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The management of patients with stroke is often multidisciplinary, involving various specialties and healthcare professionals. Given the common shared risk factors for stroke and cardiovascular disease, input may also be required from the cardiovascular teams, as well as patient caregivers and next-of-kin. Ultimately, the patient is central to all this, requiring a coordinated and uniform approach to the priorities of post-stroke management, which can be consistently implemented by different multidisciplinary healthcare professionals, as part of the patient ‘journey’ or ‘patient pathway,’ supported by appropriate education and tele-medicine approaches. All these aspects would ultimately aid delivery of care and improve patient (and caregiver) engagement and empowerment. Given the need to address the multidisciplinary approach to holistic or integrated care of patients with heart disease and stroke, the European Society of Cardiology Council on Stroke convened a Task Force, with the remit to propose a consensus on Integrated care management for optimizing the management of stroke and associated heart disease. The present position paper summarizes the available evidence and proposes consensus statements that may help to define evidence gaps and simple practical approaches to assist in everyday clinical practice. A post-stroke ABC pathway is proposed, as a more holistic approach to integrated stroke care, would include three pillars of management: A: Appropriate Antithrombotic therapy.B: Better functional and psychological status.C: Cardiovascular risk factors and Comorbidity optimization (including lifestyle changes).

Background and ObjectivesEarly consciousness disorder (ECD) after acute ischemic stroke (AIS) is understudied. ECD may influence outcomes and the decision to withhold or withdraw life-sustaining treatment.MethodsWe studied patients with AIS from 2010 to 2019 across 122 hospitals participating in the Florida Stroke Registry. We studied the effect of ECD on in-hospital mortality, withholding or withdrawal of life-sustaining treatment (WLST), ambulation status on discharge, hospital length of stay, and discharge disposition.ResultsOf 238,989 patients with AIS, 32,861 (14%) had ECD at stroke presentation. Overall, average age was 72 years (Q1 61, Q3 82), 49% were women, 63% were White, 18% were Black, and 14% were Hispanic. Compared to patients without ECD, patients with ECD were older (77 vs 72 years), were more often female (54% vs 48%), had more comorbidities, had greater stroke severity as assessed by the National Institutes of Health Stroke Scale (score ≥5 49% vs 27%), had higher WLST rates (21% vs 6%), and had greater in-hospital mortality (9% vs 3%). Using adjusted models accounting for basic characteristics, patients with ECD had greater in-hospital mortality (odds ratio [OR] 2.23, 95% CI 1.98–2.51), had longer hospitalization (OR 1.37, 95% CI 1.33–1.44), were less likely to be discharged home or to rehabilitation (OR 0.54, 95% CI 0.52–0.57), and were less likely to ambulate independently (OR 0.61, 95% CI 0.57–0.64). WLST significantly mediated the effect of ECD on mortality (mediation effect 265; 95% CI 217–314). In temporal trend analysis, we found a significant decrease in early WLST (2 0.7, p = 0.002) and an increase in late WLST (≥2 days) (R2 0.7, p = 0.004).DiscussionIn this large prospective multicenter stroke registry, patients with AIS presenting with ECD had greater mortality and worse discharge outcomes. Mortality was largely influenced by the WLST decision.

Background and ObjectivesThere are disparities in the prevalence of obesity by race, and the relationship between obesity and cognitive decline is unclear. The objective of this study was to determine whether obesity is independently associated with cognitive decline and whether the association between obesity and cognitive decline differs in Black and White adults. We hypothesized that obesity is associated with greater cognitive decline compared with normal weight and that the effect of obesity on cognitive decline is more pronounced in Black adults compared with their White counterparts.MethodsWe pooled data from 28,867 participants free of stroke and dementia (mean, SD: age 61 [10.7] years at the first cognitive assessment, 55% female, 24% Black, and 29% obese) from 6 cohorts. The primary outcome was the annual change in global cognition. We performed linear mixed-effects models with and without time-varying cumulative mean systolic blood pressure (SBP) and fasting plasma glucose (FPG). Global cognition was set to a t-score metric (mean 50, SD 10) at a participant's first cognitive assessment; a 1-point difference represents a 0.1 SD difference in global cognition across the 6 cohorts. The median follow-up was 6.5 years (25th percentile, 75th percentile: 5.03, 20.15).ResultsObese participants had lower baseline global cognition than normal-weight participants (difference in intercepts, −0.36 [95% CI, −0.46 to −0.17];p< 0.001). This difference in baseline global cognition was attenuated but was borderline significant after accounting for SBP and FPG (adjusted differences in intercepts, −0.19 [95% CI, −0.39 to 0.002];p= 0.05). There was no difference in the rate of decline in global cognition between obese and normal-weight participants (difference in slope, 0.009 points/year [95% CI, −0.009 to 0.03];p= 0.32). After accounting for SBP and FPG, obese participants had a slower decline in global cognition (adjusted difference in slope, 0.03 points/year slower [95% CI, 0.01 to 0.05];p< 0.001). There was no evidence that race modified the association between body mass index and global cognitive decline (p= 0.34).DiscussionThese results suggest that obesity is associated with lower initial cognitive scores and may potentially attenuate declines in cognition after accounting for BP and FPG.

Background and ObjectivesTo examine whether high white matter hyperintensity (WMH) burden is associated with greater stroke severity and worse functional outcomes in lesion pattern–specific ways.MethodsMR neuroimaging and NIH Stroke Scale data at index stroke and the modified Rankin Scale (mRS) score at 3–6 months after stroke were obtained from the MRI–Genetics Interface Exploration study of patients with acute ischemic stroke (AIS). Individual WMH volume was automatically derived from fluid-attenuated inversion recovery images. Stroke lesions were automatically segmented from diffusion-weighted imaging (DWI) images, parcellated into atlas-defined brain regions and further condensed to 10 lesion patterns via machine learning–based dimensionality reduction. Stroke lesion effects on AIS severity and unfavorable outcomes (mRS score >2) were modeled within purpose-built Bayesian linear and logistic regression frameworks. Interaction effects between stroke lesions and a high vs low WMH burden were integrated via hierarchical model structures. Models were adjusted for age, age2, sex, total DWI lesion and WMH volumes, and comorbidities. Data were split into derivation and validation cohorts.ResultsA total of 928 patients with AIS contributed to acute stroke severity analyses (age: 64.8 [14.5] years, 40% women) and 698 patients to long-term functional outcome analyses (age: 65.9 [14.7] years, 41% women). Stroke severity was mainly explained by lesions focused on bilateral subcortical and left hemispherically pronounced cortical regions across patients with both a high and low WMH burden. Lesions centered on left-hemispheric insular, opercular, and inferior frontal regions and lesions affecting right-hemispheric temporoparietal regions had more pronounced effects on stroke severity in case of high compared with low WMH burden. Unfavorable outcomes were predominantly explained by lesions in bilateral subcortical regions. In difference to the lesion location–specific WMH effects on stroke severity, higher WMH burden increased the odds of unfavorable outcomes independent of lesion location.DiscussionHigher WMH burden may be associated with an increased stroke severity in case of stroke lesions involving left-hemispheric insular, opercular, and inferior frontal regions (potentially linked to language functions) and right-hemispheric temporoparietal regions (potentially linked to attention). Our findings suggest that patients with specific constellations of WMH burden and lesion locations may have greater benefits from acute recanalization treatments. Future clinical studies are warranted to systematically assess this assumption and guide more tailored treatment decisions.

Background and Purpose: IV tPA (intravenous thrombolysis with alteplase) and mechanical thrombectomy (MT) utilization increased in acute ischemic stroke hospitalizations in the United States over the last decade. It is uncertain whether this increase occurred equally across all age, sex, and racial groups. Methods: Adult acute ischemic stroke hospitalizations (weighted n=4 442 657) contained in the 2008 to 2017 National Inpatient Sample were identified using International Classification of Diseases codes. Proportions of hospitalizations with IV tPA and MT were computed according to age, sex, and race. Joinpoint and multivariable-adjusted logistic regression models were used to evaluate trends over time. Results: Across this period, 32.4% of all hospitalizations were in patients ≥80 years, and 64.7% of these were women. IV tPA and MT use differed by age with highest proportion of utilization of both treatments in patients aged 18 to 39 years (IV tPA, 12.3%) and lowest percentage in patients aged ≥90 years (IV tPA, 7.9%). Utilization of both procedures increased over time in all age groups, but the pace of increase was faster in patients ≥90 years compared with patients aged 18 to 39 years (MT: odds ratio, 1.25 [95% CI, 1.20–1.35] per unit increase in year, P interaction 10% in all demographic subgroups except in Black patients 60 to 79 years and Black patients ≥80 years. Analysis of race-by-time interaction revealed the Black-vs-White treatment gaps for IV tPA (odds ratio, 1.02 [95% CI, 1.01–1.03]) and MT (odds ratio, 1.08 [95% CI,1.05–1.12]) declined over time (both P interaction Conclusions: Age- and sex-related treatment gaps in IV tPA and MT reduced over the last decade. Racial disparity in IV tPA and MT utilization persists with particularly lower frequency of usage of both acute stroke treatments in Black patients compared with White patients, but race-associated treatment gaps also declined over time.

BACKGROUND: Prolonged monitoring of cardiac rhythm has been used to screen for subclinical atrial fibrillation (AF); little is known about other arrhythmias in the general population, especially in the elderly, who are at higher risk of arrhythmias. METHODS: We evaluated the frequency of arrhythmias in the tri-ethnic (white, Black, Hispanic), community-based Subclinical Atrial Fibrillation and Risk of Ischemic Stroke (SAFARIS) study using a patch-based recorder for up to 14 days in 527 participants free of AF, congestive heart failure (CHF) or history of stroke. Differences according to gender, age, ethnicity and presence of hypertension, diabetes and pertinent ECG and echocardiographic variables were examined. RESULTS: Mean age was 77.2±6.8 years (37.2% men, 62.8% women). AF was present in 10 participants (1.9%), only 2 of them symptomatic. Supraventricular tachycardia (SVT) and ventricular tachycardia (VT) episodes were observed in 84.4% and 25.0% but only 13.5% and 10.6% of participants reported symptoms, respectively. Severe bradycardia (75 years; ventricular arrhythmias and severe bradycardia were more common in men. Whites had significantly more episodes of AF than Hispanics, SVT than Blacks and VT≥10 beats than Hispanics and Blacks. Hypertensives had more episodes of severe bradycardia. LV hypertrophy or LVEF

Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of stroke worldwide and confers a high risk of stroke recurrence, despite aggressive management of risk factors.This study identified the role of risk factors and risk of vascular events in subjects with asymptomatic ICAS for improved risk stratification.Stroke-free participants in the NOMAS (Northern Manhattan Study) trial, prospectively followed since 1993, underwent a brain magnetic resonance angiogram from 2003 to 2008. The study rated stenosis in 11 brain arteries as: 0: no stenosis; 1: 50% or luminal irregularities; 2: 50%-69%; and 3: ≥70% stenosis or flow gap. The study ascertained vascular events during the post-magnetic resonance imaging (MRI) period. Proportional odds regression quantified the association of pre-MRI exposures, and proportional hazard adjusted models were built to identify the risk of events in the post-MRI period.The included sample included 1,211 participants from NOMAS (mean age: 71 ± 9 years; 59% women; 65% Hispanic; 45% had any stenosis). Older age (OR: 1.02 per year; 95% CI: 1.01 to 1.04), hypertension duration (OR: 1.01 per year; 95% CI: 1.00 to 1.02), higher number of glucose-lowering drugs (OR: 1.64 per each medication; 95% CI: 1.24 to 2.15), and high-density lipoprotein (OR: 0.96 per mg/dL; 95% CI: 0.92 to 0.99) were associated with ICAS. The highest event risk was noted among participants with ICAS ≥70% (5.5% annual risk of vascular events; HR: 2.1; 95% CI:1.4 to 3.2; compared with those with no ICAS).ICAS is an imaging marker of established atherosclerotic disease in stroke-free subjects, and incidental diagnosis of ICAS should trigger a thorough assessment of vascular health.

Background and Purpose: Acute ischemic stroke is a known complication of intracranial dolichoectasia (IDE). However, the frequency of IDE causing brain infarction is unknown. We aim to determine the prevalence and clinical correlates of IDE in acute ischemic stroke by employing an objective IDE definition for major intracranial arteries of the anterior and posterior circulation. Methods: Consecutive patients with acute ischemic stroke admitted to a tertiary-care hospital during a 4-month period were analyzed. Intracranial arterial diameter, length, and tortuosity were determined by semiautomatic vessel segmentation and considered abnormal if ≥2 SDs from the study population mean. Either ectasia (increased diameter) or dolichosis (increased length or tortuosity) of at least one proximal intracranial artery defined IDE. Symptomatic IDE was considered when the infarct was located in the territory supplied by an affected artery in the absence of any alternative pathogenic explanation. Multivariate models were fitted to determine IDE clinical correlates. Results: Among 211 cases screened, 200 patients (mean age 67±14 years, 47.5% men) with available intracranial vessel imaging were included. IDE was identified in 24% cases (5% with isolated ectasia, 9.5% with isolated dolichosis, and 9.5% with both ectasia and dolichosis). IDE was considered the most likely pathogenic mechanism in 12 cases (6% of the entire cohort), which represented 23.5% of strokes initially categorized as undetermined cause. In addition, 21% of small-artery occlusion strokes had the infarct territory supplied by a dolichoectatic vessel (3% of the entire cohort). IDE was independently associated with male sex (odds ratio, 4.2 [95% CI, 1.7–10.6]) and its component of ectasia was associated with advanced age (odds ratio, 3.5 [95% CI, 1.3–9.5]). Vascular risk profile was similar across patients with stroke with and without IDE. Conclusions: Our findings suggest that IDE is an arteriopathy frequently found in patients with acute ischemic stroke and is likely responsible for a sizable fraction of strokes initially categorized as of undetermined cause and perhaps also in those with small-artery occlusion.

The association between cervical internal carotid artery (cICA) tortuosity and atherosclerosis is a matter of debate. Additionally, some genetic syndromes characterized by connective tissue remodeling are associated with arterial tortuosity, raising the possibility that cICA tortuosity may not only be atherosclerotic. In this study, we hypothesized that cICA tortuosity is not associated with imaging biomarkers of atherosclerosis.The Northern Manhattan Study (NOMAS) was a prospective, multiethnic cohort of stroke-free individuals who underwent brain MRA, carotid ultrasound and transthoracic echocardiogram from 2003-2008. The cICA tortuosity was scored in each carotid as 0 = no tortuosity, 1 = tortuosity90°, 2 = tortuosity ≥90°. A summary cICA tortuosity score (possible range 0-4) was created by adding up the tortuosity score from each carotid. Participants were assessed for atherosclerotic markers by using B‑mode carotid sonography and transthoracic echocardiography.Of 558 participants 178 (31.9%) had any cervical ICA tortuosity (tortuosity score0). The cICA tortuosity score was higher in women and was associated with diastolic and systolic blood pressures and height (all P 0.05). In models adjusted for demographics and risk factors, only the association with diastolic blood pressure remained significant (β = 0.002, P = 0.02). Similarly, cICA tortuosity was associated with larger aortic root diameter (B = 1.03 ± 0.36, P = 0.004) but not with other markers of carotid or aortic atherosclerosis.Cervical ICA tortuosity is associated with a higher diastolic blood pressure and larger aortic root diameter but not with other measures of atherosclerosis. Determining the risks of vascular events associated with this non-atherosclerotic phenotype may help for a better risk stratification for individuals with cICA tortuosity.

Background and Purpose: Although most strokes present with mild symptoms, these have been poorly represented in clinical trials. The objective of this study is to describe multidimensional outcomes, identify predictors of worse outcomes, and explore the effect of thrombolysis in this population. Methods: This prospective observational study included patients with ischemic stroke or transient ischemic attack, a baseline National Institutes of Health Stroke Scale (NIHSS) score 0 to 5, presenting within 4.5 hours from symptom onset. The primary outcome was a 90-day modified Rankin Scale score of 0 to 1; secondary outcomes included good outcomes in the Barthel Index, Stroke Impact Scale-16, and European Quality of Life. Multivariable models were created to determine predictors of outcomes and the effect of alteplase. Results: A total of 1765 participants were included from 100 Get With The Guidelines-Stroke participating hospitals (age, 65±14; 42% women; final diagnosis of ischemic stroke, 90%; transient ischemic attack, 10%; 57% received alteplase). At 90 days, 37% were disabled and 25% not independent. Worse outcomes were noted for older individuals, women, non-Hispanic Blacks and Hispanics, Medicaid recipients, smokers, those with diabetes, atrial fibrillation, prior stroke, higher baseline NIHSS, visual field defects, and extremity weakness. Similar outcomes were noted for the alteplase-treated and untreated groups. Alteplase-treated patients were younger (64±13 versus 67±1.4) with higher NIHSS (2.9±1.4 versus 1.7±1.4). After adjusting for age, sex, race/ethnicity, and baseline NIHSS, we did not identify an effect of alteplase on the primary outcome but did find an association with Stroke Impact Scale-16 in the restricted sample of baseline NIHSS score 3–5. Few symptomatic intracerebral hemorrhages were recorded ( Conclusions: A large proportion of stroke patients presenting with low NIHSS have a disabled outcome. Baseline predictors of worse outcomes are described. An effect of alteplase on outcomes was not identified in the overall cohort, but a suggestion of efficacy was noted in the NIHSS 3–5 subgroup. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02072681.

Background and Purpose: Patent foramen ovale (PFO) may increase the risk of embolic stroke of undetermined source (ESUS). Guidelines suggest anticoagulation may be more effective than antiplatelets in preventing stroke in patients with ESUS and PFO when interventional closure is not performed. Methods: Patients with ESUS randomized to dabigatran (150/110 mg BID) or aspirin (100 mg QD) from the RE-SPECT ESUS study (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) were included. The rate of recurrent stroke (primary end point) and ischemic stroke was reported for patients with and without baseline PFO. A meta-analysis comparing the effects of anticoagulant and antiplatelet therapy on ischemic stroke in patients with PFO was updated to include RE-SPECT ESUS. Results: PFO was present in 680 of 5388 (12.6%) patients with documented PFO status. The risk of recurrent stroke with dabigatran versus aspirin was similar in patients with and without PFO ( P for interaction, 0.8290). In patients with PFO, the meta-analysis found no statistically significant difference between anticoagulant and antiplatelet therapy (odds ratio, 0.70 [95% CI, 0.43–1.14]) for ischemic stroke. Conclusions: There is insufficient evidence to recommend anticoagulation over antiplatelet therapy for patients with ESUS and a PFO. More data are needed to guide antithrombotic therapy in this population. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02239120.

Background We sought to determine recurrent stroke predictors among patients with embolic strokes of undetermined source (ESUS). Methods and Results We applied Cox proportional hazards models to identify clinical features associated with recurrent stroke among participants enrolled in RE‐SPECT ESUS (Randomized, Double‐Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) trial, an international clinical trial evaluating dabigatran versus aspirin for patients with ESUS. During a median follow‐up of 19 months, 384 of 5390 participants had recurrent stroke (annual rate, 4.5%). Multivariable models revealed that stroke or transient ischemic attack before the index event (hazard ratio [HR], 2.27 [95% CI, 1.83–2.82]), creatinine clearance 2 DS 2 ‐VASc ≥4 (HR, 1.55 [95% CI, 1.15–2.08] and HR, 1.66 [95% CI, 1.21–2.26] for scores of 4 and ≥5, respectively) versus CHA 2 DS 2 ‐VASc of 2 to 3, were independent predictors for recurrent stroke. Conclusions In RE‐SPECT ESUS trial, expected risk factors previously linked to other common stroke causes were associated with stroke recurrence. These data help define high‐risk groups for subsequent stroke that may be useful for clinicians and for researchers designing trials among patients with ESUS. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02239120.

Numerous epidemiological studies have demonstrated stroke disparities across race and ethnic groups. The goal of the NOMAS (Northern Manhattan Study) was to evaluate race and ethnic differences in stroke within a community with 3 different race-ethnic groups. Starting as a population-based incidence and case-control study, the study evolved into a cohort study. Results from NOMAS have demonstrated differences in stroke incidence, subtypes, risk factors, and outcomes. Disparities in ideal cardiovascular health can help explain many differences in stroke incidence and call for tailored risk factor modification through innovative portals to shift more diverse subjects to ideal cardiovascular health. The results of NOMAS and multiple other studies have provided foundational data to support interventions. Conceptual models to address health disparities have called for moving from detecting disparities in disease incidence, to determining the underlying causes of disparities and developing interventions, and then to testing interventions in human populations. Further actions to address race and ethnic stroke disparities are needed including innovative risk factor interventions, stroke awareness campaigns, quality improvement programs, workforce diversification, and accelerating policy changes.

Objectives Recently, more sophisticated blood pressure (BP) measurements, such as central and ambulatory BP (ABP), have proven to be stronger predictors of future cardiovascular disease than conventional office BP. Their predictive value for atrial fibrillation development is not established. We investigated the prognostic impact for incident atrial fibrillation of office, central and ambulatory BP measurements in a predominantly older population-based cohort. Methods Of 1004 participants in the Cardiovascular Abnormalities and Brain Lesions (CABL) study, 769 in sinus rhythm with no history of atrial fibrillation or stroke (mean age 70.5 years) underwent ABP and arterial wave reflection analysis for central BP determination. Fine and Gray's proportional subdistribution hazards models were used to assess the association of BP parameters with incident atrial fibrillation. Results During 9.5 years, atrial fibrillation occurred in 83 participants. No office BP variable showed a significant association with incident atrial fibrillation. Central SBP and central pulse pressure were marginally associated with incident atrial fibrillation in multivariate analysis. Among ABP variables, 24-h SBP [adjusted hazard ratio per 10 mmHg, 1.24; 95% confidence interval (CI) 1.07--1.44; P = 0.004], daytime SBP (adjusted hazard ratio per 10 mmHg, 1.21; 95% CI 1.04--1.40; P = 0.011) and night-time SBP (adjusted hazard ratio per 10 mmHg, 1.22; 95% CI 1.07--1.39; P = 0.002) were significantly associated with incident atrial fibillation. Conclusion In a predominantly older, stroke-free community-based cohort, ABP was a better independent predictor of incident atrial fibrillation than central BP, whereas office BP was inadequate for this purpose.

ObjectiveTo examine etiologic stroke subtypes and vascular risk factor profiles and their association with white matter hyperintensity (WMH) burden in patients hospitalized for acute ischemic stroke (AIS).MethodsFor the MRI Genetics Interface Exploration (MRI-GENIE) study, we systematically assembled brain imaging and phenotypic data for 3,301 patients with AIS. All cases underwent standardized web tool–based stroke subtyping with the Causative Classification of Ischemic Stroke (CCS). WMH volume (WMHv) was measured on T2 brain MRI scans of 2,529 patients with a fully automated deep-learning trained algorithm. Univariable and multivariable linear mixed-effects modeling was carried out to investigate the relationship of vascular risk factors with WMHv and CCS subtypes.ResultsPatients with AIS with large artery atherosclerosis, major cardioembolic stroke, small artery occlusion (SAO), other, and undetermined causes of AIS differed significantly in their vascular risk factor profile (all p < 0.001). Median WMHv in all patients with AIS was 5.86 cm3 (interquartile range 2.18–14.61 cm3) and differed significantly across CCS subtypes (p < 0.0001). In multivariable analysis, age, hypertension, prior stroke, smoking (all p < 0.001), and diabetes mellitus (p = 0.041) were independent predictors of WMHv. When adjusted for confounders, patients with SAO had significantly higher WMHv compared to those with all other stroke subtypes (p < 0.001).ConclusionIn this international multicenter, hospital-based cohort of patients with AIS, we demonstrate that vascular risk factor profiles and extent of WMH burden differ by CCS subtype, with the highest lesion burden detected in patients with SAO. These findings further support the small vessel hypothesis of WMH lesions detected on brain MRI of patients with ischemic stroke.

OBJECTIVE:To determine whether brain volume is associated with functional outcome after acute ischemic stroke (AIS). PATIENTS AND METHODS:This study was conducted between July 1, 2014, and March 16, 2019. We analyzed cross-sectional data of the multisite, international hospital-based MRI-Genetics Interface Exploration study with clinical brain magnetic resonance imaging obtained on admission for index stroke and functional outcome assessment. Poststroke outcome was determined using the modified Rankin Scale score (0-6; 0 = asymptomatic; 6 = death) recorded between 60 and 190 days after stroke. Demographic characteristics and other clinical variables including acute stroke severity (measured as National Institutes of Health Stroke Scale score), vascular risk factors, and etiologic stroke subtypes (Causative Classification of Stroke system) were recorded during index admission. RESULTS:Utilizing the data from 912 patients with AIS (mean ± SD age, 65.3±14.5 years; male, 532 [58.3%]; history of smoking, 519 [56.9%]; hypertension, 595 [65.2%]) in a generalized linear model, brain volume (per 155.1 cm3) was associated with age (β -0.3 [per 14.4 years]), male sex (β 1.0), and prior stroke (β -0.2). In the multivariable outcome model, brain volume was an independent predictor of modified Rankin Scale score (β -0.233), with reduced odds of worse long-term functional outcomes (odds ratio, 0.8; 95% CI, 0.7-0.9) in those with larger brain volumes. CONCLUSION:Larger brain volume quantified on clinical magnetic resonance imaging of patients with AIS at the time of stroke purports a protective mechanism. The role of brain volume as a prognostic, protective biomarker has the potential to forge new areas of research and advance current knowledge of the mechanisms of poststroke recovery.

Stroke remains the second-leading cause of death and the third-leading cause of death and disability combined (as expressed by disability-adjusted life-years lost – DALYs) in the world. The estimated global cost of stroke is over US$721 billion (0.66% of the global GDP). From 1990 to 2019, the burden (in terms of the absolute number of cases) increased substantially (70.0% increase in incident strokes, 43.0% deaths from stroke, 102.0% prevalent strokes, and 143.0% DALYs), with the bulk of the global stroke burden (86.0% of deaths and 89.0% of DALYs) residing in lower-income and lower-middle-income countries (LMIC). This World Stroke Organisation (WSO) Global Stroke Fact Sheet 2022 provides the most updated information that can be used to inform communication with all internal and external stakeholders; all statistics have been reviewed and approved for use by the WSO Executive Committee as well as leaders from the Global Burden of Disease research group.

Introduction Genetic and imaging studies demonstrate a link between vascular morphology and migraine with aura (MA). We examined the relationship between basilar artery (BA) curvature and MA in a population-based cohort of stroke-free participants. Methods This cross-sectional study included participants from the MRI substudy of the Northern Manhattan Study. Participants had structured migraine assessments at enrollment and underwent brain MR angiography. BA curvature was defined as the sum of the total BA horizontal deviation from midline at the distal tip, mid-pons, and vertebrobasilar junction, and was the primary independent variable in logistic regression analyses. BA measurements were obtained blinded to migraine status. We compared groups of all migraine vs no migraine, migraine without aura (MwoA) vs no migraine, and MA vs no migraine. Results Of 880 participants, 146 had MwoA and 32 had MA. Average BA curvatures were 15.2 ± 8.9 mm in non-migraineurs, 15.8 ± 9.3 mm in MwoA, and 18.5 ± 11.4 mm in MA. In an adjusted model, greater BA curvature was associated with MA (OR 1.042 per mm, 95% CI 1.006–1.080) but not with MwoA (OR 1.014 per mm, 95% CI 0.993–1.035), when compared to non-migraineurs. Conclusions Greater BA curvature was associated with MA. Given aura typically originates from the occipital cortex, understanding the physiopathology of this association may provide clues to migraine's underlying mechanisms and relationship with stroke.

ObjectiveTo determine the contribution of common genetic variants to risk of early onset ischemic stroke (IS).MethodsWe performed a meta-analysis of genome-wide association studies of early onset IS, ages 18-59, using individual level data or summary statistics in 16,927 cases and 576,353 non-stroke controls from 48 different studies across North America, Europe, and Asia. We further compared effect sizes at our most genome-wide significant loci between early and late onset IS and compared polygenic risk scores for venous thromboembolism between early versus later onset IS.ResultsWe observed an association between early onset IS and ABO, a known stroke locus. The effect size of the peak ABO SNP, rs8176685, was significantly larger in early compared to late onset IS (OR 1.17 (95% C.I.: 1.11-1.22) vs 1.05 (0.99-1.12); p for interaction = 0.008). Analysis of genetically determined ABO blood groups revealed that early onset IS cases were more likely to have blood group A and less likely to have blood group O compared to both non-stroke controls and to late onset IS cases. Using polygenic risk scores, we observed that greater genetic risk for venous thromboembolism, another prothrombotic condition, was more strongly associated with early, compared to late, onset IS (p=0.008).ConclusionThe ABO locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with early onset IS, compared with late onset IS, supporting a stronger role of prothrombotic factors in early onset IS.

Background and Purpose: Clinical fluctuations in ischemic stroke symptoms are common, but fluctuations before hospital arrival have not been previously characterized. Methods: A standardized qualitative assessment of fluctuations before hospital arrival was obtained in an observational study that enrolled patients with mild ischemic stroke symptoms (National Institutes of Health Stroke Scale [NIHSS] score of 0–5) present on arrival to hospital within 4.5 hours of onset, in a subset of 100 hospitals participating in the Get With The Guidelines–Stroke quality improvement program. The number of fluctuations, direction, and the overall improvement or worsening was recorded based on reports from the patient, family, or paramedics. Baseline NIHSS on arrival and at 72 hours (or discharge if before) and final diagnosis and stroke subtype were collected. Outcomes at 90 days included the modified Rankin Scale, Barthel Index, Stroke Impact Scale 16, and European Quality of Life. Prehospital fluctuations were examined in relation to hospital NIHSS change (admission to 72 hours or discharge) and 90-day outcomes. Results: Among 1588 participants, prehospital fluctuations, consisting of improvement, worsening, or both were observed in 35.5%: 25.1% improved once, 5.3% worsened once, and 5.1% had more than 1 fluctuation. Those who improved were less likely and those who worsened were more likely to receive alteplase. Those who improved before hospital arrival had lower change in the hospital NIHSS than those who did not fluctuate. Better adjusted 90-day outcomes were noted in those with prehospital improvement compared to those without any fluctuations. Conclusions: Fluctuations in neurological symptoms and signs are common in the prehospital setting. Prehospital improvement was associated with better 90-day outcomes, controlling for admission NIHSS and alteplase treatment. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT 02072681.

Background and Purpose: Mild ischemic stroke patients enrolled in randomized controlled trials of thrombolysis may have a different symptom severity distribution than those treated in routine clinical practice. Methods: We compared the distribution of the National Institutes of Health Stroke Scale (NIHSS) scores, neurological symptoms/severity among patients enrolled in the PRISMS (Potential of r-tPA for Ischemic Strokes With Mild Symptoms) randomized controlled trial to those with NIHSS score ≤5 enrolled in the prospective MaRISS (Mild and Rapidly Improving Stroke Study) registry using global P values from χ 2 analyses. Results: Among 1736 participants in MaRISS, 972 (56%) were treated with alteplase and 764 (44%) were not. These participants were compared with 313 patients randomized in PRISMS. The median NIHSS scores were 3 (2–4) in MaRISS alteplase-treated, 1 (1–3) in MaRISS non–alteplase-treated, and 2 (1–3) in PRISMS. The percentage with an NIHSS score of 0 to 2 was 36.3%, 73.3%, and 65.2% in the 3 groups, respectively ( P P Conclusions: Patients randomized in PRISMS had comparable deficit and syndromic severity to patients not treated with alteplase in the MaRISS registry and lesser severity than patients treated with alteplase in MaRISS. The PRISMS trial cohort is representative of mild patients who do not receive alteplase in current broad clinical practice.

Background and Purpose— To test the hypothesis that covert brain infarcts (CBIs) are more likely to be located in noneloquent brain areas compared with clinical strokes and that CBI etiological subtypes carry a differential risk of vascular events compared with people without CBI. Methods— We used brain magnetic resonance imaging from 1290 stroke-free participants in the NOMAS (Northern Manhattan Study) to evaluate for CBI. We classified CBI as cardioembolic (ie, known atrial fibrillation), large artery atherosclerosis (extracranial and intracranial), penetrating artery disease, and cryptogenic (no apparent cause). CBI localized in the nonmotor areas of the right hemisphere were considered noneloquent. We then evaluated risk of events by CBI subtype with adjusted Cox proportional models. Results— At the time of magnetic resonance imaging, 236 participants (18%) had CBI (144 [61%] distal cryptogenic, 29 [12%] distal cardioembolic, 26 [11%] large artery atherosclerosis, and 37 [16%] penetrating artery disease). Smaller (per mm, odds ratio, 0.8 [0.8–0.9]) and nonbrain stem infarcts (odds ratio, 0.2 [0.1–0.6]) were more likely to be covert. During the follow-up period (10.4±3.1 years), 398 (31%) died (162 [13%] of vascular death) and 117 (9%) had a stroke (99 [85%]) were ischemic. Risks of events varied by CBI subtype, with the highest risk of stroke (hazard ratio, 2.2 [1.3–3.7]) and vascular death (hazard ratio, 2.24 [1.29–3.88]) noted in participants with intracranial large artery atherosclerosis-related CBI. Conclusions— CBI can be classified into subtypes that have differential outcomes. Certain CBI subtypes such as those related to intracranial large artery atherosclerosis have a high risk of adverse vascular outcomes and could warrant consideration of treatment trials.

The increasing burden of stroke and dementia emphasizes the need for new, well-tolerated and cost-effective primary prevention strategies that can reduce the risks of stroke and dementia worldwide, and specifically in low- and middle-income countries (LMICs). This paper outlines conceptual frameworks of three primary stroke prevention strategies: (a) the “polypill” strategy; (b) a “population-wide” strategy; and (c) a “motivational population-wide” strategy. (a) A polypill containing generic low-dose ingredients of blood pressure and lipid-lowering medications (e.g. candesartan 16 mg, amlodipine 2.5 mg, and rosuvastatin 10 mg) seems a safe and cost-effective approach for primary prevention of stroke and dementia. (b) A population-wide strategy reducing cardiovascular risk factors in the whole population, regardless of the level of risk is the most effective primary prevention strategy. A motivational population-wide strategy for the modification of health behaviors (e.g. smoking, diet, physical activity) should be based on the principles of cognitive behavioral therapy. Mobile technologies, such as smartphones, offer an ideal interface for behavioral interventions (e.g. Stroke Riskometer app) even in LMICs. (c) Community health workers can improve the maintenance of lifestyle changes as well as the adherence to medication, especially in resource poor areas. An adequate training of community health workers is a key point. Conclusion An effective primary stroke prevention strategy on a global scale should integrate pharmacological (polypill) and lifestyle modifications (motivational population-wide strategy) interventions. Side effects of such an integrative approach are expected to be minimal and the benefits among individuals at low-to-moderate risk of stroke could be significant. In the future, pragmatic field trials will provide more evidence.

Rationale Although mild and rapidly improving stroke symptoms are the most common first stroke presentation, this group has been understudied in acute stroke trials. Observational and retrospective studies suggest residual disability in one third of patients. Aims To elucidate long-term outcomes of patients with mild and rapidly improving stroke, evaluate the predictors of outcome, and examine the association with alteplase treatment. Sample size The initial estimate of 2650 participants to detect a 9% difference in non-disabled 90-day outcomes between alteplase-treated and untreated participants was revised to 2000 after a pre-planned re-estimation based on actual treatment rates. Methods and design Prospective observational study of patients with mild ischemic stroke (NIHSS ≤ 5) or rapidly improving stroke symptoms evaluated within 4.5 h from onset. Outcomes The primary outcome is the proportion of patients with modified Rankin Scale (mRS) ≥ 2 at 90 days; the primary safety outcome is symptomatic hemorrhagic transformation within 36 h among those treated with alteplase. Secondary outcomes include the 90-day Barthel Index, Stroke Impact Scale 16, European Quality of Life scale, mRS at 30 days, and 30- and 90-day mortality. Discussion MaRISS will define outcomes and their predictors and clarify the effects of alteplase in patients with mild and rapidly improving stroke symptoms, providing clinicians with important information to manage this population.

Background and Purpose— We aimed to evaluate the current practice patterns, safety and outcomes of patients who receive endovascular therapy (EVT) having mild neurological symptoms. Methods— From Jan 2010 to Jan 2018, 127,794 ischemic stroke patients were enrolled in the Florida-Puerto Rico Stroke Registry. Patients presenting within 24 hours of symptoms who received EVT were classified into mild (National Institutes of Health Stroke Scale [NIHSS] ≤5) or moderate/severe (NIHSS>5) categories. Differences in clinical characteristics and outcomes were evaluated using multivariable logistic regression. Results— Among 4110 EVT patients (median age, 73 [interquartile range=20] years; 50% women), 446 (11%) had NIHSS ≤5. Compared with NIHSS >5, those with NIHSS ≤5 arrived later to the hospital (median, 138 versus 101 minutes), were less likely to receive intravenous alteplase (30% versus 43%), had a longer door-to-puncture time (median, 167 versus 115 minutes) and more likely treated in South Florida (64% versus 53%). In multivariable analysis younger age, private insurance (versus Medicare), history of hypertension, prior independent ambulation and hospital size were independent characteristics associated with NIHSS ≤5. Among EVT patients with NIHSS ≤5, 76% were discharged home/rehabilitation and 64% were able to ambulate independently at discharge as compared with 53% and 32% of patients with NIHSS >5. Symptomatic intracerebral hemorrhage occurred in 4% of mild stroke EVT patients and 6.4% in those with NIHSS >5. Conclusions— Despite lack of evidence-based recommendations, 11% of patients receiving EVT in clinical practice have mild neurological presentations. Individual, hospital and geographic disparities are observed among endovascularly treated patients based on the severity of clinical symptoms. Our data suggest safety and overall favorable outcomes for EVT patients with mild stroke.

Stroke survivors carry a high risk of recurrence. Antithrombotic medications are paramount for secondary prevention and thus crucial to reduce the overall stroke burden. Appropriate antithrombotic agent selection should be based on the best understanding of the physiopathological mechanism that led to the initial ischemic injury. Antiplatelet therapy is preferred for lesions characterized by atherosclerosis and endothelial injury, whereas anticoagulant agents are favored for cardiogenic embolism and highly thrombophilic conditions. Large randomized controlled trials have provided new data to support recommendations for the evidence-based use of antiplatelet agents and anticoagulant agents after stroke. In this review, the authors cover recent trials that have altered clinical practice, cite systematic reviews and meta-analyses, review evidence-based recommendations based on older landmark trials, and indicate where there are still evidence-gaps and new trials being conducted.

ObjectiveTo examine associations between measures of obesity in middle to early-old age with later-life MRI markers of brain aging.MethodsWe analyzed data from the Northern Manhattan MRI Sub-Study (n = 1,289). Our exposures of interest were body mass index (BMI), waist circumference (WC), waist-to-hip ratio, and plasma adiponectin levels. Our outcomes of interest were total cerebral volume (TCV), cortical thickness, white matter hyperintensity volume (WMHV), and subclinical brain infarcts (SBI). Using multivariable linear and logistic regression models adjusted for sociodemographics, health behaviors, and vascular risk factors, we estimated β coefficients (or odds ratios) and 95% confidence intervals (CIs) and tested interactions with age, sex, and race/ethnicity.ResultsOn average at baseline, participants were aged 64 years and had 10 years of education; 60% were women and 66% were Caribbean Hispanic. The mean (SD) time lag between baseline and MRI was 6 (3) years. Greater BMI and WC were significantly associated with thinner cortices (BMI β [95% CI] −0.089 [−0.153, −0.025], WC β [95% CI] −0.103 [−0.169, −0.037]) in fully adjusted models. Similarly, compared to those with BMI ConclusionsAdiposity in early-old age is related to reduced global gray matter later in life in this diverse sample. Future studies are warranted to elucidate causal relationships and explore region-specific associations.

Supplemental Digital Content is available in the text., Background and Purpose: Lifelong treatment with antiplatelet drugs is recommended following a transient ischemic attack or ischemic stroke. Bleeding complications may offset the benefit of antiplatelet drugs in patients at increased risk of bleeding and low risk of recurrent ischemic events. We aimed to investigate the net benefit of antiplatelet treatment according to an individuals’ bleeding risk. Methods: We pooled individual patient data from 6 randomized clinical trials (CAPRIE [Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events], ESPS-2 [European Stroke Prevention Study-2], MATCH [Management of Atherothrombosis With Clopidogrel in High-Risk Patients], CHARISMA [Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance], ESPRIT [European/Australasian Stroke Prevention in Reversible Ischemia Trial], and PRoFESS [Prevention Regimen for Effectively Avoiding Second Strokes]) investigating antiplatelet therapy in the subacute or chronic phase after noncardioembolic transient ischemic attack or stroke. Patients were stratified into quintiles according to their predicted risk of major bleeding with the S2TOP-BLEED score. The annual risk of major bleeding and recurrent ischemic events was assessed per quintile for 4 scenarios: (1) aspirin monotherapy, (2) aspirin-clopidogrel versus aspirin or clopidogrel monotherapy, (3) aspirin-dipyridamole versus clopidogrel, and (4) aspirin versus clopidogrel. Net benefit was calculated for the second, third, and fourth scenario. Results: Thirty seven thousand eighty-seven patients were included in the analyses. Both risk of major bleeding and recurrent ischemic events increased over quintiles of predicted bleeding risk, but risk of ischemic events was consistently higher (eg, from 0.7%/y (bottom quintile) to 3.2%/y (top quintile) for major bleeding on aspirin and from 2.5%/y to 10.2%/y for risk of ischemic events on aspirin). Treatment with aspirin-clopidogrel led to more major bleedings (0.9%–1.7% per year), than reduction in ischemic events (ranging from 0.4% to 0.9/1.0% per year) across all quintiles. There was no clear preference for either aspirin-dipyridamole or clopidogrel according to baseline bleeding risk. Conclusions: Among patients with a transient ischemic attack or ischemic stroke included in clinical trials of antiplatelet therapy, the risk of recurrent ischemic events and of major bleeding increase in parallel. Antiplatelet treatment cannot be individualized solely based on bleeding risk assessment.

Hypertension is the most prevalent modifiable risk factor for stroke. Office blood pressure (BP) measurements may have limitations in defining the impact of hypertension on stroke. Our aim was to compare the stroke risk for office, central, and ambulatory BP measurements in a predominantly older population-based prospective cohort. Participants in the CABL study (Cardiovascular Abnormalities and Brain Lesions; n=816; mean age, 70.8±9.0 years; 39.8% men) underwent applanation tonometry of the radial artery for central BP and 24-hour ambulatory BP monitoring. During a follow-up of 9.6±3.1 years, stroke occurred in 76 participants (9.3%). Among office BP variables, only diastolic BP was associated with stroke in multivariable competing risk model ( P =0.016). None of the central BP variables showed a significant association with stroke. Conversely, all ambulatory systolic and diastolic BP variables were significantly associated with stroke after adjustment for clinical confounders (all P P

Acute ischemic stroke affects men and women differently. In particular, women are often reported to experience higher acute stroke severity than men. We derived a low-dimensional representation of anatomical stroke lesions and designed a Bayesian hierarchical modeling framework tailored to estimate possible sex differences in lesion patterns linked to acute stroke severity (National Institute of Health Stroke Scale). This framework was developed in 555 patients (38% female). Findings were validated in an independent cohort (n = 503, 41% female). Here, we show brain lesions in regions subserving motor and language functions help explain stroke severity in both men and women, however more widespread lesion patterns are relevant in female patients. Higher stroke severity in women, but not men, is associated with left hemisphere lesions in the vicinity of the posterior circulation. Our results suggest there are sex-specific functional cerebral asymmetries that may be important for future investigations of sex-stratified approaches to management of acute ischemic stroke., Acute ischemic stroke impacts men and women differently. Here, the authors show how different lesion patterns in men and women are linked to the extent of stroke severity.

Importance Intracerebral hemorrhage and arterial ischemic disease share risk factors, to our knowledge, but the association between the 2 conditions remains unknown. Objective To evaluate whether intracerebral hemorrhage was associated with an increased risk of incident ischemic stroke and myocardial infarction. Design, Setting, and Participants An analysis was conducted of pooled longitudinal participant-level data from 4 population-based cohort studies in the United States: the Atherosclerosis Risk in Communities (ARIC) study, the Cardiovascular Health Study (CHS), the Northern Manhattan Study (NOMAS), and the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. Patients were enrolled from 1987 to 2007, and the last available follow-up was December 31, 2018. Data were analyzed from September 1, 2019, to March 31, 2020. Exposure Intracerebral hemorrhage, as assessed by an adjudication committee based on predefined clinical and radiologic criteria. Main Outcomes and Measures The primary outcome was an arterial ischemic event, defined as a composite of ischemic stroke or myocardial infarction, centrally adjudicated within each study. Secondary outcomes were ischemic stroke and myocardial infarction. Participants with prevalent intracerebral hemorrhage, ischemic stroke, or myocardial infarction at their baseline study visit were excluded. Cox proportional hazards regression was used to examine the association between intracerebral hemorrhage and subsequent arterial ischemic events after adjustment for baseline age, sex, race/ethnicity, vascular comorbidities, and antithrombotic medications. Results Of 55 131 participants, 47 866 (27 639 women [57.7%]; mean [SD] age, 62.2 [10.2] years) were eligible for analysis. During a median follow-up of 12.7 years (interquartile range, 7.7-19.5 years), there were 318 intracerebral hemorrhages and 7648 arterial ischemic events. The incidence of an arterial ischemic event was 3.6 events per 100 person-years (95% CI, 2.7-5.0 events per 100 person-years) after intracerebral hemorrhage vs 1.1 events per 100 person-years (95% CI, 1.1-1.2 events per 100 person-years) among those without intracerebral hemorrhage. In adjusted models, intracerebral hemorrhage was associated with arterial ischemic events (hazard ratio [HR], 2.3; 95% CI, 1.7-3.1), ischemic stroke (HR, 3.1; 95% CI, 2.1-4.5), and myocardial infarction (HR, 1.9; 95% CI, 1.2-2.9). In sensitivity analyses, intracerebral hemorrhage was associated with arterial ischemic events when updating covariates in a time-varying manner (HR, 2.2; 95% CI, 1.6-3.0); when using incidence density matching (odds ratio, 2.3; 95% CI, 1.3-4.2); when including participants with prevalent intracerebral hemorrhage, ischemic stroke, or myocardial infarction (HR, 2.2; 95% CI, 1.6-2.9); and when using death as a competing risk (subdistribution HR, 1.6; 95% CI, 1.1-2.1). Conclusions and Relevance This study found that intracerebral hemorrhage was associated with an increased risk of ischemic stroke and myocardial infarction. These findings suggest that intracerebral hemorrhage may be a novel risk marker for arterial ischemic events.

Background: Although most strokes present with mild symptoms, these have been poorly represented in clinical trials. The objective is to describe multidimensional outcomes, identify predictors of worse outcomes and explore the effect of thrombolysis in this population. Methods: This prospective observational study included patients with ischemic stroke or TIA presenting with stroke symptoms and a baseline NIHSS 0-5 within 4.5 hours from symptom onset. The primary outcome was a 90-day modified Rankin Scale (mRS) 0-1; secondary outcomes included good outcomes in the Barthel Index, Stroke Impact Scale-16 (SIS-16) and European Quality of Life. Multivariable models were created to determine predictors of outcomes and the effect of alteplase. Results: A total of 1765 participants were included from 100 Get With The Guidelines (GWTG)-Stroke participating hospitals (age 65 + 14, 42% women, final diagnosis ischemic stroke 90%, TIA 10%, 57% received alteplase). At 90 days, 37% were disabled and 25% not independent. Worse outcomes were noted for older individuals, women, non-Hispanic Blacks and Hispanics, Medicaid, smokers, those with diabetes, atrial fibrillation, prior stroke, higher baseline NIHSS, visual field defects, arm and leg weakness. Similar outcomes were noted for the alteplase-treated and the untreated groups. Alteplase treated patients were younger (64 + 13 vs. 67 + 1.4) with a higher NIHSS (2.9 + 1.4 vs. 1.7 + 1.4). After adjusting for age, sex, race-ethnicity, and baseline NIHSS, we did not identify an effect of alteplase on the primary outcome but did find an effect on SIS-16 in the restricted sample of baseline NIHSS 3-5. Very few symptomatic hemorrhages were recorded (3/999). Conclusions: A large proportion of stroke patients presenting with a low NIHSS have a disabled outcome. Baseline predictors of worse outcomes are described. An effect of alteplase on outcomes was not identified in the overall cohort but an indication of efficacy was noted in the NIHSS 3-5 subgroup.

Introduction: Characterizing the population of ischemic stroke (IS) patients presenting in the delayed reperfusion window is important to ensure equitable implementation of recently updated acute IS treatment guidelines. Methods: Florida Stroke Registry (FSR) data from Jan 2010 - Jan 2020, provided a complete dataset of 98,372 IS cases presenting within 24 hrs of symptom onset. Generalized linear regression analysis was used to identify differences between delayed IS cases (>4.5 hours) versus those presenting within the early time window (≤ 4.5 hr). Results: A total of 60,311 presented with 4.5 hr (median age 74 (interquartile range (IQR) 62-83), 49% women, 67% white, 15% Black, 18% Hispanic), and 38,061 presented in the delayed window (median age 72 (IQR 61- 82), 49% women, 63% white, 18% Black, 19% Hispanic). As compared to early presenters, delayed window patients were younger (OR 1.23, 95% confidence interval (CI) 1.17-1.29); more Black vs. White (OR 1.12, 95% CI 1.06-1.18), have higher NIHSS (OR 1.05, 95% 1.01-1.10), insured (OR 1.18, 95% 1.11-1.25), presenting to an academic hospital (OR 1.24, 95% CI 1.09-1.40) in South Florida (OR 1.23, 95% CI (1.08, 1.41)); less likely to arrive by EMS (OR 0.59, 95% CI 0.56-0.62) and less likely to receive reperfusion therapies (OR 0.86, 95% CI 0.79-0.94). In multivariable analysis adjusting for age, race, NIHSS, EMS, reperfusion therapies, hospital academic status and region, delayed window presentation was negatively associated with discharge home (OR 0.82, 95% CI 0.76-0.89), and ambulatory status at discharge (OR 0.89, 95% CI 0.84-0.93). Conclusion: We found significant race, ethnic, socioeconomic and geographical disparities amongst those presenting in the delayed vs early reperfusion time windows with consequential effects on patient outcomes. Stroke education to younger minorities and adaptation of regional stroke systems of care are urgently needed.

Introduction: Social determinants of health (SDH) are major contributors to stroke incidence and disparities, yet their relationship with severity and disability is relatively unexplored. The purpose of this study is to provide preliminary findings on SDH measures at the individual- and ZIP code-level across outcomes of stroke severity and disability. Methods: We used data from 344 stroke patients from the ongoing Transitions of Care Stroke Disparities Study (TCSDS) enrolled 2018-2020 from sites throughout Florida. TCSDS aims to identify disparities in hospital-to-home transition of stroke care. Individual-level SDH were collected by a trained interviewer at discharge; ZIP-level SDH data were obtained from a contracted data company. Outcomes included stroke severity at admission measured by the NIH Stroke Scale (NIHSS; Mild: 0-4; Moderate: 5-14; Severe: ≥15) and obtained from the AHA Get with the Guidelines-Stroke program; and disability at discharge measured by the modified Rankin Scale (mRS; 0-1; 2-5). Non-parametric statistical tests were used to compare individual- and ZIP-level SDH by NIHSS and mRS scores. Results: Most patients were older (median age 62 years, IQR: 19), male (58%), non-Hispanic White (39%) or Hispanic (35%) and suffered mild strokes (median NIHSS, IQR: 2, 4) with mild disability (median mRS: 1, 4). Those living with children (LWC) had more moderate strokes, while those living with a spouse/partner (LWP) had more severe strokes (p=0.004). Less than high school (HS)-, HS-, and college-educated patients had more moderate, mild, and severe strokes, respectively (p=0.02). ZIP-level unemployment rate was positively associated with NIHSS (p=0.031). Higher mRS was seen among Spanish and Haitian Creole speakers (p=0.005); HS- and less than HS-educated patients (p=0.005); and those with lower levels of social support (p=0.019). LWC had higher mRS scores, while the opposite was true for LWP (p=0.001). Conclusions: Despite the intersectional nature of SDH, these findings highlight possible mechanisms by which education, economic conditions and psychosocial factors may influence stroke severity and disability after stroke. More data are necessary to determine whether these SDH influence long term stroke outcomes post-discharge.

Background Less than 40% of acute stroke patients have computed tomography (CT) imaging performed within 25 minutes of hospital arrival. We aimed to examine the race‐ethnic and sex differences in door‐to‐CT (DTCT) ≤25 minutes in the FSR (Florida Stroke Registry). Methods and Results Data were collected from 2010 to 2018 for 63 265 patients with acute ischemic stroke from the FSR and secondary analysis was performed on 15 877 patients with intravenous tissue plasminogen activator‐treated ischemic stroke. Generalized estimating equation models were used to determine predictors of DTCT ≤25. DTCT ≤25 was achieved in 56% of cases of suspected acute stroke, improving from 36% in 2010 to 72% in 2018. Women (odds ratio [OR], 0.90; 95% CI, 0.87–0.93) and Black (OR, 0.88; CI, 0.84–0.94) patients who had strokes were less likely, and Hispanic patients more likely (OR, 1.07; CI, 1.01–1.14), to achieve DTCT ≤25. In a secondary analysis among intravenous tissue plasminogen activator‐treated patients, 81% of patients achieved DTCT ≤25. In this subgroup, women were less likely to receive DTCT ≤25 (0.85, 0.77–0.94) whereas no significant differences were observed by race or ethnicity. Conclusions In the FSR, there was considerable improvement in acute stroke care metric DTCT ≤25 in 2018 in comparison to 2010. However, sex and race‐ethnic disparities persist and require further efforts to improve performance and reduce these disparities.

Introduction: Prior literature has reported differences in outcomes following stroke by race/ethnicity. While more attention has been focused on ischemic stroke, we sought to identify race/ethnic disparities in hospital outcomes at discharge following intracerebral hemorrhage (ICH). Methods: Data were obtained from the Florida Stroke Registry (FSR) consisting of stroke centers utilizing the Get With the Guidelines-Stroke (GWTG-S) tool. Pearson Chi-square and Kruskall-Wallis tests were used to compare descriptive statistics by race/ethnicity on 26,113 Florida cases with ICH discharged 2010-2018. Outcomes at discharge included in-hospital mortality, disposition, ambulation, modified Rankin Scale score & timing of initiation of comfort measures only (CMO). Generalized estimating equations logistic models accounted for age, sex, insurance, smoking, hypertension, diabetes, dyslipidemia, prior anti-coagulant/platelet use, history of stroke/TIA, admission NIHSS, ICH score, arrival mode, hospital size, teaching status & years in GWTG-S. Results: 65% were non-Hispanic White (NHW), 20% non-Hispanic Black (NHB) and 15% Hispanic. NHB were younger at ICH onset (median 60, IQR 52-71; NHW: 71, 58-81; Hispanic: 69, 52-80; p < 0.0001), had higher risk of hypertension (HTN; 74%; NHW: 66%; Hispanic: 64%; p < 0.0001), diabetes (29%; NHW: 20%; Hispanic: 27%; p < 0.0001), smoking (14%; NHW: 12%; Hispanic: 9%; p < 0.0001) and chronic renal insufficiency (8%; NHW: 4%; Hispanic: 4% ; p < 0.0001). NHW had higher risk of dyslipidemia (35%; NHB: 21%; Hispanic: 27%; p < 0.0001), atrial fibrillation/flutter (20%; NHB: 6%; Hispanic: 10%; p < 0.0001) and a higher use of prior anticoagulants (13%; NHB: 6%, Hispanic: 8%, p < 0.0001). NHB had lower odds of in-hospital mortality (adjusted OR=0.77, 95% CI=[0.61-0.96]) and CMO on days 0/1 (0.63, 0.45-0.87) compared to NHW. Conclusions: Differences in risk factor profiles, such as higher rates of HTN in NHB and greater use of anticoagulants among NHW, raises the possibility of tailoring preventive and acute care responses to ICH by race/ethnicity. Moreover, despite observing persistently lower odds of mortality and CMO among NHB after adjustment, more data are needed to identify the unobserved effects leading to these disparities.

Introduction: Prolonged cardiac monitoring after cryptogenic stroke reveals a cardiac cause in up to 30% of patients; however, practice patterns for monitoring vary widely. We sought to evaluate overall and race/ethnic trends in the rate of ECG monitoring and types of cardiac monitoring performed after ischemic stroke and transient ischemic attack (TIA) across a network of hospitals in Florida and Puerto Rico(PR). Methods: We identified 46,878 ischemic stroke and TIA cases with data on ECG monitoring in the Florida Stroke Registry from 2016-18. Univariate analysis was performed to determine the overall rate of ECG monitoring and the characteristics of patients who received cardiac surface monitoring ≤7days and >7days, and implantable cardiac monitoring. Multivariate logistic regression was performed to identify factors associated with the types of monitoring. Results: Overall, 39,333 (84%) patients admitted for stroke/TIA received ECG monitoring during hospital admission (mean age 71±14 years; 49% female; 63% white, 18% black, 15% FL-Hispanic, 4% PR-Hispanic). Compared to patients who received ECG monitoring, patients who did not were more likely to be younger (mean age 70±15 years), PR-Hispanic (24% vs 4.3%), and have TIA (13% vs 8%), Medicare (42% vs 35%), large vessel disease (14% vs 9%) and greater admission NIHSS (median score 5 vs 4). After adjustment, smokers and patients >80years were less likely to receive ECG monitoring overall (OR 0.95, 95% CI 0.9-0.99 for both). Black race was associated with receiving extended surface monitoring >7 days (OR 1.15, 95%CI 1.04-1.26), but negatively associated with implantable cardiac monitoring (OR 0.81, 95%CI 0.68-0.96). Patients with moderate/severe stroke had higher odds of extended surface monitoring >7days (OR 2.29, 95%CI 1.89-2.77), yet lower odds of implantable cardiac monitoring (OR 0.80, 95%CI 0.71-0.89). Conclusion: The majority of patients received ECG monitoring during hospital admission for stroke/TIA; however, significant differences were found with respect to age, race/ethnicity and stroke severity across the various types and duration of cardiac monitoring. Further research is needed to understand and address the underlying drivers of these differences.

IntroductionNeuroimaging measurements of brain structural integrity are thought to be surrogates for brain health, but precise assessments require dedicated advanced image acquisitions. By means of describing the texture of conventional images beyond what meets the naked eye, radiomic analyses hold potential for evaluating brain health. We sought to: 1) evaluate this novel approach to assess brain structural integrity by predicting white matter hyperintensities burdens (WMH) and 2) uncover associations between predictive radiomic features and patients’ clinical phenotypes.MethodsOur analyses were based on a multi-site cohort of 4,163 acute ischemic strokes (AIS) patients with T2-FLAIR MR images and corresponding deep-learning-generated total brain and WMH segmentation. Radiomic features were extracted from normal-appearing brain tissue (brain mask–WMH mask). Radiomics-based prediction of personalized WMH burden was done using ElasticNet linear regression. We built a radiomic signature of WMH with the most stable selected features predictive of WMH burden and then related this signature to clinical variables (age, sex, hypertension (HTN), atrial fibrillation (AF), diabetes mellitus (DM), coronary artery disease (CAD), and history of smoking) using canonical correlation analysis.ResultsRadiomic features were highly predictive of WMH burden (R2=0.855±0.011). Seven pairs of canonical variates (CV) significantly correlated the radiomics signature of WMH and clinical traits with respective canonical correlations of 0.81, 0.65, 0.42, 0.24, 0.20, 0.15, and 0.15 (FDR-corrected p-valuesCV1-6CV7=.012). The clinical CV1 was mainly influenced by age, CV2 by sex, CV3 by history of smoking and DM, CV4 by HTN, CV5 by AF and DM, CV6 by CAD, and CV7 by CAD and DM.ConclusionRadiomics extracted from T2-FLAIR images of AIS patients capture microstructural damage of the cerebral parenchyma and correlate with clinical phenotypes. Further research could evaluate radiomics to predict the progression of WMH.Research in contextEvidence before this studyWe did a systematic review on PubMed until December 1, 2020, for original articles and reviews in which radiomics were used to characterize stroke or cerebrovascular diseases. Radiomic analyses cover a broad ensemble of high-throughput quantification methods applicable to digitalized medical images that extract high-dimensional data by describing a given region of interest by its size, shape, histogram, and relationship between voxels. We used the search terms “radiomics” or “texture analysis”, and “stroke”, “cerebrovascular disease”, “small vessel disease”, or “white matter hyperintensities”. Our research identified 24 studies, 18 studying radiomics of stroke lesions and 6 studying cerebrovascular diseases. All the latter six studies were based on MRI (T1-FLAIR, dynamic contrast-enhanced imaging, T1 & T2-FLAIR, T2-FLAIR post-contrast, T2-FLAIR, and T2-TSE images). Four studies were describing small vessel disease, and two were predicting longitudinal progression of WMH. The average sample size was small with 96 patients included (maximum: 204). One study on 141 patients identified 7 T1-FLAIR radiomic features correlated with cardiovascular risk factors (age and hyperlipidemia) using univariate correlations. All studies were monocentric and performed on a single MRI scanner.Added value of this studyTo date and to the best of our knowledge, this is the largest radiomics study performed on cerebrovascular disease or any topic, and one of the very few to include a great diversity of participating sites with diverse clinical MRI scanners. This study is the first one to establish a radiomic signature of WMH and to interpret its relationship with common cardiovascular risk factors. Our findings add to the body of evidence that damage caused by small vessel disease extend beyond the visible white matter hyperintensities, but the added value resides in the detection of that subvisible damage on routinely acquired T2-FLAIR imaging. It also suggests that cardiovascular phenotypes might manifest in distinct textural patterns detectable on conventional clinical-grade T2-FLAIR images.Implications of all the available evidenceAssessing brain structural integrity has implications for treatment selection, follow-up, prognosis, and recovery prediction in stroke patients but also other neurological disease populations. Measuring cerebral parenchymal structural integrity usually requires advanced imaging such as diffusion tensor imaging or functional MRI. Translation of those neuroimaging biomarkers remains uncommon in clinical practice mainly because of their time-consuming and costly acquisition. Our study provides a potential novel solution to assess brains’ structural integrity applicable to standard, routinely acquired T2-FLAIR imaging.Future research could, for instance, benchmark this radiomics approach against diffusion or functional MRI metrics in the prediction of cognitive or functional outcomes after stroke.