Migraine Disorders: Frese A

Anonymous00234, Evers S, Afra J, Frese A, Goadsby PJ, Linde M, May A, Sándor PS. · Department of Neurology, University of Münster, Germany. European Federation of NeurologicalSocieties · Eur J Neurol. · Pubmed #16796580 No free full text.

Abstract: Migraine is one of the most frequent disabling neurological conditions with a major impact on the patients' quality of life. To give evidence-based or expert recommendations for the different drug treatment procedures of the different migraine syndromes based on a literature search and an consensus in an expert panel. All available medical reference systems were screened for all kinds of clinical studies on migraine with and without aura and on migraine-like syndromes. The findings in these studies were evaluated according to the recommendations of the EFNS resulting in level A,B, or C recommendations and good practice points. For the acute treatment of migraine attacks, oral non-steroidal anti-inflammatory drugs (NSAIDs) and triptans are recommended. The administration should follow the concept of stratified treatment. Before intake of NSAIDs and triptans, oral metoclopramide or domperidon is recommended. In very severe attacks, intravenous acetylsalicylic acid or subcutaneous sumatriptan are drugs of first choice. A status migrainosus can probably be treated by steroids. For the prophylaxis of migraine, betablockers (propranolol and metoprolol), flunarizine, valproic acid, and topiramate are drugs of first choice. Drugs of second choice for migraine prophylaxis are amitriptyline, naproxen, petasites, and bisoprolol.

Frese A, Evers S. · Department of Neurology, University of Münster, Münster, Germany. · Cephalalgia. · Pubmed #18494989 No free full text.

Abstract: Upper cervical pain is frequent in different primary headaches and not sufficient evidence for cervicogenic headache (CH). Biological markers should help to differentiate CH from other headache disorders. In most cases, imaging techniques of the cervical spine are not helpful for the diagnosis of CH. Symptoms and signs of neck involvement, such as a mechanical precipitation of attacks, a restriction in range of motion of the cervical spine, and the existence of ipsilateral neck, shoulder, or arm pain, seem to be reasonably valid for the diagnosis of CH, but its reliability and validity should be confirmed in larger studies. Positive diagnostic blockades of cervical structures or its nerve supply are not specific for CH. Neurophysiological investigations give some insight into the pathophysiological mechanisms of CH but are not diagnostic. In CH, calcitonin gene-related peptide levels do not differ between the symptomatic and the asymptomatic side, between the jugular and the cubital blood, and between days with and without headache. There is no evidence for an activation of the trigeminovascular system in CH. It can be concluded that CH is not just a migraine variant triggered by neck dysfunction but a functional entity.

Frese A, Schilgen M, Husstedt IW, Evers S. · Klinik und Poliklinik für Neurologie, Universitätsklinikum Münster. · Schmerz. · Pubmed #12695893 No free full text.

Abstract: Cervicogenic headache (CH) originates from disorders of the neck but is recognized as a referred pain in the head. Primary sensory afferents from the cervical roots C1-C3 converge with afferents from the occiput and trigeminal afferents on the same second-order neuron in the upper cervical spine. Consequently, the anatomical structures innervated by the cervical roots C1-C3 are potential sources of CH. In normal volunteers, the painful stimulation of different anatomical structures of the neck produced headache. In CH, particular structures have been selectively anesthetized in order to identify possible sources of pain. In summary, CH can origin from different muscles and ligaments of the neck, from intervertebral discs,and, particularly, from the atlantooccipital, atlantoaxial, and C2/C3 zygapophyseal joints. Diagnosis of CH should adhere strictly to the published diagnostic criteria to avoid misdiagnosis and confusion with primary headache disorders such as migraine and tension type headache.

Evers S, Vollmer-Haase J, Schwaag S, Rahmann A, Husstedt IW, Frese A. · Department of Neurology, University of Münster, Germany. · Cephalalgia. · Pubmed #15377314 No free full text.

Abstract: Botulinum toxin A has been suggested to be effective in the prophylactic treatment of migraine. However, only very few randomized, double-blind, placebo-controlled studies are available. We designed such a study with a specific focus on different injection sites. Sixty patients with a migraine according to the criteria of the International Headache Society were randomly assigned to receive either placebo in the frontal and neck muscles, or to receive 16 U botulinum toxin A in the frontal muscles and placebo in the neck muscles, or to receive in total 100 U botulinum toxin A in the frontal and neck muscles. The observation period was 3 months. In both treatment groups, 30% of patients showed a reduction of migraine frequency in month 3 by at least 50% compared with baseline, in the placebo group 25% of the patients showed such a reduction (P = 0.921). There were no significant differences between the three study groups with respect to reduction of migraine frequency, number of days with migraine, and the number of total single doses to treat a migraine attack. In the post hoc analysis, the reduction of all accompanying symptoms was significantly higher in the 16 U treatment group compared with the placebo group. In the 100 U treatment group significantly more adverse events occurred compared with the placebo group. All adverse events were mild and transient. Our study did not show any efficacy of botulinum toxin A in the prophylactic treatment of migraine. Only accompanying symptoms were significantly reduced in the 16 U but not in the 100 U treatment group. Future studies should focus on the efficacy of botulinum toxin A in specific subgroups of patients, on the efficacy of repetitive injections, and on other injection sites.

Evers S, Rüschenschmidt J, Frese A, Rahmann A, Husstedt IW. · Department of Neurology, University of Münster, Germany. · Headache. · Pubmed #14629247 No free full text.

Abstract: OBJECTIVE: To evaluate potential cognitive impairment caused by acute antimigraine drugs. METHODS: We conducted a placebo-controlled, double-blind, crossover study to detect the short-term impact of sumatriptan, zolmitriptan, and ergotamine tartrate on cognitive processing as measured by event-related potentials and a d2 test. Sixteen healthy subjects were enrolled in the study and given placebo, sumatriptan 100 mg, zolmitriptan 2.5 mg, and ergotamine tartrate 2 mg on different days and in random order. Before and 2 hours after drug administration, visually evoked event-related potentials and a d2 test were measured. RESULTS: The N2 latency was significantly increased after ergotamine intake. No other significant differences could be observed in all other event-related potential parameters. In the d2 test, the GZ value was unchanged after ingestion of zolmitriptan and ergotamine, but improved significantly after taking placebo and sumatriptan. The number of relative errors and the concentration value did not change significantly. All results fell within the reference values for the d2 test in all examinations. CONCLUSION: Our data suggest that there may be a slight cognitive decline 2 hours after ingestion of ergotamine tartrate and, to an even lesser extent, zolmitriptan, but not after ingestion of sumatriptan or placebo. All changes recorded were very mild and unlikely to be clinically relevant.

Biehl K, Frese A, Marziniak M, Husstedt IW, Evers S. · Department of Neurology, University of Münster, Münster, Germany. · Cephalalgia. · Pubmed #18355349 No free full text.

Abstract: To investigate the possible association between migraine and left-handedness, we enrolled 100 patients with a diagnosis of migraine according to the International Headache Society diagnostic criteria and 100 age- and sex-matched control subjects into a case-control study. Handedness was determined by the Edinburgh Handedness Inventory. There was no significant difference in the frequency or grade of left-handedness between the two groups. Additionally, we pooled our data with those from five similar studies, which did not alter the result. Thus, neither our study nor the meta-analysis support Geschwind and Behan's hypothesis of an association between migraine and left-handedness.

Biehl K, Evers S, Frese A. · Department of Neurology, University of Münster, Münster, Germany. · Cephalalgia. · Pubmed #17655717 No free full text.

Abstract: In order to investigate the comorbidity of migraine and headache associated with sexual activity (HSA), we performed a case-control study based on migraine patients. By means of a questionnaire and a personal interview, 100 migraine patients and 100 control subjects were examined regarding a diagnosis of HSA. In five subjects from the migraine group vs. none from the control group, a diagnosis of HSA could be established (P = 0.021). Previous studies that have demonstrated comorbidity of migraine and HSA were all based on HSA patients. Thus, it can now be concluded that the association between the two headache disorders is bilateral. In addition, the prevalence of HSA in the general population can be estimated to average around at least 0.9%, which concurs with previously published data.

Evers S, Heuel T, Frese A, Akova-Oztürk E, Husstedt IW. · Department of Neurology, University of Münster, Germany. · Cephalalgia. · Pubmed #16886927 No free full text.

Abstract: Clinical and experimental data suggest that ergotamine compounds and triptans may contribute to vascular events such as myocardial infarction and stroke. The role of blood cell aggregation in this context is, however, not clarified. We aimed to evaluate the impact of different acute antimigraine compounds on platelet and erythrocyte aggregation in a human ex vivo experimental design. In 20 healthy subjects without migraine and in 20 healthy subjects with migraine without aura, platelet and erythrocyte aggregation were measured before and after intake of placebo, acetylsalicylic acid, ergotamine tartrate, zolmitriptan and sumatriptan. Platelet aggregation was measured by the so-called platelet reactivity index. Erythrocyte aggregation was measured by photometric assessment in an aggregometer. Ergotamine tartrate induced a significant increase of platelet aggregation, whereas acetylsalicylic acid induced a significant decrease in both subject groups. After placebo, after sumatriptan and after zolmitriptan, no significant changes of platelet aggregation were noted. Erythrocyte aggregation was affected by neither compound. We can conclude that platelet aggregation, but not erythrocyte aggregation, is increased after intake of ergotamine tartrate. This may in part contribute to vascular side-effects of this compound. Acetylsalicylic acid and the triptans appeared to be safe with respect to platelet and erythrocyte aggregation.

Evers S, Rahmann A, Kraemer C, Kurlemann G, Debus O, Husstedt IW, Frese A. · Department of Neurology, University of Münster, Germany. · Neurology. · Pubmed #16775229 No free full text.

Abstract: The authors conducted a double-blind, placebo-controlled, crossover study to investigate the efficacy of oral zolmitriptan in the treatment of migraine in children and adolescents. Patients (n = 32) received placebo, zolmitriptan 2.5 mg, and ibuprofen 200 to 400 mg to treat three consecutive migraine attacks. Pain relief rates after 2 hours were 28% for placebo, 62% for zolmitriptan, and 69% for ibuprofen (p < 0.05). Both drugs are well tolerated with only mild side effects.

Evers S, Frese A. · Department of Neurology, University of Münster, Münster, Germany. · Curr Opin Anaesthesiol. · Pubmed #16534293 No free full text.

Abstract: PURPOSE OF REVIEW: In past years, important advances have been made in the treatment of idiopathic headache disorders. New controlled trials have been published for the acute and the prophylactic drug and non-drug therapies. Furthermore, new headache entities have been described by the International Headache Society for which treatment recommendations can be given. RECENT FINDINGS: Triptans and non-steroidal anti-inflammatory drugs are still the drugs of first choice for the treatment of migraine attacks. Recent studies show that early treatment is clearly effective in migraine and that differential therapy with triptans can be helpful. New drugs with new mechanisms are being developed such as a calcitonin gene-related peptide antagonist. For the prophylaxis of migraine, topiramate has been introduced as an effective new drug. Botulinum toxin did not show convincing evidence of efficacy in migraine and tension-type headache. For migraine and cluster headache, surgical procedures such as the closure of the patent foramen ovale (migraine) and neurostimulation of the hypothalamus (cluster headache) are also under evaluation. A group of miscellaneous headaches (group 4 of the International Headache Society classification) is also described, for which treatment recommendations, in particular indomethacin in most cases, can now be given although no placebo-controlled trials have been performed. SUMMARY: Recent advances in headache treatment comprise growing evidence for an appropriate drug administration and for differential drug therapy rather than the development of new drugs or procedures. Surgical and other non-drug treatment procedures are under discussion and might be an additional tool for headache treatment in future years.

Frese A, Schilgen M, Edvinsson L, Frandsen E, Evers S. · Department of Neurology, University of Münster, Germany. · Cephalalgia. · Pubmed #16109051 No free full text.

Abstract: Trigeminovascular activation is involved in the pathophysiology of migraine and cluster headache. The marker evaluated best for trigeminovascular activation is calcitonin gene-related peptide (CGRP) in the cranial circulation. It is unknown whether trigeminovascular activation plays any role in cervicogenic headache (CEH). The objective of this study was to investigate CGRP plasma levels in CEH patients in relation to headache state. To compare plasma CGRP levels between the peripheral and the cranial circulation. Blood from both external jugular veins and from the antecubital vein was drawn from 11 patients with CEH. Plasma CGRP levels were measured by radioimmunoassay. No difference was found between CGRP levels assessed on days with and without headache. There was no difference between CGRP levels from the symptomatic and the asymptomatic external jugular vein and the antecubital vein. There is no evidence for an activation of the trigeminovascular system in CEH. In certain cases, clinical differentiation between CEH and migraine without aura is difficult. Plasma CGRP levels might serve as a biological marker to distinguish the two headache entities.

Frese A, Eikermann A, Frese K, Schwaag S, Husstedt IW, Evers S. · Department of Neurology, University of Münster, Germany. · Neurology. · Pubmed #14504323 No free full text.

Abstract: OBJECTIVE:S: To provide data on the demography, clinical features, and comorbidity of headache associated with sexual activity (HSA). METHODS: Between 1996 and 2001, 51 patients with the diagnosis of HSA were questioned using a structured interview. RESULTS: The mean age at onset was 39.2 (+/-11.1) years. There was a clear male preponderance (2.9:1). The age at onset had two peaks, with a first peak between the 20th and 24th (n = 13) years of life and a second peak between the 35th and 44th (n = 20) years of life. Eleven patients had HSA type 1 (dull subtype), which gradually increased with increasing sexual excitement. The remaining (n = 40) had HSA type 2 (explosive subtype). The pain was predominantly bilateral (67%), and diffuse or occipital (76%). The quality was nearly equally distributed among dull, throbbing, and stabbing. HSA was not dependent on specific sexual habits and most often occurred during sexual activity with the usual partner (94%) and during masturbation (35%). There was a high comorbidity with migraine (25%), benign exertional headache (29%), and tension-type headache (45%). HSA types 1 and 2 did not significantly differ in demography, clinical features, or comorbidity, except for a higher probability of stopping the attack by breaking off sexual activity in HSA type 1. There were no cases with HSA type 3 (postural subtype). CONCLUSION: Mean age at onset, a male preponderance, a predominantly bilateral and occipital pain, and a high comorbidity with other primary headaches are in concordance with case reports in the literature. The authors found two peaks for the age at onset, however. There was no clinical evidence proving subtypes 1 and 2 to be distinct disorders. HSA types 1 and 2 may be different manifestations of the same disease rather than distinct entities.

Frese A, Frese K, Ringelstein EB, Husstedt IW, Evers S. · Department of Neurology, University of Münster, Münster, Germany. · Cephalalgia. · Pubmed #12950381 No free full text.

Abstract: Cognitive processing in headache associated with sexual Cognitive processing as measured by event-related potentials (ERP) in patients suffering from the explosive subtype of headache associated with sexual activity (HSA type 2) was investigated. Visual ERP were measured in 24 patients with HSA type 2 outside the headache period. The differences of the first and the second part of measurement were evaluated separately to determine the amount of cognitive habituation. Twenty-four sex- and age-matched healthy subjects and 24 patients with migraine without aura served as controls. A missing increase of P3 latency during the second part of the measurement was found in 79% of patients with HSA type 2 and in 75% with migraine, but only in 17% of the healthy controls (P < 0.001). The P3 amplitude was increased during the second part in 71% of patients with HSA type 2 and in 79% with migraine, but only in 33% of the healthy controls (P = 0.02). Mean P3 latency was decreased and mean P3 amplitude was increased during the second part of the measurement in HSA type 2 and in migraine but not in the healthy control group. Patients with HSA type 2 have a loss of cognitive habituation as measured by ERP. This specific information processing is very similar to that in migraine observed in previous studies.

Evers S, Schmidt O, Frese A, Husstedt IW, Ringelstein EB. · Department of Neurology, University of Münster, Albert-Schweitzer-Strasse 33, 48129 Münster, Germany. · Pain. · Pubmed #12620598 No free full text.

Abstract: Headache associated with sexual activity is an idiopathic headache disorder and regarded to be a vascular headache but no pathophysiological studies have been performed to date to elucidate the underlying mechanisms. We investigated 12 patients with the explosive type of sexual headache according to the criteria of the International Headache Society during a headache-free state by means of acetazolamide test and of stress Doppler sonography. Twelve age-matched migraine patients and 14 healthy subjects served as control groups. Changes of blood pressure, cerebral blood flow velocity (CBFV), and pulsatility index (PI) were evaluated. Patients with sexual headache showed a significantly higher increase of blood pressure during standardized physical exercise as compared to healthy subjects and migraine patients. Changes of CBFV by physical exercise were not different between the three examination groups. After 1g acetazolamide, CBFV showed a significantly higher increase in patients with sexual headache (plus 66%+/-16%) than in healthy subjects (plus 46%+/-18%), and PI showed a significantly lower decrease as compared to healthy subjects and migraine patients. These data suggest that in patients with sexual headache the metabolic rather than the myogenic component of the cerebral vasoneuronal coupling is impaired.

Schwaag S, Nabavi DG, Frese A, Husstedt IW, Evers S. · Department of Neurology, University of Münster, Germany. · Headache. · Pubmed #12558760 No free full text.

Abstract: BACKGROUND: Several studies suggest an association between migraine and juvenile stroke. Because of some shortcomings, we designed another case-control study of a homogenous group of patients with juvenile cerebral ischemia. This study is part of a larger German epidemiological research project on the association of migraine with cerebrovascular disease. METHODS: We enrolled 160 consecutive patients under the age of 46 years with first-ever ischemic stroke or transient ischemic attack and 160 strictly sex- and age-matched controls. Patients suffering from arterial dissection, brain hemorrhage, cranial sinus thrombosis, lacunar stroke, or from migrainous infarction were excluded. Migraine was diagnosed according to the criteria of the International Headache Society by the same 2 independent interviewers. For analyzing the data, nonparametric statistical methods including odds ratio and 95% confidence interval were used. RESULTS: Migraine was a significant risk factor for juvenile stroke for the total sample with an odds ratio of 2.11 (confidence interval, 1.16 to 3.82). The odds ratio was even higher in the subgroup under the age of 35 (3.26) and in the female subgroup (2.68). We found migraine to be independent from other vascular risk factors, from etiology, and from the territory of stroke. CONCLUSION: We can confirm the findings of previous studies showing a significant association between migraine and juvenile stroke in women. Furthermore, our data suggest migraine to be an even more significant risk factor for patients under the age of 35 and to be independent from other vascular risk factors.

Frese A, Evers S, May A. · Department of Neurology, University of Münster, Germany. · Cephalalgia. · Pubmed #12534584 No free full text.

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Frese A, Husstedt IW, Evers S. · Klinik und Poliklinik für Neurologie Westfälische Wilhelms-Universität Münster. · MMW Fortschr Med. · Pubmed #11692846 No free full text.

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Evers S, Bauer B, Suhr B, Voss H, Frese A, Husstedt IW. · Department of Neurology, University of Münster, Germany. · Neurology. · Pubmed #10430426 No free full text.

Abstract: BACKGROUND: Cognitive processing in migraine is characterized by a loss of habituation during the interval and increased latencies in an attack. No studies are available on event-related potentials (ERPs) in cluster headache or chronic paroxysmal hemicrania. OBJECTIVE: To determine the involvement of cognitive processing in cluster headache and chronic paroxysmal hemicrania as measured by ERPs. METHODS: Visually evoked ERPs were measured in 50 patients with episodic cluster headache, 11 patients with chronic cluster headache, and 12 patients with chronic paroxysmal hemicrania. Measurements were performed in the cluster period outside an attack with and without prophylactic medication and not in the cluster period. RESULTS: Latencies of the endogenous ERP components were significantly increased during the cluster period as compared with outside the cluster period and with healthy subjects. In chronic cluster headache, latencies of both endogenous and exogenous components were increased. Medication with prophylactic drugs normalized the ERP latencies in episodic cluster headache; in chronic cluster headache, ERP latencies were decreased without complete normalization. No changes of ERP latencies and amplitudes could be observed in chronic paroxysmal hemicrania. A loss of cognitive habituation as it is known in migraine could not be observed in either cluster headache or chronic paroxysmal hemicrania. CONCLUSIONS: Our data suggest that central structures generating ERPs are involved in the pathophysiology of cluster headache during the cluster period but not outside the cluster period. This is in concordance with recent neuroimaging findings on the central role of the hypothalamus and the right frontal cortex in cluster headache and supports the hypothesis of a central origin of cluster headache. Furthermore, the data suggest that cluster headache and chronic paroxysmal hemicrania are distinct entities.