Biomedical subjects
Publications and source records attributed to K H Grotemeyer.
Chronic headache is an independent clinical picture. Headaches are to be interpreted as a warning sign from the body until this is excluded through differential diagnostics. The clarification and the initial treatment should be carried out by a neurologist to ensure sufficient diagnostic certainty.
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Piracetam has been shown to inhibit platelet aggregation. Therefore, we performed a double-blind, randomized, parallel group study to compare the efficacy of daily 1600 mg piracetam t.i.d. vs. 200 mg acetylsalicylic acid (ASA) t.i.d. in secondary stroke prophylaxis. 563 patients after stroke as confirmed by computed tomography (CT) or magnetic resonance imaging (MRI) were enrolled and received either piracetam or ASA during a 2 year follow-up period. The primary endpoint was the rate of stroke, transient ischaemic attack (TIA), or death from vascular cause. The secondary endpoint was the rate of adverse events leading to a premature discontinuation of the study medication. Patients were visited at home every 3 months and were examined in hospital after 1 and 2 years. At every visit, the platelet function was evaluated. No significant difference and no significant equivalence could be shown for the primary endpoint between the piracetam and the ASA group both in the intention-to-treat and in the per-protocol analysis. However, there was a not significant trend in favor of ASA (11.7 vs. 15.2%). After excluding those patients who did not respond to antiplatelet medication in vitro, however, piracetam and ASA were equivalent in secondary stroke prophylaxis (stroke, TIA, or vascular death 10.1% in the piracetam group vs. 9.7% in the ASA group). Piracetam was significantly superior to ASA in the secondary endpoint (P=0.0039). The data suggest that the overall efficacy of piracetam in secondary stroke prophylaxis is not as good as that of ASA but that piracetam is better tolerated. However, our data furthermore show that nonresponders to pharmacological inhibition of platelet function are more frequent under piracetam therapy and that they may influence the results of large studies on secondary prophylaxis in vascular diseases.
OBJECTIVES: A total of 670 patients were screened for distal symmetric HIV-associated polyneuropathy during CDC stages 1-3 and its correlation to immunological deterioration. MATERIAL AND METHODS: Clinical examinations of 670 patients admitted to the neurological outpatient clinic at the Department of Neurology, University of Munster. Neurophysiological investigations were performed on the sural and peroneal nerve for detection of axonal and myelin lesion. RESULTS: Clinical examination proved progressive clinical signs and symptoms indicating distal symmetric polyneuropathy from CDC 1 (32%) to CDC 3 (55%). At least one neurophysiological result was impaired in CDC 1 in 25% and in CDC 3 in 45%. Significant correlation between neurophysiological changes and CDC4(+)-cells and beta-microglobuline were detected for stage CDC 3 C. CONCLUSION: Results show stage related prevalence of distal symmetric polyneuropathy already in early stages. In late stages of HIV-infection prevalence of distal symmetric polyneuropathy seems to be directly correlated to immunodeficiency syndrome. The pathogenesis of distal symmetric polyneuropathy during HIV-infection is up to now incompletely understood, but results indicate a clear dependency between progressive immunological dysfunction and neuropathy. High active antiretroviral therapy in patients suffering from distal symmetric polyneuropathy is a main topic of future studies.
The effects of a bioflavonoid mixture, Pycnogenol, were assessed on platelet function in humans. Cigarette smoking increased heart rate and blood pressure. These increases were not influenced by oral consumption of Pycnogenol or Aspirin just before smoking. However, increased platelet reactivity yielding aggregation 2 hours after smoking was prevented by 500 mg Aspirin or 100 mg Pycnogenol in 22 German heavy smokers. In a group of 16 American smokers, blood pressure increased after smoking. It was unchanged after intake of 500 mg Aspirin or 125 mg Pycnogenol. In another group of 19 American smokers, increased platelet aggregation was more significantly reduced by 200 than either 150 mg or 100 mg Pycnogenol supplementation. This study showed that a single, high dose, 200 mg Pycnogenol, remained effective for over 6 days against smoking-induced platelet aggregation. Smoking increased platelet aggregation that was prevented after administration of 500 mg Aspirin and 125 mg Pycnogenol. Thus, smoking-induced enhanced platelet aggregation was inhibited by 500 mg Aspirin as well as by a lower range of 100-125 mg Pycnogenol. Aspirin significantly (p<0.001) increased bleeding time from 167 to 236 seconds while Pycnogenol did not. These observations suggest an advantageous risk-benefit ratio for Pycnogenol.
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Ergotamine abuse and subsequent ergotamine-induced headache is a common problem in the pharmacological treatment of migraine and other headache types; often, withdrawal therapy is necessary. This study investigated whether ergotamine abuse affects information processing and whether withdrawal therapy can lead to an improvement of information processing. We designed a standardized neurophysiological retrospective (ergotamine abuse) and prospective (ergotamine withdrawal) study in a supraregional headache outpatient clinic. Seventy-one patients abusing ergotamine derivatives with subsequent daily headache were enrolled and compared to 36 migraine patients without ergotamine intake and 36 healthy subjects. Information processing was evaluated by latencies and amplitudes of visually evoked event-related potentials (ERP) before and after ergotamine withdrawal therapy. P3 latency of the ERP was significantly increased in ergotamine abuse (442 +/- 45 ms) versus migraine (415 +/- 40 ms) and healthy subjects (410 +/- 33 ms), there was no difference between ergotamine tartrate and dihydroergotamine abuse. The migraine specific loss of habituation in information processing as measured by P3 latency could not be observed in migraine patients with ergotamine abuse. After successful withdrawal therapy in 36 patients, the abnormally prolonged P3 latency was significantly shortened (452 +/- 47 ms versus 433 +/- 30 ms; P < 0.004). Our findings imply that information processing is impaired by ergotamine abuse and can be improved but not normalized after withdrawal therapy. Furthermore, our data provide strong evidence that ergotamine, besides its peripheral effects, has a central mode of action.
Drug-induced headache is well known to result 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.
Migraine patients show a specific cognitive processing with a loss of habituation in the interval and a normal habituation in the attack as measured by event-related potentials (ERPs). It is unknown whether the loss of habituation changes during the migraine interval or is a stable state. Serotonin (5HT) metabolism is involved in the pathophysiology of migraine and also in the generation of ERPs. We enrolled 14 patients with regular migraine attacks in order to measure visually evoked ERPs repetitively during the migraine interval and in the migraine attack. Cognitive habituation was evaluated by analysis of P3 latency. Platelet serotonin content and free serotonin plasma level were measured at the same time points. The loss of habituation increased continuously during the migraine interval and abruptly normalized in the migraine attack (p < 0.05, time series analysis). The platelet 5HT content decreased significantly in the migraine attack (p < 0.03) and was at its maximum in the middle of the interval. The P3 latency was significantly increased in the attack (p < 0.01) and was significantly inversely correlated with the platelet 5HT content (r = -0.44, p < 0.001). Free 5HT plasma levels did not show any significant change. Our findings suggest that loss of cognitive habituation continuously increases during the migraine interval until its normalization in the migraine attack. This phenomenon cannot be attributed to serotonergic transmission. In patients with regular changes of cognitive habituation before the migraine attack, it might be possible to predict the attack by analysing ERPs.
This paper reviews the effects of piracetam on platelet function and the evidence for its antiplatelet effect which is mediated mainly by inhibition of platelet aggregation. Piracetam also possesses antithrombotic activity in vivo. It has been shown to normalize platelet aggregation in patients with increased platelet aggregability in various disorders including acute stroke, transient cerebral ischemic attacks and diabetes mellitus. This, together with clinical improvement, has also been shown in patients with Raynaud's phenomenon. The results of recent studies are presented in which piracetam showed similar efficacy to aspirin in the secondary prophylaxis of ischemic stroke.
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.
OBJECTIVE: To investigate progression of peripheral and central sensory tract lesion and its correlation to immunological deterioration. METHODS: Clinical and neurophysiological investigation (evoked potentials of the median and tibial nerve) and immunological parameters (CD4-cells, beta 2-microglobuline) were followed up in 160 patients (24 females, 136 males, HIV infection for 2.7 +/- 2.3 years, mv +/- 1 sd) up to four times over approximately 3 years regardless of disease stage and evidence of neurological symptoms. Recordings were done using needle electrodes over the Th12 and C7 spinous process and from the scalp (10/20 system) in the conventional manner. Statistical analysis was performed intraindividually and in comparison to normal laboratory values (n = 96). RESULTS: All parameters deteriorated during the follow-up period. Statistical analysis showed significant differences between probands and patients for evoked potentials, but also a significant deterioration for evoked potentials after three years at the end of the follow-up study. A significant correlation between progressive impairment of evoked potentials and laboratory data was found. CONCLUSION: HIV infection induces a progressive lesion of the ascending sensory tracts. The results indicate a peripheral neuropathy as well as a progressive lesion of the ascending central sensory tracts. Pathogenesis of polyneuropathy and of central sensory tract lesion is up to now conjectural. Laboratory investigations indicate a clear-cut correlation between immunological alterations induced by HIV infection and its neurologic manifestation on ascending sensory tracts.
We investigated the impact of antiretroviral treatment on event-related potentials (ERP) as a possible marker of AIDS dementia. A total of 154 HIV-infected patients without central nervous system (CNS) neoplasm or opportunistic infection were examined and randomized to receive either zidovudine 500 mg/day or no antiretroviral treatment. The participants were prospectively examined by visually evoked ERP in a longitudinal design. Latencies and amplitudes of ERP were evaluated at the beginning of the study, after 1 year, and after 2 years. After 1 year, 98 patients could be analyzed, 47 of whom were taking zidovudine. In the treatment group, P3 latency was 419 +/- 55 msec at baseline and 424 +/- 52 msec at follow-up (not significant). In the patients without treatment, P3 latency was 437 +/- 42 msec at baseline and 462 +/- 53 msec at follow-up (p < .0001, Wilcoxon test). A significant inverse correlation existed between P3 latency and CD4 cell count in both groups. The increase of P3 latency in untreated patients and a stable P3 latency in treated patients could be confirmed in a subgroup analysis of 21 patients with a follow-up of three examinations in a 2-year period. Our data suggest that zidovudine has a positive impact on AIDS dementia as measured by ERP. This finding was observed in patients in different stages of HIV infection, thus suggesting that zidovudine is indicated in all stages of HIV infection to treat encephalopathy.
The central effects of acetylsalicylic acid (ASA) are discussed controversially. In animal models, it has been shown that ASA can interact with the central serotonergic and catecholaminergic neuronal system. However, the relevance of this interaction for humans is still unknown. We performed a study on the influence of ASA on central cognitive processing. In 25 healthy subjects (age 21-56 years), visually evoked event-related potentials (ERP) and reaction time under IV ASA medication were recorded. ERP were evoked by an oddball paradigm. As compared to placebo, ASA decreased the latency of the P3 component significantly in a time interval of 20-40 min after administration. The latency of the N2 component was significantly decreased about 25 min after administration; the latency of the exogenous P2 component was not influenced by ASA. The mean choice reaction time was significantly decreased by ASA 35 min after administration. At this time point, there was a significant correlation between decrease in reaction time and increase in ASA plasma level. The data show that IV administration of ASA has an accelerating effect on the endogenous components of visual ERP and on reaction time. This finding suggests that ASA can influence central cognitive processing, possibly by ASA induced changes of neurotransmitters. Since serotonin can be released by ASA and serotonin release leads to a decrease of ERP latencies. we assume that ASA most likely influences cognitive processing via the central serotonergic transmitter system.
Chronic renal failure frequently causes uremic encephalopathy with impairment of different cognitive functions, but the pathophysiology of uremic encephalopathy is still unknown. We measured visually evoked event-related potentials (ERPs) in 33 neurologically asymptomatic patients before and after they underwent hemodialysis and compared their data with those of a strictly age-matched healthy control group. Before hemodialysis, the patients' P3 latency was significantly increased and P3 amplitude was significantly decreased as compared with that of the healthy control group. After hemodialysis, P3 latency of the patients showed a significant decrease (457+/-56 before and 438+/-54 ms after hemodialysis) and the P3 latency habituation during the ERP measurement was also significantly decreased. Patients with higher levels of blood urea nitrogen (BUN), creatinine, and uric acid performed better in ERP measurement than did patients with lower levels. Hemoglobin did not influence ERP latencies and amplitudes. Our data suggest that impaired cognitive processing can be disclosed by ERP even in neurologically asymptomatic chronic renal disease. Removal of uremic toxins by hemodialysis leads to an improvement in cognitive processing.
There is strong evidence for a loss of habituation during cognitive processing in migraine as measured by P300 and contingent negative variation in adults. Event-related potentials evoked by an oddball paradigm have not yet been studied in children and adolescents suffering from different primary headache types. We recorded visually evoked event-related potentials (two consecutive trials, 200 stimuli each) in 48 children and adolescents suffering from migraine without or with aura, from episodic tension-type headache, and from ergotamine-induced headache and analyzed the latencies, amplitudes, and reaction times. No statistically significant differences were noted between all headache types and healthy controls analyzing the averaged parameters for the whole measurement. However, a highly significant loss of cortical habituation as measured by P300 amplitude and latency could be observed in migraine without and with aura by analyzing the first and the second trial of measurement separately. This phenomenon increased with age and could not be seen in healthy controls, or patients with tension-type headache or ergotamine-induced headache. Our data suggest a specific cognitive processing in migraine even in children and adolescents. Measurement of the habituation effect in P300 latency and amplitude provides a specific method to differentiate between primary headache types in childhood and adolescence.
BACKGROUND: Hyperhomocysteinemia has been shown to be a mild independent risk factor for premature atherosclerosis, and there is evidence of an increased rate of peripheral vascular occlusive disease, myocardial infarction, and stroke. OBJECTIVE: To evaluate clinical, biochemical, and neurophysiological findings in patients with ischemic stroke with and without hyperhomocysteinemia. SUBJECTS: One hundred twenty-five consecutive patients with a history of stroke and 60 healthy control subjects. METHODS: Patients were divided into those with and those without hyperhomocysteinemia, which was defined as blood levels beyond the mean total plasma homocysteine level plus 2 SDs of the healthy control group. History, symptoms, cause, patterns of infarction, biochemical data, continuous and transcranial Doppler sonography, and event-related potentials were recorded in all patients. RESULTS: Twenty-seven patients had hyperhomocysteinemia. Compared with the 98 patients without hyperhomocysteinemia, they had an increased rate of hypertension (odds ratio, 3.5; 95% confidence interval, 1.0-12.6), an increased level of uric acid (P < .007), an increased hematocrit (P < .02), a higher rate of microangiopathy (odds ratio, 2.8; 95% confidence interval, 1.1-7.2), and a trend to a higher rate of multiple infarction. Furthermore, the P3 latency of the event-related potential was significantly increased in hyperhomocysteinemia (P < .004). CONCLUSIONS: Hyperhomocysteinemia is probably an independent risk factor for stroke, with a prevalence of about 20% in all patients with a history of stroke; however, additional factors (eg, hypertension, hyperuricemia) may have an enhancing effect. There are significant differences in stroke patterns between patients with and without hyperhomocysteinemia, with a higher rate of lesions typical of cerebral microangiopathy and a trend to multiple infarctions in the former. Impairment of cognitive processing as measured by visual event-related potential is more pronounced in hyperhomocysteinemia.