Key design elements of successful acute ischemic stroke treatment trials.

PURPOSE: We review key design elements of positive randomized controlled trials (RCTs) in acute ischemic stroke (AIS) treatment and summarize their main characteristics. METHOD: We searched Medline, Pubmed and Cochrane databases for positive RCTs in AIS treatment. Trials were included if (1) they had a randomized controlled design, with (at least partial) blinding for endpoints, (2) they tested against placebo (or on top of standard therapy in a superiority design) or against approved therapy; (3) the protocol was registered and/or published before trial termination and unblinding (if required at study commencement); (4) the primary endpoint was positive in the intention to treat analysis; and (5) the study findings led to approval of the investigational product and/or high ranked recommendations. A topical approach was used, therefore the findings were summarized as a narrative review. FINDINGS: Seventeen positive RCTs met the inclusion criteria. The majority of trials included less than 1000 patients (n = 15), had highly selective inclusion criteria (n = 16), used the modified Rankin score as a primary endpoint (n = 15) and had a frequentist design (n = 16). Trials tended to be national (n = 12), investigator-initiated and performed with public funding (n = 11). DISCUSSION: Smaller but selective trials are useful to identify efficacy in a particular subgroup of stroke patients. It may also be of advantage to limit the number of participating countries and centers to avoid heterogeneity in stroke management and bureaucratic burden. CONCLUSION: The key characteristics of positive RCTs in AIS treatment described here may assist in the design of further trials investigating a single intervention with a potentially high effect size.

Histological stroke clot analysis after thrombectomy: Technical aspects and recommendations.

The recent advent of endovascular procedures has created the unique opportunity to collect and analyze thrombi removed from cerebral arteries, instigating a novel subfield in stroke research. Insights into thrombus characteristics and composition could play an important role in ongoing efforts to improve acute ischemic stroke therapy. An increasing number of centers are collecting stroke thrombi. This paper aims at providing guiding information on thrombus handling, procedures, and analysis in order to facilitate and standardize this emerging research field.

Angioplasty in asymptomatic carotid artery stenosis vs. endarterectomy compared to best medical treatment: One-year interim results of SPACE-2.

BACKGROUND: Treatment of individuals with asymptomatic carotid artery stenosis is still handled controversially. Recommendations for treatment of asymptomatic carotid stenosis with carotid endarterectomy (CEA) are based on trials having recruited patients more than 15 years ago. Registry data indicate that advances in best medical treatment (BMT) may lead to a markedly decreasing risk of stroke in asymptomatic carotid stenosis. The aim of the SPACE-2 trial (ISRCTN78592017) was to compare the stroke preventive effects of BMT alone with that of BMT in combination with CEA or carotid artery stenting (CAS), respectively, in patients with asymptomatic carotid artery stenosis of ≥70% European Carotid Surgery Trial (ECST) criteria. METHODS: SPACE-2 is a randomized, controlled, multicenter, open study. A major secondary endpoint was the cumulative rate of any stroke (ischemic or hemorrhagic) or death from any cause within 30 days plus an ipsilateral ischemic stroke within one year of follow-up. Safety was assessed as the rate of any stroke and death from any cause within 30 days after CEA or CAS. Protocol changes had to be implemented. The results on the one-year period after treatment are reported. FINDINGS: It was planned to enroll 3550 patients. Due to low recruitment, the enrollment of patients was stopped prematurely after randomization of 513 patients in 36 centers to CEA (n = 203), CAS (n = 197), or BMT (n = 113). The one-year rate of the major secondary endpoint did not significantly differ between groups (CEA 2.5%, CAS 3.0%, BMT 0.9%; p = 0.530) as well as rates of any stroke (CEA 3.9%, CAS 4.1%, BMT 0.9%; p = 0.256) and all-cause mortality (CEA 2.5%, CAS 1.0%, BMT 3.5%; p = 0.304). About half of all strokes occurred in the peri-interventional period. Higher albeit statistically non-significant rates of restenosis occurred in the stenting group (CEA 2.0% vs. CAS 5.6%; p = 0.068) without evidence of increased stroke rates. INTERPRETATION: The low sample size of this prematurely stopped trial of 513 patients implies that its power is not sufficient to show that CEA or CAS is superior to a modern medical therapy (BMT) in the primary prevention of ischemic stroke in patients with an asymptomatic carotid stenosis up to one year after treatment. Also, no evidence for differences in safety between CAS and CEA during the first year after treatment could be derived. Follow-up will be performed up to five years. Data may be used for pooled analysis with ongoing trials.

Predictors of symptomatic intracranial haemorrhage in off-label thrombolysis: an analysis of the Safe Implementation of Treatments in Stroke registry.

BACKGROUND AND PURPOSE: Intravenous thrombolysis (IVT) is the only approved pharmacological treatment for acute ischemic stroke. Off-label IVT for ischemic stroke is common. We aimed to analyse its safety in a large database. METHODS: This was a retrospective analysis of the safe implementation of treatments in stroke (SITS) thrombolysis registry with regard to 11 off-label criteria according to the European licence for alteplase. Symptomatic intracranial haemorrhage (SICH) according to SITS was defined as primary safety endpoint and SICH according to the European Cooperative Acute Stroke Study (ECASS II) definition and the National Institute of Neurological Disorders and Stroke definition as secondary safety endpoints. Multivariable logistic regression analyses after replacing missing values using multiple imputations were performed. RESULTS: Patients from 793 centres in 44 countries were included, mainly (95%) in Europe. A total of 56 258 patients who were treated with intravenous alteplase were included. Median age was 71 (IQR 61-78) years and median National Institutes of Health Stroke Scale score was 12 (IQR 7-17). A total of 16 740 (30%) patients received off-label IVT and 1037 (1.8%) patients suffered from SICH according to the SITS definition (SICH SITS). Median percentage of missing values per variable was 0.4%. The only two off-label criteria constituting independent positive and negative predictors for SICH SITS were high blood pressure (odds ratio, 1.39; 95% confidence interval, 1.08-1.80; P = 0.012) and minor stroke (odds ratio, 0.51; 95% confidence interval, 0.33-0.78; P = 0.002). Very severe stroke, previous stroke and diabetes, age and high glucose levels were additional independent predictors of SICH according to the ECASS II and National Institute of Neurological Disorders and Stroke definitions. CONCLUSIONS: Thrombolysis appears to be safe with regard to SICH for most of the off-label criteria, especially for minor stroke, but is risky in patients with high blood pressure. Individual risk-benefit evaluation should be performed.

The Impact of Conscious Sedation versus General Anesthesia for Stroke Thrombectomy on the Predictive Value of Collateral Status: A Post Hoc Analysis of the SIESTA Trial.

BACKGROUND AND PURPOSE: Radiologic selection criteria to identify patients likely to benefit from endovascular stroke treatment are still controversial. In this post hoc analysis of the recent randomized Sedation versus Intubation for Endovascular Stroke TreAtment (SIESTA) trial, we aimed to investigate the impact of sedation mode (conscious sedation versus general anesthesia) on the predictive value of collateral status. MATERIALS AND METHODS: Using imaging data from SIESTA, we assessed collateral status with the collateral score of Tan et al and graded it from absent to good collaterals (0-3). We examined the association of collateral status with 24-hour improvement of the NIHSS score, infarct volume, and mRS at 3 months according to the sedation regimen. RESULTS: In a cohort of 104 patients, the NIHSS score improved significantly in patients with moderate or good collaterals (2-3) compared with patients with no or poor collaterals (0-1) (P = .011; mean, -5.8 ± 7.6 versus -1.1 ± 10.7). Tan 2-3 was also associated with significantly higher ASPECTS before endovascular stroke treatment (median, 9 versus 7; P < .001) and smaller mean infarct size after endovascular stroke treatment (median, 35.0 versus 107.4; P < .001). When we differentiated the population according to collateral status (0.1 versus 2.3), the sedation modes conscious sedation and general anesthesia were not associated with significant differences in the predictive value of collateral status regarding infarction size or functional outcome. CONCLUSIONS: The sedation mode, conscious sedation or general anesthesia, did not influence the predictive value of collaterals in patients with large-vessel occlusion anterior circulation stroke undergoing thrombectomy in the SIESTA trial.

[Mission (im)possible : Setting up a neurological center 12,000 km away with telemedicine]. / "Mission (im)possible" : Aufbau eines neurologischen Zentrums 12.000 km entfernt mittels Telemedizin.

BACKGROUND: Specialized neurological treatment decreases the mortality and morbidity of stroke patients. In many regions of the world an extensive coverage is not available. The cooperation between the Krankenhaus Nordwest (KHNW, Frankfurt, Germany) and the Government of Brunei Darussalam describes the set-up process of a specialized neurological center, including stroke unit, science and rehabilitation center. AIM: The aim of this project called to teach to treat - to treat to teach was to set up a center of excellence in neurology in Brunei Darussalam over a distance of 12,000 km. Treatment options were elucidated by teaching and taught by case examples. MATERIAL AND METHODS: The construction of the Brunei Neuroscience Stroke and Rehabilitation Center (BNSRC) began in July 2010. To overcome the large distance between the department of neurology and neuroradiology at the KHNW and the BNSRC, a telemedical network was established. We provided daily teleteaching for all professions involved in patient care as well as 24/7 availability of teleneurological services from Germany to support the local team on site. RESULTS: In the BNSRC unit over 1000 patients with ischemic and hemorrhagic stroke and all the various acute neurological conditions were treated from July 2010 until July 2016 as inpatients and over 5000 were treated as outpatients. Since 2010, a total of 52 patients with stroke were treated by thrombolysis within the thrombolytic window and 81 hemicraniectomies were performed. CONCLUSION: The project has shown that it is possible to convey specialized neurological knowledge over large distances to provide significant benefits for patients and caregivers.

Setting up a Neuroscience Stroke and Rehabilitation Centre in Brunei Darussalam by a transcontinental on-site and telemedical cooperation.

Due to the world-wide aging population, there is a need for specialist neurological knowledge, treatment and care. Stroke treatment is effective in reducing mortality and disability, but it is still not available in many areas of the world. We describe the set-up process of a specialized Neuroscience, Stroke and Rehabilitation Centre in Brunei Darussalam (BNSRC) in cooperation with a German hospital. This study details the setup of a stroke-, neurological intensive care- and neurorehabilitation unit, laboratories and a telemedical network to perform all evidence-based stroke treatments. All neurological on-site services and the telemedical network were successfully established within a short time. After setup, 1386 inpatients and 1803 outpatients with stroke and stroke mimics were treated. All evidence-based stroke treatments including thrombolysis and hemicraniectomy could be performed. It is possible to establish evidence-based modern stroke treatment within a short time period by a transcontinental on-site and telemedical cooperation.

SPACE-2: A Missed Opportunity to Compare Carotid Endarterectomy, Carotid Stenting, and Best Medical Treatment in Patients with Asymptomatic Carotid Stenoses.

BACKGROUND: Because of recent advances in best medical treatment (BMT), it is currently unclear whether any additional surgical or endovascular interventions confer additional benefit, in terms of preventing late ipsilateral carotid territory ischemic stroke in asymptomatic patients with significant carotid stenoses. The aim was to compare the stroke-preventive effects of BMT alone, with that of BMT in combination with carotid endarterectomy (CEA) or carotid artery stenting (CAS) in patients with high grade asymptomatic extracranial carotid artery stenosis. METHODS: SPACE-2 was planned as a three-armed, randomized controlled trial (BMT alone vs. CEA plus BMT vs. CAS plus BMT, ISRCTN 78592017). However, because of slow patient recruitment, the three-arm study design was amended (July 2013) to become two parallel randomized studies (BMT alone vs. CEA plus BMT, and BMT alone vs. CAS plus BMT). RESULTS: The change in study design did not lead to any significant increase in patient recruitment, and trial recruitment ceased after recruiting 513 patients over a 5 year period (CEA vs. BMT (n = 203); CAS vs. BMT (n = 197), and BMT alone (n = 113)). The 30 day rate of death/stroke was 1.97% for patients undergoing CEA, and 2.54% for patients undergoing CAS. No strokes or deaths occurred in the first 30 days after randomization in patients randomized to BMT. There were several potential reasons for the low recruitment rates into SPACE-2, including the ability for referring doctors to refer their patients directly for CEA or CAS outwith the trial, an inability to convince patients (who had come "mentally prepared" that an intervention was necessary) to accept BMT, and other economic constraints. CONCLUSIONS: Because of slow recruitment rates, SPACE-2 had to be stopped after randomizing only 513 patients. The German Research Foundation will provide continued funding to enable follow up of all recruited patients, and it is also planned to include these data in any future meta-analysis prepared by the Carotid Stenosis Trialists Collaboration.

Pulmonary and circulatory parameter guided anesthesia in patients with ischemic stroke undergoing endovascular recanalization.

BACKGROUND AND PURPOSE: Endovascular recanalization in ischemic stroke is often performed under general anesthesia. Some studies have shown a detrimental effect of general anesthesia. The reasons are unknown. METHODS: This was an observational study with retrospective and prospective phases. From 2008 to 2010, 60 patients treated by endovascular recanalization due to proximal vessel occlusion were analyzed with regard to ventilation parameters, blood gas values, blood pressure, and clinical parameters (pre-protocol phase). Subsequently, a protocol with target values for end-tidal CO2 (Petco2) and systolic blood pressure (SBP) was introduced and prospectively analyzed in 64 patients in 2012 (protocol phase). RESULTS: In the pre-protocol phase, significant hypocapnia (<30 mm Hg), a decrease in SBP after intervention (p<0.001), and an increase in SBP after extubation (p<0.001) were observed. After implementing the protocol in 2012, 63% of Petco2 values and 55% of SBP values (median) of the duration of intervention were within the predefined range. Severe hypocapnia and hypotension (SBP <100 mm Hg) after the intervention were significantly reduced. Longer duration of Petco2 values within 40-45 mm Hg, intracerebral hemorrhage, longer door to needle time, older age, unsuccessful recanalization, longer duration of endovascular treatment, and higher cumulative dose of norepinephrine were associated with an unfavorable outcome (modified Rankin Scale score >2). Intracerebral hemorrhage (OR 0.028, p=0.001), age (OR 0.9, p=0.013), and cumulative dose of norepinephrine (OR 0.142, p=0.003) were independent predictors of an unfavorable outcome. CONCLUSIONS: In patients receiving endovascular stroke treatment under general anesthesia, the cumulative dose of norepinephrine was an independent predictor of an unfavorable outcome. Further studies are needed to evaluate the optimal management of blood pressure in these patients, and whether avoidance of catecholamines could partly explain the improved outcomes for patients treated under conscious sedation in retrospective studies.

Intravenous thrombolysis for acute ischaemic stroke in the elderly: data from the Baden-Wuerttemberg stroke registry.

BACKGROUND AND PURPOSE: In Europe intravenous thrombolysis (IVT) for ischaemic stroke is still not approved for patients aged >80 years. However, elderly patients are frequently treated based on individual decision making. In a retrospective observational study a consecutive and prospective stroke registry in southwest Germany was analysed. METHODS: The data registry collected 101,349 patients with ischaemic stroke hospitalized from January 2008 to December 2012. Of these, 38,575 (38%) were aged 80 years and older and 10 286 (10.1%) underwent IVT. Favourable outcome at discharge was defined as modified Rankin Scale (mRS) ≤1 or not worse than prior to stroke. Multiple logistic regression models stratified by 10-year age groups were used to assess the relationship between IVT and mRS at discharge, adjusted for patient characteristics, admitting facility and length of hospital stay. RESULTS: The highest IVT rate was 15% in patients aged <50 years, with a continuous decline down to 8% in patients aged ≥90 years. Adjusted odds ratios and 95% confidence intervals for patients 80-89 years of age were 2.20 (1.95-2.47) (P < 0.0001) and 1.25 (0.88-1.78) (P = 0.21) for patients >90 years of age, compared to patients of the same age decade not treated with IVT. CONCLUSIONS: The evidence from routine hospital care in southwest Germany indicates that IVT is an effective treatment also for aged patients with ischaemic stroke in an age range between 80 and 89 years. Although no clear evidence for the effectiveness of IVT beyond 90 years was found, treatment should also be carefully considered in these patients. High age should not discourage from treatment.

[Intensive care therapy of space-occupying large hemispheric infarction. Summary of the NCS/DGNI guidelines]. / Intensivtherapie des raumfordernden ischämischen Hemisphäreninfarkts. Zusammenfassung der NCS/DGNI-Leitlinie.

Large hemispheric infarction (LHI), synonymously called malignant middle cerebral artery (MCA) infarction, is a severe neurological disease with a high mortality and morbidity. Treating physicians as well as relatives are often faced with few and low quality data when attempting to apply optimal treatment to these patients and make decisions. While current stroke treatment guidelines focus on risk factors, prevention and acute management, they include only limited recommendations concerning intensive care management of LHI. The Neurocritical Care Society (NCS) and the German Society for Neurocritical and Emergency Medicine (DGNI) organized an interdisciplinary consensus conference on intensive care management of LHI to meet this demand. European and American experts in neurology, neurocritical care, neurosurgery, neuroradiology and neuroanesthesiology were selected based on their expertise and research focus. Subgroups for several main topics elaborated a number of central clinical questions concerning this topic and evaluated the quality of the currently available data according to the grading of recommendation assessment, development and evaluation (GRADE) guideline system. Subsequently, evidence-based recommendations were compiled after weighing the advantages against the disadvantages of certain management options. This is a commented abridged version of the results of the consensus conference.

[Mechanical thrombectomy in acute ischemic stroke. What is the position after the latest study results?]. / Mechanische Thrombektomie bei akutem ischämischem Schlaganfall : Wo stehen wir nach den jüngsten Studienergebnissen?

Mechanical devices for the recanalization of vessel occlusions in severe acute ischemic stroke have been developed for more than a decade. Several devices have been approved for clinical use on the basis of uncontrolled case series. Many neurologists have asked for randomized clinical trials comparing the new devices with standard treatment, e.g. thrombolytic therapy within a 4.5 h time window. The first 3 investigator initiated randomized trials published in 2013 failed to show superiority of mechanical thrombectomy over standard treatment. In the aftermath of these negative results several new trials with changes in design (e.g. shorter time window and only proximal vessel occlusions) and the use of modern devices with proven higher recanalization rates, so called stent retrievers, have been launched. In October 2014 the first of these new trials was presented and showed a clear superiority of thrombectomy. Based on this result interim analyses of five other studies were performed and most were prematurely terminated because of overwhelming efficacy. Only one trial testing another type of recanalization device failed to reach a statistically significant result. Currently five studies have already been published and two more studies have been presented at scientific conferences. This article provides an overview of the study protocols and the results of the individual studies, their common features and the characteristics of patients who benefit from this treatment. Finally, the consequences that these results may have for the treatment of patients with severe stroke caused by proximal vessel occlusion are discussed.

Volatile sedation with sevoflurane in intensive care patients with acute stroke or subarachnoid haemorrhage using AnaConDa®: an observational study.

BACKGROUND: The anaesthetic conserving device, AnaConDa(®), allows use of inhaled anaesthetics for sedation in the intensive care unit. We prospectively measured cerebral and cardiopulmonary parameters in patients with acute stroke or subarachnoid haemorrhage during a switch from i.v. to inhalative sedation. METHODS: 25 patients were switched from i.v. to an indefinite period of inhaled sedation with sevoflurane. Mean arterial (MAP), intracranial (ICP), and cerebral perfusion pressure (CPP), middle cerebral artery mean flow velocity (MFV) and fractional tissue oxygen extraction (FTOE), systemic cardiopulmonary parameters, and administered drugs were assessed before and after the change (-6 to +12 h). RESULTS: In 8 patients, critically reduced MAP or ICP crisis led to premature termination of sevoflurane sedation. In the other 17 patients, after the first hour, mean ICP increased [2.4 (4.5) mm Hg; P=0.046], MAP decreased [7.8 (14.1) mm Hg; P=0.036] and thus CPP decreased also [-10.2 (15.1) mm Hg; P=0.014]. MFV and FTOE did not change. Over a 12 hour post switch observational period, [Formula: see text] increased slightly [0.3 (0.8) kPa; P=0.104], ICP did not change [0.2 (3.9) mm Hg; P=0.865], but MAP [-6 (6.9) mm Hg; P=0.002] and thus CPP decreased [-6 (8.5) mm Hg; P=0.010]. CONCLUSION: Sevoflurane led to sufficient sedation, but decreased MAP and CPP in a selected cerebrovascular neurocritical care population. In about a third of these patients, severe adverse reactions, including intolerable ICP increases, were observed.

Statins reduce peri-procedural complications in carotid stenting.

BACKGROUND: In primary and secondary prevention, statins significantly reduce cardiovascular and cerebrovascular events. Pre-interventional statin medication shows a benefit in carotid artery stenosis patients treated with endarterectomy; however, there are few data available for patients treated with stent-angioplasty. The aim of this study was to investigate whether pre-interventional statin therapy is associated with decreased peri-interventional risk of stroke, myocardial infarction, and mortality in patients undergoing stent-angioplasty for internal carotid stenosis. METHODS: Data for 344 consecutively documented patients with internal carotid artery stenosis treated with stent-angioplasty in the years 2002-2012 at the same stroke center were collected in a prospectively defined database. Risk factors, medication, and indication for therapy were documented. Univariate and multivariate analysis was performed to investigate independent reduction of peri-interventional stroke, myocardial infarction, or death by statin medication prior to stent-angioplasty. RESULTS: The median age was 70 years (p25: 63, p75: 76), 75.5% of patients were male, and the median stenosis was 85% according to ECST criteria (p25: 80%, p75: 90%). 20.1% of patients had asymptomatic stenoses, and 60.2% had statin medication before stenting. As per multivariate analysis, pre-interventional statin medication was a predictor for significant peri-interventional risk reduction regarding primary endpoint ischemic stroke, myocardial infarction (MI), or death (odds ratio (OR) 0.31, p = .006). Statins also had a significant protective effect in secondary endpoint ischemic stroke, intracranial bleeding or death (OR 0.39, p = .014), and ischemic stroke or myocardial infarction (OR 0.20; p = .002). CONCLUSIONS: This study shows that pre-interventional statin medication has a protective effect against peri-interventional stroke, MI, or death in patients with internal carotid artery stenosis treated with stent-angioplasty. Accordingly, statins could be considered as a standard pre-interventional medical therapy in carotid stenting.

[Therapeutic options in malignant cerebral venous and sinus thrombosis]. / Therapiemöglichkeiten bei schweren, intensivpflichtigen Sinus- und Venenthrombosen.

BACKGROUND: Cerebral venous and sinus thrombosis (CVST) constitutes less than 0.5-1 % of all strokes and occurs predominantly in young female adults. In general the clinical outcome is favorable but 3-15 % of patients die in the acute phase and in the majority of cases due to cerebral herniation. Intensive care treatment analogous to that of severe ischemic infarct leads to an aggressive interdisciplinary therapy concept that can achieve good clinical outcome. Based on five cases of severe CVST treatment options will be presented. RESULTS: All five patients were affected by impending or incipient cerebral herniation and severe focal neurological deficits which resulted in the decision to implement thrombectomy, thrombolysis or hemicraniectomy. Despite the severe course and many intensive care complications which suggested a poor prognosis, all five patients could be transferred to rehabilitation after having survived the acute phase and achieved an amazingly good overall clinical outcome. CONCLUSION: Considering the life-threatening course of severe CVST, aggressive interdisciplinary management by endovascular thrombectomy and hemicraniectomy can lead to a scarcely expected clinical outcome without disability or severe dependency. This treatment should be performed early and in an escalatory manner in patients with severe CVST who have an increased risk of an unfavorable outcome due to edema, infarction and hemorrhage.

[Clinical course of cerebral sinus venous thrombosis. Data from a monocentric cohort study over 15 years]. / Verlauf der zerebralen Sinus-/Venenthrombose. Daten einer monozentrischen Kohortenstudie über 15 Jahre.

INTRODUCTION: Thrombosis of cerebral veins or sinuses (CVST) is a rare condition. In a monocentric retrospective cohort study the clinical characteristics, risk factors, radiological findings as well as course and prognosis of patients over the past 15 years were examined. METHODS: Between January 1998 and March 2013 all patients who were treated as inpatients for CVST at the department of neurology of the University of Heidelberg were systematically registered in a database. Along with all relevant clinical data the modified Rankin scale (MRS) was used to measure the clinical severity. A follow-up visit was performed at three time points. The odds ratios (OR) were calculated to establish predictors of good outcome (MRS 0-2), mortality at discharge and at follow-up. Significant variables after univariate analysis were tested for independency in a multivariate logistic regression model. RESULTS: A total of 143 patients were included in the study. The median age was 43 years (range 17-74 years) and 67.4 % of patients were female. The most common symptoms were headache (70.6 %), seizures (50.4 %) and paresis (37.8 %). The most prominent clinical risk factor was oral contraception (40.4 %). The two most common localizations of thrombosis were the transversal sinus with the sigmoid sinus (66.4 %) and the sagittal superior sinus (47.6 %). On admission 42.7 % of patients suffered additionally from intracerebral hemorrhage and 12.6 % from congestive infarction. Of the patients 9.5 % (10 out of 105) showed a pathologically reduced activated protein C (APC) resistance and 8.4 % (6 out of 94) a prothrombin mutation. All patients were initially treated with heparin and 88.7 % were switched to cumarin during the course of the disease. The median duration of anticoagulation was 15.75 months (range 1-121 months). On discharge 77.7 % had a good outcome and the in-hospital mortality was 4.7 %. The median time to follow-up in 108 patients was 36 months (range 3-132 months), 74.1 % of patients had a good outcome (MRS 0-2) and 18.5 % died. Independent predictors of in-hospital mortality were MRS on admission (OR 2.2, 95 % CI 1.03-4.7) and of mortality at follow-up the presence of a malignant disease (OR 50.2, 6-423) and intracerebral hemorrhage on admission (OR 10.3, 1.7-62.6). DISCUSSION: The results of this study are in line with previously published data on CVST. The most prominent clinical risk factors for CVST were female gender and oral contraception. At discharge from hospital and 3 years after CVST approximately 75 % of patients achieved a good clinical outcome. A severe clinical syndrome and the presence of an intracerebral hemorrhage on admission were independent predictors of mortality.