Background Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has been associated with a significant risk of thrombotic events in critically ill patients. Aim To summarize the findings of a multinational observational cohort of patients with SARS-CoV-2 and cerebrovascular disease. Methods Retrospective observational cohort of consecutive adults evaluated in the emergency department and/or admitted with coronavirus disease 2019 (COVID-19) across 31 hospitals in four countries (1 February 2020–16 June 2020). The primary outcome was the incidence rate of cerebrovascular events, inclusive of acute ischemic stroke, intracranial hemorrhages (ICH), and cortical vein and/or sinus thrombosis (CVST). Results Of the 14,483 patients with laboratory-confirmed SARS-CoV-2, 172 were diagnosed with an acute cerebrovascular event (1.13% of cohort; 1130/100,000 patients, 95%CI 970–1320/100,000), 68/171 (40.5%) were female and 96/172 (55.8%) were between the ages 60 and 79 years. Of these, 156 had acute ischemic stroke (1.08%; 1080/100,000 95%CI 920–1260/100,000), 28 ICH (0.19%; 190/100,000 95%CI 130–280/100,000), and 3 with CVST (0.02%; 20/100,000, 95%CI 4–60/100,000). The in-hospital mortality rate for SARS-CoV-2-associated stroke was 38.1% and for ICH 58.3%. After adjusting for clustering by site and age, baseline stroke severity, and all predictors of in-hospital mortality found in univariate regression (p < 0.1: male sex, tobacco use, arrival by emergency medical services, lower platelet and lymphocyte counts, and intracranial occlusion), cryptogenic stroke mechanism (aOR 5.01, 95%CI 1.63–15.44, p < 0.01), older age (aOR 1.78, 95%CI 1.07–2.94, p = 0.03), and lower lymphocyte count on admission (aOR 0.58, 95%CI 0.34–0.98, p = 0.04) were the only independent predictors of mortality among patients with stroke and COVID-19. Conclusions COVID-19 is associated with a small but significant risk of clinically relevant cerebrovascular events, particularly ischemic stroke. The mortality rate is high for COVID-19-associated cerebrovascular complications; therefore, aggressive monitoring and early intervention should be pursued to mitigate poor outcomes.

IMPORTANCE Direct transfer to angiography suite (DTAS) for patients with suspected large vessel occlusion (LVO) stroke has been described as an effective and safe measure to reduce workflow time in endovascular treatment (EVT). However, it is unknown whether DTAS improves long-term functional outcomes.OBJECTIVE To explore the effect of DTAS on clinical outcomes among patients with LVO stroke in a randomized clinical trial. DESIGN, SETTING, AND PARTICIPANTSThe study was an investigator-initiated, single-center, evaluator-blinded randomized clinical trial. Of 466 consecutive patients with acute stroke screened, 174 with suspected LVO acute stroke within 6 hours of symptom onset were included. Enrollment took place from September 2018 to November 2020 and was stopped after a preplanned interim analysis. Final follow-up was in February 2021.INTERVENTIONS Patients were randomly assigned (1:1) to follow either DTAS (89 patients) or conventional workflow (85 patients received direct transfer to computed tomographic imaging, with usual imaging performed and EVT indication decided) to assess the indication of EVT. Patients were stratified according to their having been transferred from a primary center vs having a direct admission. MAIN OUTCOMES AND MEASURESThe primary outcome was a shift analysis assessing the distribution of the 90-day 7-category (from 0 [no symptoms] to 6 [death]) modified Rankin Scale (mRS) score among patients with LVO whether or not they received EVT (modified intention-to-treat population) assessed by blinded external evaluators. Secondary outcomes included rate of EVT and door-to-arterial puncture time. Safety outcomes included 90-day mortality and rates of symptomatic intracranial hemorrhage. RESULTSIn total, 174 patients were included, with a mean (SD) age of 73.4 (12.6) years (range, 19-95 years), and 78 patients (44.8%) were women. Their mean (SD) onset-to-door time was 228.0 (117.9) minutes, and their median admission National Institutes of Health Stroke Scale score was 18 (interquartile range [IQR], 14-21). In the modified intention-to-treat population, EVT was performed for all 74 patients in the DTAS group and for 64 patients (87.7%) in the conventional workflow group (P = .002). The DTAS protocol decreased the median door-to-arterial puncture time (18 minutes [IQR, 15-24 minutes] vs 42 minutes [IQR, 35-51 minutes]; P < .001) and door-to-reperfusion time (57 minutes [IQR, vs 84 minutes [IQR, 63-117 minutes]; P < .001). The DTAS protocol decreased the severity of disability across the range of the mRS (adjusted common odds ratio, 2.2; 95% CI, 1.2-4.1; P = .009). Safety variables were comparable between groups. CONCLUSIONS AND RELEVANCEFor patients with LVO admitted within 6 hours after symptom onset, this randomized clinical trial found that, compared with conventional workflow, the use of DTAS increased the odds of patients undergoing EVT, decreased hospital workflow time, and improved clinical outcome.

Background and Purpose— If anterior circulation large vessel occlusion acute ischemic stroke patients presenting with ASPECTS 0–5 (Alberta Stroke Program Early CT Score) should be treated with mechanical thrombectomy remains unclear. Purpose of this study was to report on the outcome of patients with ASPECTS 0–5 treated with mechanical thrombectomy and to provide data regarding the effect of successful reperfusion on clinical outcomes and safety measures in these patients. Methods— Multicenter, pooled analysis of 7 institutional prospective registries: Bernese-European Registry for Ischemic Stroke Patients Treated Outside Current Guidelines With Neurothrombectomy Devices Using the SOLITAIRE FR With the Intention for Thrombectomy (Clinical Trial Registration—URL: https://www.clinicaltrials.gov . Unique identifier: NCT03496064). Primary outcome was defined as modified Rankin Scale 0–3 at day 90 (favorable outcome). Secondary outcomes included rates of day 90 modified Rankin Scale 0–2 (functional independence), day 90 mortality and occurrence of symptomatic intracerebral hemorrhage. Multivariable logistic regression analyses were performed to assess the association of successful reperfusion with clinical outcomes. Outputs are displayed as adjusted Odds Ratios (aOR) and 95% CI. Results— Two hundred thirty-seven of 2046 patients included in this registry presented with anterior circulation large vessel occlusion and ASPECTS 0–5. In this subgroup, the overall rates of favorable outcome and mortality at day 90 were 40.1% and 40.9%. Achieving successful reperfusion was independently associated with favorable outcome (aOR, 5.534; 95% CI, 2.363–12.961), functional independence (aOR, 5.583; 95% CI, 1.964–15.873), reduced mortality (aOR, 0.180; 95% CI, 0.083–0.390), and lower rates of symptomatic intracerebral hemorrhage (aOR, 0.235; 95% CI, 0.062–0.887). The mortality-reducing effect remained in patients with ASPECTS 0–4 (aOR, 0.167; 95% CI, 0.056–0.499). Sensitivity analyses did not change the primary results. Conclusions— In patients presenting with ASPECTS 0–5, who were treated with mechanical thrombectomy, successful reperfusion was beneficial without increasing the risk of symptomatic intracerebral hemorrhage. Although the results do not allow for general treatment recommendations, formal testing of mechanical thrombectomy versus best medical treatment in these patients in a randomized controlled trial is warranted.

BackgroundPerforming mechanical thrombectomy (MT) in patients with basilar artery occlusion (BAO) is currently not evidence-based.ObjectiveTo compare patients’ outcome, relative merits of achieving recanalization, and predictors of futile recanalization (FR) between BAO and anterior circulation large vessel occlusion (ACLVO) MT.MethodsIn the multicenter BEYOND-SWIFT registry (NCT03496064), univariate and multivariate (displayed as adjusted Odds Ratios, aOR and 95% confidence intervals, 95%-CI) outcome comparisons between BAO (N=165) and ACLVO (N=1574) were performed. The primary outcome was favorable outcome at 90 days (modified Rankin Scale, mRS 0-2). Secondary outcome included mortality, symptomatic intracranial hemorrhage (sICH) and FR. The relative merits of achieving successful recanalization between ACLVO and BAO were evaluated with interaction terms.ResultsMT in BAO was more often technically effective and equally safe in regards to mortality and sICH when compared to ACLVO. When adjusting for baseline differences, there was no significant difference between BAO vs ACLVO regarding rates of favorable outcome (aOR 0.986, 95%-CI 0.553 – 1.758). However, BAO were associated with increased rates of FR (aOR 2.146, 95%-CI 1.267 – 3.633). Predictors for FR were age, stroke severity, maneuver count and intracranial stenting. No significant heterogeneity on the relative merits of achieving successful recanalization on several outcome parameters were observed when comparing BAO and ACLVO.ConclusionsIn selected patients, similar outcomes can be achieved in BAO and ACLVO patients treated with MT. Randomized controlled trials comparing patient selection and interventional strategies seem warranted to avoid FR.Trial registration numberNCT03496064

Background and Purpose: Endovascular thrombectomy (EVT) is effective for acute ischemic stroke with large vessel occlusion (LVO) and NIHSS ≥6. However, EVT benefit for mild deficits LVOs (NIHSS<6) is uncertain. We evaluated EVT efficacy and safety in mild strokes with LVO. Methods: A retrospective cohort of patients with anterior circulation LVO and NIHSS<6 presenting within 24hours from last-seen-normal were pooled. Patients were divided into 2 groups: EVT or medical management. 90day mRS=0–1 was the primary outcome; mRS=0–2 was the secondary. Symptomatic intracerebral hemorrhage (sICH) was the safety outcome. Clinical outcomes were compared through a multivariable logistic regression after adjusting for age, presentation NIHSS, time-last-seen-normal-to-presentation, center, IV-alteplase, ASPECTS, and thrombus location. We then performed propensity score matching as a sensitivity analysis. Results were also stratified by thrombus location. Results: 214 patients (EVT-124, medical management-90) were included from 8 US and Spain centers between January/2012 and March/2017. The groups were similar in age, ASPECTS, IV-alteplase rate and time-last-seen-normal-to-presentation. There was no difference in mRS=0–1 between EVT and medical management (55.7% versus 54.4%, respectively, aOR=1.3, 95%CI=0.64–2.64, p=0.47). Similar results were seen for mRS=0–2 (63.3% EVT versus 67.8% medical management, aOR=0.9, 95%CI=0.43–1.88, p=0.77). In a propensity matching analysis, there was no treatment effect in 62 matched pairs (53.5%EVT, 48.4% medical management; OR=1.17, 95%CI=0.54–2.52, p=0.69). There was no statistically significant difference when stratified by any thrombus location; M1 approached significance (p=0.07). sICH rates were higher with thrombectomy (5.8% EVT versus 0% medical management, p=0.02). Conclusions: Our retrospective multicenter cohort study showed no improvement in excellent and independent functional outcomes in mild strokes (NIHSS<6) receiving thrombectomy irrespective of thrombus location, with increased sICH rates, consistent with the guidelines recommending the treatment for NIHSS≥6. There was a signal towards benefit with EVT only in M1 occlusions; however this needs to be further evaluated in future RCTs.

Background An increased rate of thrombotic events has been associated to Coronavirus Disease 19 (COVID-19) with a variable rate of acute stroke. Our aim is to uncover the rate of acute stroke in COVID-19 patients and identify those cases in which a possible causative relationship could exist. Methods We performed a single-center analysis of a prospective mandatory database. We studied all patients with confirmed COVID-19 and stroke diagnoses from March 2 nd to April 30 th . Demographic, clinical, and imaging data were prospectively collected. Final diagnosis was determined after full diagnostic work-up unless impossible due to death. Results Of 2050 patients with confirmed SARS-CoV-2 infection, 21 (1.02%) presented an acute ischemic stroke 21 and 4 (0.2%) suffered an intracranial hemorrhage. After the diagnostic work-up, in 60.0% ischemic and all hemorrhagic strokes patients an etiology non-related with COVID-19 was identified. Only in 6 patients the stroke cause was considered possibly related to COVID-19, all of them required mechanical ventilation before stroke onset. Ten patients underwent endovascular treatment; compared with patients who underwent EVT in the same period, COVID-19 was an independent predictor of in-hospital mortality (50% versus 15%; Odds Ratio, 6.67; 95% CI, 1.1-40.4; p 0.04). Conclusions The presence of acute stroke in patients with COVID-19 was below 2% and most of them previously presented established stroke risk factors. Without other potential cause, stroke was an uncommon complication and exclusive of patients with a severe pulmonary injury. The presence of COVID-19 in patients who underwent EVT was an independent predictor of in-hospital mortality.

Background and Purpose— Time to reperfusion is fundamental in reducing morbidity and mortality in acute stroke. We aimed to demonstrate that direct transfer to angio-suite (DTAS) of patients with suspected large vessel occlusion stroke improves workflow times and outcomes. Methods— A case-control matched study of the first 79 DTAS patients with confirmed large vessel occlusion (cases) and 145 no-DTAS patients (controls). DTAS protocol included a cone beam computed tomography in the angio-suite to rule out intracerebral hemorrhage for those patients with no prior neuroimaging in a referring center. Cases and controls were matched by location of vessel occlusion, age, baseline National Institutes of Health Stroke Scale (NIHSS) score and time from symptoms onset to Comprehensive Stroke Center arrival. Dramatic clinical improvement was defined as a decrease in NIHSS score of >10 points or final NIHSS score of ≤2. Favorable outcome was defined as modified Rankin Scale score of ≤2 at 90 days. Results— During an 18 months period a total of 97 patients were directly transferred to the angio-suite after admission: 11 (11.6%) showed an intracerebral hemorrhage on cone beam computed tomography, 7 (7.2%) did not have a large vessel occlusion on initial angiogram, and 79 (76.3%) had a large vessel occlusion and received endovascular treatment (cases). There were no differences in age, baseline NIHSS score, level of occlusion and time from onset-to-door between cases and controls. The median door-to-groin time (16 [12–20] versus 70 [45–105] minutes; P <0.01) and onset-to-groin times (222 [152–282] versus 259 [190–345] minutes; P <0.01) were shorter in the DTAS group. At 24 hours, DTAS patients presented lower NIHSS score (7 [4–16] versus 14 [4–20]; P =0.01), higher rate of dramatic improvement (50.6% Vs. 31.7%; P =0.04), and higher rate of favorable clinical outcome at 90 days (41% versus 28%; P =0.05). A logistic regression model adjusting for all matching variables showed that DTAS protocol was independently associated with 3 months favorable outcome (odds ratio, 2.5; 95% CI, 1.2–5.3; P =0.01). Conclusions— DTAS is an effective strategy to reduce workflow time which may significantly increase the odds of achieving a favorable outcome.

Background and Purpose: Different studies have pointed that CT perfusion (CTP) could overestimate ischemic core in early time window. We aim to evaluate the influence of time and collateral status on ischemic core overestimation. Methods: Retrospective single-center study including patients with anterior circulation large-vessel stroke that achieved reperfusion after endovascular treatment. Ischemic core and collateral status were automatically estimated on baseline CTP using commercially available software. CTP-derived core was considered as tissue with a relative reduction of cerebral blood flow <30%, as compared with contralateral hemisphere. Collateral status was assessed using the hypoperfusion intensity ratio (defined by the proportion of the time to maximum of tissue residue function >6 seconds with time to maximum of tissue residue function >10 seconds). Final infarct volume was measured on 24 to 48 hours noncontrast CT. Ischemic core overestimation was considered when CTP-derived core was larger than final infarct. Results: Four hundred and seven patients were included in the analysis. Median CTP-derived core and final infarct volume were 7 mL (interquartile range, 0–27) and 20 mL (interquartile range, 5–55), respectively. Median hypoperfusion intensity ratio was 0.46 (interquartile range, 0.23–0.59). Eighty-three patients (20%) presented ischemic core overestimation (median overestimation, 12 mL [interquartile range, 41–5]). Multivariable logistic regression analysis adjusted by CTP-derived core and confounding variables showed that poor collateral status (per 0.1 hypoperfusion intensity ratio increase; adjusted odds ratio, 1.41 [95% CI, 1.20–1.65]) and earlier onset to imaging time (per 60 minutes earlier; adjusted odds ratio, 1.14 [CI, 1.04–1.25]) were independently associated with core overestimation. No significant association was found with imaging to reperfusion time (per 30 minutes earlier; adjusted odds ratio, 1.17 [CI, 0.96–1.44]). Poor collateral status influence on core overestimation differed according to onset to imaging time, with a stronger size of effect on early imaging patients( P interaction <0.01). Conclusions: In patients with large-vessel stroke that achieve reperfusion after endovascular therapy, poor collateral status might induce higher rates of ischemic core overestimation on CTP, especially in patients in earlier window time. CTP reflects a hemodynamic state rather than tissue fate; collateral status and onset to imaging time are important factors to consider when estimating core on CTP.