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Background: The National Institutes of Health Stroke Scale (NIHSS) is a pivotal clinical tool used to assess patients with acute stroke. However, substantial heterogeneity in the application and interpretation of stroke scale items can occur. This systematic review aimed to elucidate heterogeneity in measuring the NIHSS., Material and Methods: A literature search was performed on PubMed/OVID/Cochran's CENTRAL from inception to 2023. The references of the included papers were reviewed for further eligible articles. Clinical characteristic, NIHSS values, and sources of heterogeneity were recorded. Non-human and non-English language articles were excluded. The study quality was assessed using MINORS and GRADE. Meta-analysis and meta-regression were performed using a random-effects model to explore the sources of heterogeneity., Results: Twenty-one papers for a total of 818 patients (mean per study: 39 ± 37) and 9696 NIHSS examinations (median per study: 8 [CI95% 2 to 42]) were included. Motor function had a higher ICC agreement (ranging from 0.85 ["Right Leg"] to 0.90 ["Right Arm"]) compared to the remaining items (ranging from 0.58 ["Facial Palsy"] to 0.85 ["Level of consciousness commands"]. The meta-regression showed a low effect size of covariates such as language version, remote evaluation, and retrospective analysis on NIHSS items (e.g., for "Level of consciousness commands," language effect was 0.30 [CI95% 0.20 to 0.48] and for "Visual", the retrospective assessment effect was -0.27 [CI95% -0.51 to -0.03])., Conclusion: The NIHSS scores showed moderate to excellent inter-rater agreement, with the highest heterogeneity in non-motor function evaluation. Using a non-English version, remote evaluation and retrospective analysis had small effects in terms of heterogeneity in the NIHSS scores., Competing Interests: Declarations. Conflict of interest: NA. Ethical approval: NA. Informed consent: NA. Guarantor: LS., (© 2024. Fondazione Società Italiana di Neurologia.)

Heart failure (HF) is an important comorbidity for patients with ischemic stroke, present in 11 %-18 % of patients, and may also independently increase the risk of first-ever and recurrent ischemic stroke. HF is categorized based on ejection fraction (EF) into HF with reduced (HFrEF), mildly-reduced (HFmrEG) and preserved ejection fraction (HFpEF), with the efficacy of HF therapies differing between the three subcategories. Despite this classification, the incidence, recurrence rates and outcomes of ischemic stroke do not appear to differ significantly between the three subtypes, even when considering the concurrent presence of atrial fibrillation. However, several randomized-controlled clinical trials of anticoagulation defined HF based on reduced EF, inevitably excluding a large proportion of patients with HFpEF. This exclusion is significant considering marked differences between heart failure phenotypes. Such discrepancies raise concerns about the broad applicability of the results of these studies, including those of primary or secondary stroke prevention in HF. Future trials should include both patients with HFrEF and HFpEF to evaluate the safety and efficacy of antiocoagulation therapies in primary and secondary stroke prevention across the spectrum of the EF., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Direct oral anticoagulants are the standard of care for stroke prevention in eligible patients with atrial fibrillation and atrial flutter; however, bleeding remains a significant concern, limiting their use. Milvexian is an oral Factor XIa inhibitor that may offer similar anticoagulant efficacy with less bleeding risk., Methods: LIBREXIA AF (NCT05757869) is a global phase III, randomized, double-blind, parallel-group, event-driven trial to compare milvexian with apixaban in participants with atrial fibrillation or atrial flutter. Participants are randomly assigned to milvexian 100 mg or apixaban (5 mg or 2.5 mg per label indication) twice daily. The primary efficacy objective is to evaluate if milvexian is noninferior to apixaban for the prevention of stroke and systemic embolism. The principal safety objective is to evaluate if milvexian is superior to apixaban in reducing the endpoint of International Society of Thrombosis and Hemostasis (ISTH) major bleeding events and the composite endpoint of ISTH major and clinically relevant nonmajor (CRNM) bleeding events. In total, 15,500 participants from approximately 1,000 sites in over 30 countries are planned to be enrolled. They will be followed until both 430 primary efficacy outcome events and 530 principal safety events are observed, which is estimated to take approximately 4 years., Conclusion: The LIBREXIA AF study will determine the efficacy and safety of the oral Factor XIa inhibitor milvexian compared with apixaban in participants with either atrial fibrillation or atrial flutter., Trial Registration: ClinicalTrials.gov NCT05757869., Competing Interests: Disclosures SSJ reports consulting fees from Bristol Myers Squibb, ARTIS Ventures, and Broadview Ventures outside of the submitted work. KWM’s financial disclosures can be reviewed at http://med.stanford.edu/profiles/kenneth-mahaffey. KSP is a member of The Thrombosis Research Institute which has received institutional research grant support from Anthos Therapeutics and Bayer Pharmaceuticals. She has received honoraria from Element Science and Artivion, Inc. WS has received honoraria (>10K USD) from Daiichi Sankyo, Nippon Boehringer Ingelheim, and Pfizer Japan, and research grants (>50K USD) from Daiichi Sankyo and Nippon Boehringer Ingelheim. CTR reports Research Grants through Institution from: Athos, AstraZeneca, Daiichi Sankyo, Janssen and Novartis. Honoraria for scientific ad boards and consulting from: Anthos, Bayer, Bristol Myers Squibb, Daiichi Sankyo, Janssen and Pfizer. He is a member of The TIMI Study Group which has received institutional research grant support through Brigham and Women's Hospital from: Abbott, Abiomed, Inc, Amgen, Anthos Therapeutics, ARCA Biopharma, Inc, AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Ionis Pharmaceuticals, Inc, Janssen Research & Development, LLC, MedImmune, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc, Roche, Saghmos Therapeutics, Inc, Siemens Healthcare Diagnostics, Inc, Softcell Medical Limited, The Medicines Company, Verve Therapeutics, Inc, Zora Biosciences. PRK reports consultancy from Anthos, J&J, BMS and Bayer. GS has received research grants from Amarin, AstraZeneca, and Sanofi; has participated in clinical trials, consulting, or speaking for Amarin, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Idorsia, Janssen, Novartis, Novo Nordisk, PhaseBio, Pfizer, and Sanofi; is a Senior Associate Editor at Circulation; and serves as the CMO for Bioquantis. RM reports institutional research payments from: Abbott, Affluent Medical, Alleviant Medical, Amgen, AstraZeneca, BAIM, Beth Israel Deaconess Medical Center, Boston Scientific, Bristol-Myers Squibb, CardiaWave, CERC, Chiesi, Concept Medical, Daiichi Sankyo, Duke, Faraday, Idorsia, Janssen, MedAlliance, Medscape, Mediasphere, Medtelligence, Medtronic, Novartis, OrbusNeich, Pi-Cardia, Protembis, RM Global Bioaccess Fund Management, Sanofi; consultant to Affluent Medical, Boehringer Ingelheim, Chiesi USA, Cordis, Esperion Science/Innovative Biopharma, Gaffney Events, Educational Trust, Global Clinical Trial Partners, Ltd., IQVIA, Medscape/WebMD Global, NovoNordisk, PeerView Institute for Medical Education, TERUMO Europe N.V., Radcliffe and honoararia from AMA and ACC. SCJ has received research support from Jansen, BMS, and AstraZeneca. GJH reports personal honoraria outside the submitted work from the American Heart Association (Associate Editor, Circulation), Bristol Myers Squibb (Steering Committee, AXIOMATIC-SSP trial of milvexian [factor XIa inhibitor] for secondary stroke prevention) and Janssen (Co-chair, Executive Committee, Librexia Stroke trial of milvexian for secondary stroke prevention). RAH has received research grants/contracts from NHLBI (ISCHEMIA), Duke/PCORI (ADAPTABLE), Janssen (Factor Xia inhibitor), CSL (HDL), Baim Institute, UColorado, Harvard (BWH), and Merck; has served as a consultant/advisor for NHLBI (COVID/CONNECTS), Atropos Health, Bitterroot Bio, Bristol Myers Squibb, Bridge Bio, Chiesi, CSL Behring, Edwards Lifesciences Corp, Element Science, Foresight, Merck, and WebMD; and serves on the Board of Directors for AHA and Cytokinetics. CSPL is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has Received research support from Novo Nordisk and Roche Diagnostics; has Served as consultant or on the Advisory Board/ Steering Committee/ Executive Committee for Alleviant Medical, Allysta Pharma, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Biopeutics, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, CardioRenal, CPC Clinical Research, Eli Lilly, Hanmi, Impulse Dynamics, Intellia Therapeutics, Ionis Pharmaceutical, Janssen Research & Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, Prosciento Inc, Quidel Corporation, Radcliffe Group Ltd., Recardio Inc, ReCor Medical, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics and Us2.ai; and serves as Co-founder and nonexecutive director of Us2.ai. The remaining authors report no relevant disclosures or competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Rates of dual antiplatelet therapy (DAPT) after high-risk transient ischemic attack or minor ischemic stroke (TIAMIS) are suboptimal. We performed a cost-effectiveness analysis to characterize the parameters of a quality improvement (QI) intervention designed to increase DAPT use after TIAMIS., Methods and Results: We constructed a decision tree model that compared current national rates of DAPT use after TIAMIS with rates after implementing a theoretical QI intervention designed to increase appropriate DAPT use. The base case assumed that a QI intervention increased the rate of DAPT use to 65% from 45%. Costs (payer and societal) and outcomes (stroke, myocardial infarction, major bleed, or death) were modeled using a lifetime horizon. An incremental cost-effectiveness ratio <$100 000 per quality-adjusted life year was considered cost-effective. Deterministic and probabilistic sensitivity analyses were performed. From the payer perspective, a QI intervention was associated with $9657 in lifetime cost savings and 0.18 more quality-adjusted life years compared with current national treatment rates. A QI intervention was cost-effective in 73% of probabilistic sensitivity analysis iterations. Results were similar from the societal perspective. The maximum acceptable, initial, 1-time payer cost of a QI intervention was $28 032 per patient. A QI intervention that increased DAPT use to at least 51% was cost-effective in the base case., Conclusions: Increasing DAPT use after TIAMIS with a QI intervention is cost-effective over a wide range of costs and proportion of patients with TIAMIS treated with DAPT after implementation of a QI intervention. Our results support the development of future interventions focused on increasing DAPT use after TIAMIS.

Introduction: Infertility treatment with assisted reproductive technologies (ARTs) has been associated with adverse vascular events in some but not all previous studies. Endothelial damage, prothrombotic factor release, and a higher prevalence of cardiovascular risk factors in those receiving ART have been invoked to explain this association. We sought to explore the relationship between ART and stroke risk using population-level data., Methods: We conducted a retrospective cohort study using data from the National Inpatient Sample registry from 2015 to 2020, including all delivery hospitalizations for patients aged 15 to 55 years. The study exposure was use of ART. The primary end point was any stroke defined as ischemic stroke, subarachnoid hemorrhage, intracerebral hemorrhage, or cerebral venous thrombosis during index delivery hospitalization. Individual stroke subtypes (ischemic stroke, subarachnoid hemorrhage, intracerebral hemorrhage, and cerebral venous thrombosis) were evaluated as secondary end points. Standard International Classification of Diseases, Tenth Revision , Clinical Modification algorithms were used to define study exposure, comorbidities, and prespecified end points. In addition to reporting population-level estimates, propensity score adjustment by inverse probability weighting was used to mimic the effects of randomization by balancing baseline clinical characteristics associated with stroke between ART and non-ART users., Results: Among 19 123 125 delivery hospitalizations identified, patients with prior ART (n=202 815, 1.1%) experienced significantly higher rates of any stroke (27.1/100 000 versus 9.1/100 000), ischemic stroke (9.9/100 000 versus 3.3/100 000), subarachnoid hemorrhage (7.4/100 000 versus 1.6/100 000), intracerebral hemorrhage (7.4/100 000 versus 2.0/100 000), and cerebral venous thrombosis (7.4/100 000 versus 2.7/100 000) in comparison to non-ART users (all P <0.001 for all unadjusted comparisons). Following inverse probability weighting analysis, ART was associated with increased odds of any stroke (adjusted odds ratios, 2.14 (95% CI, 2.02-2.26); P <0.001)., Conclusions: Using population-level data among patients hospitalized for delivery in the United States, we found an association between ART and stroke after adjustment for measured confounders., Competing Interests: Disclosures Dr Liberman is supported by National Institute for Neurological Disorders and Stroke (NINDS) research grant K23NS10764. Dr Navi has received personal fees for serving as a neurology expert witness. Dr Kamel reports PI for the ARCADIA trial (NIH/NINDS U01NS095869), which receives in-kind study drug from the BMS-Pfizer Alliance for Eliquis and ancillary study support from Roche Diagnostics; other funding from NIH (R01HL144541, R01NS123576, 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. Dr Seitz has stock in Colgate-Palmolive Company and had stock (sold December 2022) in Baxter International, Inc, Bristol Myers Squibb Company, CVS Health Corporation, Johnson & Johnson, Eli Lilly, and Company, Proctor & Gamble Company, UnitedHealth Group Incorporated, Walgreen Boots Alliance, Inc, and White Mountains Insurance.

Rigorous evidence generation with randomized controlled trials has lagged for aneurysmal subarachnoid hemorrhage (SAH) compared with other forms of acute stroke. Besides its lower incidence compared with other stroke subtypes, the presentation and outcome of patients with SAH also differ. This must be considered and adjusted for in designing pivotal randomized controlled trials of patients with SAH. Here, we show the effect of the unique expected distribution of the SAH severity at presentation (World Federation of Neurological Surgeons grade) on the outcome most used in pivotal stroke randomized controlled trials (modified Rankin Scale) and, consequently, on the sample size. Furthermore, we discuss the advantages and disadvantages of different options to analyze the outcome and control the expected distribution of the World Federation of Neurological Surgeons grades in addition to showing their effects on the sample size. Finally, we offer methods that investigators can adapt to more precisely understand the effect of common modified Rankin Scale analysis methods and trial eligibility pertaining to the World Federation of Neurological Surgeons grade in designing their large-scale SAH randomized controlled trials., Competing Interests: Disclosures Dr Saver is a consultant for Abbott Laboratories, Aeromics, Biogen, Boehringer Ingelheim (prevention only), BrainQ, BrainsGate, CSL Behring, Johnson & Johnson Health Care Systems, Inc, Medtronic USA, Inc, and Roche; has stock options in MindRhythm, Neuronics Medical, and Rapid Medical; and is on the Data and Safety Monitoring Board of MIVI Neuroscience. Dr Mack reports equity in Borvo, Cerebrotech, Endostream, Q’Apel, Radical Catheter, Vastrax, and Viseon; reports stock options in Egret, Q’Apel, Spartan Micro, and Stream Biomedical; and is a consultant for Imperative Care, Inc. Dr Kamel serves on the end point adjudication committees of AstraZeneca, Novo Nordisk, and Boehringer Ingelheim; servers on the clinical trial steering/executive committees of Medtronic and Janssen Biotech; is a consultant for Javelin Medical and the American Medical Association; and has household ownership interests in TETMedical. The other authors report no conflicts.

Background: Nontraumatic intracerebral hemorrhage (ICH) is independently associated with a long-term increased risk of major arterial ischemic events. While the relationship between ICH location and ischemic risk has been studied, whether hematoma volume influences this risk is poorly understood., Methods: We pooled individual patient data from the MISTIE III (Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation Phase 3) and the ATACH-2 (Antihypertensive Treatment of Acute Cerebral Hemorrhage-2) trials. The exposure was hematoma volume, treated as a continuous measure in the primary analysis, and dichotomized by the median in the secondary analyses. The outcome was a symptomatic, clinically overt ischemic stroke, adjudicated centrally within each trial. We evaluated the association between hematoma volume and the risk of an ischemic stroke using Cox regression analyses after adjustment for demographics, vascular comorbidities, and ICH characteristics., Results: Of 1470 patients with ICH, the mean age was 61.7 (SD, 12.8) years, and 574 (38.3%) were female. The median hematoma volume was 17.3 mL (interquartile range, 7.2-35.7). During a median follow-up of 107 days (interquartile range, 91-140), a total of 30 ischemic strokes occurred, of which 22 were in patients with a median ICH volume of ≥17.3 mL and a cumulative incidence of 4.6% (95% CI, 3.1-7.1). Among patients with a median ICH volume <17.3 mL, there were 8 ischemic strokes with a cumulative incidence of 3.1% (95% CI, 1.7-6.0). In primary analyses using adjusted Cox regression models, ICH volume was associated with an increased risk of ischemic stroke (hazard ratio, 1.02 per mL increase [95% CI, 1.01-1.04]). In secondary analyses, ICH volume of ≥17.3 mL was associated with an increased risk of ischemic stroke (hazard ratio, 2.5 [95% CI, 1.1-7.2]), compared with those with an ICH volume <17.3 mL., Conclusions: In a heterogeneous cohort of patients with ICH, initial hematoma volume was associated with a heightened short-term risk of ischemic stroke., Competing Interests: Disclosures Dr Harris reports stock holdings in Eli LIlly and stock holdings in GlaxoSmithKline. Dr Iadecola has served on the scientific advisory board for Broadview Ventures. Dr Falcone has received grants from the National Institutes of Health (NIH) and the American Heart Association outside of the submitted work. Dr Sheth reports compensation from Cerevasc for consultant services; service as President for Advanced Innovation in Medicine; a patent pending for Stroke wearables licensed to Alva Health. Dr Goldstein reports compensation from Cayuga for consultant services; compensation from Prothya for consultant services; compensation from AstraZeneca for consultant services; and compensation from Lumosa for consultant services. Dr Qureshi reports compensation from Chiesi Farmaceutici for consultant services and compensation from Chiesi USA, Inc, for consultant services. Dr Awad reports compensation from Medicoegal consulting for expert witness services. Dr Hanley reports grants from US Department of Defense; grants from National Institute of Neurological Disorders and Stroke (NINDS); grants from NINDS to other; grants from NINDS; compensation from Neurelis, Inc, for consultant services; grants from National Center for Advancing Translational Sciences; grants from NINDS; gifts from Jeffrey and Harriet Legum Professorship in Acute Neurological Medicine at Johns Hopkins University. Dr Kamel is a co-principal investigator 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 Bristol Myers Squibb-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. Dr Ziai has received grants from the NIH, serves as the Associate Editor of Neurocritical Care. Dr Murthy has received grant support from the NIH. The other authors report no conflicts.

Importance: Ischemic stroke is a serious complication of cardiac intervention, including surgery and percutaneous procedures. Endovascular thrombectomy (EVT) is an effective treatment for ischemic stroke and may be particularly important for cardiac intervention patients who often cannot receive intravenous thrombolysis., Objective: To examine trends in EVT for ischemic stroke during hospitalization of patients with cardiac interventions vs those without in the United States., Design, Setting, and Participants: This cohort study involved a retrospective analysis using data for 4888 US hospitals from the 2016-2020 National Inpatient Sample database. Participants included adults (age ≥18 years) with ischemic stroke (per codes from the International Statistical Classification of Diseases, Tenth Revision, Clinical Modification), who were organized into study groups of hospitalized patients with cardiac interventions vs without. Individuals were excluded from the study if they had either procedure prior to admission, EVT prior to cardiac intervention, EVT more than 3 days after admission or cardiac intervention, or endocarditis. Data were analyzed from April 2023 to October 2023., Exposures: Cardiac intervention during admission., Main Outcomes and Measures: The odds of undergoing EVT by cardiac intervention status were calculated using multivariable logistic regression. Adjustments were made for stroke severity in the subgroup of patients who had a National Institutes of Health Stroke Scale (NIHSS) score documented. As a secondary outcome, the odds of discharge home by EVT status after cardiac intervention were modeled., Results: Among 634 407 hospitalizations, the mean (SD) age of the patients was 69.8 (14.1) years, 318 363 patients (50.2%) were male, and 316 044 (49.8%) were female. A total of 12 093 had a cardiac intervention. An NIHSS score was reported in 218 576 admissions, 216 035 (34.7%) without cardiac intervention and 2541 (21.0%) with cardiac intervention (P < .001). EVT was performed in 23 660 patients (3.8%) without cardiac intervention vs 194 (1.6%) of those with cardiac intervention (P < .001). After adjustment for potential confounders, EVT was less likely to be performed in stroke patients with cardiac intervention vs those without (adjusted odds ratio [aOR], 0.27; 95% CI, 0.23-0.31), which remained consistent after adjusting for NIHSS score (aOR, 0.28; 95% CI, 0.22-0.35). Among individuals with a cardiac intervention, receiving EVT was associated with a 2-fold higher chance of discharge home (aOR, 2.21; 95% CI, 1.14-4.29)., Conclusions and Relevance: In this study, patients hospitalized with ischemic stroke and cardiac intervention may be less than half as likely to receive EVT as those without cardiac intervention. Given the known benefit of EVT, there is a need to better understand the reasons for lower rates of EVT in this patient population.

Importance: Atrial cardiopathy is associated with stroke in the absence of clinically apparent atrial fibrillation. It is unknown whether anticoagulation, which has proven benefit in atrial fibrillation, prevents stroke in patients with atrial cardiopathy and no atrial fibrillation., Objective: To compare anticoagulation vs antiplatelet therapy for secondary stroke prevention in patients with cryptogenic stroke and evidence of atrial cardiopathy., Design, Setting, and Participants: Multicenter, double-blind, phase 3 randomized clinical trial of 1015 participants with cryptogenic stroke and evidence of atrial cardiopathy, defined as P-wave terminal force greater than 5000 μV × ms in electrocardiogram lead V1, serum N-terminal pro-B-type natriuretic peptide level greater than 250 pg/mL, or left atrial diameter index of 3 cm/m2 or greater on echocardiogram. Participants had no evidence of atrial fibrillation at the time of randomization. Enrollment and follow-up occurred from February 1, 2018, through February 28, 2023, at 185 sites in the National Institutes of Health StrokeNet and the Canadian Stroke Consortium., Interventions: Apixaban, 5 mg or 2.5 mg, twice daily (n = 507) vs aspirin, 81 mg, once daily (n = 508)., Main Outcomes and Measures: The primary efficacy outcome in a time-to-event analysis was recurrent stroke. All participants, including those diagnosed with atrial fibrillation after randomization, were analyzed according to the groups to which they were randomized. The primary safety outcomes were symptomatic intracranial hemorrhage and other major hemorrhage., Results: With 1015 of the target 1100 participants enrolled and mean follow-up of 1.8 years, the trial was stopped for futility after a planned interim analysis. The mean (SD) age of participants was 68.0 (11.0) years, 54.3% were female, and 87.5% completed the full duration of follow-up. Recurrent stroke occurred in 40 patients in the apixaban group (annualized rate, 4.4%) and 40 patients in the aspirin group (annualized rate, 4.4%) (hazard ratio, 1.00 [95% CI, 0.64-1.55]). Symptomatic intracranial hemorrhage occurred in 0 patients taking apixaban and 7 patients taking aspirin (annualized rate, 1.1%). Other major hemorrhages occurred in 5 patients taking apixaban (annualized rate, 0.7%) and 5 patients taking aspirin (annualized rate, 0.8%) (hazard ratio, 1.02 [95% CI, 0.29-3.52])., Conclusions and Relevance: In patients with cryptogenic stroke and evidence of atrial cardiopathy without atrial fibrillation, apixaban did not significantly reduce recurrent stroke risk compared with aspirin., Trial Registration: ClinicalTrials.gov Identifier: NCT03192215.

Competing Interests: HK is a principal investigator for the ARCADIA trial (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, U01NS106513); is Deputy Editor for JAMA Neurology; is on clinical trial steering and executive committees for Medtronic and Janssen; is on endpoint adjudication committees for AstraZeneca, Novo Nordisk, and Boehringer Ingelheim; and has household ownership interests in TETMedical, Spectrum Plastics Group, and Burke Porter Group.

Patent foramen ovale (PFO) is frequently identified in young patients with ischemic stroke. Randomized controlled trials provide robust evidence supporting PFO closure in selected patients with cryptogenic ischemic stroke; however, several questions remain unanswered. This report summarizes current knowledge on the epidemiology of PFO-associated stroke, the role of PFO as a cause of stroke, and anatomic high-risk features. We also comment on breakthrough developments in patient selection algorithms for PFO closure in relation to the PFO-associated stroke causal likelihood risk stratification system. We further highlight areas for future research in PFO-associated stroke including the efficacy and safety of PFO closure in the elderly population, incidence, and long-term consequences of atrial fibrillation post-PFO closure, generalizability of the results of clinical trials in the real world, and the need for assessing the effect of neurocardiology teams on adherence to international recommendations. Other important knowledge gaps such as sex, race/ethnicity, and regional disparities in access to diagnostic technologies, PFO closure devices, and clinical outcomes in the real world are also discussed as priority research topics., Competing Interests: Disclosures Dr Sposato received speaker/consulting honoraria from Boehringer Ingelheim, Pfizer, Bayer, Gore, and Daiichi Sankyo; research grants from Boehringer Ingelheim and Bayer; Editorial Board member, Neurology; Editor, Neurocardiology section, Stroke journal. Associate Editor, JAHA. Dr Albin received research support, American Academy of Neurology; Publishing royalties, publication relating to health care; Personal compensation, Associate Editor, Continuum: Lifelong Learning in Neurology, and received compensation from Springer Nature for other services. Dr Elkind: PI, ARCADIA trial (The Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke Randomized Trial; National Institutes of Health [NIH]/National Institute of Neurological Disorders and Stroke [NINDS] U01NS095869): in-kind study drug from the Bristol-Myers Squibb (BMS)-Pfizer Alliance for Eliquis and ancillary study support from Roche Diagnostics; NIH Funding (R01NS29993; R01ES031808; 1UG3 NS119702); Royalties, UpToDate stroke chapter; Honoraria, lectures from the Atria Academy for Science and Medicine. Employment by American Heart Association. Dr Kamel: PI, ARCADIA trial (NIH/NINDS U01NS095869): in-kind study drug from BMS-Pfizer Alliance for Eliquis; Ancillary study support, Roche Diagnostics; NIH (R01HL144541, R01NS123576, U01NS106513); Deputy Editor, JAMA Neurology; Clinical trial steering/executive committees, Medtronic, Janssen, Javelin Medical; end point adjudication, AstraZeneca, Novo Nordisk, Boehringer Ingelheim; household ownership interests in TETMedical, Spectrum Plastics Group, Burke Porter Group. Compensation from American Medical Association for consultant services. Dr Saver provided study medication supplies for Novo Nordisk, Monies for drug shipping, temperature monitoring and after-hour enrollment for NINDS-funded FASTEST trial (rFVIIa for Acute Hemorrhagic Stroke Administered at Earliest Time), from neurology Department, receives monies to educational/research fund from Genentech for role on Executive Committee of Timeless Trial; Roche Pharmaceuticals, consulting; BrainsGate Ltd, consulting; Basking Biosciences, Kroger Prescription Plans Inc’s Pharmacy & Therapeutics Committee, voting committee member. Received compensation from Biogen for consultant services; compensation from Johnson & Johnson Health Care Systems Inc. for consultant services; compensation from Boehringer Ingelheim (prevention only) for consultant services; and compensation from Abbott Laboratories for consultant services.

Background: The safety and efficacy of oral anticoagulation for prevention of major adverse cardiovascular events in people with atrial fibrillation and spontaneous intracranial haemorrhage are uncertain. We planned to estimate the effects of starting versus avoiding oral anticoagulation in people with spontaneous intracranial haemorrhage and atrial fibrillation., Methods: In this prospective meta-analysis, we searched bibliographic databases and trial registries using the strategies of a Cochrane systematic review (CD012144) on June 23, 2023. We included clinical trials if they were registered, randomised, and included participants with spontaneous intracranial haemorrhage and atrial fibrillation who were assigned to either start long-term use of any oral anticoagulant agent or avoid oral anticoagulation (ie, placebo, open control, another antithrombotic agent, or another intervention for the prevention of major adverse cardiovascular events). We assessed eligible trials using the Cochrane Risk of Bias tool. We sought data for individual participants who had not opted out of data sharing from chief investigators of completed trials, pending completion of ongoing trials in 2028. The primary outcome was any stroke or cardiovascular death. We used individual participant data to construct a Cox regression model of the time to the first occurrence of outcome events during follow-up in the intention-to-treat dataset supplied by each trial, followed by meta-analysis using a fixed-effect inverse-variance model to generate a pooled estimate of the hazard ratio (HR) with 95% CI. This study is registered with PROSPERO, CRD42021246133., Findings: We identified four eligible trials; three were restricted to participants with atrial fibrillation and intracranial haemorrhage (SoSTART [NCT03153150], with 203 participants) or intracerebral haemorrhage (APACHE-AF [NCT02565693], with 101 participants, and NASPAF-ICH [NCT02998905], with 30 participants), and one included a subgroup of participants with previous intracranial haemorrhage (ELDERCARE-AF [NCT02801669], with 80 participants). After excluding two participants who opted out of data sharing, we included 412 participants (310 [75%] aged 75 years or older, 249 [60%] with CHA 2 DS 2 -VASc score ≤4, and 163 [40%] with CHA 2 DS 2 -VASc score >4). The intervention was a direct oral anticoagulant in 209 (99%) of 212 participants who were assigned to start oral anticoagulation, and the comparator was antiplatelet monotherapy in 67 (33%) of 200 participants assigned to avoid oral anticoagulation. The primary outcome of any stroke or cardiovascular death occurred in 29 (14%) of 212 participants who started oral anticoagulation versus 43 (22%) of 200 who avoided oral anticoagulation (pooled HR 0·68 [95% CI 0·42-1·10]; I 2 =0%). Oral anticoagulation reduced the risk of ischaemic major adverse cardiovascular events (nine [4%] of 212 vs 38 [19%] of 200; pooled HR 0·27 [95% CI 0·13-0·56]; I 2 =0%). There was no significant increase in haemorrhagic major adverse cardiovascular events (15 [7%] of 212 vs nine [5%] of 200; pooled HR 1·80 [95% CI 0·77-4·21]; I 2 =0%), death from any cause (38 [18%] of 212 vs 29 [15%] of 200; 1·29 [0·78-2·11]; I 2 =50%), or death or dependence after 1 year (78 [53%] of 147 vs 74 [51%] of 145; pooled odds ratio 1·12 [95% CI 0·70-1·79]; I 2 =0%)., Interpretation: For people with atrial fibrillation and intracranial haemorrhage, oral anticoagulation had uncertain effects on the risk of any stroke or cardiovascular death (both overall and in subgroups), haemorrhagic major adverse cardiovascular events, and functional outcome. Oral anticoagulation reduced the risk of ischaemic major adverse cardiovascular events, which can inform clinical practice. These findings should encourage recruitment to, and completion of, ongoing trials., Funding: British Heart Foundation., Competing Interests: Declaration of interests SJC reports institutional funding from Daiichi Sankyo. CC reports funding from the French Ministry of Health, Novartis (advisory board), and Biogen, Bayer and Bristol Myers Squibb (BMS; steering committees). HK reports funding from the US National Institutes of Health (NIH) and National Institute of Neurological Disorders and Stroke (NINDS; U01NS095869, R01HL144541, R01NS123576, and U01NS106513); funding from BMS-Pfizer Alliance; funding from Roche Diagnostics; being Deputy Editor for JAMA Neurology; participation on clinical trial steering or executive committees for Medtronic, Janssen, and Javelin Medical; participation on endpoint adjudication committees for AstraZeneca, Novo Nordisk, and Boehringer Ingelheim; and household ownership interests in TETMedical, Spectrum Plastics Group, and Burke Porter Group. CJMK and FHBMS report institutional funding from the Dutch Heart Foundation Clinical Established Investigator grant (2012T077) for APACHE-AF. DEN reports institutional funding from BMS and provision of a PET tracer from Life Molecular Imaging. APJ reports personal consulting fees and speaker fees from AstraZeneca. RA-SS reports institutional funding from the British Heart Foundation (CS/18/2/33719) for this work, institutional funding from the UK National Institute for Health and Care Research and The Stroke Association outside the submitted work, being Data Monitoring Committee chair for ELAN (NCT03148457), and consulting fees paid to the University of Edinburgh from Recursion Pharmaceuticals, Bioxodes, and Population Health Research Institute at McMaster University (Hamilton, ON, Canada). KS reports institutional funding from NIH NINDS (U01NS106513, U24NS129500, R01MD016178, R01EB31114, U24NS107215, R01NR018335, R01NS110721), American Heart Association, Hyperfine, Biogen, and Bard, and consulting fees from Astrocyte, Zoll and Sense (Data Safety and Monitoring Board), and CSL Behring. AS reports institutional funding from Heart and Stroke Foundation of Canada, Canadian Institutes of Health Research, NIH, Bayer, Daiichi Sankyo, and Servier Canada; consulting fees from Bayer, Daiichi Sankyo, Servier Canada, AstraZeneca, and Bioxodes; speaker fees from Bayer, Daiichi Sankyo, Servier Canada, and AstraZeneca; payment for expert testimony from Canadian Medical Protective Agency, support for meetings from Bayer, and Data Monitoring Committee membership for Bayer. HBvdW reports institutional funding from Stryker, Dutch Heart Foundation, and the EU, consulting fees from Bayer and TargED, and membership of the Executive Committee of the European Stroke Organisation. RV reports institutional funding from Bayer, BMS, Pfizer, Daiichi Sankyo, Boehringer, and Medtronic; consulting fees from AstraZeneca; speaker fees from BMS-Pfizer, Data Monitoring Committee participation for Bayer and Portola; stock options in Bayer and Novartis; materials from Medtronic; and chair of the World Stroke Organisation research committee. CV reports personal support from NIH NINDS (UO1NS106513). PMW reports institutional funding from Stryker, Medtronic, and Penumbra, and Data Monitoring Committee membership for PROTECT-U, TENSION, and MR CLEAN NO IV. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The Stroke Treatment Academic Industry Roundtable XII included a workshop to discuss the most promising approaches to improve outcome from acute stroke. The workshop brought together representatives from academia, industry, and government representatives. The discussion examined approaches in 4 epochs: pre-reperfusion, reperfusion, post-reperfusion, and access to acute stroke interventions. The participants identified areas of priority for developing new and existing treatments and approaches to improve stroke outcomes. Although many advances in acute stroke therapy have been achieved, more work is necessary for reperfusion therapies to benefit the most possible patients. Prioritization of promising approaches should help guide the use of resources and investigator efforts., Competing Interests: Disclosures Dr Wechsler reports compensation from Astellas Pharma for consultant services; compensation from Brainsgate for consultant services; stock options in Forest Devices; compensation from Annals of Neurology for other services; and compensation from Athersys for consultant services. Dr Adeoye reports service as Chief Medical Officer for sense diagnostics and compensation from Nico Corporation for data and safety monitoring services. Dr Alemseged reports grants from the Heart Foundation; grants from Medical Research Future Fund; and grants from Sylvia and Charles Charitable Foundation. Dr Bahr-Hosseini reports a patent issued for Transcranial Electrical Stimulation in Stroke Early After Onset. Dr Deljkich reports stock options in Imperative Care, Inc, and employment by Imperative Care, Inc. Dr Fisher reports compensation from Simcere USA for consultant services; employment by Beth Israel Deaconess Medical Center; and compensation from Lumosa for consultant services. Dr Grotta reports compensation from Frazer, Ltd, for consultant services; compensation from Acticor for consultant services; and compensation from Prolong pharma for consultant services. Dr Hill reports grants from MicroVention, Inc; grants from Medtronic; employment by the University of Calgary; grants from Boehringer Ingelheim; grants from the Canadian Institutes of Health Research; and grants from NoNO, Inc. Dr Kamel reports compensation from the American Medical Association for consultant services; compensation from AstraZeneca for end point review committee services; compensation from Novo Nordisk for end point review committee services; compensation from Medtronic for other services; employment by Weill Cornell Medical College; an ownership stake in TET Medical; compensation from Boehringer Ingelheim for end point review committee services; compensation from Javelin Medical for consultant services; and compensation from Janssen Biotech for other services. Dr Khatri reports compensation from Shionogi, Inc, for consultant services; grants from Johnson & Johnson Health Care Systems, Inc; compensation from Bayer for consultant services; compensation from Lumosa for consultant services; compensation from Translational Sciences for other services; compensation from Basking Biosciences for consultant services; royalties from UptoDate, Inc, for online publication; and grants from the National Institutes of Health (NIH). Dr Lyden reports employment by the University of Southern California; compensation from NIH Clinical Center for other services; and compensation from Apex Innnovations for consultant services. Dr Mirza reports employment by Cerenovus. Dr Nguyen reports compensation from Idorsia for other services and compensation from Brainomix for consultant services. Dr Samaniego reports compensation from iSchemaView for consultant services; compensation from Rapid Medical for consultant services; compensation from Medtronic for consultant services; and compensation from MicroVention, Inc, for consultant services. Dr Schwamm reports compensation from Life Image for consultant services; compensation from Diffusion Pharmaceuticals for data and safety monitoring services; compensation from Medtronic for consultant services; service as member of board of directors for the American Heart Association; and compensation from Penumbra, Inc, for data and safety monitoring services. Dr Selim reports grants from NIH/National Institute on Aging; grants from NIH/National Institute of Neurological Disorders and Stroke; and compensation from MedRhythms, Inc, for consultant services. Dr Silva reports compensation from Pfizer for other services; employment by Sociedade Beneficente Israelita Brasileira Albert Einstein; compensation from ISchemaView for consultant services; compensation from Boehringer Ingelheim for consultant services; compensation from Bayer for consultant services; and employment by Universidade Federal de Sao Paulo. Dr Yavagal reports compensation from Gravity Medical Technology for consultant services; stock options in Poseydon; stock holdings in Athersys; compensation from Vascular Dynamics for consultant services; stock options in Rapid Medical; compensation from Poseydon for consultant services; compensation from Stryker Corporation for consultant services; compensation from Johnson & Johnson Health Care Systems, Inc, for consultant services; compensation from Medtronic USA, Inc, for consultant services; and compensation from Athersys for consultant services. Dr Yenari reports grants from NIH. Dr Zachrison reports grants from CRICO; compensation from Wolters Klewer Health, Inc, for other services; grants from the American College of Emergency Physicians; employment by Partners Healthcare; grants from the National Institute on Aging; and grants from the Society for Academic Emergency Medicine. Dr Boltze reports compensation from Astrocyte Pharmaceuticals for consultant services; compensation from Targed Biopharmaceuticals B.V. for consultant services; and employment by the University of Warwick. The other authors report no conflicts.

Importance: The STROKE AF study found that in patients with prior ischemic stroke attributed to large-artery atherosclerotic disease (LAD) or small-vessel occlusive disease (SVD), 12% developed AF over 1 year when monitored with an insertable cardiac monitor (ICM). The occurrence over subsequent years is unknown., Objectives: To compare the rates of AF detection through 3 years of follow-up between an ICM vs site-specific usual care in patients with prior ischemic stroke attributed to LAD or SVD., Design, Setting, and Participants: This multicenter, randomized (1:1) clinical trial took place at 33 sites in the US with enrollment between April 2016 and July 2019 and 3-year follow-up through July 2022. Eligible patients were aged 60 years or older, or aged 50 to 59 years with at least 1 additional stroke risk factor and had an index ischemic stroke attributed to LAD or SVD within 10 days prior to ICM insertion. Of the 496 patients enrolled, 492 were randomized and 4 were excluded., Interventions: ICM monitoring vs site-specific usual care., Main Outcomes and Measures: The prespecified long-term outcome of the trial was AF detection through study follow-up (up to 3 years). AF was defined as an episode lasting more than 30 seconds, adjudicated by an expert committee., Results: In total, 492 patients were randomized and included in the analyses (median [IQR] age, 66 [60-74] years; 307 men [62.4%] and 185 women [37.6%]), of whom 314 completed 3-year follow-up (63.8%). The incidence rate of AF at 3 years was 21.7% (46 patients) in the ICM group vs 2.4% (5 patients) in the control group (hazard ratio, 10.0; 95% CI, 4.0-25.2; P < .001)., Conclusions and Relevance: Patients with ischemic stroke attributed to LAD or SVD face an increasing risk of AF over time and most of the AF occurrences are not reliably detected by standard medical monitoring methods. One year of negative monitoring should not reassure clinicians that patients who have experienced stroke will not develop AF over the next 2 years., Trial Registration: ClinicalTrials.gov Identifier: NCT02700945.

Background: Survivors of intracerebral hemorrhage (ICH) face an increased risk of ischemic cardiovascular events. Current ICH guidelines do not provide definitive recommendations regarding the use of antithrombotic and statin therapies. We, therefore, sought to study practice patterns and factors associated with the use of such medications after ICH., Methods: This was a cross-sectional study of patients with ICH in the Get With The Guidelines-Stroke registry, between 2011 and 2021. Patients transferred to another hospital, those who died during hospitalization, and those with missing information on discharge medications were excluded. The study exposure was the proportion of patients who were prescribed antithrombotic or statin medications. We first ascertained the proportion of patients prescribed antithrombotic and lipid-lowering medications at discharge overall and across strata defined by pre-ICH use and history of previous ischemic vascular disease or atrial fibrillation. We then studied factors associated with the discharge prescription of these medications after ICH, using multiple logistic regressions., Results: In the final cohort, 50 416 (10.4%) of 486 586 patients with ICH were prescribed antiplatelet medications, 173 322 (35.1%) of 493 491 patients with ICH were prescribed statins, and 27 085 (5.4%) of 486 585 patients with ICH were prescribed anticoagulation therapy at discharge. The proportion of patients with antiplatelet therapy was 16.6% with pre-ICH use and 15.6% in those with previous ischemic vascular disease. Statins were prescribed to 41.1% and 43.7% of patients on previous lipid-lowering therapy and ischemic vascular disease, respectively. Anticoagulation therapy was restarted in 11.1% of patients. In logistic regression analysis, factors associated with higher use of antithrombotic or statin therapies after ICH were younger age, male sex, pre-ICH medication use, previous ischemic vascular disease, atrial fibrillation, lower admission National Institutes of Health Stroke Scale, longer length of stay, and favorable discharge outcome., Conclusions: Few patients with ICH are prescribed antithrombotic or statin therapies at hospital discharge. Given the emerging association between ICH and future major cardiovascular events, trials examining the net benefit of antiplatelet and lipid-lowering therapy after ICH are warranted., Competing Interests: Disclosures Dr Murthy has received grants from the National Institutes of Health (NIH) and reports personal fees for medicolegal consulting in stroke and neurological disorders. W.C. Ziai has received grants from the NIH, serves as the associate editor of Neurocritical Care, and reports personal fees from C.R. Bard DMC outside the submitted work. Dr Schwamm reported receiving personal fees from the Massachusetts Department of Public Health, Genentech, Penumbra, Diffusion Pharma, and Medtronic; grants from Medtronic and the National Institute of Neurological Disorders and Stroke outside the submitted work; and serving as a volunteer chair of the American Heart Association/American Stroke Association Get With The Guidelines-Stroke ClinicalWork Group and as a consultant to Coverdell grant. Dr Fonarow reported receiving personal fees from AstraZeneca, Amgen, Bayer, Eli Lilly, Janssen, Merck, Novartis, and Pfizer outside the submitted work. Dr Smith reported consulting for Eli Lilly outside the submitted work. Dr Bhatt discloses the following relationships: advisory board: Angiowave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, Stasys; board of director: Angiowave (stock options), Boston VA Research Institute, Bristol Myers Squibb (stock), DRS. LINQ (stock options), High Enroll (stock), Society of Cardiovascular Patient Care, and TobeSoft; inaugural chair: American Heart Association Quality Oversight Committee; consultant: Broadview Ventures and Hims; Data Monitoring Committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial (Portico Re-Sheathable Transcatheter Aortic Valve System US IDE Trial), funded by St. Jude Medical, now Abbott), Boston Scientific (chair, PEITHO trial [Higher-Risk Pulmonary Embolism Thrombolysis Study]), Cleveland Clinic (including for the ExCEED trial [CENTERA THV System in Intermediate Risk Patients Who Have Symptomatic, Severe, Calcific, Aortic Stenosis], funded by Edwards), Contego Medical (chair, PERFORMANCE 2 [Protection Against Emboli During Carotid Artery Stenting Using the Neuroguard System]), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial [Edoxaban Versus Vitamin K Antagonist for Atrial Fibrillation After Transcatheter Aortic Valve Replacement], funded by Daiichi Sankyo; for the ABILITY-DM trial [Randomized Comparison of Abluminus + Sirolimus-Eluting Stents Versus Everolimus-Eluting Stents in Coronary Artery Disease Patients With Diabetes Mellitus], funded by Concept Medical), Novartis, Population Health Research Institute, Rutgers University (for the NIH-funded MINT trial [Myocardial Ischemia and Transfusion]); honoraria: American College of Cardiology (senior associate editor, Clinical Trials and News, ACC.org; chair, American College of Cardiology Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial [Randomized Evaluation of Dual Antithrombotic Therapy With Dabigatran vs Triple Therapy With Warfarin in Patients With Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention] steering committee funded by Boehringer Ingelheim; AEGIS-II [Apolipoprotein A-I Event Reducing in Ischemic Syndrome] executive committee funded by CSL Behring), Belvoir Publications (editor in chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial [A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease], funded by Ferring Pharmaceuticals), HMP Global (editor in chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (guest editor; associate editor), K2P (cochair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (Continuing Medical Education [CME] steering committees), MJH Life Sciences, Oakstone CME (course director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS [Rivaroxaban With or Without Aspirin in Stable Cardiovascular Disease] operations committee, publications committee, steering committee, and USA national coleader, funded by Bayer), Slack Publications (chief medical editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (secretary/treasurer), WebMD (CME steering committees), Wiley (steering committee); other: Clinical Cardiology (deputy editor), NCDR-ACTION Registry Steering Committee (chair), VA CART Research and Publications Committee (chair); patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women’s Hospital who assigned to Lexicon; neither the author nor Brigham and Women’s Hospital receive any income from this patent); research funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, 89Bio; royalties: Elsevier (editor, Braunwald’s Heart Disease); site coinvestigator: Abbott, Biotronirk, Boston Scientific, Cardiovascular Systems Incorporated, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, Vascular Solutions; trustee: American College of Cardiology; and unfunded research: Flow Co, Takeda. Dr Kamel is a co-principal investigator for the ARCADIA trial [Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke]; (NIH/National Institute of Neurological Disorders and Stroke U01NS095869), which received in-kind study drug from the Bristol Myers Squibb-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. Dr Sheth reported receiving grants from the NIH, the American Heart Association, Bard, Hyperfine, and Biogen. He received consulting fees from Zoll and Sense for Data Safety Monitoring Board (DSMB) Committees service and consulting fees from Astrocyte, CSL Behring, and Rhaeos. He also holds equity in Alva outside the submitted work. The other authors report no conflicts.

Background Cerebrovascular dysregulation syndromes, posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS), are challenging to diagnose because they are rare and require advanced neuroimaging for confirmation. We sought to estimate PRES/RCVS misdiagnosis in the emergency department and its associated factors. Methods and Results We conducted a retrospective cohort study of PRES/RCVS patients using administrative claims data from 11 states (2016-2018). We defined patients with a probable PRES/RCVS misdiagnosis as those with an emergency department visit for a neurological symptom resulting in discharge to home that occurred ≤14 days before PRES/RCVS hospitalization. Proportions of patients with probable misdiagnosis were calculated, characteristics of patients with and without probable misdiagnosis were compared, and regression analyses adjusted for demographics and comorbidities were performed to identify factors affecting probable misdiagnosis. We identified 4633 patients with PRES/RCVS. A total of 210 patients (4.53% [95% CI, 3.97-5.17]) had a probable preceding emergency department misdiagnosis; these patients were younger (mean age, 48 versus 54 years; P <0.001) and more often female (80.4% versus 69.3%; P <0.001). Misdiagnosed patients had fewer vascular risk factors except prior stroke (36.3% versus 24.2%; P <0.001) and more often had comorbid headache (84% versus 21.4%; P <0.001) and substance use disorder (48.8% versus 37.9%; P <0.001). Facility-level factors associated with probable misdiagnosis included smaller facility, lacking a residency program (62.2% versus 73.7%; P <0.001), and not having on-site neurological services (75.7% versus 84.3%; P <0.001). Probable misdiagnosis was not associated with higher likelihood of stroke or subarachnoid hemorrhage during PRES/RCVS hospitalization. Conclusions Probable emergency department misdiagnosis occurred in ≈1 of every 20 patients with PRES/RCVS in a large, multistate cohort.

Background: Although coronary calcification quantification is an established approach for cardiovascular risk assessment, the value of quantifying carotid calcification is less clear. As a result, we performed a systematic review and meta-analysis to evaluate the association between extracranial carotid artery plaque calcification burden and ipsilateral cerebrovascular ischemic events., Methods: A comprehensive literature search was performed in the following databases: Ovid MEDLINE(R) 1946 to July 6, 2022; OVID Embase 1974 to July 6, 2022; and The Cochrane Library (Wiley). We performed meta-analyses including studies in which investigators performed a computed tomography assessment of calcification volume, percentage, or other total calcium burden summarizable in a single continuous imaging biomarker and determined the association of these features with the occurrence of ipsilateral stroke or transient ischemic attack., Results: Our overall meta-analysis consisted of 2239 carotid arteries and 9 studies. The presence of calcification in carotid arteries ipsilateral to ischemic stroke or in stroke patients compared with asymptomatic patients did not demonstrate a significant association with ischemic cerebrovascular events (relative risk of 0.75 [95% CI, 0.44-1.28]; P =0.29). When restricted to studies of significant carotid artery stenosis (>50%), the presence of calcification was associated with a reduced risk of ischemic stroke (relative risk of 0.56 [95% CI, 0.38-0.85]; P =0.006). When the analysis was limited to studies of patients with mainly nonstenotic plaques, there was an increased relative risk of ipsilateral ischemic stroke of 1.72 ([95% CI, 1.01-2.91]; P =0.04). Subgroup meta-analyses of total calcium burden and morphological features of calcium showed wide variability in their strength of association with ischemic stroke and demonstrated significant heterogeneity., Conclusions: The presence of calcification in carotid plaque confers a reduced association with ipsilateral ischemic events, although these results seem to be limited among carotid arteries with higher degrees of stenosis. Adoption of carotid calcification measures in clinical decision-making will require additional studies providing more reproducible and standardized methods of calcium characterization and testing these imaging strategies in prospective studies., Competing Interests: Disclosures Dr Kamel serves as a PI for the ARCADIA trial ([Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke]; National Institutes of Health/National Institute of Neurological Disorders and Stroke U01NS095869), which receives in-kind study drug from the BMS-Pfizer Alliance for Eliquis and ancillary study support from Roche Diagnostics; as Deputy Editor for JAMA Neurology; on clinical trial steering/executive committees for Medtronic, Janssen, and Javelin Medical; and on end point adjudication committees for AstraZeneca, Novo Nordisk, and Boehringer Ingelheim. He has an ownership interest in TETMedical Inc. Dr Kamel has served as a consultant for the American Medical Association, for which he has received compensation. The American Medical Association had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the article, or in the decision to publish the results. The other authors report no conflicts.

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.

Chronic liver disease (CLD) is a highly prevalent condition. There is burgeoning recognition that there are many people with subclinical liver disease that may nonetheless be clinically significant. CLD has a variety of systemic aberrations relevant to stroke, including thrombocytopenia, coagulopathy, elevated liver enzymes, and altered drug metabolism. There is a growing body of literature on the intersection of CLD and stroke. Despite this, there have been few efforts to synthesize these data, and stroke guidelines provide scant guidance on this topic. To fill this gap, this multidisciplinary review provides a contemporary overview of CLD for the vascular neurologist while appraising data regarding the impact of CLD on stroke risk, mechanisms, and outcomes. Finally, the review addresses acute and chronic treatment considerations for patients with stroke-ischemic and hemorrhagic-and CLD., Competing Interests: Disclosures Dr Parikh: personal compensation for medicolegal consulting. Dr Kamel: Principal Investigator (ARCADIA [Atrial Cardiopathy and Antithrombotic Drugs In Prevention After Cryptogenic Stroke], NINDS (National Institute of Neurological Disorders and Stroke) U01NS095869; in-kind study drug [BMS (Bristol Myers Squibb)-Pfizer Alliance for Eliquis]; ancillary study support [Roche Diagnostics]); Deputy Editor (JAMA Neurology); member, clinical trial steering/executive committees (Medtronic, Janssen, and Javelin Medical); member, End Point Adjudication Committees (AstraZeneca, Novo Nordisk, and Boehringer Ingelheim); and ownership interest (TETMedical, Inc). Dr VanWagner: research support (W.L. Gore & Associates; NHLBI (National Heart, Lung, and Blood Institute) R56 HL155093); consultant (Gerson Lehrman Group, Numares, Slingshot Insights, and Noble Consultants); medicolegal consulting; and associate editor (Liver Transplantation). The other authors report no conflicts.

Neurologists in both the inpatient and outpatient settings are increasingly using ultrasound to diagnose and manage common neurological diseases. Advantages include cost-effectiveness, the lack of exposure to ionizing radiation, and the ability to perform at the bedside to provide real-time data. There is a growing body of literature that supports using ultrasonography to improve diagnostic accuracy and aid in performing procedures. Despite the increasing utilization of this imaging modality in medicine, there has been no comprehensive review of the clinical applications of ultrasound in the field of neurology. We discuss the current uses and limitations of ultrasound for various neurological conditions. We review the role for ultrasound in commonly performed neurologic procedures including lumbar puncture, botulinum toxin injections, nerve blocks, and trigger point injections. We specifically discuss the technique for ultrasound-assisted lumbar puncture and occipital nerve block as these are commonly performed. We then focus on the utility of ultrasound in the diagnosis of neurologic conditions. This includes neuromuscular diseases such as motor neuron disorders, focal neuropathies, and muscular dystrophy as well as vascular conditions such as stroke and vasospasm in subarachnoid hemorrhage. We also address ultrasound's use in critically ill patients to aid in identifying increased intracranial pressure, hemodynamics, and arterial and/or venous catheterization. Finally, we address the importance of standardized ultrasound curricula in trainee education and make recommendations for the future directions of research and competency guidelines within our specialty., (© 2023 American Society of Neuroimaging.)

Background Small spotty calcifications in the coronary arteries are associated with an increased risk of myocardial infarction. We examined the association between spotty calcifications near the carotid bifurcations and ipsilateral ischemic stroke in patients with <50% luminal stenosis of the extracranial carotid arteries. Methods and Results We used data from the CAESAR (Cornell Acute Stroke Academic Registry), a prospective registry of all patients with acute ischemic stroke admitted to our institution. We included patients who met criteria for cryptogenic stroke and underwent computed tomography angiography and brain magnetic resonance imaging. Patients with extracranial carotid artery stenosis ≥50% and patients with posterior or bilateral anterior circulation infarcts were excluded. We examined the carotid bifurcations for spotty calcifications, defined as ≥1 contiguous regions of luminal calcification ≤3 mm along the long axis of the vessel. We also measured low-density plaque and maximum plaque thickness. The eligible cohort consisted of 117 patients with a mean age of 66.7±1.65 years with a median National Institute of Health Stroke Scale stroke at the time of arrival of 6 (range, 3-13). The number of spotty calcifications present within a low-density plaque was significantly associated with ipsilateral infarction (0.3±0.8 versus 0.1±0.4, P =0.02). Maximum plaque thickness was also significantly associated with ipsilateral infarction (1.4 mm ±1.5 versus 1.0 mm ±1.1, P =0.004). Conclusions Spotty calcifications associated with low-density plaque and maximum plaque thickness were associated with ipsilateral ischemic stroke in patients with nonstenotic carotid atherosclerosis, suggesting a role as imaging markers of high-risk plaque.

Objective: Patients with posterior reversible encephalopathy syndrome (PRES) can develop seizures during the acute phase. We sought to determine the long-term risk of seizure after PRES., Methods: We performed a retrospective cohort study using statewide all-payer claims data from 2016-2018 from nonfederal hospitals in 11 US states. Adults admitted with PRES were compared to adults admitted with stroke, an acute cerebrovascular disorder associated with long-term risk of seizure. The primary outcome was seizure diagnosed during an emergency room visit or hospital admission after the index hospitalization. The secondary outcome was status epilepticus. Diagnoses were determined using previously validated ICD-10-CM codes. Patients with seizure diagnoses before or during the index admission were excluded. We used Cox regression to evaluate the association of PRES with seizure, adjusting for demographics and potential confounders., Results: We identified 2095 patients hospitalized with PRES and 341,809 with stroke. Median follow-up was 0.9 years (IQR, 0.3-1.7) in the PRES group and 1.0 years (IQR, 0.4-1.8) in the stroke group. Crude seizure incidence per 100 person-years was 9.5 after PRES and 2.5 after stroke. After adjustment for demographics and comorbidities, patients with PRES had a higher risk of seizure than patients with stroke (HR, 2.9; 95% CI, 2.6-3.4). Results were unchanged in a sensitivity analysis that applied a two-week washout period to mitigate detection bias. A similar relationship was observed for the secondary outcome of status epilepticus., Interpretation: PRES was associated with an increased long-term risk of subsequent acute care utilization for seizure compared to stroke., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Smoking cessation rates after stroke and transient ischemic attack are suboptimal, and smoking cessation interventions are underutilized. We performed a cost-effectiveness analysis of smoking cessation interventions in this population., Methods: We constructed a decision tree and used Markov models that aimed to assess the cost-effectiveness of varenicline, any pharmacotherapy with intensive counseling, and monetary incentives, compared with brief counseling alone in the secondary stroke prevention setting. Payer and societal costs of interventions and outcomes were modeled. The outcomes were recurrent stroke, myocardial infarction, and death using a lifetime horizon. Estimates and variance for the base case (35% cessation), costs and effectiveness of interventions, and outcome rates were imputed from the stroke literature. We calculated incremental cost-effectiveness ratios and incremental net monetary benefits. An intervention was considered cost-effective if the incremental cost-effectiveness ratio was less than the willingness-to-pay threshold of $100 000 per quality-adjusted life-year (QALY) or when the incremental net monetary benefit was positive. Probabilistic Monte Carlo simulations modeled the impact of parameter uncertainty., Results: From the payer perspective, varenicline and pharmacotherapy with intensive counseling were associated with more QALYs (0.67 and 1.00, respectively) at less total lifetime costs compared with brief counseling alone. Monetary incentives were associated with 0.71 more QALYs at an additional cost of $120 compared with brief counseling alone, yielding an incremental cost-effectiveness ratio of $168/QALY. From the societal perspective, all 3 interventions provided more QALYs at less total costs compared with brief counseling alone. In 10 000 Monte Carlo simulations, all 3 smoking cessation interventions were cost-effective in >89% of runs., Conclusions: For secondary stroke prevention, it is cost-effective and potentially cost-saving to deliver smoking cessation therapy beyond brief counseling alone.

Background The duration and magnitude of increased stroke risk after a hospitalization for acute systolic heart failure (HF) remains uncertain. Methods and Results The authors performed a retrospective cohort study using claims (2008-2018) from a nationally representative 5% sample of Medicare beneficiaries aged ≥66 years. Cox regression models were fitted separately for the groups with and without acute systolic HF to examine its association with the incidence of ischemic stroke after adjustment for demographics, stroke risk factors, and Charlson comorbidities. Corresponding survival probabilities were used to compute the hazard ratio (HR) in each 30-day interval after discharge. The authors stratified patients by the presence of atrial fibrillation (AF) before or during the hospitalization for acute systolic HF. Among 2 077 501 eligible beneficiaries, 94 641 were hospitalized with acute systolic HF. After adjusting for demographics, stroke risk factors, and Charlson comorbidities, the risk of ischemic stroke was highest in the first 30 days after discharge from an acute systolic HF hospitalization for patients with AF (HR, 2.4 [95% CI, 2.1-2.7]) and without AF (HR, 4.6 [95% CI, 4.0-5.3]). The risk of stroke remained elevated for 60 days in patients with AF (HR, 1.4 [95% CI, 1.2-1.6]) and was not significantly elevated afterward. The risk of stroke remained significantly elevated through 330 days in patients without AF (HR, 2.1 [95% CI, 1.7-2.7]) and was no longer significantly elevated afterward. Conclusions A hospitalization for acute systolic HF is associated with an increased risk of ischemic stroke up to 330 days in patients without concomitant AF.

Background: Administrative data can be useful for stroke research but have historically lacked data on stroke severity. Hospitals increasingly report the National Institutes of Health Stroke Scale (NIHSS) score using an International Classification of Diseases , Tenth Revision ( ICD-10 ) diagnosis code, but this code's validity remains unclear., Methods: We examined the concordance of ICD-10 NIHSS scores versus NIHSS scores recorded in CAESAR (Cornell Acute Stroke Academic Registry). We included all patients with acute ischemic stroke from October 1, 2015, when US hospitals transitioned to ICD-10 , through 2018, the latest year in our registry. The NIHSS score (range, 0-42) recorded in our registry served as the reference gold standard. ICD-10 NIHSS scores were derived from hospital discharge diagnosis code R29.7xx, with the latter 2 digits representing the NIHSS score. Multiple logistic regression was used to explore factors associated with availability of ICD-10 NIHSS scores. We used ANOVA to examine the proportion of variation ( R 2 ) in the true (registry) NIHSS score that was explained by the ICD-10 NIHSS score., Results: Among 1357 patients, 395 (29.1%) had an ICD-10 NIHSS score recorded. This proportion increased from 0% in 2015 to 46.5% in 2018. In a logistic regression model, only higher registry NIHSS score (odds ratio per point, 1.05 [95% CI, 1.03-1.07]) and cardioembolic stroke (odds ratio, 1.4 [95% CI, 1.0-2.0]) were associated with availability of the ICD-10 NIHSS score. In an ANOVA model, the ICD-10 NIHSS score explained almost all the variation in the registry NIHSS score ( R 2 =0.88). Fewer than 10% of patients had a large discordance (≥4 points) between their ICD-10 and registry NIHSS scores., Conclusions: When present, ICD-10 codes representing NIHSS scores had excellent agreement with NIHSS scores recorded in our stroke registry. However, ICD-10 NIHSS scores were often missing, especially in less severe strokes, limiting the reliability of these codes for risk adjustment.

Importance: The Stroke of Known Cause and Underlying Atrial Fibrillation (STROKE AF) trial found that approximately 1 in 8 patients with recent ischemic stroke attributed to large- or small-vessel disease had poststroke atrial fibrillation (AF) detected by an insertable cardiac monitor (ICM) at 12 months. Identifying predictors of AF could be useful when considering an ICM in routine poststroke clinical care., Objective: To determine the association between commonly assessed risk factors and poststroke detection of new AF in the STROKE AF cohort monitored by ICM., Design, Setting, and Participants: This was a prespecified analysis of a randomized (1:1) clinical trial that enrolled patients between April 1, 2016, and July 12, 2019, with primary follow-up through 2020 and mean (SD) duration of 11.0 (3.0) months. Eligible patients were selected from 33 clinical research sites in the US. Patients had an index stroke attributed to large- or small-vessel disease and were 60 years or older or aged 50 to 59 years with at least 1 additional stroke risk factor. A total of 496 patients were enrolled, and 492 were randomly assigned to study groups (3 did not meet inclusion criteria, and 1 withdrew consent). Patients in the ICM group had the index stroke within 10 days before insertion. Data were analyzed from October 8, 2021, to January 28, 2022., Interventions: ICM monitoring vs site-specific usual care (short-duration external cardiac monitoring)., Main Outcomes and Measures: The ICM device automatically detects AF episodes 2 or more minutes in length; episodes were adjudicated by an expert committee. Cox regression multivariable modeling included all parameters identified in the univariate analysis having P values <.10. AF detection rates were calculated using Kaplan-Meier survival estimates., Results: The analysis included the 242 participants randomly assigned to the ICM group in the STROKE AF study. Among 242 patients monitored with ICM, 27 developed AF (mean [SD] age, 66.6 [9.3] years; 144 men [60.0%]; 96 [40.0%] women). Two patients had missing baseline data and exited the study early. Univariate predictors of AF detection included age (per 1-year increments: hazard ratio [HR], 1.05; 95% CI, 1.01-1.09; P = .02), CHA2DS2-VASc score (per point: HR, 1.54; 95% CI, 1.15-2.06; P = .004), chronic obstructive pulmonary disease (HR, 2.49; 95% CI, 0.86-7.20; P = .09), congestive heart failure (CHF; with preserved or reduced ejection fraction: HR, 6.64; 95% CI, 2.29-19.24; P < .001), left atrial enlargement (LAE; HR, 3.63; 95% CI, 1.55-8.47; P = .003), QRS duration (HR, 1.02; 95% CI, 1.00-1.04; P = .04), and kidney dysfunction (HR, 3.58; 95% CI, 1.35-9.46; P = .01). In multivariable modeling (n = 197), only CHF (HR, 5.06; 95% CI, 1.45-17.64; P = .05) and LAE (HR, 3.32; 1.34-8.19; P = .009) remained significant predictors of AF. At 12 months, patients with CHF and/or LAE (40 of 142 patients) had an AF detection rate of 23.4% vs 5.0% for patients with neither (HR, 5.1; 95% CI, 2.0-12.8; P < .001)., Conclusions and Relevance: Among patients with ischemic stroke attributed to large- or small-vessel disease, CHF and LAE were associated with a significantly increased risk of poststroke AF detection. These patients may benefit most from the use of ICMs as part of a secondary stroke prevention strategy. However, the study was not powered for clinical predictors of AF, and therefore, other clinical characteristics may not have reached statistical significance., Trial Registration: ClinicalTrials.gov Identifier: NCT02700945.

Background: Posterior reversible encephalopathy syndrome (PRES) can cause short-term cerebrovascular complications, such as brain infarction and hemorrhage. We hypothesized that PRES is also associated with an increased long-term risk of stroke., Methods: We performed a retrospective cohort study in the United States using statewide all-payer claims data from 2016 to 2018 on all admissions to nonfederal hospitals in 11 states. Adults with PRES were compared with adults with renal colic (negative control) and transient ischemic attack (TIA; positive control). Any stroke and the secondary outcomes of ischemic and hemorrhagic stroke were ascertained using International Classification of Diseases, Tenth Revision, Clinical Modification codes . We excluded prevalent stroke. We used time-to-event statistics to calculate incidence rates and Cox proportional hazards analyses to evaluate the association between PRES and stroke, adjusting for demographics and stroke risk factors. In a sensitivity analysis, outcomes within 2 weeks of index admission were excluded., Results: We identified 1606 patients with PRES, 1192 with renal colic, and 38 216 with TIA. Patients with PRES had a mean age of 56±17 years; 72% were women. Over a median follow-up of 0.9 years, the stroke incidence per 100 person-years was 6.1 (95% CI, 5.0-7.4) after PRES, 1.0 (95% CI, 0.62-1.8) after renal colic, and 9.7 (95% CI, 9.4-10.0) after TIA. After statistical adjustment for patient characteristics and risk factors, patients with PRES had an elevated risk of stroke compared with renal colic (hazard ratio [HR], 2.3 [95% CI, 1.7-3.0]), but lower risk than patients with TIA (HR, 0.67 [95% CI, 0.54-0.82]). In secondary analyses, compared with TIA, PRES was associated with hemorrhagic stroke (HR, 2.0 [95% CI, 1.4-2.9]). PRES was associated with ischemic stroke when compared with renal colic (HR, 1.9 [95% CI, 1.4-2.7]) but not when compared with TIA (HR, 0.49 [95% CI, 0.38-0.63]). Results were similar with 2-week washout., Conclusions: Patients with PRES had an elevated risk of incident stroke.

Objective: To evaluate whether patients discharged to home after an emergency department (ED) visit for headache face a heightened short-term risk of stroke., Background: Stroke hospitalizations that occur soon after ED visits for headache complaints may reflect diagnostic error., Methods: We conducted a retrospective cohort study using statewide administrative claims data for all ED visits and admissions at nonfederal hospitals in Florida 2005-2018 and New York 2005-2016. Using standard International Classification of Diseases (ICD) codes, we identified adult patients discharged to home from the ED (treat-and-release visit) with a benign headache diagnosis (cohort of interest) as well as those with a diagnosis of renal colic or back pain (negative controls). The primary study outcome was hospitalization within 30 days for stroke (ischemic or hemorrhagic) defined using validated ICD codes. We assess the relationship between index ED visit discharge diagnosis and stroke hospitalization adjusting for patient demographics and vascular comorbidities., Results: We identified 1,502,831 patients with an ED treat-and-release headache visit; mean age was 41 (standard deviation: 17) years and 1,044,520 (70%) were female. A total of 2150 (0.14%) patients with headache were hospitalized for stroke within 30 days. In adjusted analysis, stroke risk was higher after headache compared to renal colic (hazard ratio [HR]: 2.69; 95% confidence interval [CI]: 2.29-3.16) or back pain (HR: 4.0; 95% CI: 3.74-4.3). In the subgroup of 26,714 (1.78%) patients with headache who received brain magnetic resonance imaging at index ED visit, stroke risk was only slightly elevated compared to renal colic (HR: 1.47; 95% CI: 1.22-1.78) or back pain (HR: 1.49; 95% CI: 1.24-1.80)., Conclusion: Approximately 1 in 700 patients discharged to home from the ED with a headache diagnosis had a stroke in the following month. Stroke risk was three to four times higher after an ED visit for headache compared to renal colic or back pain., (© 2022 American Headache Society.)

Background: In patients with intracerebral hemorrhage (ICH), it is unclear whether early neurological deterioration, hematoma expansion (HE), and outcome vary by supratentorial ICH location (deep versus lobar). Herein, we assessed these relationships in a clinical trial cohort that underwent brain imaging early after symptom onset. We hypothesized that HE would occur more frequently, and outcome would be worse in patients with deep ICH., Methods: We performed a post hoc analysis of the FAST (Factor-VII-for-Acute-Hemorrhagic-Stroke-Treatment) trial including all patients with supratentorial hemorrhage. Enrolled patients underwent brain imaging within 3 hours of symptom onset and 24 hours after randomization. Multivariable regression was used to test the association between ICH location and 3 outcomes: HE (increase of ≥33% or 6mL), early neurological deterioration (decrease in Glasgow Coma Scale score ≥2 points or increase in National Institutes of Health Stroke Scale ≥4 points within 24 hours of admission), and 90-day outcome (modified Rankin Scale)., Results: Of 841 FAST trial patients, we included 728 (mean age 64 years, 38% women) with supratentorial hemorrhages (deep n=623, lobar n=105). HE (44 versus 27%, P =0.001) and early neurological deterioration (31 versus 17%, P =0.001) were more common in lobar hemorrhages. Deep hemorrhages were smaller than lobar hemorrhages at baseline (12 versus 35mL, P <0.001) and 24 hours (14 versus 38mL, P <0.001). Unadjusted 90-day outcome was worse in lobar compared with deep ICH (median modified Rankin Scale score 5 versus 4, P =0.03). However, when adjusting for variables included in the ICH score including ICH volume, deep location was associated with worse and lobar location with better outcome (odds ratio lobar location, 0.58 [95% CI, 0.38-0.89]; P =0.01)., Conclusions: In this secondary analysis of randomized trial patients, lobar ICH location was associated with larger ICH volume, more HE and early neurological deterioration, and worse outcome than deep ICH. After adjustment for prognostic variables, however, deep ICH was associated with worse outcome, likely due to their proximity to eloquent brain structures.

Background: There is considerable variation in circle of Willis morphology among the general population, and these variations have been correlated with risk of aneurysms, cerebral ischemia, and other clinical events., Purpose: To investigate the relationship between circle of Willis variants and stroke outcome., Materials and Methods: We performed a retrospective study involving 297 patients from our institution's acute stroke academic registry. All received MRA examinations of the head upon admission for acute strokes. All imaging was reviewed to assess for circle of Willis variants (particularly A1 and P1 aplasia or hypoplasia) along with vertebral artery aplasia or hypoplasia. Stroke outcome was defined as good (walking independently at the time of discharge) or poor (inability to walk at discharge, assistance needed to walk at discharge, or death). Severity of stroke was assessed using the National Institute of Health Stroke Scale., Results: An incomplete circle of Willis was seen in 34% of subjects. There was no significant association between age, gender, hypertension, or presence of arterial stenosis and circle of Willis completeness. Using logistic regression, we found that the presence of an incomplete circle of Willis decreased the odds of a stroke patient having a good outcome by 47% (p = 0.046, OR 0.53, 95% CI 0.281-0.988), after adjusting for age and severity of stroke at admission., Conclusion: This study suggests that an incomplete circle of Willis may be associated with a poorer prognosis for stroke patients., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Cardiovascular disease (CVD) is the leading cause of mortality and disability in developed countries. According to WHO, an estimated 17.9 million people died from CVDs in 2019, representing 32% of all global deaths. Of these deaths, 85% were due to major adverse cardiac and cerebral events. Early detection and care for individuals at high risk could save lives, alleviate suffering, and diminish economic burden associated with these diseases. Carotid artery disease is not only a well-established risk factor for ischemic stroke, contributing to 10%-20% of strokes or transient ischemic attacks (TIAs), but it is also a surrogate marker of generalized atherosclerosis and a predictor of cardiovascular events. In addition to diligent history, physical examination, and laboratory detection of metabolic abnormalities leading to vascular changes, imaging of carotid arteries adds very important information in assessing stroke and overall cardiovascular risk. Spanning from carotid intima-media thickness (IMT) measurements in arteriopathy to plaque burden, morphology and biology in more advanced disease, imaging of carotid arteries could help not only in stroke prevention but also in ameliorating cardiovascular events in other territories (e.g. in the coronary arteries). While ultrasound is the most widely available and affordable imaging methods, computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), their combination and other more sophisticated methods have introduced novel concepts in detection of carotid plaque characteristics and risk assessment of stroke and other cardiovascular events. However, in addition to robust progress in usage of these methods, all of them have limitations which should be taken into account. The main purpose of this consensus document is to discuss pros but also cons in clinical, epidemiological and research use of all these techniques., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: To derive models that identify patients with COVID-19 at high risk for stroke., Materials and Methods: We used data from the AHA's Get With The Guidelines® COVID-19 Cardiovascular Disease Registry to generate models for predicting stroke risk among adults hospitalized with COVID-19 at 122 centers from March 2020-March 2021. To build our models, we used data on demographics, comorbidities, medications, and vital sign and laboratory values at admission. The outcome was a cerebrovascular event (stroke, TIA, or cerebral vein thrombosis). First, we used Cox regression with cross validation techniques to identify factors associated with the outcome in both univariable and multivariable analyses. Then, we assigned points for each variable based on corresponding coefficients to create a prediction score. Second, we used machine learning techniques to create risk estimators using all available covariates., Results: Among 21,420 patients hospitalized with COVID-19, 312 (1.5%) had a cerebrovascular event. Using traditional Cox regression, we created/validated a COVID-19 stroke risk score with a C-statistic of 0.66 (95% CI, 0.60-0.72). The CANDLE score assigns 1 point each for prior cerebrovascular disease, afebrile temperature, no prior pulmonary disease, history of hypertension, leukocytosis, and elevated systolic blood pressure. CANDLE stratified risk of an acute cerebrovascular event according to low- (0-1: 0.2% risk), medium- (2-3: 1.1% risk), and high-risk (4-6: 2.1-3.0% risk) groups. Machine learning estimators had similar discriminatory performance as CANDLE: C-statistics, 0.63-0.69., Conclusions: We developed a practical clinical score, with similar performance to machine learning estimators, to help stratify stroke risk among patients hospitalized with COVID-19., Competing Interests: Declaration of Competing Interest Alexander Merkler and Babak Navi report an institutional research grant from Weill Cornell Medicine to examine stroke risk in patients with COVID-19. Costantino Iadecola serves on the scientific advisory board for Broadview Ventures. Mitchell Elkind receives study drug in kind from Bristol Myers Squibb-Pfizer alliance for Eliquis and ancillary research funding from Roche for an NIH-funded stroke prevention trial; he also reports royalties from UpToDate for chapters on COVID-19 and neurological disease and is an uncompensated officer of the American Heart Association. Hooman Kamel serves as co-PI for the NIH-funded ARCADIA trial which receives in-kind study drug from the BMS-Pfizer Alliance and in-kind study assays from Roche Diagnostics, serves as Deputy Editor for JAMA Neurology, serves as a steering committee member of Medtronic's Stroke AF trial (uncompensated), serves on an endpoint adjudication committee for a trial of empagliflozin for Boehringer-Ingelheim, and has served on an advisory board for Roivant Sciences related to Factor XI inhibition. The other authors have no disclosures., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Ischaemic strokes have traditionally been classified according to the TOAST criteria, in which strokes with unclear aetiology are classified as cryptogenic strokes. However, the definition of cryptogenic stroke did not meet the operational criteria necessary to define patient populations for randomized treatment trials. To address this problem, the concept of embolic stroke of undetermined source (ESUS) was developed and published in 2014. A hypothesis that underpinned this concept was that most strokes in patients with ESUS are caused by embolic events, perhaps many cardioembolic, and that anticoagulation would prevent secondary ischaemic events. On this basis, two large randomized trials were conducted to compare the non-vitamin K antagonist oral anticoagulants (NOACs) dabigatran and rivaroxaban with aspirin. Neither NOAC was superior to aspirin in these trials, although subgroups of patients with ESUS seemed to benefit specifically from anticoagulation or antiplatelet therapy. The neutral results of the trials of anticoagulation and insights into ESUS from research conducted since the concept was introduced warrant reassessment of the ESUS construct as a research concept and a treatment target. In this Review, we discuss the evidence produced since the concept of ESUS was introduced, and propose updates to the criteria and diagnostic algorithm in light of the latest knowledge., (© 2022. Springer Nature Limited.)

Background: Pediatric spinal fusion may be associated with significant intraoperative blood loss, leading to complications from transfusion, hypoperfusion and coagulopathy. One emerging strategy to mediate these risks is by utilization of the anti-fibrinolytic agent tranexamic acid (TXA). However, concerns regarding potential adverse reactions, specifically postoperative seizures and thrombotic events, still exist. To assess these risks, we examined the perioperative morbidity of TXA use in a large national database., Methods: Retrospective data from pediatric patients (age 18 years or younger), discharged between January 2013 to December 2015, who underwent primary or revision posterior spinal fusions, was collected from the Premier Perspective database (Premier, Charlotte, NC). Patients were stratified by TXA use and records were assessed for complications of new onset seizures, strokes, pulmonary embolisms (PE) or deep vein thromboses (DVT) occurring during the perioperative period., Results: In this cohort of 2,633 pediatric patients undergoing posterior spinal fusions, most often to treat adolescent idiopathic scoliosis, 15% received TXA. Overall, adverse events were rare in this patient population. The incidence of seizure, stoke, PE, or DVT in the control group was 0.54% (95% CI, 0.31% to 0.94%) and not significantly different from the TXA group. There was no significant difference in the incidence of DVTs, and no incidences of stroke in either group. There were no new-onset seizures or PEs in patients who received TXA., Conclusions: The use of TXA was not associated with an increased risk of adverse events including seizure, stroke, PE, and DVT. Our findings support the safety of TXA use in pediatric patients undergoing spinal fusion surgery., (© 2022. The Author(s).)

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.

Spontaneous intracerebral hemorrhage (ICH) constitutes 10-15% of all strokes, and is a significant cause of mortality and morbidity. Survivors of ICH, especially those with atrial fibrillation (AF), are at risk for both recurrent hemorrhagic and ischemic cerebrovascular events. A conundrum in the field of vascular neurology, neurosurgery, and cardiology has been the decision to initiate or resume versus withhold anticoagulation in survivors of ICH with AF. To initiate anticoagulation would decrease the risk of ischemic stroke but may increase the risk of hemorrhage. To withhold anticoagulation maintains a lower risk of hemorrhage but does not decrease the risk of ischemic stroke. In this narrative review, we discuss the evidence for and against the use of antithrombotics in ICH survivors with AF, focusing on recently completed and ongoing clinical trials., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Continued smoking after stroke is associated with a high risk of stroke recurrence and other cardiovascular disease. We sought to comprehensively understand the epidemiology of smoking cessation in stroke survivors in the United States. Furthermore, we compared smoking cessation in stroke and cancer survivors because cancer is another smoking-related condition in which smoking cessation is prioritized., Methods: We performed a cross-sectional analysis of data from the Centers for Disease Control and Prevention Behavioral Risk Factor Surveillance System, an annual, nationally representative health survey. Using pooled data from 2013 to 2019, we identified stroke and cancer survivors with a history of smoking. We used survey procedures to estimate frequencies and summarize quit ratios with attention to demographic and geographic (state-wise and rural-urban) factors for stroke survivors. The quit ratio is conventionally defined as the proportion of ever smokers who have quit. Then, we used multivariable logistic regression to compare quit ratios in stroke and cancer survivors while adjusting for demographics and smoking-related comorbidities., Results: Among 4 434 604 Americans with a history of stroke and smoking, the median age was 68 years (interquartile range, 59-76), and 45.4% were women. The overall quit ratio was 60.8% (95% CI, 60.1%-61.6%). Quit ratios varied by age group, sex, race and ethnicity, and several geographic factors. There was marked geographic variation in quit ratios, ranging from 48.3% in Kentucky to 71.5% in California. Furthermore, compared with cancer survivors, stroke survivors were less likely to have quit smoking (odds ratio, 0.72 [95% CI, 0.67-0.79]) after accounting for differences in demographics and smoking-related comorbidities., Conclusions: There were considerable demographic and geographic disparities in smoking quit ratios in stroke survivors, who were less likely to have quit smoking than cancer survivors. A targeted initiative is needed to improve smoking cessation for stroke survivors.

Objectives: Cancer can present as stroke. Several cancer types have established screening guidelines. We investigated adherence to guideline-recommended cancer screening in stroke survivors versus the general population., Materials and Methods: We performed a cross-sectional analysis using 2012-2018 data from the CDC's Behavioral Risk Factor Surveillance System (BRFSS) survey. BRFSS is a nationally-representative telephone survey of non-institutionalized Americans that collects data about health conditions and behaviors, including cancer screening. We defined guideline-recommended colorectal, lung, and breast cancer screening based on the U.S. Preventive Services Task Force recommendations. We used survey-specific methods to estimate up-to-date screening rates for those with and without prior stroke. We used logistic regression to estimate the odds of up-to-date screening in stroke survivors compared to those without history of stroke after adjustment for potential confounders., Results: Among 1,018,440 respondents eligible for colorectal cancer screening, 66% were up-to-date. Among 6,880 respondents eligible for lung cancer screening, 16% were up-to-date. Among 548,434 women eligible for breast cancer screening, 78% were up-to-date. After adjustment for demographics and confounders, stroke survivors were more likely to have up-to-date colorectal cancer screening (OR, 1.10; 95% CI, 1.05-1.16), equally likely to undergo lung cancer screening (OR, 0.99; 95% CI, 0.62-1.59), and less likely to undergo breast cancer screening (OR, 0.87; 95% CI, 0.80-0.94)., Conclusions: In a nationwide analysis, stroke survivors had similar suboptimal adherence to guideline-recommended cancer screening as the general population., Competing Interests: Declaration of Competing Interest Hooman Kamel serves as co-PI for the NIH-funded ARCADIA trial which receives in-kind study drug from the BMS-Pfizer Alliance and in-kind study assays from Roche Diagnostics, serves as Deputy Editor for JAMA Neurology, serves as a steering committee member of Medtronic's Stroke AF trial (uncompensated), and serves on an endpoint adjudication committee for a trial of empagliflozin for Boehringer-Ingelheim. Neal Parikh has received personal fees for medicolegal consulting on stroke. Babak Navi has received personal fees for medicolegal consulting on stroke. The other authors have no disclosures., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Atrial fibrillation (AF) can be newly detected in approximately one-fourth of patients with ischemic stroke and transient ischemic attack without previously recognized AF. We present updated evidence supporting that AF detected after stroke or transient ischemic attack (AFDAS) may be a distinct clinical entity from AF known before stroke occurrence (known atrial fibrillation). Data suggest that AFDAS can arise from the interplay of cardiogenic and neurogenic forces. The embolic risk of AFDAS can be understood as a gradient defined by the prevalence of vascular comorbidities, the burden of AF, neurogenic autonomic changes, and the severity of atrial cardiopathy. The balance of existing data indicates that AFDAS has a lower prevalence of cardiovascular comorbidities, a lower degree of cardiac abnormalities than known atrial fibrillation, a high proportion (52%) of very brief (<30 seconds) AF paroxysms, and is more frequently associated with insular brain infarction. These distinctive features of AFDAS may explain its recently observed lower associated risk of stroke than known atrial fibrillation. We present an updated ad-hoc meta-analysis of randomized clinical trials in which the association between prolonged cardiac monitoring and reduced risk of ischemic stroke was nonsignificant (incidence rate ratio, 0.90 [95% CI, 0.71-1.15]). These findings highlight that larger and sufficiently powered randomized controlled trials of prolonged cardiac monitoring assessing the risk of stroke recurrence are needed. Meanwhile, we call for further research on AFDAS and stroke recurrence, and a tailored approach when using prolonged cardiac monitoring after ischemic stroke or transient ischemic attack, focusing on patients at higher risk of AFDAS and, more importantly, at higher risk of cardiac embolism.

Background It is unknown if stroke symptoms in the absence of a stroke diagnosis are a sign of subtle cardioembolic phenomena. The objective of this study was to examine associations between atrial fibrillation (AF) and stroke symptoms among adults with no clinical history of stroke or transient ischemic attack (TIA). Methods and Results We evaluated associations between AF and self-reported stroke symptoms in the national, prospective REGARDS (Reasons for Geographic and Racial Differences in Stroke) cohort. We conducted cross-sectional (n=27 135) and longitudinal (n=21 932) analyses over 8 years of follow-up of REGARDS participants without stroke/transient ischemic attack and stratified by anticoagulant or antiplatelet agent use. The mean age was 64.4 (SD±9.4) years, 55.3% were women, and 40.8% were Black participants; 28.6% of participants with AF reported stroke symptoms. In the cross-sectional analysis, comparing participants with and without AF, the risk of stroke symptoms was elevated for adults with AF taking neither anticoagulants nor antiplatelet agents (odds ratio [OR], 2.22; 95% CI, 1.89-2.59) or antiplatelet agents only (OR, 1.92; 95% CI, 1.61-2.29) but not for adults with AF taking anticoagulants (OR, 1.08; 95% CI, 0.71-1.65). In the longitudinal analysis, the risk of stroke symptoms was also elevated for adults with AF taking neither anticoagulants nor antiplatelet agents (hazard ratio [HR], 1.41; 95% CI, 1.21-1.66) or antiplatelet agents only (HR, 1.23; 95% CI, 1.04-1.46) but not for adults with AF taking anticoagulants (HR, 0.86; 95% CI, 0.62-1.18). Conclusions Stroke symptoms in the absence of a stroke diagnosis may represent subclinical cardioembolic phenomena or "whispering strokes." Future studies examining the benefit of stroke symptom screening may be warranted.

Introduction: Non-traumatic subarachnoid hemorrhage (SAH) is associated with poor long-term functional outcomes, but the risk of ischemic stroke among SAH survivors is poorly understood., Objectives: The aim of this study was to evaluate the risk of ischemic stroke among survivors of SAH., Methods: We performed a retrospective cohort study using claims data from Medicare beneficiaries from 2008 to 2015. The exposure was a diagnosis of SAH, while the outcome was an acute ischemic stroke, both identified using previously validated ICD-9-CM diagnosis codes. We used Cox regression analysis adjusting for demographics and stroke risk factors to evaluate the association between SAH and long-term risk of ischemic stroke., Results: Among 1.7 million Medicare beneficiaries, 912 were hospitalized with non-traumatic SAH. During a median follow-up of 5.2 years (IQR, 2.7-6.7), the cumulative incidence of ischemic stroke was 22 per 1,000 patients per year among patients with SAH, and 7 per 1,000 patients per year in those without SAH. In adjusted Cox models, SAH was associated with an increased risk of ischemic stroke (HR, 2.0; 95% confidence interval, 1.4-2.8) as compared to beneficiaries without SAH. Similar results were obtained in sensitivity analyses, when treating death as a competing risk (sub HR, 3.0; 95% CI, 2.8-3.3) and after excluding ischemic stroke within 30 days of SAH discharge (HR, 1.5; 95% CI, 1.1-2.3)., Conclusions: In a large, heterogeneous national cohort of elderly patients, survivors of SAH had double the long-term risk of ischemic stroke. SAH survivors should be closely monitored and risk stratified for ischemic stroke., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

[Figure: see text].

Importance: Patients with ischemic stroke attributed to large- or small-vessel disease are not considered at high risk for atrial fibrillation (AF), and the AF incidence rate in this population is unknown., Objectives: To determine whether long-term cardiac monitoring is more effective than usual care for AF detection in patients with stroke attributed to large- or small-vessel disease through 12 months of follow-up., Design, Setting, and Participants: The STROKE-AF trial was a randomized (1:1), multicenter (33 sites in the US) clinical trial that enrolled 496 patients between April 2016 and July 2019, with primary end point follow-up through August 2020. Eligible patients were aged 60 years or older or aged 50 to 59 years with at least 1 additional stroke risk factor and had an index stroke attributed to large- or small-vessel disease within 10 days prior to insertable cardiac monitor (ICM) insertion., Interventions: Patients randomized to the intervention group (n = 242) received ICM insertion within 10 days of the index stroke; patients in the control group (n = 250) received site-specific usual care consisting of external cardiac monitoring, such as 12-lead electrocardiograms, Holter monitoring, telemetry, or event recorders., Main Outcomes and Measures: Incident AF lasting more than 30 seconds through 12 months., Results: Among 492 patients who were randomized (mean [SD] age, 67.1 [9.4] years; 185 [37.6%] women), 417 (84.8%) completed 12 months of follow-up. The median (interquartile range) CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischemic attack, vascular disease, age 65 to 74 years, sex category) score was 5 (4-6). AF detection at 12 months was significantly higher in the ICM group vs the control group (27 patients [12.1%] vs 4 patients [1.8%]; hazard ratio, 7.4 [95% CI, 2.6-21.3]; P < .001). Among the 221 patients in the ICM group who received an ICM, 4 (1.8%) had ICM procedure-related adverse events (1 site infection, 2 incision site hemorrhages, and 1 implant site pain)., Conclusions and Relevance: Among patients with stroke attributed to large- or small-vessel disease, monitoring with an ICM compared with usual care detected significantly more AF over 12 months. However, further research is needed to understand whether identifying AF in these patients is of clinical importance., Trial Registration: ClinicalTrials.gov Identifier: NCT02700945.

Background: Recent clinical trials have established the efficacy of endovascular stroke therapy and intravenous thrombolysis using advanced imaging, particularly computed tomography perfusion (CTP). The availability and utilization of CTP for patients and hospitals that treat acute ischemic stroke (AIS), however, is uncertain., Methods: We performed a retrospective cross-sectional analysis using 2 complementary Medicare datasets, full sample Texas and 5% national fee-for-service data from 2014 to 2017. AIS cases were identified using International Classification of Diseases , Ninth Revision and International Classification of Diseases , Tenth Revision coding criteria. Imaging utilization performed in the initial evaluation of patients with AIS was derived using Current Procedural Terminology codes from professional claims. Primary outcomes were utilization of imaging in AIS cases and the change in utilization over time. Hospitals were defined as imaging modality-performing if they submitted at least 1 claim for that modality per calendar year. The National Medicare dataset was used to validate state-level findings, and a local hospital-level cohort was used to validate the claims-based approach., Results: Among 50 797 AIS cases in the Texas Medicare fee-for-service cohort, 64% were evaluated with noncontrast head CT, 17% with CT angiography, 3% with CTP, and 33% with magnetic resonance imaging. CTP utilization was greater in patients treated with endovascular stroke therapy (17%) and intravenous thrombolysis (9%). CT angiography (4%/y) and CTP (1%/y) utilization increased over the study period. These findings were validated in the National dataset. Among hospitals in the Texas cohort, 100% were noncontrast head CT-performing, 77% CT angiography-performing, and 14% CTP-performing in 2017. Most AIS cases (69%) were evaluated at non-CTP-performing hospitals. CTP-performing hospitals were clustered in urban areas, whereas large regions of the state lacked immediate access., Conclusions: In state-wide and national Medicare fee-for-service cohorts, CTP utilization in patients with AIS was low, and most patients were evaluated at non-CTP-performing hospitals. These findings support the need for alternative means of screening for AIS recanalization therapies.

Objective: Emerging data indicate an increased risk of cerebrovascular events with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and highlight the potential impact of coronavirus disease (COVID-19) on the management and outcomes of acute stroke. We conducted a systematic review and meta-analysis to evaluate the aforementioned considerations., Methods: We performed a meta-analysis of observational cohort studies reporting on the occurrence and/or outcomes of patients with cerebrovascular events in association with their SARS-CoV-2 infection status. We used a random-effects model. Summary estimates were reported as odds ratios (ORs) and corresponding 95% confidence intervals (CIs)., Results: We identified 18 cohort studies including 67,845 patients. Among patients with SARS-CoV-2, 1.3% (95% CI = 0.9-1.6%, I 2 = 87%) were hospitalized for cerebrovascular events, 1.1% (95% CI = 0.8-1.3%, I 2 = 85%) for ischemic stroke, and 0.2% (95% CI = 0.1-0.3%, I 2 = 64%) for hemorrhagic stroke. Compared to noninfected contemporary or historical controls, patients with SARS-CoV-2 infection had increased odds of ischemic stroke (OR = 3.58, 95% CI = 1.43-8.92, I 2 = 43%) and cryptogenic stroke (OR = 3.98, 95% CI = 1.62-9.77, I 2 = 0%). Diabetes mellitus was found to be more prevalent among SARS-CoV-2 stroke patients compared to noninfected historical controls (OR = 1.39, 95% CI = 1.00-1.94, I 2 = 0%). SARS-CoV-2 infection status was not associated with the likelihood of receiving intravenous thrombolysis (OR = 1.42, 95% CI = 0.65-3.10, I 2 = 0%) or endovascular thrombectomy (OR = 0.78, 95% CI = 0.35-1.74, I 2 = 0%) among hospitalized ischemic stroke patients during the COVID-19 pandemic. Odds of in-hospital mortality were higher among SARS-CoV-2 stroke patients compared to noninfected contemporary or historical stroke patients (OR = 5.60, 95% CI = 3.19-9.80, I 2 = 45%)., Interpretation: SARS-CoV-2 appears to be associated with an increased risk of ischemic stroke, and potentially cryptogenic stroke in particular. It may also be related to an increased mortality risk. ANN NEUROL 2021;89:380-388., (© 2020 American Neurological Association.)

Background and Purpose: Punctate ischemic lesions noted on diffusion-weighted imaging (DWI) are associated with poor functional outcomes after intracerebral hemorrhage (ICH). Whether these lesions increase long-term risk of stroke is poorly understood., Methods: We pooled individual patient data from the ATACH-2 trial (Antihypertensive Treatment of Acute Cerebral Hemorrhage) and the MISTIE III trial (Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation Phase 3). We included subjects with a magnetic resonance imaging scan. The exposure was a DWI lesion. The primary outcome was any stroke, defined as a composite of ischemic stroke or recurrent ICH, whereas secondary outcomes were incident ischemic stroke and recurrent ICH. Using multivariate Cox regression analysis, we evaluated the risk of stroke., Results: Of 505 patients with ICH with magnetic resonance imaging, 466 were included. DWI lesions were noted in 214 (45.9%) subjects, and 34 incident strokes (20 ischemic stroke and 14 recurrent ICH) were observed during a median follow-up of 324 days (interquartile range, 91-374). Presence of a DWI lesion was associated with a 6.9% (95% CI, 2.2-11.6) absolute increase in risk of all stroke (hazard ratio, 2.6 [95% CI, 1.2-5.7]). Covariate adjustment with Cox regression models also demonstrated this increased risk. In the secondary analyses, there was an increased risk of ischemic stroke (hazard ratio, 3.5 [95% CI, 1.1-11.0]) but not recurrent ICH (hazard ratio, 1.7 [95% CI, 0.6-5.1])., Conclusions: In a heterogeneous cohort of patients with ICH, presence of a DWI lesion was associated with a 2.5-fold heightened risk of stroke among ICH survivors. This elevated risk persisted for ischemic stroke but not for recurrent ICH.