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.

[Quality of care of acute ischemic stroke in Germany 2018]. / Versorgungsqualität des akuten ischämischen Schlaganfalls in Deutschland 2018.

In this overview the current quality of acute in-hospital care of stroke patients in Germany in 2018 is described based on standardized and evidence-based quality indicators. For this purpose the reports of the regional quality assurance projects for stroke care, which collaborated within the German-speaking Stroke Registers Study Group (ADSR) were analyzed. Overall, more than 280,000 acute admissions of stroke patients were documented in the included quality assurance projects. The results regarding the defined 16 quality indicators comprising diagnostics, acute treatment, rehabilitation and secondary prevention showed a high level of acute inpatient treatment of stroke in Germany. Only a few quality indicators, such as early transfer for thrombectomy indicated a great necessity for process optimization.

[Revised certification criteria for regional and national stroke units in Germany]. / Aktualisierte Zertifizierungskriterien für regionale und überregionale Stroke-Units in Deutschland.

The revised criteria for regional and national German stroke units (SU) defined by the SU commission of the German Stroke Society come into effect on 1 July 2015. Due to the already high level of quality, various aspects only needed minor adjustments and definitions; therefore, the majority of minimum structural standards were carried forward. For medical personnel thresholds for when staff further recruitment is necessary were defined for the first time. The current evidence for endovascular thrombectomy (ET) resulted in enhanced standards for acute brain vessel imaging, network formation and timely transport between regional and national SUs with and without ET capability. It further confirmed certification criteria for national SUs that have been valid since 2012: at least two neurointerventionalists as staff members enabling ET on a 24/7 basis. Diagnostic of atrial fibrillation (AF) has been newly implemented following current evidence and internal audits on an annual basis have now become obligatory. Overall, activities to ensure and improve quality must not only be restricted to the minimally required criteria of SU certification but should also incorporate recommendations of the SU commission. The continuous further development of German SU in recent years underlines the importance of the certification procedure as a guarantee of a minimum standard and as the driving force of sustainable quality improvements.

Carotid stenosis--when is revascularization appropriate?

Approximately 15% of ischemic strokes are caused by extracranial carotid stenoses. Revascularization of a symptomatic stenosis is very efficacious in carefully selected patients. This review outlines criteria which help to identify those who will benefit most from carotid endarterectomy (CEA) for symptomatic stenosis. Asymptomatic carotid stenosis is a common condition in the general population over 50 years, but nonetheless associated with a low risk of ischemic stroke. Consequently, the therapeutic yield of CEA is much lower in asymptomatic stenosis and women seem not to benefit at all. In the future, specific morphological MRI features may help to identify stenoses prone to become symptomatic. In addition to their significance for stroke, it has been demonstrated that atherosclerotic lesions can be regarded as an indicator of cardiovascular morbidity which may help to identify high-risk patients for cardiovascular events.

[Anticoagulation for stroke prevention. An update]. / Antikoagulation zur Schlaganfallprävention. Ein Update.

Given the projected rising prevalence of atrial fibrillation in the near future, an increasing number of older patients will have to be treated in order to prevent stroke and systemic embolism. This article summarizes recent developments in antithrombotic treatment and risk stratification for patients with atrial fibrillation and intends to abate the still prevailing reluctance towards anticoagulation in elderly patients.

Secondary prevention of stroke: a practical guide to drug treatment.

Stroke is a disease of the elderly and, as a result of the expected demographic changes in many industrialised countries, its incidence is likely to increase in the future. A first-ever stroke significantly increases the likelihood of further events; thus, secondary prevention is of major importance. Only a minority of recurrent strokes can be prevented by surgical or other invasive methods, meaning that most secondary preventive measures involve drug treatment, which has become increasingly sophisticated in recent years. Ischaemic stroke constitutes the vast majority of all strokes; effective secondary prevention depends on a variety of factors, of which the correct classification in terms of subtypes and aetiological mechanisms is a pivotal prerequisite, as is the assessment of the patient's cardiovascular risk profile. In addition to the evaluation of pathomechanisms, stratification of subtypes of brain infarction is mainly based on morphology seen with brain imaging techniques, which provides additional evidence for the presumed cause of the stroke. Inhibitors of platelet function and anticoagulants are the two major groups of antithrombotic drugs used for the secondary prevention of stroke. Antiplatelet agents are still indicated in the majority of patients after ischaemic stroke, especially if an arterial origin is presumed. In addition to aspirin (acetylsalicylic acid), the position of which as the first-line antiplatelet drug is increasingly being questioned, other compounds with antiplatelet activity have been developed and have proven effective in secondary stroke prevention, including ticlopidine, clopidogrel and dipyridamole. Anticoagulants are principally indicated after cardioembolic ischaemic stroke; however, their inherent bleeding risks render their use in many cases rather difficult, in particular for elderly patients. Patient compliance with the recommended treatment is of major importance, given the somewhat limited efficacy of antithrombotic agents in stroke prevention. Since 'real world' experience does not match the circumstances under which clinical trials are conducted, this article will also deal with problems not covered by specific studies, such as risk stratification for anticoagulant treatment and how to proceed in cases of unknown stroke aetiology. The management of major cardiovascular risk factors is the other mainstay of secondary stroke prevention. Recent evidence indicates that antihypertensive treatment may be as effective as antithrombotic drugs for secondary prevention of stroke. This still needs to be proven for the treatment of other cardiovascular risk factors, such as diabetes mellitus and hypercholesterolemia. Nevertheless, the results of recent studies investigating the effect of HMG-CoA reductase inhibitors ('statins') on cardiovascular events strongly suggest a stroke-preventive effect.

Navigated diffusion-weighted imaging with interpolated phase-correction for high-resolution imaging of stroke.

Stroke imaging was revolutionised with the introduction of diffusion-weighted MRI (DWI). The commonly used echoplanar DWI suffers from geometrical distortion near the skull base and the frontal regions and from reduced spatial resolution and fat suppression. To allow a voxel-by-voxel comparison between high-resolution spin-echo images, we implemented spin-echo-based DWI. Motion artefacts were eliminated by phase correction in hybrid frequency-Fourier domain using navigator echoes. In a novel approach, distorted navigator echoes which did not eliminate motion artefacts were replaced with interpolated navigator echoes, leading to restored image information. Navigated DWI yielded high-resolution images in 21 of 24 patients with brain ischaemia, allowing diagnosis of even small or diffuse zones of ischaemia. We determined the spatial distribution and mean of T(2)- and DWI signal intensity and apparent diffusion coefficients (ADC), using a multidimensional histogram-based analysis. Mean ADC were decreased in ischaemic areas less than 9 days old. The technique may also be useful for high-resolution DWI of tissue other than the brain.

R1--systemic thrombolysis in German stroke units--the experience from the German Stroke data bank.

BACKGROUND: Systemic thrombolysis with tissue plasminogen activator (t-PA) for treatment of acute ischemic stroke was approved in Germany in 2000. Up to now, only data from single centers have been available for the study of the use of thrombolysis in a hospital-based approach outside controlled trials. We therefore sought to determine the frequency of application and complications as well as the patient outcome after t-PA treatment in clinical routine of specialized stroke centers in Germany. METHODS: Within the German Stroke Data Bank Collaboration, 6234 consecutive patients with ischemic stroke were prospectively documented in 20 stroke centers between 1998 and 1999. The patients were centrally followed via telephone interview after 3 months and 1 year to assess global functional outcome using the Modified Rankin Scale. RESULTS: 250 patients (4 %) received systemic t-PA treatment during the study period. The baseline characteristics of these patients were comparable to large clinical trials and phase IV studies. Symptomatic and asymptomatic parenchymal hemorrhage occurred in 22 patients (8.8 %) and was fatal in 3 patients. Follow-up data after 3 months were obtained in 82.4 % of all patients, of which 35 % had a favorable functional outcome (mRS /= 4) and 17 % had died. CONCLUSION: The results of our study agree with the assumption that thrombolytic therapy can be performed safely and effectively in daily clinical practice. Nevertheless, the small proportion of patients receiving thrombolysis even in specialized stroke centers calls for further improvement of acute stroke management in Germany.

[Prerequisites, indications and contraindications of IV-lysis of ischemic stroke with rt-PA]. / Voraussetzungen, Indikationen und Kontraindikationen der systemischen Lysebehandlung des akuten ischämischen Insultes mit rt-PA.

BACKGROUND AND PURPOSE: To evaluate prerequisites, safety, and efficacy of i.v.-thrombolysis of ischemic stroke with rtPA in an academic medical center. METHODS: Over a period of 2 years and 10 months all patients admitted with a diagnosis of stroke were recruited. Inclusion and exclusion criteria for i.v.-thrombolysis were combined from large scale randomized controlled trials, the time window, however, could be extended up to 4 hours in subjects with a negative CT-scan. Prespecified outcome parameters were the modified Rankin Scale (mRS) and the Barthel Index (BI) at 3 months, and symptomatic hemorrhagic complications. Additionally, time parameters, such as onset-admission-time, door-Ct-time, door-needle time, and onset-needle time were recorded. RESULTS: During the reported period 103 patients underwent i.v.-thrombolysis, corresponding to 14.9% of all patients with ischemic stroke, and 47% of patients with ischemic stroke arriving in < 3 hours after symptom onset. The mean baseline NIHSS was 14, the mean mRS 13 (3-34), the mean age 70 (+/- 12) years. The following time intervals were observed: Onset-admission-time 64 min., door-CT-time 27 min., admission-needle-time 80 min., and onset-needle-time 142 min. There were 4 symptomatic intracerebral hemorrhagic transformations, including 3 parenchymal hemorrhages, 2 of them lethal, and one with almost full recovery. According to the mRS, 39% of patients had a good (mRS 0-1), 72% a good to moderate recovery (mRS 0-2). The corresponding figures for the BI were 60% BI 95-100 and 72% BI > 90. The mortality was 15%. CONCLUSION: The i.v.-thrombolysis of ischemic stroke with rt-PA demands appropriate organisation of the pre- and in-hospital phase and can be performed safely and efficaciously in daily clinical routine if inclusion and exclusion criteria as well as all safety measures during the critical phase after therapy are strictly obeyed.

Intravenous tPA for ischemic stroke team performance over time, safety, and efficacy in a single-center, 2-year experience.

BACKGROUND AND PURPOSE: Safety and efficacy concerns toward thrombolysis for ischemic stroke prevail among many neurologists because of the risks of hemorrhage and the small proportion of suitable patients. We therefore prospectively assessed feasibility, safety, efficacy, and team performance in a single center to prove whether thrombolytic treatment is practical in daily clinical routine. METHODS: Patients were prospectively recruited over a 2-year period. Major inclusion and exclusion criteria from large, randomized controlled trials were combined. Prespecified outcome parameters were the modified Rankin scale (MRS) and the Barthel Index (BI) at 3 months and symptomatic hemorrhagic complications. In addition, certain time intervals during the diagnostic process preceding thrombolysis were prospectively recorded. RESULTS: Within 2 years a total of 75 patients underwent intravenous thrombolysis, corresponding to 9.4% of all admitted patients with stroke and 14.9% of patients with ischemic stroke. Mean+/-SD age was 68+/-13 (range 34 to 90) years; median baseline National Institutes of Health Stroke Scale score was 13+/-6 (range 2 to 34). Thrombolysis was started at an average time of 144 minutes after symptom onset, and 13 patients (17.3%) were treated beyond 3 hours. Two cerebral hemorrhages (2.7%) occurred. Outcome according to the MRS was good (MRS 0 to 1) in 40%, moderate (MRS 2 to 3) in 32%, and poor (MRS 4 to 5) in 13%; the corresponding results, as measured by the BI, were 61% (BI 95 to 100, good), 16% (BI 55 to 90, moderate), and 8% (BI 0 to 50, poor). The mortality rate was 15%. Over 2 years the median door-to-CT time decreased from 30 to 22 minutes (27%), and the door-to-needle time was shortened from 96 to 73 minutes (14%). The mean number of patients treated per month increased from 2 to 4. CONCLUSIONS: Thrombolytic therapy can be performed safely and efficaciously in daily clinical routine. More than a minority of acute stroke patients might be eligible for intravenous thrombolysis. The performance of a stroke team can be improved over time, subsequently increasing the proportion of eligible patients and thereby the efficiency of the method.

Compliance with secondary prevention of ischemic stroke: a prospective evaluation.

BACKGROUND AND PURPOSE: Compliance with pharmacological therapy is essential for the efficiency of secondary prevention of ischemic stroke. Few data exist regarding patient compliance with antithrombotic and risk factor treatment outside of controlled clinical trials. The aim of the present study was to assess the rate of and predictors for compliance with secondary stroke prevention 1 year after cerebral ischemia and to identify reasons for noncompliance. METHODS: Patients with a diagnosis of ischemic stroke or TIA and antithrombotic discharge medication were prospectively recruited. At 1 year, the proportion of patients compliant with antithrombotic treatment and with medication for risk factors (eg, hypertension, diabetes, hyperlipidemia) was evaluated through structured telephone interviews. In addition, the reasons for nontreatment with antithrombotic and risk factor medication were determined. Independent predictors for compliance were analyzed by logistic regression analyses. RESULTS: Of 588 consecutive patients admitted to our stroke unit, 470 had a discharge diagnosis of cerebral ischemia (TIA 26.2%, cerebral infarct 73.8%) and recommendations for antithrombotic therapy. At 1 year, 63 patients (13.4%) had died and 21 (4.5%) were lost to follow-up, thus, 386 could finally be evaluated. Of the patients, 87.6% were still on antithrombotic medication, and 70.2% were treated with the same agent prescribed on discharge. Of the patients with hypertension, diabetes, and hyperlipidemia, 90.8%, 84.9%, and 70.2% were still treated for their respective risk factors. Logistic regression analyses revealed age (OR 1.03, 95% CI 1.00 to 1.06), stroke severity on admission (OR 1.09, 95% CI 1.00 to 1.20), and cardioembolic cause (OR 4.13, 95% CI 1.23 to 13.83) as independent predictors of compliance. CONCLUSIONS: Compliance with secondary prevention in patients with ischemic stroke is rather good in the setting of our study. Higher age, a more severe neurological deficit on admission, and cardioembolic stroke cause are associated with better long-term compliance. Knowledge of these determinants may help to further improve the quality of stroke prevention.

Diffusion-weighted magnetic resonance imaging in two patients with polycythemia rubra vera and early ischemic stroke.

Polycythemia rubra vera (PRV) is a rare myeloproliferative disorder with a high risk of ischemic stroke. Although thrombosis of large cerebral arteries is the most frequently presumed pathomechanism, various infarct patterns have been described in patients with PRV and ischemic stroke. We report two patients with mild acute ischemic strokes and known PRV, in whom a scattered lesion pattern was detected by diffusion-weighted magnetic resonance imaging (DWI), but was not visible on computed tomography (CT) and conventional magnetic resonance imaging (MRI). Further diagnostic work-up including extra- and transcranial Doppler sonography (ECD, TCD), transesophageal echocardiography (TEE), magnetic resonance angiography and Holter monitoring revealed no obvious sources of cerebral embolism in both cases. However, TEE in one patient demonstrated spontaneous echo contrast (SEC) in the left atrium. In both patients the symptomatology resolved completely. The detection of a scattered infarct pattern by DWI in patients with PRV and acute ischemic stroke has not been reported previously. DWI findings together with the SEC in one patient emphasize the assumption that a prothrombotic state with subsequent arterial embolism rather than local arterial thrombosis may be the underlying pathomechanism of stroke in some patients with PRV. Adding DWI to the diagnostic work-up may help to clarify etiology in patients with PRV and acute ischemic stroke.

Scattered brain infarct pattern on diffusion-weighted magnetic resonance imaging in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: Infarct patterns on brain imaging contribute to the etiologic classification of ischemic stroke. However, the association of specific subtypes of infarcts and etiologic mechanisms is often weak, and acute lesions are frequently missed on initial computed tomography (CT). Diffusion-weighted imaging (DWI) is superior in visualizing acute ischemic lesions as compared to CT and conventional magnetic resonance imaging (MRI). In our prospective study, we addressed the question whether a distinct pattern of infarction on DWI is associated with infarct etiology and clinical outcome. METHODS: Sixty-two patients with clinical signs of acute ischemic stroke and negative acute CT upon admission underwent DWI within 10 days after the ictus. Neurological status was documented using the NIH stroke scale. A scattered lesion pattern was defined by at least 2 separate hyperintense DWI lesions within the territory of one of the major cerebral arteries. Ischemic lesions were defined as acute if the region was demarcated strongly hyperintense in all DW images, and if the apparent diffusion coefficient was below normal. RESULTS: In 32 patients, DWI revealed a scattered lesion pattern, while in 30 patients a single acute lesion was detected. In patients with scattered lesions, potential arterial or cardiac embolic sources were detected in 26 patients (81.3%), as compared to 5 patients (16.6%) in the group with single lesions (chi(2) test, p < 0.0001). The neurological status of patients with scattered lesions improved significantly more than among patients with single lesions (Mann-Whitney test, p < 0.0003). CONCLUSION: A scattered lesion pattern on DWI in patients with acute brain infarction and negative initial CT scan is associated with an embolic etiology and may indicate a favorable clinical outcome.

Transtentorial herniation after unilateral infarction of the anterior cerebral artery.

BACKGROUND: Fatal cerebral herniation is a common complication of large ("malignant") middle cerebral artery infarcts but has not been reported in unilateral anterior cerebral artery (ACA) infarction. CASE DESCRIPTION: We report a 47-year-old woman who developed an acute left hemiparesis during an attack of migraine. Cranial CT (CCT) was normal but demonstrated narrow external cerebrospinal fluid compartments. Transcranial Doppler sonography was compatible with occlusion of the right ACA. Systemic thrombolytic therapy with tissue plasminogen activator was initiated 105 minutes after symptom onset. Follow-up CCT 24 hours after treatment revealed subtotal ACA infarction with hemorrhagic conversion. Two days later, the patient suddenly deteriorated with clinical signs of cerebral herniation, as confirmed by CCT. An extended right hemicraniectomy was immediately performed. Within 6 months, the patient regained her ability to walk but remained moderately disabled. CONCLUSIONS: This is the first reported case of unilateral ACA infarct leading to almost fatal cerebral herniation. Narrow external cerebrospinal fluid compartments in combination with early reperfusion, hemorrhagic transformation, and additional dysfunction of the blood-brain barrier promoted by tissue plasminogen activator and migraine may have contributed to this unusual course.

Prophylactic antipyretic treatment with acetaminophen in acute ischemic stroke: a pilot study.

Fever is associated with poor outcome in acute stroke. Forty-two consecutive, normothermic patients with acute ischemic stroke were, within 24 hours from symptom onset, randomized to either receive 4 g acetaminophen daily (n = 20) or matched placebo (n = 22). Fever of greater than 37.5 degrees C occurred in 36.4% of patients in the placebo group, compared with 5.0% in the acetaminophen group (Fisher's exact test, p = 0.014). Prophylactic antipyretic treatment with acetaminophen may be effective in the prevention of fever after acute ischemic stroke.

Neurogenic hypertension. A new MRI protocol for the evaluation of neurovascular compression of the cranial nerves IX and X root-entry zone.

OBJECTIVE: Neurovascular compression of the rostral ventrolateral medulla (RVLM) has been implicated in the pathogenesis of essential hypertension. Although MRI has been widely used to evaluate the morphologic relation of structures in this region, spatial resolution of the previously used techniques was limited. This article describes the use of a new MRI protocol that combines two sequences with improved spatial resolution and complementary image information as well as a set of defined criteria for image analysis. METHODS: MRI of the brain stem was performed in 60 hypertensive and 50 normotensive subjects using a 3D-CISS and a 3D-FISP-MRA sequence. Neurovascular contact in the RVLM was independently assessed by four readers using predefined criteria and compared with a consensus finding. Agreement was expressed by kappa statistics on a 0 to 1 scale. RESULTS: Left-sided neurovascular contact within the RVLM was found in 13 (22%) hypertensive and 6 (12%) control subjects. The inter-reader agreement for positive and negative findings ranged from 0.47 to 0.79; agreement to the consensus finding ranged from 0.65 to 0.90. CONCLUSIONS: The combination of 3D-CISS and arterial flow-sensitive 3D-FISP, together with the evaluation criteria defined in this study, can be used for describing the finer anatomic features of the brain stem, and in particular for investigation of neurovascular contact of the IX/X cranial nerve root-entry zone. The high quality of images and the substantial or almost perfect reader-consensus agreement should make this protocol useful for future investigations of the neurovascular compression syndrome in patients with essential hypertension and possibly in other neurovascular compression syndromes, such as trigeminal neuralgia and hemifacial spasm.