New recommendations on cerebral venous and dural sinus thrombosis from the German consensus-based (S2k) guideline.

Over the last years, new evidence has accumulated on multiple aspects of diagnosis and management of cerebral venous and dural sinus thrombosis (CVT) including identification of new risk factors, studies on interventional treatment as well as treatment with direct oral anticoagulants. Based on the GRADE questions of the European Stroke Organization guideline on this topic, the new German guideline on CVT is a consensus between expert representatives of Austria, Germany and Switzerland. New recommendations include:• CVT occurring in the first weeks after SARS-CoV-2 vaccination with vector vaccines may be associated with severe thrombocytopenia, indicating the presence of a prothrombotic immunogenic cause (Vaccine-induced immune thrombotic thrombocytopenia; VITT).• D-dimer testing to rule out CVT cannot be recommended and should therefore not be routinely performed.• Thrombophilia screening is not generally recommended in patients with CVT. It should be considered in young patients, in spontaneous CVT, in recurrent thrombosis and/or in case of a positive family history of venous thromboembolism, and if a change in therapy results from a positive finding.• Patients with CVT should preferably be treated with low molecular weight heparine (LMWH) instead of unfractionated heparine in the acute phase.• On an individual basis, endovascular recanalization in a neurointerventional center may be considered for patients who deteriorate under adequate anticoagulation.• Despite the overall low level of evidence, surgical decompression should be performed in patients with CVT, parenchymal lesions (congestive edema and/or hemorrhage) and impending incarceration to prevent death.• Following the acute phase, oral anticoagulation with direct oral anticoagulants instead of vitamin K antagonists should be given for 3 to 12 months to enhance recanalization and prevent recurrent CVT as well as extracerebral venous thrombosis.• Women with previous CVT in connection with the use of combined hormonal contraceptives or pregnancy shall refrain from continuing or restarting contraception with oestrogen-progestagen combinations due to an increased risk of recurrence if anticoagulation is no longer used.• Women with previous CVT and without contraindications should receive LMWH prophylaxis during pregnancy and for at least 6 weeks post partum.Although the level of evidence supporting these recommendations is mostly low, evidence from deep venous thrombosis as well as current clinical experience can justify the new recommendations.This article is an abridged translation of the German guideline, which is available online.

Correction to: Features of intracranial hemorrhage in cerebral venous thrombosis.

The original version of this article unfortunately contained mistakes. The correct information is given below.

Features of intracranial hemorrhage in cerebral venous thrombosis.

BACKGROUND: Cerebral venous thrombosis (CVT) is associated with intracranial hemorrhage. AIM: To identify clinical and imaging features of CVT-associated intracranial hemorrhage. We hypothesized that higher clot burden would be associated with a higher risk of intracranial hemorrhage. METHODS: We performed a retrospective analysis of an international, multicenter cohort of patients with confirmed cerebral venous thrombosis who underwent computed tomography within 2 weeks of symptom onset. Clinical and imaging features were compared between patients with and without intracranial hemorrhage. Clot burden was assessed by counting the number of thrombosed venous sinuses and veins on confirmatory imaging. RESULTS: We enrolled 260 patients from 10 institutions in Europe and Mexico. The mean age was 42 years and 74% were female. Intracranial hemorrhage was found in 102 (39%). Among them parenchymal hemorrhage occurred in 64 (63%), in addition, small juxta-cortical hemorrhage was found in 30 (29%), subarachnoid hemorrhage in 24 (24%) and subdural hemorrhage in 11 (11%). Multiple concomitant types of hemorrhage occurred in 23 (23%). Older age and superior sagittal thrombosis involvement were associated with presence of hemorrhage. The number of thrombosed venous sinuses was not associated with intracranial hemorrhage (median number IQRInterquartile ratio] of sinuses/veins involved with hemorrhage 2 (1-3) vs. 2 (1-3) without hemorrhage, p = 0.4). CONCLUSION: The high rate of intracranial hemorrhage in cerebral venous thrombosis is not explained by widespread involvement of the venous sinuses. Superior sagittal sinus involvement is associated with higher bleeding risk.

Colchicine for stroke prevention in patients with coronary artery disease: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Although clinical trials suggest that colchicine may reduce the risk of vascular events in patients with a history of coronary artery disease, its effect on the prevention of cerebrovascular events still remains unclear. METHODS: A systematic review and meta-analysis was performed of all available randomized controlled trials (RCTs) reporting on incident strokes during the follow-up of patients with a history of cardiovascular disease randomized to colchicine treatment or control (placebo or usual care). RESULTS: Four RCTs were identified, including a total of 5553 patients (mean age 61 years, 81% males), with a follow-up ranging from 1 to 36 months. Colchicine treatment was associated with a significantly lower risk of incident stroke during follow-up compared to control (risk ratio 0.31, 95% confidence interval 0.13-0.71), without heterogeneity across included studies (I2  = 0%). Based on the pooled incident stroke rate of control groups (0.9%) in the included RCTs, it was estimated that administration of low-dose colchicine to 161 patients with coronary artery disease would prevent one stroke during a follow-up of 23 months. CONCLUSION: Colchicine treatment decreases stroke risk in patients with a history of coronary artery disease. The effect of colchicine in secondary stroke prevention is currently being evaluated in an ongoing RCT.

[Availability of mechanical thrombectomy for acute stroke : Analysis of the health care reality in Germany]. / Verfügbarkeit der mechanischen Thrombektomie bei akutem Hirninfarkt : Analyse der Versorgungsrealität in Deutschland.

BACKGROUND: Mechanical thrombectomy (MT) has become an evidence-based therapy for stroke patients with proximal vessel occlusion of the anterior cerebral circulation. Nationwide availability of MT for all eligible patients within the shortest possible time window is a major challenge. AIM OF THE STUDY: Nationwide analysis of the rates of systemic thrombolysis (STL) and MT in Germany according to region and hospital-based evaluation. METHODS: The evaluation involved data analysis of the diagnosis-related groups (DRG) statistics and structured quality reports of hospitals for 2010 and 2014. The rates and changes of STL and MT were evaluated in the 413 German districts with reference to the corresponding case number of patients with acute ischemic stroke. RESULTS: Nationwide recanalization treatment rates increased from 2010 to 2014 both for STL (from 8.0% to 11.6%) and MT (from 0.7% to 2.3%). High variations were observed depending on the patient's place of residence (STL = 3.4-36.7%, MT = 0-7.4%). In 2014 a total of 5526 MT were coded in a total of 244,757 ischemic strokes. A total of 134 hospitals with more than 2 MT per year were identified; however, 21% of the nationwide MTs were performed in only 7 hospitals with more than 100 MT/year. In 308 (75%) of the 413 districts, not a single MT was performed. CONCLUSION: Due to a narrow net of certified stroke units with nationwide availability of STL, excellent structural conditions for treatment of acute stroke patients are already established in Germany. With regard to the nationwide availability of MT, there is still a need for optimization. Despite the increasing number of hospitals providing MT as an emergency procedure, a trend toward large intervention centers with supraregional catchment areas can be observed.

[Treatment reality of internal carotid artery stenosis in Germany : requirement and reality in international comparison and in light of the current S3 guidelines]. / Versorgungsrealität von Karotisstenosen in Deutschland : Forderung und Wirklichkeit im internationalen Vergleich und im Lichte der aktuellen S3-Leitlinie.

BACKGROUND: Severe atherosclerotic extracranial carotid artery stenosis accounts for 5-10 % of all ischemic strokes. Currently, therapeutic recommendations are undergoing changes, particularly regarding the treatment of asymptomatic stenosis. Consolidated knowledge on the indications, nationwide distribution and numbers of cases are not available. Moreover, the impact and grade of implementation of the recently published national S3 guidelines on the reality of medical treatment remain unclear. METHODS: Analysis of administrative hospital data involving the diagnosis-related groups (DRG) statistics and structured quality reports for 2010 and 2013 to evaluate the procedural therapy trends concerning operative and interventional approaches for symptomatic and asymptomatic carotid artery stenoses. RESULTS: In Germany approximately 37,000 carotid endarterectomies (CEA) and approximately 5,000 carotid angioplasties with stenting (CAS) are carried out per year. Approximately 94 % of CEA and 62 % of CAS are performed in centers with more than 25 procedures per year. Only 33 % of CEA and 39 % of CAS are related to symptomatic stenosis. CONCLUSION: Mathematically, an undertreatment of symptomatic and an overtreatment of asymptomatic carotid artery stenoses become apparent. Efforts should be made to achieve inpatient medical treatment conforming to the national S3 guidelines, in particular to adequately reduce the risk of stroke recurrence in patients with atherosclerotic symptomatic carotid artery stenosis.

[New aspects of stroke medicine]. / Neues aus der Schlaganfallmedizin.

Systemic thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) remains the only effective and approved medical treatment of acute ischemic stroke. Several studies have demonstrated the importance of rapid recanalization. The efficacy of thrombectomy has so far not been sufficiently shown in randomized clinical trials; therefore, inclusion of suitable patients in one of the currently ongoing randomized trials is of great importance. The early treatment with magnesium after acute ischemic stroke during the pre-hospital phase did not prove to be neuroprotective. Intermittent pneumatic compression of the lower extremities in immobilized stroke patients effectively prevents deep venous thrombosis and pulmonary embolism. In patients with lacunar stroke the combination of aspirin and clopidogrel is not superior to aspirin alone and causes more bleeding complications. The novel oral anticoagulants are superior to warfarin in secondary prevention and carry a lower risk of intracranial and systemic bleeding complications. New studies will investigate whether dabigatran or rivaroxaban are superior to aspirin in secondary prevention after cryptogenic stroke.

B-type natriuretic peptide predicts stroke of presumable cardioembolic origin in addition to coronary artery calcification.

BACKGROUND AND PURPOSE: B-type natriuretric peptide (BNP) is a marker of cardiac dysfunction that is released from myocytes in response to ventricular wall stress. Previous studies suggested that BNP predicts stroke events in addition to classical risk factors. It was suggested that the BNP-associated risk results from coronary atherosclerosis or atrial fibrillation. METHODS: Three thousand six hundred and seventy five subjects from the population-based Heinz Nixdorf Recall study (45-75 years; 47.6% men) without previous stroke, coronary heart disease, myocardial infarcts, open cardiac valve surgery, pacemakers and defibrillators were followed up over 110.1 ± 23.1 months. Cox proportional hazards regressions were used to examine BNP as a stroke predictor in addition to vascular risk factors (age, gender, systolic blood pressure, low-density lipoprotein, high-density lipoprotein, diabetes, smoking), renal insufficiency, atrial fibrillation/known heart failure and coronary artery calcification. RESULTS: Eighty-nine incident strokes occurred (80 ischaemic, 9 hemorrhagic). Subjects suffering stroke had significantly higher BNP values at baseline than the remaining subjects [26.3 (Q1; Q3 = 12.9; 51.0) vs. 17.4 (9.4; 31.4); P < 0.001]. In a multivariable regression, log10 BNP was an independent stroke predictor [hazard ratio 1.96, 95% confidence interval (CI) 1.13-3.41; P = 0.017] in addition to age (1.24 per 5 years, CI 1.04-1.49; P = 0.016), systolic blood pressure (1.25 per 10 mmHg, CI 1.14-1.38; P < 0.001), smoking (2.05, CI 1.24-3.39; P = 0.005), atrial fibrillation/heart failure (2.25, CI 1.05-4.83; P = 0.037) and computed-tomography-based log10 (coronary artery calcification + 1) (1.47, CI 1.15-1.88; P = 0.002). Log10 BNP predicted stroke in men but not women, both in subjects ≤65 and >65 years. In subsequent analyses, BNP discriminated the incidence of cardioembolic stroke (P for trend = 0.001), but not stroke of macroangiopathic (P = 0.555), microangiopathic (P = 0.809) or unknown (P = 0.367) origin. CONCLUSIONS: BNP predicts presumable cardioembolic stroke independent of coronary calcification.

Use of paracetamol in ischaemic stroke patients: evidence from VISTA.

OBJECTIVES: Paracetamol is frequently prescribed for pain and fever control in acute stroke patients, but its effect on stroke outcome is unclear. The aim was to investigate the safety and benefit of paracetamol administration in the acute phase of ischaemic stroke. METHODS: We analysed the impact of paracetamol exposure on functional outcome at 90 days among ischaemic stroke patients registered in a clinical trials archive. We used an adjusted Cochran-Mantel-Haenszel test to test for significance (P) followed by proportional odds logistic regression analysis to estimate the odds ratios (OR) for more favourable modified Rankin Scale score. RESULTS: Data were available for 6015 patients, of whom 2435 had received paracetamol. No association of paracetamol-use with overall stroke outcome could be detected among those patients who experienced pain and/or fever (OR 1.03, 95% CI 0.86-1.20, P = 0.931). In patients without recorded pain and/or fever events and a baseline temperature below 37°C, in whom paracetamol was started within 3 days of stroke, paracetamol was associated with worse outcome (OR 0.58, 95% CI 0.47-0.72, P = <0.001). CONCLUSION: This retrospective analysis is discouraging for prophylactic use of paracetamol in acute stroke patients, but underlines the need for a sufficiently powered randomized controlled trial.

[Diagnostic and treatment of acute ischemic stroke]. / Akutdiagnostik und Akuttherapie des ischämischen Insultes.

The incidence of first stroke in Germany is about 200.000, most of which are ischemic. The benefit of stroke unit treatment and systemic thrombolysis has been shown in large randomized trials. Diagnostic work-up besides neurologic examination includes cerebral imaging by CT or MR imaging including angiography, ultrasound of brain supplying arteries, ECG and Holter ECG and - if indicated - transesophageal echocardiography. Aspirin is the cornerstone of early secondary prevention in the acute phase, thereafter secondary prevention is determined by stroke etiology. Carotid endarterectomy or stent-assisted angioplasty are indicated in patients with hemodynamic or arterio-arterial stroke etiologies due to high-grade carotid stenosis. For cardioembolism due to atrial fibrillation, oral anticoagulation with vitamin K-antagonists or new oral anticoagulants should be started after the acute phase. In patients with non-cardioembolic stroke etiologies, platelet inhibitors are used for secondary prevention.

Does the cognitive measure Cog-4 show improvement among patients treated with thrombolysis after acute stroke?

BACKGROUND: Although the established measure of disability post stroke, the modified Rankin Scale emphasizes motor function and may underestimate the importance of cognitive impairment in more disabled patients. A subset of four items from the National Institutes of Health Stroke Scale has been proposed to assess cognitive function after stroke (Cog-4), and to correlate with modified Rankin Scale. Items correspond to orientation, executive function, language, and inattention. We investigated responsiveness of Cog-4 to treatment with thrombolysis and whether it offers information that supplements modified Rankin Scale. METHODS: We included 6268 patients from the Virtual International Stroke Trials Archive: 2734 received intravenous thrombolysis and 3534 were treated conservatively. We compared day 90 outcomes between treated and untreated groups, by modified Rankin Scale (illustrative) and by Cog-4 (primary measure) adjusting for age, baseline National Institutes of Health stroke scale, hemispheric lateralisation as well as baseline Cog-4 and baseline National Institutes of Health Stroke Scale excluding baseline Cog-4 separately. Analysis of Cog-4 was repeated within strata of 90 day modified Rankin Scale. Statistical analyses included proportional odds logistic regression and Cochran-Mantel-Haenszel test. RESULTS: Modified Rankin Scale showed a difference between treatment groups of expected magnitude (odds ratio 1·56; 95% confidence interval 1·43-1·72; P < 0·001). After adjustment for imbalance in baseline prognostic factors, the distribution of Cog-4 scores at 90 days was better in thrombolysed patients compared with nonthrombolysed patients (odds ratio 1·31; 95% confidence interval 1·18-1·47; P = 0·006). However, Cog-4 analysis stratified by 90-day modified Rankin Scale was neutral between treatment groups (OR 1·01; 95% CI 0·90-1·14), and Cog-4 was not responsive to treatment group even within modified Rankin Scale categories 4 and 5 despite substantial cognitive deficits in these patients. CONCLUSION: Although Cog-4 may be responsive to treatment effects, it does not provide additional information beyond modified Rankin Scale assessment.

Randomized comparison of synchronous CABG and carotid endarterectomy vs. isolated CABG in patients with asymptomatic carotid stenosis: the CABACS trial.

RATIONALE: High-grade carotid artery stenosis is present in 6-8% of patients undergoing coronary artery bypass graft surgery. Many cardiovascular surgeons advocate staged or synchronous carotid endarterectomy to reduce the high perioperative and long-term risk of stroke associated with multivessel disease. However, no randomized trial has assessed whether a combined synchronous or staged carotid endarterectomy confers any benefit compared with isolated coronary artery bypass grafting in these patients. AIMS: The objective of this study is to compare the safety and efficacy of isolated coronary artery bypass grafting vs. synchronous coronary artery bypass grafting and carotid endarterectomy in patients with asymptomatic high-grade carotid artery stenosis. DESIGN: Coronary Artery Bypass graft surgery in patients with Asymptomatic Carotid Stenosis (CABACS) is a randomized, controlled, open, multicenter, group sequential trial with two parallel arms and outcome adjudication by blinded observers. Patients with asymptomatic high-grade carotid stenosis scheduled for elective coronary artery bypass grafting will be assigned to either isolated coronary artery bypass grafting or synchronous coronary artery bypass grafting and carotid endarterectomy by 1 : 1 block-stratified randomization with three different stratification factors (age, gender, modified Rankin scale). STUDY: The trial started in December 2010 aiming at recruiting 1160 patients in 25 to 30 German cardiovascular centers. The composite primary efficacy end point is the number of strokes and deaths from any cause (whatever occurs first) within 30 days after operation. A 4·5% absolute difference (4% compared to 8·5%) in the 30-day rate of the above end points can be detected with >80% power. OUTCOMES: The results of this trial are expected to provide a basis for defining an evidence-based standard and will have a wide impact on managing this disease.

Why do acute ischemic stroke patients with a preceding transient ischemic attack present with less severe strokes? Insights from the German Stroke Study.

BACKGROUND: The effect of ischemic preconditioning (IP) is well established in animal models of brain ischemia. There are conflicting data from human observational studies whether IP is also induced by a preceding transient ischemic attack (TIA) resulting in a lower stroke severity in these patients. METHODS: Data from 7,611 consecutive patients with first-ever acute ischemic stroke from the prospective German Stroke Study Collaboration were analyzed. A multivariate linear regression analysis was used to evaluate whether a preceding TIA was associated with a lower National Institutes of Health Stroke Scale (NIH-SS) score at admission. Furthermore, stroke severity was stratified by the latency between a preceding TIA and subsequent acute ischemic stroke (≤7 days vs. >7 days and ≤72 h vs. >72 h). RESULTS: A previous TIA was documented in 452 (5.9%) patients, and a significantly lower NIH-SS score at admission was found in these patients compared with patients without TIA. A previous TIA remained significantly associated with a lower NIH-SS score in multivariate analysis corrected for the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, cardiovascular risk factors, age, sex and premorbid disability. The NIH-SS score at admission did not significantly differ in 96 patients with a TIA within 7 days compared with 137 patients with a TIA more than 7 days before ischemic stroke. Similarly, there were no significant differences in stroke severity in patients with a TIA within 72 h. CONCLUSIONS: The significantly lower stroke severity observed in patients with a preceding TIA is not confounded by stroke etiology in our large-scale observational study. Data on latency between the TIA and subsequent ischemic stroke do not support a neuroprotective effect caused by TIA-induced IP in human ischemic stroke.

Recurrent stroke after lobar and deep intracerebral hemorrhage: a hospital-based cohort study.

BACKGROUND: Recurrent stroke rates after intracerebral hemorrhage (ICH) vary widely between observational studies due to differences in ICH etiology and risk for thromboembolic events. We therefore aimed to assess the patient characteristics and prognosis after deep and lobar ICH in a well-characterized, multicenter, hospital-based cohort. METHODS: Patients were prospectively documented in 13 German neurological stroke centers. Of 744 patients with spontaneous ICH discharged alive, 516 (69.4%) gave informed consent and 496 (66.7%) could be followed up by central telephone interview over a mean duration of 2 years. RESULTS: In patients with deep ICH, the Kaplan-Meier estimate for stroke during the first year was 5.8% (95% CI 2.9-8.7) and the overall annual rate (calculated over a 3-year period) was 2.9% (95% CI 1.6-4.1). In patients with lobar ICH, the Kaplan-Meier estimate for stroke during the first year was 7.8% (95% CI 3.1-12.5) and the overall annual rate was 7.2% (95% CI 3.8-10.6). At the last follow-up before recurrent stroke or end of study, 141 patients (28.4%) overall received antiplatelet agents, and 12 (2.4%) received oral anticoagulation. No difference could be found for recurrent ICH under antiplatelet agents versus no antithrombotic medication. CONCLUSION: The risk of recurrent stroke after lobar ICH remains high beyond the first year, whereas it decreases after 1 year in patients with deep ICH. Antiplatelets are prescribed in a considerable number of patients even though the risk-benefit ratio after ICH remains unknown.

Symptomatic intracranial atherosclerotic stenoses: prevalence and prognosis in patients with acute cerebral ischemia.

BACKGROUND: In Caucasian patients with acute stroke or transient ischemic attack (TIA) due to symptomatic intracranial atherosclerotic stenoses (ICAS), only limited data on the recurrent stroke rate and its associated risk factors have been reported. In view of the increasing options for endovascular interventions, we sought to investigate the prevalence, risk for recurrent stroke and mortality in these patients. METHODS: A total of 304 consecutive patients with acute ischemic stroke or TIA due to 50-99% ICAS were prospectively documented in 19 German stroke centers. In 201 patients (68.1% of the survivors), a central biannual telephone follow-up could assess recurrent stroke and mortality up to a median of 2 years after the index event. RESULTS: An ischemic cerebrovascular event attributable to symptomatic ICAS was found in 2.24% of the consecutively admitted patients. The overall cumulative recurrent stroke rate after admission was 17.9% (95% CI = 13.4-23.5) for the first year and 23.3% (95% CI = 17.8-29.8) over 3 years. After correction for age and sex, only previous stroke (HR = 2.11, 95% CI = 1.14-3.91) and diabetes (HR = 2.41, 95% CI = 1.33-4.37) were significantly associated with recurrent stroke. CONCLUSION: Although the prevalence of this etiology seems very low in patients admitted to German stroke centers, we found a high risk of recurrent stroke in patients with symptomatic ICAS. Whether endovascular interventions can reduce this high risk needs to be determined in a randomized trial.