D2 receptor blockade by flunarizine and cinnarizine explains extrapyramidal side effects. A SPECT study.

Twenty-six patients under treatment with the calcium channel blockers flunarizine (Fz) or cinnarizine (Cz) were examined-with single-photon emission computed tomography using [123I]iodobenzamide as a ligand. The striatal dopamine D2 receptor-binding potential was determined and found to be reduced by 14 to 63% (39.5 +/- 15.0%; p < 0.0001) in patients compared with age-matched control values. This reduction was larger in 12 patients with extrapyramidal symptoms and was only slowly reversible after discontinuation of treatment. Patients treated for > 6 months had significantly larger reductions than patients treated for a shorter period. Parkinsonian symptoms were only seen in patients older than 50 years. Our findings prove a neuroleptic-like action of Fz and Cz, which seems to be the major reason for their extrapyramidal side effects. Older age and long-term treatment are predisposing factors for these effects.

Epileptic negative myoclonus: An EEG-single-photon emission CT study indicating involvement of premotor cortex.

We report a combined EEG-single-photon emission CT (SPECT) study on a patient with epileptic negative myoclonus (ENM). Clinically, the ENM was characterized by brief repetitive lapses in postural tone of the right upper extremity when the arms were held outstretched, whereas no movement effect was observed during rest. Ictal EEG showed repetitive left frontal spikes with a maximum at electrodes EC1 and F1. EMG silent periods lasting from 100 to 200 ms followed the onset of the EEG transients by a latency of 20 to 40 ms. The N20 component of median nerve somatosensory evoked potentials-representing a biological marker of the location of central fissure-showed a phase reversal between electrodes P3 and C1 and thus was located considerably posterior to the spike maximum. We obtained accurate anatomic reference of cerebral blood flow changes visible on SPECT by a special coregistration technique of MRI and SPECT. SPECT performed during ENM showed a marked regional hyperperfusion in the left middle frontal gyrus and a less pronounced increase in tracer uptake in the left supramarginal gyrus. Our results suggest that ENM is generated by epileptic activity in the premotor area in the middle frontal gyrus corresponding to Brodmann's area 6.

Clinical seizure lateralization in mesial temporal lobe epilepsy: differences between patients with unitemporal and bitemporal interictal spikes.

OBJECTIVE: To compare the reliability of clinical seizure lateralization in temporal lobe epilepsy patients with unitemporal and bitemporal independent interictal spikes and unilateral hippocampal atrophy or sclerosis (HA/HS) on MRI scan. PATIENTS AND METHODS: We studied 11 patients with unitemporal and 10 patients with bitemporal interictal spikes. We calculated a spike ratio by dividing the number of spikes ipsilateral to the side of HA/HS by those occurring contralaterally. RESULTS: Clinical seizure lateralization was correct, i.e., ipsilateral to the side of HA/HS, significantly more often in the unitemporal group. Spike ratios were significantly higher in seizures that were lateralized correctly as compared with both incorrectly and nonlateralized seizures. Within the individual patients, a significant positive correlation between spike ratios and the proportion of correctly lateralized seizures was found. We identified three categories of symptoms according to lateralization accuracy. Category 1 symptoms (version, postictal paresis, and early ictal vomiting/retching) lateralized to the side of HA/HS in 100% of patients in the uni- and bitemporal groups. Category 2 symptoms (dystonic posturing, mouth deviation, postictal dysnomia/dysphasia, and ictal speech) provided a 100% correct lateralization in the unitemporal but not in the bitemporal patients. Category 3 symptoms (nonversive early head turning and unilateral upper extremity automatisms) yielded erroneous lateralization in both patient groups. CONCLUSIONS: We conclude that reliable clinical seizure lateralization in mesial temporal lobe epilepsy can only be achieved in patients with unitemporal interictal spikes, whereas clinical lateralization in patients with bitemporal spikes must be viewed cautiously.

Propagation of interictal epileptic activity in temporal lobe epilepsy.

We recorded interictal spikes with closely spaced scalp electrodes and sphenoidal electrodes in four patients with temporal lobe epilepsy. We used multiple dipole modeling to study the number, three-dimensional intracerebral location, time activity, and functional relationship of the neuronal sources underlying the epileptic spike complexes. In all patients, we found two significant sources generating the interictal spikes which showed considerable overlap in both space and time. Source 1 was located in the mesiobasal temporal lobe and generated a restricted negativity at the ipsilateral sphenoidal electrode and a widespread positivity over the vertex. Source 2 could be attributed to the lateral temporal neocortex and was associated with a relatively restricted negativity at the ipsilateral temporal electrodes and a more widespread positivity over the contralateral hemisphere. The sources were well separated in space, with an average distance of 45 mm between them. The time activities of both sources showed similar biphasic patterns, with the mesial source leading the lateral source by approximately 40 msec, suggesting propagation of interictal epileptic activity from the mesiobasal to the lateral temporal lobe.

Genital automatisms in complex partial seizures.

OBJECTIVE: To determine which brain region is responsible for the generation of sexual automatisms. METHODS: Ninety consecutive patients with medically refractory focal epilepsy (74 with temporal lobe and 16 with frontal lobe epilepsy) referred to an epilepsy monitoring unit were studied. The occurrence of the following sexual automatisms was assessed during prolonged video-EEG monitoring: 1) repeatedly grabbing or fondling the genitals and 2) pelvic or truncal thrusting or similar movements. RESULTS: Five patients repeatedly fondled or grabbed their genitals during or immediately after some of their seizures. All five had temporal lobe epilepsy, as evidenced from prolonged video-EEG monitoring, high-resolution MRI, and good to excellent outcome after epilepsy surgery. Sexual automatisms did not occur with frontal lobe epilepsy. CONCLUSION: Sexual automatisms cannot be related exclusively to frontal lobe seizures. As previously proposed, apparently sexual hypermotoric pelvic or truncal movements are common in frontal lobe seizures, but this study suggests that discrete genital automatisms, like fondling and grabbing the genitals, are more common in seizures evolving from the temporal lobe.

Dynamic changes of plasma lipids and lipoproteins in patients after transient ischemic attack or minor stroke.

PURPOSE: Only few data are available concerning variations of lipids and lipoproteins in the acute stage after ischemic cerebrovascular events. It was the aim of this study to investigate whether the lipid and lipoprotein levels obtained in the first few days after a transient ischemic attack (TIA) or a minor stroke (MS) actually reflect "correct' values or "changed' (ie, false low) values, as in patients after acute myocardial infarction. PATIENTS AND METHODS: Total cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), and triglyceride (TG) levels of 37 unselected patients with TIA or MS were determined within 12-48 hours (Group A) or within 49-168 hours (Group B) after the acute event. After a mean observation period of 15.3 months, all patients were re-examined; the results were compared with those of the baseline evaluation. RESULTS: At the time of the baseline evaluation, TC and LDL-C levels of Group B patients were significantly lower than Group A levels. At the end of the observation period, however, Group A and Group B patients did not differ with regard to all four parameters. In comparison with the baseline examination, the values of Group A patients had not changed. In Group B patients, however, TC, HDL-C, LDL-C, and TG levels had significantly increased. CONCLUSION: Our results strongly suggest that lipid and lipoprotein levels of patients with TIA or MS should be assessed within a maximum of 48 hours after the acute event. If the examination cannot be performed within that period, the determination of reliable values is possible only after several weeks or months.

Preictal SPECT in temporal lobe epilepsy: regional cerebral blood flow is increased prior to electroencephalography-seizure onset.

UNLABELLED: Peri-ictal SPECT provides unique information on the dynamic changes in regional cerebral blood flow (rCBF) that occur during seizure evolution and, thus, could be useful in clarifying the poorly understood interplay of the interictal and ictal states in human focal epilepsy. The regional hyperperfusion observed on ictal SPECT is generally believed to be a consequence of electrical seizure activity. However, recent studies using invasive long-term cortical CBF monitoring have demonstrated that rCBF changes occur up to 20 min prior to ictal electroencephalography (EEG) onset. Because of apparent technical difficulties, no preictal SPECT studies have been reported so far. Therefore, we present our results on two patients with temporal lobe epilepsy in whom preictal SPECT scans were performed fortuitously under continuous video-EEG monitoring control. METHODS: Technetium-99m-hexamethyl propyleneamine oxime was injected 11 min (Patient 1) and 12 min (Patient 2) before clinical and EEG seizure onset, as documented from simultaneous video-EEG monitoring in two patients with temporal lobe epilepsy. We obtained accurate anatomical reference of CBF changes visible on SPECT by a special coregistration technique of MRI and SPECT. RESULTS: Whereas interictal SPECT showed a hypoperfusion of the temporal lobe ipsilateral to the seizure focus, on preictal SPECT, a significant increase in rCBF in the epileptic temporal lobe could be observed. These rCBF changes were not accompanied by any significant changes of the ongoing EEG. CONCLUSION: Our study provides evidence that rCBF is increased in the epileptic temporal lobe several minutes before EEG seizure onset. Thus, rCBF changes observed on peri-ictal SPECT scan cannot be considered a mere consequence of EEG seizure activity but may rather reflect a change in neuronal activity precipitating the transition from the interictal to the ictal state.

C677T MTHFR mutation and factor V Leiden mutation in patients with TIA/minor stroke: a case-control study.

A common C677T mutation in the gene for the enzyme 5,10-methylenetetrahydrofolate reductase (5,10-MTHFR) has been linked to elevated levels of homocysteine and was therefore suspected to be a candidate genetic risk factor for arterial occlusive disease. Another mutation, factor V Leiden, has been established as a common hereditary risk factor for venous thrombosis, but its role in arterial disease remains controversial. We investigated the prevalence of both the C677T MTHFR mutation and the factor V Leiden mutation in 81 patients with transient ischemic attack (TIA) or minor stroke (MS) and in 81 age- and sex-matched control subjects free from clinically manifest vascular disease. We further compared clinical and laboratory data as well as clinical course of patients carrying the factor V Leiden mutation alone or in combination with the C677T MTHFR mutation and mutation-free patients. The prevalence of the MTHFR mutation did not differ between patients and control subjects with 11.1% homozygous carriers in both groups (OR for homozygous carriers 1.0; 95% CI 0.38-2.66). However, there was a trend towards a higher prevalence of carriers of factor V Leiden in patients (12.3%) than in control subjects (4.9%) (OR 2.75; 95% CI 0.83-9.17;p=0.09). Furthermore, we found some evidence that the combined occurrence of the C677T MTHFR mutation and factor V Leiden might unfavorably affect the clinical course of the disease, but the number of respective patients was small. Larger studies with a greater number of carriers of both the C677T MTHFR mutation and factor V Leiden seem therefore warranted.

677C to T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene and plasma homocyst(e)ine levels in patients with TIA or minor stroke.

It was the aim of this study to determine the associations of clinical and laboratory data with plasma homocyst(e)ine levels in patients with transient ischemic attack (TIA) or minor stroke (MS), with special reference to their 677C to T mutation status in the 5,10-methylenetetrahydrofolate reductase (5,10-MTHFR) gene. Seventy-six patients with TIA or MS were investigated at least 3 months after their (last) clinical event. By means of univariate analysis, significant correlations of homocyst(e)ine levels with male gender (P<0.02), age (P<0.0005), creatinine levels (P<0.0002), folate levels (inversely, P<0.05), and alcohol use (P<0.02) were found, but not with vitamin B12 levels. Multivariate regression analysis, including age, creatinine levels, and folate levels as independent variables, revealed age (P<0.01) and creatinine levels (P<0.02) to be significantly correlated with homocyst(e)ine levels. After adjustment for age, creatinine levels and homocyst(e)ine levels remained significantly correlated to each other (P<0.005), whereas the relation between folate levels and homocyst(e)ine levels was no longer significant (P=0.10). Mutation-positive patients exhibited moderately and statistically non-significantly higher homocyst(e)ine levels than mutation-negative patients, particularly those who were homozygous positive. Homocyst(e)ine levels were closely correlated with creatinine levels (P<0.0002) and with folate levels (inversely, P<0.05), but only in mutation-positive and not in mutation-negative patients. Homozygous positive, heterozygous positive, and mutation-negative patients did not differ with respect to clinical and laboratory data concerning 'risk factors for stroke' or co-existing vascular disease. In conclusion, the associations of creatinine levels and, inversely, of folate levels with plasma homocyst(e)ine levels in patients with TIA or MS are dependent on the 5,10-MTHFR mutation status. Significant correlations between these variables were found only in mutation-positive but not in mutation-negative patients.

The relation between erythrocyte volume and folate levels is influenced by a common mutation in the methylenetetrahydrofolate reductase (MTHFR) gene (C677T).

BACKGROUND: The enzyme 5,10 methylenetetrahydrofolate reductase (MTHFR) plays an important role in folate metabolism and folate-dependent reactions. Homozygosity for a common polymorphism in the MTHFR gene (C677T, Ala to Val) is associated with an increased risk of neural tube defects and hyperhomocysteinemia in individuals with low folate levels. Homozygous carriers of the polymorphism with adequate folate levels, on the other hand, seem to be at lower risk for colorectal cancer. Homozygous carriers of the polymorphism (5-15% of the white population) probably represent a subpopulation with increased folate needs. Hematological sequelae of folate deficiency have been recognized for a long time. However, no data exist concerning the relation between the C677T MTHFR polymorphism, folate levels, and hematological parameters. METHODS: We investigated associations between the C677T MTHFR polymorphism, folate levels, total plasma homocysteine, and hematological parameters in 94 patients with cerebrovascular disease (transient ischemic attack/minor stroke) and in 82 healthy subjects. RESULTS: Homozygous carriers (VV) of the polymorphism with low folate levels showed significantly higher homocysteine levels than mutation-negative (AA) and heterozygous (AV) subjects (P = 0.038). Furthermore, VV subjects in the lowest folate quartile exhibited significantly higher mean erythrocyte volumes (MCV) and a tendency towards higher erythrocyte hemoglobin content (MCH) than AA and AV subjects (P = 0.008 and 0.069, respectively). Although MCV was not influenced by folate levels in AA and AV subjects, in VV subjects a significant inverse correlation with folate levels could be demonstrated (P = 0.544 and 0.020, respectively). CONCLUSION: We demonstrate an association between the C677T polymorphism, folate levels, and hematological parameters. The elevation of MCV in homozygous carriers of the polymorphism with low folate levels indicates impaired DNA synthesis and/or methylation in these subjects. Considering our data and the results of previous studies, the polymorphism may have contrary effects on homocysteine metabolism and DNA synthesis/methylation dependent on a subject's folate supply. Although the polymorphism is disadvantageous in homozygous carriers with low folate levels, its presence may be beneficial in individuals with adequate folate supply.

Health-related quality of life (HRQOL), activity of daily living (ADL) and depressive mood disorder in temporal lobe epilepsy patients.

We determined the interrelations of chronological age, age at seizure onset, duration of seizure disorder, cognitive functioning (IQ), scales of activities of daily living, depressive mood disorder and measures of health-related quality of life (HRQOL). Furthermore, we investigated the association of the laterality of seizure onset zone and absence/presence of hippocampal atrophy and/or sclerosis (HA/HS) with measures of HRQOL, activities of daily living (ADL) and depressive mood disorder. In the setting of pre-surgical epilepsy evaluation, a sample of 56 patients with temporal lobe epilepsy (TLE) was studied using the Bonner Skalen für Epilepsie (BPSE) and the depression inventory D-S of von Zerssen. Patients reported high levels of dependency on others and poor coping capabilities. Our data also showed specific ADL-behaviour suggesting social withdrawal and isolation. Our results indicate emotional impairment as a major problem in TLE, because 45% of our patients scored in the depressive range of the D-S depression scale. Depression score was found to be a powerful predictor of self-reported quality of life after adjusting for seizure-related variables, demographic variables and cognitive functioning (IQ). The only scale showing a significant laterality effect was ADL-home. No relationship between the dependent measures of HRQOL, ADL-social, ADL-cultural, depressive mood disorder and laterality of the epileptogenic zone or absence/presence of HA/HS was found. HRQOL and depressive mood disorder are strongly interrelated indicating that patients with depressive symptoms report lower quality of life and specific patterns of ADL. HRQOL, ADL and depressive mood disorder are largely independent of biological markers such as laterality of seizure onset zone and absence/presence of HA/HS in TLE.

[Polypragmasy in chronic tension headache?]. / Polypragmasie beim Spannungskopfschmerz?

The various forms of treatment (drugs as well as non-drug therapy) of patients suffering from tension type headache are presented. Analgesics and non-steroidal antirheumatics are used in the management of episodic tension type headache, as well as acute exacerbation of chronic tension type headache. In view of the presumably multifactorial pathogenesis, a multidimensional therapeutic approach is required in patients with chronic tension type headache. Antidepressive drugs (thymoleptics) are usually prescribed as basic therapy. Additional implementation of non-drug therapeutic measures tailored to individual symptomatology is advisable, such as EMG biofeedback, other relaxation techniques, massage, physiotherapy and--in selected cases--psychotherapy or acupuncture.

[Cocaine abuse--with special reference to cerebrovascular complications]. / Cocain-Missbrauch--unter besonderer Berücksichtigung zerebrovaskulärer Komplikationen.

The role of drug abuse as a risk factor for cerebrovascular events has been underestimated, particularly in patients with juvenile stroke. The drug most often associated with acute cerebrovascular events is cocaine. After cocaine hydrochloride abuse intracerebral hemorrhages or subarachnoid hemorrhages--predominantly caused by ruptured aneurysms or arteriovenous malformations--are by far the most frequently observed cerebrovascular complications, whereas on abuse with the alkaloidal form ("crack") intracranial hemorrhages and ischemic strokes are encountered with equal frequency. In most cases, the time interval between drug abuse and the cerebrovascular event is less than 3 hours. Several pathophysiological mechanisms are discussed as serving as triggers for the cerebrovascular event, either alone or in combination. No specific antidote to cocaine is known. Nevertheless drug screening (urine analysis) should be performed immediately to allow optimal management of patients with drug-associated acute cerebrovascular events, especially in cases with juvenile stroke.

[Tension headache--new evaluation of symptomatology based on International Headache Society diagnostic criteria]. / Spannungskopfschmerz--Neubewertung der Symptomatologie anhand der IHS-Diagnosekriterien.

This study presents the history and clinical findings in 80 patients suffering from tension-type headache diagnosed according to the criteria (group 2) proposed in 1988 by the Headache Classification Committee of the International Headache Society (IHS). The aim of this investigation was to evaluate the extent to which the symptomatology in our cases still corresponds with the clinical picture of tension headache described in the older literature. A positive family history of headache was obtained in 59% of the patients; mothers of headache patients were affected five times more often than fathers; a history of migraine was reported as frequently as tension-type headache in the families of the investigated patients. The first manifestation of headaches arose almost exclusively in the first four decades of life, whereby two peaks (15-20 and 35-40 years) were observed in patients with the episodic form. Headache in younger patients showed no distinct diurnal pattern; headache in older patients, however, predominantly occurred immediately after awakening from sleep or in the morning. Changes of weather and psychosocial stress were the most frequent precipitating factors; additionally, the premenstrual period, occupational stress, and sleep deprivation were precipitating factors in female patients. Bilateral pain was most often located in the occipital/nuchal, in the frontal, and the periorbital regions. Headache was usually described as pressing/tightening in quality. Difficulties in concentration and the need of rest were the most important associated symptoms. Photophobia, phonophobia and autonomic symptoms were less frequent and are probably partially drug-related and may also be due to the fact that the selected group of patients suffered from severe forms of headache. 33 of our 80 patients belonged to the subgroup "with disorders of pericranial muscles" (IHS criteria: groups 2.1.1., 2.2.1). A remarkable low percentage of patients, especially of the male sufferers, reported regular smoking and/or drinking habits. Oral contraceptives influenced neither frequency nor intensity of headache attacks. Signs of depressive disorders were present in 28% of the female patients. The differences in symptomatology of tension-type headache between patients with episodic and chronic forms, between female and male patients, and also between younger and elderly patients are documented and have to be taken into account in the diagnostik evaluation of this condition.

[The postictal state. A clinically oriented observation of patients with epilepsy]. / Der postiktale Zustand. Eine klinisch orientierte Betrachtung bei Patienten mit Epilepsie.

UNLABELLED: Epileptic seizures are followed by dynamic alterations in neurologic function in the postictal period which have received little attention by clinicians over a long period of time. We therefore retrospectively studied videotapes of 160 patients with focal epilepsy who underwent presurgical evaluation, for the occurrence of postictal symptoms to determine whether these phenomena have any localizing or lateralizing value in defining the seizure onset zone. RESULTS: (1) We found postictal paresis in 22 of 160 patients (18.8%) in each case contralateral to the hemisphere of seizure onset. (2) 'Perservative' automatisms which start during the ictus and continue in the postictal period occurred in 25.2% of 135 patients with temporal lobe epilepsy but not in patients with frontal lobe epilepsy. (3) Sexual automatisms defined as manipulations of the genitals were found exclusively in patients with temporal lobe epilepsy (in 5.9% of 135 patients). (4) Postictal 'Nose-wiping' was evident in 51.3% of 76 temporal lobe epilepsy patients but only in 12.0% of 25 extratemporal lobe epilepsy patients and was performed with the hand ipsilateral to the hemisphere of seizure onset in 86.5% of all temporal lobe seizures. (5) Postictal language disturbances were observed only in patients with temporal lobe epilepsy (34% of 97 patients) and pointed to a seizure onset in the dominant hemisphere in 80.8%. We conclude that postictal phenomena can provide reliable information for the localization of the seizure onset zone in patients with complex partial seizures. Thus, more attention should be given to the postictal state during presurgical epilepsy monitoring.

Clinical symptoms in psychogenic seizures.

PURPOSE: To develop a classification system of psychogenic seizures based on characteristic clinical symptom clusters and sequences in order to facilitate the correct differential diagnosis of epileptic seizures. METHODS: We analysed the symptoms: clonic movements, hypermotor movements, trembling and tonic posturing of the upper/lower extremities, pelvic thrusting, stiffening of the body, version, side-to-side-head movements, non-versive head-turning and falling to the floor. We did this in a series of 16 patients with psychogenic seizures documented with prolonged video EEG monitoring. Nine patients (7 with frontal lobe epilepsy and 2 with primary generalised epilepsy with tonic, clonic seizures) served as a control group. RESULTS: We classified psychogenic seizures into 3 groups, namely (1) atonic psychogenic seizures, (2) psychogenic motor seizures and (3) psychogenic hypermotor seizures characterised by (1) falling to the ground, (2) trembling in the upper/lower extremities and (3) pelvic thrusting in combination with beating and kicking. While version exclusively occurred in epileptic seizures (incidence = 20%) and side-to-side head movements were only observed during psychogenic seizures (incidence = 8%), all other analysed symptoms were observed in both psychogenic and epileptic seizures. CONCLUSION: Our classification scheme should be useful in terms of permitting a more comprehensive clinical assessment of psychogenic seizures and their underlying psychiatric disorders. Furthermore, the differential diagnosis of psychogenic seizures should be considerably improved.

[Sumatriptan--side effects and problems in routine clinical practice]. / Sumatriptan--Nebenwirkungen und Probleme beim Einsatz im klinischen Alltag.

AIM: The study tried to investigate the efficacy, adverse events and possible risk factors of sumatriptan in daily clinical practice. PATIENTS AND METHODS: 72 outdoor patients, who had treated their headaches at least once with sumatriptan, partly prescribed to them by outdoor physicians, were asked about their experiences with the drug. According to the criteria of the International Headache Society (1988) 55 patients were suffering from migraine, 11 from cluster headache and 6 from tension-type headache. RESULTS: Migraine and cluster patients rated the drug as effective as described in literature. Adverse events were reported by 69% of the patients which was more frequent than in most clinic studies described. Adverse events were usually not serious and transient. They were reported significantly more often by migraine patients than by patients with cluster headache and might not all be correlated to the therapy of sumatriptan. CONCLUSION: Sumatriptan has shown to be effective in the treatment of an acute migraine- and cluster-headache. The risk as to severe adverse events, especially cardial adverse events, exists if contraindications for sumatriptan are not considered. Sumatriptan should therefore only be prescribed to carefully diagnosed migraine and cluster headache patients. It should, however, not be given to patients suffering from drug abuse, because they might just change over to sumatriptan.

[Stroke and intracranial hemorrhage after cocaine abuse]. / Schlaganfälle und intrakranielle Blutungen nach Kokainmissbrauch.

Cocaine abuse as a risk factor for acute cerebrovascular events has received too little attention, in particular in young patients. Cocaine hydrochloride causes mainly intracerebral and subarachnoidal bleeding, while crack (freebase) causes intracranial hemorrhage and ischemic infarctions with equal frequency. Although no specific antidote is known, an attempt should be made to detect the substance or its metabolites in the urine so as to provide optimal management, and encourage the patient to seek expert counselling.

Heparin lowers plasma levels of activated factor VII.

Based on heparin's antithrombin and anti-FXa activity and its in vitro inhibition of activated factor VII (FVIIa) activity, we hypothesized that unfractionated heparin (UFH) may decrease plasma levels of FVIIa in humans. Therefore, 10 healthy young male volunteers received an intravenous UFH infusion over 24 h. Heparin decreased FVIIa levels by 30% (95% CI 14-47%) at 12 h, which was sustained until 24 h. In contrast, neither the substrate pool (i.e. total factor VII) as measured by FVII antigen nor FVII activity were affected by UFH. These results may improve our understanding of the regulation of FVIIa levels and heparin's mode of action.

[Hyperhomocyst(e)inemia--an independent risk factor of stroke]. / Hyperhomocyst(e)inämie--ein unabhängiger Risikofaktor des Schlaganfalls.

The total of free and protein-bound homocysteine including its derivatives is usually summarised as "homocyst(e)ine [H(e)]". Several congenital enzyme deficiencies may cause markedly elevated H(e) plasma levels, leading to the well-known clinical syndromes of homocystinuria. Recently, mild hyperhomocyst(e)inemia has been recognised as an independent risk factor for ischaemic cerebrovascular disease, coronary heart disease, and peripheral artery disease. H(e) levels are also related to the extent of atherosclerotic vessel wall alterations. The role of mild hyperhomocyst(e)inemia in venous thromboembolic disease, however, is not yet clear. A considerable proportion of patients with mild hyperhomocyst(e)inemia suffers from a deficiency of folate, vitamin B12, and/or vitamin B6. Supplementation of these agents--alone or combined with betain--leads to a decrease or even to a normalisation of elevated H(e) levels in the majority of such patients. Hitherto, no prospective randomised studies dealing with the clinical efficacy of such a--probably innocuous--supplementation have been performed. In the meantime, adequate alimentary intake of folate should be ensured.