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Objective: Neurological symptoms can present relevant co-morbidities in SARS-Cov-2 infection but potential underlying pathomechanistic patterns remain unclear. Interestingly, the presence of SARS-Cov-2 RNA and protein has been shown to in anatomically distinct areas of the brain but remains undetected [for full text, please go to the a.m. URL]

Microvesicles are released by various cell types upon activation by outward-blebbing of the cell membrane and contain surface markers and contents of the parent cell. In an experiemental setting, endothelial microvesicles (EMV) have been shown to mediate endothelial dysfunction. Clinical studies have shown an association with cardiovascular risk factors and poor outcome in cardiovascular diseases such as myocardial infarction. In ischemic stroke patients, as well as other neurological diseases, microvesicle (MV) levels are elevated after the acute event compared to healthy controls. The potential prognostic role of circulating EMV and MV of other origins for long-term cardiovascular outcome after ischemic stroke has not yet been studied. The PROSpective Cohort with Incident Stroke Berlin (PROSCIS-B) is an observational cohort study enrolling patients with first-ever ischemic stroke with a follow-up period of three years. The primary combined endpoint was predefined as recurrent stroke, myocardial infarction (MI), and all-cause mortality. Citrate-blood samples were taken on day 4 (IQR 3-5) after stroke. Levels of endothelial (Annexin V+ CD45- CD41- CD31+/CD144+/CD146+), leukocyte-derived (LMV) (Annexin V+ CD45+ CD41-), monocytic (MMV) (Annexin V+ CD14+ CD41-), and platelet-derived microvesicles (PMV) (Annexin V+ CD41+) were measured using flow cytometry. Kaplan-Meier survival analysis, the log-rank test and Cox proportional hazards models were used to calculate the impact of MV levels on the combined endpoint within three years after adjustment for potential confounding variables. Between January 2010 and June 2013, 621 patients with mild to moderate stroke were recruited of whom 571 had MV measurements (median age 69 years, 39% female, median National Institutes of Health Stroke Scale (NIHSS) 2, interquartile range (IQR) 1-4). During the follow-up period, 95 endpoints (42 recurrent strokes, 5 MI and 48 deaths) occurred. Ischemic stroke patients with levels of EMV (hazard ratio (HR) 2.5, 95% confidence interval (CI) 1.2-4.9) or LMV (HR 3.1, 95% CI 1.4-6.8) in the top quartile suffered more often a combined endpoint than participants with lower levels. This relationship was weaker for PMV (HR 1.7, 95% CI 0.9-3.2) and for MMV (HR 1.1, 95% CI 0.6-1.8) it was not detectable. In the present study, high levels of EMV and LMV were associated with an increased incidence of secondary cardiovascular events or death after mild to moderate ischemic stroke in the long term. These results enhance the significance of endothelial dysfunction and vascular inflammation for post-stroke outcome. EMV and LMV therefore might be potential cofactors for risk prediction after ischemic stroke., Mirkovesikel werden von unterschiedlichen Zelltypen bei Aktivierung durch Ausst��lpung der Zellmembran freigesetzt und enthalten Oberfl��chenmarker und teilweise Inhalte der Ursprungszelle. Endotheliale Mikrovesikel sind durch experimentelle Studien als Surrogatmarker f��r endotheliale Dysfunktion etabliert und in kardiovaskul��ren Erkrankungen wie dem Myokardinfarkt mit schlechtem Outcome assoziiert. In der Akutphase isch��mischer Schlaganf��lle sind Mikrovesikelkonzentrationen verglichen zu gesunden Kontrollen deutlich erh��ht und zeigen einen Zusammenhang mit Schlaganfallschwere. Die Bedeutung zirkulierender Mikrovesikel verschiender Ursprungszellen im kardiovaskul��ren Langzeit-Outcome nach isch��mischem Schlaganfall ist derzeit noch unklar. In der Studie PROSpective Cohort with Incident Stroke Berlin (PROSCIS-B) wurden PatientInnen mit erstmaligem isch��mischen Schlaganfall f��r drei Jahre beobachtet. Der vordefinierte prim��re kombinierte Endpunkt beinhaltete Rezidivschlaganf��lle, Myokardinfarkte und Gesamtmortalit��t. Die Konzentrationen von endothelialen (Annexin V+ CD45- CD41- CD31+/CD144+/CD146+), leukozyt��ren (Annexin V+ CD45+ CD41-), monozyt��ren (Annexin V+ CD14+ CD41-) und thrombozyt��ren Mikrovesikeln (Annexin V+ CD41+) wurden mittels Durchflusszytometrie im Median am 4. Tag (IQR 3-4) nach Schlaganfall im Citratplasma bestimmt. Zur Berechnung der Effektst��rke von Mikrovesikeln auf den kombinierten Endpunkt innerhalb drei Jahre wurden die Kaplan-Meier ��berlebensanalyse, der Log-Rank Test und die adjustierte Cox Regressionsanalyse angewendet. Zwischen Januar 2010 und Juni 2013 wurden 621 Patienten mit milden bis moderaten Schlaganf��llen rekrutiert, von denen 571 Mikrovesikelmessungen erhielten (medianes Alter 69 Jahre, 39% weiblich, medianer NIHSS 2, IQR 1-4). Im Beobachtungszeitraum traten 95 Endpunkte (42 sekund��re Schlaganf��lle, 5 Myokardinfarkte, 48 Todesf��lle) auf. Schlaganfallpatienten mit Konzentrationen in den h��chsten Quartilen von endothelialen (HR 2.5, 95% CI 1.2-4.9) oder leukozyt��ren Mirkovesikeln (HR 3.1, 95% CI 1.4-6.8) erlitten h��ufiger einen kombinierten Endpunkt als Patienten mit niedrigeren Konzentrationen. Dieser Zusammenhang war f��r thrombozyt��re Mirkovesikel weniger deutlich (HR 1.7, 95% CI 0.9-3.2) und f��r monozyt��re nicht erkennbar (HR 1.1, 95% CI 0.6-1.8). In dieser Studie waren hohe Konzentrationen endothelialer und leukozyt��rer Mikrovesikel mit einer langfristig erh��hten Inzidenz sekund��rer kardiovaskul��rer Ereignisse oder Tod nach mildem bis moderatem Schlaganfall assoziiert. Diese Ergebnisse verdeutlichen die Signifikanz endothelialer Dysfunktion und vaskul��rer Inflammation f��r das Outcome nach Schlaganfall. In der Risikopr��diktion nach isch��mischem Schlaganfall k��nnten endotheliale und leukozyt��re Mikrovesikel daher potenziell eine wichtige Rolle spielen.

Background Recent evidence suggests cardiac troponin levels to be a marker of increased vascular risk. We aimed to assess whether levels of high-sensitivity cardiac troponin T (hs-cTnT) are associated with recurrent vascular events and death in patients with first-ever, mild to moderate ischemic stroke. Methods and Results We used data from the PROSCIS-B (Prospective Cohort With Incident Stroke Berlin) study. We computed Cox proportional hazards regression analyses to assess the association between hs-cTnT levels upon study entry (Roche Elecsys, upper reference limit, 14 ng/L) and the primary outcome (composite of recurrent stroke, myocardial infarction, and all-cause death). A total of 562 patients were analyzed (mean age, 67 years [SD 13]; 38.6% women; median National Institutes of Health Stroke Scale=2; hs-cTnT above upper reference limit, 39.2%). During a mean follow-up of 3 years, the primary outcome occurred in 89 patients (15.8%), including 40 (7.1%) recurrent strokes, 4 (0.7%) myocardial infarctions, and 51 (9.1%) events of all-cause death. The primary outcome occurred more often in patients with hs-cTnT above the upper reference limit (27.3% versus 10.2%; adjusted hazard ratio, 2.0; 95% CI, 1.3-3.3), with a dose-response relationship when the highest and lowest hs-cTnT quartiles were compared (15.2 versus 1.8 events per 100 person-years; adjusted hazard ratio, 4.8; 95% CI, 1.9-11.8). This association remained consistent in sensitivity analyses, which included age matching and stratification for sex. Conclusions Hs-cTnT is dose-dependently associated with an increased risk of recurrent vascular events and death within 3 years after first-ever, mild to moderate ischemic stroke. These findings support further studies of the utility of hs-cTnT for individualized risk stratification after stroke. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01363856.