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Background: Recently, common genetic risk factors for intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (ASAH) were found to explain a large amount of disease heritability and therefore have potential to be used for genetic risk prediction. We constructed a genetic risk score to (1) predict ASAH incidence and IA presence (combined set of unruptured IA and ASAH) and (2) assess its association with patient characteristics. Methods: A genetic risk score incorporating genetic association data for IA and 17 traits related to IA (so-called metaGRS) was created using 1161 IA cases and 407 392 controls from the UK Biobank population study. The metaGRS was validated in combination with risk factors blood pressure, sex, and smoking in 828 IA cases and 68 568 controls from the Nordic HUNT population study. Furthermore, we assessed association between the metaGRS and patient characteristics in a cohort of 5560 IA patients. Results: Per SD increase of metaGRS, the hazard ratio for ASAH incidence was 1.34 (95% CI, 1.20–1.51) and the odds ratio for IA presence 1.09 (95% CI, 1.01–1.18). Upon including the metaGRS on top of clinical risk factors, the concordance index to predict ASAH hazard increased from 0.63 (95% CI, 0.59–0.67) to 0.65 (95% CI, 0.62–0.69), while prediction of IA presence did not improve. The metaGRS was statistically significantly associated with age at ASAH (β=−4.82×10 −3 per year [95% CI, −6.49×10 −3 to −3.14×10 −3 ]; P =1.82×10 −8 ), and location of IA at the internal carotid artery (odds ratio=0.92 [95% CI, 0.86–0.98]; P =0.0041). Conclusions: The metaGRS was predictive of ASAH incidence, although with limited added value over clinical risk factors. The metaGRS was not predictive of IA presence. Therefore, we do not recommend using this metaGRS in daily clinical care. Genetic risk does partly explain the clinical heterogeneity of IA warranting prioritization of clinical heterogeneity in future genetic prediction studies of IA and ASAH.

Background: Hematoma and perihematomal edema volumes are important radiographic markers in spontaneous intracerebral hemorrhage. Accurate, reliable, and efficient quantification of these volumes will be paramount to their utility as measures of treatment effect in future clinical studies. Both manual and semi-automated quantification methods of hematoma and perihematomal edema volumetry are time-consuming and susceptible to inter-rater variability. Efforts are now underway to develop a fully automated algorithm that can replace them. A (QUANTUM) study to establish inter-quantification method measurement equivalency, which deviates from the traditional use of measures of agreement and a comparison hypothesis testing paradigm to indirectly infer quantification method measurement equivalence, is described in this article. The Quantification of Hematoma and Perihematomal Edema Volumes in Intracerebral Hemorrhage study aims to determine whether a fully automated quantification method and a semi-automated quantification method for quantification of hematoma and perihematomal edema volumes are equivalent to the hematoma and perihematomal edema volumes of the manual quantification method. Methods/Design: Hematoma and perihematomal edema volumes of supratentorial intracerebral hemorrhage on 252 computed tomography scans will be prospectively quantified in random order by six raters using the fully automated, semi-automated, and manual quantification methods. Primary outcome measures for hematoma and perihematomal edema volumes will be quantified via computed tomography scan on admission (Discussion: By allowing direct equivalence hypothesis testing, the Quantification of Hematoma and Perihematomal Edema Volumes in Intracerebral Hemorrhage study offers advantages over radiology validation studies which utilize measures of agreement to indirectly infer measurement equivalence and studies which mistakenly try to infer measurement equivalence based on the failure of a comparison two-sided null hypothesis test to reach the significance level for rejection. The equivalence hypothesis testing paradigm applied to artificial intelligence application validation is relatively uncharted and warrants further investigation. The challenges encountered in the design of this study may influence future studies seeking to translate artificial intelligence medical technology into clinical practice.

ObjectiveGenome-wide association studies have identified1q22as a susceptibility locus for cerebral small vessel diseases (CSVDs), including non-lobar intracerebral hemorrhage (ICH) and lacunar stroke. In the present study we performed targeted high-depth sequencing of1q22in ICH cases and controls to further characterize this locus and prioritize potential causal mechanisms, which remain unknown.Methods95,000 base pairs spanning1q22, includingSEMA4A, SLC25A44andPMF1/PMF1-BGLAPwere sequenced in 1,055 spontaneous ICH cases (534 lobar and 521 non-lobar) and 1,078 controls. Firth regression and RIFT analysis were used to analyze common and rare variants, respectively. Chromatin interaction analyses were performed using Hi-C, ChIP-Seq and ChIA-PET databases. Multivariable Mendelian randomization (MVMR) assessed whether alterations in gene-specific expression relative to regionally co-expressed genes at1q22could be causally related to ICH risk.ResultsCommon and rare variant analyses prioritized variants inSEMA4A5’-UTR andPMF1intronic regions, overlapping with active promoter and enhancer regions based on ENCODE annotation. Hi-C data analysis determined that1q22is spatially organized in a single chromatin loop and that the genes therein belong to the same Topologically Associating Domain. ChIP-Seq and ChIA-PET data analysis highlighted the presence of long-range interactions between theSEMA4A-promoter andPMF1-enhancer regions prioritized by association testing. MVMR analyses demonstrated thatPMF1overexpression could be causally related to non-lobar ICH risk.InterpretationAltered promoter-enhancer interactions leading toPMF1overexpression, potentially dysregulating polyamine catabolism, could explain demonstrated associations with non-lobar ICH risk at1q22, offering a potential new target for prevention of ICH and CSVD.

This study aimed to investigate the influence of stroke lesions in pre-defined highly interconnected (rich club) brain regions on functional outcome post-stroke, determine their spatial specificity and explore the effects of biological sex on their relevance.We analyzed MRI data recorded at index stroke and ∼3-months modified Rankin Scale (mRS) data from patients with acute ischemic stroke (AIS) enrolled in the multisite MRI-GENIE study. Structural stroke lesions were spatially normalized and parcellated into 108 atlas-defined bilateral (sub)cortical brain regions. Unfavorable outcome (mRS>2) was modeled in a Bayesian logistic regression framework that relied on both lesion location, as well as the covariates: age, sex, total DWI lesion volume and comorbidities. Effects of individual brain regions were captured as two compound effects for (i) six bilateral rich club and (ii) all further non-rich club regions. Via model comparisons, we first tested whether the rich club region model was superior to a baseline model considering clinical covariates and lesion volume only. In spatial specificity analyses, we randomized the split into “rich club” and “non-rich club” regions and compared the effect of the actual rich club regions to the distribution of effects from 1,000 combinations of six random regions. In sex-specific analyses, we introduced an additional hierarchical level in our model structure to compare male and female-specific rich club region effects.A total of 822 patients (age: 64.7 (standard deviation: 15.0), 39% women, 27.7% with mRS>2) were analyzed. The rich club model substantially outperformed the baseline model (weights of model comparison: rich club model: 0.96; baseline: 0.04). Rich club regions had substantial relevance in explaining unfavorable functional outcome (mean of posterior distribution: 0.08, area under the curve: 0.8). In particular, the rich club-combination had a higher relevance than 98.4% of random constellations (15/1,000 random constellations with higher mean posterior values). Among the these 15 random constellations with higher means, the most frequently selected regions were the inferior temporal gyrus (posterior division, 8/15), the putamen (8/15), the cingulate gyrus (7/15) and the superior parietal lobule (6/15). Rich club regions were substantially more important in explaining long-term outcome in women than in men (mean of the difference distribution:-0.107, 90%-HDPI:-0.193 to -0.0124).Lesions in rich club regions were associated with increased odds of unfavorable outcome. These effects were spatially specific, i.e., the majority of random combinations of six regions had comparably smaller effects on long-term outcome. Effects were substantially more pronounced in women.

ObjectiveTo develop a simple and effective risk score for predicting which stroke patients will have persistent impairment of upper extremity motor function at 90 days.DesignPost hoc analysis of clinical trial patients hospitalized with acute ischemic stroke who were followed for 90 days to determine functional outcome.SettingPatient were hospitalized at facilities across the United States.ParticipantsWe created a harmonized cohort of individual patients (N=1653) from the NINDS tPA, ALIAS part 2, IMS-III, DEFUSE 3, and FAST-MAG trials. We split the cohort into balanced derivation and validation samples.InterventionsNot applicable.Main outcome measuresThe primary outcome was persistent arm impairment, defined as a National Institutes of Health Stroke Scale (NIHSS) arm domain score of 2 to 4 at 90 days in patients who had a 24-hour NIHSS arm score of 1 or more. We used least absolute shrinkage and selection operator regression to determine the elements of the persistent upper extremity impairment (PUPPI) index, which we validated as a predictive tool.ResultsWe included 1653 patients (827 derivation, 826 validation), of whom 803 (48.6%) had persistent arm impairment. The PUPPI index gives 1 point each for age 55 years or older and NIHSS values of worse arm (4), worse leg (>2), facial palsy (3), and total NIHSS (≥10). The optimal cutpoint for the PUPPI index was 3 or greater, at which the area under the curve was greater than 0.75 for the derivation and validation cohorts and when using NIHSS values from either 24 hours or in a subacute or discharge time window. Results were similar across different levels of stroke severity.ConclusionThe PUPPI index uses readily available information to accurately predict persistent upper extremity motor impairment at 90 days poststroke. The PUPPI index can be administered in minutes and could be used as inclusion criterion in recovery-related clinical trials or, with additional development, as a prognostic tool for patients, caregivers, and clinicians.

BackgroundIn this genome wide association study (GWAS) we aimed to discover single nucleotide polymorphisms (SNPs) associated with motor recovery post-stroke.MethodsWe used the Vitamin Intervention for Stroke Prevention (VISP) dataset of 2,100 genotyped patients with non-disabling stroke. Of these, 488 patients had motor impairment at enrollment. Genotyped data underwent strict quality control and imputation. The GWAS utilized logistic regression models with generalized estimating equations (GEE) to leverage the repeated NIH Stroke Scale (NIHSS) motor score measurements spanning 6 time points over 24 months. The primary outcome was a decrease in the motor drift score of ≥ 1 vs.<1 at each timepoint. Our model estimated the odds ratio of motor improvement for each SNP after adjusting for age, sex, race, days from stroke to visit, initial motor score, VISP treatment arm, and principal components.ResultsAlthough no associations reached genome-wide significance (p<5 × 10−8), our analysis detected 115 suggestive associations (p<5 × 10−6). Notably, we found multiple SNP clusters near genes with plausible neuronal repair biology mechanisms. The CLDN23 gene had the most convincing association which affects blood-brain barrier integrity, neurodevelopment, and immune cell transmigration.ConclusionWe identified novel suggestive genetic associations with the first ever motor-specific post stroke recovery GWAS. The results seem to describe a distinct stroke recovery phenotype compared to prior genetic stroke outcome studies that use outcome measures, like the mRS. Replication and further mechanistic investigation are warranted. Additionally, this study demonstrated a proof-of-principle approach to optimize statistical efficiency with longitudinal datasets for genetic discovery.

Objective: To perform a genome wide association study (GWAS) of stroke recovery phenotypes as defined by the trajectories of patients’ NIH stroke scale scores over time. Background: Stroke recovery research entails tracking multiple domains of neurologic impairment over time that are measured on differing scales. This presents challenges for analytic approaches commonly used to study stroke genetics. Here, we present a novel approach using a network science-based method, Trajectory Profile Clustering (TPC), to define stroke recovery phenotypes for GWAS. Design/Methods: We analyzed data from 3,679 patients in the VISP dataset (Vitamin Intervention for Stroke Prevention) on 15 NIHSS impairment measures at 6 time points spanning 24 months post-stroke. The 4 identified TPC profiles (Figure, Panel A), were used as phenotypes for a subsequent GWAS on the 2,099 genotyped VISP patients. We used a multinomial generalized regression with TPC profiles as the response variable. The model adjusted for age, sex, treatment group, and the first ten principal components. Results: TOPMed imputation and strict quality control resulted in 6,392,745 SNPs. Although none of our loci reached genome wide significance, the GWAS identified several suggestive loci (p Conclusion: Phenotypes defined using TPC, even in this limited sample, identified multiple suggestive genetic associations with biological relevance for both stroke risk and stroke recovery.

Background: Understanding the magnitude and causes of missing data is crucial to ensuring scientific integrity of clinical trials. Missing data threaten statistical and ecological validity, as results will only generalize to those who remain represented in the sample. Goal: Identify factors associated with loss at follow-up in acute ischemic stroke trials. Methods: We harmonized patient-level data from multiple NIH-funded acute ischemic stroke trials including NINDS IV-tPA, ALIAS part 2, SHINE, FAST-MAG, IMS-III, POINT, and DEFUSE 3, all of which had a 90-day study outcome. The primary outcome was the proportion of missing modified Rankin Scale (mRS) scores at 90 days. We compared patients with and without a 90-day mRS score among a variety of baseline patient characteristics. Results: Among 9580 subjects, 459 (4.8%) were missing their 90-day mRS. Age and race were associated with missingness. Compared to those with complete data, participants with missing data were younger (62 vs 66 years, p Conclusion: Bias due to missingness is an important consideration for all clinical trials, including genetic studies. Disparities in the availability of genetic data compounded by missing phenotypic data creates a twofold disadvantage for underrepresented groups. Long term, we need to understand the biomedical and sociological causes of these associations and develop recruitment and retention strategies to ensure the generalizability of trial results.

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.

Endogenous apolipoprotein (apo) E mediates neuroinflammatory responses and recovery after brain injury. Exogenously administered apoE-mimetic peptides effectively penetrate the central nervous system compartment and downregulate acute inflammation. CN-105 is a novel apoE-mimetic pentapeptide with excellent evidence of functional and histological improvement in preclinical models of intracerebral hemorrhage (ICH). The CN-105 in participants with Acute supraTentorial intraCerebral Hemorrhage (CATCH) trial is a first-in-disease-state multicenter open-label trial evaluating safety and feasability of CN-105 administration in patients with acute primary supratentorial ICH. Eligible patients were aged 30–80 years, had confirmed primary supratentorial ICH, and were able to intiate CN-105 administration (1.0 mg/kg every 6 h for 72 h) within 12 h of symptom onset. A priori defined safety end points, including hematoma volume, pharmacokinetics, and 30-day neurological outcomes, were analyzed. For clinical outcomes, CATCH participants were compared 1:1 with a closely matched contemporary ICH cohort through random selection. Hematoma volumes determined from computed tomography images on days 0, 1, 2, and 5 and ordinal modified Rankin Scale score at 30 days after ICH were compared. In 38 participants enrolled across six study sites in the United States, adverse events occurred at an expected rate without increase in hematoma expansion or neurological deterioration. CN-105 treatment had an odds ratio (95% confidence interval) of 2.69 (1.31–5.51) for lower 30-day modified Rankin Scale score, after adjustment for ICH score, sex, and race/ethnicity, as compared with a matched contemporary cohort. CN-105 administration represents an excellent translational candidate for treatment of acute ICH because of its safety, dosing feasibility, favorable pharmacokinetics, and possible improvement in neurological recovery.

Background Recent randomised trials showed benefit for anti-inflammatory therapies in coronary disease but excluded stroke. The prognostic value of blood inflammatory markers after stroke is uncertain and guidelines do not recommend their routine measurement for risk stratification. Methods We performed a systematic review and meta-analysis of studies investigating the association of C-reactive protein (CRP), interleukin-6 (IL-6) and fibrinogen and risk of recurrent stroke or major vascular events (MVEs). We searched EMBASE and Ovid Medline until 10/1/19. Random-effects meta-analysis was performed for studies reporting comparable effect measures. Results Of 2,515 reports identified, 39 met eligibility criteria (IL-6, n = 10; CRP, n = 33; fibrinogen, n = 16). An association with recurrent stroke was reported in 12/26 studies (CRP), 2/11 (fibrinogen) and 3/6 (IL-6). On random-effects meta-analysis of comparable studies, CRP was associated with an increased risk of recurrent stroke [pooled hazard ratio (HR) per 1 standard-deviation (SD) increase in loge-CRP (1.14, 95% CI 1.06-1.22, p Conclusion Despite evidence suggesting an association between inflammatory markers and post-stroke vascular recurrence, substantial methodological heterogeneity was apparent between studies. Individual-patient pooled analysis and standardisation of methods are needed to determine the prognostic role of blood inflammatory markers and to improve patient selection for randomised trials of inflammatory therapies.

Background: Multi-phenotype analysis of genetically correlated phenotypes can increase the statistical power to detect loci associated with multiple traits, leading to the discovery of novel loci. This is the first study to date to comprehensively analyze the shared genetic effects within different hemostatic traits, and between these and their associated disease outcomes. Objectives: To discover novel genetic associations by combining summary data of correlated hemostatic traits and disease events. Methods: Summary statistics from genome wide-association studies (GWAS) from seven hemostatic traits (factor VII [FVII], factor VIII [FVIII], von Willebrand factor [VWF] factor XI [FXI], fibrinogen, tissue plasminogen activator [tPA], plasminogen activator inhibitor 1 [PAI-1]) and three major cardiovascular (CV) events (venous thromboembolism [VTE], coronary artery disease [CAD], ischemic stroke [IS]), were combined in 27 multi-trait combinations using metaUSAT. Genetic correlations between phenotypes were calculated using Linkage Disequilibrium Score Regression (LDSC). Newly associated loci were investigated for colocalization. We considered a significance threshold of 1.85 × 10−9 obtained after applying Bonferroni correction for the number of multi-trait combinations performed (n = 27). Results: Across the 27 multi-trait analyses, we found 4 novel pleiotropic loci (XXYLT1, KNG1, SUGP1/MAU2, TBL2/MLXIPL) that were not significant in the original individual datasets, were not described in previous GWAS for the individual traits, and that presented a common associated variant between the studied phenotypes. Conclusions: The discovery of four novel loci contributes to the understanding of the relationship between hemostasis and CV events and elucidate common genetic factors between these traits.

GE Healthcare©announced on April 19, 2022, that their main factory and distributor of iodinated contrast had experienced a temporary shutdown because of COVID-19 outbreak in Shanghai, China. This, along with other supply chain issues, led to a worldwide shortage of iodinated contrast agents, Omnipaque and Visipaque. Our Comprehensive Stroke Center was confronted with the cascading effect of this iodinated contrast material shortage. We took immediate steps to revise our protocols and processes to continue to provide high-quality care to our stroke patients. A multidisciplinary working group comprised of representatives of our stroke center, including vascular neurology, diagnostic neuroradiology, and neurovascular surgery, urgently met to brainstorm how to mitigate the shortage. We established parameters and local guidelines for the use of CT angiography, CT perfusion, and digital subtraction angiography for stroke patients. In this article, we propose “best practice” recommendations from a single Joint Commission approved Comprehensive Stroke Center that can be used as blueprint by other hospital systems when navigating potential future supply chain issues, to provide consistent high-quality stroke care.

BackgroundThe benefit of complete reperfusion (modified Thrombolysis in Cerebral Infarction (mTICI) 3) over near-complete reperfusion (≥90%, mTICI 2c) remains unclear. The goal of this study is to compare clinical outcomes between mechanical thrombectomy (MT)-treated stroke patients with mTICI 2c versus 3.MethodsThis is a retrospective study from the Stroke Thrombectomy and Aneurysm Registry (STAR) comprising 33 centers. Adults with anterior circulation arterial vessel occlusion who underwent MT yielding mTICI 2c or mTICI 3 reperfusion were included. Patients were categorized based on reperfusion grade achieved. Primary outcome was modified Rankin Scale (mRS) 0–2 at 90 days. Secondary outcomes were mRS scores at discharge and 90 days, National Institutes of Health Stroke Scale score at discharge, procedure-related complications, and symptomatic intracerebral hemorrhage.ResultsThe unmatched mTICI 2c and mTICI 3 cohorts comprised 519 and 1923 patients, respectively. There was no difference in primary (42.4% vs 45.1%; p=0.264) or secondary outcomes between the unmatched cohorts. Reperfusion status (mTICI 2c vs 3) was also not predictive of the primary outcome in non-imputed and imputed multivariable models. The matched cohorts each comprised 191 patients. Primary (39.8% vs 47.6%; p=0.122) and secondary outcomes were also similar between the matched cohorts, except the 90-day mRS which was lower in the matched mTICI 3 cohort (p=0.049). There were increased odds of the primary outcome with mTICI 3 in patients with baseline mRS ≥2 (36% vs 7.7%; p=0.011; pinteraction=0.014) and a history of stroke (42.3% vs 15.4%; p=0.027; pinteraction=0.041).ConclusionsComplete and near-complete reperfusion after MT appear to confer comparable outcomes in patients with acute stroke.

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.

OBJECTIVEThe utility of ICP monitoring and its benefit with respect to outcomes after ICH is unknown. The aim of this study was to compare intracerebral hemorrhage (ICH) outcomes in patients who underwent intracranial pressure (ICP) monitoring to those who were managed by care-guided imaging and/or clinical examination alone.METHODSThis was a retrospective analysis of data from the Ethnic/Racial variations of Intracerebral Hemorrhage (ERICH) study between 2010 and 2015. ICH patients who underwent ICP monitoring were propensity-score matched, in a 1:1 ratio, to those who did not undergo ICP monitoring. The primary outcome was 90-day mortality. Secondary outcomes were in-hospital mortality, hyperosmolar therapy use, ICH evacuation, length of hospital stay, and 90-day modified Rankin Scale (mRS) score, excellent outcome (mRS score 0–1), good outcome (mRS score 0–2), Barthel Index, and health-related quality of life (HRQoL; measured by EQ-5D and EQ-5D visual analog scale [VAS] scores). A secondary analysis for patients without intraventricular hemorrhage was performed.RESULTSThe ICP and no ICP monitoring cohorts comprised 566 and 2434 patients, respectively. The matched cohorts comprised 420 patients each. The 90-day and in-hospital mortality rates were similar between the matched cohorts. Shift analysis of 90-day mRS favored no ICP monitoring (p < 0.001). The rates of excellent (p < 0.001) and good (p < 0.001) outcome, Barthel Index (p < 0.001), EQ-5D score (p = 0.026), and EQ-5D VAS score (p = 0.004) at 90 days were lower in the matched ICP monitoring cohort. Rates of mannitol use (p < 0.001), hypertonic saline use (p < 0.001), ICH evacuation (p < 0.001), and infection (p = 0.001) were higher, and length of hospital stay (p < 0.001) was longer in the matched ICP monitoring cohort. In the secondary analysis, the matched cohorts comprised 111 patients each. ICP monitoring had a lower rate of 90-day mortality (p = 0.041). Shift analysis of 90-day mRS, Barthel Index, and HRQoL metrics were comparable between the matched cohorts.CONCLUSIONSThe findings of this study do not support the routine utilization of ICP monitoring in patients with ICH.

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.

Ischemic stroke (IS), caused by obstruction of cerebral blood flow, is one of the leading causes of death. While neurologists agree on delineation of IS into three subtypes (cardioembolic stroke (CES), large artery stroke (LAS), and small vessel stroke (SVS)), several subtyping systems exist. The most commonly used systems are TOAST (Trial of Org 10172 in Acute Stroke Treatment) and CCS (Causative Classification System for Stroke), but agreement is only moderate. We have compared two approaches to combining the existing subtyping systems for a phenotype suited for a genome-wide association study (GWAS). We used the NINDS Stroke Genetics Network dataset (SiGN, 11,477 cases with CCS and TOAST subtypes and 28,026 controls). We defined two new phenotypes: the intersect, for which an individual must be assigned the same subtype by CCS and TOAST; and the union, for which an individual must be assigned a subtype by either CCS or TOAST. The union yields the largest sample size while the intersect yields a phenotype with less potential misclassification. We performed GWAS for all subtypes, using the original subtyping systems, the intersect, and the union as phenotypes. In each subtype, heritability was higher for the intersect compared with the other phenotypes. We observed stronger effects at known IS variants with the intersect compared with the other phenotypes. With the intersect, we identify rs10029218:G>A as an associated variant with SVS. We conclude that this approach increases the likelihood to detect genetic associations in ischemic stroke.

Background There are several reports of the association between SARS-CoV-2infection (COVID-19) and cerebral venous sinus thrombosis (CVST). In this study, we aimed to compare the hospitalization rate of CVST before and during the COVID-19 pandemic (before vaccination program). Methods In this retrospective cohort study, the hospitalization rate of adult CVST patients in Namazi hospital, a tertiary referral center in the south of Iran, was compared in two periods of time. We defined March 2018 to March 2019 as the pre-COVID-19 period and March 2020 to March 2021 as the COVID-19 period. Results 50 and 77 adult CVST patients were hospitalized in the pre-COVID-19 and COVID-19 periods, respectively. The crude CVST hospitalization rate increased from 14.33 in the pre-COVID-19 period to 21.7 per million in the COVID-19 era (P=0.021). However, after age and sex adjustment, the incremental trend in hospitalization rate was not significant (95% CrI: -2.2, 5.14). Patients > 50-year-old were more often hospitalized in the COVID-19 period. (P=0.042) SARS-CoV-2 PCR test was done in 49.3% out of all COVID-19 period patients, which were positive in 6.5%. Modified Rankin Scale (mRS) score ≥3 at three-month follow-up was associated with age (P=0.015) and malignancy (P=0.014) in pre-COVID period; and was associated with age (P=0.025), altered mental status on admission time (P

Background: While research has focused on the trajectory of functional recovery after ischemic stroke, the trajectory of quality of life (QoL) has not been fully explored, nor has its relation to functional recovery. Methods: In a post hoc analysis of the IMS-III trial, we included patients with an imaging-confirmed large vessel occlusion and QoL assessed as EQ-5D at 5 study visits up to 1 year after ischemic stroke onset. We used group-based trajectory modelling (GBTM) to identify trajectories of EQ-5D index values with US-based weights and report patient demographics in each trajectory and the modified Rankin Scale (mRS) score at 90 days. Results: We included 266 patients, who had QoL measured at a mean of 4.6, 93.0, 184.3, 274.3, and 367.6 days after stroke onset. GBTM identified four trajectories with excellent fit (Figure). These QoL trajectories can be described as [1] persistent low, [2] low to medium, [3] persistent medium, and [4] medium to high. The corresponding mRS at 90 days are shown in the Figure, demonstrating a clustering of trajectories by mRS but also a diversity of trajectories. In particular, low to medium and persistent medium trajectories are represented across all mRS scores. Patient demographics are shown by trajectory in the Table, with significant differences in sex, baseline NIHSS, infarct volume, WMH burden, and diabetes. Conclusion: We demonstrate four distinct trajectories of QoL in the year after large vessel occlusion stroke, with a diversity of functional recovery and unique demographic compositions. Early recognition of a likely future QoL trajectory could suggest patient-specific rehabilitation therapies and inform prognostication and goals of care.

Background: Cervical Artery Dissection (CeAD) is an important cause of stroke in the young. Data on incidence and associations of recurrent CeAD are lacking. Increased Vertebral Artery Tortuosity Index (VTI) has been reported in patients with CeAD and associated with earlier age of arterial dissection in patients with connective tissue disease. We hypothesized that VTI may be associated with recurrent CeAD. Methods: We reviewed data from a large single-center registry of CeAD patients enrolled between 2011-2021. CT angiography (CTA) was reviewed for neck length, vertebral artery length (VAL), linear distance from the vertebral artery origin to the vertebrobasilar junction (VOBJ), and VTI [((VAL/VOBJ)–1)*100]. Recurrence was defined as radiographic diagnosis of a new dissection during a follow-up period between initial CTA imaging and July 1, 2021. Incidence rate of recurrent dissection was calculated using Poisson regression. Differences between groups were analyzed using the Kruskal-Wallis rank sum test and Fisher’s exact test. Results: The cohort included 155 patients: women (56%), mean (SD) age 42 (±10) years, and 116 single (carotid or vertebral) and 39 multiple artery dissections. Eight (5%) had a recurrence with a 10 year incidence rate (95% CI) of 1.23 events (0.53, 2.38) per 100 person-years. The recurrent group had a lower mean VTI than the nonrecurrent group (39.2 vs. 45.8; p = 0.024) and trended towards a lower mean age (34.6 vs. 42.3; p = 0.058). Participants with vertebral artery dissection were younger than those with carotid artery dissection with mean ages of 38.5 and 45.1 respectively (p < 0.001) and did not differ in mean VTI (46.0 vs. 44.9; p = 0.747). Morphometric characteristics of height, neck length, and BMI were not associated with recurrence. Conclusion: In this single center cohort of patients with CeAD, greater VTI was associated with a decreased risk of recurrent dissection. This finding is hypothesis generating as adults with recurrent dissections may have distinct mechanistic or genetic factors contributing to their risk of dissection. This study is limited by relatively small sample size and the retrospective analysis. Further study of VTI and risk of incident CeAD in larger independent cohorts is warranted.

Background: Studies have shown that patients with ischemic stroke (IS) and concurrent COVID-19 have increased stroke severity. These analyses were limited by use of prepandemic era controls or by utilization of a sample from the early pandemic period when stroke care delivery was affected by lockdown. Studies on the severity of hemorrhagic stroke (HS) in patients with concurrent COVID-19 are few and limited by small sample sizes. Methods: Using the National Institute of Health (NIH) National COVID Cohort Collaborative (N3C) database, we identified patients diagnosed with stroke between Mar 1, 2020 - Feb 28, 2021. Hospitalized stroke patients with concurrent COVID-19 (stroke within 3 months after or one week prior to positive SARS-COV-2 PCR or AG lab test) were matched to all other hospitalized stroke patients in a 1:3 ratio. Nearest neighbor matching with a caliper of 0.25 was used for most clinical and demographic factors; exact matching for race/ethnicity and site. Within our matched sample, we used Poisson regression to calculate stroke severity incident rate ratio (IRR). Results: Our query identified 10,394 patients hospitalized with IS with available NIHSS scores upon admission (802 with concurrent COVID-19 and 9,592 without) and 2138 patients hospitalized with HS (181 with concurrent COVID-19 and 1957 without). Average NIHSS was greater in concurrent groups with both IS and HS (11.1 vs 7.68, p < 0.001 and 15.7 vs 11.7, p < 0.001 respectively). Propensity matched analysis also demonstrated that stroke patients with concurrent COVID-19 had increased initial NIHSS (IS: IRR = 1.4, 95% CI:1.3-1.5, p-value < 0.001; HS: IRR = 1.3, 95% CI:1.2-1.5, p < 0.001). Average NIHSS in both IS and HS patients was greater in the Mar-Apr 2020 epoch than in all other 2 month epochs studied in these respective groups. Conclusions: This analysis suggests that the association between increased stroke severity and concurrent COVID-19 that was observed during the early pandemic was present throughout the pandemic as stroke care utilization normalized. Further work will center on the interaction between COVID-19 illness severity and stroke severity.

Introduction: Epidemiologic studies of intracerebral hemorrhage (ICH) have consistently demonstrated variation in incidence, location, comorbidity burden, age-of-onset, and outcome by race and ethnicity, and genetic studies have identified differences in risk mediated by genetic risk factors such as Apolipoprotein E (APOE). We report the design and methods of the largest multi-ethnic genome-wide association study (GWAS) of ICH risk and outcome conducted to date. Methods: The Ethnic/Racial Variations of ICH Genetics (ERICH-GENE) study is an international, multi-center, genetic case-control study of ICH. Cases are individuals with confirmed primary ICH with biosample availability and consent compatible with shareable genome-wide genotyping or previous genotyping. Central neuroimaging phenotype harmonization of case status, hemorrhage location, and imaging characteristics of cerebral small vessel disease including leukoaraiosis, atrophy, microbleeds, intraventricular hemorrhage severity and volume of ICH measurements will be performed. Controls are ICH-free individuals of compatible age and race/ethnicity from existing studies and biorepositories. Results: As of August 2021, 2,002 ICH cases have been collected and genotyped, in addition to 2,558 already-genotyped ICH cases from the multi-ethnic ERICH study. 5,600 total new ICH cases will be genotyped under ERICH-GENE, with planned meta-analyses across existing ICH GWAS datasets and international biobanks totaling >20,000 cases. We are on schedule to meet our genotyping goal within the study period. Non-European ancestry cases are being prioritized for genotyping and ~66% of the previously genotyped ERICH cases are black or Hispanic. From available cases, a total of 10,621 neuroimaging studies have been uploaded for central adjudication to date with 6,278 having undergone harmonization. Conclusions: ERICH-GENE is a large, multi-ethnic, international, centrally harmonized GWAS of ICH risk and outcome that will identify genetic risk factors across diverse populations for biological discovery and population-specific risk stratification.

Introduction: Genetic reference panels and imputation approaches have improved greatly in the last 10 years. The development of the TOPMed reference plane has led to enhanced imputation quality and quantity of single nucleotide polymorphisms (SNPs) due to greater sample diversity among various population ancestries. We revisited our prior GWAS of recurrent stroke by utilizing the TOPMed imputation server. Methods: This GWAS used a Cox proportional hazards model of time to recurrent stroke with the Vitamin Intervention for Stroke Prevention clinical trial cohort. There were 2,100 genotyped patients (64% male) in total with an average age of 67.2 (±10.8) years and ancestry distribution of 1,725 (82%) European, 258 (12%) African, and 117 (6%) Other or Mixed ancestry. Genotyped samples underwent a strict quality control process. We utilized TOPMed for imputation which totaled 10,467,887 biallelic SNPs which was 14 times greater in number compared the original analysis. Results: Recurrent stroke was observed in 182 (8.7%) patients. We identified seven novel SNPS on chromosome 1 in addition to our previous finding, rs6664786. Interestingly all chromosome 1 SNPs were located within the LINCO1362 gene. This gene has an acute change in expression in the presence of smoking even after adjustment of relevant clinical factors. Two novel SNPs were found on chromosome 16 located in gene desert nearest the pseudo-gene RNU6-21P in an intergenic region downstream of the Cadherin-8 (CDH8) gene. Both SNPs and RNU6-21P have no previously reported clinical relevance, except for their relative position to CDH8. CDH8 is highly expressed in brain tissue. Conclusions: We identified several novel SNPs associated with recurrent stroke. Capitalizing on genetic imputation advancements allows potential new insights and discoveries with past trial cohorts. Understanding these insights may provide further mechanistic knowledge of recurrent stroke to develop potential therapeutic targets.

From April 1, 2011, through September 30, 2011, Neurology ® received 2,167 new and 643 revised manuscripts. During this interval, 3,909 peer reviews were received (compared to 3,758 during the same period in 2010), with the average turnaround time after assignment being 8.5 days. Average time from submission to first decision for papers chosen for review remained at 33 days. Limitations in the number of pages we can publish allow us to accept only a minority of papers submitted. Your specific comments regarding the uniqueness of study populations, novel methods, studies that are especially educational, or new strategies for diagnosing and treating neurologic disease are appreciated; these comments help us immeasurably when we make final decisions regarding which articles we believe will most benefit our authors and readers, as well as improve patient care. Manuscripts for the Resident & Fellow Section of Neurology are often submitted by trainees who have less experience in preparing articles for publication, and it is the goal of the Section to help these junior authors improve their clinical and scientific writing abilities. We especially appreciate the constructive feedback provided by reviewers of these manuscripts. We recently posted an Information for Reviewers (IFR) link on www.neurology.org. Click on this link for information on expectations of reviewers regarding confidentiality, timeliness, and reviewer conflicts of interest. The IFR also provides instructions for formatting the comments to editors and authors in order to make communication with authors most effective. In appreciation of your dedication to Neurology , we offer an hour of CME credit, if requested, for each manuscript you review for the Journal (maximum of 15 credits per year as determined by ACCME). To receive credit, it should be evident that the reviewer has read and understood the content of the manuscript, accompanying figures and tables, supplementary …

Cervical Artery Dissection is an important cause of stroke in the young. Data on incidence and associations of recurrence in patients with cervical artery dissection are lacking. Increased Vertebral Artery Tortuosity Index has been reported in patients with cervical artery dissection and associated with earlier age of arterial dissection in patients with connective tissue disease.To test the hypothesis that increased vertebral artery tortuosity is associated with recurrent cervical artery dissection.We reviewed data from a single-center registry of cervical artery dissection patients enrolled between 2011-2021. CT angiography was reviewed for neck length, vertebral artery dominance, and vertebral artery tortuosity index. Incidence rate of recurrent dissection was calculated using Poisson regression. Differences between groups were analyzed using the Kruskal-Wallis rank sum test and Fisher's exact test.The cohort included 155 patients: women (56%), mean (SD) age 42 (±10) years, and 116 single and 39 multiple artery dissections. Eleven (7.1%) had a recurrence with an incidence rate (95% CI) of 1.91 (1.06, 3.44) per 100 person-years. Vertebral artery tortuosity did not differ significantly between single and recurrent groups (median (IQR) 46.81 (40.85, 53.91) vs 44.97 (40.68, 50.62) p = 0.388). Morphometric characteristics of height, neck length, and BMI were not associated with recurrence. There was no difference in vertebral artery tortuosity by dissection location (carotid vs vertebral).In this single center cohort of patients with cervical artery dissection, there was no difference in VTI between single and recurrent groups.

ObjectiveTo 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 National Institutes of Health Stroke Scale data at index stroke, as well as modified Rankin Scale (mRS) at 3-6 months post-stroke were obtained from MRI-GENIE study of acute ischemic stroke (AIS) patients. Individual WMH volume was automatically derived from FLAIR-images. Stroke lesions were automatically segmented from DWI-images, spatially normalized and parcellated into atlas-defined brain regions. Stroke lesion effects on AIS severity and unfavorable outcomes (mRS>2) were modeled within a purpose-built machine learning and Bayesian regression framework. In particular, interaction effects between stroke lesions and a high versus low WMH burden were integrated via hierarchical model structures. Models were adjusted for the covariates age, age2, sex, total DWI-lesion and WMH volumes, and comorbidities. Data were split into derivation and validation cohorts.ResultsA total of 928 AIS patients contributed to stroke severity analyses (mean age: 64.8(14.5), 40% women), 698 patients to functional outcome analyses (mean age: 65.9(14.7), 41% women). Individual stroke lesions were represented in five anatomically distinct left-hemispheric and five right-hemispheric lesion patterns. Across all patients, acute stroke severity was substantially explained by three of these patterns, that were particularly focused on bilateral subcortical and left-hemispherically pronounced cortical regions. In high WMH burden patients, two lesion patterns consistently emerged as more pronounced in case of stroke severity: the first pattern was centered on left-hemispheric insular, opercular and inferior frontal regions, while the second pattern combined right-hemispheric temporo-parietal regions. Bilateral subcortical regions were most relevant in explaining long term unfavorable outcome. No WMH-specific lesion patterns of functional outcomes were substantiated. However, a higher overall WMH burden was associated with higher odds of unfavorable outcomes.ConclusionsHigher WMH burden increases stroke severity in case of stroke lesions involving left-hemispheric insular, opercular and inferior frontal regions (potentially linked to language functions) and right-hemispheric temporo-parietal regions (potentially linked to attention). These findings may contribute to augment stroke outcome predictions and motivate a WMH burden and stroke lesion pattern-specific clinical management of AIS patients.

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.

While chronological age is one of the most influential determinants of post-stroke outcomes, little is known of the impact of neuroimaging-derived biological brain age. We here first examine whether radiomics analysis of the texture of brain T2-FLAIR MRI images can be used to predict brain age in stroke patients. We then assess the clinical determinants of accelerated brain aging and, finally, its impact on post-stroke functional outcomes. Leveraging a multisite cohort of 4,163 ischemic stroke patients, we show that older-appearing patients have more hypertension, diabetes mellitus, prior strokes, and smoking history and are more likely to develop worse post-stroke outcomes than their younger-appearing counterparts. Our results strengthen the importance of preventive medicine for maintaining brain health in stroke patients as they age and suggest a novel methodology to capture previously undescribed prognostic information available on commonly acquired MRI sequences during routine stroke care.

Key Points Question Does the prevalence and burden of risk factors for lobar and nonlobar intracerebral hemorrhage (ICH) differ among Black, Hispanic, and White populations? Findings In this case-control study of 3000 cases of ICH among Black, Hispanic, and White patients, the ɛ2 and ɛ4 alleles of APOE, the gene encoding apolipoprotein E, were associated with lobar ICH in White but not Black and Hispanic patients; hypertension was a risk factor for both lobar and nonlobar ICH in all groups; and the mean age for ICH among Black and Hispanic patients was more than 10 years younger than that of their White counterparts. Black and Hispanic patients had a higher attributable risk percentage for treated or untreated hypertension and lack of health insurance than White patients. Meaning These findings suggest that potentially modifiable risk factors and social determinants of health are important contributors to the disproportionate ICH burden experienced by Black and Hispanic populations., This case-control study examines the prevalence, odds, and population attributable risk for established and novel risk factors for intracerebral hemorrhage, stratified by intracerebral hemorrhage location and racial/ethnic group., Importance Black and Hispanic individuals have an increased risk of intracerebral hemorrhage (ICH) compared with their White counterparts, but no large studies of ICH have been conducted in these disproportionately affected populations. Objective To examine the prevalence, odds, and population attributable risk (PAR) percentage for established and novel risk factors for ICH, stratified by ICH location and racial/ethnic group. Design, Setting, and Participants The Ethnic/Racial Variations of Intracerebral Hemorrhage Study was a case-control study of ICH among 3000 Black, Hispanic, and White individuals who experienced spontaneous ICH (1000 cases in each group). Recruitment was conducted between September 2009 and July 2016 at 19 US sites comprising 42 hospitals. Control participants were identified through random digit dialing and were matched to case participants by age (±5 years), sex, race/ethnicity, and geographic area. Data analyses were conducted from January 2019 to May 2020. Main Outcomes and Measures Case and control participants underwent a standardized interview, physical measurement for body mass index, and genotyping for the ɛ2 and ɛ4 alleles of APOE, the gene encoding apolipoprotein E. Prevalence, multivariable adjusted odds ratio (OR), and PAR percentage were calculated for each risk factor in the entire ICH population and stratified by racial/ethnic group and by lobar or nonlobar location. Results There were 1000 Black patients (median [interquartile range (IQR)] age, 57 [50-65] years, 425 [42.5%] women), 1000 Hispanic patients (median [IQR] age, 58 [49-69] years; 373 [37.3%] women), and 1000 White patients (median [IQR] age, 71 [59-80] years; 437 [43.7%] women). The mean (SD) age of patients with ICH was significantly lower among Black and Hispanic patients compared with White patients (eg, lobar ICH: Black, 62.2 [15.2] years; Hispanic, 62.5 [15.7] years; White, 71.0 [13.3] years). More than half of all ICH in Black and Hispanic patients was associated with treated or untreated hypertension (PAR for treated hypertension, Black patients: 53.6%; 95% CI, 46.4%-59.8%; Hispanic patients: 46.5%; 95% CI, 40.6%-51.8%; untreated hypertension, Black patients: 45.5%; 95% CI, 39.%-51.1%; Hispanic patients: 42.7%; 95% CI, 37.6%-47.3%). Lack of health insurance also had a disproportionate association with the PAR percentage for ICH in Black and Hispanic patients (Black patients: 21.7%; 95% CI, 17.5%-25.7%; Hispanic patients: 30.2%; 95% CI, 26.1%-34.1%; White patients: 5.8%; 95% CI, 3.3%-8.2%). A high sleep apnea risk score was associated with both lobar (OR, 1.68; 95% CI, 1.36-2.06) and nonlobar (OR, 1.62; 95% CI, 1.37-1.91) ICH, and high cholesterol was inversely associated only with nonlobar ICH (OR, 0.60; 95% CI, 0.52-0.70); both had no interactions with race and ethnicity. In contrast to the association between the ɛ2 and ɛ4 alleles of APOE and ICH in White individuals (eg, presence of APOE ɛ2 allele: OR, 1.84; 95% CI, 1.34-2.52), APOE alleles were not associated with lobar ICH among Black or Hispanic individuals. Conclusions and Relevance This study found sleep apnea as a novel risk factor for ICH. The results suggest a strong contribution from inadequately treated hypertension and lack of health insurance to the disproportionate burden and earlier onset of ICH in Black and Hispanic populations. These findings emphasize the importance of addressing modifiable risk factors and the social determinants of health to reduce health disparities.

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.