Search

Introduction: Hospitals around the world introduced considerable visitation restrictions to reduce risk of infection during epidemic spread of SARS-CoV2. Understanding of negative impacts of visitation restrictions on subgroups of patients may help to balance and adjust policies accordingly or introduce further measures to mitigate their impact. We aimed to investigate the association of visitation restrictions with delirium incidence in stroke-unit patients. Methods: In a non-randomized observational design, data from 5,779 stroke-unit cases with transient ischemic attack or stroke (ischemic/hemorrhagic) admitted between January 2017 and November 2021 were compared between three groups depending on visitation policy implemented at time of admission: pandemic-associated absolute visitation restriction (n = 1,087), limited visitation policy (n = 862), and pre-pandemic visitation policy (n = 3,830). Univariate comparison and multiple logistic regression analyses were conducted to evaluate the association of delirium with visitation restrictions. Results: We observed delirium incidences of 6.3% during pandemic-associated absolute visitation restriction, 5.8% with limited visitation policy, and 5.1% with pre-pandemic visitation policy (p = 0.239). In multiple logistic regression analyses adjusting for clinically relevant variables, we found the presence of any pandemic-associated visitation restriction (odds ratio [OR] 1.363, 95% confidence interval [CI]: 1.066–1.744, p = 0.014) and specifically absolute visitation restriction (OR 1.368, 95% CI: 1.016–1.843, p = 0.039) independently associated with delirium in patients with acute cerebrovascular disease. Other factors independently associated with delirium were older age, male sex, stroke versus transient ischemic attack, acute infection, history of dementia, and longer duration of hospital stay. Conclusion: Pandemic-associated visitation restrictions and specifically absolute visitation restrictions are associated with a higher incidence of delirium among stroke-unit patients with acute cerebrovascular disease. Benefit and harm of visitation restrictions should be carefully weighed and adjustments considered for patients otherwise at increased risk for delirium.

The optimal treatment for patients with asymptomatic carotid artery stenosis is under debate. Since best medical treatment (BMT) has improved over time, the benefit of carotid endarterectomy (CEA) or carotid artery stenting (CAS) is unclear. Randomised data comparing the effect of CEA and CAS versus BMT alone are absent. We aimed to directly compare CEA plus BMT with CAS plus BMT and both with BMT only.SPACE-2 was a multicentre, randomised, controlled trial at 36 study centres in Austria, Germany, and Switzerland. We enrolled participants aged 50-85 years with asymptomatic carotid artery stenosis at the distal common carotid artery or the extracranial internal carotid artery of at least 70%, according to European Carotid Surgery Trial criteria. Initially designed as a three-arm trial including one group for BMT alone (with a randomised allocation ratio of 2·9:2·9:1), the SPACE-2 study design was amended (due to slow recruitment) to become two substudies with two arms each comparing CEA plus BMT with BMT alone (SPACE-2a) and CAS plus BMT with BMT alone (SPACE-2b); in each case in a 1:1 randomisation. Participants and clinicians were not masked to allocation. The primary efficacy endpoint was the cumulative incidence of any stroke or death from any cause within 30 days or any ipsilateral ischaemic stroke within 5 years. The primary safety endpoint was any stroke or death from any cause within 30 days after CEA or CAS. The primary analysis was by intention-to treat, which included all randomly assigned patients in SPACE-2, SPACE-2a, and SPACE-2b, analysed using meta-analysis of individual patient data. We did two-step hierarchical testing to first show superiority of CEA and CAS to BMT alone then to assess non-inferiority of CAS to CEA. Originally, we planned to recruit 3640 patients; however, the study had to be stopped prematurely due to insufficient recruitment. This report presents the primary analysis at 5-year follow-up. This trial is registered with ISRCTN, number ISRCTN78592017.513 patients across SPACE-2, SPACE-2a, and SPACE-2b were recruited and surveyed between July 9, 2009, and Dec 12, 2019, of whom 203 (40%) were allocated to CEA plus BMT, 197 (38%) to CAS plus BMT, and 113 (22%) to BMT alone. Median follow-up was 59·9 months (IQR 46·6-60·0). The cumulative incidence of any stroke or death from any cause within 30 days or any ipsilateral ischaemic stroke within 5 years (primary efficacy endpoint) was 2·5% (95% CI 1·0-5·8) with CEA plus BMT, 4·4% (2·2-8·6) with CAS plus BMT, and 3·1% (1·0-9·4) with BMT alone. Cox proportional-hazard testing showed no difference in risk for the primary efficacy endpoint for CEA plus BMT versus BMT alone (hazard ratio [HR] 0·93, 95% CI 0·22-3·91; p=0·93) or for CAS plus BMT versus BMT alone (1·55, 0·41-5·85; p=0·52). Superiority of CEA or CAS to BMT was not shown, therefore non-inferiority testing was not done. In both the CEA group and the CAS group, five strokes and no deaths occurred in the 30-day period after the procedure. During the 5-year follow-up period, three ipsilateral strokes occurred in both the CAS plus BMT and BMT alone group, with none in the CEA plus BMT group.CEA plus BMT or CAS plus BMT were not found to be superior to BMT alone regarding risk of any stroke or death within 30 days or ipsilateral stroke during the 5-year observation period. Because of the small sample size, results should be interpreted with caution.German Federal Ministry of Education and Research (BMBF) and German Research Foundation (DFG).

Background: Patients with symptomatic internal carotid artery (ICA) stenosis are at high risk of recurrent ischemic stroke and require early interventional treatment and antiplatelet therapy. Increased bleeding rates might counterbalance the periprocedural efficacy of intensified platelet inhibition. We aim to investigate, whether Revacept, a competitive antagonist of glycoprotein VI, adjunct to standard antiplatelet therapy reduces the occurrence of ischemic lesions in patients with symptomatic ICA stenosis. Methods: International, multicenter (16 sites), 3-arm, randomized (1:1:1), double-blind, and placebo-controlled study with parallel groups, including patients with symptomatic ICA stenosis. A single infusion over 20 minutes of either placebo, 40 mg or 120 mg Revacept in addition to guideline-conform antiplatelet therapy was evaluated with regard to the exploratory efficacy end point: Number of new ischemic lesions on diffusion-weighted magnetic resonance imaging after treatment initiation. Main clinical outcome was the combined safety and efficacy end point including any stroke or death, transient ischemic attack, myocardial infarction, coronary intervention, and bleeding complications during follow-up. Results: Out of 160 randomized patients, 158 patients (68±10.1 years, 24% female) received study medication (51 patients placebo, 54 patients 40 mg Revacept and 53 patients 120 mg Revacept) and were followed for 11.2±2.3 months. A total of 1.16 (95% CI, 0.88–1.53)/1.05 (95% CI, 0.78–1.42; P =0.629)/0.63 (95% CI, 0.43–0.93) new diffusion-weighted magnetic resonance imaging lesions per patient were detected in the placebo/40 mg/120 mg Revacept groups, without statistical evidence of a difference. A reduction of the combined safety and efficacy end point during the study period was observed in patients who received 120 mg (HR, 0.46 [95% CI, 0.21–0.99]; P =0.047), but not 40 mg Revacept compared with placebo (HR, 0.72 [95% CI, 0.37–1.42]; P =0.343). Conclusions: Revacept 120 mg reduced the combined safety and efficacy end point in patients with symptomatic ICA stenosis. Registration: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT01645306.

Background: Strokes in the working-age population represent a relevant share of ischemic strokes and re-employment is a major factor for well-being in these patients. Income differences by sex have been suspected a barrier for women in returning to paid work following ischemic stroke. We aim to identify predictors of (not) returning to paid work in patients with large vessel occlusion treated with mechanical thrombectomy (MT) to identify potential areas of targeted vocational rehabilitation. Methods: From 6635 patients enrolled in the German Stroke Registry Endovascular Treatment between 2015 and 2019, data of 606 patients of the working population who survived large vessel occlusion at least 90 days past MT were compared based on employment status at day 90 follow-up. Univariate analysis, multiple logistic regression and analyses of area under the curve were performed to identify predictors of re-employment. Results: We report 35.6% of patients being re-employed 3 months following MT (median age 54.0 years; 36.1% of men, 34.5% of women [ P =0.722]). We identified independent negative predictors against re-employment being female sex (odds ratio [OR], 0.427 [95% CI, 0.229–0.794]; P =0.007), higher National Institutes of Health Stroke Scale (NIHSS) score 24 hours after MT (OR, 0.775 [95% CI, 0.705–0.852]; P P =0.049) and longer hospital stay (OR, 0.930 [95% CI, 0.868–0.998]; P =0.043). Positive predictors favoring re-employment were excellent functional outcome (modified Rankin Scale score of 0–1) at 90 day follow-up (OR, 11.335 [95% CI, 4.864–26.415]; P P =0.035). Multiple regression modeling increased predictive power of re-employment status significantly over prediction by best single functional outcome parameter (National Institutes of Health Stroke Scale 24 hours after MT ≤5; R 2 : 0.582 versus 0.432; area under the receiver operating characteristic curve: 0.887 versus 0.835, P Conclusions: There is more to re-employment after MT than functional outcome alone. In particular, attention should be paid to possible systemic barriers deterring women from resuming paid work. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03356392.

Supplemental Digital Content is available in the text., Background and Purpose: Endovascular therapy is the standard of care in the treatment of acute ischemic stroke due to large-vessel occlusion. A direct association between the number of device passes and the occurrence of symptomatic intracranial hemorrhage (SICH) has been suggested. This study represents an in-depth investigation of the hypothesis that >3 retrieval attempts is associated with an increased rate of SICH in a large multicenter patient cohort. Methods: Two thousand six hundred eleven patients from the prospective German Stroke Registry were analyzed. Patients who received Endovascular therapy for acute large-vessel occlusion of the anterior circulation with known admission National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT Score, final Thrombolysis in Cerebral Infarction, and number of retrieval passes were included. The primary outcome was defined as SICH. The secondary outcome was any type of radiologically confirmed intracranial hemorrhage within the first 24 hours. Multivariate mixed-effects models were used to adjust for cluster effects of the participating centers, as well as for confounders. Results: Five hundred ninety-three patients fulfilled the inclusion criteria. The median number of retrieval passes was 2 [interquartile range, 1–3]. SICH occurred in 26 cases (4.4%), whereas intracranial hemorrhage was identified by neuroimaging in 85 (14.3%) cases. More than 3 retrieval passes was the strongest predictor for SICH (odds ratio, 3.61 [95% CI, 1.38–9.42], P=0.0089) following adjustment for age, admission National Institutes of Health Stroke Scale, admission Alberta Stroke Program Early CT Score, and Thrombolysis in Cerebral Infarction, as well as time from symptom onset to flow restoration. Baseline Alberta Stroke Program Early CT Score of 8 to 9 (odds ratio, 0.26 [95% CI, 0.07–0.89], P=0.032) or 10 (odds ratio, 0.21 [95% CI, 0.06–0.78], P=0.020) were significant protective factors against the occurrence of SICH. Conclusions: More than 3 retrieval attempts is associated with a significant increase in SICH risk, regardless of patient age, baseline National Institutes of Health Stroke Scale, or procedure time. This should be considered when deciding whether to continue a procedure, especially in patients with large baseline infarctions. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03356392.

Background and Purpose: Tandem lesions in the anterior circulation account for up to 30% of all large vessel occlusion strokes. The optimal periprocedural approach in these lesions is still a matter of debate. Methods: Data from the German Stroke Registry—Endovascular Treatment between June 2015 and December 2019 were analyzed. The German Stroke Registry—Endovascular Treatment is an academic, independent, prospective, multicenter, observational registry study with 25 participating stroke centers from all over Germany enrolling consecutive mechanical thrombectomy patients. Tandem lesions were defined as a combination of a relevant extracranial internal carotid artery (ICA) pathology (ipsilateral stenosis >70% or occlusion) and concomitant intracranial large vessel occlusion. Successful reperfusion was defined as modified Thrombolysis in Cerebral Infarction score of 2b-3. The modified Rankin Scale score of 0 to 2 at 3 months indicated good outcome. The aim of this study was to investigate the safety and efficacy of different technical strategies in tandem lesions. Results: Out of 6635 patients, 874 (13.2%) presented with tandem lesions. Of these, 607 (69.5%) underwent acute treatment of the extracranial ICA. Acute treatment of the extracranial ICA lesion led to a higher probability of successful reperfusion (odds ratio, 40.63 [95% CI, 30.03–70.06]) compared with patients who did not undergo acute treatment of the extracranial ICA lesion and was associated with good clinical outcome (39.5% versus 29.3%, P P P =0.035) and intravenous thrombolysis (odds ratio, 10.58 [95% CI, 10.04–20.4]; P =0.033). Intracranial-first approach (n=227) compared with extracranial-first approach (n=267) resulted in a shorter time to flow restoration (53.5 versus 72.0 minutes, P P =0.24) without differences in periprocedural complications. Conclusions: In tandem lesions in the anterior circulation, acute treatment of the extracranial ICA lesion is associated with better clinical outcome and lower mortality. The intracranial-first approach might provide advantages.

ObjectiveTo investigate the aetiology, subsequent preventive strategies and outcomes of stroke despite anticoagulation in patients with atrial fibrillation (AF).MethodsWe analysed consecutive patients with AF with an index imaging-proven ischaemic stroke despite vitamin K-antagonist (VKA) or direct oral anticoagulant (DOAC) treatment across 11 stroke centres. We classified stroke aetiology as: (i) competing stroke mechanism other than AF-related cardioembolism; (ii) insufficient anticoagulation (non-adherence or low anticoagulant activity measured with drug-specific assays); or, (iii) AF-related cardioembolism despite sufficient anticoagulation. We investigated subsequent preventive strategies with regard to the primary (composite of recurrent ischaemic stroke, intracranial haemorrhage, death) and secondary endpoint (recurrent ischaemic stroke) within 3 months after index stroke.ResultsAmong 2946 patients (median age 81 years; 48% women; 43% VKA, 57% DOAC), stroke aetiology was competing mechanism in 713 patients (24%), insufficient anticoagulation in 934 (32%) and cardioembolism despite sufficient anticoagulation in 1299 (44%). We found high rates of the primary (27% of patients; completeness 91.6%) and secondary endpoint (4.6%; completeness 88.5%). Only DOAC (vs VKA) treatment after index stroke showed lower odds for both endpoints (primary: adjusted OR (aOR) (95% CI) 0.49 (0.32 to 0.73); secondary: 0.44 (0.24 to 0.80)), but not switching between different DOAC types. Adding antiplatelets showed higher odds for both endpoints (primary: aOR (95% CI) 1.99 (1.25 to 3.15); secondary: 2.66 (1.40 to 5.04)). Only few patients (1%) received left atrial appendage occlusion as additional preventive strategy.ConclusionsStroke despite anticoagulation comprises heterogeneous aetiologies and cardioembolism despite sufficient anticoagulation is most common. While DOAC were associated with better outcomes than VKA, adding antiplatelets was linked to worse outcomes in these high-risk patients. Our findings indicate that individualised and novel preventive strategies beyond the currently available anticoagulants are needed.Trial registration numberISRCTN48292829.

Background: Early neurological status has been described as predictor of functional outcome in patients with anterior circulation stroke after mechanical thrombectomy. It remains unclear to what proportion the improvement of functional outcome at day 90 is already apparent at 24 hours and at hospital discharge and how later factors impact outcome. Methods: All patients enrolled in the German Stroke Registry (June 2015–December 2019) with anterior circulation stroke and availability of baseline data and neurological status were included. A mediation analysis was conducted to investigate the effect of successful recanalization (Thrombolysis in Cerebral Infarction scale score ≥2b) on good functional outcome (modified Rankin Scale score ≤2 at day 90) with mediation through neurological status (National Institutes of Health Stroke Scale [NIHSS] at 24 hours and at hospital discharge). Results: Three thousand fifty-seven patients fulfilled the inclusion criteria, thereof 2589 (85%) with successful recanalization and 1180 (39%) with good functional outcome. In a multivariate logistic regression analysis, probability of good outcome was significantly associated with age (odds ratio [95% CI], 0.95 [0.94–0.96]), prestroke modified Rankin Scale (0.48 [0.42–0.55]), admission-NIHSS (0.96 [0.94–0.98]), 24-hour NIHSS (0.83 [0.81–0.84]), diabetes (0.56 [0.43–0.72]), proximal middle cerebral artery occlusions (0.78 [0.62–0.97]), passes (0.88 [0.82–0.95]), Alberta Stroke Program Early CT Score (1.07 [1.00–1.14]), successful recanalization (2.39 [1.68–3.43]), intracerebral hemorrhage (0.51 [0.35–0.73]), and recurrent strokes (0.54 [0.32–0.92]). Mediation analysis showed a 20 percentage points (95% CI‚ 17–24 percentage points) increase of probability of good functional outcome after successful recanalization. Fifty-four percent (95% CI‚ 44%–66%) of the improvement in functional outcome was explained by 24-hour NIHSS and 75% (95% CI‚ 62%–90%) by NIHSS at hospital discharge. Conclusions: Fifty-four percent of the improvement in functional outcome after successful recanalization is apparent in NIHSS at 24 hours, 75% in NIHSS at hospital discharge. Other unknown factors not apparent in NIHSS at the 2 time points investigated account for the remaining effect on long term outcome, suggesting, among others, clinical relevance of delayed neurological improvement and deterioration. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03356392.

Introduction Previous studies showed insufficient control of cardiovascular risk factors (CVRF) and high stroke recurrence rates among ischemic stroke patients in Germany. Currently, no structured secondary prevention program exists in clinical routine. We present the trial design and pilot phase results of a complex intervention to improve stroke care after hospital discharge in Germany. Patients and methods SANO is a cluster-randomized trial with 30 participating regions across Germany aiming to enrol 2,790 patients (drks.de, DRKS00015322). Study intervention combines both structural and patient-centred elements. Study development was based on the Medical Research Council framework for complex interventions. In 15 intervention regions, a cross-sectoral multidisciplinary network is established to enhance CVRF control as well as detection and treatment of post-stroke complications. Recommendations on CVRF are based on high-quality secondary prevention guidelines. Study physicians use motivational interviewing and agree with patients on therapeutic targets. While hospitalised, patients also receive dietary counselling and a health-passport to track their progress. During regular visits, CVRF management and potential complications are monitored. The intervention is compared to 15 regions providing usual care. The primary endpoint is the combination of recurrent stroke, myocardial infarction and death assessed 12 months after enrolment and adjudicated in a blinded manner. Results Eighteen patients were enrolled in a pilot phase that demonstrated feasibility of patient recruitment and study procedures. Conclusion SANO is investigating a program to reduce outcome events after ischemic stroke by implementing a complex intervention. If successful, the program may be implemented in routine care on national level in Germany.

Background and Purpose— Diagnosing paroxysmal atrial fibrillation (pAF) can be challenging after acute ischemic stroke. Enhanced and prolonged Holter-ECG monitoring (EPM) improves the detection rate but is not feasible for all patients. We hypothesized that brain natriuretic peptide (BNP) may help to identify patients with stroke at high risk for pAF to select patients for EPM more effectively. Methods— Patients with acute cerebral ischemia ≥60 years presenting in sinus rhythm and without history of AF were included into a prospective, randomized multicenter study to receive either EPM (3× 10-day Holter-ECG) or usual stroke care diagnostic work-up. BNP plasma levels were measured on randomization and 3 months thereafter. Levels were compared between patients with and without pAF detected by means of EPM or usual care. Furthermore, the number needed to screen for EPM depending on BNP cut offs was calculated. Results— A total of 398 patients were analyzed. In 373 patients (93.7%), BNP was measured at baseline and in 275 patients (69.1%) after 3 months. pAF was found in 27 patients by means of EPM and in 9 patients by means of usual care ( P =0.002). Median BNP was higher in patients with pAF as compared to patients without AF in both study arms at baseline (57.8 versus 28.3 pg/mL in the EPM arm, P =0.0003; 46.2 versus 27.7 pg/mL, P =0.28 in the control arm) and after 3 months (74.9 versus 31.3 pg/mL, P =0.012 in the EPM arm, 99.3 versus 26.3 pg/mL, P =0.02 in the control arm). Applying a cut off of 100 pg/mL, the number needed to screen was reduced from 18 by usual care to 3 by EPM. Conclusions— BNP measured early after ischemic stroke identifies a subgroup of patients with stroke at increased risk for AF, in whom EPM is particularly efficacious. Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT01855035.

BackgroundMechanical thrombectomy (MT) rates for the treatment of acute ischaemic stroke due to large vessel occlusion are steadily increasing, but are delivered in heterogenic settings. We aim to investigate effects of procedural load in centers with established MT-structures by comparing high- vs. low-volume centers with regard to procedural characteristics and functional outcomes.MethodsData from 5,379 patients enrolled in the German Stroke Registry Endovascular Treatment (GSR-ET) between June 2015 and December 2019 were compared between three groups: high volume: ≥180 MTs/year, 2,342 patients; medium volume: 135–179 MTs/year, 2,202 patients; low volume: ResultsWe identified high- vs. low-volume centers to be an independent predictor of shorter intra-hospital (admission to groin puncture: 60 vs. 82 min, β = −26.458; p < 0.001) and procedural times (groin puncture to flow restoration: 36 vs. 46.5 min; β = −12.452; p < 0.001) after adjusting for clinically relevant factors. Moreover, high-volume centers predicted a shorter duration of hospital stay (8 vs. 9 days; β = −2.901; p < 0.001) and favorable medical facility at discharge [transfer to neurorehabilitation facility/home vs. hospital/nursing home/in-house fatality, odds ratio (OR) 1.340, p = 0.002]. Differences for functional outcome at 90-day follow-up were observed only on univariate level in the subgroup of primarily to MT center admitted patients (mRS 0–2 38.5 vs. 32.8%, p = 0.028), but did not persist in multivariate analyses.ConclusionDifferences in efficiency measured by procedural times call for analysis and optimization of in-house procedural workflows at regularly used but comparatively low procedural volume MT centers.

Background Idarucizumab is a monoclonal antibody fragment with high affinity for dabigatran reversing its anticoagulant effects within minutes. Thereby, patients with acute ischemic stroke who are on dabigatran treatment may become eligible for thrombolysis with recombinant tissue-type plasminogen activator (rt-PA). In patients on dabigatran with intracerebral hemorrhage idarucizumab could prevent lesion growth. Aims To provide insights into the clinical use of idarucizumab in patients under effective dabigatran anticoagulation presenting with signs of acute ischemic stroke or intracranial hemorrhage. Methods Retrospective data collected from German neurological/neurosurgical departments administering idarucizumab following product launch from January 2016 to August 2018 were used. Results One-hundred and twenty stroke patients received idarucizumab in 61 stroke centers. Eighty patients treated with dabigatran presented with ischemic stroke and 40 patients suffered intracranial bleeding (intracerebral hemorrhage (ICH) in n = 27). In patients receiving intravenous thrombolysis with rt-PA following idarucizumab, 78% showed a median improvement of 7 points in National Institutes of Health Stroke Scale. No bleeding complications were reported. Hematoma growth was observed in 3 out of 27 patients with ICH. Outcome was favorable with a median National Institutes of Health Stroke Scale improvement of 4 points and modified Rankin score 0–3 in 61%. Six out of 40 individuals (15%) with intracranial bleeding died during hospital stay. Conclusion Administration of rt-PA after reversal of dabigatran activity with idarucizumab in case of acute ischemic stroke seems feasible, effective, and safe. In dabigatran-associated intracranial hemorrhage, idarucizumab appears to prevent hematoma growth and to improve outcome.

Background and Purpose— Ischemic stroke causes major disability as a consequence of neuronal loss and recurrent ischemic events. Biomarkers predicting tissue damage or stroke recurrence might be useful to guide an individualized stroke therapy. NfL (neurofilament light chain) is a promising biomarker that might be used for this purpose. Methods— We used individual data of patients with an acute ischemic stroke and clinical long term follow-up. Serum NfL (sNfL) was quantified within 24 hours after admission and after 1 year and compared with other biomarkers (GDF15 [growth differentiation factor 15], S100, NT-proBNP [N-terminal pro-B-type natriuretic peptide], ANP [atrial natriuretic peptide], and FABP [fatty acid–binding protein]). The primary end point was functional outcome after 90 days and cerebrovascular events and death (combined cardiovascular end point) within 36 months of follow-up. Results— Two hundred eleven patients (mean age, 68.7 years; SD, ±12.6; 41.2% women) with median clinical severity on the National Institutes of Health Stroke Scale (NIHSS) score of 3 (interquartile range, 1–5) and long-term follow-up with a median of 41.8 months (interquartile range, 40.0–44.5) were prospectively included. We observed a significant correlation between sNfL and NIHSS at hospital admission (r=0.234; P P P =0.048) together with NIHSS (OR, 1.303; 95% CI, 1.164–1.458; P P =0.022). Similarly, sNfL was valuable for the prediction of the combined cardiovascular end point (OR, 2.002; 95% CI, 1.213–3.302; P =0.007), besides NIHSS (OR, 1.110; 95% CI, 1.000–1.232; P =0.049), diabetes mellitus (OR, 2.942; 95% CI, 1.306–6.630; P =0.005), and age-related white matter change rating (severe; OR, 4.816; 95% CI, 1.206–19.229; P =0.026) after multivariate regression analysis. Kaplan-Meier analysis revealed significantly more combined cardiovascular end points (18 [14.1%] versus 38 [45.8%], log-rank test P Conclusions— sNFL is a valuable biomarker for functional independence 90 days after ischemic stroke and predicts cardiovascular long-term outcome. Clinical Trial Registration— URL: http://www.isrctn.com . Unique identifier: ISRCTN 46104198.

ZusammenfassungNeurovaskuläre Erkrankungen gehören zu den häufigsten Erkrankungen im neurologischen Fachgebiet. Vor dem Hintergrund der immer älter werdenden Gesellschaft spielt der Schlaganfall und damit dessen Diagnostik eine herausragende Rolle. Für den Neurologen in eigener Hand ermöglicht der Ultraschall nicht nur die Einschätzung der Gefäßsituation in der Primärprophylaxe, sondern selbstverständlich v. a. beim akuten Schlaganfall bei Beantwortung der Fragestellung hinsichtlich einer Thrombektomie oder Thrombolyse. Auch im Verlauf hilft der Ultraschall bei der ätiologischen Zuordnung und somit wichtige Therapieentscheidungen zu treffen. Hier sind neben arteriosklerotischen Obstruktionen insbesondere Dissektionen zu nennen. In der Zukunft wird aufgrund der neuen Studienlage pro invasiver Therapie auch die sonografische Detektion eines kardialen Rechts-Links-Shunts mittels transkranieller Doppler- oder Duplexsonografie von noch größerer Bedeutung sein. Nach therapeutischen Eingriffen insbesondere an der extrakraniellen Arteria carotis interna wird die Sonografie zur Beurteilung des Operations- oder Interventionsergebnisses und bei der Verlaufskontrolle genutzt. Ebenso gelingt mit dem Ultraschall auch die Verlaufsbeurteilung intrakranieller Stenosen. Wertvoll ist der transkranielle Ultraschall auch in der Diagnostik auf der Intensivstation, bspw. zur Detektion erhöhten Hirndrucks oder in der Hirntoddiagnostik. Andere Anwendungen sind bspw. die Detektion von intrakraniellen Vasospasmen nach Subarachnoidalblutungen, die Diagnostik von Vaskulitiden der hirnversorgenden Gefäße, und neuerdings auch der transorbitale Ultraschall bei ischämischen Ophthalmopathien. Therapeutisch wird der Ultraschall in der Neurologie bisher überwiegend auf wissenschaftlicher Basis im Rahmen von Studien zur Sonothrombolyse eingesetzt. Die Anwendung transkranieller Sonografie zeigte beim akuten Mediaverschluss eine höhere Rekanalisationsrate, es kam allerdings auch zu etwas häufigeren, statistisch nicht signifikanten symptomatischen Einblutungen. In den meisten Fällen ist bei der alltäglichen Anwendung der Duplexsonografie der Vorzug zu geben, aber auch die einfache Dopplersonografie gehört nach wie vor zum Standardrepertoire der meisten Ultraschallabore. In diesem Artikel möchten wir Ihnen über die wichtigsten Anwendungen des Ultraschalls in der Neurologie einen Überblick geben.

Background and Purpose Prolonged electrocardiography (ECG)-monitoring in stroke patients improves the detection of paroxysmal atrial fibrillation (pAF). However, most randomized studies only had short follow-up. We aimed to provide 3-year follow-up data for AF detection and stroke recurrence risk.Methods We randomized 402 patients aged ≥60 years with acute ischemic strokes without AF to either enhanced and prolonged monitoring (EPM; 3×10-day Holter-ECG-monitoring) or standard-of-care (≥24 hours ECG-monitoring). The endpoint of the current analysis was AF within 36 months analyzed by intention to treat. Long-term follow-up was performed for 36 months.Results Two hundred and seventy-four patients (80%) participated in the extended follow-up (median duration of follow-up was 36 months [interquartile range, 12 to 36]). During the first 6 months, more AF was documented in the EPM arm compared to the control arm (13.5% vs. 5.1%; 95% confidence interval, 2.9% to 14.4%; P=0.004). During months 6 to 36, AF was less detected in the EPM intervention arm than in the control arm (2.0% vs. 7.3%; 95% confidence interval, 0.7% to 9.9%; P=0.028). Overall, the detection rate of AF within 36 months was numerically higher within the EPM group (15.0% vs. 11.1%, P=0.30). Numerically less patients in the EPM arm had recurrent ischemic strokes (5.5% vs. 9.1%, P=0.18), transient ischemic attacks (3.0% vs. 4.5%, P=0.44) or died (4.5% vs. 6.6%, P=0.37).Conclusions Enhanced and prolonged ECG monitoring increased AF detection during the first six months, but there was significantly more clinical AF during months 6 to 36 observed in the usual-care arm. This suggests that EPM leads to an earlier detection of clinically relevant AF.

Background and Purpose: Endovascular therapy is the standard of care in the treatment of acute ischemic stroke due to large-vessel occlusion. Often, more than one retrieval attempt is needed to achieve reperfusion. We aimed to quantify the influence of endovascular therapy on clinical outcome depending on the number of retrievals needed for successful reperfusion in a large multi-center cohort. Methods: For this observational cohort study, 2611 patients from the prospective German Stroke Registry included between June 2015 and April 2018 were analyzed. Patients who received endovascular therapy for acute anterior circulation stroke with known admission National Institutes of Health Stroke Scale score and Alberta Stroke Program Early CT Score, final Thrombolysis in Cerebral Infarction score, and number of retrievals were included. Successful reperfusion was defined as a Thrombolysis in Cerebral Infarction score of 2b or 3. The primary outcome was defined as functional independence (modified Rankin Scale score of 0–2) at day 90. Multivariate mixed-effects models were used to adjust for cluster effects of the participating centers and confounders. Results: The inclusion criteria were met by 1225 patients. The odds of good clinical outcome decreased with every retrieval attempt required for successful reperfusion: the first retrieval had the highest odds of good clinical outcome (adjusted odds ratio, 6.45 [95% CI, 4.0–10.4]), followed by the second attempt (adjusted odds ratio, 4.56 [95% CI, 2.7–7.7]), and finally the third (adjusted odds ratio, 3.16 [95% CI, 1.8–5.6]). Conclusions: Successful reperfusion within the first 3 retrieval attempts is associated with improved clinical outcome compared with patients without reperfusion. We conclude that at least 3 retrieval attempts should be performed in endovascular therapy of anterior circulation strokes. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03356392.

In Deutschland treten 262.000 Schlaganfalle pro Jahr auf. Das Alter ist einer der wichtigsten nicht modifizierbaren Risikofaktoren, so dass allein durch die demografische Entwicklung mit einer weiteren Zunahme zu rechnen ist. Lebensstil-Risikofaktoren wie Nikotinkonsum, Ubergewicht und korperliche Inaktivitat bieten neben klassischen Faktoren wie arterielle Hypertonie und Diabetes mellitus optimale Ansatzpunkte fur die Primarpravention. Durch das Nichtraucherschutzgesetz konnte in Deutschland eine Abnahme des Nikotinkonsums und bereits eine Reduktion kardiovaskularer Ereignisse beobachtet werden. Einer Zunahme des Korpergewichtes in der Gesamtbevolkerung konnte mit Hilfe einer verbesserten Gesundheitserziehung (korperliche Aktivitat, Ernahrung) und Lebensmittelkennzeichnung begegnet werden. In der medikamentosen Primarprophylaxe hat der Einsatz von ASS aufgrund von Blutungsnebenwirkungen an Stellenwert verloren, wahrend der Einsatz von Statinen patientenindividuell diskutiert wird.

Summary Background Systematic electrocardiogram (ECG) monitoring improves detection of covert atrial fibrillation in stroke survivors but the effect on secondary prevention is unknown. We aimed to assess the effect of systematic ECG monitoring of patients in hospital on the rate of oral anticoagulant use after 12 months. Methods In this investigator-initiated, randomised, open-label, parallel-group multicentre study with masked endpoint adjudication, we recruited patients aged at least 18 years with acute ischaemic stroke or transient ischaemic attack without known atrial fibrillation in 38 certified stroke units in Germany. Patients were randomly assigned (1:1) to usual diagnostic procedures for atrial fibrillation detection (control group) or additional Holter-ECG recording for up to 7 days in hospital (intervention group). Patients were stratified by centre using a random permuted block design. The primary outcome was the proportion of patients on oral anticoagulants at 12 months after the index event in the intention-to-treat population. Secondary outcomes included the number of patients with newly diagnosed atrial fibrillation in hospital and the composite of recurrent stroke, major bleeding, myocardial infarction, or death after 6 months, 12 months, and 24 months. This trial was registered with ClinicalTrials.gov , NCT02204267 , and is completed and closed for participants. Findings Between Dec 9, 2014, and Sept 11, 2017, 3465 patients were randomly assigned, 1735 (50·1%) to the intervention group and 1730 (49·9%) to the control group. Oral anticoagulation status was available in 2920 (84·3%) patients at 12 months (1484 [50·8%] in the intervention group and 1436 [49·2%] in the control group). For the primary outcome, at 12 months, 203 (13·7%) of 1484 patients in the intervention group versus 169 (11·8%) of 1436 in the control group were on oral anticoagulants (odds ratio [OR] 1·2 [95% CI 0·9–1·5]; p=0·13). Atrial fibrillation was newly detected in patients in hospital in 97 (5·8%) of 1714 in the intervention group versus 68 (4·0%) of 1717 in the control group (hazard ratio [HR] 1·4 [95% CI 1·0–2·0]; p=0·024). The composite of cardiovascular outcomes and death did not differ between patients randomly assigned to the intervention group versus the control group at 24 months (232 [13·5%] of 1714 vs 249 [14·5%] of 1717; HR 0·9 [0·8–1·1]; p=0·43). Skin reactions due to study ECG electrodes were reported in 56 (3·3%) patients in the intervention group. All-cause death occured in 73 (4·3%) patients in the intervention group and in 103 (6·0%) patients in the control group (OR 0·7 [0·5–0·9]). Interpretation Systematic core centrally reviewed ECG monitoring is feasible and increases the detection rate of atrial fibrillation in unselected patients hospitalised with acute ischaemic stroke or transient ischaemic attack, if added to usual diagnostic care in certified German stroke units. However, we found no effect of systematic ECG monitoring on the rate of oral anticoagulant use after 12 months and further efforts are needed to improve secondary stroke prevention. Funding Bayer Vital. Translation For the German translation of the abstract see Supplementary Materials section.

Patients with stroke or transient ischemic attacks (TIAs) and internal carotid artery stenosis harbor an increased risk of recurrent stroke especially within 2 weeks after the first event. In addition, the revascularization procedure itself (carotid endarterectomy [CEA] or carotid artery stenting [CAS]) is associated with both clinically apparent and silent brain infarctions, mainly caused by the embolic nature of the ruptured carotid plaque. The glycoprotein VI (GPVI) fusion protein Revacept is a highly specific antithrombotic drug without direct inhibition of systemic platelet function that might reduce periprocedural distal embolization from the vulnerable ruptured plaque located at the internal carotid artery. By shielding collagen at the site of vascular injury, Revacept inhibits plaque-mediated platelet adhesion and aggregation, while not directly affecting systemic hemostasis. In this phase II study, 158 patients with symptomatic carotid artery stenosis with recent TIA or stroke were randomized to receive a single dose of either Revacept (40 or 120 mg) or placebo. All patients were on standard secondary preventive therapy (statins and platelet inhibition) and underwent CEA, CAS, or best medical therapy according to current guidelines. The efficacy of Revacept was evaluated by exploratory assessment of new diffusion-weighted imaging lesions on magnetic resonance imaging after the revascularization procedure; a combination of cardiovascular events (ischemic and hemorrhagic stroke, TIA, myocardial infarction, or coronary intervention) and bleeding complications served to assess clinically critical patients' outcome and safety. This exploratory phase II randomized, double-blind clinical trial provides valuable insights on the safety, tolerability, and efficacy of Revacept in patients with symptomatic carotid artery stenosis.

Background Patients aged ≥90 were excluded or under‐represented in past thrombectomy trials; thus, uncertainty remains whether treatment benefits can be expected regardless of age. This study investigates outcome and safety of thrombectomy in nonagenarians to improve decision making in a real‐world setting. Methods and Results All currently available data of patients aged ≥90 enrolled in the GSR‐ET (German Stroke Registry–Endovascular Treatment) were combined with a smaller cohort from 3 tertiary stroke centers. Baseline characteristics, procedural (Thrombolysis in Cerebral Infarction scale) and functional outcomes (modified Rankin Scale; mRS ), as well as complications (symptomatic intracranial hemorrhage, serious adverse events; SAEs) were analyzed. Good functional outcome was defined as mRS ≤3 at 90‐days. 203 patients with anterior circulation stroke and prestroke mRS ≤3 were included. The rate of successful recanalization (Thrombolysis in Cerebral Infarction scale ≥2b) was 75.9% (154/203). Good functional outcome ( mRS ≤3) was observed in 21.6% (41 of 193) at 90‐days. In‐hospital mortality was 27.1% (55 of 203) and increased significantly at 90 days to 48.9% (93 of 190; P CI , 1.01–3.70; P =0.046) and initial National Institute of Health Stroke Scale (adjusted odds ratio, 0.85; 95% CI , 0.76–0.97; P =0.014) as independent predictors for good outcome. Patients with successful recanalization had a significant ( P =0.001) shift of mRS distribution with higher rates of good functional outcomes (23.8% [34 of 143] versus 14.9% [7 of 47]) and lower mortality at 90‐days (46.8% [67 of 143] versus 55.3% [26 of 47]). Conclusions Despite high mortality and less frequent favorable outcome, our data suggest that thrombectomy is still effective and safe for nonagenarians. Decision making for thrombectomy in patients aged ≥90 should be based on a case‐by‐case basis with regard to initial National Institute of Health Stroke Scale and Alberta Stroke Program Early CT Score.

Introduction: Revacept is a novel vascular lesion-directed inhibitor of platelet adhesion and thrombus formation, exhibiting no effects on the homeostatic functions of circulating platelets. Objective: The effects of Revacept on plaque-mediated thrombosis were investigated in patients with symptomatic stenosis of the internal carotid artery (at least 50%, following ECST-criteria). Methods: Within an international, prospective, multicenter (n=16), randomized trial 158 patients could be randomized to receive placebo, or 40/120 mg Revacept by intravenous infusion over 20 minutes. Cerebrovascular events and cardiovascular complications were followed up to 3 months. Results: 158 patients were finally included in the study. Of these, 127 (80.4%) received carotid endarterectomy, 12 received carotid stenting (7.6%) and 19 were referred to intensified conservative treatment (12.0%). Safety data showed cardiovascular events such as transitory ischemic attack (TIA) and ischemic stroke 24 hours after drug administration in 1 (0.6%) and 5 (3.1%) patients, and 3 months after drug administration in 5 (3.1%) and 9 (5.7%) patients, respectively. With regard to bleeding complications, intracerebral hemorrhage was not observed in any of the patients within 24 hours, and in 1 patient (0.6%) at 3 months follow up. Postoperative hematoma of any kind was observed in 9 patients (5.7%). Two other bleeding events (GI-bleeding and ear-bleeding) occurred within 3 months follow up. Coronary vascular events, defined as Troponin-I-elevation, were observed in 2 patients (1.3%) at 24 hours, and in 7 patients (4.4%) at 3 months after drug administration. Coronary intervention was necessary in 1 patient (0.6%) and 5 patients (3.1%), 24 hours and 3 months after Revacept infusion, respectively. These complications rates are comparable to the rate at day 30 follow up within the ICSS-study: ischemic stroke (91 patients 5.3%), intracerebral hemorrhage (8 patients, 0.5%) and any wound hematoma (81 patients, 4.7%) Conclusions: The addition of Revacept to guideline-recommended anti-thrombotic therapy in patients with symptomatic stenosis of the internal carotid artery did not increase bleeding complications within the overall study population compared to previous studies.

Dieser CME-Fortbildungsartikel soll einen strukturierten Untersuchungsgang der Doppler- und Duplexsonografie der hirnversorgenden Gefase vermitteln und dabei auf besondere Schwierigkeiten/Fallstricke hinweisen. Im Einzelnen werden Kriterien zur Stenosegraduierung, haufig auftretende Fehlermoglichkeiten sowie anatomische und methodische Besonderheiten dargestellt. This CME article presents a structured examination of duplex sonography of the brain-supplying arteries, especially focusing on difficulties and pitfalls. Criteria for stenosis grading and common mistakes as well as anatomical and methodical characteristics are described in detail.

Zusammenfassung Hintergrund Demografischer Wandel, Urbanisierung sowie eine zunehmende Spezialisierung der Akutversorgung von Schlaganfallpatienten erfordern eine Anpassung von Versorgungsstrukturen mit dem Ziel, auch Patienten in ländlichen Regionen leitliniengerecht behandeln zu können. Methodik Im Frühjahr 2016 wurde ein landesweites telemedizinisches Schlaganfallnetzwerk unter Einbeziehung aller 6 überregionalen Stroke Units im Land Rheinland-Pfalz etabliert. Die Zuständigkeit für den Konsildienst wechselt täglich zwischen den Kliniken und steht rund um die Uhr zur Verfügung. Alle Kriterien des OPS 8.98b werden erfüllt. Am Netzwerk teilnehmen können alle regionalen Stroke Units und Kliniken, die prädefinierte Kriterien erfüllen und nicht in regionaler Konkurrenz mit etablierten Stroke Units stehen. Ergebnisse Zu Projektbeginn am 01.04. 2016 nahmen 6 Kliniken teil, die alle eine regionale Stroke Unit unter internistischer Leitung besitzen. Innerhalb des ersten Jahres erfolgten 1568 telemedizinische Konsile. Die Diagnosen waren ischämische Infarkte (n = 802 Patienten; 51,2 %), intrazerebrale Blutungen (n = 46; 2,9%), transitorisch ischämische Attacken (TIA; n = 319; 20,4 %) und nicht vaskuläre Ursachen (sog. Stroke Mimics; n = 400; 25,5 %). Die Latenz zwischen Klinikaufnahme und Konsilbeginn betrug im Median 21 Minuten (Interquartilrange (IQR) 22 Minuten), die mediane Konsildauer lag bei 24 Minuten (IQR 22 Minuten). Bei den Patienten mit ischämischen Schlaganfällen betrug die Lyserate 12,5 % (n = 100). Eine mechanische Thrombektomie wurde nach Weiterverlegung in eines der Zentren bei 4,6 % (n = 37) der Patienten durchgeführt. Schlussfolgerung Die telemedizinische Netzwerkbildung ist geeignet, die landesweite Versorgung von Schlaganfallpatienten sicherzustellen. Weitere Analysen, insbesondere zum Outcome, werden benötigt.

ZusammenfassungVerkürzte Liegezeiten, wachsender administrativer Aufwand, eine zunehmende Komplexität in Diagnostik und Therapie und der wirtschaftliche Druck gehen mit einer Zunahme der Arbeitsdichte für Ärzte in neurologischen Kliniken einher. Eine zu hohe Arbeitsdichte kann die Behandlungsqualität beeinträchtigen und die Ausbildung von Assistenzärzten gefährden. In der Pflege, in psychiatrischen Kliniken und im Bereich der neurologischen Rehabilitation gibt es aktuell Ansätze, Mindestpersonalstandards einzuführen. Vor diesem Hintergrund plädieren die Autoren für:– die Einführung von Personaluntergrenzen für Ärzte in neurologischen Kliniken, aber auch für andere Berufsgruppen und andere medizinische Fächer– die Entwicklung eines Personalbemessungsinstruments, mit dessen Hilfe für jede Klinik ein angemessener Personalschlüssel festgelegt werden kann– eine Verbindlichkeit der Personalstandards einschließlich einer kompletten Gegenfinanzierung – realistische Übergangsfristen angesichts des aktuellen Ärztemangels

Objective:Prolonged ECG monitoring after stroke frequently reveals short paroxysmal atrial fibrillation (pAF) and supraventricular (SV) runs. The minimal duration of atrial fibrillation (AF) required to induce cardioembolism, the relevance of SV runs, and whether short pAF results from cerebral damage itself are currently being debated. We aimed to study the relevance of SV runs and short pAF detected by prolonged Holter ECG after cerebral ischemia during long-term follow-up.Methods:Analysis is from the prospective Find-AF trial (ISRCTN46104198). We included patients with acute cerebral ischemia. Those without AF on admission received 7-day Holter ECG monitoring. We differentiated patients with AF on admission (AF-adm), with pAF (>30 seconds), with SV runs (>5 beats but Results:A total of 254 of 281 initially included patients were analyzed (mean age 70.0 years, 45.3% female). Forty-three (16.9%) had AF-adm. A total of 211 received 7-day Holter ECG monitoring: 27 (12.8%) had pAF, 67 (31.8%) had SV runs, and 117 (55.5%) were controls. During a mean 3.7 years of follow-up, the SV runs group had more recurrent strokes (p = 0.04) and showed numerically more novel AF (12% vs 5%, p = 0.09) than the controls. Seventy-five percent of the patients with manifest pAF detected after cerebral ischemia still had AF during follow-up (50% paroxysmal, 50% persisting/permanent).Conclusions:Patients with cerebral ischemia and SV runs had more recurrent strokes and numerically more novel AF during follow-up and could benefit from further prolonged ECG monitoring. pAF detected after stroke is not a temporal phenomenon.

Background and purpose Prolonged electrocardiogram (ECG) monitoring after ischaemic stroke increases the diagnostic yield of paroxysmal atrial fibrillation (pAF). In order to facilitate the additional workload involved in ECG analysis due to prolonged monitoring times, we investigated the effectiveness of pAF detection with an automated software algorithm (SA) in comparison to the routine staff-based analysis (RA) during standard stroke-unit care. Therefore, patients with acute ischaemic stroke or transitory ischaemic attack presenting with sinus rhythmus on the admission ECG and no history of atrial fibrillation were prospectively included. Methods A 24-h Holter ECG assessment was performed using either RA based on a computer-aided evaluation and subsequent review by a cardiologist or a commercially available automated SA. In the case of discordant results concerning the occurrence of pAF between the two methods, the data underwent an independent external rating. Results Of 809 prospectively enrolled patients, 580 patients fulfilled the inclusion criteria. pAF was ultimately diagnosed in 3.3% of the cohort (19 patients). SA and RA correctly diagnosed pAF in 17 patients resulting in a comparable diagnostic effectiveness of the analysis methods (sensitivity: SA 89.5% vs. RA 89.5%; specificity: SA 99.3% vs. RA 99.1%; κ, 0.686; P < 0.001; 95% confidence interval, 0.525–0.847). RA revealed clinically relevant ECG abnormalities in an additional seven patients. Conclusions Although it should not completely replace RA, SA-based evaluation of Holter ECG reaches a high diagnostic effectiveness for the detection of pAF and can be used for a rapid and resource-saving analysis of ECG data to deal with prolonged monitoring times.

Background and purpose The detection of paroxysmal atrial fibrillation (pAF) in patients presenting with ischaemic stroke shifts secondary stroke prevention to oral anticoagulation. In order to deal with the time- and resource-consuming manual analysis of prolonged electrocardiogram (ECG)-monitoring data, we investigated the effectiveness of pAF detection with an automated algorithm (AA) in comparison to a manual analysis with software support within the IDEAS study [study analysis (SA)]. Methods We used the dataset of the prospective IDEAS cohort of patients with acute ischaemic stroke/transient ischaemic attack presenting in sinus rhythm undergoing prolonged 72-h Holter ECG with central adjudication of atrial fibrillation (AF). This adjudicated diagnosis of AF was compared with a commercially available AA. Discordant results with respect to the diagnosis of pAF were resolved by an additional cardiological reference confirmation. Results Paroxysmal AF was finally diagnosed in 62 patients (5.9%) in the cohort (n = 1043). AA more often diagnosed pAF (n = 60, 5.8%) as compared with SA (n = 47, 4.5%). Due to a high sensitivity (96.8%) and negative predictive value (99.8%), AA was able to identify patients without pAF, whereas abnormal findings in AA required manual review (specificity 96%; positive predictive value 60.6%). SA exhibited a lower sensitivity (75.8%) and negative predictive value (98.5%), and showed a specificity and positive predictive value of 100%. Agreement between the two methods classified by kappa coefficient was moderate (0.591). Conclusion Automated determination of 'absence of pAF' could be used to reduce the manual review workload associated with review of prolonged Holter ECG recordings.

Summary Background S44819, a selective GABAA α5 receptor antagonist, reduces tonic post-ischaemic inhibition of the peri-infarct cortex. S44819 improved stroke recovery in rodents and increased cortical excitability in a transcranial magnetic stimulation study in healthy volunteers. The Randomized Efficacy and Safety Trial of Oral GABAA α5 antagonist S44819 after Recent ischemic Event (RESTORE BRAIN) aimed to evaluate the safety and efficacy of S44819 for enhancing clinical recovery of patients with ischaemic stroke. Methods RESTORE BRAIN was an international, randomised, double-blind, parallel-group, placebo-controlled, multicentre phase 2 trial that evaluated the safety and efficacy of oral S44189 in patients with recent ischaemic stroke. The study was done in specialised stroke units in 92 actively recruiting centres in 14 countries: ten were European countries (Belgium, Czech Republic, France, Germany, Hungary, Italy, Netherlands, Poland, Spain, and the UK) and four were non-European countries (Australia, Brazil, Canada, and South Korea). Patients aged 18–85 years with acute ischaemic stroke involving cerebral cortex (National Institute of Health Stroke Scale [NIHSS] score 7–20) without previous disability were eligible for inclusion. Participants were randomly assigned to receive 150 mg S44819 twice a day, 300 mg S44819 twice a day, or placebo twice a day by a balanced, non-adaptive randomisation method with a 1:1:1 ratio. Treatment randomisation and allocation were centralised via the interactive web response system using computer-generated random sequences with a block size of 3. Blinding of treatment was achieved by identical appearance and taste of all sachets. Patients, investigators and individuals involved in the analysis of the trial were masked to group assignment. The primary endpoint was the modified Rankin Scale (mRS) score 90 days from onset of treatment, evaluated by shift analysis (predefined main analysis) or by dichotomised analyses using 0–1 versus 2–6 and 0–2 versus 3–6 cutoffs (predefined secondary analysis). Secondary endpoints were the effects of S44819 on the NIHSS and Montreal Cognitive Assessment (MoCA) scores, time needed to complete parts A and B of the Trail Making Test, and the Barthel index. Efficacy analyses were done on all patients who received at least one dose of treatment and had at least one mRS score taken after day 5 (specifically, on or after day 30). Safety was compared across treatment groups for all patients who received at least one dose of treatment. The study was registered at ClinicalTrials.gov , NCT02877615 . Findings Between Dec 19, 2016, and Nov 16, 2018, 585 patients were enrolled in the study. Of these, 197 (34%) were randomly assigned to receive 150 mg S44819 twice a day, 195 (33%) to receive 300 mg S44819 twice a day, and 193 (33%) to receive placebo twice a day. 189 (96%) of 197 patients in the 150 mg S44819 group, 188 (96%) of 195 patients in the 300 mg S44819 group, and 191 (99%) patients in the placebo group received at least one dose of treatment and had at least one mRS score taken after day 5, and were included in efficacy analyses. 195 (99%) of 197 patients in the 150 mg S44819 group, 194 (99%) of 195 patients in the 300 mg S44819 group, and 193 (100%) patients in the placebo group received at least one dose of treatment, and were included in safety analyses. The primary endpoint of mRS at day 90 did not differ between each of the two S44819 groups and the placebo group (OR 0·91 [95% CI 0·64–1·31]; p=0·80 for 150 mg S44819 compared with placebo and OR 1·17 [95% CI 0·81–1·67]; p=0·80 for 300 mg S44819 compared with placebo). Likewise, dichotomised mRS scores at day 90 (mRS 0–2 vs 3–6 or mRS 0–1 vs 2–6) did not differ between groups. Secondary endpoints did not reveal any significant group differences. The median NIHSS score at day 90 did not differ between groups (4 [IQR 2–8] in 150 mg S44819 group, 4 [2–7] in 300 mg S44819 group, and 4 [2–6] in placebo group), nor did the number of patients at day 90 with an NIHSS score of up to 5 (95 [61%] of 156 in 150 mg S44819 group, 106 [66%] of 161 in 300 mg S44819 group, and 104 [66%] of 157 in placebo group) versus more than 5 (61 [39%] in 150 mg S44819 group, 55 [34%] in 300 mg S44819 group, and 53 [34%] in placebo group). Likewise, the median MoCA score (22·0 [IQR 17·0–26·0] in 150 mg S44819 group, 23·0 [19·0–26·5] in 300 mg S44819 group, and 22·0 [17·0–26·0] in placebo group), time needed to complete parts A (50 s [IQR 42–68] in 150 mg S44819 group, 49 s [36–63] in 300 mg S44819 group, and 50 s [38–68] in placebo group) and B (107 s [81–144] in 150 mg S44819 group, 121 s [76–159] in 300 mg S44819 group, and 130 s [86–175] in placebo group) of the Trail Making Test, and the Barthel index (90 [IQR 60–100] in 150 mg S44819 group, 90 [70–100] in 300 mg S44819 group, and 90 [70–100] in placebo group) were similar in all groups. Number and type of adverse events were similar between the three groups. There were no drug-related adverse events and no drug-related deaths. Interpretation There was no evidence that S44819 improved clinical outcome in patients after ischaemic stroke, and thus S44819 cannot be recommended for stroke therapy. The concept of tonic inhibition after stroke should be re-evaluated in humans. Funding Servier.

Background and Purpose- Diagnosing paroxysmal atrial fibrillation (pAF) can be challenging after acute ischemic stroke. Enhanced and prolonged Holter-ECG monitoring (EPM) improves the detection rate but is not feasible for all patients. We hypothesized that brain natriuretic peptide (BNP) may help to identify patients with stroke at high risk for pAF to select patients for EPM more effectively. Methods- Patients with acute cerebral ischemia ≥60 years presenting in sinus rhythm and without history of AF were included into a prospective, randomized multicenter study to receive either EPM (3× 10-day Holter-ECG) or usual stroke care diagnostic work-up. BNP plasma levels were measured on randomization and 3 months thereafter. Levels were compared between patients with and without pAF detected by means of EPM or usual care. Furthermore, the number needed to screen for EPM depending on BNP cut offs was calculated. Results- A total of 398 patients were analyzed. In 373 patients (93.7%), BNP was measured at baseline and in 275 patients (69.1%) after 3 months. pAF was found in 27 patients by means of EPM and in 9 patients by means of usual care (

Background: The cardiac diagnostic workup of stroke patients, especially the value of echocardiography and prolonged and enhanced Holter-ECG monitoring (EPM), is still a matter of debate. We aimed to analyse the impact of pathologies detected by echocardiography and ECG monitoring on therapeutic decisions and prognosis. Methods: Find-AF RANDOMISED was a prospective multicenter study which randomised 398 acute ischemic stroke patients ≥ 60 years to EPM or usual stroke unit care. Therapeutic consequences of echocardiography and routine Holter-ECG or EPM, respectively, were compared and one-year mortality was calculated. Results: 50.3% received EPM and 49.7% routine ECG monitoring. 82.9 % underwent transthoracic echocardiography (TTE), 38.9 % transesophageal echocardiography (TEE) and 25.6 % both procedures. 14/90 TEE pathologies and 1/89 TTE pathology led to a change in therapy, resulting in a number needed to change decision (NNCD) of 12 and 334, respectively. In comparison, EPM found atrial fibrillation (AF) in 27 of 200 patients, and routine ECG monitoring in twelve of 198 patients, leading to therapeutic changes in all patients (NNCD 8 and 17, respectively). We found a trend towards a higher one-year mortality in patients with pathologic echocardiographic findings (p = 0.093). Conclusions: Most changes in therapeutic decisions were caused by EPM, which should therefore play a more prominent role in future guidelines. Echocardiography identifies a patient group at high cardiovascular risk, but rarely result in therapeutic changes. Whether this patient group requires further cardiovascular workup remains unknown. This should be further investigated by interdisciplinary neurocardiologic teams and in appropriate future trials.

Background: Detecting concealed paroxysmal atrial fibrillation (pAF) is a major focus of the workup of ischemic-stroke-patients, but requires elaborate ECG-monitoring. We aimed to evaluate pre-specified predictors to determine stroke patients with an increased probability of underlying pAF. We applied cut-off-levels recently suggested by the German Stroke Society 1 . Methods: The Find-AF RANDOMISED -trial (NCT01855035) evaluated 3x10-day Holter-ECG vs. standard-care in 398 patients > 60 years with acute ischemic strokes. The primary endpoint was novel pAF after 6 months. 27 patients in the intervention arm (13.5 %) and 9 patients in the control arm (9.0 %) met the primary endpoint (p=0.002). We used Pearson’s Chi 2 -test and the Mann-Whitney-U-test, as applicable. In variables with p Results: Table 1 shows known pAF-risk-factors in relation to whether patients had pAF. The absence of a clinical lacunar syndrome (p=0.007) or lacunar lesions (p=0.018), increased NIHSS-Score (p=0.003), frequent atrial premature beats (APB, p=0.003), prolonged supraventricular runs (p=0.01), enlarged left atria (p=0.07) and increased brain-natriuretic-peptide-levels (p=0.001) were associated with underlying pAF. Frequent APB differentiated best between those with and without pAF (area under the curve, AUC: 0.71). Conclusions: Several of the evaluated markers are useful to preselect stroke patients for enhanced ECG-monitoring. APB and comprehensive measures of both left atrial size and function (LAVI/a’) showed the highest AUC and should be used when preselecting stroke patients for prolonged ECG-monitoring.

Introduction: Serum neurofilament light chains (sNFL) are a marker of axonal injury in various neurologic diseases. We aimed to address their diagnostic and prognostic value in patients following acute ischemic stroke. Methods: We selected patients from the Find-AF trial (ISRCTN 46104198) with available serum samples 24 h after hospital admission and further brain imaging (MRI or CT-Scans with minimum 3 days after symptom onset). sNFL levels were measured using the SIMOA technique. Infarct size on brain imaging was classified as lacunar (< 10 cm 3 ) or non-lacunar (>10 cm 3 ). We assessed whether sNFL was associated with: (I) clinical severity on admission (II) lesion volume in brain imaging and (III) functional outcome after 3 and 12 months. Results: 58 patients fulfilled the inclusion criteria with a median age of 73 years (IQR 61-79), median NIHSS at baseline of 4 (IQR 2-8) and median modified Rankin Scale (mRS) at baseline of 3 (IQR 2-4). Among patients with acute ischemic stroke, sNFL levels were not associated with clinical severity (measured by NIHSS and mRS; p = 0.83 and p = 0.43, respectively) or lesion size in brain imaging at baseline (lacunar 80.3 pg/ml, non-lacunar 122.9 pg/ml, p = 0.16). Nevertheless, baseline sNFL levels correlated with functional outcome as measured by mRS after 90 days: mRS ≤ 2, 75.9 pg/ml; mRS > 2, 110.8 pg/ml; p = 0.018. This prognostic ability of sNFL was preserved for functional outcome measurements after 12 month: mRS ≤ 1, 71.3 pg/ml; mRS > 1, 99.7 pg/ml; p = 0.044. The prognostic accuracy for prediction of stroke outcome is reflected by an AUC of 0.71 for the 3-month outcome and an AUC of 0.69 for the 12-month outcome (see Figure 1). Conclusion: sNFL levels after ischemic stroke predict clinical outcome after 3 and 12 months.