I. W. Husstedt

Two-year follow-up of aspirin responder and aspirin non responder. A pilot-study including 180 post-stroke patients.

Aspirin is proposed to be effective in stroke-prophylaxis because it completely inhibits the platelet prostanoid-pathway. In about 90% of stroke victims, increased platelet reactivity (PR) can be reduced to the normal range by aspirin. Twelve hours later, about one third of them show an enhanced PR again. These patients are called secondary aspirin non responders (SANR). In this study the potential pathogenetic and prognostic impact of this biological feature on stroke recurrence was evaluated. Before discharge from the hospital, PR was determined 12 hours after an oral administration of 500 mg aspirin in 180 patients aged 58 +/- 15 years; 74 were female and 106 male. All had suffered a stroke in the internal carotid artery territory. Patients were treated with 3 x 500 mg aspirin/d and were followed up over a 24-month period. Major endpoints of this study were stroke, myocardial infarction or vascular death. On discharge from the hospital, 120 of the 180 patients showed a normal PR under aspirin treatment. High test values were found in 60 patients (SANR). Six patients were lost for follow-up. Because of side effects 36 (20%) of the 180 patients enrolled discontinued medication. Major endpoints occurred in 4 of these 36 patients (11%) and in 25 of the 138 remaining patients (18.1%); 19 patients died in consequence of a vascular event during the observation period. Major endpoints were seen in only 5 of 114 (4.4%) of the aspirin responders, but in 24 out of 60 SANR (40%, p < 0.0001). It may be assumed that early identification of SANRs is a clinically useful tool to classify patients at high risk for recurrence of vascular events.

Botulinum toxin A in the prophylactic treatment of migraine--a randomized, double-blind, placebo-controlled study.

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.

Cognitive Processing in Primary Headache A Study on Event-related Potentials

Background: There is experimental evidence for loss of cognitive habituation in migraine but not in other types of headache and not by visual event-related potentials (ERP). Objective: Determining the latencies (msec) and amplitudes (micro V) of ERP components and the differences of these values in a two-trial analysis representing the amount of cognitive habituation. Participants: Two hundred thirty-three patients with a headache diagnosis according to the criteria of the International Headache Society: migraine without aura (N = 77); migraine with aura (N = 31); cluster headache during period (N = 26); cluster headache during interval (N = 11); chronic paroxysmal hemicrania (N = 8); episodic tension-type headache (N = 33); ergotamine-induced headache (N = 47). Thirty age-matched healthy subjects served as a control group. Methods: ERPs were evoked by a visual oddball paradigm consisting of 2 x 200 flashes of light (85% white light; 15% red light). Evaluation of ERP components was done separately for the first 200 and the second 200 stimuli as well as for the entire series of stimuli. Results: We found an acceleration of the P3 latency during the second trial in migraine with and without aura, but not in the other headache types, and not in healthy controls. Ergotamine and sumatriptan abolished this loss of habituation in migraine patients. Increased ERP latencies as compared with healthy controls were present in patients with cluster headache, tension-type headache, ergotamine-induced headache, and migraine with aura, but not in migraine without aura. Conclusion: There is a loss of cognitive habituation in migraine, which may serve as a specific but not sensitive diagnostic tool. The pathophysiologies of migraine and cluster headache have a specific modifying property on cognitive processing reflected by a loss of cognitive habituation or an increased cognitive processing time. These effects can, in part, be counterbalanced by antimigraine medication. NEUROLOGY 1997;48: 108-113

Headache associated with sexual activity: demography, clinical features, and comorbidity.

Objectives: 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.

Treatment of Headache with Botulinum Toxin A—a Review According To Evidence-Based Medicine Criteria

The aim of this review is to evaluate the studies available from reference systems and published congress contributions on the prophylactic treatment of idiopathic and cervicogenic headache with botulinum toxin A, and to classify these studies according to evidence-based medicine (EBM) criteria. The studies were analysed with respect to the study design, the number of patients enrolled, the efficacy parameters, and the significance of results. We used the following classification of EBM. I: randomized, controlled study with sufficient number of patients; II: well-designed, controlled study (or randomized, controlled study with insufficient number of patients, no exact diagnosis, missing data of botulinum toxin A dose); III: well-designed, descriptive study; IV: case reports, opinions of experts. For tension-type headache, two studies were found with negative evidence of I with respect to the primary endpoint. There are about as many positive as negative studies with evidence of II or III. For the therapy of migraine, one study with both negative and positive evidence of I, one in part positive study of II, and three positive studies classified as III are available. Two studies on cervicogenic headache with evidence of II and III are contradictory. In addition, we found several positive case reports. For patients with cluster headache, there are positive and negative case reports. We found one positive case report for the treatment of chronic paroxysmal hemicrania. As a result of this analysis, we consider no sufficient positive evidence for a general treatment of idiopathic and cervicogenic headaches with botulinum toxin A to date. Further studies are needed for a definite evaluation of subgroups with benefit from such treatment.

Treatment of childhood migraine attacks with oral zolmitriptan and ibuprofen

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.

Drug-induced headache: long-term results of stationary versus ambulatory withdrawal therapy

Drug-induced headache is a well-known complication of the treatment of primary headache disorders, and its successful management is only possible by withdrawal therapy. However, it is unknown whether ambulatory or stationary withdrawal is the therapy preferred. We conducted a prospective study on the outcome of stationary versus ambulatory withdrawal therapy in patients with drug-induced headache according to the International Headache Society criteria. Out of 257 patients with the diagnosis of drug-induced headache during the study period, 101 patients (41 after ambulatory and 60 after stationary withdrawal therapy) could be followed up for 5.9 ± 4.0 years. The total relapse rate after successful withdrawal therapy was 20.8% (14.6% after ambulatory and 25.0% after stationary withdrawal therapy, p <0.2). The main risk factors for a relapse were male sex (OR=3.9, CI=1.3-11.6), intake of combined analgesic drugs (OR=3.8, CI=1.4-10.3), administration of naturopathy (OR=6.0, CI=1.2-29.3), and a trend to tension-type headache as the primary headache disorder (OR=1.9, CI=0.6-53.0). Our data suggest that neither the method of withdrawal therapy nor the kind of analgesic and other antimigraine drugs has a major impact on the long-term result after successful withdrawal therapy. Patients with risk factors according to our findings should be informed and monitored regularly, and combined drugs should be avoided. Furthermore, our data suggest that there is a need for research on individual psychological and behavioral risk factors for relapse after successful withdrawal therapy in drug-induced headache.

Hypnic Headache - the First German Cases Including Polysomnography

We report the first four German cases of hypnic headache according to the criteria suggested in the literature. Furthermore, we present the results of polysomnography in two theses cases with hypnic headache occurring during REM sleep. In one case, hypnic headache was also associated with periodic limb movements. Although mean nocturnal oxygen saturation was decreased in another patient, nightly oxygen inhalation did not result in an improvement of the headache.

Alternatives in drug treatment of chronic paroxysmal hemicrania

Indomethacin is the drug of first choice in chronic paroxysmal hemicrania with clear relief of pain as a diagnostic criterion. In a few cases, indomethacin is not tolerated because of side effects. Therefore, the efficacy of carbamazepine, verapamil. sumatriptan. acetylsalicylic acid, and oxygen as drugs in the prophylactic or acute treatment of chronic paroxysmal hemicrania was studied in a prospective open trial with 10 patients suffering from chronic paroxysmal hemicrania. The trial results, in accordance with a review of the literature. suggest that acetylsalicylic acid (and probably naproxen and diclofenac) and verapamil are the most effective drugs of second choice in chronic paroxysmal hemicrania. The efficacy of sumatriptan in this condition needs still to be clarified. although there is evidence for partial efficacy. Carbamazepine and oxygen did not show any significant influence on chronic paroxysmal hemicrania.

Phantom eye syndrome Its prevalence, phenomenology, and putative mechanisms

This study presents data on the clinical characteristics and possible mechanisms of the phantom eye syndrome in 112 patients after removal of one eye. The prevalence of phantom eye pain was 26%, nonpainful phantom sensations 29%, and visual hallucinations 31%. Headaches and preoperative eye pain were associated with the presence of phantom experiences. These results suggest that pain is an important cofactor for the development of phantom eye phenomena.