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This review explores the extensive evidence linking hypertension with vascular cognitive impairment and dementia, emphasizing its role as a treatable risk factor. Drawing on observational data, it will elucidate how the chronicity of hypertension at different life stages amplifies cognitive decline risk. It explores the mechanisms underlying hypertension's association with dementia, assesses the neuroprotective properties of antihypertensive therapy, and evaluates novel blood pressure metrics and monitoring methods for their diagnostic and therapeutic potential in dementia management., Competing Interests: Disclosure Dr A. de Havenon has received consultant fees from Novo Nordisk, royalty fees from UpToDate, and has equity in TitinKM and Certus. Dr K.N. Sheth reports compensation from Sense and Zoll, for data and safety monitoring services; compensation from Cerevasc, CSL Behring, Rhaeos and Astrocyte for consultant services; a patent for Stroke wearables licensed to Alva Health. Dr A.M. Brickman serves as a scientific advisor/consultant to Cognito Therapeutics, Cognition Therapeutics, and CogState. He serves on data safety and monitoring boards for Albert Einstein College of Medicine and University of Illinois. Dr A.M. Brickman has a patent for white matter hyperintensity quantification (patent # 9867566) and a patent pending for microbleed detection (publication #20230298170). Dr E.A. Mistry receives consultant fees from AbbVie and RAPID AI., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Thrombolytic therapies for acute ischemic stroke are widely available but only result in recanalization early enough, to be therapeutically useful, in 10% to 30% of cases. This large gap in treatment effectiveness could be filled by novel therapies that can increase the effectiveness of thrombus clearance without significantly increasing the risk of harm. This focused update will describe the current state of emerging adjuvant treatments for acute ischemic stroke reperfusion. We focus on new treatments that are designed to (1) target different components that make up a stroke thrombus, (2) enhance endogenous fibrinolytic systems, (3) reduce stagnant blood flow, and (4) improve recanalization of distal thrombi and postendovascular thrombectomy., Competing Interests: Dr Mistry reports compensation from American Heart Association, AbbVie, RAPID AI, and American Heart Association for consultant services; compensation from Silver Creek Pharmaceuticals Inc and Translational Sciences for other services; employment by University of Cincinnati; and grants from National Institutes of Health, Society of Vascular and Interventional Neurology, National Institute of Neurological Disorders and Stroke, Patient-Centered Outcomes Research Institute, and National Institutes of Health. Dr Hill reports grants from Boehringer Ingelheim, Canadian Institutes of Health Research, Medtronic, and NoNO Inc; employment by University of Calgary; stock options in Basking Bioscience LLC; and compensation from Brainsgate Ltd for consultant services. Dr Coutts reports employment by Hotchkiss Brain Institute, University of Calgary. Dr Nogueira reports compensation from Anaconda Biomed, Medtronic USA Inc, Cerenovus, Genentech, Viz-AI, Prolong Pharmaceuticals, Perfuze, Biogen Inc, Shanghai Wallaby, Brainomix, Hybernia, RapidPulse, Imperative Care, Corindus Inc, NeuroVasc Technologies Inc, Corindus Vascular Robotics, Vesalio, Cerebrotech, Astrocyte, Ceretrieve, Phenox Inc, Philips, Anaconda, and Stryker Corporation for consultant services; compensation from Synchron for data and safety monitoring services; stock options in Ceretrieve, Brainomix, Corindus Inc, Perfuze, Truvic, Viz-AI, Reist/Q?Apel Medical, Vesalio, Cerebrotech, and Viseon Inc; stock holdings in Piraeus Medical, Brain4Care, and Quantanosis AI; and grants from Stryker and Cerenovus. Dr Nguyen reports compensation from Brainomix and Aruna for consultant services; and compensation from American Stroke Association for other services. Dr Medcalf reports grants from National Health and Medical Research Council. Dr Broderick reports grants from Genentech to other; compensation from Brainsgate, F. Hoffmann-La Roche, Basking Bioscience, and Kroger Prescription Plans Inc for consultant services; and grants from Novo Nordisk to other. Dr De Meyer reports grants from KU Leuven and Research Foundation Flanders. The other authors report no conflicts.

Background: Patients with suspected ischemic stroke and use of Direct Oral Anticoagulants (DOACs) within 48 h are excluded from thrombolysis. We aimed to determine practice patterns across institutions in the NIH StrokeNet, a network of hospitals to conduct NIH-funded stroke clinical trials, in the United States., Methods: A survey was sent electronically to all NIH StrokeNet regional coordinating centers. The survey questions were geared towards understanding practice patterns with intravenous thrombolysis use in patients on DOACs. We reported proportions and percentages answers to the questions. We compared the likelihood of thrombolysis use in patients with recent DOAC ingestion (never vs. all other responses) across characteristics of survey responder using Chi Square., Results: A total of 83 site principal investigators completed the survey; 78.3 % would never give thrombolysis to an otherwise eligible patients within 12-24 h from last DOAC ingestion and 54.2 % would never give thrombolysis to an otherwise eligible patient within 24-48 h from last DOAC ingestion. A higher proportion of vascular neurologists would never give thrombolysis in patients with DOAC ingestion within 12-48 h compared to other subspecialties (60.7 % vs. 36.4 %, p = 0.05). Nearly, 80 % would change their practice if a well-designed prospective study demonstrated that the symptomatic intracranial hemorrhage rate is not >5 %., Conclusions: A well-designed prospective study with a set safety threshold is likely to change practice patterns in giving thrombolysis in patients with recent DOAC ingestion, particularly among vascular neurologists who are more likely to never give thrombolysis in this setting., Competing Interests: Declaration of competing interest The authors have relevant disclosures or conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Perfusion abnormalities in the infarct and salvaged penumbra have been proposed as a potential reason for poor clinical outcome (modified Rankin Scale score >2) despite complete angiographic reperfusion (Thrombolysis in Cerebral Infarction [TICI3]). In this study, we aimed to identify different microvascular perfusion patterns and their association with clinical outcomes among TICI3 patients., Methods: University Hospital Bern's stroke registry of all patients between February 2015 and December 2021. Macrovascular reperfusion was graded using the TICI scale. Microvascular reperfusion status was evaluated within the infarct area on cerebral blood volume and cerebral blood flow perfusion maps obtained 24-hour postintervention. Primary outcome was functional independence (90-day modified Rankin Scale score 0-2) evaluated with the logistic regression analysis adjusted for age, sex, and 24-hour infarct volume from follow-up imaging., Results: Based on microvascular perfusion findings, the entire cohort (N=248) was stratified into one of the 4 clusters: (1) normoperfusion (no perfusion abnormalities; n=143/248); (2) hyperperfusion (hyperperfusion on both cerebral blood volume and cerebral blood flow; n=54/248); (3) hypoperfusion (hypoperfusion on both cerebral blood volume and cerebral blood flow; n=14/248); and (4) mixed (discrepant findings, eg, cerebral blood volume hypoperfusion and cerebral blood flow hyperperfusion; n=37/248). Compared with the normoperfusion cluster, patients in the hypoperfusion cluster were less likely to achieve functional independence (adjusted odds ratio, 0.3 [95% CI, 0.1-0.9]), while patients in the hyperperfusion cluster tended to have better outcomes (adjusted odds ratio, 3.3 [95% CI, 1.3-8.8])., Conclusions: In around half of TICI3 patients, perfusion abnormalities on the microvascular level can be observed. Microvascular hypoperfusion, despite complete macrovascular reperfusion, is rare but may explain the poor clinical course among some TICI3 patients, while a detrimental effect of hyperperfusion after reperfusion could not be confirmed.

Background and Objectives: Few studies have examined trends and disparities in long-term outcome after stroke in a representative US population. We used a population-based stroke study in the Greater Cincinnati Northern Kentucky region to examine trends and racial disparities in poststroke 5-year mortality., Methods: All patients with acute ischemic strokes (AISs) and intracerebral hemorrhages (ICHs) among residents ≥20 years old were ascertained using ICD codes and physician-adjudicated using a consistent case definition during 5 periods: July 1993-June 1994 and calendar years 1999, 2005, 2010, and 2015. Race was obtained from the medical record; only those identified as White or Black were included. Premorbid functional status was assessed using the modified Rankin Scale, with a score of 0-1 being considered "good." Mortality was assessed with the National Death Index. Trends and racial disparities for each subtype were analyzed with logistic regression., Results: We identified 8,428 AIS cases (19.3% Black, 56.3% female, median age 72) and 1,501 ICH cases (23.5% Black, 54.8% female, median age 72). Among patients with AIS, 5-year mortality improved after adjustment for age, race, and sex (53% in 1993/94 to 48.3% in 2015, overall effect of study year p = 0.009). The absolute decline in 5-year mortality in patients with AIS was larger than what would be expected in the general population (5.1% vs 2.8%). Black individuals were at a higher risk of death after AIS (odds ratio [OR] 1.23, 95% CI 1.08-1.39) even after adjustment for age and sex, and this effect was consistent across study years. When premorbid functional status and comorbidities were included in the model, the primary effect of Black race was attenuated but race interacted with sex and premorbid functional status. Among male patients with a good baseline functional status, Black race remained associated with 5-year mortality (OR 1.4, 95% CI 1.1-1.7, p = 0.002). There were no changes in 5-year mortality after ICH over time (64.4% in 1993/94 to 69.2% in 2015, overall effect of study year p = 0.32)., Discussion: Long-term survival improved after AIS but not after ICH. Black individuals, particularly Black male patients with good premorbid function, have a higher mortality after AIS, and this disparity did not change over time.

Background: As stroke endovascular thrombectomy (EVT) treatment indications expand, understanding population-based EVT eligibility becomes critical for resource planning. We aimed to project current and future population-based EVT eligibility in the United States., Methods: We conducted a post hoc analysis of the physician-adjudicated GCNKSS (Greater Cincinnati Northern Kentucky Stroke Study; 2015 epoch), a population-based, cross sectional, observational study of stroke incidence, treatment, and outcomes across a 5-county region. All hospitalized patients ≥18 years of age with acute ischemic stroke were ascertained using the International Classification of Diseases, Ninth Revision codes 430-436 and Tenth Revision codes I60-I67 and G45-G46 and extrapolated to the US adult census 2020. We determined the rate of EVT eligibility within the GCNKSS population using time from last known well to presentation (0-5 versus 5-23 hours), presenting National Institutes of Health Stroke Scale, and prestroke modified Rankin Scale. Both conservative and liberal estimates of prevalence of large vessel occlusion and large core were then applied based on literature review (unavailable within the 2015 GCNKSS). This eligibility was then extrapolated to the 2020 US population., Results: Of the 1 057 183 adults within GCNKSS in 2015, 2741 had an ischemic stroke and 2176 had data available for analysis. We calculated that 8659 to 17 219 patients (conservative to liberal) meet the current guideline-recommended EVT criteria (nonlarge core, no prestroke disability, and National Institutes of Health Stroke Scale score ≥6) in the United States. Estimates (conservative to liberal) for expanded EVT eligibility subpopulations include (1) 5316 to 10 635 by large core; (2) 10 635 to 21 270 by mild presenting deficits with low National Institutes of Health Stroke Scale score; (3) 13 572 to 27 089 by higher prestroke disability; and (4) 7039 to 14 180 by >1 criteria. These expanded eligibility subpopulations amount to 36 562 to 73 174 patients., Conclusions: An estimated 8659 to 17 219 adult patients in the United States met strict EVT eligibility criteria in 2020. A 4-fold increase in population-based EVT eligibility can be anticipated with incremental adoption of recent or future positive trials. US stroke systems need to be rapidly optimized to handle all EVT-eligible patients with stroke., Competing Interests: E.A. Mistry reports compensation from AbbVie for consultant services; compensation from RAPID AI for consultant services; compensation from the American Heart Association for consultant services; compensation from Translational Sciences for other services; grants from Patient-Centered Outcomes Research Institute; grants from the National Institutes of Health (NIH); and compensation from Silver Creek Pharmaceuticals, Inc, for other services. Dr Khoury reports grants from the NIH. Dr Kissela reports service as Board of Directors, Member for American Academy of Neurology, and employment by the University of Cincinnati. K.S. Alwell reports grants from the NIH. Dr Ferioli reports employment by the University of Cincinnati. Dr De Los Rios La Rosa reports employment by The Neurology Group; compensation from AstraZeneca for other services; and employment by Baptist Health South Florida. Dr Walsh reports grants from Jan Medical, Inc; grants from Sense Diagnostics LLC; grants from NIH Clinical Center; and grants from the American Heart Association. Dr Slavin reports grants from the NIH. M. Haverbusch reports employment by the University of Cincinnati. Dr Mackey reports grants from the NIH. Dr Woo reports grants from NIH. Dr Heldner reports grants from the Swiss Heart Foundation; grants from SITEM Research Funds; and grants from the Swiss National Science Foundation. Dr Fischer reports compensation from Biogen for expert witness services; employment by Universität Basel; and compensation from Boehringer Ingelheim for expert witness services. Dr Jadhav reports employment by Barrow Brain and Spine; stock options in Gravity Medical Technology; compensation from Basking Biosciences for consultant services; a patent issued for Novel Stent Retriever device licensed to Basking Biosciences; and travel support from Johnson and Johnson. Dr Jovin reports grants from Stryker Corporation; stock options in Basking; stock options in Kandu; grants from Medtronic USA, Inc; stock options in Anaconda; compensation from Contego Medical, Inc, for consultant services; stock options in StataDx; stock options in Freeox Biotech; stock options in Gravity; stock options in Route92; stock options in Methinks; compensation from Johnson & Johnson Cerenovus for data and safety monitoring services; stock options in viz-AI; and stock options in Galaxy. Dr Albers reports compensation from Genentech for consultant services; stock holdings in iSchemaView; and compensation from iSchemaView for consultant services. Dr Nogueira reports compensation from RapidPulse for consultant services; compensation from Cerebrotech for consultant services; compensation from Phenox for consultant services; compensation from Medtronic USA, Inc, for consultant services; compensation from Vesalio for consultant services; compensation from Corindus Vascular Robotics for consultant services; compensation from Anaconda for consultant services; compensation from Genentech for consultant services; stock options in Ceretrieve; stock options in Viseon, Inc; compensation from Biogen, Inc, for consultant services; stock options in Truvic; compensation from Brainomix for consultant services; compensation from Prolong Pharmaceuticals for consultant services; compensation from Ceretrieve for consultant services; compensation from Cerenovus for consultant services; stock holdings in Piraeus Medical; compensation from viz-AI for consultant services; stock options in Corindus, Inc; grants from Cerenovus; stock options in Perfuze; compensation from Genentech for consultant services; compensation from Philips for consultant services; compensation from Ceretrieve for consultant services; stock options in viz-AI; compensation from Stryker Corporation for consultant services; stock holdings in Brain4Care; compensation from Perfuze for consultant services; compensation from Brainomix for consultant services; compensation from Cerenovus for consultant services; compensation from viz-AI for consultant services; grants from Stryker; stock options in viz-AI; compensation from Phenox, Inc, for consultant services; compensation from Hybernia for consultant services; compensation from Perfuze for consultant services; compensation from Anaconda Biomed for consultant services; compensation from Imperative Care, Inc, for consultant services; compensation from NeuroVasc Technologies, Inc, for consultant services; compensation from Shanghai Wallaby for consultant services; stock options in Reist/Q’Apel Medical; stock holdings in Quantanosis AI; compensation from Prolong Pharmaceuticals for consultant services; stock options in Vesalio; compensation from Biogen, Inc, for consultant services; compensation from Synchron for data and safety monitoring services; compensation from Stryker for consultant services; compensation from Medtronic USA, Inc, for consultant services; compensation from Imperative Care for consultant services; compensation from RapidPulse for consultant services; stock options in Cerebrotech; compensation from Corindus, Inc, for consultant services; compensation from Astrocyte for consultant services; stock options in Brainomix; and stock options in Perfuze. Dr Khatri reports compensation from Translational Sciences for other services; compensation from Lumosa for consultant services; grants from Johnson & Johnson Health Care Systems, Inc; compensation from Basking Biosciences for consultant services; grants from NIH; compensation from Shionogi, Inc, for consultant services; and Online publication for Royalties from UptoDate, Inc, for online publication. The other authors report no conflicts.

Objectives: Hyperglycemia is associated with poor outcome in large vessel occlusion (LVO) stroke, with mechanism for this effect unknown., Materials and Methods: We used our prospective, multicenter, observational study, Blood Pressure After Endovascular Stroke Therapy (BEST), of anterior circulation LVO stroke undergoing endovascular therapy (EVT) from 11/2017-7/2018 to determine association between increasing blood glucose (BG) and intracerebral hemorrhage (ICH). Our primary outcome was degree of ICH, classified as none, asymptomatic ICH, or symptomatic ICH (≥4-point increase in National Institutes of Health Stroke Scale [NIHSS] at 24 h with any hemorrhage on imaging). Secondary outcomes included 24 h NIHSS, early neurologic recovery (ENR, NIHSS 0-1 or NIHSS reduction by ≥8 within 24 h), and 90-day modified Rankin Scale (mRS) using univariate and multivariable regression., Results: Of 485 enrolled patients, increasing BG was associated with increasing severity of ICH (adjusted OR, aOR 1.06, 95 % CI 1.02-1.1, p < 0.001), higher 24 h NIHSS (aOR 1.22, 95 % CI 1.11-1.34, p < 0.001), ENR (aOR 0.90, 95 % CI 0.82-1.00, p < 0.002), and 90-day mRS (aOR 1.06, 95 % CI 1.03-1.09, p < 0.001) when adjusted for age, presenting NIHSS, ASPECTS, 24-hour peak systolic blood pressure, time from last known well, and successful recanalization., Conclusions: In the BEST study, increasing BG was associated with greater odds of increasing ICH severity. Further study is warranted to determine whether treatment of will decrease ICH severity following EVT., Competing Interests: Declaration of competing interest There are no competing interests, and we have no disclosures to report., (Copyright © 2024. Published by Elsevier Inc.)

Importance: Stroke secondary prevention trials have disproportionately enrolled participants with mild or no disability. The impact of this bias remains unclear., Objective: To investigate the association between poststroke disability and the rate of recurrent stroke during long-term follow up., Design, Setting, and Participants: This cohort study is a post hoc analysis of the Prevention Regimen For Effectively Avoiding Second Strokes (PRoFESS) and Insulin Resistance Intervention After Stroke (IRIS) secondary prevention clinical trial datasets. PRoFESS enrolled patients from 2003 to 2008, and IRIS enrolled patients from 2005 to 2015. Data were analyzed from September 23, 2023, to May 16, 2024., Exposure: The exposure was poststroke functional status at study baseline, defined as modified Rankin Scale (mRS; range, 0-5; higher score indicates more disability) score of 0 vs 1 to 2 vs 3 or greater., Main Outcomes and Measures: The primary outcome was recurrent stroke. The secondary outcome was major cardiovascular events (MACE), defined as recurrent stroke, myocardial infarction, new or worsening heart failure, or vascular death., Results: A total of 20 183 PRoFESS participants (mean [SD] age, 66.1 [8.5] years; 12 931 [64.1%] male) and 3265 IRIS participants (mean [SD] age, 62.7 [10.6] years; 2151 [65.9%] male) were included. The median (IQR) follow-up was 2.4 (1.9-3.0) years in PRoFESS and 4.7 (3.2-5.0) years in IRIS. In PRoFESS, the recurrent stroke rate was 7.2%, among patients with an mRS of 0, 8.7% among patients with an mRS of 1 or 2, and 10.6% among patients with an mRS of 3 or greater (χ22 = 27.1; P < .001); in IRIS the recurrent stroke rate was 6.4% among patients with an mRS of 0, 9.0% among patients with an mRS of 1 or 2, and 11.7% among patients with an mRS of 3 or greater (χ22 = 11.1; P < .001). The MACE rate was 10.1% among patients with an mRS of 0, 12.2% among patients with an mRS of 1 or 2, and 17.2% among patients with an mRS of 3 or greater (χ22 = 103.4; P < .001) in PRoFESS and 10.9% among patients with an mRS of 0, 13.3% among patients with an mRS of 1 or 2, and 15.3% among patients with an mRS of 3 or greater (χ22 = 5.8; P = .06) in IRIS. Compared with patients with an mRS of 0, patients with an mRS of 3 or greater had increased hazard for recurrent stroke in PRoFESS (hazard ratio [HR], 1.63; 95% CI, 1.38-1.92; P < .001) and in IRIS (HR, 1.91; 95% CI, 1.28-2.86; P = .002). There was also increased hazard for MACE in PRoFESS (HR, 1.90; 95% CI, 1.66-2.18; P < .001) and in IRIS (HR, 1.45; 95% CI, 1.03-2.03; P = .03)., Conclusions and Relevance: This cohort study found that higher baseline poststroke disability was associated with increased rates of recurrent stroke and MACE. Including more patients with greater baseline disability in stroke prevention trials may improve the statistical power and generalizability of these studies.

Background: It is uncertain whether antiplatelets or anticoagulants are more effective in preventing early recurrent stroke in patients with cervical artery dissection. Following the publication of the observational Antithrombotic for STOP-CAD (Stroke Prevention in Cervical Artery Dissection) study, which has more than doubled available data, we performed an updated systematic review and meta-analysis comparing antiplatelets versus anticoagulation in cervical artery dissection., Methods: The systematic review was registered in PROSPERO (CRD42023468063). We searched 5 databases using a combination of keywords that encompass different antiplatelets and anticoagulants, as well as cervical artery dissection. We included relevant randomized trials and included observational studies of dissection unrelated to major trauma. Where studies were sufficiently similar, we performed meta-analyses for efficacy (ischemic stroke) and safety (major hemorrhage, symptomatic intracranial hemorrhage, and death) outcomes using relative risks., Results: We identified 11 studies (2 randomized trials and 9 observational studies) that met the inclusion criteria. These included 5039 patients (30% [1512] treated with anticoagulation and 70% [3527]) treated with antiplatelets]. In meta-analysis, anticoagulation was associated with a lower ischemic stroke risk (relative risk, 0.63 [95% CI, 0.43 to 0.94]; P =0.02; I 2 =0%) but higher major bleeding risk (relative risk, 2.25 [95% CI, 1.07 to 4.72]; P =0.03, I 2 =0%). The risks of death and symptomatic intracranial hemorrhage were similar between the 2 treatments. Effect sizes were larger in randomized trials. There are insufficient data on the efficacy and safety of dual antiplatelet therapy or direct oral anticoagulants., Conclusions: In this study of patients with cervical artery dissection, anticoagulation was superior to antiplatelet therapy in reducing ischemic stroke but carried a higher major bleeding risk. This argues for an individualized therapeutic approach incorporating the net clinical benefit of ischemic stroke reduction and bleeding risks. Large randomized clinical trials are required to clarify optimal antithrombotic strategies for management of cervical artery dissection., Competing Interests: Disclosures Dr Henninger has received funding from the National Institutes of Health ([NIH]; NS131756, NR020231) during the conduct of this study, unrelated to the present work. Dr Nguyen discloses advisory board for Brainomix and Aruna and is an Associate Editor for Stroke. Dr Siegler has served as a consultant for AstraZeneca and has received funding from the NIH (R61NS135583), vizai, Philips, and Medtronic, unrelated to this work. Dr Field has received in-kind study medication from Bayer and discloses advisory board participation for Bayer, AstraZeneca, Roche, HLS Therapeutics, and Novartis, is on the board of DESTINE Health, and has served as an expert witness. Dr Mistry receives funding from the NIH/National Institute of Neurological Disorders and Stroke and Patient Centered Outcomes Research Institute. She serves as a consultant for AbbVie and RAPID AI and serves on the steering committee for SilverCreek Pharmaceuticals. She reports a nonfinancial relationship with Translational Sciences Inc. She is also an Associate Editor for Stroke and is employed by the University of Cincinnati. Dr de Havenon is a consultant for Integra, TitinKM, and Novo Nordisk, own stocks in Certus, and receives grant support from the NIH. Dr Fletcher received funds from the Library association and is an officer of the Association of College and Research Libraries and the Medical Library Association. Dr Furie is a consultant for Janssen Biotech. Dr Markus receives infrastructural support provided by the Cambridge British Heart Foundation Centre of Research Excellence (RE/18/1/34212) and by the Cambridge University Hospitals NIHR Biomedical Research Centre (NIHR203312).

Competing Interests: Disclosures Dr Albers reports compensation from Genentech and iSchemaView for consultant services and stock holdings in iSchemaView. Dr Heit reports compensation from Medtronic, iSchemaView, and MicroVention Inc for consultant services. Dr Derdeyn reports grants from Siemens Healthineers and other from Penumbra, Silk Road, NoNo, and Euphrates Vascular outside the submitted work. Dr Inoue reports speaker fees from Bayer, Bristol Myers Squibb, Daichi Sankyo, and Nippon Boehringer Ingelheim. Dr Yedavalli reports consulting fees from MRIOnline and iSchemaView (RapidAI). Dr Seners reports consulting fees for Acticor Biotech. Dr Cereda reports compensation from iSchemaView for consultant services. Dr Mistry serves as a consultant for AbbVie, RAPID AI, and SilverCreek Pharmaceuticals and the American Heart Association. She reports a nonfinancial relationship with Translational Sciences Inc. She reports research funding from the NIH/NINDS and Patient Centered Outcomes Research Institute (PCORI). Dr Chattrerjee reports consulting fees from MDReview and Penumbra Inc. Dr Derdeyn reports Euphrates Vascular - stock options; Silk Road (NITE trial DSMB); Penumbra (MIND and THUNDER trial DSMBs); NoNO (ESCAPE NEXT and FRONTIER DSMBs). Dr Khatri has received a research grant from Cerenovus/Johnson & Johnson (ENDOLOW trial); consulting fees for scientific advisory roles from Lumosa, Basking Biosciences and Shionogi; drug and assays from Translation Sciences (for NIH-funded SISTER trial); royalties from UpToDate (online publication royalties); and funding from NIH STEP Grant (NINDS OT2NS129366). Dr Olivot reports grants from the French Minstry of Health; compensation from Abbvie, Acticor, and Boehringer Ingelheim; and speaker fees from Bristol Myers Squibb. Dr Hill reports grants from Medtronic, Boehringer Ingelheim, NoNO Inc, the Canadian Institutes of Health Research, and MicroVention Inc; compensation from Brainsgate Ltd, for consultant services; a patent issued for Systems and Methods for Assisting in Decision-Making and Triaging for Acute Stroke Patients licensed to Circle NVI; and employment by the University of Calgary. Dr Saver reports consulting fees for advising on rigorous and safe clinical trial design and conduct from Abbott, Acticor, Aeromics, Amgen, Argenica, Astrocyte, Bayer, Biogen, Boehringer Ingelheim, BrainsGate, BrainQ, CSL Behring, Filterlex, Genentech, Johnson&Johnson, MindRhythm, Medtronic, NeuroMerit, Neuronics, Novo Nordisk, Occlutech, Phenox, Phillips, QuantalX, Rapid Medical, Roche, and Stream Biomedical. Dr Fisher reports compensation from Simcere USA and Lumosa for consultant services; employment by Beth Israel Deaconess Medical Center and Beth Israel Deaconess Medical Center. The other authors report no conflicts.

Competing Interests: Disclosures Dr Broderick received multiple research awards from the National Institute of Neurological Disorders and Stroke (NINDS). Novo Nordisk supplies study medication and monetary support for temperature monitoring and after-hour enrollment for ongoing NINDS-funded FASTEST trial (rFVIIa for Acute Hemorrhagic Stroke Administered at Earliest Time). The Department of Neurology and Rehabilitation Medicine received monies to an educational/research fund from Genentech for his role on the Executive Committee of the TIMELESS Trial (Tenecteplase in Stroke Patients Between 4.5 and 24 Hours); from Roche, from BrainsGate Ltd; from Basking Biosciences; and from the Pharmacy and Therapeutics Committee of Kroger Prescription Plans, Inc, as a voting member of the committee. E.A. Mistry receives consulting fees from AbbVie and RAPID AI, financial support for American Academy of Neurology for speaking and from American Heart Association for editorial activities, and research grants from NINDS and Patient-Centered Outcomes Research Institute (PCORI).

Background and Objectives: Poverty is associated with greater stroke incidence. The relationship between poverty and stroke recurrence is less clear., Methods: In this population-based study, incident strokes within the Greater Cincinnati/Northern Kentucky region were ascertained during the 2015 study period and followed up for recurrence until December 31, 2018. The primary exposure was neighborhood socioeconomic status (nSES), defined by the percentage of households below the federal poverty line in each census tract in 4 categories (≤5%, >5%-10%, >10%-25%, >25%). Poisson regression models provided recurrence rate estimates per 100,000 residents using population data from the 2015 5-year American Community Survey, adjusting for age, sex, and race. In a secondary analysis, Cox models allowed for the inclusion of vascular risk factors in the assessment of recurrence risk by nSES among those with incident stroke., Results: Of 2,125 patients with incident stroke, 245 had a recurrent stroke during the study period. Poorer nSES was associated with increased stroke recurrence, with rates of 12.5, 17.5, 25.4, and 29.9 per 100,000 in census tracts with ≤5%, >5%-10%, >10%-25%, and >25% below the poverty line, respectively ( p < 0.01). The relative risk (95% CI) for recurrent stroke among Black vs White individuals was 2.54 (1.91-3.37) before adjusting for nSES, and 2.00 (1.47-2.74) after adjusting for nSES, a 35.1% decrease. In the secondary analysis, poorer nSES (HR 1.74, 95% CI 1.10-2.76 for lowest vs highest category) and Black race (HR 1.31, 95% CI 1.01-1.70) were both independently associated with recurrence risk, though neither retained significance after full adjustment. Age, diabetes, and left ventricular hypertrophy were associated with increased recurrence risk in fully adjusted models., Discussion: Residents of poorer neighborhoods had a dose-dependent increase in stroke recurrence risk, and neighborhood poverty accounted for approximately one-third of the excess risk among Black individuals. These results highlight the importance of poverty, race, and the intersection of the 2 as potent drivers of stroke recurrence.

Objectives: Prognostication for cerebral venous thrombosis (CVT) remains difficult. We sought to validate the SI 2 NCAL 2 C score in an international cohort., Materials and Methods: The SI 2 NCAL 2 C score was originally developed to predict poor outcome (modified Rankin Scale (mRS) 3-6) at 6 months, and mortality at 30 days and 1 year using data from the International CVT Consortium. The SI 2 NCAL 2 C score uses 9 variables: the absence of any female-sex-specific risk factors, intracerebral hemorrhage, central nervous system infection, focal neurological deficits, coma, age, lower level of hemoglobin, higher level of glucose, and cancer. The ACTION-CVT study was an international retrospective study that enrolled consecutive patients across 27 centers. The poor outcome score was validated using 90-day mRS due to lack of follow-up at the 6-month time-point in the ACTION-CVT cohort. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and calibration plots. Missing data were imputed using the additive regression and predictive mean matching methods. Bootstrapping was performed with 1000 iterations., Results: Mortality data were available for 950 patients and poor outcome data were available for 587 of 1,025 patients enrolled in ACTION-CVT. Compared to the International CVT Consortium, the ACTION-CVT cohort was older, less often female, and with milder clinical presentation. Mortality was 2.5% by 30 days and 6.0% by one year. At 90-days, 16.7% had a poor outcome. The SI 2 NCAL 2 C score had an AUC of 0.74 [95% CI 0.69-0.79] for 90-day poor outcome, 0.72 [0.60-0.82] for mortality by 30 days, and 0.82 [0.76-0.88] for mortality by one year., Conclusions: The SI 2 NCAL 2 C score had acceptable to good performance in an international external validation cohort. The SI 2 NCAL 2 C score warrants additional validation studies in diverse populations and clinical implementation studies., Competing Interests: Declaration of competing interest Thanh Nguyen reports research support from Medtronic and the Society of Vascular and Interventional Neurology; advisory board with Brainomix, Aruna Bio; Associate Editor of Stroke. Erik Lindgren reports research support from the Swedish state, ALF agreement (ALFGBG 942851), the Swedish Neurological Society, Elsa and Gustav Lindh's Foundation, Wennerström's Foundation, P-O Ahl's Foundation, and the Rune and Ulla Amlöv's Foundation. Katarina Jood reports research support from the Swedish state ALF agreement (ALFGBG-965417). Mirjam R. Heldner reports grants from SITEM Research Support Funds and Swiss National Science Foundation, Swiss Heart Foundation, not directly related to this manuscript. Thalia S Field reports honoraria for advisory board work for HLS Therapeutics, Roche Canada, AstraZeneca, in-kind study medication from Bayer Canada, is on the board of DESTINE Health, and is supported by a Heart and Stroke/Sauder Family Professorship of Stroke Research at the University of British Columbia. Christoph Stretz reports departmental funding (funds managed by Rhode Island Hospital) for his site's participation in the Neuro AFib study from Massachusetts General Hospital/BSC. Nils Henninger was supported by NINDS R21NS131756 during the conduct of this study (unrelated). Turgut Tatlisumak serves or has served on advisory boards for Astra Zeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Inventiva, and Portola Pharma and received research funding from European Union, Sahlgrenska University Hospital, University of Gothenburg, and Wennerström's Foundation. Diana Aguiar de Sousa reports advisory board participation for Astrazenica, Organon, and Johnson & Johnson, speaker fees from Bial, Bayer, and Astrazeneca, and DSMB participation for the SECRET trial (all unrelated)., (Copyright © 2024. Published by Elsevier Inc.)

Background: Hypertension is a stroke risk factor with known disparities in prevalence and management between Black and White patients. We sought to identify if racial differences in presenting blood pressure (BP) during acute ischemic stroke exist., Methods and Results: Adults with acute ischemic stroke presenting to an emergency department within 24 hours of last known normal during study epochs 2005, 2010, and 2015 within the Greater Cincinnati/Northern Kentucky Stroke Study were included. Demographics, histories, arrival BP, National Institutes of Health Stroke Scale score, and time from last known normal were collected. Multivariable linear regression was used to determine differences in mean BP between Black and White patients, adjusting for age, sex, National Institutes of Health Stroke Scale score, history of hypertension, hyperlipidemia, smoking, stroke, body mass index, and study epoch. Of 4048 patients, 853 Black and 3195 White patients were included. In adjusted analysis, Black patients had higher presenting systolic BP (161 mm Hg [95% CI, 159-164] versus 158 mm Hg [95% CI, 157-159], P <0.01), diastolic BP (86 mm Hg [95% CI, 85-88] versus 83 mm Hg [95% CI, 82-84], P <0.01), and mean arterial pressure (111 mm Hg [95% CI, 110-113] versus 108 mm Hg [95% CI, 107-109], P <0.01) compared with White patients. In adjusted subanalysis of patients <4.5 hours from last known normal, diastolic BP (88 mm Hg [95% CI, 86-90] versus 83 mm Hg [95% CI, 82-84], P <0.01) and mean arterial pressure (112 mm Hg [95% CI, 110-114] versus 108 mm Hg [95% CI, 107-109], P <0.01) were also higher in Black patients., Conclusions: This population-based study suggests differences in presenting BP between Black and White patients during acute ischemic stroke. Further study is needed to determine whether these differences influence clinical decision-making, outcome, or clinical trial eligibility.

Increased blood pressure variability (BPV) is linked to cardiovascular disease and mortality, yet few modifiable BPV risk factors are known. We aimed to assess the relationship between sleep quality and activity level on longitudinal BPV in a cohort of community-dwelling adults (age ≥18) from 17 countries. Using Withings home measurement devices, we examined sleep quality and physical activity over one year, operationalized as mean daily step count and number of sleep interruptions, both transformed into tertiles. The primary study outcome was high BPV, defined as the top tertile of systolic blood pressure standard deviation. Our cohort comprised 29,375 individuals (mean age = 58.6 years) with 127.8±90.1 mean days of measurements. After adjusting for age, gender, country, body mass index, measurement days, mean blood pressure, and total time in bed, the odds ratio of having high BPV for those in the top tertile of sleep interruptions (poor sleep) was 1.37 (95% CI, 1.28-1.47) and 1.44 (95% CI, 1.35-1.54) for those in the lowest tertile of step count (physically inactive). Combining these exposures revealed a significant excess relative risk of 0.20 (95% CI, 0.04-0.35, p = 0.012), confirming their super-additive effect. Comparing individuals with the worst exposure status (lowest step count and highest sleep interruptions, n = 2,690) to those with the most optimal status (highest step count and lowest sleep interruptions, n = 3,531) yielded an odds ratio of 2.01 (95% CI, 1.80-2.25) for high BPV. Our findings demonstrate that poor sleep quality and physical inactivity are associated with increased BPV both independently and super-additively., Competing Interests: The authors have read the journal’s policy and have the following competing interests: AdH has received consultant fees from Integra and Novo Nordisk outside of the submitted work. AdH has also received royalty fees from UpToDate outside of the submitted work. AdH also has equity in TitinKM and Certus outside of the submitted work. KS reports compensation from Sense and Zoll for data and safety monitoring services outside of the submitted work. KS also received consultant fees from Cerevasc, CSL Behring, Astrocyte Pharmaceuticals, Rhaeos, and Certus outside of the submitted work. KS also declares the following patent application associated with this research: Stroke wearables licensed to Alva Health. WTK reports sponsored research agreements from Hyperfine, Biogen, and NControl Therapeutics outside of the submitted work. WTK has also received consultant fees from Biogen, NControl Therapeutics, Acasti Pharma, and Astrocyte Pharmaceuticals outside of the submitted work. WTK also reports equity options from Acasti Pharma and equity from Woolsey Pharmaceuticals outside of the submitted work. SP reports funding from UpToDate as a contributor, and salary support from NIH and AHRQ as an investigator, outside of the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Havenon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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.

Cervical artery dissection is an important cause of stroke, particularly in young adults. Data conflict on the diagnostic evaluation and treatment of patients with suspected cervical artery dissection, leading to variability in practice. We aim to provide an overview of cervical artery dissection in the setting of minor or no reported mechanical trigger with a focus on summarizing the available evidence and providing suggestions on the diagnostic evaluation, treatment approaches, and outcomes. Writing group members drafted their sections using a literature search focused on publications between January 1, 1990, and December 31, 2022, and included randomized controlled trials, prospective and retrospective observational studies, meta-analyses, opinion papers, case series, and case reports. The writing group chair and vice chair compiled the manuscript and obtained writing group members' approval. Cervical artery dissection occurs as a result of the interplay among risk factors, minor trauma, anatomic and congenital abnormalities, and genetic predisposition. The diagnosis can be challenging both clinically and radiologically. In patients with acute ischemic stroke attributable to cervical artery dissection, acute treatment strategies such as thrombolysis and mechanical thrombectomy are reasonable in otherwise eligible patients. We suggest that the antithrombotic therapy choice be individualized and continued for at least 3 to 6 months. The risk of recurrent dissection is low, and preventive measures may be considered early after the diagnosis and continued in high-risk patients. Ongoing longitudinal and population-based observational studies are needed to close the present gaps on preferred antithrombotic regimens considering clinical and radiographic prognosticators of cervical artery dissection.

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: Asymptomatic intracerebral hemorrhage (aICH) occurs in approximately 35% of patients with acute ischemic stroke after endovascular thrombectomy. Unlike symptomatic ICH, studies evaluating the effect of aICH on outcomes have been inconclusive. We performed a systematic review and meta-analysis to evaluate the long-term effects of postendovascular thrombectomy aICH., Methods and Results: The meta-analysis protocol was submitted to the International Prospective Register of Systematic Reviews a priori. PubMed, Scopus, and Web of Science were searched from inception through September 2023, yielding 312 studies. Two authors independently reviewed all abstracts. Included studies contained adult patients with ischemic stroke undergoing endovascular thrombectomy with follow-up imaging assessment of ICH reporting comparative outcomes according to aICH versus no ICH. After screening, 60 papers were fully reviewed, and 10 studies fulfilled inclusion criteria (n=5723 patients total, 1932 with aICH). Meta-analysis was performed using Cochrane RevMan v5.4. Effects were estimated by a random-effects model to estimate summary odds ratio (OR) of the effect of aICH versus no ICH on primary outcomes of 90-day modified Rankin Scale 3 to 6 and mortality. The presence of aICH was associated with a higher odds of 90-day mRS 3 to 6 (OR, 2.17 [95% CI, 1.81-2.60], P <0.0001, I 2 46% Q 19.15) and mortality (OR, 1.72 [95% CI, 1.17-2.53], P :0.005, I 2 79% Q 27.59) compared with no ICH. This difference was maintained following subgroup analysis according to hemorrhage classification and recanalization status., Conclusions: The presence of aICH is associated with worse 90-day functional outcomes and higher mortality. Further studies to evaluate the factors predicting aICH and treatments aimed at reducing its occurrence are warranted.

Background and Objectives: Understanding the current status of and temporal trends of stroke epidemiology by age, race, and stroke subtype is critical to evaluate past prevention efforts and to plan future interventions to eliminate existing inequities. We investigated trends in stroke incidence and case fatality over a 22-year time period., Methods: In this population-based stroke surveillance study, all cases of stroke in acute care hospitals within a 5-county population of southern Ohio/northern Kentucky in adults aged ≥20 years were ascertained during a full year every 5 years from 1993 to 2015. Temporal trends in stroke epidemiology were evaluated by age, race (Black or White), and subtype (ischemic stroke [IS], intracranial hemorrhage [ICH], or subarachnoid hemorrhage [SAH]). Stroke incidence rates per 100,000 individuals from 1993 to 2015 were calculated using US Census data and age-standardized, race-standardized, and sex-standardized as appropriate. Thirty-day case fatality rates were also reported., Results: Incidence rates for stroke of any type and IS decreased in the combined population and among White individuals (any type, per 100,000, 215 [95% CI 204-226] in 1993/4 to 170 [95% CI 161-179] in 2015, p = 0.015). Among Black individuals, incidence rates for stroke of any type decreased over the study period (per 100,000, 349 [95% CI 311-386] in 1993/4 to 311 [95% CI 282-340] in 2015, p = 0.015). Incidence of ICH was stable over time in the combined population and in race-specific subgroups, and SAH decreased in the combined groups and in White adults. Incidence rates among Black adults were higher than those of White adults in all time periods, and Black:White risk ratios were highest in adults in young and middle age groups. Case fatality rates were similar by race and by time period with the exception of SAH in which 30-day case fatality rates decreased in the combined population and White adults over time., Discussion: Stroke incidence is decreasing over time in both Black and White adults, an encouraging trend in the burden of cerebrovascular disease in the US population. Unfortunately, however, Black:White disparities have not decreased over a 22-year period, especially among younger and middle-aged adults, suggesting the need for more effective interventions to eliminate inequities by race.

Background: The modified Rankin Scale (mRS) is a clinician-reported scale that measures the degree of disability in patients who suffered a stroke. Patients' perception of a meaningful recovery from severe stroke, expected value of a stroke intervention, and the effect of disparities are largely unknown., Methods: We conducted a survey of patients, their family members, and accompanying visitors to understand their personal preferences and expectations for acute strokes potentially eligible for acute endovascular intervention using a hypothetical scenario of a severe stroke in a standardized questionnaire., Results: Of 164 survey respondents, 65 (39.6%) were the patient involved, 93 (56.7%) were a family member, and six (3.7%) were accompanied visitors (friends, other). Minimally acceptable disability after a stroke intervention was considered as mRS 2 by 42 respondents (25.6%), as mRS 3 by 79 (48.2%), and as mRS 4 by 43 (26.2%) respondents. Race was associated with different views on this question ( p  < 0.001; Hispanic and Black patients being more likely to accept disability than Caucasian and Asian patients), while sex ( p  = 0.333) and age ( p  = 0.560) were not. Sixty-three respondents (38.4%) viewed minimally acceptable probability of improvement with an intervention as over 50%, 57 (34.8%) as 10-50%, and 44 (26.8%) as less than 10%., Conclusions: A wide range of acceptable outcomes were reported regardless of gender or age. However, race was associated with different acceptable outcome. This is an important finding to demonstrate because of the persistent racial and ethnic disparities in the utilization of endovascular therapy for acute stroke in the United States., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The Stroke Treatment Academic Industry Roundtable (STAIR) convened a session and workshop regarding enrollment in acute stroke trials during the STAIR XII meeting on March 22, 2023. This forum brought together stroke physicians and researchers, members of the National Institute of Neurological Disorders and Stroke, industry representatives, and members of the US Food and Drug Administration to discuss the current status and opportunities for improving enrollment in acute stroke trials. The workshop identified the most relevant issues impacting enrollment in acute stroke trials and addressed potential action items for each. Focus areas included emergency consent in the United States and other countries; careful consideration of eligibility criteria to maximize enrollment and representativeness; investigator, study coordinator, and pharmacist availability outside of business hours; trial enthusiasm/equipoise; site start-up including contractual issues; site champions; incorporation of study procedures into standard workflow as much as possible; centralized enrollment at remote sites by study teams using telemedicine; global trials; and coenrollment in trials when feasible. In conclusion, enrollment of participants is the lifeblood of acute stroke trials and is the rate-limiting step for testing an exciting array of new approaches to improve patient outcomes. In particular, efforts should be undertaken to broaden the medical community's understanding and implementation of emergency consent procedures and to adopt designs and processes that are easily incorporated into standard workflow and that improve trials' efficiencies and execution. Research and actions to improve enrollment in ongoing and future trials will improve stroke outcomes more broadly than any single therapy under consideration., Competing Interests: Disclosures Dr Broderick receives monies from National Institute of Neurological Disorders and Stroke (NINDS) for research grants, receives study medication and monies for temperature monitoring and after-business hour enrollments from Novo Nordisk for NINDS-funded FASTEST Trial (rFVIIa for Acute Hemorrhagic Stroke Administered at Earliest Time Trial). The Department of Neurology receives monies to an educational/research fund from Genentech for his role on Executive Committee of Timeless Trial; from Roche Pharmaceuticals for consulting, from BrainsGate Ltd for consulting; from Basking Biosciences, from Kroger Prescription Plans Inc’s Pharmacy &Therapeutics Committee as voting member of committee. Dr Silva reports funding from the Brazilian Ministry of Health for the Resilient and OPTIMAL trials; consulting and speaker fees from AstraZeneca, Biogen, Boehringer Ingelheim, and Pfizer; consulting fees from IschemaView and Bayer, and speaker fees from Abbott. Dr Selim receives grant funding from the NINDS and NIA (related to and outside of the current work), and royalties from Up to Date and Cambridge University Press and is on the Advisory Board of MedRhythms Inc. Dr Kasner has received grant funding (to institution) from Genentech, Diamedica, Bristol-Myers Squibb, Bayer, Stryker, and Medtronic; consulting fees from Shionogi, Abbvie, Artivion, AstraZeneca, and NeuExcell; and royalties from UpToDate and Elsevier. Dr Adeoye receives funding from NINDS and has equity in and is the Chief Medical Officer for Sense Diagnostics, Inc and receives compensation from NICO Corporation for data and safety monitoring services. Dr Hill reports grants from MicroVention Inc; employment by University of Calgary; grants from Medtronic; grants from Boehringer Ingelheim; grants from Medtronic; grants from Medtronic; grants from Canadian Institutes of Health Research; grants from Biogen Inc; compensation from Brainsgate Ltd for consultant services; and grants from NoNO Inc. Dr Mistry receives funding from National Institutes of Health/NINDS and Patient-Centered Outcomes Research Institute (PCORI) and receives monies for consulting for RAPID AI, Abbvie, and the American Heart Association. Dr Smith is an employee of AbbVie Inc, and holds AbbVie stock and stock options. All inputs to this article are based on personal experiences and opinions, and do not necessarily reflect AbbVie’s views. J. Sutherland is the Clinical Operations Manager for Revalesio. Dr Lyden receives royalty Income for “Thrombolytic Therapy for Acute Stroke” Third Edition Springer Press, is the PI for NINDS grants U24 NS13006000 and UG3 NS119199, and monies for consulting for Apex Innovations. Dr Jauch receives monies for consulting for RapidAI, and reports compensation from Schultz & Pogue, LLP, and McLeod Law Group for expert witness services. Dr Hernandez-Jimenez works for aptaTargets Dr Mocco receives grant funding from Stryker Neurovascular, Penumbra, and Microvention, as well as a research award from PCORI. Dr Mocco reports stock holdings in Endostream; stock holdings in Viz.ai; stock options in Neuroradial Technologies; stock options in Echovate; compensation from CVAid for consultant services; compensation from Penumbra Inc for other services; stock options in Whisper; compensation from RIST Neurovascular, Inc, for consultant services; stock options in Neurotechnology Investors, LLC, Managers; stock holdings in Q’Apel; grants from PCORI; compensation from Stryker for other services; compensation from MicroVention Inc for other services; stock holdings in Vastrax; stock holdings in Imperative Care Inc; compensation from Synchron for consultant services; stock holdings in Blinktbi; stock holdings in Cerebrotech; stock options in Sim&Cure; stock holdings in Spinaker; stock options in Spinaker; compensation from CVAid for consultant services; stock options in Songbird; stock options in E8; compensation from Perflow for consultant services; employment by Mount Sinai Health System; stock options in Tulavi; stock options in Borvo; stock holdings in Viseon Inc; stock options in Radical; and stock options in Neurolutions. E. Deljkich is Vice President, Clinical Affairs, Imperative Care. Dr Kamel is the PI for the ARCADIA trial (Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke; NIH/NINDS U01NS095869), which received in-kind study drug from the BMS-Pfizer Alliance for Eliquis and ancillary study support from Roche Diagnostics; other funding from NIH (R01HL144541, R01NS123576, and U01NS106513); Deputy Editor for JAMA Neurology; clinical trial steering/executive committees for Medtronic, Janssen, and Javelin Medical; end point adjudication committees for AstraZeneca, Novo Nordisk, and Boehringer Ingelheim; and household ownership interests in TETMedical, Spectrum Plastics Group, and Burke Porter Group.

Importance: The effects of moderate systolic blood pressure (SBP) lowering after successful recanalization with endovascular therapy for acute ischemic stroke are uncertain., Objective: To determine the futility of lower SBP targets after endovascular therapy (<140 mm Hg or 160 mm Hg) compared with a higher target (≤180 mm Hg)., Design, Setting, and Participants: Randomized, open-label, blinded end point, phase 2, futility clinical trial that enrolled 120 patients with acute ischemic stroke who had undergone successful endovascular therapy at 3 US comprehensive stroke centers from January 2020 to March 2022 (final follow-up, June 2022)., Intervention: After undergoing endovascular therapy, participants were randomized to 1 of 3 SBP targets: 40 to less than 140 mm Hg, 40 to less than 160 mm Hg, and 40 to 180 mm Hg or less (guideline recommended) group, initiated within 60 minutes of recanalization and maintained for 24 hours., Main Outcomes and Measures: Prespecified multiple primary outcomes for the primary futility analysis were follow-up infarct volume measured at 36 (±12) hours and utility-weighted modified Rankin Scale (mRS) score (range, 0 [worst] to 1 [best]) at 90 (±14) days. Linear regression models were used to test the harm-futility boundaries of a 10-mL increase (slope of 0.5) in the follow-up infarct volume or a 0.10 decrease (slope of -0.005) in the utility-weighted mRS score with each 20-mm Hg SBP target reduction after endovascular therapy (1-sided α = .05). Additional prespecified futility criterion was a less than 25% predicted probability of success for a future 2-group, superiority trial comparing SBP targets of the low- and mid-thresholds with the high-threshold (maximum sample size, 1500 with respect to the utility-weighted mRS score outcome)., Results: Among 120 patients randomized (mean [SD] age, 69.6 [14.5] years; 69 females [58%]), 113 (94.2%) completed the trial. The mean follow-up infarct volume was 32.4 mL (95% CI, 18.0 to 46.7 mL) for the less than 140-mm Hg group, 50.7 mL (95% CI, 33.7 to 67.7 mL), for the less than 160-mm Hg group, and 46.4 mL (95% CI, 24.5 to 68.2 mL) for the 180-mm Hg or less group. The mean utility-weighted mRS score was 0.51 (95% CI, 0.38 to 0.63) for the less than 140-mm Hg group, 0.47 (95% CI, 0.35 to 0.60) for the less than 160-mm Hg group, and 0.58 (95% CI, 0.46 to 0.71) for the high-target group. The slope of the follow-up infarct volume for each mm Hg decrease in the SBP target, adjusted for the baseline Alberta Stroke Program Early CT score, was -0.29 (95% CI, -0.81 to ∞; futility P = .99). The slope of the utility-weighted mRS score for each mm Hg decrease in the SBP target after endovascular therapy, adjusted for baseline utility-weighted mRS score, was -0.0019 (95% CI, -∞ to 0.0017; futility P = .93). Comparing the high-target SBP group with the lower-target groups, the predicted probability of success for a future trial was 25% for the less than 140-mm Hg group and 14% for the 160-mm Hg group., Conclusions and Relevance: Among patients with acute ischemic stroke, lower SBP targets less than either 140 mm Hg or 160 mm Hg after successful endovascular therapy did not meet prespecified criteria for futility compared with an SBP target of 180 mm Hg or less. However, the findings suggested a low probability of benefit from lower SBP targets after endovascular therapy if tested in a future larger trial., Trial Registration: ClinicalTrials.gov Identifier: NCT04116112.

Background: The Safety and Efficacy of Intensive Blood Pressure Lowering after Successful Endovascular Therapy in Acute Ischaemic Stroke (BP TARGET) trial demonstrated no benefit from intensive systolic blood pressure (SBP) treatment after successful reperfusion with endovascular therapy. However, it remains unknown if the response to blood pressure treatment is modified by other factors., Objective: To carry out a post hoc analysis of the BP TARGET trial data to determine if the response to blood pressure treatment is modified by factors such as age, history of hypertension, recanalization status, location of occlusion, diabetes, hyperglycemia, or pretreatment with intravenous thrombolysis., Methods: This is a post hoc analysis of the BP TARGET trial. Patients were divided into groups based on age, diabetes, blood glucose, site of occlusion, history of hypertension, and pretreatment with intravenous thrombolysis. The primary outcome was any intraparenchymal hemorrhage., Results: 318 patients were included. Diabetes modified the treatment effect on favorable functional outcome (P heteogenity =0.041). There was a trend towards benefit from intensive SBP treatment in diabetic patients (OR=2.81; 95% CI 0.88 to 8.88; p=0.08) but not in non-diabetic patients (OR=0.75; 95% 0.45 to 126; p 0.28). Age, location of occlusion, admission SBP, pretreatment with intravenous thrombolysis, and history of hypertension did not modify the effect of intensive SBP treatment on any of the outcomes., Conclusion: The effect of SBP lowering treatment was not modified by age, location of occlusion history of hypertension, intravenous thrombolysis, and admission SBP. Diabetes modified the effect of intensive SBP lowering treatment, and there was a trend towards benefit from intensive SBP treatment in diabetic patients. This finding is hypothesis generating and requires further validation., Competing Interests: Competing interests: RB, MP declare institutional fees for teaching presentations from Stryker, MicroVention, Balt; MM declares institutional fees for teaching presentations from Boerhinger Ingelheim, Amgen, and consulting fees from Boerhinger Ingelheim, Air liquide, Acticor Biotech; AdH declares grants from Regeneron Pharmaceuticals, Inc.; grants from AMAG Pharmaceuticals, Inc.; compensation from Integra for consultant services; and stock options in Certus., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Large vessel occlusion stroke due to underlying intracranial atherosclerotic disease (ICAD-LVO) is prevalent in 10 to 30% of LVOs depending on patient factors such as vascular risk factors, race and ethnicity, and age. Patients with ICAD-LVO derive similar functional outcome benefit from endovascular thrombectomy as other mechanisms of LVO, but up to half of ICAD-LVO patients reocclude after revascularization. Therefore, early identification and treatment planning for ICAD-LVO are important given the unique considerations before, during, and after endovascular thrombectomy. In this review of ICAD-LVO, we propose a multistep approach to ICAD-LVO identification, pretreatment and endovascular thrombectomy considerations, adjunctive medications, and medical management. There have been no large-scale randomized controlled trials dedicated to studying ICAD-LVO, therefore this review focuses on observational studies., Competing Interests: Disclosures Dr de Havenon reports compensation from Novo Nordisk for consultant services; grants from American Heart Association; stock options in TitinKM; compensation from Integra for consultant services; and stock options in Certus. Dr Nguyen reports compensation from Medtronic for other services and grants from Society of Vascular and Interventional Neurology. Dr Mazighi reports compensation from Boehringer-Ingelheim for consultant services; compensation from Novo Nordisk for consultant services; and compensation from acticor biotech for consultant services. Dr Mistry reports employment by University of Cincinnati; grants from National Institutes of Health; compensation from RAPID AI for consultant services; and compensation from American Heart Association for consultant services. Dr Yaghi reports compensation from Medtronic USA, Inc, for other services and employment by Brown University. Dr Derdeyn reports employment by University of Iowa; compensation from Penumbra, Inc. for data and safety monitoring services; compensation from noNO for data and safety monitoring services; compensation from Silk Road Medical, Inc. for data and safety monitoring services; and stock options in Euphrates Vascular. Dr Al Kasab reports compensation from Stryker for other services.

Background and Objectives: There is a rising incidence of infective endocarditis-related stroke (IERS) in the United States attributed to the opioid epidemic. A contemporary epidemiologic description is necessary to understand the impact of the opioid epidemic on clinical characteristics of IERS. We describe and analyze trends in the demographics, risk factors, and clinical features of IERS., Methods: This is a retrospective cohort study within a biracial population of 1.3 million in the Greater Cincinnati/Northern Kentucky region. All hospitalized patients with hemorrhagic or ischemic stroke were identified and physician verified from the 2005, 2010, and 2015 calendar years using ICD-9 and ICD-10 codes. IERS was defined as an acute stroke attributed to infective endocarditis meeting modified Duke Criteria for possible or definite endocarditis. Unadjusted comparison of demographics, risk factors, outcome, and clinical characteristics was performed between each study period for IERS and non-IERS. An adjusted model to compare trends used the Cochran-Armitage test for categorical variables and a general linear model or Kruskal-Wallis test for numerical variables. Examination for interaction of endocarditis status in trends was performed using a general linear or logistic model., Results: A total of 54 patients with IERS and 8,204 without IERS were identified during the study periods. Between 2005 and 2015, there was a decline in rates of hypertension (91.7% vs 36.0%; p = 0.0005) and increased intravenous drug users (8.3% vs 44.0%; p = 0.02) in the IERS cohort. The remainder of the stroke population demonstrated a significant rise in hypertension, diabetes, atrial fibrillation, and perioperative stroke. Infective endocarditis status significantly interacted with the trend in hypertension prevalence ( p = 0.001)., Discussion: From 2005 to 2015, IERS was increasingly associated with intravenous drug use and fewer risk factors, specifically hypertension. These trends likely reflect the demographics of the opioid epidemic, which has affected younger patients with fewer comorbidities., (Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Background: Our primary objective was to evaluate if disparities in race, sex, age, and socioeconomic status (SES) exist in utilization of advanced neuroimaging in year 2015 in a population-based study. Our secondary objective was to identify the disparity trends and overall imaging utilization as compared with years 2005 and 2010., Methods: This was a retrospective, population-based study that utilized the GCNKSS (Greater Cincinnati/Northern Kentucky Stroke Study) data. Patients with stroke and transient ischemic attack were identified in the years 2005, 2010, and 2015 in a metropolitan population of 1.3 million. The proportion of imaging use within 2 days of stroke/transient ischemic attack onset or hospital admission date was computed. SES determined by the percentage below the poverty level within a given respondent's US census tract of residence was dichotomized. Multivariable logistic regression was used to determine the odds of advanced neuroimaging use (computed tomography angiogram/magnetic resonance imaging/magnetic resonance angiogram) for age, race, gender, and SES., Results: There was a total of 10 526 stroke/transient ischemic attack events in the combined study year periods of 2005, 2010, and 2015. The utilization of advanced imaging progressively increased (48% in 2005, 63% in 2010, and 75% in 2015 [ P <0.001]). In the combined study year multivariable model, advanced imaging was associated with age and SES. Younger patients (≤55 years) were more likely to have advanced imaging compared with older patients (adjusted odds ratio, 1.85 [95% CI, 1.62-2.12]; P <0.01), and low SES patients were less likely to have advanced imaging compared with high SES (adjusted odds ratio, 0.83 [95% CI, 0.75-0.93]; P <0.01). A significant interaction was found between age and race. Stratified by age, the adjusted odds of advanced imaging were higher for Black patients compared with White patients among older patients (>55 years; adjusted odds ratio, 1.34 [95% CI, 1.15-1.57]; P <0.01), but no racial differences among the young., Conclusions: Racial, age, and SES-related disparities exist in the utilization of advanced neuroimaging for patients with acute stroke. There was no evidence of a change in trend of these disparities between the study periods.

Introduction: Observational studies have found an increased risk of hemorrhagic transformation and worse functional outcomes in patients with higher systolic blood pressure variability (BPV). However, the time-varying behavior of BPV after endovascular thrombectomy (EVT) and its effects on functional outcome have not been well characterized., Patients and Methods: We analyzed data from an international cohort of patients with large-vessel occlusion stroke who underwent EVT at 11 centers across North America, Europe, and Asia. Repeated time-stamped blood pressure data were recorded for the first 72 h after thrombectomy. Parameters of BPV were calculated in 12-h epochs using five established methodologies. Systolic BPV trajectories were generated using group-based trajectory modeling, which separates heterogeneous longitudinal data into groups with similar patterns., Results: Of the 2041 patients (age 69 ± 14, 51.4% male, NIHSS 15 ± 7, mean number of BP measurements 50 ± 28) included in our analysis, 1293 (63.4%) had a poor 90-day outcome (mRS ⩾ 3) or a poor discharge outcome (mRS ⩾ 3). We identified three distinct SBP trajectories: low (25%), moderate (64%), and high (11%). Compared to patients with low BPV, those in the highest trajectory group had a significantly greater risk of a poor functional outcome after adjusting for relevant confounders (OR 2.2; 95% CI 1.2-3.9; p  = 0.008). In addition, patients with poor outcomes had significantly higher systolic BPV during the epochs that define the first 24 h after EVT ( p  < 0.001)., Discussion and Conclusions: Acute ischemic stroke patients demonstrate three unique systolic BPV trajectories that differ in their association with functional outcome. Further research is needed to rapidly identify individuals with high-risk BPV trajectories and to develop treatment strategies for targeting high BPV., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Spiotta reports grants and personal fees from Penumbra, grants and personal fees from Stryker, grants from Medtronic, non-financial support from RAPID, personal fees from Terumo, and personal fees from Cerenovus outside the submitted work. Dr. Liman reports personal fees from Stryker outside the submitted work. Dr. de Havenon reports grants from AMAG and grants from Regeneron outside the submitted work. Dr. Ortega-Gutierrez reports grants from Stryker, IschemiaView, Viz.ai, and Siemens; personal fees from Medtronic and personal fees from Stryker outside the submitted work. Dr. Sheth reports grants from NIH, grants from AHA, grants from Hyperfine, grants from Biogen, grants from Zoll, and other support from Alva outside the submitted work., (© European Stroke Organisation 2022.)

Background and Objective: There are significant racial disparities in stroke in the United States, with Black individuals having a higher risk of incident stroke even when adjusted for traditional stroke risk factors. It is unknown whether Black individuals are also at a higher risk of recurrent stroke., Methods: Over an 18-month period spanning 2014-2015, we ascertained index stroke cases within the Greater Cincinnati/Northern Kentucky population of 1.3 million. We then followed up all patients for 3 years and determined the risk of recurrence. Multivariable survival analysis was performed to determine the effect of Black race on recurrence., Results: There were 3,816 patients with index stroke/TIA events in our study period, and 476 patients had a recurrent event within 3 years. The Kaplan-Meier estimate of 3-year recurrence rate was 15.4%. Age-adjusted and sex-adjusted stroke recurrence rate was higher in Black individuals (HR 1.34, 95% CI 1.1-1.6; p = 0.003); however, when adjusted for traditional stroke risk factors including hypertension, diabetes, smoking status, age, and left ventricular hypertrophy, the association between Black race and recurrence was significantly attenuated and became nonsignificant (HR 1.1, 95% CI 0.9-1.36, p = 0.32). At younger ages, Black race was more strongly associated with recurrence, and this effect may not be fully attenuated by traditional stroke risk factors., Discussion: Recurrent stroke was more common among Black individuals, but the magnitude of the racial difference was substantially attenuated and became nonsignificant when adjusted for traditional stroke risk factors. Interventions targeting these risk factors could reduce disparities in stroke recurrence., (© 2022 American Academy of Neurology.)

Background and Objective: Cerebral venous thrombosis (CVT) is a rare cause of stroke carrying a nearly 4% risk of recurrence after 1 year. There are limited data on predictors of recurrent venous thrombosis in patients with CVT. In this study, we aim to identify those predictors., Methods: This is a secondary analysis of the ACTION-CVT study which is a multicenter international study of consecutive patients hospitalized with a diagnosis of CVT over a 6-year period. Patients with cancer-associated CVT, CVT during pregnancy, or CVT in the setting of known antiphospholipid antibody syndrome were excluded per the ACTION-CVT protocol. The study outcome was recurrent venous thrombosis defined as recurrent venous thromboembolism (VTE) or de novo CVT. We compared characteristics between patients with vs without recurrent venous thrombosis during follow-up and performed adjusted Cox regression analyses to determine important predictors of recurrent venous thrombosis., Results: Nine hundred forty-seven patients were included with a mean age of 45.2 years, 63.9% were women, and 83.6% had at least 3 months of follow-up. During a median follow-up of 308 (interquartile range 120-700) days, there were 5.05 recurrent venous thromboses (37 VTE and 24 de novo CVT) per 100 patient-years. Predictors of recurrent venous thrombosis were Black race (adjusted hazard ratio [aHR] 2.13, 95% CI 1.14-3.98, p = 0.018), history of VTE (aHR 3.40, 95% CI 1.80-6.42, p < 0.001), and the presence of one or more positive antiphospholipid antibodies (aHR 3.85, 95% CI 1.97-7.50, p < 0.001). Sensitivity analyses including events only occurring on oral anticoagulation yielded similar findings., Discussion: Black race, history of VTE, and the presence of one or more antiphospholipid antibodies are associated with recurrent venous thrombosis among patients with CVT. Future studies are needed to validate our findings to better understand mechanisms and treatment strategies in patients with CVT., (© 2022 American Academy of Neurology.)

Background: High level evidence for direct oral anticoagulants (DOACs) in patients with cerebral venous thrombosis is lacking. We performed a systematic review and meta-analysis to assess the efficacy and safety of DOACs versus vitamin K antagonists in patients with cerebral venous thrombosis., Methods: This systematic review was registered in PROSPERO (CRD42021228800). We searched MEDLINE (via Ovid), EMBASE, CINAHL, and the Web of Science Core Collection between January 1, 2007 and Feb 22, 2022. Search terms included a combination of keywords and controlled vocabulary terms for cerebral venous thrombosis, vitamin K antagonists/warfarin, and DOACs. We included both randomized and nonrandomized studies that compared vitamin K antagonists and DOACs in 5 or more patients with cerebral venous thrombosis. Where studies were sufficiently similar, we performed meta-analyses for efficacy (recurrent venous thromboembolism and complete recanalization) and safety (major hemorrhage) outcomes, using relative risks (RRs)., Results: Out of 10 665 records identified, we screened 254 as potentially eligible. Nineteen studies (16 observational studies [n=1735] and 3 randomized controlled trials [n=215]) met the inclusion criteria. All 3 randomized controlled trials had some concerns, and all 16 observational studies had at least moderate risk of bias. When compared with vitamin K antagonist treatment, DOAC had comparable risks of recurrent venous thromboembolism (relative risk [RR], 0.85 [95% CI, 0.52-1.37], I 2 =0%), major hemorrhage (RR, 0.70 [95% CI, 0.40-1.21], I 2 =0%), intracranial hemorrhage (RR, 0.58 [95% CI, 0.30-1.12]; I 2 =0%), death (RR, 1.14 [95% CI, 0.54-2.43], I 2 =1%), and complete venous recanalization (RR, 0.98 [95% CI, 0.87-1.11]; I 2 =0%)., Conclusions: This systematic review and meta-analysis suggest that in patients with cerebral venous thrombosis, DOACs, and warfarin may have comparable efficacy and safety. Given the limitations of the studies included (low number of randomized controlled trials, modest total sample size, rare outcome events), our findings should be interpreted with caution pending confirmation by ongoing randomized controlled trials and large, prospective, observational studies.

Background: Though stroke risk factors such as substance use may vary with age, less is known about trends in substance use over time or about performance of toxicology screens in young adults with stroke., Methods: Using the Greater Cincinnati Northern Kentucky Stroke Study, a population-based study in a 5-county region comprising 1.3 million people, we reported the frequency of documented substance use (cocaine/marijuana/opiates/other) obtained from electronic medical record review, overall and by race/gender subgroups among physician-adjudicated stroke events (ischemic and hemorrhagic) in adults 20 to 54 years of age. Secondary analyses included heavy alcohol use and cigarette smoking. Data were reported for 5 one-year periods spanning 22 years (1993/1994-2015), and trends over time were tested. For 2015, to evaluate factors associated with performance of toxicology screens, multiple logistic regression was performed., Results: Overall, 2152 strokes were included: 74.5% were ischemic, mean age was 45.7±7.6, 50.0% were women, and 35.9% were Black. Substance use was documented in 4.4%, 10.4%, 19.2%, 24.0%, and 28.8% of cases in 1993/1994, 1999, 2005, 2010, and 2015, respectively ( P trend <0.001). Between 1993/1994 and 2015, documented substance use increased in all demographic subgroups. Adjusting for gender, comorbidities, and National Institutes of Health Stroke Scale, predictors of toxicology screens included Black race (adjusted odds ratio, 1.58 [95% CI, 1.02-2.45]), younger age (adjusted odds ratio, 0.70 [95% CI, 0.53-0.91], per 10 years), current smoking (adjusted odds ratio, 1.62 [95% CI, 1.06-2.46]), and treatment at an academic hospital (adjusted odds ratio, 1.80 [95% CI, 1.14-2.84]). After adding chart-reported substance use to the model, only chart-reported substance abuse and age were significant., Conclusions: In a population-based study of young adults with stroke, documented substance use increased over time, and documentation of substance use was higher among Black compared with White individuals. Further work is needed to confirm race-based disparities and trends in substance use given the potential for bias in screening and documentation. Findings suggest a need for more standardized toxicology screening.

Background: Whether the composition of intravenous crystalloid solutions affects outcomes in adults with aneurysmal subarachnoid hemorrhage (aSAH) remains unknown. Therefore, we determined whether the use of saline is associated with lower risk of disability and death in aSAH patients compared to balanced crystalloids., Methods: We conducted a post hoc subgroup analysis of the Isotonic Solutions and Major Adverse Renal Events Trial (SMART), a pragmatic, unblinded, cluster-randomized, multiple-crossover clinical trial that enrolled 15,802 adults between June 2015 and April 2017. We compared intravenous administration of saline to balanced crystalloids in consecutively enrolled aSAH patients aged 18 years or older whose ruptured aneurysm was procedurally secured at a single academic center in the United States. The primary outcome was the score on the modified Rankin scale (mRS, range, 0 [no symptoms] to 6 [death]) at 90 days obtained from a prospective institutional stroke registry. Secondary outcome included death by 90 days. Logistic or proportional odds regression models were used to test for between-group differences adjusted for age, hypertension, aSAH grade, and procedure type., Results: Of the 79 aSAH patients procedurally treated during the SMART study period, 78 were enrolled (median age, 58 years; IQR, 49 to 64.5; 64% female), with 41 (53%) assigned to saline and 37 (47%) to balanced crystalloids. Plasma-Lyte was the primary balanced crystalloid used. Among 72 patients with 90-day mRS assessment, the adjusted common odds ratio, aOR, for mRS was 0.68 (95% CI, 0.28-1.63; P=0.39), with values less than 1.0 favoring saline. By 90 days, 2/39 patients (5%) in the saline group and 9/35 (26%) in the balanced-crystalloids group had died (aOR, 0.06; 95% CI, 0.00-0.50; P=0.02)., Conclusions: Among procedurally treated aSAH patients, the risk of disability or death at 90 days did not significantly differ between saline and balanced crystalloids. Death occurred less frequently with saline than balanced crystalloids.

Background: There are limited data about the epidemiology and secondary stroke prevention strategies used for patients with depressed left ventricular ejection fraction (LVEF) and sinus rhythm following an acute ischemic stroke (AIS). We sought to describe the prevalence of LVEF ≤40% and sinus rhythm among patients with AIS and antithrombotic treatment practice in a multi-center cohort from 2002 to 2018., Methods: This was a multi-center, retrospective cohort study comprised of patients with AIS hospitalized in the Greater Cincinnati Northern Kentucky Stroke Study and 4 academic, hospital-based cohorts in the United States. A 1-stage meta-analysis of proportions was undertaken to calculate a pooled prevalence. Univariate analyses and an adjusted multivariable logistic regression model were performed to identify demographic, clinical, and echocardiographic characteristics associated with being prescribed an anticoagulant upon AIS hospitalization discharge., Results: Among 14 338 patients with AIS with documented LVEF during the stroke hospitalization, the weighted pooled prevalence of LVEF ≤40% and sinus rhythm was 5.0% (95% CI, 4.1-6.0%; I 2 , 84.4%). Of 524 patients with no cardiac thrombus and no prior indication for anticoagulant who survived postdischarge, 200 (38%) were discharged on anticoagulant, 289 (55%) were discharged on antiplatelet therapy only, and 35 (7%) on neither. There was heterogeneity by site in the proportion discharged with an anticoagulant (22% to 45%, P <0.0001). Cohort site and National Institutes of Health Stroke Severity scale >8 (odds ratio, 2.0 [95% CI, 1.1-3.8]) were significant, independent predictors of being discharged with an anticoagulant in an adjusted analysis., Conclusions: Nearly 5% of patients with AIS have a depressed LVEF and are in sinus rhythm. There is significant variation in the clinical practice of antithrombotic therapy prescription by site and stroke severity. Given this clinical equipoise, further study is needed to define optimal antithrombotic treatment regimens for secondary stroke prevention in this patient population.

National Institutes of Health Stroke Scale (NIHSS), measured a few hours to days after stroke onset, is an attractive outcome measure for stroke research. NIHSS at the time of presentation (baseline NIHSS) strongly predicts the follow-up NIHSS. Because of the need to account for the baseline NIHSS in the analysis of follow-up NIHSS as an outcome measure, a common and intuitive approach is to define study outcome as the change in NIHSS from baseline to follow-up (ΔNIHSS). However, this approach has important limitations. Analyzing ΔNIHSS implies a very strong assumption about the relationship between baseline and follow-up NIHSS that is unlikely to be satisfied, drawing into question the validity of the resulting statistical analysis. This reduces the precision of the estimates of treatment effects and the power of clinical trials that use this approach to analysis. ANCOVA allows for the analysis of follow-up NIHSS as the dependent variable while adjusting for baseline NIHSS as a covariate in the model and addresses several challenges of using ΔNIHSS outcome using simple bivariate comparisons (eg, a t test, Wilcoxon rank-sum, linear regression without adjustment for baseline) for stroke research. In this article, we use clinical trial simulations to illustrate that variability in NIHSS outcome is less when follow-up NIHSS is adjusted for baseline compared to ΔNIHSS and how a reduction in this variability improves the power. We outline additional, important clinical and statistical arguments to support the superiority of ANCOVA using the final measurement of the NIHSS adjusted for baseline over, and caution against using, the simple bivariate comparison of absolute NIHSS change (ie, delta).

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: A small randomized controlled trial suggested that dabigatran may be as effective as warfarin in the treatment of cerebral venous thrombosis (CVT). We aimed to compare direct oral anticoagulants (DOACs) to warfarin in a real-world CVT cohort., Methods: This multicenter international retrospective study (United States, Europe, New Zealand) included consecutive patients with CVT treated with oral anticoagulation from January 2015 to December 2020. We abstracted demographics and CVT risk factors, hypercoagulable labs, baseline imaging data, and clinical and radiological outcomes from medical records. We used adjusted inverse probability of treatment weighted Cox-regression models to compare recurrent cerebral or systemic venous thrombosis, death, and major hemorrhage in patients treated with warfarin versus DOACs. We performed adjusted inverse probability of treatment weighted logistic regression to compare recanalization rates on follow-up imaging across the 2 treatments groups., Results: Among 1025 CVT patients across 27 centers, 845 patients met our inclusion criteria. Mean age was 44.8 years, 64.7% were women; 33.0% received DOAC only, 51.8% received warfarin only, and 15.1% received both treatments at different times. During a median follow-up of 345 (interquartile range, 140-720) days, there were 5.68 recurrent venous thrombosis, 3.77 major hemorrhages, and 1.84 deaths per 100 patient-years. Among 525 patients who met recanalization analysis inclusion criteria, 36.6% had complete, 48.2% had partial, and 15.2% had no recanalization. When compared with warfarin, DOAC treatment was associated with similar risk of recurrent venous thrombosis (aHR, 0.94 [95% CI, 0.51-1.73]; P =0.84), death (aHR, 0.78 [95% CI, 0.22-2.76]; P =0.70), and rate of partial/complete recanalization (aOR, 0.92 [95% CI, 0.48-1.73]; P =0.79), but a lower risk of major hemorrhage (aHR, 0.35 [95% CI, 0.15-0.82]; P =0.02)., Conclusions: In patients with CVT, treatment with DOACs was associated with similar clinical and radiographic outcomes and favorable safety profile when compared with warfarin treatment. Our findings need confirmation by large prospective or randomized studies.

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.)

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

Background: It is unclear what factors clinicians consider when deciding about endovascular thrombectomy (EVT) in acute ischemic stroke patients with a pre-existing disability. We aimed to explore international practice patterns and preferences for EVT in patients with a pre-stroke disability, defined as a modified Rankin score (mRS) ≥ 2. Methods: Electronic survey link was sent to principal investigators of five major EVT trials and members of a professional interventional neurology society. Results: Of the 81 survey-responding clinicians, 57% were neuro-interventionalists and 33% were non-interventional stroke clinicians. Overall, 64.2% would never or almost never consider EVT for a patient with pre-stroke mRS of 4-5, and 49.3% would always or almost always offer EVT for a patient with pre-stroke mRS 2-3. Perceived benefit of EVT (89%) and severity of baseline disability (83.5%) were identified as the most important clinician-level and patient-level factors that influence EVT decisions in these patients. Conclusion: In this survey of 80 respondents, we found that EVT practice for patients with pre-stroke disability across the world is heterogenous and depends upon patient characteristics. Individual clinician opinions substantially alter EVT decisions in pre-stroke disabled patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Salwi, Niec, Hassan, Lindsell, Khatri, Mocco, Saver and Mistry.)

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

Background: Elevated systolic blood pressure (SBP) in the acute phase after endovascular therapy (EVT) is associated with worse outcome. However, the association between systolic blood pressure reduction (SBPr) and the outcome of EVT is not well understood., Objective: To determine the association between SBPr and clinical outcomes after EVT in a prospective multicenter cohort., Methods: A post hoc analysis of the Blood Pressure after Endovascular Stroke Therapy (BEST) prospective observational cohort study was carried out. SBPr was defined as the absolute difference between admission SBP and mean SBP in the first 24 hours after EVT. Logistic regression was used to assess the association between SBPr and poor functional outcome (modified Rankin Scale score 3-6) at 90 days., Results: A total of 259/433 (58.5%) patients had poor outcome. SBPr was higher in the poor outcome group than in the good outcome group (26.6±27.4 vs 19.0±22.3 mm Hg; p<0.001). However, in adjusted models, SBPr was not independently associated with poor outcome (OR=1.00 per 1 mm Hg increase, 95% CI 0.99 to 1.01) or death (OR=0.9 per 1 mm Hg increase; 95% CI 0.98 to 1.00). No association remained when SBPr was divided into tertiles. Subgroup analyses based on history of hypertension, revascularization status, and antihypertensive treatment yielded similar results., Conclusion: The reduction in baseline SBP following EVT was not associated with poor functional outcomes. Most of the cohort (88%) achieved successful recanalization, and therefore, these results mainly apply to patients with successful recanalization., Competing Interests: Competing interests: EAM reports grants from the Society of Vascular and Interventional Neurology, University of Cincinnati Gardner Neuroscience Institute, and Vanderbilt Faculty Research Scholar Program. AdH reports a research grant from NIH/NINDS (K23NS105924)., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: According to evidence-based clinical practice guidelines, patients presenting with disabling stroke symptoms should be treated with intravenous tissue plasminogen activator (IV tPA) within 4.5 h of time last known well. However, 25% of strokes are detected upon awakening (i.e., wake-up stroke [WUS]), which renders patients ineligible for IV tPA administered via time-based treatment algorithms, because it is impossible to establish a reliable time of symptom onset. We performed a systematic review and meta-analysis of the efficacy and safety of IV tPA compared with normal saline, placebo, or no treatment in patients with WUS using imaging-based treatment algorithms., Methods: We searched MEDLINE, Web of Science, and Scopus between January 1, 2006 and April 30, 2020. We included controlled trials (randomized or nonrandomized), observational cohort studies (prospective or retrospective), and single-arm studies in which adults with WUS were administered IV tPA after magnetic resonance imaging (MRI)- or computed tomography (CT)-based imaging. Our primary outcome was recovery at 90 days (defined as a modified Rankin Scale [mRS] score of 0-2), and our secondary outcomes were symptomatic intracranial hemorrhage (sICH) within 36 h, mortality, and other adverse effects., Results: We included 16 studies that enrolled a total of 14,017 patients. Most studies were conducted in Europe (37.5%) or North America (37.5%), and 1757 patients (12.5%) received IV tPA. All studies used MRI-based (five studies) or CT-based (10 studies) imaging selection, and one study used a combination of modalities. Sixty-one percent of patients receiving IV tPA achieved an mRS score of 0 to 2 at 90 days (95% confidence interval [CI]: 51%-70%, 12 studies), with a relative risk (RR) of 1.21 compared with patients not receiving IV tPA (95% CI: 1.01-1.46, four studies). Three percent of patients receiving IV tPA experienced sICH within 36 h (95% CI: 2.5%-4.1%; 16 studies), which is an RR of 4.00 compared with patients not receiving IV tPA (95% CI: 2.85-5.61, seven studies)., Conclusions: This systematic review and meta-analysis suggests that IV tPA is associated with a better functional outcome at 90 days despite the increased but acceptable risk of sICH. Based on these results, IV tPA should be offered as a treatment for WUS patients with favorable neuroimaging findings., (© 2021 European Academy of Neurology.)

Introduction: The National Inpatient Sample (NIS) has led to several breakthroughs via large sample size. However, utility of NIS is limited by the lack of admission NIHSS and 90-day modified Rankin score (mRS). This study creates estimates for stroke severity at admission and 90-day mRS using NIS data for acute ischemic stroke (AIS) patients treated with mechanical thrombectomy (MT)., Methods: Three patient cohorts undergoing MT for AIS were utilized: Cohort 1 (N = 3729) and Cohort 3 (N = 1642) were derived from NIS data. Cohort 2 (N=293) was derived from a prospectively-maintained clinical registry. Using Cohort 1, Administrative Stroke Outcome Variable (ASOV) was created using disposition and mortality. Factors reflective of stroke severity were entered into a stepwise logistic regression predicting poor ASOV. Odds ratios were used to create the Administrative Data Stroke Scale (ADSS). Performances of ADSS and ASOV were tested using Cohort 2 and compared with admission NIHSS and 90-day mRS, respectively. ADSS performance was compared with All Patient Refined-Diagnosis Related Group (APR-DRG) severity score using Cohort 3., Results: Agreement of ASOV with 90-day mRS > 2 was fair (κ = 0.473). Agreement with 90-day mRS > 3 was substantial (κ = 0.687). ADSS significantly correlated (p < 0.001) with clinically-significant admission NIHSS > 15. ADSS performed comparably (AUC = 0.749) to admission NIHSS (AUC = 0.697) in predicting 90-day mRS > 2 and mRS > 3 (AUC = 0.767, 0.685, respectively). ADSS outperformed APR-DRG severity score in predicting poor ASOV (AUC = 0.698, 0.682, respectively)., Conclusion: We developed and validated measures of stroke severity at admission (ADSS) and outcome (ASOV, estimate for 90-day mRS > 3) to increase utility of NIS data in stroke research., Competing Interests: Declarations of Competing Interest Dr. Rohan V. Chitale Dr. Rohan V. Chitale receives research grants from Medtronic, Cerenovus, and Microvention; and serves as a consultant for Medtronic. Dr. Eva A. Mistry receives grant support from NIH/NINDS (K23NS113858). All other authors have no significant financial disclosures., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background/purpose: Our study aimed to assess the impacts of neighborhood socioeconomic status on mechanical thrombectomy (MT) outcomes for acute ischemic stroke (AIS)., Methods: We conducted a prospective observational study of consecutive adult AIS patients treated with MT at one US comprehensive stroke center from 2012 to 2018. A composite neighborhood socioeconomic score (nSES) was created using patient home address, median household income, percentage of households with interest, dividend, or rental income, median value of housing units, percentage of persons 25 or older with high school degrees, college degrees or holding executive, managerial or professional specialty occupations. Using this score, patients were divided into low, middle and high nSES tertiles. Outcomes included 90-day functional independence, in-hospital mortality, length of hospital stay, discharge location, time to recanalization, successful recanalization, and symptomatic intracranial hemorrhage (sICH)., Results: 328 patients were included. Between the three nSES groups, proportion of White patients, time-to-recanalization and admission NIH stroke scale differed significantly (p<0.05). Patients in the high nSES tertile were more likely to be functionally dependent at 90 days (unadjusted OR, 95% CI, 1.91 [1.10, 3.36]) and were less likely to die in the hospital (unadjusted OR, 95% CI, 0.46, [0.20, 0.98]). Further, patients in the high nSES tertile had decreased times to recanalization (median time in minutes, low=335, mid=368, high=297, p=0.04). However, after adjusting for variance in race and severity of stroke, the differences in clinical outcomes were not significant., Conclusion: This study highlights how unadjusted neighborhood socioeconomic status is significantly associated with functional outcome, mortality, and time-to-recanalization following MT for AIS. Since adjustment modifies the significant association, the socioeconomic differences may be influenced by differences in pre-hospital factors that drive severity of stroke and time to recanalization. Better understanding of the interplay of these factors may lead to timelier evaluation and improvement in patient outcomes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Purpose: The Alberta Stroke Program Early Computed Tomography (CT) Score (ASPECTS) and CT perfusion (CTP) are commonly used to predict the ischemic core in acute ischemic strokes. CT angiography source images (CTA-SI) can also provide additional information to identify the extent of ischemia. Our objective was to investigate the correlation of noncontrast CT (NCCT) ASPECTS and CTA-SI ASPECTS with CTP core volumes., Methods: We utilized a single institutional, retrospective registry of consecutive patients with acute ischemic stroke with large vessel occlusion between May 2016 and May 2018. We graded ASPECTS both on baseline NCCT and CTA-SI and measured CTP core using automated RAPID software (cerebral blood flow <30%). We used Spearman's correlation coefficients to evaluate the correlation between continuous variables., Results: A total of 52 patients fit the inclusion criteria of large vessel occlusion in 6 to 24 hours and baseline imaging work up of NCCT, CTA, and CTP. The median age was 63 (interquartile range=53.5-75) and 38.46% were female. The median NCCT ASPECTS was 7 (interquartile range=6-9), CTA-SI ASPECTS was 5 (interquartile range=4-7), and CTP core was 14.5 mL (interquartile range=0-46 mL). There was a moderate correlation between NCCT ASPECTS and CTP core (r s =-0.55, P <0.0001) and between CTA-SI ASPECTS and CTP core (r s =-0.50, P =0.0002). The optimal NCCT ASPECTS cutoff score to detect CTP core ≤70 mL was ≥6 (sensitivity, 0.84; specificity, 0.57; positive predictive value, 0.93; negative predictive value, 0.36) and the optimal CTA-SI ASPECTS was ≥5 (sensitivity, 0.76; specificity, 0.71; positive predictive value, 0.94; negative predictive value, 0.31)., Conclusions: There was a moderate correlation between NCCT and CTA-SI ASPECTS in predicting CTP defined ischemic core in delayed time windows. Further studies are needed to determine if NCCT and CTA imaging could be used for image-based patient selection when CTP imaging is not available.

Background and Purpose: Anticoagulation therapy not only reduces the risk of ischemic stroke in atrial fibrillation (AF) but also predisposes patients to hemorrhagic complications. There is limited knowledge on the risk of first-ever ischemic stroke in patients with AF after extracranial hemorrhage (ECH)., Methods: We conducted a retrospective study using the California State Inpatient Database including all nonfederal hospital admissions in California from 2005 to 2011. The exposure variable was hospitalization with a diagnosis of ECH with a previous diagnosis of AF. The outcome variable was a subsequent hospitalization with acute ischemic stroke. We excluded patients with stroke before or at the time of ECH diagnosis. We calculated adjusted hazard ratios for ischemic stroke during follow-up and at 6-month intervals using Cox regression models adjusted for pertinent demographics and comorbidities. In subgroup analyses, subjects were stratified by primary ECH diagnosis, severity/type of ECH, age, CHA 2 DS 2 -VASc score, or the presence/absence of a gastrointestinal or genitourinary cancer., Results: We identified 764 257 patients with AF (mean age 75 years, 49% women) without a documented history of stroke. Of these, 98 647 (13%) had an ECH-associated hospitalization, and 22 748 patients (3%) developed an ischemic stroke during the study period. Compared to patients without ECH, subjects with ECH had ≈15% higher rate of ischemic stroke (overall adjusted hazard ratio, 1.15 [95% CI, 1.11-1.19]). The risk appeared to remain elevated for at least 18 months after the index ECH. In subgroup analyses, the risk was highest in subjects with a primary admission diagnosis of ECH, severe ECH, gastrointestinal-type ECH, with gastrointestinal or genitourinary cancer, and age ≥60 years., Conclusions: Patients with AF hospitalized with ECH may have a slightly elevated risk for future ischemic stroke. Particular consideration should be given to the optimal balance between the benefits and risks of anticoagulation therapy and the use of nonanticoagulant alternatives, such as left atrial appendage closure in this vulnerable population.