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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).

There have been reports suggesting an increased incidence of acute ischemic stroke among anti-SARS-CoV-2 vaccinees. We aimed to systematically review the literature to summarize the available evidence on the association between SARS-CoV-2 vaccination and acute ischemic stroke.A systematic literature search on MEDLINE, LitCovid and LIVIVO databases was performed for eligible randomized controlled trials, observational studies, registries and case reports that reported on imaging-confirmed acute ischemic stroke in the context of any SARS-CoV-2 vaccination with BNT162b2, mRNA-1273, Ad26.COV2.S, ChAdOx1 or Gam-COVID-Vac. Literature search was limited to English and German languages and publication date before October 19, 2021.We identified a total of 395,105,670 individuals who underwent vaccination. We found 21 sources, including 2 cohort studies, 4 registry studies, 3 randomized clinical trials, and 12 case reports. Individuals included in these studies were at least 16 years old. Cari et al observed a higher likelihood of acute ischemic stroke in vaccinees aged 18-64 years, compared to Whiteley et al observing vaccinees older than 70 years when vaccinated. In addition, differences in the likelihood of acute ischemic stroke were found among the vaccines studied, although no overall increased stroke incidence was demonstrated with vaccination.In this systematic review of the available literature, we found that the risk of acute ischemic stroke does not appear to be increased in vaccinated individuals who have received any of the currently licensed SARS-CoV-2 vaccines compared with the baseline incidence of stroke.

Background Treatment of ischemic stroke with recombinant tissue plasminogen activator for intravenous thrombolysis (IVT) must be delivered within a narrow time window after symptom onset. This effective hyperacute treatment can be administered after ruling out active anticoagulation with direct oral anticoagulants (DOACs). Whenever this is impractical, e.g., due to aphasia, plasmatic DOAC levels are measured with a consequent delay in the IVT decision-making process ranging from 30 to 60 minutes of time. This study will test the hypothesis that hyperacute point-of-care assessment of clotting time in the patient's whole blood has sufficient diagnostic accuracy to determine immediately whether stroke patients are pretreated with DOAC. Methods and Design This will be a prospective single-center diagnostic accuracy study in 1,850 consecutive acute ischemic stroke patients at a tertiary stroke center in Saxony, Germany. Presence of active anticoagulation with DOAC will be determined by point-of-care quantification of clotting time via whole blood viscoelastic testing (ClotPro) using Russell venom viper and ecarin assay compared with high-performance liquid chromatography-tandem mass spectrometry as the reference standard. Discussion Viscoelastic point-of-care assessment of clotting time in whole blood might improve swift delivery of time-sensitive hyperacute treatment with IVT in stroke patients.

Background: The “1-3-6-12-day rule” for starting direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation after acute ischemic stroke or transient ischemic attack recommends timings that may be later than used in clinical practice. We investigated more practical optimal timing of DOAC initiation according to stroke severity. Methods: The combined data of prospective registries in Japan, Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-nonvalvular atrial fibrillation (September 2011 to March 2014) and RELAXED (February 2014 to April 2016) were used. Patients were divided into transient ischemic attack and 3 stroke subgroups by the National Institutes of Health Stroke Scale score: mild (0–7), moderate (8–15), and severe (≥16). The early treatment group was defined as patients starting DOACs earlier than the median initiation day in each subgroup. Outcomes included a composite of recurrent stroke or systemic embolism, ischemic stroke, and severe bleeding within 90 days. Six European prospective registries were used for validation. Results: In the 1797 derivation cohort patients, DOACs were started at median 2 days after transient ischemic attack and 3, 4, and 5 days after mild, moderate, and severe strokes, respectively. Stroke or systemic embolism was less common in Early Group (n=785)—initiating DOACS within 1, 2, 3, and 4 days, respectively—than Late Group (n=1012) (1.9% versus 3.9%; adjusted hazard ratio, 0.50 [95% CI, 0.27–0.89]), as was ischemic stroke (1.7% versus 3.2%, 0.54 [0.27–0.999]). Major bleeding was similarly common in the 2 groups (0.8% versus 1.0%). On validation, both ischemic stroke (2.4% versus 2.2%) and intracranial hemorrhage (0.2% versus 0.6%) were similarly common in Early (n=547) and Late (n=1483) Groups defined using derivation data. Conclusions: In Japanese and European populations, early DOAC initiation within 1, 2, 3, or 4 days according to stroke severity seemed to be feasible to decrease the risk of recurrent stroke or systemic embolism and no increase in major bleeding. These findings support ongoing randomized trials to better establish the optimal timing of DOAC initiation.

Introduction: Pilot data suggests that organized post-stroke care enhances achievement of secondary prevention goals in stroke patients. We aimed to further investigate whether organized post-stroke care favourably affects stroke recurrence and survival. Methods: Prospective, quasi-experimental study of consecutive stroke patients admitted at two tertiary stroke centers in Saxony, Germany. According to health insurance provider status, patients were non-randomly assigned to either 12-months post-stroke pathway plus conventional care or conventional care alone. The organized post-stroke care pathway was facilitated by certified case managers and included pre-scheduled home- and phone visits aiming at educational intervention and achievement of guideline-based secondary prevention treatment goals. Primary outcomes were stroke recurrence and vascular death at 12-months. Further outcomes included favourable functional outcome (i.e. mRS 0-1), health-related quality of life and vascular risk factor control at 12-months. Results: In total, 1109 patients were recruited between 11/2011 and 12/2020. Of these, 1009 patients (91%) were assigned to organized post-stroke care and 100 (9%) to conventional care (mean age 70.6±12.8 years, 54% male, median NIHSS 3 [IQR, 1-5] points, 77.5% AIS, 17.9% TIA and 4.6% ICH). Baseline demographics and clinical characteristics were well balanced between both groups (p≥0.05). At 12-months, recurrent stroke rate was lower in the post-stroke care than in the conventional care group (5.5% vs. 14%; aOR 0.35, 95%CI 0.18-0.66; p=0.001). This association was not modified by stroke severity (TIA/minor stroke versus major stroke). Vascular death occurred in 0.2% in the post-stroke care and 3% in the conventional care group (aOR 0.07, 95%CI 0.01-0.41; p=0.003). Organized post-stroke care more frequently yielded individual treatment goals for hypertension, lipids, HbA1c, body-mass-index and secondary prevention adherence than conventional care (p Conclusions: Our results substantiate the effectiveness of case management-based post-stroke care in unselected stroke patients.

Introduction: Recent meta-analytic evidence supported efficacy and safety of bridging intravenous thrombolysis (IVT) prior to endovascular therapy (EVT) for large vessel occlusion (LVO) but large confirmatory trials are still lacking and optimal candidates for treatment have been a topic of contention lately. Objectives: We aimed to determine a cut-off in treatment times that allows identification of those who would benefit most from bridging IVT. Methods: We analyzed prospectively collected data from consecutive LVO patients who underwent EVT at a tertiary stroke center in Germany from 01/2017 to 12/2021. Patients underwent detailed cardiovascular phenotyping, repeated cranial imaging, and received standardized multidisciplinary stroke unit care. Functional outcome was assessed via modified Rankin scale three months after discharge. Ordinary ridge regression models were built to assess the impact of treatment time cut-offs on functional outcome with adjustment for age, sex, cardiovascular risk factors, baseline NIHSS, cerebrovascular territory, ASPECT score, stroke etiology and carotid artery stenting. Results: Out of 935 patients who had undergone EVT, 170 received bridging IVT (median age 74 [63-82, IQR], 52.4% females), fulfilled our criteria and were included in our analysis. Overall, onset-to-recanalization time but not onset-to-needle time was associated with functional outcome (β1=0.36, 95%CI [0.14,0.58], p=0.001 vs. p=ns). However, those who received EVT with a time delay longer than 190 minutes additionally displayed an association of onset-to-needle time and functional outcome (β1=0.64, 95%CI [0.25,1.04], p=0.02 vs. β2= 2.96, 95%CI [1.32,4.60], p=0.016). Conclusions: Our data indicates that the beneficial effect of swift bridging IVT on functional outcome is most pronounced in cases where initiation of subsequent EVT is substantially delayed.

Purpose Post-stroke depression (PSD) occurs in one-third of stroke survivors, leading to a substantial decrease in quality of life as well as delayed functional and neurological recovery. Early detection of patients at risk and initiation of tailored preventive measures may reduce the medical and socioeconomic burden associated with PSD. We sought to review the current evidence on pharmacological and non-pharmacological prevention of PSD. Materials and Methods We conducted a systematic review using PubMed/MEDLINE and bibliographies of identified papers following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, including randomized controlled studies. Eligible studies were included when performed within 1 year after the index cerebrovascular event. Animal and basic research studies, studies lacking a control group, review papers, and case reports were excluded. Results Out of 150 studies screened, 37 met our criteria. Among the strategies identified, administration of antidepressants displayed the most robust evidence for preventing PSD, whereas non-pharmacological interventions such as psychotherapy appear to be the most frequently used approaches to prevent depression after stroke. Research suggests that the efficacy of PSD prevention increases with the duration of preventive treatment. Seven out of 11 studies (63%) that used pharmacological and eight out of 16 (50%) that used non-pharmacological interventions reported a positive preventive effect on PSD. Conclusion Overall, the current literature on PSD prevention shows heterogeneity, substantiating a need for well-designed randomized controlled trials to test the safety and efficacy of pharmacological as well as non-pharmacological and composite prevention regimens to minimize the risk of PSD in stroke survivors. Integrative strategies combining personalized non-pharmacological interventions such as educational, mental, and physical health support, and pharmacological strategies such as SSRIs may be the most promising approach to prevent PSD.

ZusammenfassungDass COVID-19 mit einem erhöhten Risiko für das Auftreten ischämischer Schlaganfälle einhergeht, wurde bereits in den ersten Monaten nach dem weltweiten Bekanntwerden des Ausbruchs der Pandemie im Ground Zero Wuhan deutlich. Spätere Kohortenanalysen, Fallserien und Meta-Analysen bestätigten diesen Zusammenhang. Eine nicht unerhebliche geographische Variabilität der Prävalenz COVID-19-bezogener Schlaganfälle verdeutlicht allerdings den fortbestehenden Bedarf an umfassenden epidemiologischen Analysen. Im Übrigen fanden sich zunehmend Hinweise dafür, dass dem mit COVID-19 assoziierten Schlaganfall ein multifaktorieller pathophysiologischer Mechanismus zugrundeliegenden könnte. Neben einer durch die SARS-CoV-2-Infektion verursachten Hyperkoagubilität, die sowohl im mikrovaskulären System als auch in Großgefäßen thrombogen wirkt, scheinen vaskulitische arterielle Veränderungen und kardiogene Embolien infolge virusassoziierter myokardialer Schädigung bei der Ätiologie des COVID-19-assoziierten Schlaganfalls eine Rolle zu spielen. Die Versorgung von Schlaganfallpatienten/innen in Zeiten der Pandemie durch multidisziplinäre Teams scheint in insgesamt kompensierten Kliniken im Wesentlichen nicht kompromittiert zu sein. Hinweise, dass Patienten/innen mit COVID-19-assoziiertem Schlaganfall von einem intensivierten Monitoring und einer aggressiveren Sekundärprävention profitieren, bedarf klinischer Prüfung.

We sought to determine the diagnostic agreement between the revised ultrasonography approach by the German Society of Ultrasound in Medicine (DEGUM) and the established Society of Radiologists in Ultrasound (SRU) consensus criteria for the grading of carotid artery disease. Post-hoc analysis of a prospective multicenter study, in which patients underwent ultrasonography and digital subtraction angiography (DSA) of carotid arteries for validation of the DEGUM approach. According to DEGUM and SRU ultrasonography criteria, carotid arteries were independently categorized into clinically relevant NASCET strata (normal, mild [1-49 %], moderate [50-69 %], severe [70-99 %], occlusion). On DSA, carotid artery findings according to NASCET were considered the reference standard. We analyzed 158 ultrasonography and DSA carotid artery pairs. There was substantial agreement between both ultrasonography approaches for severe (κw 0.76, CI95 %: 0.66-0.86), but only fair agreement for moderate (κw 0.38, CI95 %: 0.19-0.58) disease categories. Compared with DSA, both ultrasonography approaches were of equal sensitivity (79.7 % versus 79.7 %; p = 1.0) regarding the identification of severe stenosis, yet the DEGUM approach was more specific than the SRU approach (70.2 % versus 56.4 %, p = 0.0002). There was equality of accuracy parameters (p 0.05) among both ultrasonography approaches for the other ranges of carotid artery disease. While the sensitivity was equivalent, false-positive identification of severe carotid artery stenosis appears to be more frequent when using the SRU ultrasonography approach than the revised multiparametric DEGUM approach.ZIEL: Bestimmung der diagnostischen Übereinstimmung zwischen den multiparametrischen Ultraschallkriterien der Deutschen Gesellschaft für Ultraschall in der Medizin (DEGUM) und den Konsenskriterien der Society of Radiologists in Ultrasound (SRU) hinsichtlich der Graduierung von Karotisstenosen. Post-hoc-Analyse einer prospektiven multizentrischen Studie, welche die multiparametrischen DEGUM-Ultraschallkriterien mit der digitalen Subtraktionsangiografie validierte. Die Graduierung von Karotisstenosen in klinisch relevante NASCET-Kategorien (normal, leichtgradig (1–49 %), mittelgradig (50–69 %), hochgradig (70–99 %), Verschluss) erfolgte verblindet gemäß der DEGUM- und SRU-Ultraschallkriterien. Als Referenz wurde der nach NASCET bestimmte angiografische Stenosegrad verwendet. Wir analysierten 158 konsekutive Untersuchungen aus Ultraschall und Angiografie. Zwischen beiden sonografischen Graduierungsansätzen fand sich eine gute Übereinstimmung für hochgradige (κw 0,76; 95 %-KI 0,66–0,86) und eine mäßige Übereinstimmung für mittelgradige Stenosen (κw 0,38; 95 %-KI 0,19–0,58). Verglichen mit der Referenzangiografie fand sich kein Unterschied hinsichtlich Sensitivität für hochgradige Stenosen (79,7 % versus 79,7 %; p = 1,0), jedoch eine höhere Spezifität der DEGUM-Kriterien (70,2 % versus 56,4 %; p = 0,0002). In den sonstigen Stenosekategorien bestanden keine Unterschiede der Güteparameter (p 0,05). Verglichen mit den SRU-Kriterien weist die Graduierung nach DEGUM eine höhere Spezifität bei der Detektion hochgradiger Stenosen auf. Die Integration von mehr hämodynamischen Parametern scheint somit die Anzahl falsch positiver Diagnosen zu verringern.

Objective To determine whether a history of cerebrovascular disease (CVD) increases risk of severe coronavirus disease 2019 (COVID-19). Methods In a retrospective multicenter study, we retrieved individual data from in-patients treated March 1 to April 15, 2020 from COVID-19 registries of three hospitals in Saxony, Germany. We also performed a systematic review and meta-analysis following PRISMA recommendations using PubMed, EMBASE, Cochrane Library databases and bibliographies of identified papers (last search on April 11, 2020) and pooled data with those deriving from our multicenter study. Of 3762 records identified, 11 eligible observational studies of laboratory-confirmed COVID-19 patients were included in quantitative data synthesis. Risk ratios (RR) of severe COVID-19 according to history of CVD were pooled using DerSimonian and Laird random effects model. Between-study heterogeneity was assessed using Cochran’s Q and I2-statistics. Severity of COVID-19 according to definitions applied in included studies was the main outcome. Sensitivity analyses were conducted for clusters of studies with equal definitions of severity. Results Pooled analysis included data from 1906 laboratory-confirmed COVID-19 patients (43.9% females, median age ranging from 39 to 76 years). Patients with previous CVD had higher risk of severe COVID-19 than those without [RR 2.07, 95% confidence interval (CI) 1.52–2.81; p p p p Conclusion A history of CVD might constitute an important risk factor of unfavorable clinical course of COVID-19 suggesting a need of tailored infection prevention and clinical management strategies for this population at risk.

Introduction The aim of this study in patients with acute posterior ischaemic stroke (PS) and atrial fibrillation (AF) was to evaluate (1) the risks of recurrent ischaemic event and severe bleeding and (2) these risks in relation with oral anticoagulant therapy (OAT) and its timing. Materials and Methods Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of stroke recurrence, transient ischaemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke. Results A total of 2470 patients were available for the analysis: 473 (19.1%) with PS and 1997 (80.9%) with AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39–2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16–1.80). Discussion our findings suggest that, when deciding the time to initiate oral anticoagulation, the location of stroke, either anterior or posterior, does not predict the risk of outcome events. Conclusions Patients with PS or AS and AF appear to have similar risks of ischaemic or haemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT.

Background and Purpose: This study aims to assess the number of patients with acute ischemic cerebrovascular events seeking in-patient medical emergency care since the implementation of social distancing measures in the coronavirus disease 2019 (COVID-19) pandemic. Methods: In this retrospective multicenter study, data on the number of hospital admissions due to acute ischemic stroke or transient ischemic attack and numbers of reperfusion therapies performed in weeks 1 to 15 of 2020 and 2019 were collected in 4 German academic stroke centers. Poisson regression was used to test for a change in admission rates before and after the implementation of extensive social distancing measures in week 12 of 2020. The analysis of anonymized regional mobility data allowed for correlations between changes in public mobility as measured by the number and length of trips taken and hospital admission for stroke/transient ischemic attack. Results: Only little variation of admission rates was observed before and after week 11 in 2019 and between the weeks 1 and 11 of 2019 and 2020. However, reflecting the impact of the COVID-19 pandemic, a significant decrease in the number of admissions for transient ischemic attack was observed (−85%, −46%, −42%) in 3 of 4 centers, while in 2 of 4 centers, stroke admission rates decreased significantly by 40% and 46% after week 12 in 2020. A relevant effect on reperfusion therapies was found for 1 center only (thrombolysis, −60%; thrombectomy, −61%). Positive correlations between number of ischemic events and mobility measures in the corresponding cities were identified for 3 of 4 centers. Conclusions: These data demonstrate and quantify decreasing hospital admissions due to ischemic cerebrovascular events and suggest that this may be a consequence of social distancing measures, in particular because hospital resources for acute stroke care were not limited during this period. Hence, raising public awareness is necessary to avoid serious healthcare and economic consequences of undiagnosed and untreated strokes and transient ischemic attacks.

Neurologic manifestations are increasingly reported in patients with coronavirus disease 2019 (COVID-19). Yet, data on prevalence, predictors and relevance for outcome of neurological manifestations in patients requiring intensive care are scarce. We aimed to characterize prevalence, risk factors and impact on outcome of neurologic manifestations in critically ill COVID-19 patients.In the prospective, multicenter, observational registry study PANDEMIC (Pooled Analysis of Neurologic DisordErs Manifesting in Intensive care of COVID-19), we enrolled COVID-19 patients with neurologic manifestations admitted to 19 German intensive care units (ICU) between April 2020 and September 2021. We performed descriptive and explorative statistical analyses. Multivariable models were used to investigate factors associated with disorder categories and their underlying diagnoses as well as to identify predictors of outcome.Of the 392 patients included in the analysis, 70.7% (277/392) were male and the mean age was 65.3 (SD ± 3.1) years. During the study period, a total of 2681 patients with COVID-19 were treated at the ICUs of 15 participating centers. New neurologic disorders were identified in 350 patients, reported by these centers, suggesting a prevalence of COVID-19-associated neurologic disorders of 12.7% among COVID-19 ICU patients. Encephalopathy (46.2%; 181/392), cerebrovascular (41.0%; 161/392) and neuromuscular disorders (20.4%; 80/392) were the most frequent categories identified. Out of 35 cerebrospinal fluid analyses with reverse transcriptase PCR for SARS-COV-2, only 3 were positive. In-hospital mortality was 36.0% (140/389), and functional outcome (mRS 3 to 5) of surviving patients was poor at hospital discharge in 70.9% (161/227). Intracerebral hemorrhage (OR 6.2, 95% CI 2.5-14.9, p 0.001) and acute ischemic stroke (OR 3.9, 95% CI 1.9-8.2, p 0.001) were the strongest predictors of poor outcome among the included patients.Based on this well-characterized COVID-19 ICU cohort, that comprised 12.7% of all severe ill COVID-19 patients, neurologic manifestations increase mortality and morbidity. Since no reliable evidence of direct viral affection of the nervous system by COVID-19 could be found, these neurologic manifestations may for a great part be indirect para- or postinfectious sequelae of the infection or severe critical illness. Neurologic ICU complications should be actively searched for and treated.

Introduction: Stroke accounts for 4% of patients with acute vertigo, which is missed in up to one third of cases. Hypothesis: We hypothesized that detection of stroke underlying acute vertigo using HINTS plus (head-impulse test, nystagmus type, test of skew, hearing loss) can be improved by videooculography for automated analysis of head-impulse test (V-HIT). Materials and Methods: We evaluated patients with acute vestibular syndrome (AVS) presenting to the emergency room using HINTS plus and V-HIT-assisted HINTS plus in a randomized sequence. In addition, patients underwent cranial MRI and caloric testing. Image-confirmed posterior circulation stroke or vertebrobasilar TIA were defined as reference standard to calculate accuracy of applied vertigo assessment protocols. After study completion, we repeated statistical analysis for a third protocol that was composed post hoc by replacing the results of head-impulse test with those derived from caloric testing in the HINTS plus protocol. Results: We included 30 AVS patients (ages 55.4 ± 17.2 years, 14 females). Of these, 11 (36.7%) had MRI-confirmed posterior circulation ischemic stroke (n=4) or vertebrobasilar TIA (n=7). Conducting V-HIT-assisted HINTS plus as part of the emergency work up was feasible and displayed a tendency toward higher accuracy than conventional HINTS plus (sensitivity: 81.8%, 95%CI 48.2-97.7%; specificity 31.6%, 95%CI 12.6-56.6% vs. sensitivity 72.7%, 95%CI 39.0-94.0%; specificity 36.8%, 95%CI 16.3-61.6%). (Figure) The new caloric-supported algorithm displayed high accuracy (sensitivity 100%, 95%CI 66.4%-100%; specificity 66.7%, 95%CI 41%-86.7%). Conclusions: Our study provides pilot data on the capacity of videooculography to improve accuracy of acute vertigo assessment using HINTS plus and indicates potential value of acute caloric testing as integrative part of standardized AVS emergency work up.

With the onset of the COVID-19 pandemic, it became apparent that, in addition to pulmonary infection, extrapulmonary manifestations such as cardiac injury and acute cerebrovascular events are frequent in patients infected with SARS-CoV-2, worsening clinical outcome. We reviewed the current literature on the pathophysiology of cardiac injury and its association with acute ischaemic stroke. Several hypotheses on heart and brain axis pathology in the context of stroke related to COVID-19 were identified. Taken together, a combination of disease-related coagulopathy and systemic inflammation might cause endothelial damage and microvascular thrombosis, which in turn leads to structural myocardial damage. Cardiac complications of this damage such as tachyarrhythmia, myocardial infarction or cardiomyopathy, together with changes in hemodynamics and the coagulation system, may play a causal role in the increased stroke risk observed in COVID-19 patients. These hypotheses are supported by a growing body of evidence, but further research is necessary to fully understand the underlying pathophysiology and allow for the design of cardioprotective and neuroprotective strategies in this at risk population.

Journal of neurology 269(7), 3389-3399 (2022). doi:10.1007/s00415-022-11034-w, Published by Steinkopff, [Darmstadt]

Background: While intravenous thrombolysis (IVT) in ischemic stroke can be safely applied in telestroke networks within 3 h from symptom onset, there is a lack of evidence for safety in the expanded 3- to 4. 5-h time window. We assessed the safety and short-term efficacy of IVT in acute ischemic stroke (AIS) in the expanded time window delivered through a hub-and-spoke telestroke network.Methods: Observational study of patients with AIS who received IVT at the Stroke Eastern Saxony Telemedical Network between 01/2014 and 12/2015. We compared safety data including symptomatic intracerebral hemorrhage (sICH; according to European Cooperative Acute Stroke Study II definition) and any intracerebral hemorrhage (ICH) between patients admitted to telestroke spoke sites and patients directly admitted to a tertiary stroke center representing the hub of the network. We also assessed short-term efficacy data including favorable functional outcome (i.e., modified Rankin Scale ≤ 2) and National Institutes of Health Stroke Scale (NIHSS) at discharge, hospital discharge disposition, and in-hospital mortality.Results: In total, 152 patients with AIS were treated with IVT in the expanded time window [spoke sites, n = 104 (26.9%); hub site, n = 48 (25.9%)]. Patients treated at spoke sites had less frequently a large vessel occlusion [8/104 (7.7) vs. 20/48 (41.7%); p < 0.0001], a determined stroke etiology (p < 0.0001) and had slightly shorter onset-to-treatment times [210 (45) vs. 228 (58) min; p = 0.02] than patients who presented to the hub site. Both cohorts did not display any further differences in demographics, vascular risk factors, median baseline NIHSS scores, or median baseline Alberta stroke program early CT score (p > 0.05). There was no difference in the frequency of sICH (4.9 vs. 6.3%; p = 0.71) or any ICH (8.7 vs. 16.7%; p = 0.15). Neither there was a difference regarding favorable functional outcome (44.1 vs. 39.6%; p = 0.6) nor median NIHSS [3 (5.5) vs. 2.5 (5.75); p = 0.92] at discharge, hospital discharge disposition (p = 0.28), or in-hospital mortality (9.6 vs. 8.3%; p = 1.0). Multivariable modeling did not reveal an association between telestroke and sICH or favorable functional outcome (p > 0.05).Conclusions: Delivery of IVT in the expanded 3- to 4.5-h time window through a telestroke network appears to be safe with equivalent short-term functional outcomes for spoke-and-hub center admissions.

Background: The constantly increasing incidence of stroke in younger individuals substantiates an urgent need for research to elucidate underlying risk factors and etiologies. Heretofore, the vast majority of studies on stroke in the young have been carried out in European and North American regions. We aimed to characterize cerebrovascular risk profiles in a Saudi Arabic cohort of consecutive young stroke patients.Methods: We retrospectively analyzed data from consecutive ischemic stroke patients aged 15 to 49 years who underwent detailed cardiocerebrovascular evaluation at a tertiary stroke care center in Makkah, Saudi Arabia. Distributions of risk factors and stroke etiologies were assessed in the entire cohort and in two strata of very young (15–40 years) and young to middle-aged patients (41–49) to account for variability in suggested age cutoffs.Results: In the entire cohort [n = 63, ages 44 (34–47) median, interquartile range], dyslipidemia (71.4%) and small vessel occlusion (31.7%) displayed highest prevalence followed by diabetes (52.4%) and cardioembolism (19%). In very young patients, cardioembolism was the most prevalent etiology (27.3%). Risk profiles were similar between both age strata except for a higher prevalence of diabetes among the older cohort (31.8 vs. 63.4%, p = 0.01). Logistic regression identified diabetes as strongest predictor for association to the older strata (odds ratio = 4.2, 95% confidence interval = 1.2–14.1, p = 0.02).Conclusion: Cerebrovascular risk profiles and stroke etiologies in our cohort of young stroke patients differ from those of previous cohorts, suggesting the need for tailored prevention strategies that take into account local epidemiological data on cerebrovascular health.

BACKGROUND A major reason for the low number of organ donors in Germany is a deficit in the recognition of patients who may have impending irreversible loss of brain function (ILBF) in hospitals capable of organ retrieval. METHODS We used anonymized data from the German Organ Procurement Organization (Deutsche Stiftung Organtransplantation, DSO) to compare two 12-month periods (a reference period and an evaluation period) before and after the implementation of an electronic screening tool (DETECT) at the University Hospital Dresden (UKD) with four other university hospitals without tool implementation (comparative cohort). DETECT is intended to aid in the recognition of potentially impending ILBF. The study endpoints encompassed patients with potentially unrecognized ILBF, patients with recognized ILBF, organ donations performed, and reports to the DSO. Changes in absolute risk were compared with Breslow-Day tests. RESULTS 309 patients who died with primary or secondary brain lesions were identified in the UKD in the reference and evaluation periods (164 and 145 patients, respectively), and 1060 (529, 531) in the comparative cohort. In the UKD, the number of unrecognized cases of possibly impending ILBF was 14/164 (8.54%) in the reference period and 1/145 (0.69%) in the evaluation period, yielding an absolute reduction of 7.85% (95% confidence interval [-3.36; -12.33]); by contrast, in the comparative cohort, there was a 0.55% absolute increase between the two periods ([-2.21; 3.30]; p = 0.002 for the comparison between the two cohorts). Only minor differences in absolute risk change were seen with regard to the probability of recognized ILBF (7.09% [0.29; 13.88] vs. 2.42% [1.18; 6.01]; p = 0.234), organ donation (4.70% [-0.89; 10.28] vs. 0.55% [-2.17; 3.26]; p = 0.214), or reporting to the DSO (4.17% [-1.77; 10.11] vs. 2.22% [-1.44; 5.89; p = 0.447); these changes may have arisen by chance. CONCLUSION These findings suggest that the use of DETECT can help to reduce the deficit in the recognition of patients with impending or manifest ILBF.

Background: Neuroprotective and neurorestorative effects have been postulated for selective serotonin-reuptake inhibitors (SSRI). We hypothesized that sertraline, which is characterized by less severe adverse effects and more stable pharmacokinetics than classic SSRI, is associated with improved functional recovery in acute ischemic stroke patients with motor deficits. Methods: Prospective observational study of consecutive acute ischemic stroke patients who received sertraline for clinically suspected post-stroke depression (PSD) or at high risk for PSD. Eligibility comprised acute motor deficit caused by ischemic stroke (≥2 points on NIHSS motor items) and functional independence pre-stroke (mRS ≤1). Decision to initiate treatment with SSRI during hospital stay was at the discretion of the treating stroke physician. Patients not receiving sertraline served as control group. Favorable functional recovery defined as mRS ≤2 was prospectively assessed at 3 months. Multivariable logistic regression analysis was used to explore the effects of sertraline on 3-months functional recovery. Secondary outcomes were frequency of any and incident PSD (defined by BDI ≥10) at 3 months. Results: During the study period (03/2017–12/2018), 114 patients were assigned to sertraline (n = 72, 62.6%) or control group (n = 42, 37.4%). At study entry, patients in sertraline group were more severely neurologically affected than patients in the control group (NIHSS: 8 [IQR, 5–11] vs. 5 [IQR, 4–7]; p = 0.002). Also, motor NIHSS scores were more pronounced in sertraline than in control group (4 [IQR 2–7] vs. 2 [IQR 2–4], p = 0.001). After adjusting for age and baseline NIHSS, multivariable regression analysis revealed a significant association between sertraline intake and favorable functional outcome at 3 months (OR 3.10, 95% CI 1.02–9.41; p = 0.045). There was no difference between both groups regarding the frequency of any depression at 3 months (26/53 [49.1%] vs. 14/28 [50.0%] patients, p = 0.643, BDI ≥10). However, fewer incident depressions were observed in sertraline group patients compared to patients in control group (0/53 [0%] vs. 5/28 [17.9%] patients, p = 0.004). Conclusions: In this non-randomized comparison, early treatment with sertraline tended to favor functional recovery in patients with acute ischemic stroke. While exploratory in nature, this hypothesis needs further investigation in a clinical trial.

Strychnine poisoning should be considered in the differential of generalized tetanic-like muscle contractions with normal mental status—a sine qua non condition of this rare intoxication.

Background: The clinical benefit from endovascular therapy (EVT) for patients with acute ischemic stroke is time-dependent. We tested the hypothesis that team prenotification results in faster procedure times prior to initiation of EVT.Methods: We analyzed data from our prospective database (01/2016–02/2018) including all patients with acute ischemic stroke who were evaluated for EVT at our comprehensive stroke center. We established a standardized algorithm (EVT-Call) in 06/2017 to prenotify team members (interventional neuroradiologist, neurologist, anesthesiologist, CT and angiography technicians) about patient transfer from remote hospitals for evaluation of EVT, and team members were present in the emergency department at the expected patient arrival time. We calculated door-to-image, image-to-groin and door-to-groin times for patients who were transferred to our center for evaluation of EVT, and analyzed changes before (–EVT-Call) and after (+EVT-Call) implementation of the EVT-Call.Results: Among 494 patients in our database, 328 patients were transferred from remote hospitals for evaluation of EVT (208 -EVT-Call and 120 +EVT-Call, median [IQR] age 75 years [65–81], NIHSS score 17 [12–22], 49.1% female). Of these, 177 patients (54%) underwent EVT after repeated imaging at our center (111/208 [53%) -EVT-Call, 66/120 [55%] +EVT-Call). Median (IQR) door-to-image time (18 min [14–22] vs. 10 min [7–13]; p < 0.001), image-to-groin time (54 min [43.5–69.25] vs. 47 min [38.3–58.75]; p = 0.042) and door-to-groin time (74 min [58–86.5] vs. 60 min [49.3–71]; p < 0.001) were reduced after implementation of the EVT-Call.Conclusions: Team prenotification results in faster patient assessment and initiation of EVT in patients with acute ischemic stroke. Its impact on functional outcome needs to be determined.

Background: We assessed whether detection of stroke underlying acute vertigo using HINTS plus (head-impulse test, nystagmus type, test of skew, hearing loss) can be improved by video-oculography for automated head-impulse test (V-HIT) analysis. Methods: We evaluated patients with acute vestibular syndrome (AVS) presenting to the emergency room using HINTS plus and V-HIT-assisted HINTS plus in a randomized sequence followed by cranial MRI and caloric testing. Image-confirmed posterior circulation stroke or vertebrobasilar TIA were the reference standards to calculate diagnostic accuracy. We repeated statistical analysis for a third protocol that was composed post hoc by replacing the head-impulse test with caloric testing in the HINTS plus protocol. Results: We included 30 AVS patients (ages 55.4 ± 17.2 years, 14 females). Of these, 11 (36.7%) had posterior circulation stroke (n = 4) or TIA (n = 7). Acute V-HIT-assisted HINTS plus was feasible and displayed tendentially higher accuracy than conventional HINTS plus (sensitivity: 81.8%, 95% CI 48.2–97.7%, specificity 31.6%, 95% CI 12.6–56.6% vs. sensitivity 72.7%, 95% CI 39.0–94.0%, specificity 36.8%, 95% CI 16.3–61.6%). The new caloric-supported algorithm showed high accuracy (sensitivity 100%, 95% CI 66.4–100%, specificity 66.7%, 95% CI 41–86.7%). Conclusions: Our study provides pilot data on V-HIT-assisted HINTS plus for acute AVS assessment and indicates the diagnostic value of integrated acute caloric testing.

Background: The constantly increasing incidence of stroke in younger individuals substantiates an urgent need for research to elucidate underlying risk factors and etiologies. Heretofore, the vast majority of studies on stroke in the young have been carried out in European and North American regions. We aimed to characterize cerebrovascular risk profiles in a Saudi Arabic cohort of consecutive young stroke patients. Methods: We retrospectively analyzed data from consecutive ischemic stroke patients aged 15 to 49 years who underwent detailed cardiocerebrovascular evaluation at a tertiary stroke care center in Makkah, Saudi Arabia. Distributions of risk factors and stroke etiologies were assessed in the entire cohort and in two strata of very young (15–40 years) and young to middle-aged patients (41–49) to account for variability in suggested age cutoffs. Results: In the entire cohort [n = 63, ages 44 (34–47) median, interquartile range], dyslipidemia (71.4%) and small vessel occlusion (31.7%) displayed highest prevalence followed by diabetes (52.4%) and cardioembolism (19%). In very young patients, cardioembolism was the most prevalent etiology (27.3%). Risk profiles were similar between both age strata except for a higher prevalence of diabetes among the older cohort (31.8 vs. 63.4%, p = 0.01). Logistic regression identified diabetes as strongest predictor for association to the older strata (odds ratio = 4.2, 95% confidence interval = 1.2–14.1, p = 0.02). Conclusion: Cerebrovascular risk profiles and stroke etiologies in our cohort of young stroke patients differ from those of previous cohorts, suggesting the need for tailored prevention strategies that take into account local epidemiological data on cerebrovascular health.

We aimed to assess how evidence-based stroke care changed over the two waves of the COVID-19 pandemic. We analyzed acute stroke patients admitted to a tertiary care hospital in Germany during the first (2 March 2020–9 June 2020) and second (23 September 2020–31 December 2020, 100 days each) infection waves. Stroke care performance indicators were compared among waves. A 25.2% decline of acute stroke admissions was noted during the second (n = 249) compared with the first (n = 333) wave of the pandemic. Patients were more frequently tested SARS-CoV-2 positive during the second than the first wave (11 (4.4%) vs. 0; p < 0.001). There were no differences in rates of reperfusion therapies (37% vs. 36.5%; p = 1.0) or treatment process times (p > 0.05). However, stroke unit access was more frequently delayed (17 (6.8%) vs. 5 (1.5%); p = 0.001), and hospitalization until inpatient rehabilitation was longer (20 (1, 27) vs. 12 (8, 17) days; p < 0.0001) during the second compared with the first pandemic wave. Clinical severity, stroke etiology, appropriate secondary prevention medication, and discharge disposition were comparable among both waves. Infection control measures may adversely affect access to stroke unit care and extend hospitalization, while performance indicators of hyperacute stroke care seem to be untainted.

Background and Purpose— Bridging therapy with low-molecular-weight heparin reportedly leads to a worse outcome for acute cardioembolic stroke patients because of a higher incidence of intracerebral bleeding. However, this practice is common in clinical settings. This observational study aimed to compare (1) the clinical profiles of patients receiving and not receiving bridging therapy, (2) overall group outcomes, and (3) outcomes according to the type of anticoagulant prescribed. Methods— We analyzed data of patients from the prospective RAF and RAF-NOACs studies. The primary outcome was defined as the composite of ischemic stroke, transient ischemic attack, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after the acute stroke. Results— Of 1810 patients who initiated oral anticoagulant therapy, 371 (20%) underwent bridging therapy with full-dose low-molecular-weight heparin. Older age and the presence of leukoaraiosis were inversely correlated with the use of bridging therapy. Forty-two bridged patients (11.3%) reached the combined outcome versus 72 (5.0%) of the nonbridged patients ( P =0.0001). At multivariable analysis, bridging therapy was associated with the composite end point (odds ratio, 2.3; 95% CI, 1.4–3.7; P P =0.005) and hemorrhagic (odds ratio, 2.4; 95% CI, 1.2–4.9; P =0.01) end points separately. Conclusions— Our findings suggest that patients receiving low-molecular-weight heparin have a higher risk of early ischemic recurrence and hemorrhagic transformation compared with nonbridged patients.

Endovascular therapy (EVT) trials enrolled ischemic stroke patients with good pre-stroke functional status. However, this information needed for rapid decision-making is commonly lacking in clinical practice. We hypothesized that initial misjudgment of pre-stroke functional status attenuates clinical outcomes of EVT. Data were derived from our prospective registry of ischemic stroke patients undergoing EVT for anterior circulation large vessel occlusion (01/2016–12/2017). Considering all information accumulated during hospital course, pre-stroke modified Rankin scale (mRS) was independently re-assessed and compared with pre-EVT assessments. Misjudgment was defined as any difference in mRS categories between first- and second-look assessments. Multivariable model was built to adjust for confounding variables of unfavorable outcome (mRS 3–6) and death at 90 days. Overall, we studied 217 patients: median age 75 years (IQR 64–81), 54% women, median NIHSS 17 (12–20) points. Second-look assessment of pre-stroke mRS revealed 73 (34%) cases initially being misjudged by ≥ 1 category and 17 (8%) by ≥ 2 categories. None of the second-look mRS assessments resulted in a lower mRS category than initially rated. Patients whose pre-stroke mRS score was misjudged prior to EVT showed more frequently unfavorable outcome (62/73 [84.9%] vs. 94/144 [65.3%], p = 0.002) or were deceased (30/73 [41.1%] vs. 25/144 [17.4%], p

Depressive disorders are among the most important health problems and are predicted to constitute the leading cause of disease burden by the year 2030. Aside significant impact on quality of life, psychosocial well-being and socioeconomic status of affected patients, depression is associated with impaired cardiovascular health and increased mortality. The link between affective and cardiovascular disease has largely been attributed to dysregulation of the autonomic nervous system resulting in a chronic shift toward increased sympathetic and decreased parasympathetic activity and, consecutively, cardiac dysautonomia. Among proposed surrogate parameters to capture and quantitatively analyze this shift, heart rate variability (HRV) and baroreflex sensitivity have emerged as reliable tools. Attenuation of these parameters is frequently seen in patients suffering from depression and is closely linked to cardiovascular morbidity and mortality. Therefore, diagnostic and therapeutic strategies were designed to assess and counteract cardiac dysautonomia. While psychopharmacological treatment can effectively improve affective symptoms of depression, its effect on cardiac dysautonomia is limited. HRV biofeedback is a non-invasive technique which is based on a metronomic breathing technique to increase parasympathetic tone. While some small studies observed beneficial effects of HRV biofeedback on dysautonomia in patients with depressive disorders, larger confirmatory trials are lacking. We reviewed the current literature on cardiac dysautonomia in patients suffering from depression with a focus on the underlying pathophysiology as well as diagnostic workup and treatment.

Dass COVID-19 mit einem erhöhten Risiko für das Auftreten ischämischer Schlaganfälle einhergeht, wurde bereits in den ersten Monaten nach dem weltweiten Bekanntwerden des Ausbruchs der Pandemie im Ground Zero Wuhan deutlich. Spätere Kohortenanalysen, Fallserien und Meta-Analysen bestätigten diesen Zusammenhang. Eine nicht unerhebliche geographische Variabilität der Prävalenz COVID-19-bezogener Schlaganfälle verdeutlicht allerdings den fortbestehenden Bedarf an umfassenden epidemiologischen Analysen. Im Übrigen fanden sich zunehmend Hinweise dafür, dass dem mit COVID-19 assoziierten Schlaganfall ein multifaktorieller pathophysiologischer Mechanismus zugrundeliegenden könnte. Neben einer durch die SARS-CoV-2-Infektion verursachten Hyperkoagubilität, die sowohl im mikrovaskulären System als auch in Großgefäßen thrombogen wirkt, scheinen vaskulitische arterielle Veränderungen und kardiogene Embolien infolge virusassoziierter myokardialer Schädigung bei der Ätiologie des COVID-19-assoziierten Schlaganfalls eine Rolle zu spielen. Die Versorgung von Schlaganfallpatienten/innen in Zeiten der Pandemie durch multidisziplinäre Teams scheint in insgesamt kompensierten Kliniken im Wesentlichen nicht kompromittiert zu sein. Hinweise, dass Patienten/innen mit COVID-19-assoziiertem Schlaganfall von einem intensivierten Monitoring und einer aggressiveren Sekundärprävention profitieren, bedarf klinischer Prüfung.The notion of an increased risk of acute ischemic stroke in patients with COVID-19 emerged during the first months after the outbreak of the COVID-19 pandemic at ground zero in Wuhan. Subsequently, this association was confirmed by multiple case reports, cohort studies and meta-analyses. However, substantial geographical variability in prevalence of COVID-19 associated stroke underscores a persistent need of encompassing epidemiological study. Accumulative evidence suggested a rather complex underlying pathophysiology. Possible mechanisms include small and large vessel thromboembolism induced by systemic hypercoagubility, vasculitis and cardiac embolism caused by virus-induced cardiomyopathy. Multidisciplinary care of acute stroke patients in general does not seem to be compromised by the pandemic in otherwise compensated hospitals. However, it remains to be answered whether more aggressive approaches of secondary prevention and intensified monitoring strategies after COVID-19 related stroke are necessary to optimize clinical outcomes.

Background and Objective The term myxedema psychosis (MP) was introduced to describe the occurrence of psychotic symptoms in patients with untreated hypothyroidism, but the optimal assessment and treatment of this condition are unclear. We aimed to synthesize data from the literature to characterize the clinical presentation and management of MP. Methods We performed a systematic review according to the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines in PubMed (Medline), Embase, Google Scholar, and Cochrane databases, including observational studies, case series, and case reports published from 1/1/1980 to 31/12/2019 in the English language. Descriptive statistics along with univariate and multivariate analysis were used for data synthesis. Results Out of 1583 articles screened, 71 case reports met our inclusion criteria providing data on 75 MP cases. The median age at diagnosis was 42 years [32–56]. About 53% had no prior hypothyroidism diagnosis. Delusions occurred in 91%, with a predominance of persecutory ideas (84%), while hallucinations occurred in 78%. Physical symptoms and signs of hypothyroidism were absent in 37% and 26%, respectively. If symptoms occurred, nonspecific fatigue was seen most frequently (63%). The median thyroid-stimulating hormone value was 93 mIU/L [60–139]. Thyroid peroxidase antibodies were found positive in 75% (23/33) of reported cases. Creatinine kinase was reported abnormal in seven cases. Cranial imaging (CT or MRI) and electroencephalogram were normal in 89%, 75%, and 73% of the cases reported. The majority of patients were treated orally with thyroxine in combination with short-term antipsychotics. More than 90% of them showed complete recovery. Univariate analysis revealed a trend towards a shorter duration of psychosis with IV thyroid hormone therapy (p= 0.0502), but the effect was not consistent in a multivariate analysis. Conclusion While we identified a substantial lack of published research on MP, our pooled analysis of case observations suggests that the condition presents a broad spectrum of psychiatric and physical symptoms lending support to the value of screening for thyroid dysfunction in patients with first-ever psychosis. Prospero Registration Number CRD42020160310.

BACKGROUND AND PURPOSE Hypothermia may be neuroprotective in acute ischemic stroke. Patients with anterior circulation large vessel occlusion (acLVO) are frequently hypothermic after endovascular therapy (EVT). We sought to determine whether this inadvertent hypothermia is associated with improved outcome. METHODS We extracted data of consecutive patients (January 2016 to May 2019) who received EVT for acLVO from our prospective EVT register of all patients screened for EVT at our tertiary stroke center. We assessed functional outcome at 3 months and performed multivariate analysis to calculate adjusted risk ratios (aRRs) for favorable outcome (modified Rankin Scale scores = 0-2) and mortality across patients who were hypothermic (

Background: Neurocardiac dysfunction worsens clinical outcome and increases mortality in stroke survivors. We hypothesized that heart rate variability (HRV) biofeedback improves neurocardiac function by modulating autonomic nervous system activity after acute ischaemic stroke (AIS). Methods: We randomly allocated (1:1) 48 acute ischaemic stroke patients to receive nine sessions of HRV- or sham biofeedback over 3 days in addition to comprehensive stroke unit care. Before and after the intervention patients were evaluated for HRV via standard deviation of normal-to-normal intervals (SDNN, primary outcome), root mean square of successive differences between normal heartbeats (RMSSD), a predominantly parasympathetic measure, and for sympathetic vasomotor and sudomotor function. Severity of autonomic symptoms was assessed via survey of autonomic symptom scale total impact score (TIS) at baseline and after 3 months. Results: We included 48 patients with acute ischaemic stroke [19 females, ages 65 (4.4), median (interquartile range)]. Treatment with HRV biofeedback increased HRV post intervention [SDNN: 43.5 (79.0) ms vs. 34.1 (45.0) ms baseline, p = 0.015; RMSSD: 46.0 (140.6) ms vs. 29.1 (52.2) ms baseline, p = 0.015] and alleviated autonomic symptoms after 3 months [TIS 3.5 (8.0) vs. 7.5 (7.0) baseline, p = 0.029], which was not seen after sham biofeedback (SDNN: p = 0.63, RMSSD: p = 0.65, TIS: 0.06). There were no changes in sympathetic vasomotor and sudomotor function (p = ns). Conclusions: Adding HRV biofeedback to standard stroke unit care led to improved neurocardiac function and sustained alleviation of autonomic symptoms after acute ischaemic stroke, which was likely mediated by a predominantly parasympathetic mechanism. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03865225.

Background: We hypothesized that autotitrating bilevel positive airway pressure (auto-BPAP) favorably affects short-term clinical outcomes in hyperacute ischemic stroke.Methods: In a multicenter, randomized, controlled trial patients with large vessel steno-occlusive stroke and clinically suspected sleep apnea were allocated to auto-BPAP or standard stroke care alone. Auto-BPAP was initiated within 24 h from stroke onset and performed over 48 h during diurnal and nocturnal sleep. Sleep apnea was assessed using cardiorespiratory polygraphy. Primary endpoint was early neurological improvement on National Institutes of Health Stroke Scale (NIHSS) score at 72 h. Safety and tolerability of BPAP, functional independence [modified Rankin Scale (mRS) 0–2], stroke recurrence, and mortality at 90 days were assessed.Results: Due to low recruitment, the trial was prematurely stopped after 24 patients had been randomized (auto-BPAP, n = 14; control, n = 10): median baseline NIHSS 13 (5.5–18), 88% large vessel occlusion, and 12% large vessel stenosis. Polygraphy confirmed sleep apnea in 64% of auto-BPAP and 88% of control patients (p = 0.34). Adherence to auto-BPAP was achieved by 9 of the 14 (64%) patients. Between auto-BPAP and control patients, no differences were observed in early neurological improvement (median NIHSS change: −2.0, IQR = 7 points vs. −0.5, IQR = 3 points), 90 days functional independence (21 vs. 30%, p = 0.67), stroke recurrence (0 vs. 20%, p = 0.16), and death (14 vs. 20%, p = 1.0). No safety concerns were identified.Conclusions: In this prematurely terminated trial, auto-BPAP was safe but did not show an effect on short-term clinical outcomes in selected ischemic stroke patients. Its tolerability, however, may be limited in hyperacute stroke care and needs to be improved before larger trials are conducted.Clinical Trial Registration:ClinicalTrials.gov, identifier: NCT01812993.

Introduction: To explore kidney safety profile of osmotic diuretic mannitol in patients with malignant middle cerebral artery (MCA) infarction. Methods: We analyzed data from consecutive patients with malignant MCA infarction (01/2008-12/2017). Malignant MCA infarction was defined according to clinical and radiographic DESTINY criteria. Clinical and laboratory variables were collected for all patients. We compared clinical endpoints including acute kidney failure (AKF; according to Kidney Disease: Improving Global Outcomes [KDIGO] definition) and hemodialysis between patients who received mannitol and those who did not. Multivariable model was built to explore predictor variables of AKF, in-hospital death and functional outcome at discharge. Results: Overall, 228 patients with malignant MCA infarction were analyzed: median age 67 years (IQR, 56-76), 58% men, median NIHSS 23 (17-32) points. Decompressive craniectomy was performed in 103/228 (45.2%) patients. Mannitol was administered in 100/228 (43.9%) patients over an average of 85 (30.3-139.3) hours. Average dosage was 700 (250-1050) g. Patients treated with mannitol more frequently suffered from AKF (40% vs. 7.9%; p0.05). Conclusions: Acute kidney failure appears to be a frequent complication of osmotic diuretic mannitol in patients with malignant MCA infarction. Given the lack of evidence supporting effectiveness of mannitol in these patients, its use should be carefully considered.

Introduction: Recent studies linked coronavirus disease 2019 (COVID-19) to thromboembolic complications likely mediated by increased blood coagulability and inflammatory endothelial impairment. Objective: We aimed to assess the risk of acute stroke in patients with COVID-19 related to clinical severity of the disease. Methods: We conducted an observational multicenter cohort study in four participating hospitals in Saxony, Germany to characterize consecutive patients with laboratory-confirmed COVID-19 who experienced acute stroke during hospitalization. Furthermore, we performed a systematic review using PubMed/MEDLINE, EMBASE, Cochrane Library and bibliographies of identified articles following PRISMA guidelines including data from observational studies of acute stroke in COVID-19 patients. Data was extracted by two independent reviewers and pooled with multicenter data to calculate risk ratios (RR) and 95% confidence intervals (95%CIs) for acute stroke related to COVID-19 severity using random effects model. Between-study heterogeneity was assessed using Cochran’s Q and I 2 -statistics. PROSPERO identifier : CRD42020187194. Results: Of 165 patients hospitalized for COVID-19 (49.1% males, median age 67 [57-79], 72.1% severe or critical) included in the multicenter study, overall stroke rate was 4.2% (95%CI: 1.9-8.7). Systematic literature search identified two observational studies involving 576 patients that were eligible for meta-analysis. Among 741 pooled COVID-19 patients overall stroke rate was 2.9% (95%CI: 1.9-4.5). Risk of acute stroke was increased for patients with severe compared to non-severe COVID-19 (RR 4.12, 95%CI 1.7-10.25; p=0.002) with no evidence of heterogeneity (I 2 =0%, p=0.82). Conclusions: Synthesized analysis of data from our multicenter study and previously published cohorts demonstrate that severity of COVID-19 is associated with an increased risk of acute stroke, underscoring the necessity of neurological monitoring in patients infected with SARS-CoV-2.

Background: There is little information regarding the safety of intravenous tissue plasminogen activator (IV-tPA) in patients with stroke and COVID-19. Methods: This multicenter study included consecutive stroke patients with and without COVID-19 treated with IV-tPA between February 18, 2019, to December 31, 2020, at 9 centers participating in the CASCADE initiative. Clinical outcomes included modified Rankin Scale (mRS) at hospital discharge, in-hospital mortality, the rate of hemorrhagic transformation. Using Bayesian multiple regression and after adjusting for variables with significant value in univariable analysis, we reported the posterior adjusted odds ratio (OR, with 95% Credible Intervals [CrI]) of the main outcomes. Results: A total of 545 stroke patients, including 101 patients with COVID-19 were evaluated. Patients with COVID-19 had a more severe stroke at admission. In the study cohort, 85 (15.9%) patients had a hemorrhagic transformation, and 72 (13.1%) died in the hospital. After adjustment for confounding variables, discharge mRS score >2 (OR: 0.73, 95% CrI: 0.16, 3.05), in-hospital mortality (OR: 2.06, 95% CrI: 0.76, 5.53), and hemorrhagic transformation (OR: 1.514, 95% CrI: 0.66, 3.31) were similar in COVID-19 and non COVID-19 patients. High -sensitivity C reactive protein level was a predictor of hemorrhagic transformation in all cases (OR:1.01, 95%CI: 1.0026, 1.018), including those with COVID-19 (OR:1.024, 95%CI:1.002, 1.054). Conclusion: IV-tPA treatment in patients with acute ischemic stroke and COVID-19 was not associated with an increased risk of disability, mortality, and hemorrhagic transformation compared to those without COVID-19. IVtPA should continue to be considered as the standard of care in patients with hyper acute stroke and COVID-19.

An ultrasound examination of the extracranial portions of the vertebral artery constitutes an inexpensive and widely available screening method (being a mandatory part of a carotid duplex examination) to diagnose atherosclerotic disease and a variety of other findings and to further identify candidates for more invasive diagnostic evaluations. Furthermore, duplex scanning of the vertebral artery can help determine the pathogenic mechanism of an ischemic stroke and can lead to an early initiation of a mechanism-specific stroke treatment or prevention. Extracranial vertebral duplex scanning should be performed in conjunction with transcranial Doppler or color-coded duplex scanning in patients with stroke and transient ischemic attacks. The aim of this chapter is to describe the methods of vertebral artery color duplex scanning, practical criteria for interpretation, and relevance of these findings to patient management.

To assess the kidney safety profile of mannitol in patients with malignant middle cerebral artery (MCA) infarction.We studied consecutive patients with malignant MCA infarction (01/2008-01/2018). Malignant MCA infarction was defined according to DESTINY criteria. We compared clinical endpoints including acute kidney injury (AKI; according to Kidney Disease: Improving Global Outcomes [KDIGO]) and dialysis between patients with and without mannitol. Multivariable model was built to explore predictor variables of AKI and in-hospital death.Overall, 219 patients with malignant MCA infarction were included. Mannitol was administered in 93/219 (42.5%) patients with an average dosage of 650 g (250-950 g). Patients treated with mannitol more frequently suffered from AKI (39.8% vs. 11.9%; p 0.001) and required hemodialysis (7.5% vs. 0.8%; p = 0.01) than patients without mannitol. At discharge, more patients in the mannitol group had persistent AKI than control patients (23.7% vs. 6.4%, p 0.001). In multivariable model, mannitol emerged as independent predictor of AKI (OR 5.02, 95%CI 2.36-10.69; p 0.001).Acute kidney injury appears to be a frequent complication of hyperosmolar therapy with mannitol in patients with malignant MCA infarction. Given the lack of evidence supporting effectiveness of mannitol in these patients, its routine use should be carefully considered.

Background and PurposeThe novel severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), now named coronavirus disease 2019 (COVID-19), may change the risk of stroke through an enhanced systemic inflammatory response, hypercoagulable state, and endothelial damage in the cerebrovascular system. Moreover, due to the current pandemic, some countries have prioritized health resources towards COVID-19 management, making it more challenging to appropriately care for other potentially disabling and fatal diseases such as stroke. The aim of this study is to identify and describe changes in stroke epidemiological trends before, during, and after the COVID-19 pandemic.MethodsThis is an international, multicenter, hospital-based study on stroke incidence and outcomes during the COVID-19 pandemic. We will describe patterns in stroke management, stroke hospitalization rate, and stroke severity, subtype (ischemic/hemorrhagic), and outcomes (including in-hospital mortality) in 2020 during COVID-19 pandemic, comparing them with the corresponding data from 2018 and 2019, and subsequently 2021. We will also use an interrupted time series (ITS) analysis to assess the change in stroke hospitalization rates before, during, and after COVID-19, in each participating center.ConclusionThe proposed study will potentially enable us to better understand the changes in stroke care protocols, differential hospitalization rate, and severity of stroke, as it pertains to the COVID-19 pandemic. Ultimately, this will help guide clinical-based policies surrounding COVID-19 and other similar global pandemics to ensure that management of cerebrovascular comorbidity is appropriately prioritized during the global crisis. It will also guide public health guidelines for at-risk populations to reduce risks of complications from such comorbidities.

Highlights • Despite rigorous universal testing in a protected code stroke protocol, none of the consecutive 116 stroke patients tested were positive for SARS-CoV-2. • Universal testing did not adversely affect hyperacute stroke care. • Information on SARS-CoV-2 status can be used to guide protective measures in patients with acute stroke., Objective Stroke patients are thought to be at increased risk of Coronavirus Disease 2019 (COVID-19). To evaluate yield of universal laboratory testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in acute stroke patients and its impact on hyperacute stroke care. Methods Between weeks 14 and 18 in 2020, a protected code stroke protocol including infection control screening and laboratory testing for SARS-CoV-2 was prospectively implemented for all code stroke patients upon arrival to the emergency department. If infection control screen was positive, patients received protective hygienic measures and laboratory test results were available within four hours from testing. In patients with negative screen, laboratory results were available no later than the next working day. Door-to-imaging times of patients treated with thrombolysis or thrombectomy were compared with those of patients treated during the preceding weeks 1 to 13 in 2020. Results During the 4-weeks study period, 116 consecutive code stroke patients underwent infection control screen and laboratory testing for SARS-CoV-2. Among 5 (4.3%) patients whose infection control screen was positive, no patient was tested positive for SARS-CoV-2. All patients with negative infection control screens had negative test results. Door-to-imaging times of patients treated with thrombolysis and/or thrombectomy were not different to those treated during the preceding weeks (12 [9-15] min versus 13 [11-17] min, p = 0.24). Conclusions Universal laboratory testing for SARS-CoV-2 provided useful information on patients’ infection status and its implementation into a protected code stroke protocol did not adversely affect hyperacute stroke care.

Background Hepatitis E infection affects over 20 million people worldwide. Reports of neurological manifestations are largely limited to the peripheral nervous system. We report a middle-aged genotype 3c male patient with acute hepatitis E virus (HEV) infection and severe neurological deficits with evidence of multiple disseminated inflammatory lesions of the central nervous system. Case presentation A 42-year-old male patient presented to our emergency department with musculoskeletal weakness, bladder and bowel retention, blurred vision and ascending hypoesthesia up to the level of T8. Serology showed elevated liver enzymes and positive IgM-titers of hepatitis E. Analysis of cerebrospinal fluid (CSF) showed mild pleocytosis and normal levels of glucose, lactate and protein. HEV-RNA-copies were detected in the CSF and stool. Within 3 days after admission the patient became paraplegic, had complete visual loss and absent pupillary reflexes. MRI showed inflammatory demyelination of the optic nerve sheaths, multiple subcortical brain regions and the spinal cord. Electrophysiology revealed axonal damage of the peroneal nerve on both sides with absent F-waves. Treatment was performed with methylprednisolone, two cycles of plasma exchange (PLEX), one cycle of intravenous immunoglobulins (IVIG) and ribavirin which was used off-label. Liver enzymes normalized after 1 week and serology was negative for HEV-RNA after 3 weeks. Follow-up MRI showed progressive demyelination and new leptomeningeal enhancement at the thoracic spine and cauda equina 4 weeks after admission. Four months later, after rehabilitation was completed, repeated MRI showed gliotic transformation of the spinal cord without signs of an active inflammation. Treatment with rituximab was initiated. The patient remained paraplegic and hypoesthesia had ascended up to T5. Nevertheless, he regained full vision. Conclusions Our case indicates a possible association of acute HEV infection with widespread disseminated central nervous system inflammation. Up to now, no specific drugs have been approved for the treatment of acute HEV infection. We treated our patient off-label with ribavirin and escalated immunomodulatory therapy considering clinical progression and the possibility of an autoimmune response targeting nerve cell structures. While response to treatment was rather limited in our case, detection of HEV in patients with acute neurological deficits might help optimize individual treatment strategies.

Introduction: Arterial hypertension is the most frequent cause for spontaneous intracerebral hemorrhage (sICH) and may also cause left ventricular hypertrophy (LVH). We sought to analyze whether hypertensive sICH etiology is associated with LVH. Methods: We analyzed consecutive patients with sICH who were admitted to our tertiary stroke center during a four-year period and underwent transthoracic echocardiography (TTE) as part of the diagnostic work-up. We defined hypertensive sICH as typical localization of hemorrhage in patients with arterial hypertension and no other identified sICH etiology. We defined an increased end-diastolic interventricular septal wall thickness of &ge, 11 mm on TTE as a surrogate parameter for LVH. Results: Among 395 patients with sICH, 260 patients (65.8%) received TTE as part of their diagnostic work-up. The median age was 71 years (interquartile range (IQR) 17), 160 patients (61.5%) were male, the median baseline National Institute of Health Stroke Scale (NIHSS) score was 8 (IQR 13). Of these, 159 (61.2%) patients had a hypertensive sICH and 156 patients (60%) had LVH. In univariable (113/159 (71.1%) vs. 43/101 (42.6%), odds ratio (OR) 3.31, 95% confidence interval (CI95%) 1.97&ndash, 5.62), and multivariable (adjusted OR 2.95, CI95% 1.29&ndash, 6.74) analysis, hypertensive sICH was associated with LVH. Conclusions: In patients with sICH, LVH is associated with hypertensive bleeding etiology. Performing TTE is meaningful for diagnosis of comorbidities and clarification of bleeding etiology in these patients. Future studies should include long-term outcome parameters and assess left ventricular mass as main indicator for LVH.

Introduction: Hypothermia may be neuroprotective in acute ischemic stroke. Stroke patients with anterior circulation large vessel occlusion (acLVO) who receive endovascular therapy (EVT) are frequently hypothermic after the procedure. We sought to analyze whether this unintended hypothermia was associated with improved functional outcome. Methods: We extracted data of consecutive patients (01/2016-04/2019) from our prospective EVT database that includes all patients screened for EVT at our center. We included patients with acLVO who received EVT and analyzed recanalization (mTICI 2b-3) and complications (i.e., pneumonia, bradyarrhythmia, venous thromboembolism) during the hospital course. We assessed functional outcome at 3 months and analyzed risk ratios (RR) for good outcome (mRS scores 0-2) and mortality of patients who were hypothermic (> 36°C) after EVT. We compared the frequency of complications and calculated RRs for good outcome and mortality in the subgroup with recanalization. Results: Among 674 patients with anterior circulation ischemic stroke, 372 patients received EVT for acLVO (178 [47%] male, age 77 years [65-82], NIHSS score 16 [12 - 20]). Of these, 186 patients (50%) were hypothermic (median [IQR] temperature 35.2°C [34.7-35.6]) and 186 patients were normothermic (media temperature 36.4 [36.2-36.8]) after EVT. At 3 months, 54 of 186 (29.0%) hypothermic patients compared with 65 of 186 (35.0%) normothermic patients had a good outcome (RR, 0.83; 95%CI 0.62-1.12) and 52 of 186 (27.9%) hypothermic patients compared with 46 of 186 (24.7%) normothermic patients had died (RR, 1.13; 95%CI 0.8-1.59). This relation was consistent in 307 patients (82.5% of all EVTs) with successful recanalization (good outcome: RR, 0.85; 95%CI 0.63-1.14.; mortality: RR, 1.05; 95%CI 0.7-1.57). More hypothermic patients suffered pneumonia (37.8% vs. 24.7%; p=0.003) or bradyarrhythmia (55.6% vs. 18.3%; p Conclusion: Unintended hypothermia following EVT for acLVO was not associated with improved functional outcome or reduced mortality but an increased complication rate in patients with acute ischemic stroke.

Introduction: In patients with acute ischaemic stroke (AIS) dysregulation of cardiac function with decreased heart rate variability (HRV) due to impaired integrity of the autonomic nervous system is a frequent complication which is associated with increased mortality and worsening of clinical outcome. HRV biofeedback has previously been suggested to improve cardiac autonomic function by increasing parasympathetic tone. Hypothesis: We hypothesized that HRV biofeedback can be used to complement stroke unit care and alleviate autonomic cardiac dysfunction following AIS. Methods: We randomly allocated patients with AIS to either receive 9 sessions of HRV (n=24) or sham (n=24) biofeedback in addition to standard stroke unit care. These patients underwent detailed assessment of autonomic cardiac function including analysis of HRV via standard deviation of NN intervals (SDNN) and spectral analysis. Furthermore, we assessed vasomotor and sudomotor autonomic function, severity of autonomic symptoms and neurological and functional outcomes. Results: We included 48 patients (19 females, ages 65±14 years, baseline NIHSS 2.2 ± 2.2, mean ± standard deviation). Patients who had undergone HRV biofeedback displayed improved cardiac function compared to baseline (SDNN 72.6 ± 52.4 ms vs. 45.5 ± 34.7 ms, p Discussion: HRV biofeedback can modulate autonomic cardiac function post AIS to increase HRV and alleviate autonomic symptoms which might be beneficial in facilitating recovery from functional impairment. This seems to be mediated by a predominantly parasympathetic mechanism of action.