Outcome of heparin-treated patients with acute cerebral venous sinus thrombosis: influence of the temporal pattern of intracerebral haemorrhage.

BACKGROUND AND PURPOSE: The influence of temporal patterns of intracerebral haemorrhage (ICH) on the outcome of heparin-treated patients with cerebral venous sinus thrombosis (CVST) has not been examined systematically. METHODS: Temporal patterns of ICH and their influence on survival without disability (modified Rankin Scale score ≤1 point) at hospital discharge were examined in 141 consecutive hospital-admitted patients with acute CVST who were treated with intravenous unfractionated heparin. RESULTS: Of all 141 patients (median age 40 years; 73% women), 59 (42%) had ICH at the time of diagnosis (early ICH). Of these, seven (12%) subsequently had extension of ICH and 13 (22%) had additional ICHs at other locations (delayed ICH). Of 82 patients without early ICH, nine (11%) later had delayed ICH. After a median hospital stay of 26 days, 107 patients (76%) were discharged without disability. Patients with early ICH were less likely to survive without disability until discharge than those without early ICH [63% vs. 85%; risk ratio (RR) 0.73; P = 0.005]. The association was attenuated after adjusting for age, sex and impaired consciousness on admission (RR 0.83; P = 0.03). Taking temporal patterns of ICH into account, early ICH with subsequent complication (extension or delayed ICH) had a larger influence on survival without disability (RR 0.57; 95% confidence interval 0.35-0.95) than early ICH without complications (RR 0.78; 95% confidence interval 0.67-0.91). CONCLUSIONS: Heparin-treated CVST patients were less likely to survive without disability when ICH was present on admission. This association may largely be driven by subsequent extension of haemorrhage or additionally occurring delayed haemorrhage.

Prevalence of stroke and stroke symptoms: a population-based survey of 28,090 participants.

BACKGROUND: Stroke is associated with a considerable burden of disease worldwide. Data about prevalence needs regular updating to facilitate health care planning and resource allocation. The purpose of the present study was to determine stroke prevalence in a large urban population in an easy and reliable way. METHODS: In a population survey a total of 75,720 households with at least 1 person >or=50 years received information about stroke symptoms by mail. In addition, the Stroke Symptom Questionnaire assessing the prevalence of stroke and of stroke symptoms was sent. Stroke prevalence was determined by a single physician-diagnosed stroke-screening question or by the combination of the latter with reported visual impairment and/or articulation problems in the past. RESULTS: A total of 28,090 persons responded (37.5%). Mean (+/-SD) age was 64.4 +/- 9.7 years, 62.9 +/- 8.9 for men (43.3%), and 65.5 +/- 10.2 for women. Of all participants 2.7% reported impaired vision, 2.8% facial weakness, 2.8% articulation problems, 3.9% limb weakness, and 5% sensory disturbances. A total of 4.5% reported a physician-diagnosed stroke (women 4.3%; men 4.9%). Combining reported stroke history with reported impaired vision and/or articulation problems, the prevalence of stroke increased to 7.6% (men 8.4%; women 7.2%). Factors associated with higher prevalence were higher age, male gender, non-German nationality, lower education, positive family history of stroke, and living alone. CONCLUSIONS: The combination of questions concerning a prior stroke and stroke symptoms is a useful and easy approach to assess prevalence. It results in prevalence numbers which might compensate for an underestimation of stroke numbers.

Emergency department delays in acute stroke - analysis of time between ED arrival and imaging.

We determined the factors leading to emergency department (ED) delays in patients with acute stroke. Data were collected prospectively in four Berlin inner-city hospitals by ED documentation, medical records, imaging files and patient interviews. An extended Cox proportional hazards model was fitted to the data. Analyses were performed in 558 patients with confirmed diagnosis of stroke. Median time from admission at ED to beginning of computed tomography/magnetic resonance imaging (CT/MRI) was 108 min. In a subgroup of patients potentially eligible for thrombolysis with a pre-hospital delay <120 min and a National Institutes of Health Stroke Scale (NIHSS) >4 (n = 74), the median interval to imaging was 68 min. Multivariable analysis revealed that a more severe initial NIHSS, a pre-hospital delay <3 h, admission at two specific hospitals, admission at weekends, and private health insurance were significantly associated with reduced delays. In stroke patients, the time interval between ED admission and imaging depends both on factors that emerge from clinical needs and on factors independent of clinical necessities. Considering the urgency of therapeutic measures in acute stroke, there is necessity and room for both improvement of in-hospital management and of medical and non-medical factors influencing pre-hospital delays.

Vertebral artery dissections after chiropractic neck manipulation in Germany over three years.

Vertebral artery dissection (VAD) has been observed in association with chirotherapy of the neck. However, most publications describe only single case reports or a small number of cases. We analyzed data from neurological departments at university hospitals in Germany over a three year period of time of subjects with vertebral artery dissections associated with chiropractic neck manipulation. We conducted a country-wide survey at neurological departments of all medical schools to identify patients with VAD after chirotherapy followed by a standardized questionnaire for each patient. 36 patients (mean age 40 + 11 years) with VAD were identified in 13 neurological departments. Clinical symptoms consistent with VAD started in 55% of patients within 12 hours after neck manipulation. Diagnosis of VAD was established in most cases using digital subtraction angiography (DSA), magnetic resonance angiography (MRA) or duplex sonography. 90% of patients admitted to hospital showed focal neurological deficits and among these 11 % had a reduced level of consciousness. 50% of subjects were discharged after 20 +/- 14 hospital days with focal neurological deficits, 1 patient died and 1 was in a persistent vegetative state. Risk factors associated with artery dissections (e. g. fibromuscular dysplasia) were present in only 25% of subjects. In summary, we describe the clinical pattern of 36 patients with vertebral artery dissections and prior chiropractic neck manipulation.

Petasites hybridus root (butterbur) is an effective preventive treatment for migraine.

OBJECTIVE: To evaluate the clinical efficacy of a standardized special root extract from the plant Petasites hybridus as a preventive therapy for migraine. METHODS: This is a three-arm, parallel-group, randomized trial comparing Petasites extract 75 mg bid, Petasites extract 50 mg bid, or placebo bid in 245 patients with migraine. Eligible patients met International Headache Society criteria for migraine, were ages 18 to 65, and had at least two to six attacks per month over the preceding 3 months. The main outcome measure was the decrease in migraine attack frequency per month calculated as percentage change from baseline over a 4-month treatment period. RESULTS: Over 4 months of treatment, in the per-protocol analysis, migraine attack frequency was reduced by 48% for Petasites extract 75 mg bid (p = 0.0012 vs placebo), 36% for Petasites extract 50 mg bid (p = 0.127 vs placebo), and 26% for the placebo group. The proportion of patients with a > or =50% reduction in attack frequency after 4 months was 68% for patients in the Petasites extract 75-mg arm and 49% for the placebo arm (p < 0.05). Results were also significant in favor of Petasites 75 mg at 1, 2, and 3 months based on this endpoint. The most frequently reported adverse reactions considered possibly related to treatment were mild gastrointestinal events, predominantly burping. CONCLUSIONS: Petasites extract 75 mg bid is more effective than placebo and is well tolerated as a preventive therapy for migraine. Petasites 50 mg PO bid was not significantly more effective than placebo on the primary study endpoints.

High-dose riboflavin treatment is efficacious in migraine prophylaxis: an open study in a tertiary care centre.

The aim of this study was to investigate the efficacy of riboflavin for the prevention of migraine. An open label study was performed in a specialized outpatient clinic. Patients received 400 mg riboflavin capsules per day. Headache frequency, duration, intensity and the use of abortive drugs were recorded at baseline and 3 and 6 months after treatment. Headache frequency was significantly reduced from 4 days/month at baseline to 2 days/month after 3 and 6 months (P < 0.05). The use of abortive drugs decreased from 7 units/month to 4.5 units/month after 3 and 6 months of treatment (P < 0.05). In contrast, headache hours and headache intensity did not change significantly. We could demonstrate a significant reduction of headache frequency following riboflavin treatment. In addition, the number of abortive anti-migraine tablets was reduced. In line with previous studies our findings show that riboflavin is a safe and well-tolerated alternative in migraine prophylaxis.

The management of refractory generalised convulsive and complex partial status epilepticus in three European countries: a survey among epileptologists and critical care neurologists.

OBJECTIVE: To survey the current clinical treatment of refractory status epilepticus and to identify steps in its management which may need further investigation. METHODS: Epileptologists and critical care neurologists were surveyed using a standardised postal questionnaire. RESULTS: Sixty three of 91 participants (69%) returned the questionnaires. Two thirds of the respondents applied another non-anaesthetising anticonvulsant after failure of first line drugs. General anaesthesia for ongoing complex partial status epilepticus (CPSE) was part of the therapeutic regimen of 75% of the interviewees. A non-barbiturate as general anaesthetic of first choice was used by 42%. Up to 70% titrated the anaesthetic to achieve a burst suppression pattern in the electroencephalogram, indicating deep sedation, and 94% reduce anaesthesia within 48 hours. CONCLUSIONS: The management of refractory status epilepticus is heterogeneous in many aspects, even among clinicians who are most familiar with this severe condition. Randomised trials are needed to compare the efficacy, side effects, optimal duration, and depth of general anaesthesia.

Matched-pair comparison of three different approaches for thymectomy in myasthenia gravis.

BACKGROUND: Because of the lack of evidence-based data comparing different techniques for thymectomy (Thx), a matched-pair study was conducted to evaluate the role of thoracoscopic Thx (tThx) more objectively. METHODS: Of 182 patients who underwent Thx, 3 groups according to the operation technique were matched for myasthenia gravis (MG) without thymoma, age, gender, and severity of MG. Twenty patients each who had Thx through anterolateral thoracotomy (aThx), extended median sternotomy (sThx), and tThx were compared for length of operation, postoperative morbidity, complete remission, quantification of improvement of MG, and cosmetic results. RESULTS: Complete tThx required 197 +/- 35 min as compared to 113 +/- 43 min for sThx and 82 +/- 27 min for aThx (P <0.001). With zero mortality the overall postoperative morbidity rate was 25% for sThx versus 15% for aThx and 5% for tThx (P <0.05). There was no difference in complete remission of MG. The median activities of daily living (ADL) scores improved by 6.0 (1-19) after tThx, 5.5 (2-4) after sThx, and 7.5 (0-12) after aThx. Best cosmetic results were achieved after tThx. CONCLUSIONS: There was adequate cumulative medium-term improvement of MG and less postoperative morbidity after tThx, which may become the preferred technique for Thx.

Venous collateral blood flow assessed by Doppler ultrasound after unilateral radical neck dissection.

Removal of the internal jugular vein (IJV) in unilateral radical neck dissection (rND) necessitates redirection of cerebrovenous blood to collateral pathways. If adaptation is insufficient, neurologic sequelae develop that are due to impaired venous drainage and increased intracranial pressure. The authors studied venous hemodynamic effects of unilateral rND using Doppler and duplex ultrasound in 17 patients. Blood flow velocities (BFVs) were recorded from the distal IJV (dIJV) and the vertebral vein (VV) before and 9 to 88 days after surgery. A preoperative compression test of the dIJV was performed to identify the side of dominant drainage. The BFV increased in the contralateral dIJV after right-sided rND (n = 10) by 111% (range, 50% to 320%), and after left-sided rND (n = 7) by 34% (range, 5% to 105%). In the contralateral VV, a rise of BFV by 75% was found. Our results confirm the role of the contralateral dIJV as the predominant collateral pathway. The VVs serve as an important additional major outflow. Doppler ultrasound may help to identify patients at risk of insufficient cerebrovenous drainage after rND.

Valproic acid is effective in migraine prophylaxis at low serum levels: a prospective open-label study.

OBJECTIVE: We evaluated the efficacy of prophylactic valproic acid treatment (6 months) on the frequency of migraine attacks and the number of migraine headache days with respect to serum levels. BACKGROUND: Valproic acid, a GABAergic drug, has been shown to be effective for migraine prophylaxis. Results from several dose- and serum level-adjusted studies have recommended valproic acid doses within a range of 500 to 1500 mg per day for migraine prophylaxis. DESIGN AND METHODS: In this prospective open-label study, 52 patients received valproic acid doses of 300 to 1200 mg per day; 45 patients were treated per protocol. Valproic acid serum levels increased linearly in relation to the valproic acid dose and were between 21 and 107 microg/mL at the end of the treatment period. Patients were divided into two groups: those with valproic acid serum levels less than 50 microg/mL (group 1) and those with serum levels greater than 50 microg/mL (group 2). RESULTS: The frequency of migraine attacks was significantly reduced in group 1 from 3.5 +/- 0.9 to 2.0 +/- 0.9 attacks per month. Migraine headache days also decreased (6.4 +/- 3.5 to 4.6 +/- 2.9 days per month). In the high serum level group, a reduction of migraine attacks from 3.5 +/- 0.9 to 2.8 +/- 1.0 attacks per month and only a slight decrease in headache days (6.4 +/- 3.5 to 6.1 +/- 2.4 days per month) was observed. The outcome of group 1 (low serum level) was significantly better than that of group 2 with respect to both parameters (P<.05). Side effects were generally mild and temporary. CONCLUSIONS: Due to the lack of additional benefit from higher valproic acid doses (more than 600 mg per day), we recommend daily valproic acid doses of 500 to 600 mg with a target serum level less than 50 microg/mL for the prophylactic treatment of migraine.

Neurostimulation of the ventral intermediate thalamic nucleus in inherited myoclonus-dystonia syndrome.

We report on the effects of bilateral neurostimulation of the ventral intermediate thalamic nucleus (VIM) in a patient with medically intractable and progressing inherited myoclonus dystonia syndrome (IMDS). Postoperatively, the patient improved by approximately 80% on the modified version of a myoclonus score without any significant change in the dystonic symptoms. This suggests that neurostimulation of the VIM may be an effective treatment for myoclonus in pharmacologically intractable IMDS.

Perfusion and diffusion magnetic resonance imaging in human cerebral venous thrombosis.

BACKGROUND: Diagnosis of cerebral venous thrombosis (CVT) is usually achieved by digital subtraction angiography or magnetic resonance angiography, while structural brain tissue damage can be assessed by computed tomography or magnetic resonance imaging (MRI). Using perfusion and diffusion weighted imaging (PWI, DWI) we aimed in this study to identify pathophysiological patterns corresponding to only functional and hence reversible tissue involvement. METHODS: PWI, DWI, and conventional MRI were performed in six CVT patients acutely and after 16-26 days when their clinical condition had improved. All patients were treated with partial thromboplastin time-effective intravenous heparin. After intravenous administration of a paramagnetic contrast agent, bolus track PWI allows pixel based determination of mean transit time (MTT) and cerebral blood volume (CBV). DWI was performed with two different b values (0, 1000 s/mm2) for calculation of apparent diffusion coefficient (ADC) maps. RESULTS: In five of six cases increased MTT values were observed initially, whereas the CBV was normal, indicating a reduction of cerebral blood flow. ADC values were normal. On follow up after clinical recovery MTT prolongations had resolved. Areas with prolonged MTT did not evolve into structural lesions. CONCLUSION: In patients with CVT, prolongations of MTT in the absence of changes in CBV and ADC seem to indicate reversible involvement of brain tissue, a situation corresponding to the ischaemic penumbra.

Ischaemia triggered by spreading neuronal activation is inhibited by vasodilators in rats.

It has been previously shown that spreading neuronal activation can generate a cortical spreading ischaemia (CSI) in rats. The purpose of the present study was to investigate whether vasodilators cause CSI to revert to a normal cortical spreading depression (CSD).A KCl-induced CSD travelled from an open cranial window to a closed window where the cortex was superfused with physiological artificial cerebrospinal fluid (ACSF). At the closed window, recordings revealed a short-lasting negative slow potential shift accompanied by a variable, small and short initial hypoperfusion followed by hyperaemia and then oligaemia. In contrast, spreading neuronal activation locally induced CSI at the closed window when ACSF contained a NO. synthase (NOS) inhibitor, N(G)-nitro-L-arginine, and an increased K+ concentration ([K+]ACSF). CSI was characterised by a sharp and prolonged initial cerebral blood flow decrease to 29 +/- 11 % of the baseline and a prolonged negative potential shift. Co-application of a NOá donor, S-nitroso-N-acetylpenicillamine, and NOS inhibitor with high [K+]ACSF re-established a short-lasting negative potential shift and spreading hyperaemia typical of CSD. Similarly, the NO.-independent vasodilator papaverine caused CSI to revert to a pattern characteristic of CSD. In acute rat brain slices, NOS inhibition and high [K+]ACSF did not prolong the negative slow potential shift compared to that induced by high [K+]ACSF alone. The data indicate that the delayed recovery of the slow potential was caused by vasoconstriction during application of high [K+]ACSF and a NOS inhibitor in vivo. This supports the possibility of a vicious circle: spreading neuronal activation induces vasoconstriction, and vasoconstriction prevents repolarisation during CSI. Speculatively, this pathogenetic process could be involved in migraine-induced stroke.

[Apomorphine therapy versus deep rain stimulation. Clinical and economic aspects in patients with advanced Parkinson disease]. / Apomorphintherapie versus tiefe Hirnstimulation. Klinische und ökonomische Aspekte bei Patienten mit fortgeschrittenem Morbus Parkinson.

Long-term dopaminergic treatment of Parkinson's disease is complicated by the occurrence of dyskinesia and motor fluctuations and is responsible for increasing the costs of treatment. In these patients, continuous subcutaneous therapy with the dopamine agonist apomorphine or deep-brain stimulation represents a promising strategy. While the costs for the treatment with apomorphine are covered by health insurance, separate reimbursement for deep-brain stimulation does not exist in Germany. The case reports (n = 3) presented here emphasize that deep-brain stimulation is less cost-intensive than subcutaneous treatment with apomorphine in selected patients. Even in the first postoperative year costs for medication and hospital stays were reduced by approximately 60%. Moreover, in all three patients, motor complications improved after deep-brain stimulation in comparison to previous subcutaneous application of apomorphine. Thus, to further ensure deep-brain stimulation in parkinsonian patients it is mandatory to find a mode of reimbursement for the institutions concerned.

Products of hemolysis in the subarachnoid space inducing spreading ischemia in the cortex and focal necrosis in rats: a model for delayed ischemic neurological deficits after subarachnoid hemorrhage?

OBJECT: The pathogenesis of delayed ischemic neurological deficits after subarachnoid hemorrhage has been related to products of hemolysis. Topical brain superfusion of artificial cerebrospinal fluid (ACSF) containing the hemolysis products K+ and hemoglobin (Hb) was previously shown to induce ischemia in rats. Superimposed on a slow vasospastic reaction, the ischemic events represent spreading depolarizations of the neuronal-glial network that trigger acute vasoconstriction. The purpose of the present study was to investigate whether such spreading ischemias in the cortex lead to brain damage. METHODS: A cranial window was implanted in 31 rats. Cerebral blood flow (CBF) was measured using laser Doppler flowmetry, and direct current (DC) potentials were recorded. The ACSF was superfused topically over the brain. Rats were assigned to five groups representing different ACSF compositions. Analyses included classic histochemical and immunohistochemical studies (glial fibrillary acidic protein and ionized calcium binding adaptor molecule) as well as a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay. Superfusion of ACSF containing Hb combined with either a high concentration of K+ (35 mmol/L, 16 animals) or a low concentration of glucose (0.8 mmol/L, four animals) reduced CBF gradually. Spreading ischemia in the cortex appeared when CBF reached 40 to 70% compared with baseline (which was deemed 100%). This spreading ischemia was characterized by a sharp negative shift in DC, which preceded a steep CBF decrease that was followed by a slow recovery (average duration 60 minutes). In 12 of the surviving 14 animals widespread cortical infarction was observed at the site of the cranial window and neighboring areas in contrast to findings in the three control groups (11 animals). CONCLUSIONS: The authors conclude that subarachnoid Hb combined with either a high K+ or a low glucose concentration leads to widespread necrosis of the cortex.

Acute treatment of hypertension increases infarct sizes in spontaneously hypertensive rats.

We studied the effect of dihydralazine treatment of hypertension in spontaneously hypertensive stroke-prone rats in a model of permanent focal cerebral ischemia (stroke). After occlusion of the middle cerebral artery systemic arterial pressure (SAP) was lowered with a computer controlled infusion device from 163 to 135 or 117 mm Hg for 24h. In the control group SAP was not manipulated. Reduction of SAP to normotension (117 mm Hg) significantly worsened outcome and increased infarct volume measured 7 days after induction of ischemia, whereas a mild reduction of SAP (to 137 mm Hg) had no statistically significant effect on outcome or infarct volume. We conclude that pharmacological treatment of hypertension may negatively affect neurological outcome and infarct volume in a rat stroke model.