Does spatial cueing affect line bisection in chronic hemianopia?

Patients with homonymous hemianopia often show a contralesional shift towards their blind field when bisecting horizontal lines ("hemianopic line bisection error", HLBE). The reasons for this spatial bias are not well understood and debated. Cueing of spatial attention modulates line bisection significantly in patients with visuospatial neglect. Moreover, recent evidence showed that attention training significantly improves deficits of visual search in hemianopia. Here, we tested in 20 patients with chronic homonymous hemianopia (10 left-sided, 10 right-sided) without visual neglect, 10 healthy control subjects, 10 neurological control patients, and 3 patients with left visuospatial neglect and leftsided hemianopia whether spatial cueing influences the HLBE. Subjects indicated verbally the midpoint of horizontal lines in a computerized line bisection task under four experimental cue positions (cue far left, mid-left, mid-right or far-right within the horizontal line). All 20 hemianopic patients showed the typical HLBE towards their blind field, while the two control samples showed only a small but significant leftward shift (pseudoneglect). None of the 4 cueing manipulations had a significant effect on the HLBE in the hemianopic patients. Moreover, no differential effects of cueing on line bisection results were obtained when analyzed in lesion subgroups of hemianopic patients with circumscribed occipital lesions (N=8) as contrasted with patients having more extended (occipito-temporal or temporal) lesions (N=12). This null-effect contrasts with marked cueing effects observed in 3 neglect patients with left hemianopia in the same tasks, showing the principal efficacy of our cueing manipulation. These results argue against attentional explanations of the HLBE.

[Comprehensive stroke unit]. / Erweiterte Stroke-Unit.

The concept of a "comprehensive stroke unit" (in German: Erweiterte Stroke-Unit) is an additional structural option for those stroke units already certified in Germany. Its aim is to complement the semi-intensive management of stroke unit patients in Germany by early mobilisation and neuropsychological rehab procedures. This concept is recommended in many European countries as well. It is based on the proof of efficacy of the combined treatment package in several randomised controlled trials. According to the Helsingborg Declaration, every stroke patient in Europe should have access to a chain of care best provided by a comprehensive stroke unit. Both early mobilisation and rehabilitation treatment can be integrated and continued without creating an interface between the acute stroke unit and the general neurological or medical ward. The monitoring beds of the acute stroke unit and the non-monitoring "enhanced care" beds are located within the same geographical area of the hospital and are run as a comprehensive stroke care entity. Continuous management of the acute stroke patients by the same team on the same unit means an increase in quality of care, better usage of staff resources and an additional gain in time. The scientific background of the advantages of a comprehensive stroke unit is described as are the structural and staff requirements. The clientel particularly benefiting from treatment on wards with enhanced care beds is described, and the spectrum of treatment services is defined. This concept will be used as the basis for an add-on qualification of already certified German stroke units. An important step was to fit the requirements of the comprehensive stroke unit to the already existing facilities and their infrastructures. From an economic point of view, the comprehensive stroke unit is expected to be cost-effective, either balanced or even positive.

[Headache as a warning symptom]. / Warnsymptom oder eigenständiges Krankheitsbild. Erkennen Sie "gefährliche" Kopfschmerzen?

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.

[Tension headache]. / Spannungskopfschmerz.

The life time prevalence of episodic tension headache ranges between 13-66%, of chronic tension headache between 1-3%. In most studies a slight preponderance of women was found. Approximately 20% of persons afflicted by tension headache seek for medical help. The costs of tension headache are mainly indirect ones due to lost work days. Increased pain sensitivity of the pericranial muscles, psychosocial stress and psychiatric disorders are discussed as main pathophysiological mechanisms. Taking into consideration the uncertainty of the entity "tension headache" tricyclic antidepressants and psychotherapy (biofeedback, stress management therapy, autogenic training) are effective. The superiority of a multicomponent therapy with tricyclic antidepressants and stress management therapy over pharmaceutical and psychotherapeutic treatment or placebo alone was demonstrated in one study.

[Dysfunctional syndromes: their diagnostics and treatment]. / Diagnostik und Therapie funktioneller Schmerzsyndrome.

If a patient presents with symptoms of a functional somatic pain syndrome in the primary care setting, it is important to confirm the diagnosis based on a thorough history and physical examination including selected diagnostic tests to exclude somatic diseases with a similar clinical presentation. Important aspects of psychosomatic medicine in the primary care setting are to discuss the diagnosis, treatment options, and prognosis of the functional psychosomatic pain syndromes with the patient in detail. Patients who present with a functional somatic pain syndrome to secondary or tertiary care centers, should be screened for additional functional pain syndromes. A psychiatric-psychosomatic evaluation might be indicated. Based on criteria of evidence-based medicine, psychotherapy and/or tricyclic antidepressants seem to be the most promising treatment approaches for the functional somatic pain syndromes.

Piracetam versus acetylsalicylic acid in secondary stroke prophylaxis. A double-blind, randomized, parallel group, 2 year follow-up study.

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.

Screening for HIV-associated distal-symmetric polyneuropathy in CDC-classification stages 1, 2, and 3.

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.

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

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.

Inhibition of smoking-induced platelet aggregation by aspirin and pycnogenol.

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.

Dynamic changes of cognitive habituation and serotonin metabolism during the migraine interval.

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.

Piracetam and platelets--a review of laboratory and clinical data.

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.

The impact of ergotamine-induced headache and ergotamine withdrawal on information processing.

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: 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 influence of acetylsalicylic acid on cognitive processing: an event-related potentials study.

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.

Event-related potentials (P300) in primary headache in childhood and adolescence.

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.

Progressive peripheral and central sensory tract lesion in HIV-infected patients evidenced by evoked potentials (a three-year follow-up study).

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.

Influence of end-stage renal failure and hemodialysis on event-related potentials.

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.