralose group). In all cases this inhibitory effect was reversible. In four animals the administration of nitrous oxide (66%) reduced the inspired concentration of isoflurane required to inhibit SD by 0.75%. This study suggests that halothane, and to a lesser extent isoflurane and nitrous oxide, protect against the initiation of cortical SD. This observation may partially explain why SD has not been demonstrated in human neocortex during surgery. Further studies are needed to determine if SD may occur under pathological conditions, such as during migraine with aura, where the cortex may be predisposed to SD.
Familial Hemiplegic Migraine: A Clinical Comparison of Families Linked and Unlinked to Chromosome 19
Authors: Terwindt GM , Ophoff RA , Haan J , Frants RR , Ferrari MD ,   for the DMGRG
Published: March 2003

We compared the clinical characteristics of 50 patients from three unrelated families with familial hemiplegic migraine (FHM) linked to chromosome 19, with those of 20 patients from two families with FHM not linked to chromosome 19. We found no significant differences for age at onset, frequency and duration of attacks, duration of the paresis, and occurrence of basilar migraine symptoms. In the linked families, significantly more patients reported unconsciousness during attacks (39%, vs 15%; p<0.05) and provocation of attacks by mild head trauma (70% vs 40%; p< 0.05). In one linked family patients also displayed chronic progressive cerebellar ataxia, whereas in one unlinked family benign infantile convulsions occurred in addition to FHM. Interestingly, so far an association with cerebellar ataxia was only described in chromosome 19-linked families. FHM linked to chromosome 19 and FHM unlinked to chromosome 19 do not differ with respect to clinical features.
Effect of a Nitric Oxide Donor (Glyceryl Trinitrate) on Nociceptive Thresholds in Man
Authors: Thomsen LL , Brennum J , Iverson HK , Olesen J
Published: March 2003

Several animal studies suggest that nitric oxide (NO) plays a role in central and peripheral modulation of nociception. Glyceryl trinitrate GTN) exerts its physiological actions via donation of NO. The purpose of the present study was to examine the effect of this NO donor on nociceptive thresholds in man. On two different study days separated by at least, week 12 healthy subjects received a staircase infusion of GTN (0.015, 0.25. 1.0, 2.0 mg/kg/min. 20 min each dose) or placebo in a randomized double-blind crossover design. Before the infusion and after 15 min of infusion on each dose, pressure pain detection and tolerance thresholds were determined by pressure a gometry (Somomedic AB, Sweden) in three different anatomic regions (finger, a temporal region with interposed myofascial tissue and a temporal region without interposed myofascial tissue. Relative to placebo, the three higher GTN doses induced a decrease in both detection and tolerance thresholds in the temporal region with interposed myofascial tissue ( p=0.003 detection and p=0.002 tolerance threshold: Friedman). No such changes were observed in the other two stimulated regions. These results could reflect central facilitation of nociception by NO. However, we regard convergence, of nociceptive input from pericranial myofascial tissue and from cephalic blood vessels dilated by NO as a more likely, explanation of our findings.
Photic Driving in Migraine: Correlations with Clinical Features
Authors: Puca FM , de Tommaso M , Tota P , Sciruicchio V
Published: March 2003

Fifty-eight migraineurs were, studied by intermediate frequency steady-state visual evoked potentials (SSVEPs) during headache-free periods. Sex, age, age of onset of migraine, duration of illness, type of migraine, side of pain, sleep wake disorders, and frequency of migraine attacks did not correlate with any SSVEP abnormalities. On the other hand, visual responsiveness was significantly increased in subjects with family history of migraine, and in those with autonomic symptoms. Our results may indicate that a genetic predisposition to migraine underlies the observed abnormal visual response in migraineurs.
Prophylaxis of Migraine with Oral Magnesium: Results From A Prospective, Multi-Center, Placebo-Controlled and Double-Blind Randomized Study
Authors: Peikert A , Wilimzig C , Köhne-Volland R
Published: March 2003

In order to evaluate the prophylactic effect of oral magnesium, 81 patients aged 18–65 years with migraine according to the International Headache Society (IHS) criteria (mean attack frequency 3.6 per month) were examined. After a prospective baseline period of 4 weeks they received oral 600 mg (24 mmol) magnesium (trimagnesium dicitrate) daily for 12 weeks or placebo. In weeks 9–12 the attack frequency was reduced by 41.6% in the magnesium group and by 15.8% in the placebo group compared to the baseline ( p < 0.05). The number of days with migraine and the drug consumption for symptomatic treatment per patient also decreased significantly in the magnesium group. Duration and intensity of the attacks and the drug consumption per attack also tended to decrease compared to placebo but failed to be significant. Adverse events were diarrhea (18.6%) and gastric irritation (4.7%). High-dose oral magnesium appears to be effective in migraine prophylaxis.
311C90 (Zolmitriptan), A Novel Centrally and Peripheral Acting Oral 5-Hydroxytryptamine-1D Agonist: A Comparison of Its Absorption During A Migraine Attack and in A Migraine-Free Period
Authors: Thomsen LL , Dixon R , Lassen LH , Giboens M , Langemark M , Bendtsen L , Daugaard D , Olesen J
Published: March 2003

The oral absorption of a 10-m. oral dose of the novel 5-hydroxytryptamine (5HT1D) agonist, 311C90, was compared during a moderate or severe migraine headache and in a migraine-free period in an open, two-period study. The safety and efficacy of 311C90 in acute migraine were also assessed. Twenty patients attended the clinics during a moderate or severe migraine attack and 18 patients returned for a second dose in a migraine-free period 311C90 was less rapidly absorbed during a migraine attack compared to the migraine-free period, cons stent with gastric stasis during a migraine attack. The median area under the curve (AUC) was 15.7 ng/mlh lower during a migraine (median AUC: 18.4ng/ml.h, range: 0–60.8 ng/ml.h) compared to the migraine-free period (median AUC: 33.4 ng/ml.h, range 9.4–79.5 ng/ml.h) (95% confidence interval: 6.9,25.3) and the time to reach maximum plasma concentration was delayed ( n = 18). Eleven out of 20 patients experienced a significant improvement in migraine headache intensity at 2 h post-dose. Plasma 311C90 concentrations were generally higher in those patients who responded to treatment with 311C90 in the plasma, but there was one patient with no quantifiable 311C90 in the plasma whose headache improved. Minor adverse experiences were reported in 11 out of 20 patients during a migraine attack and in 11 out of 18 patients outside an attack. They occurred shortly following drug administration and were of short duration, but their occurrence did not appear to be related to plasma 311C90 concentration. There were no clinically significant changes in blood pressure or 12-lead ECG during the assessment period.
Migraine Without Aura and Migraine with Aura are Inherited Disorders
Authors: Russell MB , Iselius L , Olesen J
Published: March 2003

The familial occurrence and mode of inheritance were analysed in families with migraine without aura (MO) and migraine with aura (MA). The probands were found among 4000 persons from the general population. All persons with MA were included as probands, and an equivalent number of probands with MO was selected as a random sample among those with MO. Spouses and first-degree relatives were blindly interviewed. All interviews were performed by one neurological research fellow. The distinct familial patterns indicate that MO and MA have a different aetiology. Compared with the general population, the first-degree relatives of probands with MO had a 1.9-fold increased risk of MO while spouses had a 1.5-fold increased risk of MO, indicating that both genetic and environmental factors are important in MO. The first-degree relatives of probands with MA had a four-fold increased risk of MA while spouses had no increased risk of MA, indicating that MA is determined largely by genetic factors. The complex segregation analysis indicate that both MO and MA have multifactorial inheritance without generational difference.
Calcitonin Gene-Related Peptide is Released from Capsaicin-Sensitive Nerve Fibres and Induces Vasodilatation of Human Cerebral Arteries Concomitant with Activation of Adenylyl Cyclase
Authors: Jansen-Olesen I , Mortensen A , Edvinsson L
Published: March 2003

The vasomotor effects of calcilonin gene-related peptide (CGRP) analogues have been studied in circular segments of fresh human cereoral arteries obtained at neurosurgical operations using a sensitive in vitro system. Human a-CGRP, human b-CGRP, rat a-CGRP and rat b-CGRP induced strong and potent relaxation of precontracted circular vessel segments. The Imax (maximum relaxant effect) to human calcitonin was low and the pD2 (concentration for half maximum effect) 7.7 was much lower than that of CGRP. The CGRP-1, antagonist human a-CGRP8-37 blocked the response to human a-CGRP but not to human b-CGRP, while the putative antagonist [Tyr]CGRP28-37 did not. Capsaicin (10-15 - 10-8 M) caused relaxation of the cerebral arteries by 22% of precontract on. Pre-treatment with 10-6 M human a-CGRP8-37 inhibited this relaxation. Human a-CGRP increased the cyclic AMP content of human cerebral arteries in a concentration-dependent manner. This increase in adenylyl cyclase activity was blocked by human a-CGRP8-37. The results suggest that CGRP-1 receptors coupled to adenylyl cyclase are present in human cerebral arteries.
Post-Marketing Cohort Study Comparing the Safety and Efficacy of Flunarizine and Propranolol in the Prophylaxis of Migraine
Authors: Verspeelt J , De Locht P , Amery WK
Published: March 2003

A comparative post-marketing surveillance study of the safety and efficacy of flunarizine and propranolol in the treatment of migraine was carried out. General practitioners in Belgium and the Netherlands each recruited patients for whom they would prescribe one of the study medications in the normal course of their treatment and recorded all medical events on follow-up forms for up to 8 months. A total of 1601 migraine patients were enrolled; 838 in the flunarizine cohort and 763 in the propranolol cohort. Propranolol was somewhat better than flunarizine in reducing the severity of migraine attacks, although this may have been due to a selection bias. Discontinuations of therapy due to events considered likely to be treatment-related were mostly due to the recognized side effects of the two drugs. As regards the occurrence of depressions, a total of 58 patients had depressive events, 34 in the flunarizine cohort and 24 in the propranolol cohort. Whereas migraine itself appears to be associated with an increased risk of depression, the number of previous migraine treatments was shown to be an additional risk factor for the development of depression in patients receiving flunarizine as was a history of depression. Overall, there was no appreciable difference in the risk/benefit ratio between flunarizine and propranolol.
Long-term Follow-up after Flunarizine or Nimodipine Discontinuation in Migraine Patients
Authors: Nuti A , Lucetti C , Pavese N , Dell'Agnello G , Rossi G , Bonuccelli U
Published: March 2003

Various open and controlled studies have confirmed the antimigraine action of flunarizine, while the antimigraine properties of nimodipine are still open to controversy. Moreover, only a few studies include an additional follow-up after discontinuation of migraine prophylaxis with either drug. We carried out a single blind evaluation of the efficacy and tolerance of flunarizine (25 patients) in comparison with nimodipine (25 patients) and the long-term effect after discontinuation of a 6-month treatment. Both medications significantly reduced migraine frequency and severity. Flunarizine was more efficacious than nimodipine in reducing migraine frequency ( p < 0.001), pain severity ( p < 0.05), migraine index ( p < 0.05) and corrected migraine index ( p < 0.05). The positive effect lasted 8.4 ± 4.0 months after discontinuation of flunarizine and 4.9 ± 3.5 months after nimodipine ( p < 0.05). Our results suggest that flunarizine is more effective than nimodipine in the prophylactic treatment of migraine. The positive effect after drug discontinuation lasts longer with flunarizine, compared to nimodipine.
Headache Induced by a Nitric Oxide Donor (nitroglycerin) Responds to Sumatriptan. A Human Model for Development of Migraine Drugs
Authors: Iversen HK , Olesen J
Published: March 2003

Experimental “vascular” headache in humans may be used in characterizing new migraine drugs. The effects of sumatriptan on nitroglycerin-(NTG)-induced headache and arterial responses were therefore studied. Following a double-blind randomized crossover design, 10 healthy volunteers received sumatriptan 6 mg s.c. or placebo succeeded by 20 min NTG (0.12 mg/kg/min) infusion. Headache was rated on a 10 points scale. Temporal and radial artery diameters and velocity in the middle cerebral artery (MCA) were measured with ultrasound. Sumatriptan reduced the NTG-induced headache, median score 1.5 versus 4 after placebo (p<0.01) and decreased temporal and radial artery diameters 75±3 and 86±3% of baseline respectively (p<0.05), Blood velocity in the MCA was unaffected. The NTG model may prove to be a valuable tool in the development of future migraine drugs. The results suggest that NTG headache in non-migraineurs may share mechanisms with migraine headache.
Neuropeptide Changes in a case of Chronic Paroxysmal Hemicrania—Evidence for Trigemino-Parasympathetic Activation
Authors: Goadsby P J , Edvinsson L
Published: March 2003

Chronic paroxysmal hemicrania (CPH) is a rare headache syndrome of short-lasting attacks of pain, characterized clinically by trigemino-parasympathetic activation. The features of the headache are severe attacks of pain that generally last no more than minutes in association with autonomic activation, such as lacrimation or rhinorrhea. We report a patient fulfilling International Headache Society guidelines for the diagnosis of CPH in whom levels of calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) were elevated in the cranial circulation during attacks. Moreover, successful treatment of the problem with indomethacin leads to normalization of the levels of both CGRP and VIP. Given that similar neuropeptide changes are seen in cluster headache the data suggest a shared underlying pathophysiology between CPH and cluster headache.
Headache Induced by Serotonergic Agonists—a Key to the Interpretation of Migraine Pathogenesis?
Authors: Panconesi A , Sicuteri R
Published: March 2003

Serotonergic agonists such as m-chlorophenylpiperazine (m-CPP) and fenfluramine may induce migraine attacks. This has led to opposing theories concerning the role of 5-hydroxytryptamine (5HT) in triggering migraine attacks; is there hyperfunction or hypofunction of the central serotonergic system. Our review of the literature strongly suggests that m-CPP and fenfluramine provoke migraine attacks by stimulating, directly or indirectly, the 5HT2C/5HT2B receptors, although there is no total agreement with this interpretation. Central 5HT hypersensitivity in migraine patients, probably due to 5HT neuronal depletion, is proposed on the basis of review of electrophysiological tests and neuroendocrine challenge paradigms.
Classical Homeopathic Treatment of Chronic Headaches
Authors: Walach H , Haeusler W , Lowes T , Mussbach D , Schamell U , Springer W , Stritzl G , Gaus W , Haag G
Published: March 2003

We conducted a randomized, placebo-cor rolled, double-blind clinical trial in order to determine the efficacy of classical homeopathic therapy in patients with chronic headaches. After 6 weeks of baseline observation, patients received either the prescribed individualized homeopathic medication or an indistinguishable placebo for 12 weeks. Outcome parameters were headache frequency, duration, and intensity, measured daily by diary. Use of medication for acure headache was also monitored. Of the 98 patients in the sample, 37 were randomized to receive placebo, 6I received individualized homeopathic remedies. Groups were comparable at the beginning of the treatment. The median age was 48.5 years; 76% suffered from migraine, 51% from tension-type headaches, and 94% were previously treated for headache. The median headache frequency was 3 days a week. Headaches were present for 23 years (median). In both groups, patients showed an improvement of one headache day less per month. The use of medication for acute headache was reduced. The headache frequency of 11 patients was reduced by more than 40%. Thirty-nine patients either did not improve or experienced aggravations. There was no significant difference in any parameter between homeopathy and placebo.
Enhanced Nitric Oxide Release During Cortical Spreading Depression Following Infusion of Glyceryl Trinitrate in the Anaesthetized Cat
Authors: Read SJ , Smith MI , Hunter AJ , Parsons AA
Published: March 2003

Intravenous infusion of glyceryl trinitrate (GTN) into migraineurs induces an immediate headache followed by migraine. We studied the effect of GTN 10.25 g kg1 min1) on local cerebrovascular laser Doppler flux (rCBFLDF), artery diameter and NO concentration (selective NO microelectrode) in the pial middle cerebral artery perfusion territory of the anaesthetized cat, at rest and during cortical spreading depression (SD). GTN infusion induced a significant increase in pial artery diameter, rCBFLDF, and NO concentration. Following termination of infusion, NO concentrations remained significantly elevated above controls for 60 min, other parameters returned to baseliae within 10 min ( p0.05, ANOVA, post hoc Dunnett's multiple comparison procedure). Two hours after termination of infusion KCI-evoked SD was initiated. GTN-treated animals exhibited significantly ( p 0.05, Kruskal-Wallis) elevated SD-induced NO release compared to controls. All other parameters remained unaffected. Our results demonstrate that GTN induces a prolonged increase in local NO concentrations and enhances SD-induced NO release.
Release of Histamine from Dural Mast Cells by Substance P and Calcitonin Gene-Related Peptide
Authors: Ottosson A , Edvinsson L
Published: March 2003

The aim of the present study was to examine if the neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) can stimulate histamine release from mast cells in the dura mater and thereby play a role in cranial vasoregulation and local neurogenic inflammation. Dura mater mast cells were compared with peritoneal mast cells in the rat. Histamine was released from dura mater mast cells by compound 48/80, SP and CGRP but from peritoneal mast cells only by compound 8/80 and SP. NPY and VIP released quite small amounts of histamine from dural mast cells. The release on SP and CGRP from rat dura mater mast cells was blocked by the receptor antagonists FK888 and CGRP8-37 respectively, suggesting receptor mediated release mechanisms. None of the stimuli released histamine from human or porcine dural mast cells, possibly because the sampling procedure injures and incapacitates the cells.
Anginal Headache and Its Basis
Authors: Grace A , Horgan J , Breathnach K , Staunton H
Published: March 2003

A case is presented of angina manifesting itself initially solely as vertex and occipital headache, accompanied by EKG changes, provoked by exercise and relieved by rest. It was totally relieved by coronary bypass surgery and, later, by angioplasty. Its mechanism is probably a variation on the neural convergence usually invoked to explain the more typical chest pain angina.
A 40-Year Follow-Up of School Children with Migraine
Authors: Bille B
Published: March 2003

A prevalence study of 9000 Swedish school children conducted in 1955 showed that nearly 4% had migraine. The prevalence of migraine was 1.4% at 7 years of age and 5.3% at 15 years of age. From the age of 11 there was a gradual increase of migraine headache and a predominance among girls. A subgroup of 73 children with pronounced migraine and an average onset of 6 years was followed during a period of 40 years. The results showed that 23% of the children were migraine-free before the age of 25, boys significantly more often than girls. However, around the age of 50, more than half of the migraine group still had migraine attacks. A recall bias was found it that a number of the subjects in their middle-life (41%) could not remember that they had had aura symptoms previously. Of those who had become parents, 52% have in their present or previous families had one child or more who had developed recurrent headache, probably of the migraine-type.
Migraine-Associated Vertigo
Authors: Savundra PA , Carroll JD , Davies RA , Luxon LM
Published: March 2003

A retrospective analysis was performed on consecutive series of 363 patients presenting with vertigo; 32% had migraine. Of the 224 patients with no pathology other than migraine or vestibular dysfunction, migraineurs had a significantly higher prevalence of normal, central, and combined central and peripheral vestibular dysfunction compared to non-migraineurs. The combination of central and peripheral vestibular signs was a feature of migraine with aura. The results support the hypothesis that migraine-associated vertigo is a diagnostic entity.
A Clinical Review of the Adaptive Role of Vasopressin in Migraine
Authors: Gupta VK
Published: March 2003

Vasopressin is a naturally available neuropeptide that subserves important vasomotor, antinociceptive, behavior control, fluid and electrolyte balance, platelet aggregation and blood coagulation functions. This review focuses on the clinical phenomena of migraine that are likely to influence vasopressin bioavailability or efficacy as well as the modulating influence of vasopressin itself. As part of a complex homeostatic adjustment to stress and pain, the intricacies of vasopressin metabolism may have particular relevance to the pathophysiology of migraine.
Prophylactic Treatment of Migraine with Bisoprolol
Authors: van de Ven LLM , Franke CL , Koehler PJ
Published: March 2003

The objective of the present study was to assess the efficacy of bisoprolol in migraine prophylaxis. A double-blind placebo-controlled study was conducted in 226 patients with migraine with or without aura, a migraine history of at least 2 years and at least 3 documented attacks during the 28 days run-in period. The duration of treatment was 12 weeks following an initial 28 days' run-in period. Patients reported the number of attacks and their severity in a diary. Treatment with bisoprolol 5 mg resulted in a significant reduction in the frequency of migraine attacks (39% vs 22%) compared to placebo treatment ( p<0.05). Treatment had no effect on the duration and severity of the attacks. Bisoprolol was well tolerated.
Genetic Epidemiology of Migraine and Cluster Headache
Authors: Russell MB
Published: March 2003

Migraine. The present genetic epidemiological survey of migraine was based on semi-structured interviews by a physician. The operational diagnostic criteria of the International Headache Society were used. Three thousand males and 1,000 females aged 40 were drawn from the Danish National Central Person Registry. They received a questionnaire by post regarding migraine and the response rate was 87%. People with self-reported migraine and a random sample reporting no migraine were invited to a headache interview and physical and neurological examination. Those not reacting to the invitation were interviewed by telephone. The participation of the interview was 87%. Kappa was 0.77 validating self-reported migraine against a clinical interview by a physician. Non-responders did not differ from responders regarding migraine. The lifetime prevalence of MO and MA was 9.3% and 6.3% in males and 20.1% and 9.6% in females. People with MA were included as probands in the family study. An equivalent number of probands with MO and probands who had never had migraine were random samples of the people with MO) and those who had never had migraine, respectively. First-degree relatives and spouses were interviewed blindly by a physician. The 378 probands had 1,109 first-degree relatives and 229 spouses. Compared with the general population, the first-degree relatives of probands with MO had a 1.9-fold increased risk of MO and a 1.4-fold increased risk of MA, after standardization for sex and age. The first-degree relatives of probands with MA had a 3.8-fold increased risk of MA and no increased risk of MO. The first-degree relatives of probands who had never had migraine had no increased risk of either MO or MA. Spouses to pro-bands with MC) had a 1.5-fold increased risk of MO, while spouses to probands with MA had no increased risk of MA. The familial patterns indicate that MO and MA are distinct entities. The familial occurrence suggests that MO is caused by a combination of genetic and environmental factors, while MA is determined mainly or exclusively by genetic factors. The complex segregation analysis supports the importance of genetic factors and suggests multifactorial inheritance without generational difference in both MO and MA, but genetic heterogeneity cannot be excluded.
Role of the Suprachiasmatic Nucleus in the Pathogenesis of Migraine Attacks
Authors: Zurak N
Published: March 2003

Neuroanatomic, morphometric, immunocytochemical, neurobiochemical and clinical data support the hypothesis that the suprachiasmatic nucleus of the hypothalamus might be the initial site of migraine attacks. The prodromal phase of a migraine attack could be considered a syndrome of functional suprachiasmatic nucleus insufficiency, and other phases a reactive denervation hypersensitivity with the affection of the visual, nociceptive, antinoacceptive and cranial vasomotor system.
Platelet Sulphotransferase Activity, Plasma Sulphate Levels and Sulphation Capacity in Patients with Migraine and Tension Headache
Authors: Alam Z , Coombes N , Waring RH , Williams AC , Steventon GB
Published: March 2003

Activity of both the M- and P-forms of sulphotransferase (ST) was measured in platelets from patients with migraine, tension headache and controls. Mean PST values were 0.065±0.023 and 0.057±0.052 mnol/mg protein/min for migraine patients with and without aura. The corresponding values for tension headache and controls were 0.122±0.059 and 0.127:0.093 nmol/mg protein/min respectively (p<0.05). Mean MST values were not different for any of the groups, and MST and PST activities measured in two patients during a migraine attack were not significantly altered from baseline levels. Mean plasma inorganic sulphate concentrations and paracetamol metabolites were not significantly different in any of the groups studied. The results suggest that PST activity may be a factor in the aetiology of migraine.
Differential Distribution of 5Ht1D-and 5HT1B-Immunoreactivity within the Human Trigemino-Cerebrovascular System: Implications for the Discovery of New Antimigraine Drugs
Authors: Longmore J , Shaw D , Smith D , Hopkins R , McAlliste G , Pickard JD , Sirinathsinghji DJS , Butler AJ , Hill RG
Published: March 2003

Sumatriptan, a 5HT1B/1D-receptor agonist, is clinically effective as an antimigraine agent. Its therapeutic action may result partly from vasoconstriction of excessively dilated cranial blood vessels (a 5HT1B-receptor mediated response). The antimigraine activity of sumatriptan may also result from inhibition of the release of vasoactive neuropeptides from trigeminal sensory fibres within the meninges. The identity of the 5HT1B/1D-receptor subtype mediating this effect is unknown. Using 5HT1D- and 5HT1B-receptor-specific antibodies we have demonstrated a differential distribution of these receptor subtypes within the human trigemino-cerebrovascular system. Only 5HT1B-receptor protein was detected on dural arteries. In contrast, only 5HT1D-receptor protein was detected on trigeminal sensory neurones including peripheral and central projections to dural blood vessels and to the medulla. Within the medulla 5HT1D-receptor protein was confined to discrete areas associated with the trigeminal sensory system. These findings have important implications for the design of new antimigraine drugs.
A Double-Blind Provocative Study Chocolate as A Trigger of Headache
Authors: Marcus DA , Scharff L , Turk D , Gourley LM
Published: March 2003

A provocative double blind study of headache was performed using chocolate as the active agent and carob as the placebo. The chocolate and carob samples were formulated to duplicate products used in an earlier study (1) in which strong differential effects between the ability of chocolate and carob to trigger headache in migraine were shown. Sixty-three women with chronic headache (50% migraine, 37.5% tension-type, 12.5% combined migraine and tension-type) participated in the study. After 2 weeks of following a diet that restricted vasoactive amine-rich foods, each subject underwent double-blinded provocative trials with two samples of chocolate and two of carob presented in random order. Diaries were maintained by the subjects throughout the study, monitoring diet and headache. The results demonstrated that chocolate was not more likely to provoke headache than was carol in any of the headache diagnostic groups (2(2) 0.36, p=0.83). Interestingly, these results were independent of subjects' beliefs regarding the role of chocolate in the instigation of headache (2(1)=0.73, p=0.39). Headache diagnosis and the concomitant use of additional vasoactive amine-containing foods were also not associated with chocolate acting as a headache trigger. Thus, contrary to the commonly held belief of patients and physicians, chocolate does not appear to play a significant role in triggering headaches in typical migraine, tension-type, or combined headache sufferers.
Nitric Oxide Synthase Inhibition: A New Principle in the Treatment of Migraine Attacks
Authors: Lassen LH , Ashina M , Christiansen I , Ulrich V , Grover R , Donaldson J , Olesen J
Published: March 2003

Glyceryl trinitrate, an exogenous nitric oxide (NO) donor, and histamine, which causes NO formation in vascular endothelium, have been shown to trigger migraine attacks. However, it remains uncertain whether NO is involved in the subsequent phase of migraine attacks. To answer this question we studied the effect of L-NGmethylarginine hydrochloride (546C88), a NO-synthase inhibitor, on spontaneous migraine attacks. In a double-blind study design, 18 patients with migraine without aura randomly 546C88 (6 mg/ kg) or placebo (5% dextrose) iv given over 15 min for a single migraine attack (546C88: placebo, 15:3). Furthermore, 11 placebo-treated patients from previous double-blind trials with almost identical design were added to the placebo group in the statistical evaluation. Two hours after the infusion, 10 of 15 L-NGmethylarginine hydrochloride-treated patients experienced headache relief compared to 2 of 14 placebotreated patients ( p=0.01). Symptoms such as phono- and photophobia were also significantly improved. A similar trend for nausea was not significant. We conclude that NO may be involved in the pain mechanisms throughout the course of spontaneous migraine attacks.
Tolerability and Efficacy of Naratriptan Tablets with Long-Term Treatment (6 Months)
Authors: Bomhof MAM , Heywood J , Pradalier A , Enahoro H , Winter P , Hassani H
Published: March 2003

This open-label study was conducted to examine the long-term tolerability and efficacy of the novel 5HT1 agonist naratriptan tablets 2.5 mg used to treat all migraine attacks for 6 months. Patients could reduce the dose to 1 mg in the event of intolerable adverse events. The results demonstrate that the majority (median 83%) of attacks treated with naratriptan tablets 2.5 mg were not associated with an adverse event. Among attacks treated with naratriptan tablets 2.5 mg (+optional 2.5 mg for headache recurrence), the most frequently reported adverse event was nausea (4% of attacks after a single naratriptan dose). Both the overall incidence of adverse events and the incidences of specific adverse events were no higher during months 4-6 of treatment compared with months 1-3. Only 5 of 414 patients elected to reduce their naratriptan dose to 1 mg. Headache relief 4 h postdose was reported in a mean of 68% of 6770 moderate or severe migraine attacks treated with naratriptan tablets 2.5 mg. The median number of naratriptan tablets used per attack was 1.0 (mean 1.25); patients treated only a median 7% of attacks (mean 13%) with a 2nd naratriptan tablet for headache recurrence. Patients rated naratriptan tablets as good or excellent in 61% of 7566 treated attacks. In summary, the data from this study demonstrate that naratriptan tablets 2.5 mg were very well tolerated and effective for the acute treatment of migraine for 6 months in a situation closely resembling actual clinical use.
Migraine and Glaucoma: an Epidemiologic Survey of French Ophthalmologists
Authors: Pradalier A , Hamard P , Sellem E , Bringer L
Published: March 2003

Glaucoma is a common ocular disorder; a high intraocular pressure is observed in the majority of glaucoma (HIOPG) cases, but some patients have low-tension glaucoma (LTG). In the literature, some works link LTG and migraine, which is speculative of a potential role of a vasospastic factor or diathesis common to migraine and LTG. Using a standardized questionnaire based on International Headache Society (IHS) criteria, we investigated 954 glaucoma patients; 320 (33.5%) described a headache (migraine or tension-type headache) and 240 (25.1%) presented the IHS criteria for migraine. Migraine prevalence was not significantly different between HIOPG and LTG patients (22.8% and 32%, respectively) in this study.
Trigeminal Neuralgia with Lacrimation Or Sunct Syndrome?
Authors: Benoliel R , Sharav Y
Published: March 2003

An intimate relationship between trigeminal neuralgia (TN) and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) syndrome, based on similar clinical signs and symptoms and on cases demonstrating possible “transformation” from one entity to the other, has been widely accepted. We evaluated the presence of lacrimation in 22 consecutive cases that had been diagnosed as TN. Ipsilateral lacrimation was reported by 6 such cases (5M, 1F). These cases responded to antineuralgic therapy with concomitant resolution of lacrimation and were clinically very similar to TN. The differential diagnosis and the possibility of lacrimation in TN are discussed.
Hypnic Headache Syndrome: A Case with Good Response To Indomethacin
Authors: Ivañez V , Soler R , Barreiro P
Published: March 2003

Hypnic headache syndrome is a rare benign disorder which occurs in the elderly. It presents as a holocephalic or, less frequently, hemicranial headache during night sleep, lasting between 20 and 180 min; it is not associated with autonomic signs and responds well to lithium carbonate. We report a new case which responded well to indomethacin, and suggest that indomethacin may be used as an alternative treatment in this rare headache syndrome of the elderly.
Headache After Whiplash: A Historical Cohort Study Outside the Medico-Legal Context
Authors: Obelieniene D , Bovim G , Schrader H , Surkiene D , Mickeviàiene D , Miseviàiene I , Sand T
Published: March 2003

Headache is frequently reported as a chronic complaint after whiplash traumas. Criteria have been presented, but it has not been validated whether any specific headache type emerges after a trauma with whiplash mechanism. In a questionnaire-based historical cohort design, 202 adult Lithuanian individuals were interviewed 1–3 years after experiencing a rear-end car collision. The questionnaire was designed so that a diagnosis of migraine and tension-type headache in accordance with the International Headache Society criteria could be made. “Possible cervicogenic headache” was diagnosed according to Sjaastad et al.'s minimal criteria. The diagnostic panorama in those with traumas was compared with that of an age- and sex-matched control group. The introductory questions did not reveal differences in headache frequencies between the traumatized and control groups ( p=0.60). The prevalence of migraine and tension-type headache (both episodic and chronic) was also similar. A higher frequency of possible cervicogenic headache was observed in the traumatized group (10 vs 5), but the difference was not statistically significant ( p=0.28). Sixteen patients in the accident group had headache > 15 days per month, 11 of the 16 had similar complaints before the trauma, while 5 had worsened headache as compared to (the recollected headache) before the trauma. None of the patients with possible cervicogenic headache reported increased headache after the accident. Accordingly, the present results obtained outside the medico-legal context do not confirm that a specific headache pattern emerges 1–3 years after a rear-end car collision.
Effects of Zolmitriptan (ZomigTM) on Central Serotonergic Neurotransmission as Assessed by Active Oddball Auditory Event-Related Potentials in Volunteers without Migraine
Authors: Hughes AM , Dixon R , Dane A , Kemp J , Cummings L , Yates RA
Published: March 2003

In this randomized, double-blind, three-period crossover trial, 24 healthy volunteers without migraine received zolmitriptan 5 mg, dexfenfluramine 15 mg or placebo orally. At 2, 6, and 24 h postdose, auditory stimuli of 1000 Hz (nontarget tone) and 2000 Hz (target tone) were randomly and binaurally presented in an active oddball paradigm (4:1 ratio). Cortical auditory evoked responses were recorded for 500 msec poststimulus. Plasma concentrations of zolmitriptan and a 17-lead quantitative EEG were assessed at the same timepoints. Relative to placebo, zolmitriptan reduced the maximum absolute amplitude, amplitude difference (from nontarget tone noise) and area under the curve of the cortical auditory target tone event-related potential (P300 ERP). The most dramatic effect of zolmitriptan was to diminish the point estimate of noise during the 200-400 msec poststimulus epoch. The effect of zolmitriptan appeared concentration dependent. The latency of the P300 ERP was unaffected by zolmitriptan and there was no clinically significant effect on the EEG. Modification by zolmitriptan of the cortical electrical activity evoked by auditory stimuli confirms a central action of this drug in humans, which appears to affect cortical information processing without global alteration of the quantitative EEG.
Nonaneurysmal Thunderclap Headache with Diffuse, Multifocal, Segmental, and Reversible Vasospasm
Authors: Dodick DW , Brown RD , Britton JW , Huston J
Published: March 2003

Objective. To highlight the clinical profiles and angiographic findings of two patients with recurrent thunderclap headache (TCH) without subarachnoid hemorrhage (SAH) and to present modified diagnostic criteria for this unusual syndrome.

Background. TCH may be a benign recurrent headache disorder or it may represent a serious underlying process such as SAH or venous sinus thrombosis. The pathophysiology of this disorder in the absence of underlying pathology is not well understood and its potential angiographic features are not well appreciated.

Methods. Two case descriptions with illustrative angiography.

Results. Both cases demonstrated the potential for reversible intracranial vasospasm without intracranial aneurysm or SAH and a benign clinical outcome.

Conclusions. Primary TCH has a distinctive clinical and angiographic profile and must be distinguished from central nervous system vasculitis and SAH.