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Background and Objectives: This study aimed to compare outcomes of low Alberta Stroke Program Early Computed Tomography Score (ASPECTS) patients with stroke who underwent mechanical thrombectomy (MT) within 6 hours or 6 to 24 hours after stroke onset., Methods: A retrospective cohort study was conducted using data from a large multicenter international registry from 2013 to 2023. Patients with low ASPECTS (2-5) who underwent MT for anterior circulation intracranial large vessel occlusion were included. A propensity matching analysis was conducted for patients presented in the early (<6 hours) vs late (6-24 hours) time window after symptom onset or last known normal., Results: Among the 10 229 patients who underwent MT, 274 met the inclusion criteria. 122 (44.5%) patients were treated in the late window. Early window patients were older (median age, 74 years [IQR, 63-80] vs 66.5 years [IQR, 54-77]; P < .001), had lower proportion of female patients (40.1% vs 54.1%; P = .029), higher median admission National Institutes of Health Stroke Scale score (20 [IQR, 16-24] vs 19 [IQR, 14-22]; P = .004), and a higher prevalence of atrial fibrillation (46.1% vs 27.3; P = .002). Propensity matching yielded a well-matched cohort of 84 patients in each group. Comparing the matched cohorts showed there was no significant difference in acceptable outcomes at 90 days between the 2 groups (odds ratio = 0.90 [95% CI = 0.47-1.71]; P = .70). However, the rate of symptomatic ICH was significantly higher in the early window group compared with the late window group (odds ratio = 2.44 [95% CI = 1.06-6.02]; P = .04)., Conclusion: Among patients with anterior circulation large vessel occlusion and low ASPECTS, MT seems to provide a similar benefit to functional outcome for patients presenting <6 hours or 6 to 24 hours after onset., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Objective: We evaluated the efficacy of endovascular thrombectomy (EVT) on the functional outcome of patients with acute basilar artery occlusion and low posterior circulation acute stroke prognosis early computed tomography score (PC-ASPECTS)., Methods: We identified patients with acute ischemic stroke due to basilar artery occlusion and PC-ASPECTS of 6 or less, presenting within 24 h between August 2008 and April 2022. The primary outcome was a favorable functional outcome, defined as a modified Rankin Scale (mRS) score of 0-3 at 90 days. The secondary outcomes included an mRS score of 0-2, a favorable shift in the ordinal mRS scale, the occurrence of symptomatic intracranial hemorrhage (sICH), and mortality at 90 days. We compared the outcome of patients treated with EVT and those without EVT, using the inverse probability of treatment weighting methods., Results: Out of 566 patients, 55.5% received EVT. In the EVT group, 106 (33.8%) achieved favorable outcomes, compared to 56 patients (22.2%) in the conservative group. EVT significantly increased the likelihood of achieving a favorable outcome compared to conservative treatment (relative risk [RR] 1.39, 95% confidence interval [CI], 1.11-1.74, p = 0.004). EVT was associated with a favorable shift in the mRS (RR 1.85, 95% CI, 1.49-2.29, p < 0.001) and reduced mortality without an increase in the risk of sICH. It did not have an impact on achieving an mRS score of 0-2., Interpretation: Patients with acute basilar artery occlusion and a PC-ASPECTS of 6 or less might benefit from EVT without an increasing sICH. ANN NEUROL 2024;95:788-799., (© 2024 American Neurological Association.)

Background: Data on systolic blood pressure (SBP) trajectories in the first 24 hours after endovascular thrombectomy (EVT) in acute ischemic stroke are limited. We sought to identify these trajectories and their relationship to outcomes., Methods: We combined individual-level data from 5 studies of patients with acute ischemic stroke who underwent EVT and had individual blood pressure values after the end of the procedure. We used group-based trajectory analysis to identify the number and shape of SBP trajectories post-EVT. We used mixed effects regression models to identify associations between trajectory groups and outcomes adjusting for potential confounders and reported the respective adjusted odds ratios (aORs) and common odds ratios., Results: There were 2640 total patients with acute ischemic stroke included in the analysis. The most parsimonious model identified 4 distinct SBP trajectories, that is, general directional patterns after repeated SBP measurements: high, moderate-high, moderate, and low. Patients in the higher blood pressure trajectory groups were older, had a higher prevalence of vascular risk factors, presented with more severe stroke syndromes, and were less likely to achieve successful recanalization after the EVT. In the adjusted analyses, only patients in the high-SBP trajectory were found to have significantly higher odds of early neurological deterioration (aOR, 1.84 [95% CI, 1.20-2.82]), intracranial hemorrhage (aOR, 1.84 [95% CI, 1.31-2.59]), mortality (aOR, 1.75 [95% CI, 1.21-2.53), death or disability (aOR, 1.63 [95% CI, 1.15-2.31]), and worse functional outcomes (adjusted common odds ratio,1.92 [95% CI, 1.47-2.50])., Conclusions: Patients follow distinct SBP trajectories in the first 24 hours after an EVT. Persistently elevated SBP after the procedure is associated with unfavorable short-term and long-term outcomes., Competing Interests: Disclosures A.H. Katsanos serves as the PI for the Blood Pressure Management in Stroke Following Endovascular Treatment trial. The other authors report no conflicts.

Introduction: Data on the association between blood pressure variability (BPV) after endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) and outcomes are limited. We sought to identify whether BPV within the first 24 hours post EVT was associated with key stroke outcomes., Methods: We combined individual patient-data from five studies among AIS-patients who underwent EVT, that provided individual BP measurements after the end of the procedure. BPV was estimated as either systolic-BP (SBP) standard deviation (SD) or coefficient of variation (CV) over 24 h post-EVT. We used a logistic mixed-effects model to estimate the association [expressed as adjusted odds ratios (aOR)] between tertiles of BPV and outcomes of 90-day mortality, 90-day death or disability [modified Rankin Scale-score (mRS) > 2], 90-day functional impairment (⩾1-point increase across all mRS-scores), and symptomatic intracranial hemorrhage (sICH), adjusting for age, sex, stroke severity, co-morbidities, pretreatment with intravenous thrombolysis, successful recanalization, and mean SBP and diastolic-BP levels within the first 24 hours post EVT., Results: There were 2640 AIS-patients included in the analysis. The highest tertile of SBP-SD was associated with higher 90-day mortality (aOR:1.44;95% CI:1.08-1.92), 90-day death or disability (aOR:1.49;95% CI:1.18-1.89), and 90-day functional impairment (adjusted common OR:1.42;95% CI:1.18-1.72), but not with sICH (aOR:1.22;95% CI:0.76-1.98). Similarly, the highest tertile of SBP-CV was associated with higher 90-day mortality (aOR:1.33;95% CI:1.01-1.74), 90-day death or disability (aOR:1.50;95% CI:1.19-1.89), and 90-day functional impairment (adjusted common OR:1.38;95% CI:1.15-1.65), but not with sICH (aOR:1.33;95% CI:0.83-2.14)., Conclusions: BPV after EVT appears to be associated with higher mortality and disability, independently of mean BP levels within the first 24 h post EVT. BPV in the first 24 h may be a novel target to improve outcomes after EVT for AIS., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Katsanos serves as the PI for the Blood Pressure Management in Stroke Following Endovascular Treatment (DETECT) trial.

Background: The safety and efficacy of bridging therapy with intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) in patients with large core infarct has not been sufficiently studied. In this study, we compared the efficacy and safety outcomes between patients who received IVT+MT and those treated with MT alone., Methods: This is a retrospective analysis of the Stroke Thrombectomy Aneurysm Registry (STAR). Patients with Alberta Stroke Program Early CT Score (ASPECTS) ≤5 treated with MT were included in this study. Patients were divided into two groups based on pre-treatment IVT (IVT, no IVT). Propensity score matched analysis were used to compare outcomes between groups., Results: A total of 398 patients were included; 113 pairs were generated using propensity score matching analyses. Baseline characteristics were well balanced in the matched cohort. The rate of any intracerebral hemorrhage (ICH) was similar between groups in both the full cohort (41.4% vs 42.3%, P=0.85) and matched cohort (38.55% vs 42.1%, P=0.593). Similarly, the rate of significant ICH was similar between the groups (full cohort: 13.1% vs 16.9%, P=0.306; matched cohort: 15.6% vs 18.95, P=0.52). There was no difference in favorable outcome (90-day modified Rankin Scale 0-2) or successful reperfusion between groups. In an adjusted analysis, IVT was not associated with any of the outcomes., Conclusion: Pretreatment IVT was not associated with an increased risk of hemorrhage in patients with large core infarct treated with MT. Future studies are needed to assess the safety and efficacy of bridging therapy in patients with large core infarct., Competing Interests: Competing interests: MRL: Grants from the NIH (R01NS105692, R01NS088072, U24NS100654, UL1TR002319, R25NS079200) and the American Heart Association (18CDA34110295). Unrestricted educational grants from Medtronic, Stryker and Philips Volcano. Consultant for Medtronic. Minor equity/ownership interest in Proprio, Cerebrotech, Synchron. Adviser to Metis Innovative. AMS: Research support from Penumbra, Stryker, Medtronic, and Siemens. Consultant for Penumbra, Stryker, Terumo, and Arsenal. RMS: Grants from the NREF, Joe Niekro Foundation, Brain Aneurysm Foundation, Bee Foundation, the NIH (R01NS111119-01A1, UL1TR002736, KL2TR002737), the National Center for Advancing Translational Sciences, the National Institute on Minority Health and Health Disparities, and Medtronic. Consultant for Penumbra, Abbott, Medtronic, InNeuroCo and Cerenovus. JRM is on the editorial board of JNIS., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Recent clinical trials have shown that mechanical thrombectomy is superior to medical management for large vessel occlusion for up to 24 hours from onset. Our objective is to examine the safety and efficacy of thrombectomy beyond the standard of care window., Methods: A retrospective review was undertaken of the multicenter Stroke Thrombectomy and Aneurysm Registry (STAR). We identified patients who underwent mechanical thrombectomy for large vessel occlusion beyond 24 hours. We selected a matched control group from patients who underwent thrombectomy in the 6-24-hour window. We used functional independence at 3 months as our primary outcome measure., Results: We identified 121 patients who underwent thrombectomy beyond 24 hours and 1824 in the 6-24-hour window. We selected a 2:1 matched group of patients with thrombectomy 6-24 hours as a comparison group. Patients undergoing thrombectomy beyond 24 hours were less likely to be independent at 90 days (18 (18.8%) vs 73 (34.9%), P=0.005). They had higher odds of mortality at 90 days in the adjusted analysis (OR 2.34, P=0.023). Symptomatic intracerebral hemorrhage and other complications were similar in the two groups. In a multivariate analysis only lower number of attempts was associated with good outcomes (OR 0.27, P=0.022)., Conclusions: Mechanical thrombectomy beyond 24 hours appears to be safe and tolerable with no more hemorrhages or complications compared with standard of care thrombectomy. Outcomes and mortality in this time window are worse compared with an earlier time window, but the rates of good outcomes may justify this therapy in selected patients., Competing Interests: Competing interests: PK: consultant for Stryker NV and Imperative Care. On the editorial board of JNIS. DRG: Balt Italy: Consultant, Microvention Europe: Consultant, Penumbra Inc: Consultant. AMS: Penumbra: Research support, Consultant. Stryker: Research support, Consultant. Cerenovus: Consultant. Terumo: Consultant. IschemaView Inc/Rapid AI: Research support, Consultant. ASA: Consultant for Arsenal, Balt, Johnson and Johnson, Medtronic, Microvention, Penumbra, Scientia, Siemens, Stryker Research support from Balt, Medtronic, Microvention, Penumbra and Siemens Shareholder Azimuth, Bendit, Cerebrotech, Endostream, Magneto, Mentice, Neurogami, Serenity, Synchron, Triad Medical, Vastrax, VizAI. RDL: Consultant - Imperative Care, Stryker, Cerenovus, Spartan Micro. Research support – Siemens. On the editorial board of JNIS. ML: On the editorial board of JNIS. MM: On the editorial board of JNIS. JM: Consultant Stryker. On the editorial board of JNIS. MSP: Clinical Events Committee/Consultant for Medtronic. AP: consultant for Stryker and Depuy Synthes. ES: Consultant for Medtronic/Microvention/Rapid Medical., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There is limited information on the delivery of acute stroke therapies and secondary preventive measures and clinical outcomes over time in young adults with acute ischemic stroke. This study investigated whether advances in these treatments improved outcomes in this population., Methods: Using a prospective multicenter stroke registry in Korea, young adults (aged 18-50 years) with acute ischemic stroke hospitalized between 2008 and 2019 were identified. The observation period was divided into 4 epochs: 2008 to 2010, 2011 to 2013, 2014 to 2016, and 2017 to 2019. Secular trends for patient characteristics, treatments, and outcomes were analyzed., Results: A total of 7050 eligible patients (mean age, 43.1; men, 71.9%) were registered. The mean age decreased from 43.6 to 42.9 years ( P trend =0.01). Current smoking decreased, whereas obesity increased. Other risk factors remained unchanged. Intravenous thrombolysis and mechanical thrombectomy rates increased over time from 2008 to 2010 to 2017 to 2019 (9.5%-13.8% and 3.2%-9.2%, respectively; P <.001), but onset-to-door and door-to-puncture times remained constant. Secondary prevention, including dual antiplatelets for noncardioembolic minor stroke (26.7%-47.0%), direct oral anticoagulants for atrial fibrillation (0.0%-56.2%), and statins for large artery atherosclerosis (76.1%-95.3%) increased ( trend <0.01). Outcome data were available from 2011. One-year mortality (2.5% in 2011-2013 and 2.3% in 2017-2019) and 3-month modified Rankin Scale scores 0 to 1 (68.3%-69.1%) and 0 to 2 (87.6%-86.2%) remained unchanged. The 1-year stroke recurrence rate increased (4.1%-5.5%; P trend <.001), but onset-to-door and door-to-puncture times remained constant. Secondary prevention, including dual antiplatelets for noncardioembolic minor stroke (26.7%-47.0%), direct oral anticoagulants for atrial fibrillation (0.0%-56.2%), and statins for large artery atherosclerosis (76.1%-95.3%) increased ( P trend <0.01). Outcome data were available from 2011. One-year mortality (2.5% in 2011-2013 and 2.3% in 2017-2019) and 3-month modified Rankin Scale scores 0 to 1 (68.3%-69.1%) and 0 to 2 (87.6%-86.2%) remained unchanged. The 1-year stroke recurrence rate increased (4.1%-5.5%; P trend =0.04), although the difference was not significant after adjusting for sex and age., Conclusions: Improvements in the delivery of acute stroke treatments did not necessarily lead to better outcomes in young adults with acute ischemic stroke over the past decade, indicating a need for further progress., Competing Interests: Disclosures Dr Gorelick reports grants from Amerian Telephysicians, AbbVie, and Pickus Law, outside the submitted work. Dr Bae reports grants from AstraZeneca, Bayer Korea, Bristol Myers Squibb Korea, Dong-A ST, Jeil Pharmaceutical Co, Ltd, Korean Drug Co, Ltd, Samjin Pharm, Takeda Pharmaceuticals Korea Co, Ltd, and Yuhan Corporation and people fees from Amgen Korea, Bayer, Daiichi Sankyo, JW Pharmaceutical, Hanmi Pharmaceutical Co, Ltd, Otsuka Korea, SK Chemicals, and Viatris Korea, outside the submitted work. The other authors report no conflicts.

Background: Mechanical thrombectomy failure (MTF) occurs in approximately 15% of cases., Objective: To investigate factors that predict MTF., Methods: This was a retrospective review of prospectively collected data from the Stroke Thrombectomy and Aneurysm Registry. Patients who underwent mechanical thrombectomy (MT) for large vessel occlusion (LVO) were included. Patients were categorized by mechanical thrombectomy success (MTS) (≥mTICI 2b) or MTF (

Background: Reducing intracranial hemorrhage (ICH) can improve patient outcome in acute ischemic stroke (AIS) intervention. We sought to identify ICH risk factors after AIS thrombectomy., Methods: This is a retrospective review of the Stroke Thrombectomy and Aneurysm Registry (STAR) database. All patients who underwent AIS thrombectomy with available ICH data were included. Multivariable regression models were developed to identify predictors of ICH after thrombectomy. Subgroup analyses were performed stratified by symptom status and European Cooperative Acute Stroke Study (ECASS) grade., Results: The study cohort comprised 6860 patients. Any ICH and symptomatic ICH (sICH) occurred in 25% and 7% of patients, respectively. Hemorrhagic infarction 1 (HI1) occurred in 36%, HI2 in 24%, parenchymal hemorrhage 1 (PH1) in 22%, and PH2 in 17% of patients classified by ECASS grade. Intraprocedural complications independently predicted any ICH (OR 3.8083, P<0.0001), PH1 (OR 1.9053, P=0.0195), and PH2 (OR 2.7347, P=0.0004). Race also independently predicted any ICH (black: OR 0.5180, P=0.0017; Hispanic: OR 0.4615, P=0.0148), sICH (non-white: OR 0.4349, P=0.0107), PH1 (non-white: OR 3.1668, P<0.0001), and PH2 (non-white: OR 1.8689, P=0.0176), with white as the reference. Primary mechanical thrombectomy technique also independently predicted ICH. ADAPT (A Direct Aspiration First Pass Technique) was a negative predictor of sICH (OR 0.2501, P<0.0001), with stent retriever as the reference., Conclusions: This study identified ICH risk factors after AIS thrombectomy using real-world data. There was a propensity towards a reduced sICH risk with direct aspiration. Procedural complications and ethnicity were predictors congruent between categories of any ICH, sICH, PH1, and PH2. Further investigation of technique and ethnicity effects on ICH and outcomes after AIS thrombectomy is warranted., Competing Interests: Competing interests: PK, JRM, MM and MRL are members of the editorial board of JNIS., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale: The optimal duration of dual antiplatelet therapy (DAPT) with clopidogrel-aspirin for the large artery atherosclerotic (LAA) stroke subtype has been debated., Aims: To determine whether the 1-year risk of recurrent vascular events could be reduced by a longer duration of DAPT in patients with the LAA stroke subtype., Methods and Study Design: A total of 4806 participants will be recruited to detect a statistically significant relative risk reduction of 22% with 80% power and a two-sided alpha error of 0.05, including a 10% loss to follow-up. This is a registry-based, multicenter, prospective, randomized, open-label, blinded end point study designed to evaluate the efficacy and safety of a 12-month duration of DAPT compared with a 3-month duration of DAPT in the LAA stroke subtype. Patients will be randomized (1:1) to either DAPT for 12 months or DAPT for 3 months, followed by monotherapy (either aspirin or clopidogrel) for the remaining 9 months., Study Outcomes: The primary efficacy outcome of the study is a composite of stroke (ischemic or hemorrhagic), myocardial infarction, and all-cause mortality for 1 year after the index stroke. The secondary efficacy outcomes are (1) stroke, (2) ischemic stroke or transient ischemic attack, (3) hemorrhagic stroke, and (4) all-cause mortality. The primary safety outcome is major bleeding., Discussion: This study will help stroke physicians determine the appropriate duration of dual therapy with clopidogrel-aspirin for patients with the LAA stroke subtype., Trial Registration: URL: https://cris.nih.go.kr/cris. CRIS Registration Number: KCT0004407.

Background It is unclear whether statin treatment could reduce the risk of early vascular events when baseline low-density lipoprotein cholesterol (LDL-C) levels are already low, at <70 mg/dL, at the time of the index stroke. Methods and Results This study was an analysis of a prospective, multicenter, nationwide registry of consecutive patients with first-ever acute ischemic stroke with baseline low-density lipoprotein cholesterol levels <70 mg/dL and without statin pretreatment. An inverse probabilities of treatment weights method was applied to control for imbalances in baseline characteristics. The primary outcome was a composite of stroke (either hemorrhagic or ischemic), myocardial infarction, and all-cause death within 3 months. A total of 2850 patients (age, 69.5±13.4 years; men, 63.5%) were analyzed for this study. In-hospital statin treatment was used for 74.2% of patients. The primary composite outcome within 3 months occurred in 21.5% of patients in the nonstatin group and 6.7% of patients in the statin group ( P <0.001), but the rates of stroke (2.65% versus 2.33%), hemorrhagic stroke (0.16% versus 0.10%), and myocardial infarction (0.73% versus 0.19%) were not significantly different between the 2 groups. After inverse probability of treatment weighting analysis, the primary composite outcome was significantly reduced in patients with statin therapy (weighted hazard ratio [HR], 0.54 [95% CI, 0.42-0.69]). However, statin treatment did not increase the risk of hemorrhagic stroke (weighted HR, 1.11 [95% CI, 0.10-12.28]). Conclusions Approximately three-quarters of the patients with first-ever ischemic stroke with baseline low-density lipoprotein cholesterol levels <70 mg/dL received in-hospital statin treatment. Statin treatment, compared with no statin treatment, was significantly associated with a reduced risk of the 3-month primary composite outcomes and all-cause death but did not alter the rate of stroke recurrence.

Background: Endovascular thrombectomy (EVT) is the standard-of-care for proximal large vessel occlusion (LVO) stroke. Data on technical and clinical outcomes in distal vessel occlusions (DVOs) remain limited., Methods: This was a retrospective study of patients undergoing EVT for stroke at 32 international centers. Patients were divided into LVOs (internal carotid artery/M1/vertebrobasilar), medium vessel occlusions (M2/A1/P1) and isolated DVOs (M3/M4/A2/A3/P2/P3) and categorized by thrombectomy technique. Primary outcome was a good functional outcome (modified Rankin Scale ≤2) at 90 days. Secondary outcomes included recanalization, procedure-time, thrombectomy attempts, hemorrhage, and mortality. Multivariate logistic regressions were used to evaluate the impact of technical variables. Propensity score matching was used to compare outcome in patients with DVO treated with aspiration versus stent retriever RESULTS: We included 7477 patients including 213 DVOs. Distal location did not independently predict good functional outcome at 90 days compared with proximal (p=0.467). In distal occlusions, successful recanalization was an independent predictor of good outcome (adjusted odds ratio (aOR) 5.11, p<0.05) irrespective of technique. Younger age, bridging therapy, and lower admission National Institutes of Health Stroke Scale (NIHSS) were also predictors of good outcome. Procedure time ≤1 hour or ≤3 thrombectomy attempts were independent predictors of good outcomes in DVOs irrespective of technique (aOR 4.5 and 2.3, respectively, p<0.05). There were no differences in outcomes in a DVO matched cohort of aspiration versus stent retriever. Rates of hemorrhage and good outcome showed an exponential relationship to procedural metrics, and were more dependent on time in the aspiration group and attempts in the stent retriever group., Conclusions: Outcomes following EVT for DVO are comparable to LVO with similar results between techniques. Techniques may exhibit different futility metrics; stent retriever thrombectomy was influenced by attempts whereas aspiration was more dependent on procedure time., Competing Interests: Competing interests: AMA: None, RMC: None, SAK: Grant Funding-Stryker; PJ: Consultant-Balt, Cerus, Microvention, Medtronic. M-NP Honoraria - Stryker, Medtronic, Penumbra, Acandis, Phenox, Siemens Healthineers, Research Support-Swiss National Science Foundation, Bangerter-Rhyner Stiftung, Stryker, Phenox, Medtronic, Rapid, Penumbra, Siemens Healthineers; RMS: None; ASA: Consultant for Arsenal, Balt, Johnson and Johnson, Medtronic, Microvention, Penumbra, Scientia, Siemens, Stryker, Research support from Balt, Medtronic, Microvention, Penumbra and Siemens, Shareholder-Azimuth, Bendit, Cerebrotech, Endostream, Magneto, Mentice, Neurogami, Neuros, Scientia, Serenity, Synchron, Tulavi, Vastrax, VizAI; KMF: Editorial Board-JNIS; RDL: Consultant-Stryker, Imperative Care, Cerenovus, Asahi Intec, Research Funding-Hypervention, Kaneka, Siemens Healthineers, SNIS Foundation, Equity-Synchron, Endostream, Q’Apel, Spartan Micro, Editorial Board-JNIS; PK: Consultant- Stryker, Imperative Care, Microvention, Grant Support-NIH, Editorial-Board JNIS; TD: None; AR: None; RJC: None; IM: None; NG: None; SQW: Board of Directors-AANS, Associate Editor- S:VIN Journal; CMC: None; JM: PI on trials funded by- Stryker Neurovascular, Microvention, and Penumbra, Consultant-Cerebrotech, Viseon, Endostream, Vastrax, RIST, Synchron, Viz.ai, Perflow, CVAid, Stockholder-Cerebrotech, Imperative Care, Endostream, Viseon, BlinkTBI, Myra Medical, Serenity, Vastrax, NTI, RIST, Viz.ai, Synchron, Radical, and Truvic; Editorial Board-JNIS; SIT: Consultant- Microvention, Medtronic; BMH: None; LD: None; HS: None; CSO: Grant Support- Bee Foundation, Brain Aneurysm Foundation, DSMB- Medtronic; RWC: Consultant/Proctor: Medtronic, Microvention; JMa: consultant-Stryker; IF: None; MRL: Educational Grant-Stryker, Medtronic, Consultant-Medtronic, Aeaean Advisers, Travel Support-Penumbra, Editorial Board, JNIS, Stock- Hyperion Surgical, Proprio, Synchron, Cerebrotech, Fluid Biomed, Stereotaxis, Advisor-Metis Innovative; J-tK: None; MSP: DSMB-Medtronic; BG: None; AJP: Consultant-Depuy Synthes, Stryker, CM: Consultant-Silk Road, Penumbra, Microvention, Cerevasc, Stryker, Speaker-Silk Road, Penumbra; JAG: Grant Support- Georgia Research Alliance, Department of Defense, Emory Medical Care Foundation, Neurosurgery Catalyst, Stock- NTI, Cognition; AMS: Consultant- Stryker, Penumbra, Terumo, RapidAI; STAR: funded by Penumbra, Medtronic, Stryker., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The D-dimer to fibrinogen ratio (DFR) is a good indicator of clot-producing activity in thrombotic disease, but its clinical usefulness in stroke patients with nonvalvular atrial fibrillation (NVAF) has not been studied. We evaluated the association between the DFR and early neurological deterioration (END) in acute ischemic stroke (AIS) patients with NVAF., Methods: We included consecutive AIS patients with NVAF between 2013 and 2015 from the registry of a real-world prospective cohort from 11 large centers in South Korea. END was defined as an increase ≥2 in the total NIHSS score or ≥ 1 in the motor NIHSS score within the first 72 h of admission. The DFR was calculated as follows: DFR = D-dimer (mg/L)/fibrinogen (mg/dL) x 100., Results: A total of 1018 AIS patients with NVAF were evaluated. In multivariable logistic regression analysis, the highest DFR tertile was closely associated with END (adjusted odds ratio [aOR] = 2.14, 95 % confidence interval [CI]: 1.24-3.69). Hypertension (aOR = 1.71, 95 % CI: 1.09-2.70), initial NIHSS score (aOR = 1.05, 95 % CI: 1.02-1.07) and use of anticoagulants (aOR = 0.41, 95 % CI: 0.28-0.60) were also correlated with END. In addition to END, the DFR was correlated with discharge NIHSS and modified Rankin Scale (mRS) scores and the 3-month mRS score., Conclusions: High DFR values were associated with END in AIS patients with NVAF. As the DFR is an indicator directly related to the main pathological mechanism of NVAF patients (fibrinolysis and coagulation), it may be useful in predicting their prognosis., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Lipid paradox of low LDL-C may cause physicians to be reluctant to use statins in acute ischemic stroke (AIS) patients with low LDL-C levels at admission., Objective: This study investigated the association between LDL-C levels and early vascular outcomes and assessed the potential interaction effect between LDL-C and statin pretreatment on early outcomes., Patients and Methods: This was a study of a prospective, multicenter, registry of AIS patients with admission LDL-C. The subjects were divided into 3 groups according to LDL-C levels: low LDL-C (≤100 mg/dL); intermediate LDL-C (>100, <130 mg/dL); and high LDL-C (≥130 mg/dL). The primary early vascular outcome was a composite of stroke (ischemic or hemorrhagic), myocardial infarction and all-cause mortality within 3 months. The associations of LDL-C levels as a continuous variable and the risks of primary outcome using Cox proportional hazards models with restricted cubic splines were explored., Results: A total of 32,505 patients (age, 69 ± 12; male, 58.6%) were analyzed. The 3 groups showed significant differences in the 3-month primary outcome, with highest events in the low LDL-C group; after adjustment, no significant associations with the 3-month primary outcome remained. U-shaped nonlinear relationships of LDL-C levels with the 3-month primary outcome were observed (P non-linearity <0.001), with substantial relationships in the no pretreatment subgroup., Conclusions: The relationships between admission LDL-C levels and early outcomes are complex but appear to be paradoxical in patients with low LDL-C and no statin pretreatment. The results suggest that statin pretreatment might offset the paradoxical response of low LDL-C on early vascular outcomes. Further study would be warranted., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Inc.)

We hypothesized that the association between BP and endovascular treatment (EVT) outcomes would differ by baseline perfusion and recanalization status. We identified 388 ICA or M1 occlusion patients who underwent EVT ≤ 24 h from onset with successful recanalization (TICI ≥ 2b). BP was measured at 5-min intervals from arrival and during the procedure. Systolic BPs (SBP) were summarized as dropmax (the maximal decrease over two consecutive measurements), incmax (the maximal increase), mean, coefficient of variation (cv), and standard deviation. Adequate baseline perfusion was defined as hypoperfusion intensity ratio (HIR) ≤ 0.5; infarct proportion as the volume ratio of final infarcts within the T max  > 6 s region. In the adequate perfusion group, infarct proportion was closely associated with SBP dropmax (β ± SE (P-value); 1.22 ± 0.48, (< 0.01)), SBP incmax (1.12 ± 0.33, (< 0.01)), SBP cv (0.61 ± 0.15 (< 0.01)), SBP sd (0.66 ± 0.08 (< 0.01)), and SBP mean (0.71 ± 0.37 (0.053) before recanalization. The associations remained significant only in SBP dropmax , SBP incmax , and SBP mean after recanalization. SBP incmax , SBP cv and SBP sd showed significant associations with modified Rankin Scale score at 3 months in the pre-recanalization period. In the poor perfusion group, none of the SBP indices was associated with any stroke outcomes regardless of recanalization status. BP may show differential associations with stroke outcomes by the recanalization and baseline perfusion status., (© 2023. Springer Nature Limited.)

Background: Recent evidence suggests a correlation between modified Rankin Scale-based measures, an outcome measure commonly used in acute stroke trials, and mortality-based measures used by health agencies in the evaluation of hospital performance. We aimed to examine whether the 2 types of measures are interchangeable in relation to evaluation of hospital performance in acute ischemic stroke., Methods: Five outcome measures, unfavorable functional outcome (3-month modified Rankin Scale score ≥2), death or dependency (3-month modified Rankin Scale score ≥3), 1-month mortality, 3-month mortality, and 1-year mortality, were collected for 8292 individuals who were hospitalized for acute ischemic stroke between January 2014 and May 2015 in 14 hospitals participating in the Clinical Research Collaboration for Stroke in Korea - National Institute of Health registry. Hierarchical regression models were used to calculate per-hospital risk-adjusted outcome rates for each measure. Hospitals were ranked and grouped based on the risk-adjusted outcome rates, and the correlations between the modified Rankin Scale-based and mortality-based ranking and their intermeasure reliability in categorizing hospital performance were analyzed., Results: The comparison between the ranking based on the unfavorable functional outcome and that based on 1-year mortality resulted in a Spearman correlation coefficient of -0.29 and Kendall rank coefficient of -0.23, and the comparison of grouping based on these 2 types of ranks resulted in a weighted kappa of 0.123 for the grouping in the top 33%/middle 33%/bottom 33% and 0.25 for the grouping in the top 20%/middle 60%/bottom 20%, respectively. No significant correlation or similarity in grouping capacities were found between the rankings based on the functional outcome measures and those based on the mortality measures., Conclusions: This study shows that regardless of clinical correlation at an individual patient level, functional outcome-based measures and mortality-based measures are not interchangeable in the evaluation of hospital performance in acute ischemic stroke., Competing Interests: Disclosures None.

Background and Objectives: Female patients tend to have greater disability and worse long-term outcomes after stroke than male patients. To date, the biological basis of sex difference in ischemic stroke remains unclear. We aimed to (1) assess sex differences in clinical manifestation and outcomes of acute ischemic stroke and (2) investigate whether the sex disparity is due to different infarct locations or different impacts of infarct in the same location., Methods: This MRI-based multicenter study included 6,464 consecutive patients with acute ischemic stroke (<7 days) from 11 centers in South Korea (May 2011-January 2013). Multivariable statistical and brain mapping methods were used to analyze clinical and imaging data collected prospectively: admission NIH Stroke Scale (NIHSS) score, early neurologic deterioration (END) within 3 weeks, modified Rankin Scale (mRS) score at 3 months, and culprit cerebrovascular lesion (symptomatic large artery steno-occlusion and cerebral infarction) locations., Results: The mean (SD) age was 67.5 (12.6) years, and 2,641 (40.9%) were female patients. Percentage infarct volumes on diffusion-weighted MRI did not differ between female patients and male patients (median 0.14% vs 0.14%, p = 0.35). However, female patients showed higher stroke severity (NIHSS score, median 4 vs 3, p < 0.001) and had more frequent END (adjusted difference 3.5%; p = 0.002) than male patients. Female patients had more frequent striatocapsular lesions (43.6% vs 39.8%, p = 0.001) and less frequent cerebrocortical (48.2% vs. 50.7% in patients older than 52 years, p = 0.06) and cerebellar (9.1% vs. 11.1%, p = 0.009) lesions than male patients, which aligned with angiographic findings: female patients had more prevalent symptomatic steno-occlusion of the middle cerebral artery (MCA) (31.1% vs 25.3%; p < 0.001) compared with male patients, who had more frequent symptomatic steno-occlusion of the extracranial internal carotid artery (14.2% vs 9.3%; p < 0.001) and vertebral artery (6.5% vs 4.7%; p = 0.001). Cortical infarcts in female patients, specifically left-sided parieto-occipital regions, were associated with higher NIHSS scores than expected for similar infarct volumes in male patients. Consequently, female patients had a higher likelihood of unfavorable functional outcome (mRS score >2) than male patients (adjusted absolute difference 4.5%; 95% CI 2.0-7.0; p < 0.001)., Discussion: Female patients have more frequent MCA disease and striatocapsular motor pathway involvement with acute ischemic stroke, along with left parieto-occipital cortical infarcts showing greater severity for equivalent infarct volumes than in male patients. This leads to more severe initial neurologic symptoms, higher susceptibility to neurologic worsening, and less 3-month functional independence, when compared with male patients., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objective: Heritability of stroke is assumed not to be low, especially in the young stroke population. However, most genetic studies have been performed in highly selected patients with typical clinical or neuroimaging characteristics. We investigated the prevalence of 15 Mendelian stroke genes and explored the relationships between variants and the clinical and neuroimaging characteristics in a large, unselected, young stroke population., Methods: We enrolled patients aged ≤55 years with stroke or transient ischemic attack from a prospective, nationwide, multicenter stroke registry. We identified clinically relevant genetic variants (CRGVs) in 15 Mendelian stroke genes (GLA, NOTCH3, HTRA1, RNF213, ACVRL1, ENG, CBS, TREX1, ABCC6, COL4A1, FBN1, NF1, COL3A1, MT-TL1, and APP) using a customized, targeted next generation sequencing panel., Results: Among 1,033 patients, 131 (12.7%) had 28 CRGVs, most frequently in RNF213 (n = 59), followed by ABCC6 (n = 53) and NOTCH3 (n = 15). The frequency of CRGVs differed by ischemic stroke subtypes (p < 0.01): the highest in other determined etiology (20.1%), followed by large artery atherosclerosis (13.6%). It also differed between patients aged ≤35 years and those aged 51 to 55 years (17.1% vs 9.3%, p = 0.02). Only 27.1% and 26.7% of patients with RNF213 and NOTCH3 variants had typical neuroimaging features of the corresponding disorders, respectively. Variants of uncertain significance (VUSs) were found in 15.4% patients., Interpretation: CRGVs in 15 Mendelian stroke genes may not be uncommon in the young stroke population. The majority of patients with CRGVs did not have typical features of the corresponding monogenic disorders. Clinical implications of having CRGVs or VUSs should be explored. ANN NEUROL 2023;93:768-782., (© 2022 American Neurological Association.)

Importance: International guidelines recommend avoiding intravenous thrombolysis (IVT) in patients with ischemic stroke who have a recent intake of a direct oral anticoagulant (DOAC)., Objective: To determine the risk of symptomatic intracranial hemorrhage (sICH) associated with use of IVT in patients with recent DOAC ingestion., Design, Setting, and Participants: This international, multicenter, retrospective cohort study included 64 primary and comprehensive stroke centers across Europe, Asia, Australia, and New Zealand. Consecutive adult patients with ischemic stroke who received IVT (both with and without thrombectomy) were included. Patients whose last known DOAC ingestion was more than 48 hours before stroke onset were excluded. A total of 832 patients with recent DOAC use were compared with 32 375 controls without recent DOAC use. Data were collected from January 2008 to December 2021., Exposures: Prior DOAC therapy (confirmed last ingestion within 48 hours prior to IVT) compared with no prior oral anticoagulation., Main Outcomes and Measures: The main outcome was sICH within 36 hours after IVT, defined as worsening of at least 4 points on the National Institutes of Health Stroke Scale and attributed to radiologically evident intracranial hemorrhage. Outcomes were compared according to different selection strategies (DOAC-level measurements, DOAC reversal treatment, IVT with neither DOAC-level measurement nor idarucizumab). The association of sICH with DOAC plasma levels and very recent ingestions was explored in sensitivity analyses., Results: Of 33 207 included patients, 14 458 (43.5%) were female, and the median (IQR) age was 73 (62-80) years. The median (IQR) National Institutes of Health Stroke Scale score was 9 (5-16). Of the 832 patients taking DOAC, 252 (30.3%) received DOAC reversal before IVT (all idarucizumab), 225 (27.0%) had DOAC-level measurements, and 355 (42.7%) received IVT without measuring DOAC plasma levels or reversal treatment. The unadjusted rate of sICH was 2.5% (95% CI, 1.6-3.8) in patients taking DOACs compared with 4.1% (95% CI, 3.9-4.4) in control patients using no anticoagulants. Recent DOAC ingestion was associated with lower odds of sICH after IVT compared with no anticoagulation (adjusted odds ratio, 0.57; 95% CI, 0.36-0.92). This finding was consistent among the different selection strategies and in sensitivity analyses of patients with detectable plasma levels or very recent ingestion., Conclusions and Relevance: In this study, there was insufficient evidence of excess harm associated with off-label IVT in selected patients after ischemic stroke with recent DOAC ingestion.

Background: This study aimed to investigate associations of serum high-sensitivity C-reactive protein (hsCRP) and social support (SS) levels with suicidal ideation (SI), and to evaluate potential modifying effects of SS on the associations between serum hsCRP levels and SI in two longitudinal cohorts with cardio-/cerebrovascular diseases., Methods: 1152 acute coronary syndrome (ACS) and 423 stroke patients were recruited at baseline within 2 weeks of disease onset, and evaluated for: i) serum hsCRP levels; ii) SS by the Social Support Scale and Social Undermining Scale; iii) SI by the "suicidal thoughts" item of the Montgomery-Åsberg Depression Rating Scale; and iv) covariates including socio-demographics, depression, vascular risk factors, and index disease severity. At 12-month follow-up, SI was re-evaluated. Logistic regression models were used to adjust for potential covariates., Results: In the ACS cohort, higher serum hsCRP and lower SS levels were significantly associated with SI at baseline; and only lower SS levels were significantly associated with SI at follow-up. In the stroke cohort, lower SS levels were significantly associated with SI at baseline; but no other association was found. Associations of serum hsCRP levels with SI at both baseline and follow-up were only significant at higher SS levels with significant interaction terms in both cohorts., Limitations: This study evaluated SI, but not suicide attempts or death; it also used a single-center design., Conclusions: By considering SS evaluations with routine serum hsCRP levels in cardio-/cerebrovascular disease, clinical prediction of SI both at acute and chronic phases of the diseases might be improved., Competing Interests: Conflict of interest Jae-Min Kim declares research support in the last 5 years from Janssen and Lundbeck. Robert Stewart declares research support in the last 5 years from Janssen, GSK and Takeda. Sung-Wan Kim declares research support in the last 5 years from Janssen, Boehringer Ingelheim, Allergan and Otsuka. All other authors report no biomedical financial interests or potential conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aims: Whether admission hyperglycemia is differentially associated with early vascular outcomes in acute ischemic stroke (AIS) depending on stroke subtype has been incompletely delineated., Methods: In a multicenter, prospective stroke registry, patients with AIS were categorized based on admission glucose levels into normoglycemia, moderate hyperglycemia, and severe hyperglycemia (<140mg/dl, 140-179mg/dl, and ≥180mg/dl, respectively) groups. Multivariate analysis assessed the interaction between the hyperglycemia and ischemic stroke subtypes of large artery atherothrombosis (LAA), cardioembolism (CE), and small vessel occlusion (SVO) and early vascular outcomes (3-month stroke, all-cause mortality, and composite of stroke, MI, and all-cause mortality)., Results: Among the 32,772 patients (age:69.0±12.6yrs, male:58.4%) meeting eligibility criteria, 61.9% were in the normoglycemia group, 19.5% were in the moderate hyperglycemia group, and 18.7% were in the severe hyperglycemia group. Substantial interactions between hyperglycemia groups and stroke subtypes were observed for 3-month stroke (P interaction  = 0.003) and composite of stroke, MI, and all-cause mortality (P interaction  = 0.001), with differential recurrence strongest among CE, intermediate among LAA, and least among SVO., Conclusions: Hyperglycemia was differently associated with the risk of 3-month stroke by ischemic stroke subtype. The associations of hyperglycemia with 3-month stroke were greatest in CE subtype but not in SVO subtype. These results suggest that the effect of glucose-lowering treatment after AIS may differ according to stroke subtype., 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 B.V.)

Objective: The frequency, management, and outcomes of early neurologic deterioration (END) after ischemic stroke specifically due to stroke progression or stroke recurrence have not been well delineated., Materials and Methods: In a multicenter, nationwide registry, data on END due to stroke progression or recurrence confirmed by imaging were collected prospectively between January 2019 and July 2020. Patient characteristics, management strategies, and clinical outcomes were analyzed., Results: Among 14,828 consecutive ischemic stroke patients, 1717 (11.6%) experienced END, including 1221 (8.2%) with END due to stroke progression (SP) or stroke recurrence (SR). Active management after END was implemented in 64.2% of patients. Active management strategies included volume expansion (29.2%), change in antithrombotic regimen (26.1%), induced hypertension (8.6%), rescue reperfusion therapy (6.8%), intracranial pressure lowering with hyperosmolar agents (1.5%), bypass surgery (0.6%), and hypothermia (0.1%). Active management strategies that varied with patient features included volume expansion and induced hypertension, used more often in large artery atherosclerosis and small vessel occlusion, and rescue endovascular thrombectomy, more common in other (dissection), cardioembolism, and large artery atherosclerosis. Active management was associated with higher rates of freedom from disability (modified Rankin Scale, mRS, 0-1; 24.3% vs. 16.6%) and functional independence (mRS, 0-2; 41.6% vs. 27.7%) at 3 months., Conclusion: END specifically due to stroke progression or recurrence occurs in 1 in 12 acute ischemic stroke patients. In this observational study, active management, undertaken in two-thirds of patients, was most often hemodynamic or antithrombotic and was associated with improved functional outcomes., Competing Interests: Declaration of Competing Interest None, (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: The role of endovascular mechanical thrombectomy (MT) in patients presenting with "minor" stroke is uncertain. We aimed to compare outcomes after MT for ischemic stroke patients presenting with National Institutes of Health Stroke Scale (NIHSS) 5 and - within the low NIHSS cohort - identify predictors of a favorable outcome, mortality, and symptomatic intracranial hemorrhage (ICH)., Methods: We retrospectively analyzed a prospectively maintained, international, multicenter database., Results: The study cohort comprised a total of 7568 patients from 29 centers. NIHSS was low (<5) in 604 patients (8%), and > 5 in 6964 (92%). Patients with low NIHSS were younger (67 + 14.8 versus 69.6 + 14.7 years, p < 0.001), more likely to have diabetes (31.5% versus 26.9%, p = 0.016), and less likely to have atrial fibrillation (26.6% versus 37.6%, p < 0.001) compared to those with higher NIHSS. Radiographic outcomes (TICI > 2B 84.6% and 84.3%, p = 0.412) and complication rates (8.1% and 7.2%, p = 0.463) were similar between the low and high NIHSS groups, respectively. Clinical outcomes at every follow up interval, including NIHSS at 24 h and discharge, and mRS at discharge and 90 days, were better in the low NIHSS group, however patients in the low NIHSS group experienced a relative decline in NIHSS from admit to discharge. Mortality was lower in the low NIHSS group (10.4% versus 24.5%, p < 0.001)., Conclusions: Relative to patients with high NIHSS, MT is safe and effective for stroke patients with low NIHSS, and it is reasonable to offer it to appropriately selected patients presenting with minor stroke symptoms. Our findings justify efforts towards a randomized trial comparing MT versus medical management for patients with low NIHSS., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Although the optimal use of prescribed medications for stroke survivors is critical for preventing secondary stroke, longitudinal observations of the natural course of medication persistence and adherence in Korean stroke survivors are rare. Furthermore, studies are needed to identify strong predictors influencing medication adherence and to determine whether these predictors change over time., Aims and Objectives: To evaluate the longitudinal medication persistence and adherence at 3 months and 1 year after discharge in all stroke patients and to identify predictors of long-term medication adherence in patients who can self-medicate., Design: A multicentre, prospective, longitudinal descriptive study., Methods: A total of 600 consecutive ischaemic stroke patients were recruited from three stroke centres across Korea, from 1 September, 2017 to 28 February, 2019. Various factors related to medication adherence suggested by the World Health Organisation were investigated through face-to-face interviews at each centre during hospitalisation. Medication persistence and adherence were assessed at 3 months and 1 year after discharge using the eight-item Morisky Medication Adherence Scale through telephone interviews., Results: Of 537 survivors at 3 months, 526 (98.0%) were persistent and 472 (89.7%) were adherent. Of 493 survivors at 1 year, 477 (96.8%) were persistent and 392 (82.2%) were adherent. Medication belief, income and health literacy were statistically significant predictors of three-month medication adherence, which predicted one-year medication adherence with older age and low income., Conclusions: Among Korean stroke survivors, three-month and one-year medication persistence and adherence were relatively good. Medication beliefs and three-month medication adherence were important and modifiable factors predicting three-month adherence and one-year adherence, respectively., Relevance to Clinical Practice: To increase long-term adherence to medication, various strategies are needed to improve beliefs about medication, taking into account the patient's age and level of knowledge. These interventions need to be initiated during hospitalisation to form early medication habits after discharge., (© 2022 John Wiley & Sons Ltd.)

Background: We aimed to evaluate covert brain infarction (CBI), frequently encountered during the diagnostic work-up of acute ischemic stroke, as a risk factor for stroke recurrence in patients with atrial fibrillation (AF)., Methods: For this prospective cohort study, from patients with acute ischemic stroke hospitalized at 14 centers between 2017 and 2019, we enrolled AF patients without history of stroke or transient ischemic attack and divided them into the CBI (+) and CBI (-) groups. The 2 groups were compared regarding the 1-year cumulative incidence of recurrent ischemic stroke and all-cause mortality using the Fine and Gray subdistribution hazard model with nonstroke death as a competing risk and the Cox frailty model, respectively. Each CBI lesion was also categorized into either embolic-appearing (EA) or non-EA pattern CBI. Adjusted hazard ratios and 95% CIs of any CBI, EA pattern CBI only, non-EA pattern CBI only, and both CBIs were estimated., Results: Among 1383 first-ever stroke patients with AF, 578 patients (41.8%) had CBI. Of these 578 with CBI, EA pattern CBI only, non-EA pattern CBI only, and both CBIs were 61.8% (n=357), 21.8% (n=126), and 16.4% (n=95), respectively. The estimated 1-year cumulative incidence of recurrent ischemic stroke was 5.2% and 1.9% in the CBI (+) and CBI (-) groups, respectively ( P =0.001 by Gray test). CBI increased the risk of recurrent ischemic stroke (adjusted hazard ratio [95% CI], 2.91 [1.44-5.88]) but did not the risk of all-cause mortality (1.32 [0.97-1.80]). The EA pattern CBI only and both CBIs elevated the risk of recurrent ischemic stroke (2.76 [1.32-5.77] and 5.39 [2.25-12.91], respectively), while the non-EA pattern only did not (1.44 [0.40-5.16])., Conclusions: Our study suggests that AF patients with CBI might have increased risk of recurrent stroke. CBI could be considered when estimating the stroke risk in patients with AF.

Importance: There is substantial controversy with regards to the adequacy and use of noncontrast head computed tomography (NCCT) for late-window acute ischemic stroke in selecting candidates for mechanical thrombectomy., Objective: To assess clinical outcomes of patients with acute ischemic stroke presenting in the late window who underwent mechanical thrombectomy stratified by NCCT admission in comparison with selection by CT perfusion (CTP) and diffusion-weighted imaging (DWI)., Design, Setting, and Participants: In this multicenter retrospective cohort study, prospectively maintained Stroke Thrombectomy and Aneurysm (STAR) database was used by selecting patients within the late window of acute ischemic stroke and emergent large vessel occlusion from 2013 to 2021. Patients were selected by NCCT, CTP, and DWI. Admission Alberta Stroke Program Early CT Score (ASPECTS) as well as confounding variables were adjusted. Follow-up duration was 90 days. Data were analyzed from November 2021 to March 2022., Exposures: Selection by NCCT, CTP, or DWI., Main Outcomes and Measures: Primary outcome was functional independence (modified Rankin scale 0-2) at 90 days., Results: Among 3356 patients, 733 underwent late-window mechanical thrombectomy. The median (IQR) age was 69 (58-80) years, 392 (53.5%) were female, and 449 (65.1%) were White. A total of 419 were selected with NCCT, 280 with CTP, and 34 with DWI. Mean (IQR) admission ASPECTS were comparable among groups (NCCT, 8 [7-9]; CTP, 8 [7-9]; DWI 8, [7-9]; P = .37). There was no difference in the 90-day rate of functional independence (aOR, 1.00; 95% CI, 0.59-1.71; P = .99) after adjusting for confounders. Symptomatic intracerebral hemorrhage (NCCT, 34 [8.6%]; CTP, 37 [13.5%]; DWI, 3 [9.1%]; P = .12) and mortality (NCCT, 78 [27.4%]; CTP, 38 [21.1%]; DWI, 7 [29.2%]; P = .29) were similar among groups., Conclusions and Relevance: In this cohort study, comparable outcomes were observed in patients in the late window irrespective of neuroimaging selection criteria. Admission NCCT scan may triage emergent large vessel occlusion in the late window.

Background and Purpose: The purpose of this study was to determine whether underweight is associated with poststroke cardiovascular events and whether such association is different according to the presence of atrial fibrillation (AF)., Methods: Patients with acute stroke or transient ischemic attack who were prospectively registered in a multicenter stroke database from April 2008 to July 2020 were analyzed, excluding those aged 75 or older and those who were overweight. We prospectively captured major adverse cardiovascular events (MACE) within one year after stroke. Cox-proportional hazard regression analysis was conducted for each subgroup with or without AF after adjusting for predetermined vascular risk factors and potential confounders., Results: Among 30,912 patients, 1494 (4.8%) cases were underweight and 29,418 (95.2%) cases were normal weight. The cumulative event rate of 1-year MACE was higher in the underweight group (9.0%) than in the normal weight group (5.6%). In Cox-proportional regression, underweight was associated with significantly higher MACE (adjusted hazard ratio [HR]: 1.62, 95% confidence interval [CI]: 1.26-2.09) and recurrent stroke (adjusted HR: 1.42, 95% CI: 1.02-1.98) in all study patients. In patients with AF, the risk of MACE for the underweight group was not significantly increased. In contrast, in patients without AF, the underweight group had a consistently higher risk of MACE (adjusted HR: 1.66, 95% CI: 1.25-2.22) and recurrent stroke (adjusted HR: 1.50, 95% CI: 1.05-2.14)., Conclusions: Underweight increased the risk of MACE and recurrent stroke within one year after acute stroke, especially in stroke without AF., (Copyright © 2022 Elsevier Inc. All rights reserved.)

This study aimed to elucidate whether low-density lipoprotein cholesterol (LDL-C) levels differentially affect functional outcomes after intravenous thrombolysis (IVT) depending on prestroke statin use. Patients with acute ischemic stroke treated with IVT were categorized into low, intermediate, and high LDL-C groups based on LDL-C levels at admission (< 100/100-130/ > 130 mg/dl, respectively). Multivariable logistic regression analyses were performed to explore the relationships between LDL-C and clinical outcomes (good outcomes at 3 months, modified Rankin Scale scores 0-2). The interaction between LDL-C levels and prestroke statin use regarding functional outcomes was investigated. Among the 4711 patients (age, 67 ± 12 years; males, 62.1%) who met the eligibility criteria, compared with the high LDL-C group, the low and intermediate LDL-C groups were not associated with good outcomes at 3 months according to the multivariable analysis. A potential interaction between the LDL-C group and prestroke statin use on good outcomes at 3 months was observed (P interaction  = 0.07). Among patients with prestroke statin use, low (aOR 1.84 [1.04-3.26]) and intermediate (aOR 2.31 [1.20-4.47]) LDL-C groups were independently associated with a greater likelihood of having a 3-month good outcome. Our study showed that LDL-C was not associated with a 3-month good outcome, but prestroke statin use could modify the influence of LDL-C levels on functional outcomes after IVT., (© 2022. The Author(s).)

This study aimed to present the prognosis after minor acute ischemic stroke (AIS) or transient ischemic attack (TIA), using a definition of subsequent stroke in accordance with recent clinical trials. In total, 9,506 patients with minor AIS (National Institutes of Health Stroke Scale ≤ 5) or high-risk TIA (acute lesions or ≥ 50% cerebral artery steno-occlusion) admitted between November 2010 and October 2013 were included. The primary outcome was the composite of stroke (progression of initial event or a subsequent event) and all-cause mortality. The cumulative incidence of stroke or death was 11.2% at 1 month, 13.3% at 3 months and 16.7% at 1 year. Incidence rate of stroke or death in the first month was 12.5 per 100 person-months: highest in patients with large artery atherosclerosis (17.0). The risk of subsequent events shortly after a minor AIS or high-risk TIA was substantial, particularly in patients with large artery atherosclerosis., Competing Interests: Authors Lesén E, Hedberg J, Tank A and Fita EG are employees of AstraZeneca. Independent of the submitted work, Bae HJ reports: grants from AstraZeneca Korea, Bayer, BMS Korea, Boehringer Ingelheim, Daichi Sankyo, Dong-A Pharmaceutical, Korean Drug Co. Ltd., Servier, Shin Poong Pharm. Co. Ltd and Yuhan Corporation; grants and personal fees from ESAI-Korea and Shire Korea Ltd; and personal fees from Amgen Asia Holding Limited, and Otsuka Korea outside the submitted work. The other authors report no conflicts., (© 2022 The Korean Academy of Medical Sciences.)

Background: Stroke of other determined etiology (OE) includes patients with an uncommon cause of stroke. We described the general characteristics, management, and outcomes of stroke in OE and its subgroups., Methods: This study is a retrospective analysis of a prospective, multicenter, nationwide registry, the Clinical Research Center for Stroke-Korea-National Institutes of Health registry. We classified OE strokes into 10 subgroups according to the literature and their properties. Each OE subgroup was compared according to clinical characteristics, sex, age strata, lesion locations, and management. Moreover, 1-year composites of stroke and all-cause mortality were investigated according to the OE subgroups., Results: In total, 2119 patients with ischemic stroke with OE types (mean age, 55.6±16.2 years; male, 58%) were analyzed. In the Clinical Research Center for Stroke-Korea-National Institutes of Health registry, patients with OE accounted for 2.8% of all patients with stroke. The most common subtypes were arterial dissection (39.1%), cancer-related coagulopathy (17.3%), and intrinsic diseases of the arterial wall (16.7%). Overall, strokes of OE were more common in men than in women (58% versus 42%). Arterial dissection, intrinsic diseases of the arterial wall and stroke associated with migraine and drugs were more likely to occur at a young age, while disorders of platelets and the hemostatic system, cancer-related coagulopathy, infectious diseases, and hypoperfusion syndromes were more frequent at an old age. The composite of stroke and all-cause mortality within 1 year most frequently occurred in cancer-related coagulopathy, with an event rate of 71.8%, but least frequently occurred in stroke associated with migraine and drugs and arterial dissection, with event rates of 0% and 7.2%, respectively., Conclusions: This study presents the different characteristics, demographic findings, lesion locations, and outcomes of OE and its subtypes. It is characterized by a high proportion of arterial dissection, high mortality risk in cancer-related coagulopathy and an increasing annual frequency of cancer-related coagulopathy in patients with stroke of OE.

Background: The impact of renal impairment on the outcomes of patients with acute ischemic stroke treated with endovascular thrombectomy was relatively limited and contradictory. We performed a systematic review and meta-analysis to investigate this., Aims: We registered a protocol in September 2020 and searched MEDLINE, EMBASE, and Google Scholar accordingly. Renal impairment was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m 2 . Predefined outcomes included functional independence (defined as a modified Rankin Scale of 0, 1, or 2) at three months, successful reperfusion, mortality, and symptomatic intracerebral hemorrhage., Summary of Review: Eleven studies involving 3453 patients were included. For the unadjusted outcomes, renal impairment was associated with fewer functional independence (odds ratio (OR), 0.49; 95% confidence interval (CI), 0.39-0.62) and higher mortality (OR, 2.55; 95% CI, 2.03-3.21). Renal impairment was not associated with successful reperfusion (OR, 0.80; 95% CI 0.63-1.00) and symptomatic intracerebral hemorrhage (OR, 1.41; 95% CI, 0.95-2.10). For the adjusted outcomes, results derived from a multivariate meta-analysis were consistent with the respective unadjusted outcomes: functional independence (OR, 0.59; 95% CI, 0.45-0.77), mortality (OR, 2.23, 95% CI, 1.45-3.43), and symptomatic intracerebral hemorrhage (OR, 1.34; 95% CI, 0.85-2.10)., Conclusions: We presented the first systematic review to demonstrate that renal impairment is associated with fewer functional independence and higher mortality. Future endovascular thrombectomy studies should publish complete renal estimated glomerular filtration rate data to facilitate prognostic studies and permit estimated glomerular filtration rate to be analyzed in a continuous variable. Systematic Review Registration : PROSPERO CRD42020191309.

Clustering stroke patients with similar characteristics to predict subsequent vascular outcome events is critical. This study aimed to compare several clustering methods, particularly a deep neural network-based model, and identify the best clustering method with a maximally distinct 1-year outcome in patients with ischemic stroke. Prospective stroke registry data from a comprehensive stroke center from January 2011 to July 2018 were retrospectively analyzed. Patients with acute ischemic stroke within 7 days of onset were included. The primary outcomes were the composite of all strokes (either hemorrhagic or ischemic), myocardial infarction, and all-cause mortality within one year. Neural network-based clustering models (deep lifetime clustering) were compared with other clustering models (k-prototype and semi-supervised clustering, SSC) and a conventional risk score (Stroke Prognostic Instrument-II, SPI-II) to obtain a distinct distribution of 1-year vascular events. Ultimately, 7,650 patients were included, and the 1-year primary outcome event occurred in 13.1%. The DLC-Kuiper UB model had a significantly higher C-index (0.674), log-rank score (153.1), and Brier score (0.08) than the other cluster models (SSC and DLC-MMD) and the SPI-II score. There were significant differences in primary outcome events among the 3 clusters (41.7%, 13.4%, and 6.5% in clusters 0, 1, and 2, respectively) when the DLC-Kuiper UB model was used. A neural network-based clustering model, the DLC-Kuiper UB model, can improve the clustering of stroke patients with a maximally distinct distribution of 1-year vascular outcomes among each cluster. Further studies are warranted to validate this deep neural network-based clustering model in ischemic stroke., (© 2022. The Author(s).)

Background Previous literature about the effect of heart rate on poststroke outcomes is limited. We attempted to elucidate (1) whether heart rate during the acute period of ischemic stroke predicts subsequent major clinical events, (2) which heart rate parameter is best for prediction, and (3) what is the estimated heart rate cutoff point for the primary outcome. Methods and Results Eight thousand thirty-one patients with acute ischemic stroke who were hospitalized within 48 hours of onset were analyzed retrospectively. Heart rates between the 4th and 7th day after onset were collected and heart rate parameters including mean, time-weighted average, maximum, and minimum heart rate were evaluated. The primary outcome was the composite of recurrent stroke, myocardial infarction, and mortality up to 1 year after stroke onset. All heart rate parameters were associated with the primary outcome ( P 's<0.001). Maximum heart rate had the highest predictive power. The estimated cutoff point for the primary outcome was 81 beats per minute for mean heart rate and 100 beats per minute for maximum heart rate. Patients with heart rates above these cutoff points had a higher risk of the primary outcome (adjusted hazard ratio, 1.80 [95% CI, 1.57-2.06] for maximum heart rate and 1.65 [95% CI, 1.45-1.89] for mean heart rate). The associations were replicated in a separate validation dataset (N=10 000). Conclusions These findings suggest that heart rate during the acute period of ischemic stroke is a predictor of major clinical events, and optimal heart rate control might be a target for preventing subsequent cardiovascular events.

Background Unlike patients with stroke caused by other mechanisms, the effect of elevated plasma total homocysteine (tHcy) on the prognosis of patients with both ischemic stroke and atrial fibrillation (AF) is unknown. This study aimed to evaluate the association between tHcy level and the functional outcome of patients with AF-related stroke. Methods and Results We included consecutive patients with AF-related stroke between 2013 and 2015 from the registry of a real-world prospective cohort from 11 large centers in South Korea. A 3-month modified Rankin Scale score ≥3 was considered an unfavorable outcome. Since tHcy is strongly affected by renal function, we performed a subgroup analysis according to the presence of renal dysfunction. A total of 910 patients with AF-related stroke were evaluated (mean age, 73 years; male sex, 56.0%). The mean tHcy level was 11.98±8.81 μmol/L. In multivariable analysis, the tHcy level (adjusted odds ratio, 1.04; 95% CI, 1.01-1.07, per 1 μmol/L) remained significantly associated with unfavorable outcomes. In the subgroup analysis based on renal function, tHcy values above the cutoff point (≥14.60 μmol/L) showed a close association with the unfavorable outcome only in the normal renal function group (adjusted odds ratio, 3.10; 95% CI, 1.60-6.01). In patients with renal dysfunction, tHcy was not significantly associated with the prognosis of AF-related stroke. Conclusions A higher plasma tHcy level was associated with unfavorable outcomes in patients with AF-related stroke. This positive association may vary according to renal function but needs to be verified in further studies.

Background: Elevated blood pressure after endovascular thrombectomy (EVT) has been associated with an increased risk of hemorrhagic transformation and poor functional outcomes. However, the optimal hemodynamic management after EVT remains unknown, and the blood pressure course in the acute phase of ischemic stroke has not been well characterized. This study aimed to identify patient subgroups with distinct blood pressure trajectories after EVT and study their association with radiographic and functional outcomes., Methods: This multicenter retrospective cohort study included consecutive patients with anterior circulation large-vessel occlusion ischemic stroke who underwent EVT. Repeated time-stamped blood pressure data were recorded for the first 72 hours after thrombectomy. Latent variable mixture modeling was used to separate subjects into five groups with distinct postprocedural systolic blood pressure (SBP) trajectories. The primary outcome was functional status, measured on the modified Rankin Scale 90 days after stroke. Secondary outcomes included hemorrhagic transformation, symptomatic intracranial hemorrhage, and death., Results: Two thousand two hundred sixty-eight patients (mean age [±SD] 69±15, mean National Institutes of Health Stroke Scale 15±7) were included in the analysis. Five distinct SBP trajectories were observed: low (18%), moderate (37%), moderate-to-high (20%), high-to-moderate (18%), and high (6%). SBP trajectory group was independently associated with functional outcome at 90 days ( P <0.0001) after adjusting for potential confounders. Patients with high and high-to-moderate SBP trajectories had significantly greater odds of an unfavorable outcome (adjusted odds ratio, 3.5 [95% CI, 1.8-6.7], P =0.0003 and adjusted odds ratio, 2.2 [95% CI, 1.5-3.2], P <0.0001, respectively). Subjects in the high-to-moderate group had an increased risk of symptomatic intracranial hemorrhage (adjusted odds ratio, 1.82 [95% CI, 1-3.2]; P =0.04). No significant association was found between trajectory group and hemorrhagic transformation., Conclusions: Patients with acute ischemic stroke demonstrate distinct SBP trajectories during the first 72 hours after EVT that have differing associations with functional outcome. These findings may help identify potential candidates for future blood pressure modulation trials.

Background Although the effect of blood pressure on poststroke outcome is well recognized, the long-term trajectory of blood pressure after acute ischemic stroke and its influence on outcomes have not been studied well. Methods and Results We analyzed systolic blood pressure (SBP) measurements in 5514 patients with acute ischemic stroke at ≥2 of 7 prespecified time points during the first year after stroke among those enrolled in a multicenter prospective registry. Longitudinal SBPs were categorized using a group-based trajectory model. The primary outcome was a composite of stroke recurrence, myocardial infarction, and all-cause mortality up to 1 year after stroke. The study subjects were categorized into 4 SBP trajectory groups: low (27.0%), moderate (59.5%), persistently high (1.2%), and slowly dropping (12.4%). In the first 3 groups, SBP decreased during the first 3 to 7 days and remained steady thereafter. In the slowly dropping SBP group , SBPs decreased from 182 to 135 mm Hg during the first 30 days, then paralleled the trajectory of the moderate SBP group . Compared with the reference, the moderate SBP group , the slowly dropping SBP group was at higher risk for the primary outcome (adjusted hazard ratio [HR], 1.32; 95% CI, 1.05‒1.65) and mortality (adjusted HR, 1.35; 95% CI, 1.03‒1.78). Primary outcome rates were similarly high in the persistently high SBP group . Conclusions Four 1-year longitudinal SBP trajectories were identified in patients with acute ischemic stroke. Patients in the slowly dropping SBP and persistently high SBP trajectory groups were prone to adverse cardiovascular outcomes after stroke.

Background: No study has thoroughly compared the effectiveness of combined antiplatelet treatments (other than clopidogrel-aspirin) versus clopidogrel-aspirin or aspirin alone for early secondary prevention in acute ischaemic stroke., Methods: We identified patients with acute, minor, non-cardiogenic ischaemic stroke treated with aspirin alone, clopidogrel-aspirin or other combination treatment. Propensity scores considering the inverse probability of treatment weighting were used to adjust for baseline imbalances. The primary outcome was the composite of all strokes (ischaemic or haemorrhagic), myocardial infarction and all-cause mortality at 3 months., Results: Among 12 234 patients (male: 61.9%; age: 65.5±13 years) who met the eligibility criteria, aspirin, clopidogrel-aspirin and other combination treatments were administered in 52.2%, 42.9% and 4.9% of patients, respectively. In the crude analysis, the primary outcome event at 3 months occurred in 14.5% of the other combination group, 14.4% of the aspirin group and 13.0% of the clopidogrel-aspirin group. In the weighted Cox proportional hazards analysis, the 3-month primary outcome event occurred less frequently in the clopidogrel-aspirin group than in the other combination group (weighted HR: 0.82 (0.59-1.13)), while no association was found between the aspirin group (weighted HR: 1.04 (0.76-1.44)) or other combination group and the 3-month primary outcome., Conclusion: Other combined antiplatelet treatment, compared with aspirin alone or clopidogrel-aspirin, was not associated with reduced risks of primary composite vascular events or recurrent stroke during the first 3 months after stroke. Therefore, the results suggest that other combination treatments, particularly the cilostazol-based combination, may not be effective alternatives for clopidogrel-aspirin to prevent early vascular events in patients with acute minor stroke. Further exploration in clinical trials will be needed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objectives: To explore the association between blood pressure (BP) levels after endovascular thrombectomy (EVT) and the clinical outcomes of patients with acute ischemic stroke (AIS) patients with large vessel occlusion (LVO)., Methods: A study was eligible if it enrolled patients with AIS >18 years of age with an LVO treated with either successful or unsuccessful EVT and provided either individual or mean 24-hour systolic BP values after the end of the EVT procedure. Individual patient data from all studies were analyzed with a generalized linear mixed-effects model., Results: A total of 5,874 patients (mean age 69 ± 14 years; 50% women; median NIH Stroke Scale score on admission 16) from 7 published studies were included. Increasing mean systolic BP levels per 10 mm Hg during the first 24 hours after the end of the EVT were associated with a lower odds of functional improvement (unadjusted common odds ratio [OR] 0.82, 95% confidence interval [CI] 0.80-0.85; adjusted common OR 0.88, 95% CI 0.84-0.93) and modified Rankin Scale score ≤2 (unadjusted OR 0.82, 95% CI 0.79-0.85; adjusted OR 0.87, 95% CI 0.82-0.93) and a higher odds of all-cause mortality (unadjusted OR 1.18, 95% CI 1.13-1.24; adjusted OR 1.15, 95% CI 1.06-1.23) at 3 months. Higher 24-hour mean systolic BP levels were also associated with an increased likelihood of early neurologic deterioration (unadjusted OR 1.14, 95% CI 1.07-1.21; adjusted OR 1.14, 95% CI 1.03-1.24) and a higher odds of symptomatic intracranial hemorrhage (unadjusted OR 1.20, 95% CI 1.09-1.29; adjusted OR 1.20, 95% CI 1.03-1.38) after EVT., Discussion: Increased mean systolic BP levels in the first 24 hours after EVT are independently associated with a higher odds of symptomatic intracranial hemorrhage, early neurologic deterioration, 3-month mortality, and worse 3-month functional outcomes., (© 2021 American Academy of Neurology.)

Importance: Limited data are available about the outcomes of mechanical thrombectomy (MT) for real-world patients with stroke presenting with a large core infarct., Objective: To investigate the safety and effectiveness of MT for patients with large vessel occlusion and an Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of 2 to 5., Design, Setting, and Participants: This retrospective cohort study used data from the Stroke Thrombectomy and Aneurysm Registry (STAR), which combines the prospectively maintained databases of 28 thrombectomy-capable stroke centers in the US, Europe, and Asia. The study included 2345 patients presenting with an occlusion in the internal carotid artery or M1 segment of the middle cerebral artery from January 1, 2016, to December 31, 2020. Patients were followed up for 90 days after intervention. The ASPECTS is a 10-point scoring system based on the extent of early ischemic changes on the baseline noncontrasted computed tomography scan, with a score of 10 indicating normal and a score of 0 indicating ischemic changes in all of the regions included in the score., Exposure: All patients underwent MT in one of the included centers., Main Outcomes and Measures: A multivariable regression model was used to assess factors associated with a favorable 90-day outcome (modified Rankin Scale score of 0-2), including interaction terms between an ASPECTS of 2 to 5 and receiving MT in the extended window (6-24 hours from symptom onset)., Results: A total of 2345 patients who underwent MT were included (1175 women [50.1%]; median age, 72 years [IQR, 60-80 years]; 2132 patients [90.9%] had an ASPECTS of ≥6, and 213 patients [9.1%] had an ASPECTS of 2-5). At 90 days, 47 of the 213 patients (22.1%) with an ASPECTS of 2 to 5 had a modified Rankin Scale score of 0 to 2 (25.6% [45 of 176] of patients who underwent successful recanalization [modified Thrombolysis in Cerebral Ischemia score ≥2B] vs 5.4% [2 of 37] of patients who underwent unsuccessful recanalization; P = .007). Having a low ASPECTS (odds ratio, 0.60; 95% CI, 0.38-0.85; P = .002) and presenting in the extended window (odds ratio, 0.69; 95% CI, 0.55-0.88; P = .001) were associated with worse 90-day outcome after controlling for potential confounders, without significant interaction between these 2 factors (P = .64)., Conclusions and Relevance: In this cohort study, more than 1 in 5 patients presenting with an ASPECTS of 2 to 5 achieved 90-day functional independence after MT. A favorable outcome was nearly 5 times more likely for patients with low ASPECTS who had successful recanalization. The association of a low ASPECTS with 90-day outcomes did not differ for patients presenting in the early vs extended MT window.

Objective: We investigated (1) the associations of pre-stroke aspirin use with thrombus burden, infarct volume, hemorrhagic transformation, early neurological deterioration (END), and functional outcome, and (2) whether stroke subtypes modify these associations in first-ever ischemic stroke., Methods: This multicenter magnetic resonance imaging (MRI)-based study included 5,700 consecutive patients with acute first-ever ischemic stroke, who did not undergo intravenous thrombolysis or endovascular thrombectomy, from May 2011 through February 2014. Propensity score-based augmented inverse probability weighting was performed to estimate adjusted effects of pre-stroke aspirin use., Results: The mean age was 67 years (41% women), and 15.9% (n = 907) were taking aspirin before stroke. Pre-stroke aspirin use (vs nonuse) was significantly related to a reduced infarct volume (by 30%), particularly in large artery atherosclerosis stroke (by 45%). In cardioembolic stroke, pre-stroke aspirin use was associated with a ~50% lower incidence of END (adjusted difference = -5.4%, 95% confidence interval [CI] = -8.9 to -1.9). Thus, pre-stroke aspirin use was associated with ~30% higher likelihood of favorable outcome (3-month modified Rankin Scale score < 3), particularly in large artery atherosclerosis stroke and cardioembolic stroke (adjusted difference = 7.2%, 95% CI = 1.8 to 12.5 and adjusted difference = 6.4%, 95% CI = 1.7 to 11.1, respectively). Pre-stroke aspirin use (vs nonuse) was associated with 85% less frequent cerebral thrombus-related susceptibility vessel sign (SVS) in large artery atherosclerosis stroke (adjusted difference = -1.4%, 95% CI = -2.1 to -0.8, p < 0.001) and was associated with ~40% lower SVS volumes, particularly in cardioembolic stroke (adjusted difference = -0.16 cm 3 , 95% CI = -0.29 to -0.02, p = 0.03). Moreover, pre-stroke aspirin use was not significantly associated with hemorrhagic transformation (adjusted difference = -1.1%, p = 0.09)., Interpretation: Pre-stroke aspirin use associates with improved functional independence in patients with first-ever ischemic large arterial stroke by reducing infarct volume and/or END, likely by decreasing thrombus burden, without increased risk of hemorrhagic transformation. ANN NEUROL 2021;90:763-776., (© 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Objectives: This study aimed to investigate whether acute and chronic poststroke depression (PSD) were associated with cardio-cerebrovascular events (CVEs)., Methods: A total of 423 patients with recent stroke were recruited from 2006 to 2009. They were diagnosed with major or minor depressive disorder during the acute phase (within 2 weeks) after stroke. Of these, 284 completed the same diagnostic evaluation during the chronic phase (1 year) after stroke. An average 12-year (range 8.7-14.1 years) follow-up was conducted to assess composite CVEs including recurrent stroke, myocardial infarction, and vascular death after the index stroke. During the follow-up, Kaplan-Meier event rates for outcomes were calculated, and hazard ratios were estimated using Cox regression models after adjusting for a range of covariates., Results: The composite CVE incidence was higher in patients with acute or chronic PSD than in those without. Composite event incidence was highest in patients with PSD during both the acute and chronic phases., Conclusions: The presence of depression at acute and chronic phase of stroke predicted worse long-term cardio-cerebrovascular outcomes. Evaluation of PSD during both the acute and chronic phases is recommended., (© 2021 John Wiley & Sons Ltd.)

Background and Objectives: We evaluated the association between admission glycated hemoglobin (HbA1c) and subsequent risk of composite vascular events, including stroke, myocardial infarction (MI), and vascular death, in patients with acute ischemic stroke and diabetes., Methods: Patients who had a TIA or an acute ischemic stroke within 7 days of symptom onset and diabetes were included in a retrospective cohort design using the stroke registry of the Clinical Research Center for Stroke in Korea. The association between admission HbA1c and composite vascular events, including stroke, MI, and vascular death, during 1-year follow-up was estimated using the Fine-Gray model. The risk of composite vascular events according to the ischemic stroke subtype was explored using fractional polynomial and linear-quadratic models., Results: Of the 18,567 patients, 1,437 developed composite vascular events during follow-up. In multivariable analysis using HbA1c as a categorical variable, the risk significantly increased at a threshold of 6.8%-7.0%. The influence of admission HbA1c level on the risk of composite vascular events was pronounced particularly among those in whom fasting glucose at admission was ≤130 mg/dL. The optimal ranges of HbA1c associated with minimal risks for composite vascular events were lowest for the small vessel occlusion subtype (6.6 [95% confidence internal [CI], 6.3-6.9]) compared to the large artery atherosclerosis (7.3 [95% CI, 6.8-7.9]) or the cardioembolic subtype (7.4 [95% CI, 6.3-8.5])., Dicussion: In patients with ischemic stroke and diabetes, the risks of composite vascular events were significantly associated with admission HbA1c. The optimal range of admission HbA1c was below 6.8%-7.0% and differed according to the ischemic stroke subtype., (© 2021 American Academy of Neurology.)

Objective: To evaluate whether prestroke glucose control is associated with functional outcomes in patients with acute large vessel occlusive stroke and diabetes who underwent intra-arterial thrombectomy (IAT)., Research Design and Methods: From the Clinical Research Center for Stroke-Korea registry, we included patients with emergent large vessel occlusive stroke with diabetes who underwent IAT between January 2009 and March 2020. The association between the HbA 1c level at admission and functional outcomes (modified Rankin Scale at 3 months after the index stroke) was assessed., Results: A total of 1,351 patients were analyzed. Early neurological deterioration was more common in patients with higher levels of HbA 1c at admission ( P = 0.02 according to HbA 1c quintiles, P = 0.003 according to an HbA 1c cutoff value of 7.0%) than in those with lower HbA 1c levels. Higher HbA 1c levels at admission were significantly associated with decreased odds of favorable functional outcomes at a threshold of 7.0-7.1%. The association was consistently observed in subgroups divided according to age, sex, stroke subtype, occlusion site, degree of recanalization, thrombolysis modalities, time from symptom onset to groin puncture, and treatment period., Conclusions: Prestroke glucose control with a target HbA 1c of ≤7.0% may be beneficial for neurological recovery in patients with diabetes undergoing IAT for large vessel occlusive stroke, regardless of stroke subtype, bridging intravenous thrombolysis, occlusion site, degree of recanalization, and treatment period., (© 2021 by the American Diabetes Association.)

Background and Purpose: This study aimed to investigate the effectiveness and safety of intravenous infusion of tirofiban after emergent angioplasty with or without stenting in patients with intracranial atherosclerotic stenosis-related large-vessel occlusion stroke., Methods: We performed a retrospective case series study of 98 patients who underwent thrombectomy followed by angioplasty with or without stenting to treat intracranial atherosclerotic stenosis-related large-vessel occlusion. Patients were divided into 2 groups: those who received continuous intravenous infusion of tirofiban for 12 hours after procedure (intravenous tirofiban group, n=30) and those who did not receive postprocedural intravenous tirofiban (control group, n=68). The following treatment outcomes in the 2 groups were compared: early reocclusion of treated arteries on computed tomography angiography, parenchymal hematoma, symptomatic hemorrhage, and 90-day functional outcome., Results: Early reocclusion occurred in 18 patients (18.4%). The rate of early reocclusion was significantly lower in the intravenous tirofiban group than in the control group (3.3% versus 25%, P<0.001). The rates of parenchymal hematoma, symptomatic hemorrhage, 90-day good outcome, and mortality were not significantly different between the 2 groups. In multivariate logistic analysis, the only independent predictor of early reocclusion was no use of intravenous tirofiban (odds ratio, 9.212 [95% CI, 1.155-73.495], P=0.036). A good outcome (90-day modified Rankin Scale score of 0-2) was significantly less frequent in patients with early reocclusion than in those without it (16.7% versus 72.5%, P<0.001)., Conclusions: The use of intravenous tirofiban for 12 hours was associated with decreased risk of early reocclusion of treated arteries, with no increased risk of hemorrhage after emergent angioplasty, with or without stenting, in patients with intracranial atherosclerotic stenosis-related large-vessel occlusion stroke. Early reocclusion was associated with a poor outcome in such cases.

Background and Purpose: Data on the effect on vascular outcomes of concomitant atherosclerotic vascular disease (ASVD) with atrial fibrillation (AF) after stroke are limited. This study evaluated the effect of ASVD with AF versus AF only on the risk of vascular events., Methods: We retrospectively analyzed a prospectively registered multicenter database involving 3213 stroke patients with AF. ASVD included extracranial atherosclerosis measured in the proximal portion of the internal carotid artery, intracranial atherosclerosis (all ≥50% stenosis), coronary artery disease, and peripheral artery disease and was categorized into 4 strata depending on the number of ASVDs (0, 1, 2, and 3–4). The independent associations of ASVD with major adverse cardiovascular events, stroke, and all-cause death were assessed., Results: A total of 2670 patients were included (mean age, 73.5±9.8 years; median CHA2DS2-VASc score, 5; interquartile range, 4−6). During the follow-up (mean, 1.7 years), a total of 672 (25.2%) major adverse cardiovascular events, 170 (6.4%) stroke events, and 501 (18.8%) all-cause deaths were noted. The adjusted hazard ratio for major adverse cardiovascular events versus no ASVD was 1.25 (95% CI, 1.00–1.56) for ASVD 1, 1.34 (95% CI, 1.02–1.76) for ASVD 2, and 1.93 (95% CI, 1.24–2.99) for ASVD 3–4. The adjusted hazard ratio for all-cause death versus no ASVD was 1.32 (1.01–1.74), 1.47 (1.06–2.03), and 2.39 (1.47–3.89), respectively. Among ASVD components, the presence of symptomatic or asymptomatic extracranial atherosclerosis was a more potent predictor of major adverse cardiovascular events (1.27 [1.05–1.54]) and all-cause death (1.45 [1.17–1.81])., Conclusions: ASVD burden with AF can be a cumulative marker of a high risk for untoward vascular outcomes. Among ASVD components, extracranial atherosclerosis seems to have a predominant effect.

Background It remains unclear whether physicians' attitudes toward timely management of elevated blood pressure affect the risk of stroke recurrence. Methods and Results From a multicenter stroke registry database, we identified 2933 patients with acute ischemic stroke who were admitted to participating centers in 2011, survived at the 1-year follow-up period, and returned to outpatient clinics ≥2 times after discharge. As a surrogate measure of physicians' attitude, individual treatment intensification (TI) scores were calculated by dividing the difference between the frequencies of observed and expected medication changes by the frequency of clinic visits and categorizing them into 5 groups. The association between TI groups and the recurrence of stroke within 1 year was analyzed using hierarchical frailty models, with adjustment for clustering within each hospital and relevant covariates. Mean±SD of the TI score was -0.13±0.28. The TI score groups were significantly associated with increased risk of recurrent stroke compared with Group 3 (TI score range, -0.25 to 0); Group 1 (range, -1 to -0.5), adjusted hazard ratio (HR) 13.43 (95% CI, 5.95-30.35); Group 2 (range, -0.5 to -0.25), adjusted HR 4.59 (95% CI, 2.01-10.46); and Group 4 (TI score 0), adjusted HR 6.60 (95% CI, 3.02-14.45); but not with Group 5 (range, 0-1), adjusted HR 1.68 (95% CI, 0.62-4.56). This elevated risk in the lowest TI score groups persisted when confining analysis to those with hypertension, history of blood pressure-lowering medication, no atrial fibrillation, and regular clinic visits and stratifying the subjects by functional capacity at discharge. Conclusions A low TI score, which implies physicians' therapeutic inertia in blood pressure management, was associated with a higher risk of recurrent stroke. The TI score may be a useful performance indicator in the outpatient clinic setting to prevent recurrent stroke.

Serotonin (5-HT) plays an important role in cerebrovascular homeostasis and psychiatric disorders, including suicidality. Methylation of the serotonin transporter gene (SLC6A4) is associated with 5-HT expression. However, the prognostic roles of SLC6A4 methylation and suicidal ideation (SI) in long-term outcomes of stroke have not been evaluated. We investigated the independent and interactive effects of SLC6A4 methylation and SI immediately after stroke on long-term outcomes. Blood SLC6A4 methylation status and SI based on the suicide item of the Montgomery-Åsberg Depression Rating Scale were assessed in 278 patients at 2 weeks after stroke. After the index stroke, cerebro-cardiovascular events by SLC6A4 methylation status and SI were investigated over an 8-14-year follow-up period and using Cox regression models adjusted for a range of covariates. SLC6A4 hypermethylation and SI within 2 weeks of stroke both predicted worse long-term outcomes, independent of covariates. A significant interaction effect of SI and the methylation status of CpG 4 on long-term stroke outcomes was also identified. The association between SLC6A4 methylation and long-term adverse outcomes may be strengthened in the presence of SI within 2 weeks after stroke. Evaluation of methylation and SI status during the acute phase can be helpful when assessing stroke patients.

Abstract: The performance of scoring systems for risk stratification in patients with atrial fibrillation (AF) was not validated well in patients with stroke. The purpose of this study was to evaluate whether the risk scoring systems predict vascular outcomes in stroke patients with AF.Data were obtained from a nationwide multicenter registry for acute stroke with AF from January 1, 2013, to December 31, 2015. We investigated the predictive power of the CHADS2, CHA2DS2-VASc, ATRIA, and Essen stroke scores in stroke patients with AF. The subjects were further stratified into groups according to treatment with or without oral anticoagulants (OACs).A total of 3112 stroke with AF subjects were included. The rate of recurrent ischemic stroke and any stroke were not associated with the CHADS2, CHA2DS2-VASc, ATRIA, and Essen stroke risk scores. The risks of death and major adverse cerebrovascular and cardiovascular events (MACEs) increased sequentially with the increase of each risk score in OAC group. (the range of C-index 0.544-0.558 for recurrent ischemic stroke; 0.523-0.537 for any stroke; 0.580-0.597 for death; 0.564-0.583 for MACEs). However, in the group treated with OACs, all risk scores were significantly associated with the risk of MACEs. The C-statistics of the 4 scoring systems were 0.544 to 0.558, 0.523 to 0.537, 0.580 to 0.597, 0.564 to 0.583, respectively, for recurrent ischemic stroke, any stroke, death, and MACEs.The performance of the CHADS2, CHA2DS2-VASc, ATRIA, and Essen stroke risk scores for the prediction of recurrent stroke was unsatisfactory in stroke patients with AF whereas the performance for the prediction of recurrent stroke was not MACEs or death was good. A new risk stratification scheme that is specific for secondary stroke prevention in the AF population is needed., Competing Interests: The other authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To improve epidemiologic knowledge of neurologic deterioration (ND) in patients with acute ischemic stroke (AIS)., Methods: In this prospective observational study, we captured ND prospectively in 29,446 patients with AIS admitted to 15 hospitals in Korea within 7 days of stroke onset. ND was defined as an increase in NIH Stroke Scale (NIHSS) score ≥2 (total), or ≥1 (motor or consciousness), or any new neurologic symptoms. Change in incidence rate after stroke onset, causes, factors associated with ND, modified Rankin Scale (mRS) score at 3 months and 1 year, and a composite of stroke, myocardial infarction, and all-cause death at 1 year were assessed., Results: ND occurred in 4,299 (14.6%) patients. The highest rate, 6.95 per 1,000 person-hours incidence, was within the first 6 hours, which decreased to 2.09 within 24-48 hours, and 0.66 within 72-96 hours after stroke onset. Old age, female sex, diabetes, early arrival, large artery atherosclerosis as a stroke subtype, high NIHSS scores, glucose level, systolic blood pressure, leukocytosis at admission, recanalization therapy, TIA without a relevant lesion, and steno-occlusion of relevant arteries were associated with ND. The causes were stroke progression (71.8%) followed by recurrence (8.5%). Adjusted relative risks (95% CI) for poor outcome (mRS 3-6) at 3 months and 1 year were 1.75 (1.70-1.80) and 1.70 (1.65-1.75), respectively. The adjusted hazard ratio (95% CI) for the composite event was 1.59 (1.45-1.74)., Conclusions: ND should be taken into consideration as a factor that may influence the outcome in acute ischemic stroke., (© 2020 American Academy of Neurology.)