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Background and Purpose: The role of the venous compartment in cerebral small vessel disease has yet to be fully understood. As such, we evaluated how deep medullary veins integrity relates to MRI-based small vessel disease severity markers and glymphatic function assessed by DTI measures in patients with a recent small subcortical infarct., Materials and Methods: We gathered demographic, clinical, and 3 Tesla-MRI imaging data from 50 patients with a recent small subcortical infarct. We evaluate the venular integrity using two visual scales based on their appearance on SWI. We assessed the number of lacunes and microbleeds, white matter hyperintensities volume, perivascular spaces volume in basal ganglia and white matter, summary-small vessel disease score, and brain volume. Diffusivity measures in normal-appearing white matter included free water fraction, mean diffusivity and fractional anisotropy with and without free water correction, and DTI along the perivascular spaces. After categorizing the cohort in quartiles according to both venular scores, we assessed their correlations with small vessel disease markers and diffusivity measures using multivariable ordinal regression analyses adjusting for age, sex, smoking, and summary small vessel disease score., Results: In univariate analysis most of the imaging variables, except for microbleeds, perivascular spaces in white matter and DTI-along the perivascular spaces, were associated with one or both venular scores. In multivariate analysis (OR, 95% CI), free water (1.33, 1.03-1.73), mean diffusivity (4.56, 1.32-15.81), fractional anisotropy (0.77, 0.63-0.93), free water-corrected mean diffusivity and fractional anisotropy (2.39, 1.06-5.39;0.78, 0.65-0.94, respectively), associated with vein appearance, while only brain volume (0.48, 0.25-0.94), fractional anisotropy with and without free water correction (0.82,0.86-0.99; 0.83, 0.7-0.99, respectively) remained significant for vein count., Conclusions: In patients with a recent small subcortical infarct, disruption of the deep medullary veins, increased extracellular water, and white matter injury appear to be associated., Abbreviations: SVD=small vessel disease; DMV=deep medullary veins; WMH=white matter hyperintensities; PVS=perivascular spaces; DTI-ALPS=diffusion tensor image analysis along the perivascular spaces; FW=free water; MD=mean diffusivity; FA= fractional anisotropy; BG=basal ganglia., Competing Interests: The authors declare no conflicts of interest related to the content of this article., (© 2024 by American Journal of Neuroradiology.)

Introduction: Malignant middle cerebral artery infarction (MCI) needs rapid intervention. This study aimed to enhance the prediction of MCI using computed tomography perfusion (CTP) with varied quantitative benchmarks., Materials and Methods: We retrospectively analyzed 253 patients from a single-center registry presenting with acute, severe, proximal large vessel occlusion studied with whole-brain CTP imaging at hospital arrival within the first 24 h of symptoms-onset. MCI was defined by clinical and imaging criteria, including decreased level of consciousness, anisocoria, death due to cerebral edema, or need for decompressive craniectomy, together with midline shift ⩾6 mm, or infarction of more than 50% of the MCA territory. The predictive accuracy of baseline ASPECTS and CTP quantifications for MCI was assessed by receiver operating characteristic (ROC) area under the curve (AUC) while F -score was calculated as an indicator of precision and sensitivity., Results: Sixty-three out of 253 patients (25%) fulfilled MCI criteria and had worse clinical and imaging results than the non-MCI group. The capacity to predict MCI was lower for baseline ASPECTS (AUC 0.83, F -score 0.52, Youden's index 6), than with perfusion-based measures: relative cerebral blood volume threshold <40% (AUC 0.87, F -score 0.71, Youden's index 34 mL) or relative cerebral blood flow threshold <35% (AUC 0.87, F -score 0.62, Youden's index 67 mL). CTP based on rCBV measurements identified twice as many MCI as baseline CT ASPECTS., Discussion and Conclusion: CTP-based quantifications may offer enhanced predictive capabilities for MCI compared to non-contrast baseline CT ASPECTS, potentially improving the monitoring of severe ischemic stroke patients at risk of life-threatening edema and its treatment., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Importance: Prehospital transfer protocols are based on rapid access to reperfusion therapies for patients with ischemic stroke. The effect of different protocols among patients receiving a final diagnosis of intracerebral hemorrhage (ICH) is unknown., Objective: To determine the effect of direct transport to an endovascular treatment (EVT)-capable stroke center vs transport to the nearest local stroke center., Design, Setting, and Participants: This was a prespecified secondary analysis of RACECAT, a multicenter, population-based, cluster-randomized clinical trial conducted from March 2017 to June 2020 in Catalonia, Spain. Patients were evaluated by a blinded end point assessment. All consecutive patients suspected of experiencing a large vessel occlusion stroke (Rapid Arterial Occlusion Evaluation Scale [RACE] score in the field >4 on a scale of 0 to 9, with lower to higher stroke severity) with final diagnosis of ICH were included. A total of 1401 patients were enrolled in RACECAT with suspicion of large vessel occlusion stroke. The current analysis was conducted in October 2022., Intervention: Direct transport to an EVT-capable stroke center (n = 137) or to the closest local stroke center (n = 165)., Main Outcomes and Measures: The primary outcome was tested using cumulative ordinal logistic regression to estimate the common odds ratio (OR) and 95% CI of the shift analysis of disability at 90 days as assessed by the modified Rankin Scale (mRS) score (range, 0 [no symptoms] to 6 [death]) in the intention-to-treat population. Secondary outcomes, included 90-day mortality, death or severe functional dependency, early neurological deterioration, early mortality, ICH volume and enlargement, rate of neurosurgical treatment, rate of clinical complications during initial transport, and rate of adverse events until day 5., Results: Of 1401 patients enrolled, 1099 were excluded from this analysis (32 rejected informed consent, 920 had ischemic stroke, 29 had transient ischemic attack, 12 had subarachnoid hemorrhage, and 106 had stroke mimic). Thus, 302 patients were included (204 [67.5%] men; mean [SD] age 71.7 [12.8] years; and median [IQR] RACE score, 7 [6-8]). For the primary outcome, direct transfer to an EVT-capable stroke center (mean [SD] mRS score, 4.93 [1.38]) resulted in worse functional outcome at 90 days compared with transfer to the nearest local stroke center (mean [SD] mRS score, 4.66 [1.39]; adjusted common OR, 0.63; 95% CI, 0.41-0.96). Direct transfer to an EVT-capable stroke center also suggested potentially higher 90-day mortality compared with transfer to the nearest local stroke center (67 of 137 [48.9%] vs 62 of 165 [37.6%]; adjusted hazard ratio, 1.40; 95% CI, 0.99-1.99). The rates of medical complications during the initial transfer (30 of 137 [22.6%] vs 9 of 165 patients [5.6%]; adjusted OR, 5.29; 95% CI, 2.38-11.73) and in-hospital pneumonia (49 of 137 patients [35.8%] vs 29 of 165 patients [17.6%]; OR, 2.61; 95% CI, 1.53-4.44) were higher in the EVT-capable stroke center group., Conclusions and Relevance: In this secondary analysis of the RACECAT randomized clinical trial, bypassing the closest stroke center resulted in reduced chances of functional independence at 90 days for patients who received a final diagnosis of ICH., Trial Registration: ClinicalTrials.gov Identifier: NCT02795962.

Vascular endothelial function is challenged during cerebral ischemia and reperfusion. The endothelial responses are involved in inflammatory leukocyte attraction, adhesion and infiltration, blood-brain barrier leakage, and angiogenesis. This study investigated gene expression changes in brain endothelial cells after acute ischemic stroke using transcriptomics and translatomics. We isolated brain endothelial mRNA by: (i) translating ribosome affinity purification, enabling immunoprecipitation of brain endothelial ribosome-attached mRNA for translatome sequencing and (ii) isolating CD31 + endothelial cells by fluorescence-activating cell sorting for classical transcriptomic analysis. Both techniques revealed similar pathways regulated by ischemia but they showed specific differences in some transcripts derived from non-endothelial cells. We defined a gene set characterizing the endothelial response to acute stroke (24h) by selecting the differentially expressed genes common to both techniques, thus corresponding with the translatome and minimizing non-endothelial mRNA contamination. Enriched pathways were related to inflammation and immunoregulation, angiogenesis, extracellular matrix, oxidative stress, and lipid trafficking and storage. We validated, by flow cytometry and immunofluorescence, the protein expression of several genes encoding cell surface proteins. The inflammatory response was associated with the endothelial upregulation of genes related to lipid storage functions and we identified lipid droplet biogenesis in the endothelial cells after ischemia. The study reports a robust translatomic signature of brain endothelial cells after acute stroke and identifies enrichment in novel pathways involved in membrane signaling and lipid storage. Altogether these results highlight the endothelial contribution to the inflammatory response, and identify novel molecules that could be targets to improve vascular function after ischemic stroke., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Respiratory and urinary tract infections are frequent complications in patients with severe stroke. Stroke-associated infection is mainly due to opportunistic commensal bacteria of the microbiota that may translocate from the gut. We investigated the mechanisms underlying gut dysbiosis and poststroke infection., Methods: Using a model of transient cerebral ischemia in mice, we explored the relationship between immunometabolic dysregulation, gut barrier dysfunction, gut microbial alterations, and bacterial colonization of organs, and we explored the effect of several drug treatments., Results: Stroke-induced lymphocytopenia and widespread colonization of lung and other organs by opportunistic commensal bacteria. This effect correlated with reduced gut epithelial barrier resistance, and a proinflammatory sway in the gut illustrated by complement and nuclear factor-κB activation, reduced number of gut regulatory T cells, and a shift of gut lymphocytes to γδT cells and T helper 1/T helper 17 phenotypes. Stroke increased conjugated bile acids in the liver but decreased bile acids and short-chain fatty acids in the gut. Gut fermenting anaerobic bacteria decreased while opportunistic facultative anaerobes, notably Enterobacteriaceae, suffered an expansion. Anti-inflammatory treatment with a nuclear factor-κB inhibitor fully abrogated the Enterobacteriaceae overgrowth in the gut microbiota induced by stroke, whereas inhibitors of the neural or humoral arms of the stress response were ineffective at the doses used in this study. Conversely, the anti-inflammatory treatment did not prevent poststroke lung colonization by Enterobacteriaceae., Conclusions: Stroke perturbs homeostatic neuro-immuno-metabolic networks facilitating a bloom of opportunistic commensals in the gut microbiota. However, this bacterial expansion in the gut does not mediate poststroke infection., Competing Interests: Disclosures None.

Objectives: To study prehospital care process in relation to hospital outcomes in stroke-code cases first attended by 2 different levels of ambulance. To analyze factors associated with a satisfactory functional outcome at 3 months., Material and Methods: Prospective multicenter observational cohort study. All stroke-code cases attended by prehospital emergency services from January 2016 to April 2022 were included. Prehospital and hospital variables were collected. The classificatory variable was type of ambulance attending (basic vs advanced life support). The main outcome variables were mortality and functional status after ischemic strokes in patients who underwent reperfusion treatment 90 days after the ischemic episode., Results: Out of 22 968 stroke-code activations, ischemic stroke was diagnosed in 12 467 patients (54.3%) whose functional status was good before the episode. Basic ambulances attended 93.1%; an advanced ambulance was ordered in 1.6% of the patients. Even though there were differences in patient and clinical characteristics recorded during the prehospital process, type of ambulance was not independently associated with mortality (adjusted odds ratio [aOR], 1.1; 95% CI, 0.77-1.59) or functional status at 3 months (aOR, 1.05; 95% CI, 0,72-1,47)., Conclusion: The percentage of patient complications in stroke-code cases attended by basic ambulance teams is low. Type of ambulance responding was not associated with either mortality or functional outcome at 3 months in this study.

Background: We aim to compare the outcome of patients from urban areas, where the referral center is able to perform thrombectomy, with patients from nonurban areas enrolled in the RACECAT trial (Direct Transfer to an Endovascular Center Compared to Transfer to the Closest Stroke Center in Acute Stroke Patients With Suspected Large Vessel Occlusion)., Methods: Patients with suspected large vessel occlusion stroke, as evaluated by a Rapid Arterial Occlusion Evaluation score of ≥5, from urban catchment areas of thrombectomy-capable centers during RACECAT trial enrollment period were included in the Stroke Code Registry of Catalonia. Primary outcome was disability at 90 days, as assessed by the shift analysis on the modified Rankin Scale score, in patients with an ischemic stroke. Secondary outcomes included mortality at 90 days, rate of thrombolysis and thrombectomy, time from onset to thrombolysis, and thrombectomy initiation. Propensity score matching was used to assemble a cohort of patients with similar characteristics., Results: The analysis included 1369 patients from nonurban areas and 2502 patients from urban areas. We matched 920 patients with an ischemic stroke from urban areas and nonurban areas based on their propensity scores. Patients with ischemic stroke from nonurban areas had higher degrees of disability at 90 days (median [interquartle range] modified Rankin Scale score, 3 [2-5] versus 3 [1-5], common odds ratio, 1.25 [95% CI, 1.06-1.48]); the observed average effect was only significant in patients with large vessel stroke (common odds ratio, 1.36 [95% CI, 1.08-1.65]). Mortality rate was similar between groups(odds ratio, 1.02 [95% CI, 0.81-1.28]). Patients from nonurban areas had higher odds of receiving thrombolysis (odds ratio, 1.36 [95% CI, 1.16-1.67]), lower odds of receiving thrombectomy(odds ratio, 0.61 [95% CI, 0.51-0.75]), and longer time from stroke onset to thrombolysis (mean difference 38 minutes [95% CI, 25-52]) and thrombectomy(mean difference 66 minutes [95% CI, 37-95])., Conclusions: In Catalonia, Spain, patients with large vessel occlusion stroke triaged in nonurban areas had worse neurological outcomes than patients from urban areas, where the referral center was able to perform thrombectomy. Interventions aimed at improving organizational practices and the development of thrombectomy capabilities in centers located in remote areas should be pursued., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02795962.

Introduction: Current recommendations for regional stroke destination suggest that patients with severe acute stroke in non-urban areas should be triaged based on the estimated transport time to a referral thrombectomy-capable center., Methods: We performed a post hoc analysis to evaluate the association of pre-hospital workflow times with neurological outcomes in patients included in the RACECAT trial. Workflow times evaluated were known or could be estimated before transport allocation. Primary outcome was the shift analysis on the modified Rankin score at 90 days., Results: Among the 1,369 patients included, the median time from onset to emergency medical service (EMS) evaluation, the estimated transport time to a thrombectomy-capable center and local stroke center, and the estimated transfer time between centers were 65 minutes (interquartile ratio [IQR] = 43-138), 61 minutes (IQR = 36-80), 17 minutes (IQR = 9-27), and 62 minutes (IQR = 36-73), respectively. Longer time intervals from stroke onset to EMS evaluation were associated with higher odds of disability at 90 days in the local stroke center group (adjusted common odds ratio (acOR) for each 30-minute increment = 1.03, 95% confidence interval [CI] = 1.01-1.06), with no association in the thrombectomy-capable center group (acOR for each 30-minute increment = 1.01, 95% CI = 0.98-1.01, p interaction  = 0.021). No significant interaction was found for other pre-hospital workflow times. In patients evaluated by EMS later than 120 minutes after stroke onset, direct transport to a thrombectomy-capable center was associated with better disability outcomes (acOR = 1.49, 95% CI = 1.03-2.17)., Conclusion: We found a significant heterogeneity in the association between initial transport destination and neurological outcomes according to the elapse of time between the stroke onset and the EMS evaluation (ClinicalTrials.gov: NCT02795962). ANN NEUROL 2022;92:931-942., (© 2022 American Neurological Association.)

Objective: This study was undertaken to investigate whether adjunct alteplase improves brain reperfusion following successful thrombectomy., Methods: This single-center, randomized, double-blind, placebo-controlled study included 36 patients (mean [standard deviation] = 70.8 [13.5] years old, 18 [50%] women) with large vessel occlusion undergoing thrombectomy resulting in near-normal (expanded Thrombolysis in Cerebral Infarction [eTICI] b50/67/2c, n = 23, 64%) or normal angiographic reperfusion (eTICI 3, n = 13, 36%). Seventeen patients were randomized to intra-arterial alteplase (0.225mg/kg), and 19 received placebo. At 48 hours, patients had brain perfusion/diffusion-weighted magnetic resonance imaging (MRI) and MRI-spectroscopy. The primary outcome was the difference in the proportion of patients with areas of hypoperfusion on MRI. Secondary outcomes were the infarct expansion ratio (final to initial infarction volume), and the N-acetylaspartate (NAA) peak relative to total creatine as a marker of neuronal integrity., Results: The prevalence of hypoperfusion was 24% with intra-arterial alteplase, and 58% with placebo (adjusted odds ratio = 0.20, 95% confidence interval [CI] = 0.04-0.91, p = 0.03). Among 14 patients with final eTICI 3 scores, hypoperfusion was found in 1 of 7 (14%) in the alteplase group and 3 of 7 (43%) in the placebo group. Abnormal brain perfusion was associated with worse functional outcome at day 90. Alteplase significantly reduced the infarct expansion ratio compared with placebo (median [interquartile range (IQR)] = 0.7 [0.5-1.2] vs 3.2 [1.8-5.7], p = 0.01) and resulted in higher NAA peaks (median [IQR] = 1.13 [0.91-1.36] vs 1.00 [0.74-1.22], p < 0.0001)., Interpretation: There is a high prevalence of areas of hypoperfusion following thrombectomy despite successful reperfusion on angiography. Adjunct alteplase enhances brain reperfusion, which results in reduced expansion of the infarction and improved neuronal integrity. ANN NEUROL 2022;92:860-870., (© 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background and Purpose: Previous studies suggest that mechanisms and outcomes in patients with COVID-19-associated stroke differ from those in patients with non-COVID-19-associated strokes, but there is limited comparative evidence focusing on these populations. The aim of this study, therefore, was to determine if a significant association exists between COVID-19 status with revascularization and functional outcomes following thrombectomy for large vessel occlusion (LVO), after adjustment for potential confounding factors., Methods: A cross-sectional, international multicenter retrospective study was conducted in consecutively admitted COVID-19 patients with concomitant acute LVO, compared to a control group without COVID-19. Data collected included age, gender, comorbidities, clinical characteristics, details of the involved vessels, procedural technique, and various outcomes. A multivariable-adjusted analysis was conducted., Results: In this cohort of 697 patients with acute LVO, 302 had COVID-19 while 395 patients did not. There was a significant difference (p &lt; 0.001) in the mean age (in years) and gender of patients, with younger patients and more males in the COVID-19 group. In terms of favorable revascularization (modified Thrombolysis in Cerebral Infarction [mTICI] grade 3), COVID-19 was associated with lower odds of complete revascularization (odds ratio 0.33, 95% confidence interval [CI] 0.23-0.48; p &lt; 0.001), which persisted on multivariable modeling with adjustment for other predictors (adjusted odds ratio 0.30, 95% CI 0.12-0.77; p = 0.012). Moreover, endovascular complications, in-hospital mortality, and length of hospital stay were significantly higher among COVID-19 patients (p &lt; 0.001)., Conclusion: COVID-19 was an independent predictor of incomplete revascularization and poor functional outcome in patients with stroke due to LVO. Furthermore, COVID-19 patients with LVO were more often younger and had higher morbidity/mortality rates., (© 2022 European Academy of Neurology.)

In patients with infective endocarditis and neurological complications, the optimal timing for cardiac surgery is unclear due to the varied risk of clinical deterioration when early surgery is performed. The aim of this review is to summarize the best evidence on the optimal timing for cardiac surgery in the presence of each type of neurological complication. An English literature search was carried out from June 2018 through July 2022. The resulting selection, comprising observational studies, clinical trials, systematic reviews and society guidelines, was organized into four sections according to the four groups of neurological complications: ischemic, hemorrhagic, infectious, and asymptomatic complications. Cardiac surgery could be performed without delay in cases of ischemic vascular neurological complication (provided the absence of severe damage, which can be avoided with the performance of mechanical thrombectomy in cases of major stroke), as well as infectious or asymptomatic complications. In the presence of intracranial hemorrhage, a delay of four weeks is recommended for most cases, although recent studies have suggested that performing cardiac surgery within four weeks could be a suitable option for selected cases. The findings of this review are mostly in line with the recommendations of the current European and American infective endocarditis guidelines.

Objectives: After an acute ischemic stroke, patients with a large CT perfusion (CTP) predicted infarct core (pIC) have poor clinical outcome. However, previous research suggests that this relationship may be relevant for subgroups of patients determined by pretreatment and treatment-related variables while negligible for others. We aimed to identify these variables., Methods: We included a cohort of 828 patients with acute proximal carotid arterial occlusions imaged with a whole-brain CTP within 8 h from stroke onset. pIC was computed on CTP Maps (cerebral blood flow < 30%), and poor clinical outcome was defined as a 90-day modified Rankin Scale score > 2. Potential mediators of the association between pIC and clinical outcome were evaluated through first-order and advanced interaction analyses in the derivation cohort (n = 654) for obtaining a prediction model. The derived model was further validated in an independent cohort (n = 174)., Results: The volume of pIC was significantly associated with poor clinical outcome (OR = 2.19, 95% CI = 1.73 - 2.78, p < 0.001). The strength of this association depended on baseline National Institute of Health Stroke Scale, glucose levels, the use of thrombectomy, and the interaction of age with thrombectomy. The model combining these variables showed good discrimination for predicting clinical outcome in both the derivation cohort and validation cohorts (area under the receiver operating characteristic curve 0.780 (95% CI = 0.746-0.815) and 0.782 (95% CI = 0.715-0.850), respectively)., Conclusions: In patients imaged within 8 h from stroke onset, the association between pIC and clinical outcome is significantly modified by baseline and therapeutic variables. These variables deserve consideration when evaluating the prognostic relevance of pIC., Key Points: •The volume of CT perfusion (CTP) predicted infarct core (pIC) is associated with poor clinical outcome in acute ischemic stroke imaged within 8 h of onset. •The relationship between pIC and clinical outcome may be modified by baseline clinical severity, glucose levels, thrombectomy use, and the interaction of age with thrombectomy. •CTP pIC should be evaluated in an individual basis for predicting clinical outcome in patients imaged within 8 h from stroke onset., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Background: The mechanisms and outcomes in coronavirus disease (COVID-19)-associated stroke are unique from those of non-COVID-19 stroke., Objective: To describe the efficacy and outcomes of acute revascularization of large vessel occlusion (LVO) in the setting of COVID-19 in an international cohort., Methods: We conducted an international multicenter retrospective study of consecutively admitted patients with COVID-19 with concomitant acute LVO across 50 comprehensive stroke centers. Our control group constituted historical controls of patients presenting with LVO and receiving a mechanical thrombectomy between January 2018 and December 2020., Results: The total cohort was 575 patients with acute LVO; 194 patients had COVID-19 while 381 patients did not. Patients in the COVID-19 group were younger (62.5 vs 71.2; P < .001) and lacked vascular risk factors (49, 25.3% vs 54, 14.2%; P = .001). Modified thrombolysis in cerebral infarction 3 revascularization was less common in the COVID-19 group (74, 39.2% vs 252, 67.2%; P < .001). Poor functional outcome at discharge (defined as modified Ranklin Scale 3-6) was more common in the COVID-19 group (150, 79.8% vs 132, 66.7%; P = .004). COVID-19 was independently associated with a lower likelihood of achieving modified thrombolysis in cerebral infarction 3 (odds ratio [OR]: 0.4, 95% CI: 0.2-0.7; P < .001) and unfavorable outcomes (OR: 2.5, 95% CI: 1.4-4.5; P = .002)., Conclusion: COVID-19 was an independent predictor of incomplete revascularization and poor outcomes in patients with stroke due to LVO. Patients with COVID-19 with LVO were younger, had fewer cerebrovascular risk factors, and suffered from higher morbidity/mortality rates., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Importance: In nonurban areas with limited access to thrombectomy-capable centers, optimal prehospital transport strategies in patients with suspected large-vessel occlusion stroke are unknown., Objective: To determine whether, in nonurban areas, direct transport to a thrombectomy-capable center is beneficial compared with transport to the closest local stroke center., Design, Setting, and Participants: Multicenter, population-based, cluster-randomized trial including 1401 patients with suspected acute large-vessel occlusion stroke attended by emergency medical services in areas where the closest local stroke center was not capable of performing thrombectomy in Catalonia, Spain, between March 2017 and June 2020. The date of final follow-up was September 2020., Interventions: Transportation to a thrombectomy-capable center (n = 688) or the closest local stroke center (n = 713)., Main Outcomes and Measures: The primary outcome was disability at 90 days based on the modified Rankin Scale (mRS; scores range from 0 [no symptoms] to 6 [death]) in the target population of patients with ischemic stroke. There were 11 secondary outcomes, including rate of intravenous tissue plasminogen activator administration and thrombectomy in the target population and 90-day mortality in the safety population of all randomized patients., Results: Enrollment was halted for futility following a second interim analysis. The 1401 enrolled patients were included in the safety analysis, of whom 1369 (98%) consented to participate and were included in the as-randomized analysis (56% men; median age, 75 [IQR, 65-83] years; median National Institutes of Health Stroke Scale score, 17 [IQR, 11-21]); 949 (69%) comprised the target ischemic stroke population included in the primary analysis. For the primary outcome in the target population, median mRS score was 3 (IQR, 2-5) vs 3 (IQR, 2-5) (adjusted common odds ratio [OR], 1.03; 95% CI, 0.82-1.29). Of 11 reported secondary outcomes, 8 showed no significant difference. Compared with patients first transported to local stroke centers, patients directly transported to thrombectomy-capable centers had significantly lower odds of receiving intravenous tissue plasminogen activator (in the target population, 229/482 [47.5%] vs 282/467 [60.4%]; OR, 0.59; 95% CI, 0.45-0.76) and significantly higher odds of receiving thrombectomy (in the target population, 235/482 [48.8%] vs 184/467 [39.4%]; OR, 1.46; 95% CI, 1.13-1.89). Mortality at 90 days in the safety population was not significantly different between groups (188/688 [27.3%] vs 194/713 [27.2%]; adjusted hazard ratio, 0.97; 95% CI, 0.79-1.18)., Conclusions and Relevance: In nonurban areas in Catalonia, Spain, there was no significant difference in 90-day neurological outcomes between transportation to a local stroke center vs a thrombectomy-capable referral center in patients with suspected large-vessel occlusion stroke. These findings require replication in other settings., Trial Registration: ClinicalTrials.gov Identifier: NCT02795962.

Importance: It is estimated that only 27% of patients with acute ischemic stroke and large vessel occlusion who undergo successful reperfusion after mechanical thrombectomy are disability free at 90 days. An incomplete microcirculatory reperfusion might contribute to these suboptimal clinical benefits., Objective: To investigate whether treatment with adjunct intra-arterial alteplase after thrombectomy improves outcomes following reperfusion., Design, Setting, and Participants: Phase 2b randomized, double-blind, placebo-controlled trial performed from December 2018 through May 2021 in 7 stroke centers in Catalonia, Spain. The study included 121 patients with large vessel occlusion acute ischemic stroke treated with thrombectomy within 24 hours after stroke onset and with an expanded Treatment in Cerebral Ischemia angiographic score of 2b50 to 3., Interventions: Participants were randomized to receive intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) infused over 15 to 30 minutes (n = 61) or placebo (n = 52)., Main Outcomes and Measures: The primary outcome was the difference in proportion of patients achieving a score of 0 or 1 on the 90-day modified Rankin Scale (range, 0 [no symptoms] to 6 [death]) in all patients treated as randomized. Safety outcomes included rate of symptomatic intracranial hemorrhage and death., Results: The study was terminated early for inability to maintain placebo availability and enrollment rate because of the COVID-19 pandemic. Of 1825 patients with acute ischemic stroke treated with thrombectomy at the 7 study sites, 748 (41%) patients fulfilled the angiographic criteria, 121 (7%) patients were randomized (mean age, 70.6 [SD, 13.7] years; 57 women [47%]), and 113 (6%) were treated as randomized. The proportion of participants with a modified Rankin Scale score of 0 or 1 at 90 days was 59.0% (36/61) with alteplase and 40.4% (21/52) with placebo (adjusted risk difference, 18.4%; 95% CI, 0.3%-36.4%; P = .047). The proportion of patients with symptomatic intracranial hemorrhage within 24 hours was 0% with alteplase and 3.8% with placebo (risk difference, -3.8%; 95% CI, -13.2% to 2.5%). Ninety-day mortality was 8% with alteplase and 15% with placebo (risk difference, -7.2%; 95% CI, -19.2% to 4.8%)., Conclusions and Relevance: Among patients with large vessel occlusion acute ischemic stroke and successful reperfusion following thrombectomy, the use of adjunct intra-arterial alteplase compared with placebo resulted in a greater likelihood of excellent neurological outcome at 90 days. However, because of study limitations, these findings should be interpreted as preliminary and require replication., Trial Registration: ClinicalTrials.gov Identifier: NCT03876119; EudraCT Number: 2018-002195-40.

Background and Objectives: The presence of postinterventional subarachnoid hyperdensities (SA-HD) is a relatively common finding after mechanical thrombectomy (MT). We aimed to assess the incidence, characteristics, clinical relevance, and predictors of SA-HD after MT as categorized through the use of postinterventional dual-energy CT (DE-CT)., Methods: A single-center consecutive series of patients with acute stroke treated with MT was retrospectively reviewed. Posttreatment SA-HD were defined as incident extraaxial hyperdensities in a follow-up DE-CT performed within a median of 8 hours after MT. SA-HD were further classified according to their content (isolated contrast extravasation vs blood extravasation) and extension (diffuse [hyperdensities in more than one extraparenchymal compartment] vs nondiffuse). Adjusted logistic regression models assessed the association of SA-HD with pretreatment and procedural variables and with poor clinical outcome (shift towards worse categories in the ordinal Rankin Scale at 90 days)., Results: SA-HD were observed in 120 (28%) of the 424 included patients (isolated contrast extravasation n = 22, blood extravasation n = 98). In this group, SA-HD were diffuse in 72 (60%) patients (isolated contrast extravasation n = 7, blood extravasation n = 65) and nondiffuse in 48 (40%) patients (isolated contrast extravasation n = 15, blood extravasation n = 33). Diffuse SA-HD were significantly associated with worse clinical outcome in adjusted models (common odds ratio [cOR] 2.3, 95% confidence interval [CI] 1.36-4.00, p = 0.002), unlike the specific SA-HD content alone. In contrast with the absence of SA-HD, only the diffuse pattern with blood extravasation was significantly associated with worse clinical outcome (cOR 2.4, 95% CI 1.36-4.15, p = 0.002). Diffuse SA-HD patterns were predicted by M2 occlusions, more thrombectomy passes, and concurrent parenchymal hematomas., Discussion: In our cohort of patients imaged within a median of 8 hours after MT, postinterventional SA-HD showed a diffuse pattern in 17% of thrombectomies and were associated with more arduous procedures. Diffuse SA-HD but not local collections of blood or contrast extravasations were associated with an increased risk of poor outcome and death. These findings reinforce the need for improvement in reperfusion strategies., Classification of Evidence: This study provides Class IV evidence that in individuals with proximal carotid artery territory occlusions treated with MT, diffuse postinterventional SA-HD on imaging 8 hours postprocedure are associated with worse clinical outcomes at 90 days., (© 2021 American Academy of Neurology.)

Lacunar infarcts represent one of the most frequent subtypes of ischemic strokes and may represent the first recognizable manifestation of a progressive disease of the small perforating arteries, capillaries, and venules of the brain, defined as cerebral small vessel disease. The pathophysiological mechanisms leading to a perforating artery occlusion are multiple and still not completely defined, due to spatial resolution issues in neuroimaging, sparsity of pathological studies, and lack of valid experimental models. Recent advances in the endovascular treatment of large vessel occlusion may have diverted attention from the management of patients with small vessel occlusions, often excluded from clinical trials of acute therapy and secondary prevention. However, patients with a lacunar stroke benefit from early diagnosis, reperfusion therapy, and secondary prevention measures. In addition, there are new developments in the knowledge of this entity that suggest potential benefits of thrombolysis in an extended time window in selected patients, as well as novel therapeutic approaches targeting different pathophysiological mechanisms involved in small vessel disease. This review offers a comprehensive update in lacunar stroke pathophysiology and clinical perspective for managing lacunar strokes, in light of the latest insights from imaging and translational studies.

Background: Trials examining the benefit of thrombectomy in anterior circulation proximal large vessel occlusion stroke have enrolled patients considered to have salvageable brain tissue, who were randomly assigned beyond 6 h and (depending on study protocol) up to 24 h from time last seen well. We aimed to estimate the benefit of thrombectomy overall and in prespecified subgroups through individual patient data meta-analysis., Methods: We did a systematic review and individual patient data meta-analysis between Jan 1, 2010, and March 1, 2021, of randomised controlled trials of endovascular stroke therapy. In the Analysis Of Pooled Data From Randomized Studies Of Thrombectomy More Than 6 Hours After Last Known Well (AURORA) collaboration, the primary outcome was disability on the modified Rankin Scale (mRS) at 90 days, analysed by ordinal logistic regression. Key safety outcomes were symptomatic intracerebral haemorrhage and mortality within 90 days., Findings: Patient level data from 505 individuals (n=266 intervention, n=239 control; mean age 68·6 years [SD 13·7], 259 [51·3%] women) were included from six trials that met inclusion criteria of 17 screened published randomised trials. Primary outcome analysis showed a benefit of thrombectomy with an unadjusted common odds ratio (OR) of 2·42 (95% CI 1·76-3·33; p<0·0001) and an adjusted common OR (for age, gender, baseline stroke severity, extent of infarction on baseline head CT, and time from onset to random assignment) of 2·54 (1·83-3·54; p<0·0001). Thrombectomy was associated with higher rates of independence in activities of daily living (mRS 0-2) than best medical therapy alone (122 [45·9%] of 266 vs 46 [19·3%] of 238; p<0·0001). No significant difference between intervention and control groups was found when analysing either 90-day mortality (44 [16·5%] of 266 vs 46 [19·3%] of 238) or symptomatic intracerebral haemorrhage (14 [5·3%] of 266 vs eight [3·3%] of 239). No heterogeneity of treatment effect was noted across subgroups defined by age, gender, baseline stroke severity, vessel occlusion site, baseline Alberta Stroke Program Early CT Score, and mode of presentation; treatment effect was stronger in patients randomly assigned within 12-24 h (common OR 5·86 [95% CI 3·14-10·94]) than those randomly assigned within 6-12 h (1·76 [1·18-2·62]; p interaction =0·0087)., Interpretation: These findings strengthen the evidence for benefit of endovascular thrombectomy in patients with evidence of reversible cerebral ischaemia across the 6-24 h time window and are relevant to clinical practice. Our findings suggest that in these patients, thrombectomy should not be withheld on the basis of mode of presentation or of the point in time of presentation within the 6-24 h time window., Funding: Stryker Neurovascular., Competing Interests: Declaration of interests TGJ is adviser and investor for Anaconda, Route92, Viz.ai, FreeOx, Blockade Medical and Methinks. He received personal fees in his role on the Data Safety Monitoring Board and steering committee from Cerenovus and on the screening committee for Contego Medical. He received stock as an advisory board member for Corindus. He received grant support for Medtronic and from Stryker Neurovascular in his capacity as principal investigator for DAWN and AURORA. RGN reports consulting fees for advisory roles with Anaconda, Biogen, Cerenovus, Genentech, Imperative Care, Medtronic, Phenox, Prolong Pharmaceuticals, and Stryker Neurovascular and stock options for advisory roles with Astrocyte, Brainomix, Cerebrotech, Ceretrieve, Corindus Vascular Robotics, Vesalio, Viz.ai, and Perfuze. AMD is a shareholder and patent holder in Circle NVI (imaging-based software). He has also received honoraria from Medtronic for consulting services. SOM is the recipient of a research grant by the Brazilian Ministry of Health (RESILIENT trial) and has received speaker fees from Boehringer Ingelheim, Medtronic, Penumbra, Bayer, Pfizer and advisory board fees from Boehringer Ingelheim. JM is a consultant for Endostream, Viseon, Imperative Care, RIST, Synchron, Viz.ai, Perflow, CVAid, and Cerebrotech, and a shareholder in Rebound, BlinkTBI, Endostream, Viseon, Imperative Care, Serenity, Cardinal Consulting, NTI, RIST, Synchron, Viz.ai, and Cerebrotech. MR is adviser and shareholder in Anaconda Biomed and Methinks and received grants and personal fees from Medtronic, personal fees from Stryker, Cerenovus, and Apta Targets. SO-G has received consultant fees from Medtronic, Stryker, and Siemens. MDH reports personal fees from Sun Pharma, grants from Boehringer Ingelheim, Stryker, NoNO, and Medtronic, outside the submitted work; he has a patent Systems and Methods for Assisting in Decision-Making and Triaging for Acute Stroke Patients issued to US Patent office Number: 62/086,077 and owns stock in Pure Web, a company that makes, among other products, medical imaging software; is a director of the Canadian Federation of Neurological Sciences, a not-for-profit group, is a director of the Canadian Stroke Consortium, a not-for-profit group, is a director of Circle NeuroVascular, and has received grant support from Alberta Innovates Health Solutions, CIHR, Heart and Stroke Foundation of Canada, and National Institutes of Neurological Disorders and Stroke. FOL has received lecture fees from Boehringer Ingelheim. DCH serves as a consultant for Stryker and Vesalio, and holds stock options in Viz.ai. SB's employer, Bright Research Partners, has received payments from the University of Pittsburgh for the statistical work related to the current study and from the University of Calgary and Medtronic outside the current project. MG reports grants or personal fees from Medtronic, Stryker, Microvention, Cerenovus, and has a patent Systems of Acute Stroke Diagnosis issued to GE Healthcare. AHS is the recipient of NIH grants and owns stock or stock options in Adona Medical, Amnis Therapeutics, BlinkTBI, Buffalo Technology Partners, Cardinal Consultants, Cerebrotech Medical Systems, Cognition Medical, Endostream Medical, Imperative Care, International Medical Distribution Partners, Neurovascular Diagnostics, Q'Apel Medical, Radical Catheter Technologies, Rebound Therapeutics, Rist Neurovascular, Sense Diagnostics, Serenity Medical, Silk Road Medical, Spinnaker Medical, StimMed, Synchron, Three Rivers Medical, Vastrax, ICIS, and Viseon; consultant for Amnis Therapeutics, Boston Scientific, Canon Medical Systems USA, Cerebrotech Medical Systems, Cerenovus, Corindus, Integra, Medtronic, MicroVention, Minnetronix Neuro, Northwest University – DSMB Chair for HEAT Trial, Penumbra, Rapid Medical, Rebound Therapeutics, Serenity Medical, Silk Road Medical, StimMed, Stryker, Three Rivers Medical, VasSol, and W L Gore and Associates; principal investigator or on the Steering Committee for Cerenovus LARGE Trial and ARISE II Trial, Medtronic SWIFT PRIME and SWIFT DIRECT Trials, MicroVention FRED Trial and CONFIDENCE Study, POSITIVE Trial, Penumbra 3D Separator Trial, COMPASS Trial, and the INVEST Trial. JJH discloses consulting fees from Medtronic, Microvention, and iSchemaView. MPM owns stock in ThrombX Medica. DSL is consultant to Cerenovus, Genentech, Stryker, Medtronic as Imaging Core Lab. GWA is the principal investigator of the DEFUSE 3 study, which provided National Institutes of Health grant funding to Stanford University; he has equity interest in iSchemaView, and is a consultant for Genentech and iSchemaView. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: Previous studies have shown that meteorological factors may increase COVID-19 mortality, likely due to the increased transmission of the virus. However, this could also be related to an increased infection fatality rate (IFR). We investigated the association between meteorological factors (temperature, humidity, solar irradiance, pressure, wind, precipitation, cloud coverage) and IFR across Spanish provinces ( n = 52) during the first wave of the pandemic (weeks 10-16 of 2020)., Methods: We estimated IFR as excess deaths (the gap between observed and expected deaths, considering COVID-19-unrelated deaths prevented by lockdown measures) divided by the number of infections (SARS-CoV-2 seropositive individuals plus excess deaths) and conducted Spearman correlations between meteorological factors and IFR across the provinces., Results: We estimated 2,418,250 infections and 43,237 deaths. The IFR was 0.03% in < 50-year-old, 0.22% in 50-59-year-old, 0.9% in 60-69-year-old, 3.3% in 70-79-year-old, 12.6% in 80-89-year-old, and 26.5% in ≥ 90-year-old. We did not find statistically significant relationships between meteorological factors and adjusted IFR. However, we found strong relationships between low temperature and unadjusted IFR, likely due to Spain's colder provinces' aging population., Conclusion: The association between meteorological factors and adjusted COVID-19 IFR is unclear. Neglecting age differences or ignoring COVID-19-unrelated deaths may severely bias COVID-19 epidemiological analyses., (Copyright © 2021 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Context: Spinal cord infarction is a rare condition that develops as a result of insufficient vascular perfusion, sometimes related to procedures involving the aorta and vertebral arteries. Findings: We present the case of a 66-year-old woman who developed weakness on all four extremities and thermalgesic sensory deficit following an elective endovascular embolization of an incidentally diagnosed aneurysm in the posterior circulation. The procedure involved the cathetherization of both vertebral arteries, but was unremarkable and the flow into the anterior spinal artery was preserved. Radiological findings highly suggested a spinal cord infarction. She was started on corticosteroids and showed a significant neurological improvement. Clinical relevance: The present case illustrates that spinal cord infarction is a typical - but uncommon - complication that has to be suspected after vertebral artery endovascular procedures. It can result from hypoperfusion of smaller branches that irrigate the cervical spinal cord, and patients can make remarkable recoveries despite severe initial deficits.

Background and Purpose:  In real-world practice, the benefit of mechanical thrombectomy (MT) is uncertain in stroke patients with very favorable or poor prognostic profiles at baseline. We studied the effectiveness of MT versus medical treatment stratifying by different baseline prognostic factors., Methods:  Retrospective analysis of 2,588 patients with an ischemic stroke due to large vessel occlusion nested in the population-based registry of stroke code activations in Catalonia from January 2017 to June 2019. The effect of MT on good functional outcome (modified Rankin Score ≤2) and survival at 3 months was studied using inverse probability of treatment weighting (IPTW) analysis in three pre-defined baseline prognostic groups: poor (if pre-stroke disability, age >85 years, National Institutes of Health Stroke Scale [NIHSS] >25, time from onset >6 hours, Alberta Stroke Program Early CT Score <6, proximal vertebrobasilar occlusion, supratherapeutic international normalized ratio >3), good (if NIHSS <6 or distal occlusion, in the absence of poor prognostic factors), or reference (not meeting other groups' criteria)., Results:  Patients receiving MT (n=1,996, 77%) were younger, had less pre-stroke disability, and received systemic thrombolysis less frequently. These differences were balanced after the IPTW stratified by prognosis. MT was associated with good functional outcome in the reference (odds ratio [OR], 2.9; 95% confidence interval [CI], 2.0 to 4.4), and especially in the poor baseline prognostic stratum (OR, 3.9; 95% CI, 2.6 to 5.9), but not in the good prognostic stratum. MT was associated with survival only in the poor prognostic stratum (OR, 2.6; 95% CI, 2.0 to 3.3)., Conclusions:  Despite their worse overall outcomes, the impact of thrombectomy over medical management was more substantial in patients with poorer baseline prognostic factors than patients with good prognostic factors.

Introduction: Recent small subcortical infarcts (RSSI) are considered an acute manifestation of cerebral small vessel disease (CSVD). We assessed whether the topography of RSSI was related to CSVD markers on magnetic resonance imaging (MRI)., Material and Methods: We screened the local registries of two independent stroke centers in Catalonia and selected patients with a symptomatic RSSI on MRI performed during admission. RSSI location was classified into brainstem, supratentorial subcortical structures (SSS), and centrum semiovale (CSO) regions. Clinical variables, including vascular risk factors, were collected. Radiological markers of CSVD on MRI were evaluated individually and by means of the global CSVD burden score. The associations between each RSSI location and CSVD markers were studied in uni- and multivariate logistic regression analysis., Results: Among 475 patients with RSSI, 152 (32%) had an infarct in the brainstem, 227 (48%) in SSS, and 96 (20%) in CSO region. The median CSVD burden score was 2 (IQR, 1-3). After adjusting for confounding factors, a RSSI in CSO was associated with higher periventricular and deep white matter hyperintensity scores [OR 1.64 (95% CI, 1.16-2.33), and OR 1.44 (95% CI, 1.07-1.93), respectively]. Higher CSVD burden score was positively associated with CSO [OR 1.48 (95% CI, 1.22-1.81)] and inversely associated with SSS [0.85 (95% CI, 0.72-0.99)] location after adjusting for relevant confounders., Conclusions: CSO RSSI were related to a higher burden of CSVD, particularly to white matter hyperintensities, compared to other RSSI locations. The pathophysiological significance of such findings should be investigated in the future with advanced neuroimaging techniques., Competing Interests: Conflicting interests The authors declare no conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Intraoperative magnetic resonance imaging (iMRI) can be useful for cerebral cavernous malformations (CCM) surgery. However, literature on this topic is scarce. We aim to investigate its clinical utility and propose criteria for the selection of patients who may benefit the most from iMRI., Methods: From 2017 to 2019, all patients with CCMs who required surgery assisted with iMRI were included in the study. Clinical and radiological features were analyzed. Outcome measures included the need for an immediate second-look resection and clinical course in early post-surgery -Timepoint 1- (Tp1) and at the 6-to-12-month follow-up -Timepoint2- (Tp2)., Results: Out of 19 patients with 20 CCMs, 89% had bleeding in the past, and in 75% the CCM affected an eloquent area. According to the iMRI results, an immediate second-look resection was needed in 16% of them. In one patient, a remnant was not seen on iMRI. The mRS worsened in the immediate post-surgical exam (median, 1; IQR, 1) with improvements on the 6-month visit (median, 1; IQR, 2), (p = 0.018). When comparing the outcome of patients with and without symptoms at baseline, the latter fared better at Tp2 (p = 0.005)., Conclusions: iMRI is an intraoperative imaging tool that seems safe for CCM surgery and might reduce the risk of lesion remnants. In our series, it allowed additional revision for further resection in 16% of the patients. In our experience, iMRI may be especially useful for lesions in eloquent areas, those with a significant risk of brain shift and for large CCMs., Competing Interests: Declaration of Competing Interest All the authors listed in the manuscript certify that, to the best of their knowledge, no aspect of their personal or professional circumstances currently, or in the past 12 months, places any of them in the position of having a conflict of interest with any entity that may potentially benefit from, or be harmed by, the publication of the results of this study., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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.

Background: Single-center studies have suggested that the early clinical course after mechanical thrombectomy (MT) in patients with ischemic stroke is a clinical predictor of long-term outcome., Objective: To analyze the prognostic value of clinical improvement within 24 hours in a population-based multicenter cohort., Methods: From a total of 3792 patients with acute ischemic stroke in Catalonia (CICAT registry), 1951 patients were treated with MT. The National Institutes of Health Stroke Scale (NIHSS) score within 24 hours, and follow-up was available in 1666 patients. Percentage variation in the NIHSS score was calculated in relation to a baseline assessment. Good outcome was defined as a modified Rankin Scale score ≤2 at 90 days. Predictive values of clinical improvement and adjusted OR to predict good outcomes were assessed in the whole cohort and the subgroup of patients with posterior circulation stroke (n=166)., Results: Good outcome was achieved in 656/1666 patients (39%) overall. Percentage improvements both at the end of MT and at 24 hours predicted good outcome, with higher predictive capacity at 24 hours (C-statistic, 0.85 vs 0.73, p<0.001). Positive and negative predictive values were 70% and 74% for the >30% cut-off point at the end of MT, and 69% and 84% for the >50% cut-off point at 24 hours, respectively. The adjusted OR for good outcome was 5.8 (95% CI 4.2 to 8.1) and 12.9 (95% CI 9.7 to 17.1), respectively. In patients with posterior circulation stroke, the predictive value of the improvement at 24 hours was similar (C-statistic 0.90)., Conclusion: Clinical improvement of patients within 24 hours of MT is a reliable and robust predictor of long-term prognosis, including patients with posterior circulation occlusions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: Coronavirus disease 2019 (COVID-19) is associated with a small but clinically significant risk of stroke, the cause of which is frequently cryptogenic. In a large multinational cohort of consecutive COVID-19 patients with stroke, we evaluated clinical predictors of cryptogenic stroke, short-term functional outcomes and in-hospital mortality among patients according to stroke etiology., Methods: We explored clinical characteristics and short-term outcomes of consecutively evaluated patients 18 years of age or older with acute ischemic stroke (AIS) and laboratory-confirmed COVID-19 from 31 hospitals in 4 countries (3/1/20-6/16/20)., Results: Of the 14.483 laboratory-confirmed patients with COVID-19, 156 (1.1%) were diagnosed with AIS. Sixty-one (39.4%) were female, 84 (67.2%) white, and 88 (61.5%) were between 60 and 79 years of age. The most frequently reported etiology of AIS was cryptogenic (55/129, 42.6%), which was associated with significantly higher white blood cell count, c-reactive protein, and D-dimer levels than non-cryptogenic AIS patients (p

Rationale: The potential value of rescue intraarterial thrombolysis in patients with large vessel occlusion stroke treated with mechanical thrombectomy has not been assessed in randomized trials., Aim: The CHemical OptImization of Cerebral Embolectomy trial aims to establish whether rescue intraarterial thrombolysis is more effective than placebo in improving suboptimal reperfusion scores in patients with large vessel occlusion stroke treated with mechanical thrombectomy., Sample Size Estimates: A sample size of 200 patients allocated 1:1 to intraarterial thrombolysis or intraarterial placebo will have >95% statistical power for achieving the primary outcome (5% in the control versus 60% in the treatment group) for a two-sided (5% alpha, and 5% lost to follow-up)., Methods and Design: We conducted a multicenter, randomized, placebo-controlled, double blind, phase 2b trial. Eligible patients are 18 or older with symptomatic large vessel occlusion treated with mechanical thrombectomy resulting in a modified treatment in cerebral ischemia score 2b at end of the procedure. Patients will receive 20-30 min intraarterial infusion of recombinant tissue plasminogen activator or placebo (0.5 mg/ml, maximum dose limit 22.5 mg)., Study Outcome(s): The primary outcome is the proportion of patients with an improved modified treatment in cerebral ischemia score 10 min after the end of the study treatment. Secondary outcomes include the shift analysis of the modified Rankin Scale, the infarct expansion ratio, the proportion of excellent outcome (modified Rankin Scale 0-1), the proportion of infarct expansion, and the infarction volume. Mortality and symptomatic intracerebral bleeding will be assessed., Discussion: The study will provide evidence whether rescue intraarterial thrombolysis improves brain reperfusion in patients with large vessel occlusion stroke and incomplete reperfusion (modified treatment in cerebral ischemia 2b) at the end of mechanical thrombectomy.

Background and Purpose: Acute ischemic stroke and large vessel occlusion can be concurrent with the coronavirus disease 2019 (COVID-19) infection. Outcomes after mechanical thrombectomy (MT) for large vessel occlusion in patients with COVID-19 are substantially unknown. Our aim was to study early outcomes after MT in patients with COVID-19., Methods: Multicenter, European, cohort study involving 34 stroke centers in France, Italy, Spain, and Belgium. Data were collected between March 1, 2020 and May 5, 2020. Consecutive laboratory-confirmed COVID-19 cases with large vessel occlusion, who were treated with MT, were included. Primary investigated outcome: 30-day mortality., Secondary Outcomes: early neurological improvement (National Institutes of Health Stroke Scale improvement ≥8 points or 24 hours National Institutes of Health Stroke Scale 0-1), successful reperfusion (modified Thrombolysis in Cerebral Infarction grade ≥2b), and symptomatic intracranial hemorrhage., Results: We evaluated 93 patients with COVID-19 with large vessel occlusion who underwent MT (median age, 71 years [interquartile range, 59-79]; 63 men [67.7%]). Median pretreatment National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT Score were 17 (interquartile range, 11-21) and 8 (interquartile range, 7-9), respectively. Anterior circulation acute ischemic stroke represented 93.5% of cases. The rate modified Thrombolysis in Cerebral Infarction 2b to 3 was 79.6% (74 patients [95% CI, 71.3-87.8]). Thirty-day mortality was 29% (27 patients [95% CI, 20-39.4]). Early neurological improvement was 19.5% (17 patients [95% CI, 11.8-29.5]), and symptomatic intracranial hemorrhage was 5.4% (5 patients [95% CI, 1.7-12.1]). Patients who died at 30 days exhibited significantly lower lymphocyte count, higher levels of aspartate, and LDH (lactate dehydrogenase). After adjustment for age, initial National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, and successful reperfusion, these biological markers remained associated with increased odds of 30-day mortality (adjusted odds ratio of 2.70 [95% CI, 1.21-5.98] per SD-log decrease in lymphocyte count, 2.66 [95% CI, 1.22-5.77] per SD-log increase in aspartate, and 4.30 [95% CI, 1.43-12.91] per SD-log increase in LDH)., Conclusions: The 29% rate of 30-day mortality after MT among patients with COVID-19 is not negligible. Abnormalities of lymphocyte count, LDH and aspartate may depict a patient's profiles with poorer outcomes after MT. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT04406090.

Objectives: Recent small subcortical infarcts (RSSI) are considered an acute manifestation of cerebral small vessel disease. Paramagnetic signals in perforating arteries supplying RSSI may be detected on T2*-relaxation derived sequences on MRI and is defined as susceptibility vessel sign (SVS). We aimed to study the prevalence of SVS in patients with RSSI, and explore whether its identification is related to cerebral small vessel disease markers., Materials and Methods: We selected patients with RSSI identified on MRI during admission from a single-center stroke registry. The main demographic and clinical features, including vascular risk factors, were collected. Radiological features of RSSI and cerebral small vessel disease [white matter hyperintensities in deep and periventricular regions, enlarged perivascular spaces, lacunae, microbleeds, and brain atrophy] were described using validated qualitative scores. The presence of SVS was assessed on T2*gradient-echo or other susceptibility-weighted imaging. We compared the clinical and radiological features of patients with or without SVS in uni- and multivariate models., Results: Out of 210 patients with an RSSI on an MRI, 35 (17%) showed SVS. The proportion of SVS+ patients was similar in different susceptibility imaging modalities (p=.64). Risk factor profiles and clinical course were similar in SVS+ and SVS- patients. SVS+ patients had a higher grade of deep white matter hyperintensities and brain atrophy, more lacunae (p=.001, p=.034, p=.022, respectively), and a similar degree of the rest of radiological variables, compared to SVS- patients. In the multivariate analysis, the grade of deep white matter hyperintensities was the only independent factor associated with SVS [OR 3.1 (95% CI, 1.5-6.4)]., Conclusions: SVS in patients with RSSI is uncommon and related to a higher grade of deep white matter hyperintensities. Pathophysiological mechanisms underlying the deposition of hemosiderin in the path of occluded perforating arteries are uncertain and might include endothelial dysfunction or embolic mechanisms., Competing Interests: Declaration of Competing Interest The authors declared no potential conflicts of interest concerning the research, authorship, and/or publication of this article., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: The COVID-19 pandemic resulted in significant healthcare reorganizations, potentially striking standard medical care. We investigated the impact of the COVID-19 pandemic on acute stroke care quality and clinical outcomes to detect healthcare system's bottlenecks from a territorial point of view., Methods: Crossed-data analysis between a prospective nation-based mandatory registry of acute stroke, Emergency Medical System (EMS) records, and daily incidence of COVID-19 in Catalonia (Spain). We included all stroke code activations during the pandemic (March 15-May 2, 2020) and an immediate prepandemic period (January 26-March 14, 2020). Primary outcomes were stroke code activations and reperfusion therapies in both periods. Secondary outcomes included clinical characteristics, workflow metrics, differences across types of stroke centers, correlation analysis between weekly EMS alerts, COVID-19 cases, and workflow metrics, and impact on mortality and clinical outcome at 90 days., Results: Stroke code activations decreased by 22% and reperfusion therapies dropped by 29% during the pandemic period, with no differences in age, stroke severity, or large vessel occlusion. Calls to EMS were handled 42 min later, and time from onset to hospital arrival increased by 53 min, with significant correlations between weekly COVID-19 cases and more EMS calls (rho = 0.81), less stroke code activations (rho = -0.37), and longer prehospital delays (rho = 0.25). Telestroke centers were afflicted with higher reductions in stroke code activations, reperfusion treatments, referrals to endovascular centers, and increased delays to thrombolytics. The independent odds of death increased (OR 1.6 [1.05-2.4], p 0.03) and good functional outcome decreased (mRS ≤2 at 90 days: OR 0.6 [0.4-0.9], p 0.015) during the pandemic period., Conclusion: During the COVID-19 pandemic, Catalonia's stroke system's weakest points were the delay to EMS alert and a decline of stroke code activations, reperfusion treatments, and interhospital transfers, mostly at local centers. Patients suffering an acute stroke during the pandemic period had higher odds of poor functional outcome and death. The complete stroke care system's analysis is crucial to allocate resources appropriately., (© 2021 S. Karger AG, Basel.)

About half of acute stroke patients treated with mechanical thrombectomy (MT) do not show clinical improvement despite successful recanalization. Early arterial reocclusion (EAR) may be one of the causes that explain this phenomenon. We aimed to analyze the incidence and clinico-radiological correlations of EAR after successful MT. A consecutive series of patients treated with MT between 2010 and 2018 at a single-center included in a prospective registry was retrospectively reviewed. Specific inclusion criteria for the analysis were (1) successful recanalization after MT and (2) availability of pretreatment CT perfusion and follow-up MRI. EAR was evaluated in the follow-up MR angiography. Adjusted regression models were used to analyze the association of EAR with pretreatment variables, infarct growth, final infarct volume, and clinical outcome at 90 days (ordinal distribution of the modified Rankin Scale scores). Out of 831 MT performed, 218 (26%) patients fulfilled inclusion criteria, from whom 13 (6%) suffered EAR. In multivariate analysis controlled by confounders, EAR was independently associated with poor clinical outcome (aOR = 3.2, 95%CI = 1.16-9.72, p = 0.039), greater final infarct volume (aOR = 3.8, 95%CI = 1.93-7.49, p < 0.001), and increased infarct growth (aOR = 8.5, CI95% = 2.04-34.70, p = 0.003). According to mediation analyses, the association between EAR and poor clinical outcome was mainly explained through its effects on final infarct volume and infarct growth. Additionally, EAR was associated with non-cardioembolic etiology (adjusted Odds Ratio (aOR) = 10.1, 95%CI = 1.25-81.35, p = 0.030) and longer procedural time (aOR = 2.6, 95%CI = 1.31-5.40, p = 0.007). Although uncommon, EAR hampers the benefits of successful recanalization after MT resulting in increased infarct growth and larger final lesions.

Background: Transfer protocols from primary to comprehensive stroke centers are crucial for endovascular treatment success., Aim: To evaluate clinical and neuroimaging data of transferred patients and their likelihood of presenting a large infarct core at comprehensive stroke center arrival., Methods: Retrospective analysis of population-based mandatory prospective registry of acute stroke patients evaluated for endovascular treatment. Consecutive patients evaluated at primary stroke center with suspected large vessel occlusion and PSC-ASPECTS ≥ 6 transferred to a comprehensive stroke center were included. PSC and CSC-ASPECTS, time-metrics, and clinical data were analyzed., Results: During 28 months, 1185 endovascular treatment candidates were transferred from PC to comprehensive stroke center in our public stroke network, 477 had an anterior circulation syndrome and available neuroimaging information and were included. Median baseline NIHSS was 13 (8-19). On arrival to comprehensive stroke center, large vessel occlusion was confirmed in 60.2% patients, and 41.2% received endovascular treatment. Median interfacility ASPECTS decay was 1 (0-2) after a median of 150.7 (SD 101) min between both CT-acquisitions. A logistic regression analysis adjusted by age, time from symptoms to PC-CT, and time from PC-CT to CSC-CT showed that only a baseline NIHSS and PSC-ASPECTS independently predicted a CSC-ASPECTS < 6. ROC curves identified baseline NIHSS ≥ 16 and PSC-ASPECTS ≤ 7 as the best cut-off points. The rate of CSC-ASPECTS < 6 increased from 7% to 57% among patients with NIHSS ≥ 16 and PSC-ASPECS ≤ 7., Conclusion: After a median transfer time >2 h, only 11.9% showed ASPECTS < 6 at the comprehensive stroke center. Activation of endovascular treatment teams should not require confirming neuroimaging on arrival and repeating neuroimaging at comprehensive stroke center should only be performed in selected cases.

We studied the relationship between the incidence of coronavirus disease 2019 (COVID-19), demographical, and climatological measurements in different regions across the world. Lower solar irradiance and higher population density were independent predictors of greater COVID-19 outbreaks. Further studies on the potential protective effect of sunlight over COVID-19 are warranted., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background and Aims: Emergent stent placement may be required during neurothrombectomy. Our aim was to investigate the incidence, predictors and clinical relevance of early extracranial carotid stent occlusion following neurothrombectomy., Methods: We retrospectively analyzed a cohort of 761 consecutive neurothrombectomies performed at our center between May 2010 and August 2018, from whom a total of 106 patients had acute internal carotid artery occlusions. Early stent occlusion was defined as complete vessel occlusion within 24 h of neurothrombectomy. Clinical outcome was evaluated at day 90 with the modified Rankin Score scale (mRS). Pretreatment, procedural and outcome variables were recorded and analyzed using logistic regression., Results: Carotid stenting was performed in 99 (13%) patients. Of those, 22 (22%) had early stent occlusion at follow-up. Stent occlusion was associated with a lower use of post-stenting angioplasty [adjusted OR (aOR) = 11.2, 95%CI = 2.49-50.78, p = 0.002)], increased residual intrastent stenosis (aOR = 2.1, 95%CI = 1.38-3.06, p < 0.001) and unsuccesful intracranial recanalization (modified TICI score 0-2a) (aOR = 13.5, 95%CI = 1.97-92.24, p = 0.008). Stent occlusion was associated with poor clinical outcome at day 90 (poorer mRS shift, aOR = 3.9, 95%CI = 1.3-11.3, p = 0.014; mRS>2, aOR = 6.3, 95%CI = 1.8-22.7, p = 0.005), and with an increased rate of symptomatic intracranial hemorrhage at 24 h (14% versus 1%, p = 0.033)., Conclusions: Early carotid stent occlusion occurred in one out of five neurothrombectomies and was associated with periprocedural factors that included increased residual intrastent stenosis, a lower use of post-stenting angioplasty and unsuccessful intracranial recanalization. Further investigation is warranted for the evaluation of strategies aimed to prevent carotid stent occlusion., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Hemichorea and other hyperkinetic movement disorders are a rare presentation of stroke, usually secondary to deep infarctions affecting the basal ganglia and the thalamus. Chorea can also result from lesions limited to the cortex, as shown in recent reports. Still, the pathophysiology of this form of cortical stroke-related chorea remains unknown. We report 4 cases of acute ischemic cortical strokes presenting as hemichorea, with the infarction being limited to the parietal and insular cortex in perfusion computed tomography scans and magnetic resonance imaging. These cases suggest potential dysfunction of pathways connecting these cortical regions with the basal ganglia., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Purpose: Reliable recognition of large vessel occlusion (LVO) on noncontrast computed tomography (NCCT) may accelerate identification of endovascular treatment candidates. We aim to validate a machine learning algorithm (MethinksLVO) to identify LVO on NCCT., Methods: Patients with suspected acute stroke who underwent NCCT and computed tomography angiography (CTA) were included. Software detection of LVO (MethinksLVO) on NCCT was tested against the CTA readings of 2 experienced radiologists (NR-CTA). We used a deep learning algorithm to identify clot signs on NCCT. The software image output trained a binary classifier to determine LVO on NCCT. We studied software accuracy when adding National Institutes of Health Stroke Scale and time from onset to the model (MethinksLVO+)., Results: From 1453 patients, 823 (57%) had LVO by NR-CTA. The area under the curve for the identification of LVO with MethinksLVO was 0.87 (sensitivity: 83%, specificity: 71%, positive predictive value: 79%, negative predictive value: 76%) and improved to 0.91 with MethinksLVO+ (sensitivity: 83%, specificity: 85%, positive predictive value: 88%, negative predictive value: 79%)., Conclusions: In patients with suspected acute stroke, MethinksLVO software can rapidly and reliably predict LVO. MethinksLVO could reduce the need to perform CTA, generate alarms, and increase the efficiency of patient transfers in stroke networks.

Background and Purpose: Acute onset aphasia may be due to stroke but also to other causes, which are commonly referred to as stroke mimics. We hypothesized that, in patients with acute isolated aphasia, distinct brain perfusion patterns are related to the cause and the clinical outcome. Herein, we analyzed the prognostic yield and the diagnostic usefulness of computed tomography perfusion (CTP) in patients with acute isolated aphasia., Methods: From a single-center registry, we selected a cohort of 154 patients presenting with acute isolated aphasia who had a whole-brain CTP study available. We collected the main clinical and radiological data. We categorized brain perfusion studies on CTP into vascular and nonvascular perfusion patterns and the cause of aphasia as ischemic stroke, transient ischemic attack, stroke mimic, and undetermined cause. The primary clinical outcome was the persistence of aphasia at discharge. We analyzed the sensitivity, specificity, positive and negative predictive values of perfusion patterns to predict complete clinical recovery and ischemic stroke on follow-up imaging., Results: The cause of aphasia was an ischemic stroke in 58 patients (38%), transient ischemic attack in 3 (2%), stroke mimic in 68 (44%), and undetermined in 25 (16%). CTP showed vascular and nonvascular perfusion pattern in 62 (40%) and 92 (60%) patients, respectively. Overall, complete recovery occurred in 116 patients (75%). A nonvascular perfusion pattern predicted complete recovery (sensitivity 75.9%, specificity 89.5%, positive predictive value 95.7%, and negative predictive value 54.8%), and a vascular perfusion pattern was highly predictive of ischemic stroke (sensitivity 94.8%, specificity 92.7%, positive predictive value 88.7%, and negative predictive value 96.7%). The 3 patients with ischemic stroke without a vascular perfusion pattern fully recovered at discharge., Conclusions: CTP has prognostic value in the workup of patients with acute isolated aphasia. A nonvascular pattern is associated with higher odds of full recovery and may prompt the search for alternative causes of the symptoms.

Ischemic stroke causes brain tissue damage and may release central nervous system (CNS)-specific peptides to the periphery. Neural antigen presentation in the lymphoid tissue could prime immune cells and result in adaptive immune response. However, autoimmune responses against neural antigens are not commonly uncovered after stroke. We studied the brain tissue of nine fatal stroke cases and the blood of a cohort of 13 patients and 11 controls. Flow cytometry carried out in three of the brain samples showed CD8 and CD4 T cells in the cerebrospinal fluid (CSF) of the ventricles in the patient deceased 1 day poststroke, T cells with an activated phenotype in the CSF of the patient that died at day 6, and T cells in the ischemic brain tissue in the patient deceased 140 days after stroke onset. Immunohistochemistry showed higher T cell numbers in the core of the lesion of the patient deceased 18 days post-stroke than in the patients deceased from 1 to 5 days post-stroke. In blood samples, we studied whether lymphocytes were primed in the periphery against neural antigens at sequential times (on admission, day 5, and day 90) after stroke. T lymphocytes of stroke patients produced IFN-γ and TNF-α and responded to MBP peptides by increasing their production of TNF-α and IL-10 at admission, but not at later time points. In contrast, IL-4 producing T cells showed progressive increases. Higher percentages of TNF-α producing T lymphocytes at admission were independently associated with poorer outcomes at 90 days. However, we did not detect T cell responses to neural-antigen stimulation 90 days post-stroke. Altogether the results suggest acute T cell priming in the periphery in acute stroke, T cell trafficking from the CSF to the ischemic brain tissue, and the existence of active mechanisms preventing autoreactivity., (Copyright © 2020 Miró-Mur, Urra, Ruiz-Jaén, Pedragosa, Chamorro and Planas.)

Background and Purpose: The purpose of the study is to analyze how the coronavirus disease 2019 (COVID-19) pandemic affected acute stroke care in a Comprehensive Stroke Center., Methods: On February 28, 2020, contingency plans were implemented at Hospital Clinic of Barcelona to contain the COVID-19 pandemic. Among them, the decision to refrain from reallocating the Stroke Team and Stroke Unit to the care of patients with COVID-19. From March 1 to March 31, 2020, we measured the number of emergency calls to the Emergency Medical System in Catalonia (7.5 million inhabitants), and the Stroke Codes dispatched to Hospital Clinic of Barcelona. We recorded all stroke admissions, and the adequacy of acute care measures, including the number of thrombectomies, workflow metrics, angiographic results, and clinical outcomes. Data were compared with March 2019 using parametric or nonparametric methods as appropriate., Results: At Hospital Clinic of Barcelona, 1232 patients with COVID-19 were admitted in March 2020, demanding 60% of the hospital bed capacity. Relative to March 2019, the Emergency Medical System had a 330% mean increment in the number of calls (158 005 versus 679 569), but fewer Stroke Code activations (517 versus 426). Stroke admissions (108 versus 83) and the number of thrombectomies (21 versus 16) declined at Hospital Clinic of Barcelona, particularly after lockdown of the population. Younger age was found in stroke admissions during the pandemic (median [interquartile range] 69 [64-73] versus 75 [73-80] years, P =0.009). In-hospital, there were no differences in workflow metrics, angiographic results, complications, or outcomes at discharge., Conclusions: The COVID-19 pandemic reduced by a quarter the stroke admissions and thrombectomies performed at a Comprehensive Stroke Center but did not affect the quality of care metrics. During the lockdown, there was an overload of emergency calls but fewer Stroke Code activations, particularly in elderly patients. Hospital contingency plans, patient transport systems, and population-targeted alerts must act concertedly to better protect the chain of stroke care in times of pandemic.

Several pretreatment variables such as elevated glucose and hypoperfusion severity are related to brain hemorrhage after endovascular treatment of acute stroke. We evaluated whether elevated glucose and severe hypoperfusion have synergistic effects in the promotion of parenchymal hemorrhage (PH) after mechanical thrombectomy (MT). We included 258 patients MT-treated who had a pretreatment computed tomography perfusion (CTP) and a post-treatment follow-up MRI. Severe hypoperfusion was defined as regions with cerebral blood volume (CBV) values < 2.5% of normal brain [very-low CBV (VLCBV)-regions]. Median baseline glucose levels were 119 (IQR = 105-141) mg/dL. Thirty-nine (15%) patients had pretreatment VLCBV-regions, and 42 (16%) developed a PH after MT. In adjusted models, pretreatment glucose levels interacted significantly with VLCBV on the prediction of PH (p-interaction = 0.011). In patients with VLCBV-regions, higher glucose was significantly associated with PH (adjusted-OR = 3.15; 95% CI = 1.08-9.19, p = 0.036), whereas this association was not significant in patients without VLCBV-regions. CBV values measured at pretreatment CTP in coregistered regions that developed PH or infarct at follow-up were not correlated with pretreatment glucose levels, thus suggesting the existence of alternative deleterious mechanisms other than direct glucose-driven hemodynamic impairments. Overall, these results suggest that both severe hypoperfusion and glucose levels should be considered in the evaluation of adjunctive neuroprotective strategies.

Computed tomography perfusion (CTP) allows the estimation of pretreatment ischemic core after acute ischemic stroke. However, CTP-derived ischemic core may overestimate final infarct volume. We aimed to evaluate the accuracy of CTP-derived ischemic core for the prediction of final infarct volume according to time from stroke onset to recanalization in 104 patients achieving complete recanalization after mechanical thrombectomy who had a pretreatment CTP and a 24-h follow-up MRI-DWI. A range of CTP thresholds was explored in perfusion maps at constant increments for ischemic core calculation. Time to recanalization modified significantly the association between ischemic core and DWI lesion in a non-linear fashion ( p -interaction = 0.018). Patients with recanalization before 4.5 h had significantly lower intraclass correlation coefficient (ICC) values between CTP-predicted ischemic core and DWI lesion ( n  = 54; best threshold relative cerebral blood flow (rCBF) < 25%, ICC = 0.673, 95% CI = 0.495-0.797) than those with later recanalization ( n  = 50; best threshold rCBF < 30%, ICC = 0.887, 95% CI = 0.811-0.935, p  = 0.013), as well as poorer spatial lesion agreement. The significance of the associations between CTP-derived ischemic core and clinical outcome at 90 days was lost in patients recanalized before 4.5 h. CTP-derived ischemic core must be interpreted with caution given its dependency on time to recanalization, primarily in patients with higher chances of early recanalization.

Objective: The rate of progression of the ischemic lesion is variable in patients with stroke. We tested the hypothesis that the tissue saving effect of mechanical thrombectomy (MT) is greater in fast progressors., Methods: A single-center cohort of consecutive patients (n=242) with occlusions of the terminal internal carotid or M1 segment of the middle cerebral artery treated with MT (n=195) or best medical treatment (n=47), known time from onset, and full imaging (baseline CT perfusion and follow-up MRI) available was studied. The estimated infarct progression rate (eIPR) was calculated at baseline and patients were categorized as fast/slow progressors according to the median eIPR of 4.8 mL/hour. The primary outcome measure was the interaction between eIPR category and MT on infarct growth. The secondary outcomes assessed the effect of MT on final infarct volume and functional status in relation to the eIPR category. The safety outcomes were mortality and symptomatic intracranial hemorrhage., Results: The eIPR category had a modifying effect (Pi=0.017) of MT on infarct growth that was significantly reduced with MT only in fast progressors (median (IQR) 3.8 mL (-11-55) vs 41 mL (11-107) with medical treatment; p=0.009, adjusted p=0.045). There was also a significant interaction on final infarct volume (Pi=0.005), with a greater reduction after MT in fast progressors. The functional status improved with MT both in fast and slow progressors, with no significant modifying effect of eIPR category (Pi=0.201). There were also no significant interactions on safety outcomes., Conclusion: MT in stroke patients with large vessel occlusion limits infarct growth more significantly in fast progressors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The microbiological aetiology of pneumonia complicating stroke is poorly characterised. In this second Pneumonia in Stroke ConsEnsuS statement, we propose a standardised approach to empirical antibiotic therapy in pneumonia complicating stroke, based on likely microbiological aetiology, to improve antibiotic stewardship., Methods: Systematic literature searches of multiple databases were undertaken. An evidence review and a round of consensus consultation were completed prior to a final multi-disciplinary consensus meeting in September 2017, held in Barcelona, Spain. Consensus was approached using a modified Delphi technique and defined a priori as 75% agreement between the consensus group members. Findings : No randomised trials to guide antibiotic treatment of pneumonia complicating stroke were identified. Consensus was reached for the following: (1) Stroke-associated pneumonia may be caused by organisms associated with either community-acquired or hospital-acquired pneumonia; (2) Treatment for early stroke-associated pneumonia (<72 h of stroke onset) should cover community-acquired pneumonia organisms; (3) Treatment for late stroke-associated pneumonia (≥72 h and within seven days of stroke onset) should cover community-acquired pneumonia organisms plus coliforms +/- Pseudomonas spp . if risk factors; (4) No additional antimicrobial cover is required for patients with dysphagia or aspiration; (5) Pneumonia occurring after seven days from stroke onset should be treated as for hospital-acquired pneumonia; (6) Treatment should continue for at least seven days for each of these scenarios., Discussion: Consensus recommendations for antibiotic treatment of the spectrum of pneumonia complicating stroke are proposed. However, there was limited evidence available to formulate consensus on choice of specific antibiotic class for pneumonia complicating stroke., Conclusion: Further studies are required to inform evidence-based treatment of stroke-associated pneumonia including randomised trials of antibiotics and validation of candidate biomarkers., (© European Stroke Organisation 2019.)

Background and Purpose- Peripheral immune cells are activated after stroke and may in turn influence the fate of ischemic brain tissue, thus exerting a dual role in ischemic stroke. We evaluated the contribution of neutrophil and lymphocyte counts to hemorrhagic complications and functional outcome in stroke patients treated with mechanical thrombectomy (MT) with varying degrees of collateral circulation and reperfusion. Methods- We retrospectively analyzed 433 consecutive ischemic stroke patients treated with MT. Neutrophil and lymphocyte counts and the neutrophil-to-lymphocyte ratio (NLR) were collected before MT and 1 day after symptom onset. Outcome measures included categories of hemorrhagic transformation, symptomatic intracerebral hemorrhage, 3-month functional dependence (modified Rankin Scale, 3-6), and mortality. Patients were categorized according to their baseline collateral status and the degree of reperfusion after MT. Results- Neutrophil counts and NLR increased, whereas lymphocyte counts decreased after MT ( P <0.001), and changes in neutrophils and NLR at day 1 were significantly greater in patients with poor reperfusion. Neutrophil counts and NLR were significantly higher already at admission in patients with poor 3-month outcome. In adjusted analysis, the impact of neutrophilia on poor functional outcome was more substantial in patients with good collaterals achieving successful reperfusion (aOR, 3.09 per quartile; 95% CI, 1.95-4.90), whereas admission lymphopenia (aOR, 4.08 per decreasing quartile; 95% CI, 1.56-10.64) and higher NLR (aOR, 3.76 per quartile; 95% CI, 1.44-9.79) predicted subsequent symptomatic intracerebral hemorrhage in patients with poor collaterals and successful reperfusion. Conclusions- In patients treated with MT, neutrophil and lymphocyte counts are dynamic parameters associated with hemorrhagic complications and long-term outcome. The extent of collateral circulation and the success of brain reperfusion influence the strength of these associations and highlight the dual role of leukocytes in acute stroke.

Background and Purpose: Ischemic stroke (IS) and hemorrhagic stroke (HemS) typically lead to a breakdown of the blood-brain barrier with neural antigen presentation. This presentation could potentially generate destructive auto-immune responses. Pre-existing antineuronal and antiglial antibodies (AA), predominantly NMDA receptor antibodies, have been reported in patients with stroke. This article summarizes three independent prospective studies, the Lübeck cohort (LC), Barcelona cohort (BC), and Heidelberg cohort (HC), exploring the frequency and clinical relevance of AA in patients with acute stroke (AS)., Methods: In all cohorts together, 344 consecutive patients admitted with AS (322 × IS, 22 × HemS) were screened for AA in serum at admission. Clinical outcome parameters as well as a second AA screening were available at 30 days in the LC or at 90 days in the BC. A control group was included in the BC (20 subjects free from neurological disease) and the HC (78 neurological and ophthalmological patients without evidence for stroke)., Results: The rate of positivity for AA was similar in control subjects and AS patients (13%, 95% CI [7%, 22%] vs. 13%, 95% CI [10%, 17%]; p = 0.46) with no significant difference between cohorts (LC 25/171, BC 12/75, HC 9/98). No patient had developed new AA after 30 days, whereas 2 out of 60 patients had developed new AA after 90 days. AA positive patients did not exhibit significant differences to AA negative patients in stroke subtype (LC, BC), initial stroke severity (BC, LC, HC), infarct volume (BC), and functional status at admission (BC, LC, HC) and follow-up (BC, LC)., Conclusions: AS does not induce AA to a relevant degree. Pre-existing AA can be found in the serum of stroke patients, but they do not have a significant association with clinical features and outcomes.

Objective: Stroke patients with good collateral circulation achieve the best recovery after mechanical thrombectomy (MT) but strict imaging selection may result in untreated patients that could benefit from MT. We assessed whether the extent of collaterals had modifying effects on the amount of ischemic tissue saved from infarction with MT over best medical treatment (BMT)., Methods: This was a single center cohort of consecutive patients (n=339) with proximal occlusions in the carotid territory. Patients were categorized according to a four point category scale on CT angiography as having good (scores 2-3) or poor (scores 0-1) collaterals. The primary outcome measure was the interaction between collaterals and MT on infarct growth. The secondary outcome assessed the treatment effect of MT over BMT on functional status in relation to collateral status. Safety outcomes were mortality and symptomatic intracranial hemorrhage., Results: Collaterals had a modifying effect of MT on infarct growth (P=0.004), with a greater reduction in 96 patients with poor collaterals (38.8 mL) than in 243 patients with good collaterals (1.9 mL). There was also a significant (P<0.001) interaction between the effect of MT and functional outcome in relation to collateral status, with more benefits of MT in patients with poor collaterals. MT was associated with lower mortality than BMT in patients with poor collaterals only., Conclusion: Compared with BMT, the use of MT in the early time window in large vessel stroke results in a more substantial limitation of infarct growth in patients with poor collaterals., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale: Optimal pre-hospital delivery pathways for acute stroke patients suspected to harbor a large vessel occlusion have not been assessed in randomized trials., Aim: To establish whether stroke subjects with rapid arterial occlusion evaluation scale based suspicion of large vessel occlusion evaluated by emergency medical services in the field have higher rates of favorable outcome when transferred directly to an endovascular center (endovascular treatment stroke center), as compared to the standard transfer to the closest local stroke center (local-SC)., Design: Multicenter, superiority, cluster randomized within a cohort trial with blinded endpoint assessment., Procedure: Eligible patients must be 18 or older, have acute stroke symptoms and not have an immediate life threatening condition requiring emergent medical intervention. They must be suspected to have intracranial large vessel occlusion based on a pre-hospital rapid arterial occlusion evaluation scale of ≥5, be located in geographical areas where the default health authority assigned referral stroke center is a non-thrombectomy capable hospital, and estimated arrival at a thrombectomy capable stroke hospital in less than 7 h from time last seen well. Cluster randomization is performed according to a pre-established temporal sequence (temporal cluster design) with three strata: day/night, distance to the endovascular treatment stroke center, and week/week-end day., Study Outcome: The primary endpoint is the modified Rankin Scale score at 90 days. The primary safety outcome is mortality at 90 days., Analysis: The primary endpoint based on the modified intention-to-treat population is the distribution of modified Rankin Scale scores at 90 days analyzed under a sequential triangular design. The maximum sample size is 1754 patients, with two planned interim analyses when 701 (40%) and 1227 patients have completed follow-up. Hypothesized common odds ratio is 1.35.

Background and Purpose: Our aim was to revalidate the RACE scale, a prehospital tool that aims to identify patients with large vessel occlusion (LVO), after its region-wide implementation in Catalonia, and to analyze geographical differences in access to endovascular treatment (EVT)., Methods: We used data from the prospective CICAT registry (Stroke Code Catalan registry) that includes all stroke code activations. The RACE score evaluated by emergency medical services, time metrics, final diagnosis, presence of LVO, and type of revascularization treatment were registered. Sensitivity, specificity, and area under the curve (AUC) for the RACE cut-off value ≥5 for identification of both LVO and eligibility for EVT were calculated. We compared the rate of EVT and time to EVT of patients transferred from referral centers compared with those directly presenting to comprehensive stroke centers (CSC)., Results: The RACE scale was evaluated in the field in 1822 patients, showing a strong correlation with the subsequent in-hospital evaluation of the National Institute of Health Stroke Scale evaluated at hospital (r=0.74, P<0.001). A RACE score ≥5 detected LVO with a sensitivity 0.84 and specificity 0.60 (AUC 0.77). Patients with RACE ≥5 harbored a LVO and received EVT more frequently than RACE <5 patients (LVO 35% vs 6%; EVT 20% vs 6%; all P<0.001). Direct admission at a CSC was independently associated with higher odds of receiving EVT compared with admission at a referral center (OR 2.40; 95% CI 1.66 to 3.46), and symtoms onset to groin puncture was 133 min shorter., Conclusions: This large validation study confirms RACE accuracy to identify stroke patients eligible for EVT, and provides evidence of geographical imbalances in the access to EVT to the detriment of patients located in remote areas., Competing Interests: Competing interests: Not required., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)