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Objectives: We sought to provide updated incidence and trend data for cerebral venous thrombosis (CVT) in the United States from 2016-2020, examine the impact of the COVID-19 pandemic on CVT, and identify predictors of in-hospital mortality., Materials and Methods: Validated ICD-10 codes were used to identify discharges with CVT in the National Inpatient Sample (NIS). Sample weights were applied to generate nationally representative estimates, and census data were used to compute incidence rates. The first wave of the COVID-19 pandemic was defined as January-May 2020. Trend analysis was completed using Joinpoint regression., Results: From 2016 to 2020, the incidence of CVT increased from 24.34 per 1,000,000 population per year (MPY) to 33.63 per MPY (Annual Percentage Change (APC) 8.6 %; p < 0.001). All-cause in-hospital mortality was 4.9 % [95 % CI 4.5-5.4]. On multivariable analysis, use of thrombectomy, increased age, atrial fibrillation, stroke diagnosis, infection, presence of prothrombotic hematologic conditions, lowest quartile of income, intracranial hemorrhage, and male sex were associated with in-hospital mortality. CVT incidence was similar comparing the first 5 months of 2020 and 2019 (31.37 vs 32.04; p = 0.322) with no difference in median NIHSS (2 [IQR 1-10] vs. 2 [1-9]; p = 0.959) or mortality (4.2 % vs. 5.6 %; p = 0.176)., Conclusions: CVT incidence increased in the US from 2016 to 2020 while mortality did not change. Increased age, prothrombotic state, stroke diagnosis, infection, atrial fibrillation, male sex, lowest quartile of income, intracranial hemorrhage, and use of thrombectomy were associated with in-hospital mortality following CVT. During the first wave of the COVID-19 pandemic, CVT volumes and mortality were similar to the prior year., Competing Interests: Declaration of competing interest A.D.H holds royalties or licenses from UptoDate and receives consulting fees from NovoNordisk and Integra. S.Y. holds royalties or licenses from UptoDate. T.N.N participates on data safety monitoring boards of various trials, served on the advisory board of Idorsia, Brainomix, Associate Editor of Stroke, and President of SVIN society. T.S.F reports research grants from Bayer and consultancy for HLS Therapeutics. S.A.K reports compensation from Stryker for other services. A.I.Q. reports fees from AstraZeneca., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: Individual subcortical infarct scoring for the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) can be difficult and is subjected to higher inter-reader variability. This study compares performance of the 10-point ASPECTS with a new 7-point cortically-weighted score in predicting post-thrombectomy functional outcomes., Materials and Methods: Prospective registry data from two comprehensive stroke centers (Site 1 2016-2021; Site 2: 2019-2021) included patients with either M1 segment of middle cerebral artery or internal carotid artery occlusions who underwent thrombectomy. Two multivariate proportional odds training models utilizing either 10-point or 7-point ASPECTS predicting 90-day shift in modified Rankin score were generated using Site 1 data and validated with Site 2 data. Models were compared using multiclass receiver operator characteristics, corrected Akaike's Information Criterion, and likelihood ratio test., Results: Of 328 patients (Site 1 = 181, Site 2 = 147), median age was 71y (IQR 61-82), 119 (36%) had internal carotid artery occlusions, and median 10-point ASPECTS was 9 (IQR 8-10). There was no difference in performance between models using either total or cortically-weighted ASPECTS (p=0.14). Validation cohort data were correctly (i.e., predicting modified Rankin score within one point) classified 50% (cortically-weighted score model) and 56% (total score model) of the time., Conclusions: The 7-point cortically-weighted ASPECTS was similarly predictive of post-thrombectomy functional outcome as 10-point ASPECTS. Given noninferior performance, the cortically-weighted score is a potentially reliable, but simplified, alternative to the traditional scoring paradigm, with potential implications in automated image analysis tool development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Our purpose was to assess the efficacy and safety of the pRESET LITE stent retriever (Phenox, Bochum, Germany), designed for medium vessel occlusion (MeVO) in acute ischemic stroke (AIS) patients with a primary MeVO., Methods: We performed a retrospective analysis of the MAD MT Consortium, an integration of prospectively maintained databases at 37 academic institutions in Europe, North America, and Asia, of AIS patients who underwent mechanical thrombectomy with the pRESET LITE stent retriever for a primary MeVO. We subcategorized occlusions into proximal MeVOs (segments A1, M2, and P1) vs. distal MeVOs/DMVO (segments A2, M3-M4, and P2). We reviewed patient and procedural characteristics, as well as angiographic and clinical outcomes., Results: Between September 2016 and December 2021, 227 patients were included (50% female, median age 78 [65-84] years), of whom 161 (71%) suffered proximal MeVO and 66 (29%) distal MeVO. Using a combined approach in 96% of cases, successful reperfusion of the target vessel (mTICI 2b/2c/3) was attained in 85% of proximal MeVO and 97% of DMVO, with a median of 2 passes (IQR: 1-3) overall. Periprocedural complications rate was 7%. Control CT at day 1 post-MT revealed a hemorrhagic transformation in 63 (39%) patients with proximal MeVO and 24 (36%) patients with DMVO, with ECASS-PH type hemorrhagic transformations occurring in 3 (1%) patients. After 3 months, 58% of all MeVO and 63% of DMVO patients demonstrated a favorable outcome (mRS 0-2)., Conclusion: Mechanical thrombectomy using the pRESET LITE in a combined approach with an aspiration catheter appears effective for primary medium vessel occlusions across several centers and physicians., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: First pass effect (FPE), achievement of complete recanalization (mTICI 2c/3) with a single pass, is a significant predictor of favorable outcomes for endovascular treatment (EVT) in large vessel occlusion stroke (LVO). However, data concerning the impact on functional outcomes and predictors of FPE in medium vessel occlusions (MeVO) are scarce., Patients and Methods: We conducted an international retrospective study on MeVO cases. Multivariable logistic modeling was used to establish independent predictors of FPE. Clinical and safety outcomes were compared between the two study groups (FPE vs non-FPE) using logistic regression models. Good outcome was defined as modified Rankin Scale 0-2 at 3 months., Results: Eight hundred thirty-six patients with a final mTICI ⩾ 2b were included in this analysis. FPE was observed in 302 patients (36.1%). In multivariable analysis, hypertension (aOR 1.55, 95% CI 1.10-2.20) and lower baseline NIHSS score (aOR 0.95, 95% CI 0.93-0.97) were independently associated with an FPE. Good outcomes were more common in the FPE versus non-FPE group (72.8% vs 52.8%), and FPE was independently associated with favorable outcome (aOR 2.20, 95% CI 1.59-3.05). 90-day mortality and intracranial hemorrhage (ICH) were significantly lower in the FPE group, 0.43 (95% CI, 0.25-0.72) and 0.55 (95% CI, 0.39-0.77), respectively., Conclusion: Over 2/3 of patients with MeVOs and FPE in our cohort had a favorable outcome at 90 days. FPE is independently associated with favorable outcomes, it may reduce the risk of any intracranial hemorrhage, and 3-month mortality., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Regenhardt serves on a DSMB for a trial sponsored by Rapid Medical, serves as site PI for studies sponsored by Penumbra and Microvention, and receives stroke research grant funding from the National Institutes of Health, Society of Vascular and Interventional Neurology, and Heitman Stroke Foundation. Dr. Guenego reports consultancy for Rapid Medical and Phenox, not directly related to the present work. Prof. Clarençon reports conflicts of interest with Medtronic, Balt Extrusion (consultant), ClinSearch (core lab), Penumbra, Stryker (payment for reading) and Artedrone (Board); all not directly related to the present work. Dr. Henninger received support from NINDS NS131756, during the conduct of the study. Dr. Liebeskind is consultant as Imaging Core Lab to Cerenovus, Genentech, Medtronic, Stryker, Rapid Medical. Dr. Yeo reports Advisory work for AstraZeneca, Substantial support from NMRC Singapore and is a medical advisor for See-mode, Cortiro and Sunbird Bio, with equity in Ceroflo. All unrelated to the present work. Dr. Griessenauer reports a proctoring agreement with Medtronic and research funding by Penumbra. Dr. Marnat reports conflicts of interest with Microvention Europe, Stryker Neurovascular, Balt (consulting), Medtronic, Johnson & Johnson and Phenox (paid lectures), all not directly related to the present work. Dr. Nguyen reports advisory board with Idorsia and Brainomix. All other others do not report any conflict of interests related to this work.

Background: The association between sex and outcome after endovascular thrombectomy of acute ischemic stroke is unclear. The aim of this study was to compare the clinical and safety outcomes between men and women treated with endovascular thrombectomy in the late 6-to-24-hour window period., Methods: This multicenter, retrospective observational cohort study included consecutive patients who underwent endovascular thrombectomy of anterior circulation stroke in the late window from 66 clinical sites in 10 countries from January 2014 to May 2022. The primary outcome was the 90-day ordinal modified Rankin Scale score. Secondary outcomes included 90-day functional independence (FI), return of Rankin (RoR) to prestroke baseline, FI or RoR, symptomatic intracranial hemorrhage, and mortality. Multivariable and inverse probability of treatment weighting methods were used. We explored the interaction of sex with baseline characteristics on the outcomes ordinal modified Rankin Scale and FI or RoR., Results: Of 1932 patients, 1055 were women and 877 were men. Women were older (77 versus 69 years), had higher rates of atrial fibrillation, hypertension, and greater prestroke disability, but there was no difference in baseline National Institutes of Health Stroke Scale score. Inverse probability of treatment weighting analysis showed no difference between women and men in ordinal modified Rankin Scale (odds ratio, 0.98 [95% CI, 0.79-1.21]), FI or RoR (odds ratio, 0.98 [95% CI, 0.78-1.22]), severe disability or mortality (odds ratio, 0.99 [95% CI, 0.80-1.23]). The multivariable analysis of the above end points was concordant. There were no interactions between baseline characteristics and sex on the outcomes of ordinal modified Rankin Scale and FI or RoR., Conclusions: In late presenting patients with anterior circulation stroke treated with endovascular thrombectomy in the 6 to 24-hour window, there was no difference in clinical or safety outcomes between men and women., Competing Interests: Disclosures Dr Castonguay reports employment by Medtronic. Dr Cordonnier reports compensation from the University of Glasgow for data and safety monitoring services; employment by the University of Lille; compensation from Biogen for consultant services. Dr Fischer reports employment by Universität Basel; compensation from Boehringer Ingelheim and Biogen for expert witness services. Dr Dobrocky reported MicroVention consultancy. Dr Haussen reports compensation from Vesalio, Cerenovus, Chiesi USA, Inc, Stryker, Brainomix, and Poseydon Medical for consultant services; stock options in Viz.ai; compensation from Jacobs Institute for data and safety monitoring services. Dr Henon reports grants from Sanofi-Aventis U.S. LLC. Dr Kaesmacher reports grants from Swiss National Science Foundation to other. Dr Kaiser reported grants from Joachim Herz Foundation. Martinez-Majander reported grants from Finnish Medical Foundation. Dr Marto reported consulting from Amicus Therapeutics and Boehringer Ingelheim; Speaker with Boehringer Ingelheim. Dr Michel reports grants from the Swiss National Science Foundation, Swiss Heart Foundation, and the University of Lausanne to other. Dr Möhlenbruch reports grants from Medtronic, MicroVention, Inc, and Stryker to other. Dr Nagel reports compensation from Brainomix for consultant services. Dr Nguyen discloses research support from Medtronic, Society of Vascular, and Interventional Neurology to her institution; advisory board compensation from Idorsia, Brainomix; Associate Editor of Stroke. Dr Nogueira reported consultancy for Biogen, Brainomix, Corindus, Cerenovus, Stryker, Medtronic, Ceretrieve, Anaconda, Biomed, Vesalio, Imperative Care, NeuroVasc Technologies, Viz.ai, Genentech, Prolong Pharmaceuticals, Perfuze, Phenox, RapidPulse; stock options Viz.ai, Vesalio, Perfuze, Corindus, Brainomix, Ceretrieve; grants from Cerenovus, Stryker; Dr Nogueira reports compensation from Philips for consultant services; stock holdings in Quantanosis AI; compensation from Synchron for data and safety monitoring services; stock holdings in Piraeus Medical; stock options in Viseon, Inc; compensation from Hybernia for consultant services; stock options in Reist/Q’Apel Medical; stock options in Cerebrotech; compensation from Astrocyte and Cerebrotech for consultant services; stock holdings in Brain4Care; stock options in Truvic. Dr Ortega-Gutierrez reports compensation from MicroVention, Inc, Medtronic, and Stryker for consultant services; grants from Stryker, National Institutes of Health, methinks, Siemens, and MicroVention, Inc; and employment by Carver College of Medicine, University of Iowa. Dr Puetz reported as lecturer for Daiichi Sankyo. Dr Puri reports compensation from Medtronic, Stryker, Johnson & Johnson Health Care Systems, Inc, and MicroVention, Inc, for consultant services. Dr Ribo reports compensation from Philips, Stryker Corporation, Cerenovus, Medtronic MiniMed, Inc, and AptaTargets for consultant services; stock holdings in Anaconda Biomed, Methinks, and Nora. Dr Ringleb reports compensation from Daiichi Sankyo Company and Boehringer Ingelheim for consultant services; employment by Heidelberg University Hospital; travel support from Bristol-Myers Squibb and Bayer Healthcare. Dr Sakai reports compensation from Stryker, Asahi Intecc Co, Ltd, Terumo, Medtronic, Johnson & Johnson Medical Devices & Diagnostics Group, Latin America, L.L.C., Daiichi Sankyo Company Ltd, and Kaneka Medics for other services; grants from Medtronic; grants from Terumo. Dr Sheth reports compensation from Motif Neurosciences for other services; compensation from Viz.ai, Imperative Care, Inc, and Penumbra, Inc, for consultant services; grants from National Institutes of Health; employment by UTHealth McGovern Medical School. Dr Strbian reports employment by Helsingin ja Uudenmaan Sairaanhoitopiiri. Dr Uchida reports compensation from Bristol-Myers Squibb, Stryker, Daiichi Sankyo Company, Ltd, and Medtronic for other services. Dr Wouters reports grants from The Research Foundation-Flanders travel and Remmert Adriaan-Laan-Fonds. Dr Yamagami reports compensation from Otsuka Pharmaceutical Co, Ltd. Medtronic, Daiichi Sankyo Company Ltd, Bristol-Myers Squibb, Johnson and Johnson, Bayer. Daiichi Sankyo Company Ltd, and Stryker for other services; grants from Bristol-Myers Squibb. S. Yoshimura reports compensation from Bristol-Myers Squibb, Johnson & Johnson Medical Devices & Diagnostics Group, Latin America, LLC, Bayer, Kaneka Medics, Boehringer Ingelheim, Medtronic Daiichi Sankyo Company, Stryker, and Terumo for other services. S. Ning discloses research support from Society for Interventional Radiology. Dr Zaidat reports grants from Medtronic, Penumbra, Inc, Johnson and Johnson, Stryker to other; compensation from Medtronic and Johnson & Johnson Health Care Systems, Inc, and Penumbra, Inc, for consultant services; stock holdings in Penumbra Inc. The other authors report no conflicts.

Background: There is unclear added benefit of intravenous thrombolysis (IVT) with endovascular thrombectomy (EVT). We performed a cost-effectiveness analysis to assess the cost-effectiveness of comparing EVT with IVT versus EVT alone., Methods: We used a decision tree to examine the short-term costs and outcomes at 90 days after the occurrence of index stroke to compare the cost-effectiveness of EVT alone with EVT plus IVT for patients with stroke. Subsequently, we developed a Markov state transition model to assess the costs and outcomes over 1-year, 5-year, and 20-year time horizons. We estimated total and incremental cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio., Results: The average costs per patient were estimated to be $47,304, $49,510, $59,770, and $76,561 for EVT-only strategy and $55,482, $57,751, $68,314, and $85,611 for EVT with IVT over 90 days, 1 year, 5 years, and 20 years, respectively. The cost saving of EVT-only strategy was driven by the avoided medication costs of IVT (ranging from $8,178 to $9,050). The additional IVT led to a slight decrease in QALY estimate during the 90-day time horizon (loss of 0.002 QALY), but a small gain over 1-year and 5-year time horizons (0.011 and 0.0636 QALY). At a willingness-to-pay threshold of $50,000 per QALY gained, the probabilities of EVT only being cost-effective were 100%, 100%, and 99.3% over 90-day, 1-year, and 5-year time horizons., Conclusion: Our cost-effectiveness model suggested that EVT only may be cost-effective for patients with acute ischemic stroke secondary to large vessel occlusion., (© 2023 S. Karger AG, Basel.)

Objectives: To determine hospital-level factors associated with thrombectomy uptake., Materials and Methods: The Nationwide Emergency Department Sample was retrospectively queried to determine the total number of thrombectomies performed based on different hospital characteristics. Joint point analysis was used to determine which years were associated with significant increases in the number of high-volume thrombectomy centers (ostensibly defined as >50 thrombectomies/year), thrombectomy-capable centers (>15 thrombectomies/year), and total number of thrombectomies performed. Multivariable logistic regression was used to determine hospital factors associated with having an increased odds of performing thrombectomies, and of being classified as a high-volume thrombectomy or a thrombectomy-capable center., Results: Between 2007-2020 there was a stepwise increase in the number of thrombectomy-capable and high-volume thrombectomy centers in the United States. In 2020, there were a total of 15,705 thrombectomies performed, with 89 high-volume thrombectomy centers, and 359 thrombectomy-capable centers. The number of thrombectomy-capable centers significantly increased after 2011. After 2013 and 2016 there was a significant change in the growth rate of high-volume thrombectomy centers. There was also a significant increase in the total number of thrombectomies performed after 2016. Hospital characteristics that were associated with an increased likelihood of being classified as thrombectomy-capable or high-volume included trauma level 1 and 2 hospitals., Conclusions: Between 2007 and 2020, there was a marked growth in thrombectomy utilization for acute ischemic stroke. This growth outpaced new diagnoses of ischemic stroke, and was driven largely by certain hospital types, with the greatest rises following seminal publications of positive randomized thrombectomy trials., Competing Interests: Declaration of Competing Interest The authors do not have any relevant disclosures for this manuscript., (Copyright © 2023. Published by Elsevier Inc.)

Background: There is little data available to guide optimal anesthesia management during rescue intracranial angioplasty and stenting (ICAS) for failed mechanical thrombectomy (MT). We sought to compare the procedural safety and functional outcomes of patients undergoing rescue ICAS for failed MT under general anesthesia (GA) vs non-general anesthesia (non-GA)., Methods: We searched the data from the Stenting and Angioplasty In Neuro Thrombectomy (SAINT) study. In our review we included patients if they had anterior circulation large vessel occlusion strokes due to intracranial internal carotid artery (ICA) or middle cerebral artery (MCA-M1/M2) segments, failed MT, and underwent rescue ICAS. The cohort was divided into two groups: GA and non-GA. We used propensity score matching to balance the two groups. The primary outcome was the shift in the degree of disability as measured by the modified Rankin Scale (mRS) at 90 days. Secondary outcomes included functional independence (90-day mRS0-2) and successful reperfusion defined as mTICI2B-3. Safety measures included symptomatic intracranial hemorrhage (sICH) and 90-day mortality., Results: Among 253 patients who underwent rescue ICAS, 156 qualified for the matching analysis at a 1:1 ratio. Baseline demographic and clinical characteristics were balanced between both groups. Non-GA patients had comparable outcomes to GA patients both in terms of the overall degree of disability (mRS ordinal shift; adjusted common odds ratio 1.29, 95% CI [0.69 to 2.43], P=0.43) and rates of functional independence (33.3% vs 28.6%, adjusted odds ratio 1.32, 95% CI [0.51 to 3.41], P=0.56) at 90 days. Likewise, there were no significant differences in rates of successful reperfusion, sICH, procedural complications or 90-day mortality among both groups., Conclusions: Non-GA seems to be a safe and effective anesthesia strategy for patients undergoing rescue ICAS after failed MT. Larger prospective studies are warranted for more concrete evidence., Competing Interests: Competing interests: RGN: reports consulting fees for advisory roles with Stryker Neurovascular, Cerenovus, Medtronic, Phenox, Anaconda, Genentech, Biogen, Prolong Pharmaceuticals, Imperative Care and stock options for advisory roles with Brainomix, Viz-AI, Corindus Vascular Robotics, Vesalio, Ceretrieve, Astrocyte and Cerebrotech. DCH is a consultant for Stryker and Vesalio and holds stock options at Viz.AI. ARA is a consultant for Stryker Neurovascular. AEH - 1. Consultant/speaker: Medtronic, Microvention, Stryker, Penumbra, Cerenovus, Genentech, GE Healthcare, Scientia, Balt, Viz.ai, Insera therapeutics, Proximie, NovaSignal and Vesalio. 2. Principal investigator: COMPLETE study Penumbra, LVO SYNCHRONISE-Viz.ai. 3. Steering committee/publication committee member: SELECT, DAWN, SELECT 2, EXPEDITE II, EMBOLISE, CLEAR. 4. Proctor: Pipeline, FRED, Wingspan, and Onyx. 5. Supported by grants from: GE Healthcare. TNN: Research support from Medtronic, SVIN. SOG reports consulting fees for advisory roles with Stryker Neurovascular, Medtronic and microvention. Research support from Medtronic, Stryker, Microvention, VizAI. AA is consultant for Cerenovus. JB is an Advisory Board Member and consultant for Longeviti Neuro Solutions, and Consultant for Q’Apel Medical. BG is a consultant for Medtronic and Microvention. RAH: is a consultant for Medtronic, Stryker, Cerenovus, Microvention, Balt, Phenox, Rapid Medical, and Q’Apel, advisory board for MiVI, eLum, Three Rivers, Shape Medical and Corindus. Unrestricted research grant from NIH, Interline Endowment, Microvention, Stryker, CNX. Investor/stockholder for InNeuroCo, Cerebrotech, eLum, Endostream, Three Rivers Medical Inc, Scientia, RisT, BlinkTBI, and Corindus. ES: reports a speakers’ agreement with Stryker. AA: is on advisory board for iSchema View. PK is a member of the editorial board of JNIS. JF is a member of editorial board of JNIS. JES reports consulting fees from Ceribell, speakers’ bureau for AstraZeneca (both unrelated to the present work)., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Prior studies have elucidated a relationship between nonstenotic plaque in patients with cryptogenic embolic infarcts with a largely cortical topology, however, it is unclear if nonstenotic cervical internal carotid artery (ICA) plaque is relevant in subcortical cryptogenic infarct patterns., Methods: A nested cohort of consecutive patients with anterior, unilateral, and subcortical infarcts without an identifiable embolic source were identified from a prospective stroke registry (September 2019 - June 2021). Patients with extracranial stenosis >50% or cardiac sources of embolism were excluded. Patients with computed tomography angiography were included and comparisons were made according to the infarct pattern being lacunar versus non-lacunar. Prevalence estimates for cervical internal carotid artery (ICA) plaque presence were estimated with 95% confidence intervals (CI), and differences in plaque thickness and features were compared between sides., Results: Of the 1684 who were screened, 141 met inclusion criteria (n=80 due to small vessel disease, n=61 cryptogenic). The median age was 66y (interquartile range, IQR 58-73) and the National Institutes of Health Stroke Scale score was 3 (IQR 1-5). There was a higher probability of finding excess plaque ipsilateral to the stroke (41.1%, 95% CI 33.3-49.3%) than finding excess contralateral plaque (29.1%, 95% CI 22.2-37.1%; p=0.03), but this was driven by patients with non-lacunar infarcts (excess ipsilateral vs. contralateral plaque frequency of 49.2% vs. 14.8%, p<0.001) rather than lacunar infarcts (35.0% vs. 40.0%, p=0.51)., Conclusions: The probability of finding ipsilateral, nonstenotic carotid plaque in patients with subcortical cryptogenic strokes exceeds the probability of contralateral plaque and is driven by larger subcortical infarcts, classically defined as being cryptogenic. Approximately 1 in 3 unilateral anterior subcortical infarcts may be due to nonstenotic ICA plaque., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Background: We aimed to describe the safety and efficacy of mechanical thrombectomy (MT) with or without intravenous thrombolysis (IVT) for patients with tandem lesions and whether using intraprocedural antiplatelet therapy influences MT's safety with IVT treatment., Methods: This is a subanalysis of a pooled, multicenter cohort of patients with acute anterior circulation tandem lesions treated with MT from 16 stroke centers between January 2015 and December 2020. Primary outcomes included symptomatic intracranial hemorrhage (sICH) and parenchymal hematoma type 2. Additional outcomes included hemorrhagic transformation, successful reperfusion (modified Thrombolysis in Cerebral Infarction score 2b-3), complete reperfusion (modified Thrombolysis in Cerebral Infarction score 3), favorable functional outcome (90-day modified Rankin Scale score 0-2), excellent functional outcome (90-day modified Rankin Scale score 0-1), in-hospital mortality, and 90-day mortality., Results: Of 691 patients, 512 were included (218 underwent IVT+MT and 294 MT alone). There was no difference in the risk of sICH (adjusted odds ratio [aOR], 1.22 [95% CI, 0.60-2.51]; P =0.583), parenchymal hematoma type 2 (aOR, 0.99 [95% CI, 0.47-2.08]; P =0.985), and hemorrhagic transformation (aOR, 0.95 [95% CI, 0.62-1.46]; P =0.817) between the IVT+MT and MT alone groups after adjusting for confounders. Administration of IVT was associated with an increased risk of sICH in patients who received intravenous antiplatelet therapy (aOR, 3.04 [95% CI, 0.99-9.37]; P =0.05). The IVT+MT group had higher odds of a 90-day modified Rankin Scale score 0 to 2 (aOR, 1.72 [95% CI, 1.01-2.91]; P =0.04). The odds of successful reperfusion, complete reperfusion, 90-day modified Rankin Scale score 0 to 1, in-hospital mortality, or 90-day mortality did not differ between the IVT+MT versus MT alone groups., Conclusions: Our study showed that the combination of IVT with MT for tandem lesions did not increase the overall risk of sICH, parenchymal hematoma type 2, or overall hemorrhagic transformation independently of the cervical revascularization technique used. However, intraprocedural intravenous antiplatelet therapy during acute stent implantation might be associated with an increased risk of sICH in patients who received IVT before MT. Importantly, IVT+MT treatment was associated with a higher rate of favorable functional outcomes at 90 days., Competing Interests: Disclosures A.E. Hassan is a consultant/speaker at Medtronic, Microvention, Stryker, Penumbra, Cerenovus, Genentech, GE Healthcare, Scientia, Balt, vizai, Insera therapeutics, Proximie, NeuroVasc, NovaSignal, Vesalio, Rapid Medical, Imperative Care and Galaxy Therapeutics; principal investigator for COMPLETE study—Penumbra, LVO SYNCHRONISE—vizai, Millipede Stroke Trial—Perfuze, RESCUE—ICAD, Medtronic; steering committee/publication committee member for SELECT, DAWN, SELECT 2, EXPEDITE II, EMBOLISE, CLEAR, ENVI, DELPHI, DISTALS. Dr Divani performed fundings at the University of New Mexico Center for Brain Recovery and Repair Center of Biomedical Research Excellence through Grant Number (NIH P20GM109089, Pilot PI), W81XWH-17-2-0053 (PI), 1R21NS130423-01 (PI). Dr Ribo is consultant at aptaTargets, Anaconda Biomed, Philips, Medtronic, Cerenovus, Vesalio, and Rapid Pulse outside the submitted work. Dr Abraham is a consultant at Penumbra Inc, Qapel, Stryker Corporation. Dr Fifi is a consultant at Cerenovus, Stryker Corporation, Microvention Inc; received stock from Cerebrotech, Imperative Care, Sime&Cure; and received grants from viz AI. Data and Safety Monitoring: MIVI. Dr Yoo is a consultant for Johnson & Johnson Medical Devices & Diagnostics Group—Latin America, LLC, Nicolab, Penumbra Inc, Philips, Vesalio, ZOLL Circulation Inc; received grants from Genetech, USA Inc, Johnson & Johnson Medical Devices & Diagnostics Group—Latin America, LLC, Medtronic, Penumbra Inc, Stryker; Employment at HCA Healthcare; received stock from Insera, Nicolab; performed data and safety monitoring at National Institutes of Health. Dr Mokin is a consultant at Johnson & Johnson Medical Devices & Diagnostics Group—Latin America, LLC, Medtronic, MicroVention Inc, received stock from Bendit Technology, BrainQ, Serenity medical, Synchrone. Dr Yavagal is a consultant at Athersys, Gravity Medical Technology, Johnson & Johnson Health Care Systems Inc, Medtronic USA Inc, Poseydon, Stryker Corporation, Vascular Dynamics; received stock from Athersys, Poseydon, Rapid Medical. Dr Jovin is a consultant at Contego Medical Inc received stock from Anaconda, Freeox Biotech, Galaxy, Kandu, Methinks, Route92, vizai. Grant: Medtronicm, USA, Inc, Stryker Corporation; performed data and safety monitoring at Johnson & Johnson, Cerenovus. Dr Sheth is a consultant at vizAI, Penumbra, Imperative Care; received grants from NIH, vizAI; and took ownership for Motif Neuroscience (not related to this article). Dr Ortega-Gutierrez received grants from NIH-NINDS (R01NS127114-01, R03NS126804), Stryker, Medtronics, Microvention, Penumbra, IschemiaView, vizai, and Siemens; he is a consultant at Medtronic and Stryker Neurovascular. The other authors report no conflicts.

Background: The proper imaging modality for use in the selection of patients for endovascular thrombectomy (EVT) presenting in the late window remains controversial, despite current guidelines advocating the use of advanced imaging in this population. We sought to understand if clinicians with different specialty training differ in their approach to patient selection for EVT in the late time window., Methods: We conducted an international survey of stroke and neurointerventional clinicians between January and May 2022 with questions focusing on imaging and treatment decisions of large vessel occlusion (LVO) patients presenting in the late window. Interventional neurologists, interventional neuroradiologists, and endovascular neurosurgeons were defined as interventionists whereas all other specialties were defined as non-interventionists. The non-interventionist group was defined by all other specialties of the respondents: stroke neurologist, neuroradiologist, emergency medicine physician, trainee (fellows and residents) and others., Results: Of 3000 invited to participate, 1506 (1027 non-interventionists, 478 interventionists, 1 declined to specify) physicians completed the study. Interventionist respondents were more likely to proceed directly to EVT (39.5% vs. 19.5%; p < 0.0001) compared to non-interventionist respondents in patients with favorable ASPECTS (Alberta Stroke Program Early CT Score). Despite no difference in access to advanced imaging, interventionists were more likely to prefer CT/CTA alone (34.8% vs. 21.0%) and less likely to prefer CT/CTA/CTP (39.1% vs. 52.4%) for patient selection (p < 0.0001). When faced with uncertainty, non-interventionists were more likely to follow clinical guidelines (45.1% vs. 30.2%) while interventionists were more likely to follow their assessment of evidence (38.7% vs. 27.0%) (p < 0.0001)., Conclusion: Interventionists were less likely to use advanced imaging techniques in selecting LVO patients presenting in the late window and more likely to base their decisions on their assessment of evidence rather than published guidelines. These results reflect gaps between interventionists and non-interventionists reliance on clinical guidelines, the limits of available evidence, and clinician belief in the utility of advanced imaging., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background and Objectives: There is growing evidence for endovascular thrombectomy (EVT) in patients with large ischemic core infarct and large vessel occlusion (LVO). The objective of this study was to compare the efficacy and safety of EVT vs medical management (MM) using a systematic review and meta-analysis of observational studies and randomized controlled trials (RCTs)., Methods: We searched the PubMed, Embase, Cochrane Library, and Web of Science databases to obtain articles related to mechanical thrombectomy for large ischemic core from inception until February 10, 2023. The primary outcome was independent ambulation (modified Rankin Scale [mRS] 0-3). Effect sizes were computed as risk ratio (RR) with random-effect or fixed-effect models. The quality of articles was evaluated through the Cochrane risk assessment tool and the Newcastle-Ottawa Scale. This study was registered in PROSPERO (CRD42023396232)., Results: A total of 5,395 articles were obtained through the search and articles that did not meet the inclusion criteria were excluded by review of the title, abstract, and full text. Finally, 3 RCTs and 10 cohort studies met the inclusion criteria. The RCT analysis showed that EVT improved the 90-day functional outcomes of patients with large ischemic core with high-quality evidence, including independent ambulation (mRS 0-3: RR 1.78, 95% CI 1.28-2.48, p < 0.001) and functional independence (mRS 0-2: RR 2.59, 95% CI 1.89-3.57, p < 0.001), but without significantly increasing the risk of symptomatic intracranial hemorrhage (sICH: RR 1.83, 95% CI 0.95-3.55, p = 0.07) or early mortality (RR 0.95, 95% CI 0.78-1.16, p = 0.61). Analysis of the cohort studies showed that EVT improved functional outcomes of patients without an increase in the incidence in sICH., Discussion: This systematic review and meta-analysis indicates that in patients with LVO stroke with a large ischemic core, EVT was associated with improved functional outcomes over MM without increasing sICH risk. The results of ongoing RCTs may provide further insight in this patient population., (© 2023 American Academy of Neurology.)

Objective: Anticoagulation therapy is commonly interrupted in patients with atrial fibrillation (AF) for elective procedures. However, the risk factors of acute ischemic stroke (AIS) during the periprocedural period remain uncertain. We performed a nationwide analysis to evaluate AIS risk factors in patients with AF undergoing elective surgical procedures., Methods: Using the Nationwide Readmission Database, we included electively admitted adult patients with AF and procedural Diagnosis-Related Group codes from 2016 to 2019. Diagnoses were identified based on International Classification of Disease, 9th revision-Clinical Modification (ICD-10 CM) codes. We constructed a logistic regression model to identify risk factors and developed a new scoring system incorporating CHA 2 DS 2 VASc to estimate periprocedural AIS risk., Results: Of the 1,045,293 patients with AF admitted for an elective procedure, the mean age was 71.5 years, 39.2% were women, and 0.70% had a perioperative AIS during the index admission or within 30 days of discharge. Active cancer (adjusted OR [aOR] = 1.58, 95% confidence interval [CI] = 1.42-1.76), renal failure (aOR = 1.14, 95% CI = 1.04-1.24), neurological surgery (aOR = 4.51, 95% CI = 3.84-5.30), cardiovascular surgery (aOR = 2.74, 95% CI = 2.52-2.97), and higher CHA 2 DS 2 VASc scores (aOR 1.25 per point, 95% CI 1.22-1.29) were significant risk factors for periprocedural AIS. The new scoring system (area under the receiver operating characteristic curve [AUC] = 0.68, 95% CI = 0.67 to 0.79) incorporating surgical type and cancer outperformed CHA 2 DS 2 VASc (AUC = 0.60, 95% CI = 0.60 to 0.61)., Interpretation: In patients with AF, periprocedural AIS risk increases with the CHA 2 DS 2 VASc score, active cancer, and cardiovascular or neurological surgeries. Studies are needed to devise better strategies to mitigate perioperative AIS risk in these patients. ANN NEUROL 2023;94:321-329., (© 2023 American Neurological Association.)

Background: Thrombectomy for basilar artery occlusion (BAO) has proven efficacy in patients with moderate-to-severe deficits, but has unclear benefits for those with mild symptoms., Methods: Using an observational cohort design, the US National Inpatient Sample (2018-2020) was queried for adult patients with basilar artery occlusion and National Institutes of Health Stroke Scale (NIHSS) <10 for patients treated with thrombectomy versus medical management. The primary outcome of routine discharge (to home or self-care) was evaluated using multivariable logistic regression and propensity score matching, adjusted for baseline characteristics, stroke severity, and treatment with thrombolysis., Results: Of 17 019 with basilar artery occlusion, 5795 patients met the criteria for inclusion criteria for our study, and 880 (15.4%) were treated with endovascular thrombectomy. In the propensity score-matched cohort, 880 patients were treated with medical management and endovascular thrombectomy, respectively. In multivariable regression, endovascular thrombectomy was associated with both an increased odds of routine discharge (odds ratio, 1.95 [95% CI, 1.31-2.90]; P =0.001) and a decreased length of hospital stay (B, -0.74 [95% CI, -1.36 to -0.11]; P =0.02) compared with medical management. In the propensity score matched cohort, endovascular thrombectomy remained associated with greater odds of routine discharge (2.01 [95% CI, 1.21-3.34]; P =0.007) but no difference in length of hospital stay (B, -0.22 [95% CI, -0.90 to 0.46]; P =0.53)., Conclusions: Routine discharge was more common in this representative US cohort of patients with basilar artery occlusion and National Institutes of Health Stroke Scale <10 who underwent thrombectomy compared to conventional medical management. These findings suggest thrombectomy may be associated with better functional outcomes despite lower National Institutes of Health Stroke Scale and should be validated in a clinical trial setting., Competing Interests: Disclosures Dr Nguyen reports research support from SVIN and Medtronic; advisory board with Idorsia. S. Yaghi reports research support from Medtronic. Dr Prabhakaran reports research support from National Institute of Neurological Disorders and Stroke, Agency for Healthcare Research and Quality; royalties from UpToDate; consultant fees from Wolters Kluwer Health Inc. The other authors report no conflicts.

Not in the history of transmissible illnesses has there been an infection as strongly associated with acute cerebrovascular disease as the novel human coronavirus SARS-CoV-2. While the risk of stroke has known associations with other viral infections, such as influenza and human immunodeficiency virus, the risk of ischemic and hemorrhagic stroke related to SARS-CoV-2 is unprecedented. Furthermore, the coronavirus disease 2019 (COVID-19) pandemic has so profoundly impacted psychosocial behaviors and modern medical care that we have witnessed shifts in epidemiology and have adapted our treatment practices to reduce transmission, address delayed diagnoses, and mitigate gaps in healthcare. In this narrative review, we summarize the history and impact of the COVID-19 pandemic on cerebrovascular disease, and lessons learned regarding the management of patients as we endure this period of human history.

Background: The optimal management of patients with isolated posterior cerebral artery occlusion is uncertain. We compared clinical outcomes for endovascular therapy (EVT) versus medical management (MM) in patients with isolated posterior cerebral artery occlusion., Methods: This multinational case-control study conducted at 27 sites in Europe and North America included consecutive patients with isolated posterior cerebral artery occlusion presenting within 24 hours of time last well from January 2015 to August 2022. Patients treated with EVT or MM were compared with multivariable logistic regression and inverse probability of treatment weighting. The coprimary outcomes were the 90-day modified Rankin Scale ordinal shift and ≥2-point decrease in the National Institutes of Health Stroke Scale., Results: Of 1023 patients, 589 (57.6%) were male with median (interquartile range) age of 74 (64-82) years. The median (interquartile range) National Institutes of Health Stroke Scale was 6 (3-10). The occlusion segments were P1 (41.2%), P2 (49.2%), and P3 (7.1%). Overall, intravenous thrombolysis was administered in 43% and EVT in 37%. There was no difference between the EVT and MM groups in the 90-day modified Rankin Scale shift (aOR, 1.13 [95% CI, 0.85-1.50]; P =0.41). There were higher odds of a decrease in the National Institutes of Health Stroke Scale by ≥2 points with EVT (aOR, 1.84 [95% CI, 1.35-2.52]; P =0.0001). Compared with MM, EVT was associated with a higher likelihood of excellent outcome (aOR, 1.50 [95% CI, 1.07-2.09]; P =0.018), complete vision recovery, and similar rates of functional independence (modified Rankin Scale score, 0-2), despite a higher rate of SICH and mortality (symptomatic intracranial hemorrhage, 6.2% versus 1.7%; P =0.0001; mortality, 10.1% versus 5.0%; P =0.002)., Conclusions: In patients with isolated posterior cerebral artery occlusion, EVT was associated with similar odds of disability by ordinal modified Rankin Scale, higher odds of early National Institutes of Health stroke scale improvement, and complete vision recovery compared with MM. There was a higher likelihood of excellent outcome in the EVT group despite a higher rate of symptomatic intracranial hemorrhage and mortality. Continued enrollment into ongoing distal vessel occlusion randomized trials is warranted., Competing Interests: Disclosures Dr Asdaghi reported employment by the American Heart Association. Dr Dabus reported consultancy for Cerenovus, Penumbra, Route 92, Medtronic, MicroVention, and Stryker and stock holdings in RIST and InNeuroCo. Dr Fifi reported consultancy for Cerenovus, MicroVention, and Stryker; Data Safety Monitoring Board (DSMB) for MIVI; and stock holdings in Imperative Care and Sim&Cure. Dr Fischer reported research support from the Swiss National Science Foundation (SNF), Medtronic, Stryker, Rapid Medical, Penumbra, and Phenox; consultancies for Stryker and CSL Behring; and is on the advisory board for Alexion/Portola, Boehringer Ingelheim, Biogen, and Acthera. Dr Finitsis reports patent US11166738B2. Dr Haussen reported consultancy for Vesalio, Cerenovus, Stryker, Brainomix, Poseydon Medical, and Chiesi USA; DSMB from Jacobs Institute; and stock options in Viz AI. Dr Herweh reported consultancy for Brainomix and Speaker with Stryker. Dr Jadhav reports consulting with Basking Biosciences; stock options in Gravity Medical Technology; and a patent for a novel stent retriever device licensed to Basking Biosciences. Dr Kaesmacher reported grants from the Swiss Academy of Medical Sciences/Bangerter Foundation, Swiss Stroke Society, and Clinical Trials Unit Bern. Dr Kaiser reported grants from the Joachim Herz Foundation. Dr Kuramatsu reports grants from Alexion Pharmaceuticals, Bayer Healthcare, Sanofi Pasteur, and Biogen Idec. Dr Pedro Marto reported consulting from Amicus Therapeutics and Boehringer Ingelheim and Speaker with Boehringer Ingelheim. Dr Michel reported grants from the University of Lausanne and Swiss National Science Foundation (SNF). Dr Möhlenbruch reported grants from Medtronic, Stryker, and MicroVention. Dr Mokin reported stock holdings in BrainQ, Serenity Medical, Synchron, and Bendit Technology and consulting from MicroVention, Medtronic, and Johnson & Johnson. Dr Nagel reported consultancy for Brainomix and is a speaker with Boehringer Ingelheim and Pfizer. Dr Nguyen reported research support from Society of Vascular and Interventional Neurology (SVIN) and Medtronic and is on the advisory board with Idorsia. Dr Nogueira reported consultancy for Biogen, Brainomix, Corindus, Cerenovus, Stryker, Medtronic, Ceretrieve, Anaconda Biomed, Vesalio, Imperative Care, NeuroVasc Technologies, Viz AI, Genentech, Prolong Pharmaceuticals, Perfuze, Phenox, and RapidPulse; stock options in Viz AI, Vesalio, Perfuze, Corindus, Brainomix, and Ceretrieve; and grants from Cerenovus and Stryker. Dr Nolte reported compensation (other services) from Novartis, AstraZeneca, Deutsches Zentrum für Herz-Kreislaufforschung, and Deutsches Zentrum für Neurodegenerative Erkrankungen and consultancy for Daiichi Sankyo, Bayer Healthcare, Pfizer, Alexion, and Bristol Myers Squibb. Dr Psychogios reported grants from Penumbra, Rapid Medical, Medtronic, Phenox, Bangerter-Rhyner Stiftung, SNF, Siemens Healthineers, and Stryker Neurovascular; travel support from Medtronic, Siemens Healthineers, Phenox, Penumbra, and Stryker; and consultancy for Siemens Healthineers. Dr Puetz reported being a lecturer for Daiichi Sankyo. Dr Ribo reported consultancy for Medtronic MiniMed, Cerenovus, AptaTargets, Stryker, and Philips and stock holdings in Methinks, Nora, and Anaconda Biomed. Dr Ringleb reported travel support from Bayer and Bristol Myers Squibb and consultancy for Daiichi Sankyo Company and Boehringer Ingelheim. Dr Sheth reported consultancy for Imperative Care, Viz AI, and Penumbra; compensation from Motif Neurosciences (other services); and grants from the National Institutes of Health. Dr Siddiqui reported an ownership stake in Integra Lifesciences and Medtronic; consultancy for Cordis, Rapid Medical, MicroVention, Medtronic Vascular, Vassol, IRRAS USA, Boston Scientific, Amnis Therapeutics, Minnetronix Neuro, Canon Medical Systems USA, Cardinal Health 200, Johnson & Johnson–Latin America, Corindus, Penumbra, Apellis Pharmaceuticals, W.L. Gore & Associates, Stryker Corporation, and Viz AI; stock holdings in E8, Spinnaker Medical, Endostream Medical, Cerebrotech Medical Systems, Adona Medical, Bend IT Technologies, Whisper Medical, Neurotechnology Investors, Collavidence, Instylla, Q’Appel Medical, Serenity Medical, Borvo Medical, NeuroRadial Technologies, Sense Diagnostics, Tulavi Therapeutics, Synchron, Neurolutions, Viseon, BlinkTBI, Radical Catheter Technologies, and Truvic Medical; stock options in Viz AI, StimMed, Three Rivers Medical, Silk Road Medical, Imperative Care, CVAID, Cerevatech Medical, InspireMD, and PerFlow Medical; and security holdings in Vastrax, Launch NY, QAS.ai, VICIS, Neurovascular Diagnostics, Cognition Medical, and SongBird Therapy. The other authors report no conflicts.

Background and Purpose: Two early basilar artery occlusion (BAO) randomized controlled trials did not establish the superiority of endovascular thrombectomy (EVT) over medical management. While many providers continue to recommend EVT for acute BAO, perceptions of equipoise in randomizing patients with BAO to EVT versus medical management may differ between clinician specialties., Methods: We conducted an international survey (January 18, 2022 to March 31, 2022) regarding management strategies in acute BAO prior to the announcement of two trials indicating the superiority of EVT, and compared responses between interventionalists (INTs) and non-interventionalists (nINTs). Selection practices for routine EVT and perceptions of equipoise regarding randomizing to medical management based on neuroimaging and clinical features were compared between the two groups using descriptive statistics., Results: Among the 1245 respondents (nINTs = 702), INTs more commonly believed that EVT was superior to medical management in acute BAO (98.5% vs. 95.1%, p < .01). A similar proportion of INTs and nINTs responded that they would not randomize a patient with BAO to EVT (29.4% vs. 26.7%), or that they would only under specific clinical circumstances (p = .45). Among respondents who would recommend EVT for BAO, there was no difference in the maximum prestroke disability, minimum stroke severity, or infarct burden on computed tomography between the two groups (p > .05), although nINTs more commonly preferred perfusion imaging (24.2% vs. 19.7%, p = .04). Among respondents who indicated they would randomize to medical management, INTs were more likely to randomize when the National Institutes of Health Stroke Scale was ≥10 (15.9% vs. 6.9%, p < .01)., Conclusions: Following the publication of two neutral clinical trials in BAO EVT, most stroke providers believed EVT to be superior to medical management in carefully selected patients, with most indicating they would not randomize a BAO patient to medical treatment. There were small differences in preference for advanced neuroimaging for patient selection, although these preferences were unsupported by clinical trial data at the time of the survey., (© 2023 American Society of Neuroimaging.)

Importance: Approximately 10% to 20% of large vessel occlusion (LVO) strokes involve tandem lesions (TLs), defined as concomitant intracranial LVO and stenosis or occlusion of the cervical internal carotid artery. Mechanical thrombectomy (MT) may benefit patients with TLs; however, optimal management and procedural strategy of the cervical lesion remain unclear., Objective: To evaluate the association of carotid artery stenting (CAS) vs no stenting and medical management with functional and safety outcomes among patients with TL-LVOs., Design, Setting, and Participants: This cross-sectional study included consecutive patients with acute anterior circulation TLs admitted across 17 stroke centers in the US and Spain between January 1, 2015, and December 31, 2020. Data analysis was performed from August 2021 to February 2022. Inclusion criteria were age of 18 years or older, endovascular therapy for intracranial occlusion, and presence of extracranial internal carotid artery stenosis (>50%) demonstrated on pre-MT computed tomography angiography, magnetic resonance angiography, or digital subtraction angiography., Exposures: Patients with TLs were divided into CAS vs nonstenting groups., Main Outcomes and Measures: Primary clinical and safety outcomes were 90-day functional independence measured by a modified Rankin Scale (mRS) score of 0 to 2 and symptomatic intracranial hemorrhage (sICH), respectively. Secondary outcomes were successful reperfusion (modified Thrombolysis in Cerebral Infarction score ≥2b), discharge mRS score, ordinal mRS score, and mortality at 90 days., Results: Of 685 patients, 623 (mean [SD] age, 67 [12.2] years; 406 [65.2%] male) were included in the analysis, of whom 363 (58.4%) were in the CAS group and 260 (41.6%) were in the nonstenting group. The CAS group had a lower proportion of patients with atrial fibrillation (38 [10.6%] vs 49 [19.2%], P = .002), a higher proportion of preprocedural degree of cervical stenosis on digital subtraction angiography (90%-99%: 107 [32.2%] vs 42 [20.5%], P < .001) and atherosclerotic disease (296 [82.0%] vs 194 [74.6%], P = .003), a lower median (IQR) National Institutes of Health Stroke Scale score (15 [10-19] vs 17 [13-21], P < .001), and similar rates of intravenous thrombolysis and stroke time metrics when compared with the nonstenting group. After adjustment for confounders, the odds of favorable functional outcome (adjusted odds ratio [aOR], 1.67; 95% CI, 1.20-2.40; P = .007), favorable shift in mRS scores (aOR, 1.46; 95% CI, 1.02-2.10; P = .04), and successful reperfusion (aOR, 1.70; 95% CI, 1.02-3.60; P = .002) were significantly higher for the CAS group compared with the nonstenting group. Both groups had similar odds of sICH (aOR, 0.90; 95% CI, 0.46-2.40; P = .87) and 90-day mortality (aOR, 0.78; 95% CI, 0.50-1.20; P = .27). No heterogeneity was noted for 90-day functional outcome and sICH in prespecified subgroups., Conclusions and Relevance: In this multicenter, international cross-sectional study, CAS of the cervical lesion during MT was associated with improvement in functional outcomes and reperfusion rates without an increased risk of sICH and mortality in patients with TLs.

Background: Endovascular thrombectomy (EVT) is recommended in medically eligible patients with large vessel occlusions (LVO) within 24 hours of symptom onset. While there is evidence that EVT ≥24h after last known well (LKW) is associated with favorable outcomes in patients who meet DAWN/DEFUSE-3 criteria, it is unknown if more liberal criteria can be applied., Methods: A single center, prospective observational cohort of consecutive adult stroke patients was queried for symptomatic occlusions of the internal carotid (ICA) or proximal middle cerebral (M1) arteries (October 2019-January 2022), with a National Institutes of Health Stroke Scale (NIHSS) ≥6, pre-stroke modified Rankin Scale (mRS) 0-2, and Alberta Stroke Program Early Computed Tomography Scale score 3-10. These inclusion criteria were extrapolated from recently published data indicating a benefit with EVT with more liberal patient selection. Patients who underwent EVT ≥24h after LKW were compared against those treated medically. The primary outcome was a good functional outcome (90-day mRS 0-2), which was evaluated using multivariable logistic regression., Results: Of the 27 included patients, the median age was 65y (IQR 49-76) with a median NIHSS of 15 (IQR 8-26), and 17 (63.0%) underwent EVT (median LKW-to-puncture 35.5h (IQR 26.9-65.8h). The primary outcome was no different with EVT in unadjusted regression (OR 1.17, 95%CI 0.17-8.09), and there remained no association across all multivariable models tested. Age, pre-stroke disability, and M1 occlusions were non-significantly associated with the primary outcome (p>0.05). There was a non-significant trend indicating a favorable shift in 90-day mRS with EVT (proportional OR 2.04, 95%CI 0.44-9.48)., Conclusions: Using more liberal inclusion criteria for EVT in the ultra-extended window, there was no statistically significant difference in the rate of good functional outcome with EVT. Larger studies are called upon to evaluate outcomes when more liberal criteria are used to assess thrombectomy eligibility., Competing Interests: Declaration of Competing Interest Dr. Siegler reports consulting fees (Ceribell) and for medicolegal work, and speakers bureau (AstraZeneca), all of which are unrelated to the present work., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Objectives: Current guidelines do not address recommendations for mechanical thrombectomy (MT) in the extended time window (>6 hours after time last seen well [TLSW]) for large vessel occlusion (LVO) patients with preexisting modified Rankin Scale (mRS) > 1. In this study, we evaluated the outcomes of MT vs medical management in patients with prestroke disability presenting in the 6- to 24-hour time window with acute LVO., Methods: We analyzed a multinational cohort (61 sites, 6 countries from 2014 to 2020) of patients with prestroke (or baseline) mRS 2 to 4 and anterior circulation LVO treated 6-24 hours from TLSW. Patients treated in the extended time window with MT vs medical management were compared using multivariable logistic regression and inverse probability of treatment weighting (IPTW). The primary outcome was the return of Rankin (ROR, return to prestroke mRS by 90 days)., Results: Of 554 included patients (448 who underwent MT), the median age was 82 years (interquartile range [IQR] 72-87) and the National Institutes of Health Stroke Scale (NIHSS) was 18 (IQR 13-22). In both MV logistic regression and IPTW analysis, MT was associated with higher odds of ROR (adjusted OR [aOR] 3.96, 95% CI 1.78-8.79 and OR 3.10, 95% CI 1.20-7.98, respectively). Among other factors, premorbid mRS 4 was associated with higher odds of ROR (aOR, 3.68, 95% CI 1.97-6.87), while increasing NIHSS (aOR 0.90, 95% CI 0.86-0.94) and decreasing Alberta Stroke Program Early Computed Tomography Scale score (aOR per point 0.86, 95% CI 0.75-0.99) were associated with lower odds of ROR. Age, intravenous thrombolysis, and occlusion location were not associated with ROR., Discussion: In patients with preexisting disability presenting in the 6- to 24-hour time window, MT is associated with a higher probability of returning to baseline function compared with medical management., Classification of Evidence: This investigation's results provide Class III evidence that in patients with preexisting disability presenting 6-24 hours from the TLSW and acute anterior LVO stroke, there may be a benefit of MT over medical management in returning to baseline function., (© 2022 American Academy of Neurology.)

Importance: The role of endovascular thrombectomy is uncertain for patients presenting beyond 24 hours of the time they were last known well., Objective: To evaluate functional and safety outcomes for endovascular thrombectomy (EVT) vs medical management in patients with large-vessel occlusion beyond 24 hours of last known well., Design, Setting, and Participants: This retrospective observational cohort study enrolled patients between July 2012 and December 2021 at 17 centers across the United States, Spain, Australia, and New Zealand. Eligible patients had occlusions in the internal carotid artery or middle cerebral artery (M1 or M2 segment) and were treated with EVT or medical management beyond 24 hours of last known well., Interventions: Endovascular thrombectomy or medical management (control)., Main Outcomes and Measures: Primary outcome was functional independence (modified Rankin Scale score 0-2). Mortality and symptomatic intracranial hemorrhage (sICH) were safety outcomes. Propensity score (PS)-weighted multivariable logistic regression analyses were adjusted for prespecified clinical characteristics, perfusion parameters, and/or Alberta Stroke Program Early CT Score (ASPECTS) and were repeated in subsequent 1:1 PS-matched cohorts., Results: Of 301 patients (median [IQR] age, 69 years [59-81]; 149 female), 185 patients (61%) received EVT and 116 (39%) received medical management. In adjusted analyses, EVT was associated with better functional independence (38% vs control, 10%; inverse probability treatment weighting adjusted odds ratio [IPTW aOR], 4.56; 95% CI, 2.28-9.09; P < .001) despite increased odds of sICH (10.1% for EVT vs 1.7% for control; IPTW aOR, 10.65; 95% CI, 2.19-51.69; P = .003). This association persisted after PS-based matching on (1) clinical characteristics and ASPECTS (EVT, 35%, vs control, 19%; aOR, 3.14; 95% CI, 1.02-9.72; P = .047); (2) clinical characteristics and perfusion parameters (EVT, 35%, vs control, 17%; aOR, 4.17; 95% CI, 1.15-15.17; P = .03); and (3) clinical characteristics, ASPECTS, and perfusion parameters (EVT, 45%, vs control, 21%; aOR, 4.39; 95% CI, 1.04-18.53; P = .04). Patients receiving EVT had lower odds of mortality (26%) compared with those in the control group (41%; IPTW aOR, 0.49; 95% CI, 0.27-0.89; P = .02)., Conclusions and Relevance: In this study of treatment beyond 24 hours of last known well, EVT was associated with higher odds of functional independence compared with medical management, with consistent results obtained in PS-matched subpopulations and patients with presence of mismatch, despite increased odds of sICH. Our findings support EVT feasibility in selected patients beyond 24 hours. Prospective studies are warranted for confirmation.

Background: Reperfusion without functional independence (RFI) is an undesired outcome following thrombectomy in acute ischemic stroke. The primary objective was to evaluate, in patients presenting with proximal anterior circulation occlusion stroke in the extended time window, whether selection with computed tomography (CT) perfusion or magnetic resonance imaging is associated with RFI, mortality, or symptomatic intracranial hemorrhage (sICH) compared with noncontrast CT selected patients., Methods: The CLEAR study (CT for Late Endovascular Reperfusion) was a multicenter, retrospective cohort study of stroke patients undergoing thrombectomy in the extended time window. Inclusion criteria for this analysis were baseline National Institutes of Health Stroke Scale score ≥6, internal carotid artery, M1 or M2 segment occlusion, prestroke modified Rankin Scale score of 0 to 2, time-last-seen-well to treatment 6 to 24 hours, and successful reperfusion (modified Thrombolysis in Cerebral Infarction 2c-3)., Results: Of 2304 patients in the CLEAR study, 715 patients met inclusion criteria. Of these, 364 patients (50.9%) showed RFI (ie, mRS score of 3-6 at 90 days despite successful reperfusion), 37 patients (5.2%) suffered sICH, and 127 patients (17.8%) died within 90 days. Neither imaging selection modality for thrombectomy candidacy (noncontrast CT versus CT perfusion versus magnetic resonance imaging) was associated with RFI, sICH, or mortality. Older age, higher baseline National Institutes of Health Stroke Scale, higher prestroke disability, transfer to a comprehensive stroke center, and a longer interval to puncture were associated with RFI. The presence of M2 occlusion and higher baseline Alberta Stroke Program Early CT Score were inversely associated with RFI. Hypertension was associated with sICH., Conclusions: RFI is a frequent phenomenon in the extended time window. Neither magnetic resonance imaging nor CT perfusion selection for mechanical thrombectomy was associated with RFI, sICH, and mortality compared to noncontrast CT selection alone., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT04096248.

Background: The lack of superiority of anticoagulation over antiplatelet therapy in embolic stroke of undetermined source (ESUS) may be in part due to the misclassification of radiographic ESUS patterns as cardioembolic. In this imaging analysis, we sought to differentiate clinical and radiographic patterns of ESUS patients from patterns in patients with a highly probable cardioembolic source., Materials & Methods: A prospective registry of consecutive adults with acute infarction on diffusion-weighted magnetic resonance imaging was queried. Patients with infarctions due to small vessel disease, large vessel disease, and other causes were excluded. Multivariable logistic regression was used to identify independent predictors of two potentially embolic patterns: (1) multifocal and (2) cortical lesions, comparing patients with ESUS against those with atrial fibrillation (AF)., Results: Among 1243 screened patients, 343 (27.6%) experienced strokes due to ESUS or AF. Prior to the index stroke, patients with AF as compared to ESUS were older (median 75 vs. 65, p<0.01) and had more heart failure (25.9% vs. 8.4%, p<0.01). The odds of multifocal infarction were the same between patients with ESUS and both AF subtypes (p>0.05), however, cortical involvement was more associated with both AF versus ESUS (77.7% vs. 65.7%, P=0.02). A higher Fazekas grade of white matter disease was inversely associated with cortical infarction among included patients (aOR 0.77, 95% CI 0.62-0.96)., Conclusion: Cortical infarctions were twice as common among patients with AF versus ESUS. Subcortical infarct topography was strongly associated with chronic microvascular ischemic changes and therefore may not represent embolic phenomena. Larger-scale investigations are warranted to discern whether large or multifocal subcortical infarcts ought to be excluded from the ESUS designation., Competing Interests: Conflicts of Interest/Disclosures Dr. Siegler reports consulting fees (Ceribell) and for medicolegal work, and speakers bureau (AstraZeneca), all of which are unrelated to the present work., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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.)

Background and Purpose: Infarct topology is a key determinant in classification of a stroke as potentially embolic, with cortical and multifocal lesions being presumed embolic. Whether isolated subcortical multifocal infarcts are likely embolic has not been well studied., Methods: A prospective, single-center cohort study of consecutive patients with acute multifocal strokes confirmed on diffusion-weighting imaging (DWI) was queried, and patients compared according to the presence of isolated subcortical infarct topology versus cortical ± subcortical topology. Descriptive statistics and multivariable logistic regression were used to determine independent predictors of cryptogenic, subcortical infarcts., Results: Of 1739 patients screened, 743 had complete diagnostic testing with DWI evidence of acute infarction, 183 (24.6%) of whom had a multifocal stroke pattern. Isolated subcortical involvement was disproportionate among patients with ESUS (64.9%) when compared to patients with cardioembolic (24.3%) or large vessel disease (10.8%, p<0.01). Following multivariable adjustment, independent predictors of isolated subcortical multifocal infarction were milder strokes (OR 0.94, 95%CI 0.89-0.98) and higher grade Fazekas score (OR 2.32, 95%CI 1.02-5.29), while cardioembolism (OR 0.30, 95%CI 0.08-1.13) and large vessel disease (OR 0.27, 95%CI 0.08-0.91) remained inversely associated (as compared to ESUS)., Conclusions: These data suggest that multifocal subcortical infarctions are less likely to have an associated proximal embolic source than multifocal infarctions with cortical involvement. The strong association with chronic microvascular disease suggests this topology is more consistent with acute-on-chronic microvascular injury rather than an occult embolic source., Competing Interests: Declaration of competing interest Dr. Siegler reports consulting fees for Ceribell, speakers bureau for AstraZeneca, unrelated to the present work. The remaining authors report no competing interests.., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Endovascular treatment (EVT) for cerebral vein thrombosis (CVT) has not been proven to be more effective than anticoagulation based on recent results of the Thrombolysis or Anticoagulation for Cerebral Venous Thrombosis (TO-ACT) randomized clinical trial., Objective: To compare outcomes of EVT vs medical management in CVT., Methods: We compared EVT vs medical management in a retrospective multinational cohort of consecutive patients with CVT across 4 countries (USA, Italy, Switzerland, and New Zealand) and 27 sites (2015-2020), using propensity score matching (PSM) and inverse probability treatment weighting (IPTW), and meta-analyzed these results with the TO-ACT trial. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] 0-1) at 90 days., Results: Of the 987 patients, the mean age was 45.7 ± 16.9 years and 79 (8%) underwent EVT. With PSM (n = 124), there were no major differences in clinical or imaging features between groups other than a higher proportion of female patients receiving EVT (81% vs 65%, P = .04). There was no difference in the primary outcome with PSM (odds ratio [OR] 1.48, 95% CI, 0.55-3.96) or IPTW (OR 1.02, 95% CI, 0.34-3.06). EVT was associated with a higher 90-day shift in modified Rankin Scale (OR 2.00, 95% CI, 1.01-3.98) and mortality with IPTW (OR 4.60, 95% CI, 1.10-19.23) but no other differences in secondary outcomes with PSM or IPTW. A meta-analysis of primary and secondary outcomes from TO-ACT and PSM patients from anticoagulation in the treatment of cerebral venous thrombosis also showed no significant association with EVT in primary or secondary outcomes., Conclusion: In this large observational cohort, there was no evidence of benefit with EVT for CVT. These findings corroborate the results from the TO-ACT trial., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Since 2015, a series of endovascular trials transformed the management of patients with large vessel occlusion stroke. Most thrombectomy trials used restrictive eligibility criteria to optimize the chances of showing that thrombectomy could work. The problem arises when generalizing trial results into evidence-based recommendations. Many organizations, oblivious of this problem, translated verbatim restrictive trial eligibility criteria into authoritative guidelines, which limit the use of thrombectomy to highly selected patients. The clinical problem becomes as follows: what to do for all other stroke patients equally in need of care? The cycle of restrictive trial eligibility criteria, corresponding restrictive guidelines, observational studies of unvalidated practices showing other patients benefit, a new trial is needed, has been repeated often. Thrombectomy trials ought to have included all patients that could potentially benefit. If the signal that was looked for by restricting eligibility is at risk of being lost in the noise generated by the heterogeneity of patients, D. Sackett proposed a solution: to use the same criteria, not to select some patients and exclude others but to prespecify the subgroup of patients most likely to benefit. In this commentary, we propose a tiered approach, where the boundaries of treatment beneficiaries can be more rigorously tested and confirmed. Identification of these patients before the development of guidelines, which would have otherwise neglected these individuals, may open innumerable treatment opportunities to those who will instead be denied of them.

Background: Embolic stroke of undetermined source (ESUS) accounts for up to 20% of all strokes. Potential contributors to ESUS include patent foramen ovale (PFO) and non-stenotic plaque (<50%, NSP) of the ipsilateral internal carotid artery (ICA). To better differentiate these as unique mechanisms, we explored the prevalence of each in a multicenter observational cohort., Methods: A retrospective multicenter cohort of consecutive patients with ESUS was queried (2015-2021). Patients with unilateral, anterior circulation ESUS who had a computed tomography angiography neck scan and a transthoracic echocardiogram (TTE) and/or transesophageal echocardiogram (TEE) with adequate visualization of a PFO were included. Patients with prior carotid stent, endarterectomy or alternative etiologies were excluded from the study. Descriptive statistics were used to characterize patients with and without PFO, with multivariable logistic regression used to predict the presence of a PFO based on clinicoradiographic factors as well as degree of luminal stenosis and ipsilateral plaque thickness >3mm, based on previously published thresholds of clinical relevance., Results: Of the 234 included patients with unilateral anterior ESUS and adequate TTE or TEE, 17 (7.3%) had a PFO and 64 (27.4%) had ≥3mm of ipsilateral ICA plaque. Patients with PFO had significantly less NSP and less ipsilateral cervical ICA stenosis (0% [IQR 0-0%] vs. 0% [IQR 0-50%], p=0.03; Table). After adjustment for all predictors of PFO in multivariable regression (p<0.1: Hispanic ethnicity and ipsilateral plaque thickness), ipsilateral NSP was independently associated with a 62% lower odds of harboring a PFO (OR adj  per 1cm of plaque 0.48, 95%CI 0.25-0.94). No patients with a PFO had ≥3mm of ipsilateral ICA plaque., Conclusion: Ipsilateral NSP is more common in ESUS patients without a PFO. While this study is limited by the small PFO event rate, it supports the notion that NSP and PFO may be independent contributors to ESUS., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: We aimed to determine which factors influence recovery in stroke patients with pre-existing disability, as these patients are often excluded from acute treatment trials., Materials and Methods: A prospective stroke center registry of admitted patients from 2019-2021 with acute stroke was queried for patients with pre-stroke modified Rankin Scale (mRS) of 0-4. Multivariable logistic regression was used to estimate odds of functional recovery at 90 days (mRS 0-2, or return to pre-stroke mRS)., Results: Of 1228 patients, 856 (70%) included patients had pre-stroke mRS 0-4 and 90-day follow-up mRS. The median age was 68y (IQR 59-78), with a median National Institutes of Health Stroke Scale (NIHSS) of 5 (IQR 2-17). Compared to those with mRS 0-1 (n = 596), patients with pre-stroke mRS of 2 (n = 126), 3 (n = 96), or 4 (n = 38) were less likely to achieve functional recovery in univariate analysis. After multivariable adjustment, odds of functional recovery were significantly lower for patients with pre-stroke mRS of 2 (adjusted odds ratio [OR adj ] 0.45, 95% confidence interval [CI] 0.28-0.72), but not those with pre-stroke mRS of 3 (OR adj 1.14, 95%CI 0.66-1.97) or 4 (OR adj 0.50, 95%CI 0.21-1.19). Older age (OR adj per year 0.97, 95%CI 0.95-0.97) and higher NIHSS (OR adj per point 0.89, 95%CI 0.88-0.91) were associated with lower odds of functional recovery, while thrombolysis (OR adj 2.43, 95%CI 1.42-4.15) and a cryptogenic stroke mechanism (OR adj 1.57, 95%CI 1.07-2.31) were protective., Conclusions: Recovery of patients with pre-existing disability was driven by age and stroke severity. Thrombolysis remained predictive of recovery irrespective of age, stroke severity, and pre-stroke disability., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: We aimed to evaluate door-to-puncture time (DPT) and door-to-recanalization time (DRT) without directing healthcare by neuro-interventionalist support in the emergency department (ED) by workflow optimization and improving patients' outcomes., Methods: Records of 98 consecutive ischemic stroke patients who had undergone endovascular therapy (EVT) between 2018 to 2021 were retrospectively reviewed in a single-center study. Patients were divided into three groups: pre-intervention (2018-2019), interim-intervention (2020), and post-intervention (January 1 st 2021 to August 16 th , 2021). We compared door-to-puncture time, door-to-recanalization time (DRT), puncture-to-recanalization time (PRT), last known normal time to-puncture time (LKNPT), and patient outcomes (measured by 3 months modified Rankin Scale) between three groups using descriptive statistics., Results: Our findings indicate that process optimization measures could shorten DPT, DRT, PRT, and LKNPT. Median LKNPT was shortened by 70 min from 325 to 255 min(P < 0.05), and DPT was shortened by 119 min from 237 to 118 min. DRT shortened by 132 min from 338 to 206 min, and PRT shortened by 33 min from 92 to 59 min from the pre-intervention to post-intervention groups (all P < 0.05). Only 21.4% of patients had a favorable outcome in the pre-intervention group as compared to 55.6% in the interventional group (P= 0.026)., Conclusion: This study demonstrated that multidisciplinary cooperation was associated with shortened DPT, DRT, PRT, and LKNPT despite challenges posed to the healthcare system such as the COVID-19 pandemic. These practice paradigms may be transported to other stroke centers and healthcare providers to improve endovascular time metrics and patient outcomes., (© 2022. The Author(s).)

Background: Nonstenotic carotid plaque and undetected atrial fibrillation are potential mechanisms of embolic stroke of undetermined source (ESUS), but it is unclear which is more likely to be the contributing stroke mechanism. We explored the relationship between left atrial enlargement (LAE) and nonstenotic carotid plaque across age ranges in an ESUS population., Methods: A retrospective multicenter cohort of consecutive patients with unilateral, anterior circulation ESUS was queried (2015 to 2021). LAE and plaque thickness were determined by transthoracic echocardiography and computed tomography angiography, respectively. Descriptive statistics were used to compare plaque features in relation to age and left atrial dimensions., Results: Among the 4155 patients screened, 273 (7%) met the inclusion criteria. The median age was 65 years (interquartile range [IQR] 54-74), 133 (48.7%) were female, and the median left atrial diameter was 3.5 cm (IQR 3.1-4.1). Patients with any LAE more frequently had hypertension (85.9% versus 67.2%, P <0.01), diabetes (41.0% versus 25.6%, P =0.01), dyslipidemia (56.4% versus 40.0%, P =0.01), and coronary artery disease (22.8% versus 11.3%, P =0.02). Carotid plaque thickness was greater ipsilateral versus contralateral to the stroke hemisphere in the overall cohort (median 1.9 mm [IQR 0-3] versus 1.5 mm [IQR 0-2.6], P <0.01); however, this was largely driven by the subgroup of patients without any LAE (median 1.8 mm [IQR 0-2.9] versus 1.5 mm [IQR 0-2.5], P <0.01). Compared with patients ≥70 years, younger patients had more carotid plaque ipsilateral versus contralateral (mean difference 0.42 mm±1.24 versus 0.08 mm±1.54, P =0.047) and less moderate-to-severe LAE (6.3% versus 15.3%, P =0.02)., Conclusions: Younger patients with ESUS had greater prevalence of ipsilateral nonstenotic plaque, while the elderly had more LAE. The differential effect of age on the probability of specific mechanisms underlying ESUS should be considered in future studies.

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.)

Introduction: Ipsilateral nonstenotic (<50%) internal carotid artery (ICA) plaque, cardiac atriopathy, and patent foramen ovale (PFO) may account for a substantial proportion of embolic stroke of undetermined source (ESUS)., Methods: Consecutive stroke patients at our center (2019-2021) with unilateral, anterior circulation ESUS were categorized into the following mutually exclusive etiologies: (1) nonstenotic ipsilateral ICA plaque (NSP, ≥3mm in maximal axial diameter), (2) sex-adjusted mod-to-severe left atrial enlargement (LAE), (3) PFO, and (4) "occult ESUS" (patients who failed to meet criteria for these 3 groups). Descriptive statistics and multivariable logistic regression were used to model group characteristics., Results: Of 132 included patients, the median age was 65 (IQR 56-73), 74 (56%) of whom were White, and 54 (41%) were female. Twenty-one patients (16%) had NSP proximal to the infarct territory, 17 (13%) had LAE, 9 (7%) had a PFO, and 85 (64%) had no other mechanism. Patients with LAE were older (p=0.004), and had more frequent intracranial occlusions of the internal carotid and proximal middle cerebral artery (p=0.048), while tobacco use was most commonly found among patients with NSP (75%) when compared to other ESUS groups (p=0.02). Five of 9 patients with LAE who underwent outpatient telemetry had paroxysmal atrial fibrillation (56%), while zero patients with PFO or NSP had paroxysmal atrial fibrillation (p=0.005). Older age (adjusted OR [aOR] 1.05, 95%CI 1.03-1.07), coronary artery disease (aOR 3.22, 95%CI 1.61-6.44) and hypertension (aOR 2.16, 95%CI 1.14-4.06) were independently associated with LAE, while only tobacco use was associated with NSP when compared to other ESUS subclassifiers (OR 3.18, 95%CI 1.08-0.42). Age and tobacco use were both inversely associated with PFO (aOR 0.93, 95%CI 0.88-0.98, and aOR 0.10, 95%CI 0.02-0.90, respectively)., Conclusions: Certain clinical and radiographic features may be useful in predicting the proximal source of occult cerebral emboli, and can be used for cost-effective outpatient diagnostic testing., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: To analyse the clinical characteristics of COVID-19 with acute ischaemic stroke (AIS) and identify factors predicting functional outcome., Methods: Multicentre retrospective cohort study of COVID-19 patients with AIS who presented to 30 stroke centres in the USA and Canada between 14 March and 30 August 2020. The primary endpoint was poor functional outcome, defined as a modified Rankin Scale (mRS) of 5 or 6 at discharge. Secondary endpoints include favourable outcome (mRS ≤2) and mortality at discharge, ordinal mRS (shift analysis), symptomatic intracranial haemorrhage (sICH) and occurrence of in-hospital complications., Results: A total of 216 COVID-19 patients with AIS were included. 68.1% (147/216) were older than 60 years, while 31.9% (69/216) were younger. Median [IQR] National Institutes of Health Stroke Scale (NIHSS) at presentation was 12.5 (15.8), and 44.2% (87/197) presented with large vessel occlusion (LVO). Approximately 51.3% (98/191) of the patients had poor outcomes with an observed mortality rate of 39.1% (81/207). Age >60 years (aOR: 5.11, 95% CI 2.08 to 12.56, p<0.001), diabetes mellitus (aOR: 2.66, 95% CI 1.16 to 6.09, p=0.021), higher NIHSS at admission (aOR: 1.08, 95% CI 1.02 to 1.14, p=0.006), LVO (aOR: 2.45, 95% CI 1.04 to 5.78, p=0.042), and higher NLR level (aOR: 1.06, 95% CI 1.01 to 1.11, p=0.028) were significantly associated with poor functional outcome., Conclusion: There is relationship between COVID-19-associated AIS and severe disability or death. We identified several factors which predict worse outcomes, and these outcomes were more frequent compared to global averages. We found that elevated neutrophil-to-lymphocyte ratio, rather than D-Dimer, predicted both morbidity and mortality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: We have demonstrated in a multicenter cohort that the COVID-19 pandemic has led to a delay in intravenous thrombolysis (IVT) among stroke patients. Whether this delay contributes to meaningful short-term outcome differences in these patients warranted further exploration., Methods: We conducted a nested observational cohort study of adult acute ischemic stroke patients receiving IVT from 9 comprehensive stroke centers across 7 U.S states. Patients admitted prior to the COVID-19 pandemic (1/1/2019-02/29/2020) were compared to patients admitted during the early pandemic (3/1/2020-7/31/2020). Multivariable logistic regression was used to estimate the effect of IVT delay on discharge to hospice or death, with treatment delay on admission during COVID-19 included as an interaction term., Results: Of the 676 thrombolysed patients, the median age was 70 (IQR 58-81) years, 313 were female (46.3%), and the median NIHSS was 8 (IQR 4-16). Longer treatment delays were observed during COVID-19 (median 46 vs 38 min, p = 0.01) and were associated with higher in-hospital death/hospice discharge irrespective of admission period (OR per hour 1.08, 95% CI 1.01-1.17, p = 0.03). This effect was strengthened after multivariable adjustment (aOR 1.15, 95% CI 1.07-1.24, p < 0.001). There was no interaction of treatment delay on admission during COVID-19 (p interaction  = 0.65). Every one-hour delay in IVT was also associated with 7% lower odds of being discharged to home or acute inpatient rehabilitation facility (aOR 0.93, 95% CI 0.89-0.97, p < 0.001)., Conclusion: Treatment delays observed during the COVID-19 pandemic led to greater early mortality and hospice care, with a lower probability of discharge to home/rehabilitation facility. There was no effect modification of treatment delay on admission during the pandemic, indicating that treatment delay at any time contributes similarly to these short-term outcomes., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Importance: Advanced imaging for patient selection in mechanical thrombectomy is not widely available., Objective: To compare the clinical outcomes of patients selected for mechanical thrombectomy by noncontrast computed tomography (CT) vs those selected by computed tomography perfusion (CTP) or magnetic resonance imaging (MRI) in the extended time window., Design, Setting, and Participants: This multinational cohort study included consecutive patients with proximal anterior circulation occlusion stroke presenting within 6 to 24 hours of time last seen well from January 2014 to December 2020. This study was conducted at 15 sites across 5 countries in Europe and North America. The duration of follow-up was 90 days from stroke onset., Exposures: Computed tomography with Alberta Stroke Program Early CT Score, CTP, or MRI., Main Outcomes and Measures: The primary end point was the distribution of modified Rankin Scale (mRS) scores at 90 days (ordinal shift). Secondary outcomes included the rates of 90-day functional independence (mRS scores of 0-2), symptomatic intracranial hemorrhage, and 90-day mortality., Results: Of 2304 patients screened for eligibility, 1604 patients were included, with a median (IQR) age of 70 (59-80) years; 848 (52.9%) were women. A total of 534 patients were selected to undergo mechanical thrombectomy by CT, 752 by CTP, and 318 by MRI. After adjustment of confounders, there was no difference in 90-day ordinal mRS shift between patients selected by CT vs CTP (adjusted odds ratio [aOR], 0.95 [95% CI, 0.77-1.17]; P = .64) or CT vs MRI (aOR, 0.95 [95% CI, 0.8-1.13]; P = .55). The rates of 90-day functional independence (mRS scores 0-2 vs 3-6) were similar between patients selected by CT vs CTP (aOR, 0.90 [95% CI, 0.7-1.16]; P = .42) but lower in patients selected by MRI than CT (aOR, 0.79 [95% CI, 0.64-0.98]; P = .03). Successful reperfusion was more common in the CT and CTP groups compared with the MRI group (474 [88.9%] and 670 [89.5%] vs 250 [78.9%]; P < .001). No significant differences in symptomatic intracranial hemorrhage (CT, 42 [8.1%]; CTP, 43 [5.8%]; MRI, 15 [4.7%]; P = .11) or 90-day mortality (CT, 125 [23.4%]; CTP, 159 [21.1%]; MRI, 62 [19.5%]; P = .38) were observed., Conclusions and Relevance: In patients undergoing proximal anterior circulation mechanical thrombectomy in the extended time window, there were no significant differences in the clinical outcomes of patients selected with noncontrast CT compared with those selected with CTP or MRI. These findings have the potential to widen the indication for treating patients in the extended window using a simpler and more widespread noncontrast CT-only paradigm.

Background: Unprecedented workflow shifts during the coronavirus disease 2019 (COVID-19) pandemic have contributed to delays in acute care delivery, but whether it adversely affected endovascular thrombectomy metrics in acute large vessel occlusion (LVO) is unknown., Methods: We performed a retrospective review of observational data from 14 comprehensive stroke centers in nine US states with acute LVO. EVT metrics were compared between March to July 2019 against March to July 2020 (primary analysis), and between state-specific pre-peak and peak COVID-19 months (secondary analysis), with multivariable adjustment., Results: Of the 1364 patients included in the primary analysis (51% female, median NIHSS 14 [IQR 7-21], and 74% of whom underwent EVT), there was no difference in the primary outcome of door-to-puncture (DTP) time between the 2019 control period and the COVID-19 period (median 71 vs 67 min, P=0.10). After adjustment for variables associated with faster DTP, and clustering by site, there remained a trend toward shorter DTP during the pandemic (β adj =-73.2, 95% CI -153.8-7.4, Pp=0.07). There was no difference in DTP times according to local COVID-19 peaks vs pre-peak months in unadjusted or adjusted multivariable regression (β adj =-3.85, 95% CI -36.9-29.2, P=0.80). In this final multivariable model (secondary analysis), faster DTP times were significantly associated with transfer from an outside institution (β adj =-46.44, 95% CI -62.8 to - -30.0, P<0.01) and higher NIHSS (β adj =-2.15, 95% CI -4.2to - -0.1, P=0.05)., Conclusions: In this multi-center study, there was no delay in EVT among patients treated for intracranial occlusion during the COVID-19 era compared with the pre-COVID era., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Cryptogenic stroke comprises approximately 25% of all cases of ischemic stroke. The diagnostic evaluation of these patients remains a challenge in clinical practice. Transesophageal echocardiography (TEE) has been shown to have superior diagnostic accuracy in identifying potential cardioembolic sources of ischemic stroke when compared to transthoracic echocardiography (TTE). However, there has been inconsistent data on the management implications of these new cardiac findings. The addition of TEE to the comprehensive stroke evaluation will better identify potential cardiac sources of embolism (CSE) and will result in significant management changes. A prospective registry of consecutively admitted patients with acute ischemic stroke (1/1/2015-8/10/2020) was retrospectively queried. Patients 18 to 60 years of age with stroke due to mechanisms other than large or small vessel disease, or atrial fibrillation were eligible for inclusion. The primary outcome was any high-risk CSE identified on TEE following unrevealing TTE. Of the 2,404 consecutive stroke patients evaluated during the study period, 263 (11%) met inclusion criteria and the median age was 53 (IQR 46-57). TEE was performed in 108 patients (41%). A high-risk CSE was identified in 36 patients (33%), the majority of which were PFOs (n = 29). TEE led to a clinical management change in 14 patients (39%) after identification of a high-risk CSE; 6 underwent PFO closure and 8 had adjustment to their antithrombotic therapy. The addition of TEE to the comprehensive stroke evaluation led to the identification of a high-risk CSE in one in three patients resulting in significant management changes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Intracerebral hemorrhage (ICH) occurs in ~20%-30% of stroke patients undergoing endovascular therapy (EVT). However, there is conflicting evidence regarding the effect of asymptomatic ICH (aICH) on post-EVT outcomes. We sought to evaluate the effect of aICH on immediate and 90-day post-EVT neurological outcomes., Methods: In this post-hoc analysis of the multicenter, prospective Blood Pressure after Endovascular Therapy (BEST) study we identified subjects with ICH following EVT. This population was divided into no ICH, aICH, and symptomatic ICH (sICH). Associations with 90-day modified Rankin Scale (mRS) dichotomized by functional independence (0-2 vs 3-6) and early neurological recovery (ENR) were determined using univariate/multivariate logistic regression models., Results: Of 485 patients enrolled in BEST, 446 had 90-day follow-up data available. 92 (20.6%) developed aICH, and 18 (4%) developed sICH. Compared with those without ICH, aICH was not associated with worse 90-day outcome or lower ENR (OR 0.84 [0.53-1.35], P=0.55, aOR 0.84 [0.48-1.44], P=0.53 for 90-day mRS 0-2; OR 0.77 [0.48-1.23], P=0.34, aOR 0.72 [0.43-1.22] for ENR). aICH was not associated with 90-day outcome or ENR in patients with mTICI ≥2 b (OR 0.78 [0.48-1.26], P=0.33 for 90-day mRS 0-2; OR 0.89 [0.69-1.12], P=0.15 for ENR). A higher proportion of patients with aICH had mTICI ≥2 b than those without ICH (97%vs 87%, P=0.01)., Conclusions: aICH was not associated with worse outcomes in patients with large-vessel stroke treated with EVT. aICH was more frequent in patients with successful recanalization. Further validation of our findings in large cohort studies of EVT-treated patients is warranted., Competing Interests: Competing interests: RVC receives research grants from Medtronic and Cerenovus. PK receives research grant support from Cerenovus. EAM reports grant support from NIH/NINDS (K23NS113858). Remaining authors have no disclosures., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: The National Institutes of Health Stroke Scale (NIHSS) measured at an early time point is an appealing surrogate marker for long-term functional outcome of stroke patients treated with endovascular therapy. However, definitions and analytical methods for an early NIHSS-based outcome measure that optimize power and precision in clinical studies are not well-established., Methods: In this post-hoc analysis of our prospective observational study that enrolled endovascular therapy-treated patients at 12 comprehensive stroke centers across the US, we compared the ability of 24-hour NIHSS, ΔNIHSS (baseline minus 24-hour NIHSS), and percentage change (NIHSS×100/baseline NIHSS), analyzed as continuous and dichotomous measures, to predict 90-day modified Rankin Scale (mRS) using logistic regression (adjusted for age, baseline NIHSS, glucose, hypertension, Alberta Stroke Program Early CT Score, time to recanalization, recanalization status, and intravenous thrombolysis) and Spearman ρ., Results: Of 485 patients in the BEST (Blood Pressure After Endovascular Stroke Therapy) cohort, 446 (92%) with 90-day follow-up data were included. An absolute 24-hour NIHSS, adjusted for baseline in multivariable modeling, had the highest predictive power of all definitions evaluated (aR 2 0.368 and adjusted odds ratio 0.79 [0.75-0.84], P <0.001 for mRS score 0-2; aR 2 0.444 and adjusted odds ratio 0.84 [0.8-0.86] for ordinal mRS). For predicting mRS score of 0-2 with a cut point, the second most efficient approach, the optimal threshold for 24-hour NIHSS score was ≤7 (sensitivity 80.1%, specificity 80.4%; adjusted odds ratio 12.5 [7.14-20], P <0.001), followed by percent change in NIHSS (sensitivity 79%, specificity 58.5%; adjusted odds ratio 4.55 [2.85-7.69], P <0.001)., Conclusions: Twenty-four-hour NIHSS, adjusted for baseline, was the strongest predictor of both dichotomous and ordinal 90-day mRS outcomes for endovascular therapy-treated patients. A dichotomous 24-hour NIHSS score of ≤7 was the second-best predictor. Although ΔNIHSS, continuous and dichotomized at ≥4, predicted 90-day outcomes, absolute 24-hour NIHSS definitions performed better.

Objective: To characterize differences in disposition arrangement among rehab-eligible stroke patients at a Comprehensive Stroke Center before and during the COVID-19 pandemic., Materials and Methods: We retrospectively analyzed a prospective registry for demographics, hospital course, and discharge dispositions of rehab-eligible acute stroke survivors admitted 6 months prior to (10/2019-03/2020) and during (04/2020-09/2020) the COVID-19 pandemic. The primary outcome was discharge to an inpatient rehabilitation facility (IRF) as opposed to other facilities using descriptive statistics, and IRF versus home using unadjusted and adjusted backward stepwise logistic regression., Results: Of the 507 rehab-eligible stroke survivors, there was no difference in age, premorbid disability, or stroke severity between study periods (p>0.05). There was a 9% absolute decrease in discharges to an IRF during the pandemic (32.1% vs. 41.1%, p=0.04), which translated to 38% lower odds of being discharged to IRF versus home in unadjusted regression (OR 0.62, 95%CI 0.42-0.92, p=0.016). The lower odds of discharge to IRF persisted in the multivariable model (aOR 0.16, 95%CI 0.09-0.31, p<0.001) despite a significant increase in discharge disability (median discharge mRS 4 [IQR 2-4] vs. 2 [IQR 1-3], p<0.001) during the pandemic., Conclusions: Admission for stroke during the COVID-19 pandemic was associated with a significantly lower probability of being discharged to an IRF. This effect persisted despite adjustment for predictors of IRF disposition, including functional disability at discharge. Potential reasons for this disparity are explored., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The COVID-19 pandemic led to profound changes in the organization of health care systems worldwide., Aims: We sought to measure the global impact of the COVID-19 pandemic on the volumes for mechanical thrombectomy, stroke, and intracranial hemorrhage hospitalizations over a three-month period at the height of the pandemic (1 March-31 May 2020) compared with two control three-month periods (immediately preceding and one year prior)., Methods: Retrospective, observational, international study, across 6 continents, 40 countries, and 187 comprehensive stroke centers. The diagnoses were identified by their ICD-10 codes and/or classifications in stroke databases at participating centers., Results: The hospitalization volumes for any stroke, intracranial hemorrhage, and mechanical thrombectomy were 26,699, 4002, and 5191 in the three months immediately before versus 21,576, 3540, and 4533 during the first three pandemic months, representing declines of 19.2% (95%CI, -19.7 to -18.7), 11.5% (95%CI, -12.6 to -10.6), and 12.7% (95%CI, -13.6 to -11.8), respectively. The decreases were noted across centers with high, mid, and low COVID-19 hospitalization burden, and also across high, mid, and low volume stroke/mechanical thrombectomy centers. High-volume COVID-19 centers (-20.5%) had greater declines in mechanical thrombectomy volumes than mid- (-10.1%) and low-volume (-8.7%) centers (p < 0.0001). There was a 1.5% stroke rate across 54,366 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.9% (784/20,250) of all stroke admissions., Conclusion: The COVID-19 pandemic was associated with a global decline in the volume of overall stroke hospitalizations, mechanical thrombectomy procedures, and intracranial hemorrhage admission volumes. Despite geographic variations, these volume reductions were observed regardless of COVID-19 hospitalization burden and pre-pandemic stroke/mechanical thrombectomy volumes.