Karl-Heinz Grotemeyer

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.

Effects of acetylsalicylic acid in stroke patients. Evidence of nonresponders in a subpopulation of treated patients.

Platelet reactivity (PR) was tested two and 12 hours after acetylsalicylic acid (ASA) intake in 82 stroke patients, aged 59 +/- 14 years (33 female and 49 male). 10% of these patients showed a pathologically enhanced PR at least two hours after intake of 500 mg ASA (= primary ASA-nonresponder (PNR)). Only 10 hours later, a further 26% of these ASA treated patients exhibited a pathological platelet reactivity (greater than 1.25) (= secondary ASA-nonresponder (SNR)). Single ASA dosages of 500 mg or 200 mg were of identical effectiveness. Additional administration of metoclopramide in combination with 100 mg ASA was more effective as compared to a single dosage of 1000 mg ASA. Those who were SNR at onset of ASA therapy remained SNR as well 28 days later. The change from a normal, ASA corrected PR, to pathological PR values before a period of 12 hours ended seemed a sudden and irreversible event that could only be corrected by the next ASA application.

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

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.

The platelet-reactivity-test — A useful “by-product” of the blood-sampling procedure?

Blood sampling demands the insertion of a needle into the blood-vessel thereby causing a destruction of the endothelial wall of the blood-vessel. The physiological reaction of platelets is the occlusion of endothelial lesions. Reaction of platelets induced by endothelial lesions lasts about 10 ms. Each blood sampling procedure should therefore activate platelets. A simple platelet test-system was designed following these considerations. Blood samples were collected twice, in EDTA-buffer and in EDTA-formalin-buffer. Activated (aggregated) platelets were fixed by formalin or dissolved in EDTA-buffer. Platelet-reactivity (PR) was calculated as quotient of the number of platelets remaining in the supernatant of both samples after centrifugation. The PR-index-values strongly depended on the blood-sampling procedure. Standardization of the blood sampling procedure led to normal distributed PR-index-values in 110 healthy controls (0.98 +/- 0.09). PR-index-values remained constant during a period of 260 days. PR-index-values in 49 patients suffering from encephalomyelitis disseminata were 1.04 +/- 0.15 and 1.64 +/- 0.6 in 72 patients suffering from transitoric ischemic attacks. Differences between healthy controls and patients suffering from TIAs were significant (p less than 0.001).

A retrospective long-term analysis of the epidemiology and features of drug-induced headache

Abstract Drug-induced headache is well known to resul from the abuse of compounds taken for the treatment of primary headache. The features of drug-induced headache depend on various features including the availability of drugs, the regional health system, and psychogenic factors of the patients. We performed a retrospective study on a series of 257 consecutive German patients presenting with drug-induced headache during the period 1983–1996. Our aim study was to evaluate the demographic features, the frequency of various drugs used, in particular of ergotamine derivates, and changes in these features during the study period. The frequency of drug-induced headache among all headache patients was 8%, with a female preponderance of 81%. Drug-induced headache occurred in all age groups, predominantly in migraine patients (35%). The mean number of substances used was 2.7, mainly, acetaminophen (47.9%), ergotamine tartrate (45%), and combined analgesics (56%). We did not find a significant difference between the associations with ergotamine tartrate and dihydroergotamine, although the latter was taken less frequently. Comparing the early and late years of our study period, there were no changes in the frequency of drug-induced headache (8% versus 7%), although changes in the frequency of some drugs changed (barbiturates, ergotamine tartrate, and codeine intake decreased whereas nonsteroidal anti-inflationary drugs, combined analgesics, and sumatriptan intake increased). Our data suggest that changes in drug availability and the introduction of classification criteria and treatment recommendations did not have a major impact on the frequency of drug-induced headache.

Determination of cerebral perfusion by means of planar brain scintigraphy and99mTc-HMPAO in brain death, persistent vegetative state and severe coma

A total of 24 patients with clinical evidence of brain death (n=17), severe coma (n=2; GCS≈3) and apallic syndrome (n=4) underwent a comparative investigation with99mTc-HMPAO brain scintigraphy, EEG, auditory and somatosensory evoded potentials. Accompagnied by EEG and evoked potentials, brain scintigraphy enabled confirmation of cerebral death in 15/17 patients. In one case clinical examination and evoked potentials suggest brain death, but cerebral perfusion and EEG were normal (“brain stem death”). One patient with evidence of cerebral death in clinical examination, brain scintigraphy and evoked potentials, showed questionable focal EEG activity; however, autopsy revealed intravital autolysis of the entire brain. All patients with apallic syndrome and deep coma showed a distinct cerebral perfusion, but gross EEG abnormalities; evoked potentials were delayed or absent. Planar scintigraphy with99mTc-HMPAO appears to be superior to neurophysiological techniques discriminating patients with agonal cerebral dysfunction from those with brain death.

Paraneoplastic subacute cerebellar degeneration in Hodgkin's disease: Report of three cases and review of the literature

12 cases of paraneoplastic cerebellar degeneration with Hodgkins disease have so far been reported. Three additional patients (Stage II-IA/IIA/IIIB) are presented. Although CT and MR-imaging (MRI) revealed a marked cortical atrophy of the cerebellum, there was no evidence of direct brain involvement. After irradiation and chemotherapy all patients showed a complete remission. There was no evidence of primary disease after an observation period of 3/2/5 years. Cerebellar symptoms also showed a partial remission. As compared to the literature, our treatment appears to be more favorable, probably due to the fact, that therapy was more aggressive than usual.

Acetylsalicylic acid vs. metoprolol in migraine prophylaxis--a double-blind cross-over study.

SYNOPSIS

Single Photon Emission Computed Tomography with Technetium-99m Hexamethyl Propylenamino Oxime in the Pain-Free Interval of Migraine and Cluster Headache

Thirty-three headache-free patients (19 F/14 M) suffering from common (n = 9) and classic migraine (n = 19) as well as cluster headache (n = 5) were investigated using the flow tracer 99mTc-hexamethyl propylenamino oxime and single photon emmission computed tomography. A regional decrease of cerebral tracer uptake was observed in 16 patients with common migraine, but only in 3 patients with classic migraine and in no patient with cluster headache. In 10 of 15 cases with hemiplegic symptoms during migraine attack the areas of decreased tracer uptake showed a topographic relationship to neurological deficits. It appears that migraine attacks occur in connection with exacerbations of preexisting changes of neuronal activities, cerebral perfusion and metabolism.