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Zachary A King,1 Kevin N Sheth,1 W Taylor Kimberly,2 J Marc Simard3 1Department of Neurology, Division of Neurocritical Care and Emergency Neurology, Yale University School of Medicine, New Haven, CT, USA; 2Department of Neurology, Division of Neurocritical Care and Emergency Neurology, Massachusetts General Hospital, Boston, MA, USA; 3Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA Abstract: Glyburide (also known as glibenclamide) is a second-generation sulfonylurea drug that inhibits sulfonylurea receptor 1 (Sur1) at nanomolar concentrations. Long used to target KATP (Sur1–Kir6.2) channels for the treatment of diabetes mellitus type 2, glyburide was recently repurposed to target Sur1–transient receptor potential melastatin 4 (Trpm4) channels in acute central nervous system injury. Discovered nearly two decades ago, SUR1–TRPM4 has emerged as a critical target in stroke, specifically in large hemispheric infarction, which is characterized by edema formation and life-threatening brain swelling. Following ischemia, SUR1–TRPM4 channels are transcriptionally upregulated in all cells of the neurovascular unit, including neurons, astrocytes, microglia, oligodendrocytes and microvascular endothelial cells. Work by several independent laboratories has linked SUR1–TRPM4 to edema formation, with blockade by glyburide reducing brain swelling and death in preclinical models. Recent work showed that, following ischemia, SUR1–TRPM4 co-assembles with aquaporin-4 to mediate cellular swelling of astrocytes, which contributes to brain swelling. Additionally, recent work linked SUR1–TRPM4 to secretion of matrix metalloproteinase-9 (MMP-9) induced by recombinant tissue plasminogen activator in activated brain endothelial cells, with blockade of SUR1–TRPM4 by glyburide reducing MMP-9 and hemorrhagic transformation in preclinical models with recombinant tissue plasminogen activator. The recently completed GAMES (Glyburide Advantage in Malignant Edema and Stroke) clinical trials on patients with large hemispheric infarctions treated with intravenous glyburide (RP-1127) revealed promising findings with regard to brain swelling (midline shift), MMP-9, functional outcomes and mortality. Here, we review key elements of the basic science, preclinical experiments and clinical studies, both retrospective and prospective, on glyburide in focal cerebral ischemia and stroke. Keywords: glyburide, sulfonylurea receptor 1, stroke, cerebral ischemia, brain swelling, malignant edema, matrix metalloproteinase-9

OBJECTIVES: : A fundamental issue in organ donation after circulatory death is the determination of death. There are limited data regarding the incidence and timing of autoresuscitation after asystole. Prevailing guidelines suggest a 2- to 5-min observation after mechanical asystole before the declaration of death. This study tested the hypothesis that a 2-min observation period after asystole is sufficient for the declaration of death in patients being considered for organ donation after circulatory death. DESIGN: : Single-center observational study using prospectively collected data. SETTING: : University hospital, Level I trauma center. PATIENTS: : Those patients identified by the organ donation registry that underwent organ donation after circulatory death from 2000 to 2008, during which time the institutional protocol required a 5-min observation period. INTERVENTIONS: : None. MEASUREMENTS AND MAIN RESULTS: : Documentation of medical history, serial Glasgow Coma Scale scores, time of extubation, and time to asystole, hypotension, pulseless electrical activity, and declaration of death were ascertained. Seventy-three patients were identified. The most common mechanism of injury was traumatic brain injury, and eight patients were aged <18 yrs. Patients had a mean Glasgow Coma Scale score of 5 on admission and were taken to organ donation after circulatory death an average of 6.6 days after admission. The average time from extubation to death was 22 mins. No patients exhibited autoresuscitation during the 5-min waiting observation period, including the first 2 mins after asystole. CONCLUSIONS: : The absence of autoresuscitation in our series suggests that a 2-min observation period is sufficient for the determination of death after cardiac arrest, including patients younger than 18 yrs. These data may inform practice guidelines. [ABSTRACT FROM AUTHOR]

Background: Hematoma volume is a major determinant of outcome in patients with intracerebral hemorrhage (ICH). Accurate volume measurements are critical for predicting outcome and are thought to be more difficult in patients with oral anticoagulation-related ICH (OAT-ICH) due to a higher frequency of irregular shape. We examined hematoma shape and methods of volume assessment in patients with OAT-ICH.Methods: We performed a case-control analysis of a prospectively identified cohort of consecutive patients with ICH. We retrospectively reviewed 50 consecutive patients with OAT-ICH and 50 location-matched non-OAT-ICH controls. Two independent readers analyzed CT scans for hematoma shape and volume using both ABC/2 and ABC/3 methods. Readers were blinded to all clinical variables including warfarin status. Gold-standard ICH volumes were determined using validated computer-assisted planimetry.Results: Within this cohort, median INR in patients with OAT-ICH was 3.2. Initial ICH volume was not significantly different between non-OAT-ICH and OAT-ICH (35 +/- 38 cc vs. 53 +/- 56 cc, P = 0.4). ICH shape did not differ by anticoagulation status (round shape in 10% of OAT-ICH vs. 16% of non-OAT-ICH, P = 0.5). The ABC/3 calculation underestimated median volume by 9 (3-28) cc, while the ABC/2 calculation did so by 4 (0.8-12) cc.Conclusions: Hematoma shape was not statistically significantly different in patients with OAT-ICH. Among bedside approaches, the standard ABC/2 method offers reasonable approximation of hematoma volume in OAT-ICH and non-OAT-ICH. [ABSTRACT FROM AUTHOR]

Background and Objectives: Sexual and gender minority (SGM) groups have been historically underrepresented in neurologic research, and their brain health disparities are unknown. We aim to evaluate whether SGM persons are at higher risk of adverse brain health outcomes compared with cisgender straight (non-SGM) individuals., Methods: We conducted a cross-sectional study in the All of Us Research Program, a US population-based study, including all participants with information on gender identity and sexual orientation. We used baseline questionnaires to identify sexual minority (lesbian, gay, bisexual, diverse sexual orientation; nonstraight sexual orientation) and gender minority (gender diverse and transgender; gender identity different from sex assigned at birth) participants. The primary outcome was a composite of stroke, dementia, and late-life depression, assessed using electronic health record data and self-report. Secondarily, we evaluated each disease separately. Furthermore, we evaluated all subgroups of gender and sexual minorities stratified by sex assigned at birth. We used multivariable logistic regression (adjusted for age, sex assigned at birth, race/ethnicity, cardiovascular risk factors, other relevant comorbidities, and neighborhood deprivation index) to assess the relationship between SGM groups and the outcomes., Results: Of 413,457 US adults enrolled between May 31, 2017, and June 30, 2022, we included 393,041 participants with available information on sexual orientation and gender identity (mean age 51 [SD 17] years), of whom 39,632 (10%) belonged to SGM groups. Of them, 38,528 (97%) belonged to a sexual minority and 4,431 (11%) to a gender minority. Compared with non-SGM, SGM persons had 15% higher odds of the brain health composite outcome (odds ratio [OR] 1.15, 95% CI 1.08-1.22). In secondary analyses, these results persisted across sexual and gender minorities separately (all 95% CIs > 1). Assessing individual diseases, all SGM groups had higher odds of dementia (SGM vs non-SGM: OR 1.14, 95% CI 1.00-1.29) and late-life depression (SGM vs non-SGM: OR 1.27, 95% CI 1.17-1.38) and transgender women had higher odds of stroke (OR 1.68, 95% CI 1.04-2.70)., Discussion: In a large US population study, SGM persons had higher odds of adverse brain health outcomes. Further research should explore structural causes of inequity to advance inclusive and diverse neurologic care.

Background: The Get With The Guidelines-Stroke program is a quality improvement initiative designed to enhance adherence to evidence-based stroke care. Since its inception in 2003, over 2800 hospitals in the United States have participated in the program., Methods: We examined patient characteristics, adherence to performance measures, and in-hospital outcomes in patients hospitalized for acute ischemic stroke, subarachnoid hemorrhage, intracerebral hemorrhage, and transient ischemic attack in The Get With The Guidelines-Stroke hospitals from 2003 through 2022. We quantified temporal changes in performance measure adherence and clinical outcomes over time. Performance measure denominators consisted of patients who were eligible, excluding those with contraindications., Results: Over the 20 years of the program, a total of 7837 849 stroke cases (median age 71 years, 51.0% female; 69.2% ischemic strokes, 3.9% SAHs, 11.5% ICHs, and 15.3% TIAs) were entered into the registry. Except for antithrombotics at discharge, in which the baseline performance was >92%, there was sustained improvement in all performance metrics regardless of type of cerebrovascular event ( P <0.01 for all). In patients with acute ischemic stroke, large improvements were observed for anticoagulation for atrial fibrillation (55.7% in 2003 to 97.2% in 2022), smoking cessation counseling (44.7%-97.8%), dysphagia screening (53.8%-83.5%), thrombolytic treatment for patients arriving by 3.5 hours, treat by 4.5 hours (15.2%-92.9%), door-to-needle time within 60 minutes (19.0%-75.3%), and endovascular door-to-puncture time within 90 minutes (54.7%-62.8%). Similar improvements were also observed for measures relevant to patients with subarachnoid hemorrhage, intracerebral hemorrhage, and transient ischemic attack. Multivariable analysis showed that there was a sustained increase in odds of receiving each performance measure over time, independent of patient and hospital characteristics for each type of cerebrovascular event. After risk adjustment, there were temporal trends that patients were less likely to be discharged to a skilled nursing facility, and, for ischemic stroke only, more likely to be discharged directly home., Conclusions: During the first 20 years, Get With The Guidelines-Stroke participation was associated with sustained improvement in evidence-based care and outcomes for patients with stroke and transient ischemic attack in the United States.

Slow waves are a distinguishing feature of non-rapid-eye-movement (NREM) sleep, an evolutionarily conserved process critical for brain function. Non-human studies suggest that the claustrum, a small subcortical nucleus, coordinates slow waves. We show that, in contrast to neurons from other brain regions, claustrum neurons in the human brain increase their spiking activity and track slow waves during NREM sleep, suggesting that the claustrum plays a role in coordinating human sleep architecture., (© 2024. The Author(s).)

Introduction: Rocky Mountain Spotted Fever (RMSF) is a tick-borne disease caused by Rickettsia rickettsii (R. rickettsii). RMSF presents after a tick bite with fever, rash, and headache but can also cause more serious neurological manifestations. We report a case of RMSF encephalitis presenting with altered sensorium and rapid progression to coma, fever, and petechial rash, and an magnetic resonance imaging (MRI) brain notable for a "starry sky" pattern., Case Report: A 61-year-old woman presented with confusion and fever and was diagnosed with a urinary tract infection. Two days later, she became comatose. MRI brain revealed lacunar infarcts in the right centrum semiovale and splenium of the corpus callosum. Lumbar puncture was notable for neutrophilic pleocytosis and elevated protein with negative bacterial and viral cultures. Empiric meningitis therapy was initiated, and she was transferred to our institution. On transfer, she was febrile, comatose, and had a diffuse petechial rash. Repeat MRI brain demonstrated diffuse, innumerable punctate foci of diffusion restriction with susceptibility-weighted signal attenuation throughout cerebral hemispheres in a "starry sky" pattern. Skin biopsy revealed perivascular lymphocytic infiltrates. Serologic RSMF antibody titers were obtained, and doxycycline was initiated for presumed RMSF encephalitis. The family opted to pursue palliative measures, given no clinical improvement. RSMF titers and postmortem PCR from brain tissue were positive for R. rickettsii., Conclusions: This case report highlights the clinical presentation of RMSF encephalitis. RMSF encephalitis should be suspected in a patient presenting with encephalopathy, fever, petechial rash, and MRI brain findings of diffuse punctate foci of diffusion restriction and susceptibility-weighted signal attenuation in a "starry-sky" pattern., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: It is important to understand the socioeconomic and medical determinants of subjective cognitive decline (SCD) at a population level in the United States., Methods: The primary outcomes are state-level rates of SCD and SCD-related functional impairment in adults aged ≥ 45, both measured in the Behavioral Risk Factor Surveillance System from 2016 to 2022. The exposures are state-level rates of poverty, unemployment, homelessness, college education, racial and ethnic minorities, uninsurance, smoking, hypertension, diabetes, and obesity as well as household income and physician density., Results: The strongest state-level associations with rates of SCD were the prevalence of diabetes (rho = 0.64), hypertension (rho = 0.59), and poverty (rho = 0.58; all p < 0.001), and with SCD-related functional impairment were prevalence of poverty (rho = 0.71), diabetes (rho = 0.68), and hypertension (rho = 0.53; all p < 0.001)., Discussion: This study highlights critical links between SCD and socioeconomic and medical determinants in adults aged ≥ 45 in the United States, including the prevalence of poverty, diabetes, and hypertension., Highlights: State-level analysis reveals socioeconomic and medical risk factors for subjective cognitive decline (SCD) at a population level. The prevalence of poverty is a critical contributor to the state-level prevalence of SCD. The prevalence of diabetes and hypertension are also strong state-level determinants of SCD. Addressing the burden of cognitive decline at the population level necessitates targeting socioeconomic and medical factors., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: Dementia often involves comorbid Alzheimer's and vascular pathology, but their combined impact warrants additional study., Methods: We analyzed the Systolic Blood Pressure Intervention Trial and categorized white matter hyperintensity (WMH) volume into highest versus lowest/mid tertile and the amyloid beta (Aβ)42/40 ratio into lowest versus mid/highest ratio tertile. Using these binary variables, we created four exposure categories: (1) combined low risk, (2) Aβ risk, (3) WMH risk, and (4) combined high risk., Results: In the cohort of 467 participants (mean age 69.7 ± 7.1, 41.8% female, 31.9% nonwhite or Hispanic) during 4.8 years of follow-up and across the four exposure categories the rates of cognitive impairment were 5.3%, 7.8%, 11.8%, and 22.6%. Compared to the combined low-risk category, the adjusted hazard ratio for cognitive impairment was 4.12 (95% confidence interval, 1.71 to 9.94) in the combined high-risk category., Discussion: This study emphasizes the potential impact of therapeutic approaches to dementia prevention that target both vascular and amyloid pathology., Highlights: White matter hyperintensity (WMH) and plasma amyloid (Aβ42/40) are additive risk factors for the development of cognitive impairment in the SPRINT MIND trial. Individuals in the high-risk categories of both WMH and Aβ42/40 had a near fivefold increase in risk of cognitive impairment during 4.8 years of follow-up on average. These findings suggest that treatment strategies targeting both vascular health and amyloid burden warrant further research., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Clinical trials in older adults are increasingly focused on functional outcomes, and the composite outcome of dementia, disability, and death is gaining pivotal importance. Genetic variation, particularly the APOE epsilon(ε) variants, may modify responses to new treatments. Although APOE ε4 is known to influence these outcomes separately, the magnitude of its effect on this composite outcome remains unknown. We tested the hypothesis that APOE ε4 increases, whereas APOE ε2 decreases, the risk of a composite outcome of dementia, disability, and death., Methods: We evaluated clinical and genomic data from the Health and Retirement Study collected from 1992 to 2020. We used variants rs429358 and rs7412 to determine APOE genotypes, modeled dominantly (carriers/noncarriers). We conducted survival analysis, using multivariable Cox proportional hazards models with a composite endpoint of dementia, disability, and death. Our primary analysis evaluated participants with genetic data and no previous dementia or disability. In secondary analyses, we focused on persons aged > = 75 years without heart disease or stroke, a subpopulation increasingly important in clinical trials of older adults., Results: We included 14,527 participants in the primary analysis. Over a median of 18 (Interquartile Range [IQR] 12-24) years, 6711 (46%) participants developed the composite outcome. In Cox analyses, APOE ε4 associated with higher risk (HR:1.15, 95%CI:1.09-1.22) of the composite outcome, whereas APOE ε2 associated with lower risk (HR:0.92, 95%CI:0.86-0.99). In the secondary analysis, we included 3174 participants. Over a median of 7 (IQR 4-11) years, 1326 participants (42%) developed the composite outcome. In Cox analyses, APOE ε4 associated with higher risk (HR:1.25, 95%CI:1.10-1.41) of the composite outcome, whereas APOE ε2 associated with lower risk (HR:0.84, 95%CI:0.71-0.98)., Conclusions: APOE ε variants are linked to the risk of dementia, disability, and death in older adults. By examining these variants in clinical trials, we can better elucidate how they might alter the effectiveness of tested interventions. Importantly, this genetic information could help identify participants who may have greater absolute benefit from such interventions., (© 2024 The American Geriatrics Society.)

Importance: Fever is associated with worse outcomes in patients with stroke, but whether preventing fever improves outcomes is unclear., Objective: To determine whether fever prevention after acute vascular brain injury is achievable and impacts functional outcome., Design, Setting, and Participants: Open-label randomized clinical trial with blinded outcome assessment that enrolled 686 of 1176 planned critically ill patients with stroke at 43 intensive care units in 7 countries from March 2017 to April 2021 (last date of follow-up was May 12, 2022)., Intervention: Patients randomized to fever prevention (n = 339) were targeted to 37.0 °C for 14 days or intensive care unit discharge using an automated surface temperature management device. Standard care patients (n = 338) received standardized tiered fever treatment on occurrence of temperature of 38 °C or greater., Main Outcomes and Measures: Primary outcome was daily mean fever burden: the area under the temperature curve above 37.9 °C (total fever burden) divided by the total number of hours in the acute phase, multiplied by 24 hours (°C-hour). The principal secondary outcome was 3-month functional recovery by shift analysis of the 6-category modified Rankin Scale, which is scored from 0 (no symptoms) to 6 (death). Major adverse events included death, pneumonia, sepsis, and malignant cerebral edema., Results: Enrollment was stopped after a planned interim analysis demonstrated futility of the principal secondary end point. In total, 686 patients were enrolled, and 9 were consented but not randomized, leaving a primary analysis population of 677 patients (254 ischemic stroke, 223 intracerebral hemorrhage, 200 subarachnoid hemorrhage; 345 were female [51%]; median age, 62 years) with 433 (64%) completing the study through 12 months. Daily mean (SD) fever burden was significantly lower in the fever prevention group (0.37 [1.0] °C-hour; range, 0.0-8.0 °C-hour) compared with the standard care group (0.73 [1.1] °C-hour; range, 0.0-10.3 °C-hour) (difference, -0.35 [95% CI, -0.51 to -0.20]; P < .001). Between-group differences for the primary outcome by stroke subtype were -0.10 (95% CI, -0.35 to 0.15) for ischemic stroke, -0.50 (95% CI, -0.78 to -0.22) for intracerebral hemorrhage, and -0.52 (95% CI, -0.81 to -0.23) for subarachnoid hemorrhage (all P < .001 by Wilcoxon rank-sum test). There was no significant difference in functional recovery at 3 months (median modified Rankin Scale score, 4.0 vs 4.0, respectively; odds ratio for a favorable shift in functional outcome, 1.09 [95% CI, 0.81 to 1.46]; P = .54). Major adverse events occurred in 82.2% of participants in the fever prevention group vs 75.9% in the standard care group, including 33.8% vs 34.5% for infections, 14.5% vs 14.0% for cardiac disorders, and 24.5% vs 20.5% for respiratory disorders., Conclusions and Relevance: In patients with acute vascular brain injury, preventive normothermia using an automated surface temperature management device effectively reduced fever burden but did not improve functional outcomes., Trial Registration: ClinicalTrials.gov Identifier: NCT02996266.

Ischemic stroke is a major global public health concern that lacks effective treatment options. A significant challenge lies in delivering therapeutic agents to the brain due to the restrictive nature of the blood-brain barrier (BBB). The BBB's selectivity hampers the delivery of therapeutically relevant quantities of agents to the brain, resulting in a lack of FDA-approved pharmacotherapies for stroke. In this article, we review therapeutic agents that have been evaluated in clinical trials or are currently undergoing clinical trials. Subsequently, we survey strategies for synthesizing and engineering nanoparticles (NPs) for drug delivery to the ischemic brain. We then provide insights into the potential clinical translation of nanomedicine, offering a perspective on its transformative role in advancing stroke treatment strategies. In summary, existing literature suggests that drug delivery represents a major barrier for clinical translation of stroke pharmacotherapies. While nanotechnology has shown significant promise in addressing this challenge, further advancements aimed at improving delivery efficiency and simplifying formulations are necessary for successful clinical translation., Competing Interests: The authors declare no competing financial interests., (© 2024 The Authors.)

Background: Cranial nerve (CN) palsies are rare presenting symptoms of intracranial aneurysms. Our objectives were to report our institutional outcomes and study-level meta-analysis summarizing rates of improvement and identifying factors associated with recovery from CN symptoms after flow diversion., Methods: We conducted a retrospective review of our institutional database for patients with intracranial aneurysms presenting with CN palsies who underwent treatment with flow diversion between 2015 and 2023. Systematic review of the literature was performed using Medline, EMBASE, Cochrane, as well as manual citation searches. Random effects meta-analysis was used., Results: Thirteen of 136 studies were included in the meta-analysis and were combined with our institutional data. The pooled rate of improvement in any CN palsies following flow diversion was 71 % (95 %CI, 60 %-82 %, n=322). Patients presenting with CN II deficits were less likely to improve following treatment compared to other CN deficits (pooled OR [pOR] 0.32, 95 %CI, 0.16-0.63, n=224). The pooled rate of clinical improvement was 53 % in CNII deficits (95 %CI, 42 %-65 %, n=80) and 80 % in other CN deficits (95 %CI, 71 %-88 %, n=106). An increased rate of improvement was associated with acute intervention (pOR 9.12, 95 % CI, 2.26-36.73, n = 71) and radiographic aneurysm occlusion (pOR 5.29, 95 %CI, 1.66-16.90, n=118)., Conclusions: Flow diversion improves CN palsy outcomes in patients with symptomatic intracranial aneurysms. The lower rate of improvement in visual acuity compared to other CN deficits may point to a different mechanism of injury or potential recoverability in these patients., Competing Interests: Declaration of Competing Interest The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: To investigate associations between health-related behaviors as measured using the Brain Care Score (BCS) and neuroimaging markers of white matter injury., Methods: This prospective cohort study in the UK Biobank assessed the BCS, a novel tool designed to empower patients to address 12 dementia and stroke risk factors. The BCS ranges from 0 to 21, with higher scores suggesting better brain care. Outcomes included white matter hyperintensities (WMH) volume, fractional anisotropy (FA), and mean diffusivity (MD) obtained during 2 imaging assessments, as well as their progression between assessments, using multivariable linear regression adjusted for age and sex., Results: We included 34,509 participants (average age 55 years, 53% female) with no stroke or dementia history. At first and repeat imaging assessments, every 5-point increase in baseline BCS was linked to significantly lower WMH volumes (25% 95% CI [23%-27%] first, 33% [27%-39%] repeat) and higher FA (18% [16%-20%] first, 22% [15%-28%] repeat), with a decrease in MD (9% [7%-11%] first, 10% [4%-16%] repeat). In addition, a higher baseline BCS was associated with a 10% [3%-17%] reduction in WMH progression and FA decline over time., Discussion: This study extends the impact of the BCS to neuroimaging markers of clinically silent cerebrovascular disease. Our results suggest that improving one's BCS could be a valuable intervention to prevent early brain health decline.

Objective: For stroke patients with unknown time of onset, mismatch between diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) can guide thrombolytic intervention. However, access to MRI for hyperacute stroke is limited. Here, we sought to evaluate whether a portable, low-field (LF)-MRI scanner can identify DWI-FLAIR mismatch in acute ischemic stroke., Methods: Eligible patients with a diagnosis of acute ischemic stroke underwent LF-MRI acquisition on a 0.064-T scanner within 24 h of last known well. Qualitative and quantitative metrics were evaluated. Two trained assessors determined the visibility of stroke lesions on LF-FLAIR. An image coregistration pipeline was developed, and the LF-FLAIR signal intensity ratio (SIR) was derived., Results: The study included 71 patients aged 71 ± 14 years and a National Institutes of Health Stroke Scale of 6 (interquartile range 3-14). The interobserver agreement for identifying visible FLAIR hyperintensities was high (κ = 0.85, 95% CI 0.70-0.99). Visual DWI-FLAIR mismatch had a 60% sensitivity and 82% specificity for stroke patients <4.5 h, with a negative predictive value of 93%. LF-FLAIR SIR had a mean value of 1.18 ± 0.18 <4.5 h, 1.24 ± 0.39 4.5-6 h, and 1.40 ± 0.23 >6 h of stroke onset. The optimal cut-point for LF-FLAIR SIR was 1.15, with 85% sensitivity and 70% specificity. A cut-point of 6.6 h was established for a FLAIR SIR <1.15, with an 89% sensitivity and 62% specificity., Interpretation: A 0.064-T portable LF-MRI can identify DWI-FLAIR mismatch among patients with acute ischemic stroke. Future research is needed to prospectively validate thresholds and evaluate a role of LF-MRI in guiding thrombolysis among stroke patients with uncertain time of onset. ANN NEUROL 2024;96:321-331., (© 2024 American Neurological Association.)

Purpose: Computed Tomography Angiography (CTA) is the first line of imaging in the diagnosis of Large Vessel Occlusion (LVO) strokes. We trained and independently validated end-to-end automated deep learning pipelines to predict 3-month outcomes after anterior circulation LVO thrombectomy based on admission CTAs., Methods: We split a dataset of 591 patients into training/cross-validation (n = 496) and independent test set (n = 95). We trained separate models for outcome prediction based on admission "CTA" images alone, "CTA + Treatment" (including time to thrombectomy and reperfusion success information), and "CTA + Treatment  + Clinical" (including admission age, sex, and NIH stroke scale). A binary (favorable) outcome was defined based on a 3-month modified Rankin Scale ≤ 2. The model was trained on our dataset based on the pre-trained ResNet-50 3D Convolutional Neural Network ("MedicalNet") and included CTA preprocessing steps., Results: We generated an ensemble model from the 5-fold cross-validation, and tested it in the independent test cohort, with receiver operating characteristic area under the curve (AUC, 95% confidence interval) of 70 (0.59-0.81) for "CTA," 0.79 (0.70-0.89) for "CTA + Treatment," and 0.86 (0.79-0.94) for "CTA + Treatment + Clinical" input models. A "Treatment + Clinical" logistic regression model achieved an AUC of 0.86 (0.79-0.93)., Conclusion: Our results show the feasibility of an end-to-end automated model to predict outcomes from admission and post-thrombectomy reperfusion success. Such a model can facilitate prognostication in telehealth transfer and when a thorough neurological exam is not feasible due to language barrier or pre-existing morbidities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sommer, Dierksen, Zeevi, Tran, Avery, Mak, Malhotra, Matouk, Falcone, Torres-Lopez, Aneja, Duncan, Sansing, Sheth and Payabvash.)

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

Study Objective: Temperature control trials in cardiac arrest patients have not reliably conferred neuroprotective benefit but have been limited by inconsistent treatment parameters. To evaluate the presence of a time dependent treatment effect, we assessed the association between preinduction time and clinical outcomes., Methods: In this retrospective, single academic center study between 2014 and 2022, consecutive out-of-hospital cardiac arrest (OHCA) patients treated with temperature control were identified. Preinduction was defined as the time from hospital arrival to initiation of a closed-loop temperature feedback device [door to temperature control initiation time], and early door to temperature control device time was defined a priori as <3 hours. We assessed the association between good neurologic outcome (cerebral performance category 1 to 2) and door to temperature control device time using logistic regression. The proportion of patients who survived to hospital discharge was evaluated as a secondary outcome. A sensitivity analysis using inverse probability treatment weighting, created using a propensity score, was performed to minimize measurable confounding., Results: Three hundred and forty-seven OHCA patients were included; the early door to temperature control device cohort included 75 (21.6%) patients with a median (interquartile range) door to temperature control device time of 2.50 (2.03 to 2.75) hours, whereas the late door to temperature control device cohort included 272 (78.4%) patients with a median (interquartile range) door to temperature control device time of 5.18 (4.19 to 6.41) hours. In the multivariable logistic regression model, early door to temperature control device time was associated with improved good neurologic outcome and survival before [adjusted odds ratio (OR) (95% confidence interval) 2.36 (1.16 to 4.81) and 3.02 (1.54 to 6.02)] and after [adjusted OR (95% confidence interval) 1.95 (1.19 to 3.79) and 2.14 (1.33 to 3.36)] inverse probability of treatment weighting, respectively., Conclusion: In our study of OHCA patients, a shorter preinduction time for temperature control was associated with improved good neurologic outcome and survival. This finding may indicate that early initiation in the emergency department will confer benefit. Our findings are hypothesis generating and need to be validated in future prospective trials., (Copyright © 2024 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Socioeconomic status (SES) is a multi-faceted theoretical construct associated with stroke risk and outcomes. Knowing which SES measures best correlate with population stroke metrics would improve its accounting in observational research and inform interventions. Using the Centers for Disease Control and Prevention's (CDC) Population Level Analysis and Community Estimates (PLACES) and other publicly available databases, we conducted an ecological study comparing correlations of different United States county-level SES, health care access and clinical risk factor measures with age-adjusted stroke prevalence. The prevalence of adults living below 150% of the federal poverty level most strongly correlated with stroke prevalence compared to other SES and non-SES measures (correlation coefficient = 0.908, R 2  = 0.825; adjusted partial correlation coefficient: 0.589, R 2  = 0.347). ANN NEUROL 2024., (© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Introduction: The 21-point Brain Care Score (BCS) is a novel tool designed to motivate individuals and care providers to take action to reduce the risk of stroke and dementia by encouraging lifestyle changes. Given that late-life depression is increasingly recognized to share risk factors with stroke and dementia, and is an important clinical endpoint for brain health, we tested the hypothesis that a higher BCS is associated with a reduced incidence of future depression. Additionally, we examined its association with a brain health composite outcome comprising stroke, dementia, and late-life depression., Methods: The BCS was derived from the United Kingdom Biobank baseline evaluation in participants with complete data on BCS items. Associations of BCS with the risk of subsequent incident late-life depression and the composite brain health outcome were estimated using multivariable Cox proportional hazard models. These models were adjusted for age at baseline and sex assigned at birth., Results: A total of 363,323 participants were included in this analysis, with a median BCS at baseline of 12 (IQR: 11-14). There were 6,628 incident cases of late-life depression during a median follow-up period of 13 years. Each five-point increase in baseline BCS was associated with a 33% lower risk of incident late-life depression (95% CI: 29%-36%) and a 27% lower risk of the incident composite outcome (95% CI: 24%-30%)., Discussion: These data further demonstrate the shared risk factors across depression, dementia, and stroke. The findings suggest that a higher BCS, indicative of healthier lifestyle choices, is significantly associated with a lower incidence of late-life depression and a composite brain health outcome. Additional validation of the BCS is warranted to assess the weighting of its components, its motivational aspects, and its acceptability and adaptability in routine clinical care worldwide., Competing Interests: CA receives sponsored research support from the US National Institutes of Health, the American Heart Association, and Bayer AG, and has consulted for ApoPharma. GF receives sponsored research support from the National Institute of Mental Health Clinical Global Mental Health Research T32 Fellowship, receives royalties or licenses from Johns Hopkins University Press, University of Chicago Press, Belvoir Press, and the American Psychiatric Press, is on a Data Safety Monitoring Board or Advisory Board of Healthy Hearts Healthy Minds DSMB, is a Board of Directors member at the Rosalynn Carter Institute, and has stock or stock options from Revival Therapeutics Consultant. LG-M receives sponsored research support from the American Heart grant number 963719. JR receives sponsored research support from the US National Institutes of Health and the American Heart Association, and receives payments for expert testimony and consulting fees from the National Football League. EM is an employee of Regeneron Genetics Center. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.​ The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Singh, Rivier, Papier, Chemali, Gutierrez-Martinez, Parodi, Mayerhofer, Senff, Clocchiatti-Tuozzo, Nunley, Newhouse, Ouyang, Westover, Tanzi, Lazar, Pikula, Ibrahim, Brouwers, Howard, Howard, Yechoor, Littlejohns, Sheth, Rosand, Fricchione, Anderson and Falcone.)

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

Background: Predicting functional impairment after intracerebral hemorrhage (ICH) provides valuable information for planning of patient care and rehabilitation strategies. Current prognostic tools are limited in making long term predictions and require multiple expert-defined inputs and interpretation that make their clinical implementation challenging. This study aimed to predict long term functional impairment of ICH patients from admission non-contrast CT scans, leveraging deep learning models in a survival analysis framework., Methods: We used the admission non-contrast CT scans from 882 patients from the Massachusetts General Hospital ICH Study for training, hyperparameter optimization, and model selection, and 146 patients from the Yale New Haven ICH Study for external validation of a deep learning model predicting functional outcome. Disability (modified Rankin scale [mRS] > 2), severe disability (mRS > 4), and dependent living status were assessed via telephone interviews after 6, 12, and 24 months. The prediction methods were evaluated by the c-index and compared with ICH score and FUNC score., Results: Using non-contrast CT, our deep learning model achieved higher prediction accuracy of post-ICH dependent living, disability, and severe disability by 6, 12, and 24 months (c-index 0.742 [95% CI -0.700 to 0.778], 0.712 [95% CI -0.674 to 0.752], 0.779 [95% CI -0.733 to 0.832] respectively) compared with the ICH score (c-index 0.673 [95% CI -0.662 to 0.688], 0.647 [95% CI -0.637 to 0.661] and 0.697 [95% CI -0.675 to 0.717]) and FUNC score (c-index 0.701 [95% CI- 0.698 to 0.723], 0.668 [95% CI -0.657 to 0.680] and 0.727 [95% CI -0.708 to 0.753]). In the external independent Yale-ICH cohort, similar performance metrics were obtained for disability and severe disability (c-index 0.725 [95% CI -0.673 to 0.781] and 0.747 [95% CI -0.676 to 0.807], respectively). Similar AUC of predicting each outcome at 6 months, 1 and 2 years after ICH was achieved compared with ICH score and FUNC score., Conclusion: We developed a generalizable deep learning model to predict onset of dependent living and disability after ICH, which could help to guide treatment decisions, advise relatives in the acute setting, optimize rehabilitation strategies, and anticipate long-term care needs., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: J.R. reports compensation from National Football League for expert witness services from Takeda Development Center Americas and Boehringer Ingelheim for consultant services, all unrelated to this work. C.D.A. has received sponsored research support from Bayer AG and has consulted for ApoPharma unrelated to this work. E.M. is now a full-time employee of Regeneron Pharmaceuticals.

Purpose: To create and validate an automated pipeline for detection of early signs of irreversible ischemic change from admission CTA in patients with large vessel occlusion (LVO) stroke., Methods: We retrospectively included 368 patients for training and 143 for external validation. All patients had anterior circulation LVO stroke, endovascular therapy with successful reperfusion, and follow-up diffusion-weighted imaging (DWI). We devised a pipeline to automatically segment Alberta Stroke Program Early CT Score (ASPECTS) regions and extracted their relative Hounsfield unit (rHU) values. We determined the optimal rHU cut points for prediction of final infarction in each ASPECT region, performed 10-fold cross-validation in the training set, and measured the performance via external validation in patients from another institute. We compared the model with an expert neuroradiologist for prediction of final infarct volume and poor functional outcome., Results: We achieved a mean area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity of 0.69±0.13, 0.69±0.09, 0.61±0.23, and 0.72±0.11 across all regions and folds in cross-validation. In the external validation cohort, we achieved a median [interquartile] AUC, accuracy, sensitivity, and specificity of 0.71 [0.68-0.72], 0.70 [0.68-0.73], 0.55 [0.50-0.63], and 0.74 [0.73-0.77], respectively. The rHU-based ASPECTS showed significant correlation with DWI-based ASPECTS (rS = 0.39, p<0.001) and final infarct volume (rS = -0.36, p<0.001). The AUC for predicting poor functional outcome was 0.66 (95%CI: 0.57-0.75). The predictive capabilities of rHU-based ASPECTS were not significantly different from the neuroradiologist's visual ASPECTS for either final infarct volume or functional outcome., Conclusions: Our study demonstrates the feasibility of an automated pipeline and predictive model based on relative HU attenuation of ASPECTS regions on baseline CTA and its non-inferior performance in predicting final infarction on post-stroke DWI compared to an expert human reader., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: DF reports receiving personal fees from and holding an equity interest in ai4medicine outside the submitted work. CJG reports receiving honoraria from Stryker and MicroVention outside of the reported work. K.S reports equity interests in Alva Health., (Copyright: © 2024 Mak et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Delays in hospital presentation limit access to acute stroke treatments. While prior research has focused on patient-level factors, broader ecological and social determinants have not been well studied. We aimed to create a geospatial map of prehospital delay and examine the role of community-level social vulnerability., Methods: We studied patients with ischemic stroke who arrived by emergency medical services in 2015 to 2017 from the American Heart Association Get With The Guidelines-Stroke registry. The primary outcome was time to hospital arrival after stroke (in minutes), beginning at last known well in most cases. Using Geographic Information System mapping, we displayed the geography of delay. We then used Cox proportional hazard models to study the relationship between community-level factors and arrival time (adjusted hazard ratios [aHR] <1.0 indicate delay). The primary exposure was the social vulnerability index (SVI), a metric of social vulnerability for every ZIP Code Tabulation Area ranging from 0.0 to 1.0., Results: Of 750 336 patients, 149 145 met inclusion criteria. The mean age was 73 years, and 51% were female. The median time to hospital arrival was 140 minutes (Q1: 60 minutes, Q3: 458 minutes). The geospatial map revealed that many zones of delay overlapped with socially vulnerable areas (https://harvard-cga.maps.arcgis.com/apps/webappviewer/index.html?id=08f6e885c71b457f83cefc71013bcaa7). Cox models (aHR, 95% CI) confirmed that higher SVI, including quartiles 3 (aHR, 0.96 [95% CI, 0.93-0.98]) and 4 (aHR, 0.93 [95% CI, 0.91-0.95]), was associated with delay. Patients from SVI quartile 4 neighborhoods arrived 15.6 minutes [15-16.2] slower than patients from SVI quartile 1. Specific SVI themes associated with delay were a community's socioeconomic status (aHR, 0.80 [95% CI, 0.74-0.85]) and housing type and transportation (aHR, 0.89 [95% CI, 0.84-0.94])., Conclusions: This map of acute stroke presentation times shows areas with a high incidence of delay. Increased social vulnerability characterizes these areas. Such places should be systematically targeted to improve population-level stroke presentation times., Competing Interests: Disclosures Dr Dhand is Co-Founder and has stock options in ECHAS (Emergency Call for Heart Attack and Stroke). He is also a consultant for Availity and participates in expert witness activities. Dr Bergmark a consultant for Analysis Group and received grant funding from I-Mab Biopharma, and reports grants from Brigham and Women’s Hospital. Dr Fonarow is a consultant for Abbott Pharmaceuticals, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly and Company, Janssen Pharmaceuticals, Medtronic, Merck, Novartis, and Pfizer. Dr Saver is a consultant for Abbott Laboratories, Aeromics, Biogen, Boehringer Ingelheim, BrainQ, BrainGate, CSL Behring, Johnson & Johnson Health Care Systems Inc, Medtronic, MindRhythm, Neuronics Medical, Rapid Medical, Roche, and Stream Medical. He is on the data and safety monitoring board for MIVI Neuroscience. Dr Schwamm is a consultant for Genentech and Medtronic. Dr Sheth is President for Advanced Innovation in Medicine. He has stock options in BrainQ and receives grant support from BARD and Hyperfine. He is a consultant for Astrocyte, Cerevasc, CSL Behring, and Rhaeos. He is on the data and safety monitoring board for Sense. He reports a patent pending for Stroke wearables licensed to Alva Health

The Get With The Guidelines-Stroke program which, began 20 years ago, is one of the largest and most important nationally representative disease registries in the United States. Its importance to the stroke community can be gauged by its sustained growth and widespread dissemination of findings that demonstrate sustained increases in both the quality of care and patient outcomes over time. The objectives of this narrative review are to provide a brief history of Get With The Guidelines-Stroke, summarize its major successes and impact, and highlight lessons learned. Looking to the next 20 years, we discuss potential challenges and opportunities for the program., Competing Interests: Disclosures Dr Fonarow reports consulting for Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Janssen/Johnson & Johnson, Medtronic, Merck, Novartis, and Pfizer. Dr Messe reports consulting for Terumo and EmStop, a provisional patent for a stroke monitor, which has been licensed to Neuralert Technologies, and equity in Neuralert Technologies. Dr Sheth reports grant support from National Institutes of Health, American Heart Association, and Hyperfine; consulting from Astrocyte, CSL Behring, Rhaeos, Cerevasc, Bexorg Sense and Philips Data and Safety Monitoring Board; and patent with Alva. The other authors report no conflicts.

Background: Stroke prevalence varies by race/ethnicity, as do the risk factors that elevate the risk of stroke. Prior analyses have suggested that American Indian/Alaskan Natives (AI/AN) have higher rates of stroke and vascular risk factors., Methods: We included biyearly data from the 2011-2021 Behavioral Risk Factor Surveillance System (BRFSS) surveys of adults (age ≥18) in the United States. We describe survey-weighted prevalence of stroke per self-report by race and ethnicity. In patients with self-reported stroke (SRS), we also describe the prevalence of modifiable vascular risk factors., Results: The weighted number of U.S. participants represented in BRFSS surveys increased from 237,486,646 in 2011 to 245,350,089 in 2021. SRS prevalence increased from 2.9% in 2011 to 3.3% in 2021 (p<0.001). Amongst all race/ethnicity groups, the prevalence of stroke was highest in AI/AN at 5.4% and 5.6% in 2011 and 2021, compared to 3.0% and 3.4% for White adults (p<0.001). AI/AN with SRS were also the most likely to have four or more vascular risk factors in both 2011 and 2021 at 23.9% and 26.4% compared to 18.2% and 19.6% in White adults (p<0.001)., Conclusion: From 2011-2021 in the United States, AI/AN consistently had the highest prevalence of self-reported stroke and highest overall burden of modifiable vascular risk factors. This persistent health disparity leaves AI/AN more susceptible to both incident and recurrent stroke., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Introduction: Perihematomal edema (PHE) represents secondary brain injury and a potential treatment target in intracerebral hemorrhage (ICH). However, studies differ on optimal PHE volume metrics as prognostic factor(s) after spontaneous, non-traumatic ICH. This study examines associations of baseline and 24-h PHE shape features with 3-month outcomes., Patients and Methods: We included 796 patients from a multicentric trial dataset and manually segmented ICH and PHE on baseline and follow-up CTs, extracting 14 shape features. We explored the association of baseline, follow-up, difference (baseline/follow-up) and temporal rate (difference/time gap) of PHE shape changes with 3-month modified Rankin Score (mRS) - using Spearman correlation. Then, using multivariable analysis, we determined if PHE shape features independently predict outcome adjusting for patients' age, sex, NIH stroke scale (NIHSS), Glasgow Coma Scale (GCS), and hematoma volume., Results: Baseline PHE maximum diameters across various planes, main axes, volume, surface, and sphericity correlated with 3-month mRS adjusting for multiple comparisons. The 24-h difference and temporal change rates of these features had significant association with outcome - but not the 24-h absolute values. In multivariable regression, baseline PHE shape sphericity (OR = 2.04, CI = 1.71-2.43) and volume (OR = 0.99, CI = 0. 98-1.0), alongside admission NIHSS (OR = 0.86, CI = 0.83-0.88), hematoma volume (OR = 0.99, CI = 0. 99-1.0), and age (OR = 0.96, CI = 0.95-0.97) were independent predictors of favorable outcomes., Conclusion: In acute ICH patients, PHE shape sphericity at baseline emerged as an independent prognostic factor, with a less spherical (more irregular) shape associated with worse outcome. The PHE shape features absolute values over the first 24 h provide no added prognostic value to baseline metrics., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: KNS reports equity interests in Alva Health.

Determining acute ischemic stroke (AIS) etiology is fundamental to secondary stroke prevention efforts but can be diagnostically challenging. We trained and validated an automated classification tool, StrokeClassifier, using electronic health record (EHR) text from 2039 non-cryptogenic AIS patients at 2 academic hospitals to predict the 4-level outcome of stroke etiology adjudicated by agreement of at least 2 board-certified vascular neurologists' review of the EHR. StrokeClassifier is an ensemble consensus meta-model of 9 machine learning classifiers applied to features extracted from discharge summary texts by natural language processing. StrokeClassifier was externally validated in 406 discharge summaries from the MIMIC-III dataset reviewed by a vascular neurologist to ascertain stroke etiology. Compared with vascular neurologists' diagnoses, StrokeClassifier achieved the mean cross-validated accuracy of 0.74 and weighted F1 of 0.74 for multi-class classification. In MIMIC-III, its accuracy and weighted F1 were 0.70 and 0.71, respectively. In binary classification, the two metrics ranged from 0.77 to 0.96. The top 5 features contributing to stroke etiology prediction were atrial fibrillation, age, middle cerebral artery occlusion, internal carotid artery occlusion, and frontal stroke location. We designed a certainty heuristic to grade the confidence of StrokeClassifier's diagnosis as non-cryptogenic by the degree of consensus among the 9 classifiers and applied it to 788 cryptogenic patients, reducing cryptogenic diagnoses from 25.2% to 7.2%. StrokeClassifier is a validated artificial intelligence tool that rivals the performance of vascular neurologists in classifying ischemic stroke etiology. With further training, StrokeClassifier may have downstream applications including its use as a clinical decision support system., (© 2024. The Author(s).)

Background: The implementation of preventive therapies among patients with stroke remains inadequately explored, especially when compared with patients with myocardial infarction (MI), despite sharing similar vascular risk profiles. We tested the hypothesis that participants with a history of stroke have a worse cardiovascular prevention profile in comparison to participants with MI., Methods and Results: In cross-sectional analyses within the UK Biobank and All of Us Research Program, involving 14 760 (9193 strokes, 5567 MIs) and 7315 (2948 strokes, 4367 MIs) participants, respectively, we evaluated cardiovascular prevention profiles assessing low-density lipoprotein (<100 mg/dL), blood pressure (systolic, <140 mm Hg; and diastolic, <90 mm Hg), statin and antiplatelet use, and a cardiovascular prevention score that required meeting at least 3 of these criteria. The results revealed that, within the UK Biobank, patients with stroke had significantly lower odds of meeting all the preventive criteria compared with patients with MI: low-density lipoprotein control (odds ratio [OR], 0.73 [95% CI, 0.68-0.78]; P <0.001), blood pressure control (OR, 0.63 [95% CI, 0.59-0.68]; P <0.001), statin use (OR, 0.45 [95% CI, 0.42-0.48]; P <0.001), antiplatelet therapy use (OR, 0.30 [95% CI, 0.27-0.32]; P <0.001), and cardiovascular prevention score (OR, 0.42 [95% CI, 0.39-0.45]; P <0.001). Similar patterns were observed in the All of Us Research Program, with significant differences across all comparisons ( P <0.05), and further analysis suggested that the odds of having a good cardiovascular prevention score were influenced by race and ethnicity as well as neighborhood deprivation levels (interaction P <0.05 in both cases)., Conclusions: In 2 independent national cohorts, patients with stroke showed poorer cardiovascular prevention profiles and lower adherence to guideline-directed therapies compared with patients with MI. These findings underscore the need to explore the reasons behind the underuse of secondary prevention in vulnerable stroke survivors.

Background: Transcarotid artery revascularization (TCAR) is an increasingly popular technique for the management of extracranial carotid stenosis. Its off-label use in the treatment of intracranial neurovascular disease is poorly described. Our objective is to describe the use of a dedicated open transcarotid access system for the treatment of neurovascular pathologies other than extracranial carotid stenosis., Methods: We conducted a retrospective review of a prospectively maintained database of consecutive patients who underwent treatment of neurovascular disease at a single academic center using the ENROUTE Transcarotid Arterial Sheath. Demographics, procedural characteristics, and patient outcomes were reported., Results: Twenty patients were included in the study between September 2017 and March 2023. The following pathologies were treated: intracranial atherosclerotic disease (ICAD, nine patients), complex cervico-petrous carotid disease (five patients), intracranial aneurysms (three patients), and large vessel occlusion-acute ischemic stroke (three patients). Eighteen of the 20 cases were performed with active carotid flow reversal. All cases were successfully completed. There were no access-related complications. One periprocedural complication was incurred: a microguidewire perforation during an exchange maneuver for the treatment of ICAD., Conclusion: An open transcarotid approach using a dedicated transcarotid system may offer a safe alternative access strategy for the endovascular treatment of complex neurovascular pathologies when a traditional transfemoral or transradial approach is contraindicated or failed., Competing Interests: Competing interests: BJC received consulting fees from QApel, Penumbra, and Silk Road. CCM serves as site-PI for TCAR-DWI (Silk Road Medical), national-PI for NITE1 (Silk Road Medical), and is a paid consultant for Silk Road Medical., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The mortality rate of acute intracerebral hemorrhage (ICH) can reach up to 40%. Although the radiomics of ICH have been linked to hematoma expansion and outcomes, no research to date has explored their correlation with mortality. In this study, we determined the admission non-contrast head CT radiomic correlates of survival in supratentorial ICH, using the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-II) trial dataset. We extracted 107 original radiomic features from n = 871 admission non-contrast head CT scans. The Cox Proportional Hazards model, Kaplan-Meier Analysis, and logistic regression were used to analyze survival. In our analysis, the "first-order energy" radiomics feature, a metric that quantifies the sum of squared voxel intensities within a region of interest in medical images, emerged as an independent predictor of higher mortality risk (Hazard Ratio of 1.64, p < 0.0001), alongside age, National Institutes of Health Stroke Scale (NIHSS), and baseline International Normalized Ratio (INR). Using a Receiver Operating Characteristic (ROC) analysis, "the first-order energy" was a predictor of mortality at 1-week, 1-month, and 3-month post-ICH (all p < 0.0001), with Area Under the Curves (AUC) of >0.67. Our findings highlight the potential role of admission CT radiomics in predicting ICH survival, specifically, a higher "first-order energy" or very bright hematomas are associated with worse survival outcomes.

Background and Objectives: First pass effect (FPE) is a metric increasingly used to determine the success of mechanical thrombectomy (MT) procedures. However, few studies have investigated whether the duration of the procedure can modify the clinical benefit of FPE. We sought to determine whether FPE after MT for anterior circulation large vessel occlusion acute ischemic stroke is modified by procedural time (PT)., Methods: A multicenter, international data set was retrospectively analyzed for anterior circulation large vessel occlusion acute ischemic stroke treated by MT who achieved excellent reperfusion (thrombolysis in cerebral infarction 2c/3). The primary outcome was good functional outcome defined by 90-day modified Rankin scale scores of 0-2. The primary study exposure was first pass success (FPS, 1 pass vs ≥2 passes) and the secondary exposure was PT. We fit-adjusted logistic regression models and used marginal effects to assess the interaction between PT (≤30 vs >30 minutes) and FPS, adjusting for potential confounders including time from stroke presentation., Results: A total of 1310 patients had excellent reperfusion. These patients were divided into 2 cohorts based on PT: ≤30 minutes (777 patients, 59.3%) and >30 minutes (533 patients, 40.7%). Good functional outcome was observed in 658 patients (50.2%). The interaction term between FPS and PT was significant ( P = .018). Individuals with FPS in ≤30 minutes had 11.5% higher adjusted predicted probability of good outcome compared with those who required ≥2 passes (58.2% vs 46.7%, P = .001). However, there was no significant difference in the adjusted predicted probability of good outcome in individuals with PT >30 minutes. This relationship appeared identical in models with PT treated as a continuous variable., Conclusion: FPE is modified by PT, with the added clinical benefit lost in longer procedures greater than 30 minutes. A comprehensive metric for MT procedures, namely, FPE 30 , may better represent the ideal of fast, complete reperfusion with a single pass of a thrombectomy device., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Importance: Stroke is a leading cause of death and disability in the US. Accurate and updated measures of stroke burden are needed to guide public health policies., Objective: To present burden estimates of ischemic and hemorrhagic stroke in the US in 2019 and describe trends from 1990 to 2019 by age, sex, and geographic location., Design, Setting, and Participants: An in-depth cross-sectional analysis of the 2019 Global Burden of Disease study was conducted. The setting included the time period of 1990 to 2019 in the US. The study encompassed estimates for various types of strokes, including all strokes, ischemic strokes, intracerebral hemorrhages (ICHs), and subarachnoid hemorrhages (SAHs). The 2019 Global Burden of Disease results were released on October 20, 2020., Exposures: In this study, no particular exposure was specifically targeted., Main Outcomes and Measures: The primary focus of this analysis centered on both overall and age-standardized estimates, stroke incidence, prevalence, mortality, and DALYs per 100 000 individuals., Results: In 2019, the US recorded 7.09 million prevalent strokes (4.07 million women [57.4%]; 3.02 million men [42.6%]), with 5.87 million being ischemic strokes (82.7%). Prevalence also included 0.66 million ICHs and 0.85 million SAHs. Although the absolute numbers of stroke cases, mortality, and DALYs surged from 1990 to 2019, the age-standardized rates either declined or remained steady. Notably, hemorrhagic strokes manifested a substantial increase, especially in mortality, compared with ischemic strokes (incidence of ischemic stroke increased by 13% [95% uncertainty interval (UI), 14.2%-11.9%]; incidence of ICH increased by 39.8% [95% UI, 38.9%-39.7%]; incidence of SAH increased by 50.9% [95% UI, 49.2%-52.6%]). The downturn in stroke mortality plateaued in the recent decade. There was a discernible heterogeneity in stroke burden trends, with older adults (50-74 years) experiencing a decrease in incidence in coastal areas (decreases up to 3.9% in Vermont), in contrast to an uptick observed in younger demographics (15-49 years) in the South and Midwest US (with increases up to 8.4% in Minnesota)., Conclusions and Relevance: In this cross-sectional study, the declining age-standardized stroke rates over the past 3 decades suggest progress in managing stroke-related outcomes. However, the increasing absolute burden of stroke, coupled with a notable rise in hemorrhagic stroke, suggests an evolving and substantial public health challenge in the US. Moreover, the significant disparities in stroke burden trends across different age groups and geographic locations underscore the necessity for region- and demography-specific interventions and policies to effectively mitigate the multifaceted and escalating burden of stroke in the country.

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.