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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: Clinical trial enrollment and completion is challenging, with nearly half of all trials not being completed or not completed on time. In 2014, the National Institutes of Health StrokeNet in collaboration with stroke epidemiologists from GCNKSS (Greater Cincinnati/Northern Kentucky Stroke Study) began providing proposed clinical trials with formal trial feasibility assessments. Herein, we describe the process of prospective feasibility analyses using epidemiological data that can be used to improve enrollment and increase the likelihood a trial is completed. Methods: In 2014, DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3) trialists, National Institutes of Health StrokeNet, and stroke epidemiologists from GCNKSS collaborated to evaluate the initial inclusion/exclusion criteria for the DEFUSE 3 study. Trial criteria were discussed and an assessment was completed to evaluate the percent of the stroke population that might be eligible for the study. The DEFUSE 3 trial was stopped early with the publication of DAWN (Thrombectomy 6 to 24 Hours After Stroke With a Mismatch Between Deficit and Infarct), and the Wilcoxon rank-sum statistic was used to analyze whether the trial would have been stopped had the proposed changes not been made, following the DEFUSE 3 statistical analysis plan. Results: After initial epidemiological analysis, 2.4% of patients with acute stroke in the GCNKSS population would have been predicted to be eligible for the study. After discussion with primary investigators and modifying 4 key exclusion criteria (upper limit of age increased to 90 years, baseline modified Rankin Scale broadened to 0–2, time since last well expanded to 16 hours, and decreased lower limit of National Institutes of Health Stroke Scale score to Conclusions: Objectively assessing trial inclusion/exclusion criteria using a population-based resource in a collaborative and iterative process including epidemiologists can lead to improved recruitment and can increase the likelihood of successful trial completion.

Background: Our primary objective was to evaluate if disparities in race, sex, age, and socioeconomic status (SES) exist in utilization of advanced neuroimaging in year 2015 in a population-based study. Our secondary objective was to identify the disparity trends and overall imaging utilization as compared with years 2005 and 2010. Methods: This was a retrospective, population-based study that utilized the GCNKSS (Greater Cincinnati/Northern Kentucky Stroke Study) data. Patients with stroke and transient ischemic attack were identified in the years 2005, 2010, and 2015 in a metropolitan population of 1.3 million. The proportion of imaging use within 2 days of stroke/transient ischemic attack onset or hospital admission date was computed. SES determined by the percentage below the poverty level within a given respondent’s US census tract of residence was dichotomized. Multivariable logistic regression was used to determine the odds of advanced neuroimaging use (computed tomography angiogram/magnetic resonance imaging/magnetic resonance angiogram) for age, race, gender, and SES. Results: There was a total of 10 526 stroke/transient ischemic attack events in the combined study year periods of 2005, 2010, and 2015. The utilization of advanced imaging progressively increased (48% in 2005, 63% in 2010, and 75% in 2015 [ P P P 55 years; adjusted odds ratio, 1.34 [95% CI, 1.15–1.57]; P Conclusions: Racial, age, and SES-related disparities exist in the utilization of advanced neuroimaging for patients with acute stroke. There was no evidence of a change in trend of these disparities between the study periods.

Background: Hemoglobin concentration and diffusion-weighted imaging (DWI) ischemic lesions are separately known to be associated with poor intracerebral hemorrhage (ICH) outcomes. While hemoglobin concentrations have known relationships with ischemic stroke, it is unclear whether hemoglobin concentration is associated with DWI ischemic lesions after ICH. We sought to investigate the hypothesis that hemoglobin concentrations would associate with DWI lesions after ICH and further investigated their relationships with clinical outcomes. Methods: Supratentorial ICH patients enrolled between 2010 and 2016 to a prospective, multicenter, observational cohort study (ERICH study [Ethnic/Racial Variations of Intracerebral Hemorrhage]) were assessed. Patients from this study with baseline, admission hemoglobin, and hospitalization magnetic resonance imaging were analyzed. Hemoglobin was examined as the primary exposure variable defined as a continuous variable (g/dL). Magnetic resonance imaging DWI ischemic lesion presence was assessed as the primary radiographic outcome. Primary analyses assessed relationships of hemoglobin with DWI lesions. Secondary analyses assessed relationships of DWI lesions with poor 3-month outcomes (modified Rankin Scale score, 4–6). These analyses were performed using separate multivariable logistic regression models adjusting for relevant covariates. Results: Of 917 patients with ICH analyzed, mean baseline hemoglobin was 13.8 g/dL (±1.9), 60% were deep ICH, and DWI lesions were identified in 27% of the cohort. In our primary analyses, increased hemoglobin, defined as a continuous variable, was associated with DWI lesions (adjusted odds ratio, 1.21 per 1 g/dL change in hemoglobin [95% CI, 1.07–1.37]) after adjusting for sex, race, ICH severity, time to magnetic resonance imaging, and acute blood pressure change. In secondary analyses, DWI lesions were associated with poor 3-month outcomes (adjusted odds ratio, 1.83 [95% CI, 1.24–2.69]) after adjusting for similar covariates. Conclusions: We identified novel relationships between higher baseline hemoglobin concentrations and DWI ischemic lesions in patients with ICH. Further studies are required to clarify the role of hemoglobin concentration on both cerebral small vessel disease pathophysiology and ICH outcomes.

Background: Though stroke risk factors such as substance use may vary with age, less is known about trends in substance use over time or about performance of toxicology screens in young adults with stroke. Methods: Using the Greater Cincinnati Northern Kentucky Stroke Study, a population-based study in a 5-county region comprising 1.3 million people, we reported the frequency of documented substance use (cocaine/marijuana/opiates/other) obtained from electronic medical record review, overall and by race/gender subgroups among physician-adjudicated stroke events (ischemic and hemorrhagic) in adults 20 to 54 years of age. Secondary analyses included heavy alcohol use and cigarette smoking. Data were reported for 5 one-year periods spanning 22 years (1993/1994–2015), and trends over time were tested. For 2015, to evaluate factors associated with performance of toxicology screens, multiple logistic regression was performed. Results: Overall, 2152 strokes were included: 74.5% were ischemic, mean age was 45.7±7.6, 50.0% were women, and 35.9% were Black. Substance use was documented in 4.4%, 10.4%, 19.2%, 24.0%, and 28.8% of cases in 1993/1994, 1999, 2005, 2010, and 2015, respectively ( P trend Conclusions: In a population-based study of young adults with stroke, documented substance use increased over time, and documentation of substance use was higher among Black compared with White individuals. Further work is needed to confirm race-based disparities and trends in substance use given the potential for bias in screening and documentation. Findings suggest a need for more standardized toxicology screening.

The evidence linking chronic kidney disease (CKD) to spontaneous intracerebral hemorrhage (ICH) is inconclusive owing to possible confounding by comorbidities that frequently coexist in patients with these 2 diseases.To determine whether there is an association between CKD and ICH risk.A 3-stage study that combined observational and genetic analyses was conducted. First, the association between CKD and ICH risk was tested in the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study, a multicenter case-control study in the US. All participants with available data on CKD from ERICH were included. Second, this analysis was replicated in the UK Biobank (UKB), an ongoing population study in the UK. All participants in the UKB were included in this study. Third, mendelian randomization analyses were implemented in the UKB using 27 CKD-related genetic variants to test for genetic associations. ERICH was conducted from August 1, 2010, to August 1, 2017, and observed participants for 1 year. The UKB enrolled participants between 2006 and 2010 and will continue to observe them for 30 years. Data analysis was performed from November 11, 2019, to May 10, 2022.CKD stages 1 to 5.The outcome of interest was ICH, ascertained in ERICH via expert review of neuroimages and in the UKB via a combination of self-reported data and International Statistical Classification of Diseases, Tenth Revision, codes.In the ERICH study, a total of 2914 participants with ICH and 2954 controls who had available data on CKD were evaluated (mean [SD] age, 61.6 [14.0] years; 2433 female participants [41.5%]; 3435 male participants [58.5%]); CKD was found to be independently associated with higher risk of ICH (odds ratio [OR], 1.95; 95% CI, 1.35-2.89; P .001). This association was not modified by race and ethnicity. Replication in the UKB with 1341 participants with ICH and 501 195 controls (mean [SD] age, 56.5 [8.1] years; 273 402 female participants [54.4%]; 229 134 male participants [45.6%]) confirmed this association (OR, 1.28; 95% CI, 1.01-1.62; P = .04). Mendelian randomization analyses indicated that genetically determined CKD was associated with ICH risk (OR, 1.56; 95% CI, 1.13-2.16; P = .007).In this 3-stage study that combined observational and genetic analyses among study participants enrolled in 2 large observational studies with different characteristics and study designs, CKD was consistently associated with higher risk of ICH. Mendelian randomization analyses suggest that this association was causal. Further studies are needed to identify the specific biological pathways that mediate this association.

Background and ObjectivesThere is a rising incidence of infective endocarditis–related stroke (IERS) in the United States attributed to the opioid epidemic. A contemporary epidemiologic description is necessary to understand the impact of the opioid epidemic on clinical characteristics of IERS. We describe and analyze trends in the demographics, risk factors, and clinical features of IERS.MethodsThis is a retrospective cohort study within a biracial population of 1.3 million in the Greater Cincinnati/Northern Kentucky region. All hospitalized patients with hemorrhagic or ischemic stroke were identified and physician verified from the 2005, 2010, and 2015 calendar years using ICD-9 and ICD-10 codes. IERS was defined as an acute stroke attributed to infective endocarditis meeting modified Duke Criteria for possible or definite endocarditis. Unadjusted comparison of demographics, risk factors, outcome, and clinical characteristics was performed between each study period for IERS and non-IERS. An adjusted model to compare trends used the Cochran-Armitage test for categorical variables and a general linear model or Kruskal-Wallis test for numerical variables. Examination for interaction of endocarditis status in trends was performed using a general linear or logistic model.ResultsA total of 54 patients with IERS and 8,204 without IERS were identified during the study periods. Between 2005 and 2015, there was a decline in rates of hypertension (91.7% vs 36.0%;p= 0.0005) and increased intravenous drug users (8.3% vs 44.0%;p= 0.02) in the IERS cohort. The remainder of the stroke population demonstrated a significant rise in hypertension, diabetes, atrial fibrillation, and perioperative stroke. Infective endocarditis status significantly interacted with the trend in hypertension prevalence (p= 0.001).DiscussionFrom 2005 to 2015, IERS was increasingly associated with intravenous drug use and fewer risk factors, specifically hypertension. These trends likely reflect the demographics of the opioid epidemic, which has affected younger patients with fewer comorbidities.

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.

Background: TIAs serve as an opportunity to identify and modify risk factors and to prevent future events. Given known epidemiologic differences in strokes by race and sex, our objective was to investigate the rates of prior TIAs among those with incident ischemic stroke (IS) in the GCNKSS. Methods: We included all physician adjudicated, incident IS among adults age ≥20 years in the GCNKSS, a population-based stroke surveillance study in a 5-county region of southern Ohio/ northern Kentucky, in 2005, 2010, and 2015. We calculated the frequency of cases in which a TIA (sudden onset of focal neurologic symptoms lasting ≤ 24 hours) was documented in the 365 days prior to IS. Frequencies and proportions of prior TIA were compared by sex, race, and age, and location at which patients sought care for their TIA was described. Finally, multivariable logistic regression was performed to investigate demographic and clinical predictors of cases in which TIA preceded stroke; covariates were chosen a priori. Results: We included 5310 IS events; mean age was 69.7 (SD 14.8) years, 54.7% were female, and 20.4% were Black. A total of 351 patients (6.6%) had a documented TIA the year preceding their IS. Overall, 42.2% did not seek care for their TIA, 21.6% called 911 and/or came to the ED, 6.0% saw a PCP, and 6.6% sought other care. In 22.5% of cases, location of care was unknown. In adjusted results, older age, female sex, history of hypertension, and CAD were associated with having had a prior TIA, while Black race was not. NIHSS was inversely associated with prior TIA (Table). Prior TIAs were similar between study years. Conclusions: We conservatively estimate that ≥ 6% of patients with first-ever IS had a TIA in the preceding year, though underreporting is likely. Many patients did not report seeking care for the TIA, suggesting missed opportunities for risk factor modification. Further research is needed to understand the implications of sex and race differences in frequencies of prior TIA.

Background: Monitoring changes in ischemic stroke severity at the population level is important as changes in risk factors and clinical treatments could influence stroke severity. We describe trends in the distribution of NIHSS across 3 time periods in a population-based epidemiologic stroke study. Methods: In 2005, 2010, and 2015 all adult acute ischemic strokes occurring within the Greater Cincinnati area presenting to 15 hospitals were ascertained using discharge codes (ICD-9 433-436; IDC-10 I63-I68, G45-46). Following physician verification, confirmed ischemic stroke cases underwent chart abstraction including estimation of a retrospective (rNIHSS) score at presentation. Descriptive statistics (rNIHSS median, IQR) were generated by survey year, demographics, and medical history. Using a binary definition of stroke severity (median rNIHSS score &gt 4 versus &lt 4), multivariable logistic regression was used to estimate changes in stroke severity over time, adjusting for potential confounders. Random effects were used to account for multiple admissions occurring in the same subject. Results: The number of ischemic stroke admissions in the 2005, 2010, and 2015 surveys was 1778, 1903, and 1933, respectively (Table). The median (IQR) rNIHSS scores were 3 (2-7), 3 (1-6), and 2 (1-6) across the 3 surveys, respectively; the proportion of admissions with rNIHSS &gt 4 was 48%, 39% and 37%, respectively. After adjusting for demographics, medical history and pre-stroke function, compared to 2005, the odds ratio for more severe stroke was 0.69 (95% CI= 0.60-0.79, p=0.001) in 2010 and 0.63 (95% CI= 0.55-0.73, p=0.001) in 2015. Conclusions: In this population- based study there was a statistically significant change in the severity of ischemic stroke hospitalizations with increases in the proportion of milder strokes over time. Potential reasons for this change need to be explored but could include changes in risk factors, clinical treatments or diagnostic approach.

Background and objective: Small, single-center studies point to biological and clinical differences in women and men who sustain a spontaneous, non-traumatic intracerebral hemorrhage (ICH). Leveraging data from four landmark studies of ICH, we investigated the impact of sex on risk factors, location, severity and outcome of ICH. Design: Individual patient data meta-analysis of four studies of ICH, including three randomized clinical trials and one multi-ethnic observational study. Setting: Academic medical centers in the United States. Patients: Patients with neuroimaging confirmed ICH. Measurements: We conducted an individual patient data meta-analysis of four landmark studies of ICH: ERICH, ATACH-II, FAST and MISTIE-III. We evaluated whether sex was associated with specific risk factor profiles, hemorrhage location (deep or lobar), neuroimaging severity (hematoma volume and expansion), and poor 90-day functional outcomes (defined as a modified Rankin scale 4 to 6). Main Results: A total of 4,812 ICH patients were evaluated (mean age 62, 60% males). Men with ICH were younger, more likely to be smokers and diabetics, and less likely to be on anticoagulants (all p Conclusions: Men with ICH are more likely to have vascular risk factors, have larger hemorrhage volumes, and have higher risk of hemorrhage expansion. They are also more likely to have a good outcome at 90 days compared to women.

Introduction: Primary prevention reduces the burden of acute ischemic stroke (AIS), yet cerebrovascular risk factors (RF) remain underdiagnosed in certain populations. We aimed to identify predictors of undiagnosed RF among patients with cerebrovascular ischemic events in a large bi-racial population. Methods: Individuals 20 years and older with an incident TIA or AIS from the population-based Greater Cincinnati/Northern Kentucky 2015 stroke study period were screened for inclusion. We included all hospital ascertained, physician-verified cases of AIS and TIAs. Outpatient and ED-only cases were excluded. Abstracted medical record data included determination of newly diagnosed hypertension (HTN), diabetes mellitus (DM), hyperlipidemia (HLD) or atrial fibrillation (AF). Multivariable models were used to identify predictors for each undiagnosed RF. Model variables included: age, sex, race, insurance status and number of cerebrovascular RF (additionally including coronary artery disease and smoking). Results: A total of 1604 ischemic events were included (1485 stroke, 119 TIA) with 52.9% female; 22.4% Black; median age 70 (IQR 59, 82)). Only 6% (n=102) had no history of RF. The prevalence of each undiagnosed RF was: HTN 4.1%; HLD 7.9%; DM 3.1%; AF 3.2%. In unadjusted bivariate analysis, uninsured/unknown status was predictive of undiagnosed HTN (OR = 3.97, 95% CI 1.48, 10.68; p =.006) and HLD (OR=5.53, 95% CI 2.68, 11.4; p Table 1 ). No relationship was found with race. Conclusions: The most consistent predictor for an undiagnosed RF was absence of other RF and lack of insurance, both suggestive of suboptimal cardiovascular screening in this population. Further studies assessing known but undertreated RF and socioeconomic factors could be of benefit.

Intro: Enrolling women and under-represented minorities into clinical trials is a top priority for the stroke community. Common trial exclusions for medical conditions or demographics may negatively impact enrollment for these groups. We sought to describe the potential impact that various exclusion criteria have on trial eligibility of ischemic stroke (IS) patients by race and sex within the large, biracial Greater Cincinnati/Northern Kentucky Stroke Study (GCNKSS) population. Methods: The GCNKSS is a population-based study of 1.3 million people living in a 5-county area of southern Ohio/ Northern Kentucky. During 7/1/14-12/31/15 for blacks, and 2015 for whites, we captured all hospitalized ischemic strokes by screening ICD-9 codes 430-436 and ICD10 codes I60-I68, and G45-46. Commonly used exclusion criteria from stroke clinical trials were applied to the GCNKSS IS population, and were compared by sex and race. All comparisons were evaluated with chi-square test and corrected for multiple comparisons, as necessary. Results: In 2014-2015, there were 2806 ischemic stroke patients, which were 53% female, and 30% black. Table 1 presents common clinical trial exclusion criteria and the % excluded among IS patients, stratified by sex and race. Every trial exclusion evaluated had significant differences by sex, race, or both. Discussion: Within our population, we found that commonly-used age and disability clinical trial exclusion criteria exclude more women than men, and exclusion of milder strokes affects more men than women. Blood pressure, renal function, and early arrival time criteria exclude more blacks than whites, while older age exclude more whites than blacks. Optimal clinical trial design should be informed by epidemiology data to ensure representation of underrepresented populations in clinical trials. We will continue to provide epidemiology feedback on acute trial exclusion criteria to NIH StrokeNet proposals in the future.

Background: Poorer socioeconomic status (SES) is associated with higher stroke incidence. Less is known about SES and stroke recurrence. We sought to obtain updated estimates of stroke incidence stratified by aggregate measures of SES, and to explore the association between SES and stroke recurrence. Methods: The Greater Cincinnati/Northern Kentucky region includes a population of 1.3 million, representative of the US population in terms of sociodemographics and percent black race. We ascertained all hospitalized strokes in the region in 2015 by screening ICD-9 codes 430-437 and ICD-10 codes I60-69, G45-46. Recurrent strokes were ascertained from 1/1/2015-12/31/2018. Patients’ home addresses were geocoded using DeGAUSS. Population estimates were obtained from the US Census Bureau using the 2015 5-year American Community Survey. Aggregate SES was estimated by percentage below poverty in each census tract. Regional incidence and recurrence rates were adjusted for age, sex, and race and calculated both with and without SES adjustment using Poisson regression models. Results: Stroke incidence and recurrence rates stratified by SES are shown in the Table. Poorer SES was associated with greater stroke incidence (p Conclusions: Poorer SES was associated with increased risk for both incident and recurrent stroke across races. Of the excess risk for stroke incidence among black individuals, 25.5% was accounted for by SES, while 35.1% of the excess risk for recurrence was accounted for by SES.

Background: Ischemic stroke is the 5 th leading cause of death in the US. As a measure of stroke severity, initial NIHSS has been used to predict clinical outcome. We sought to identify the optimal cut-points of NIHSS at initial presentation that are associated with higher 30-day mortality. Methods: In 2005, 2010, and 2015 all hospitalized, first acute ischemic stroke events occurring within the Greater Cincinnati area were ascertained. Potential ischemic stroke cases underwent chart abstraction and physician adjudication, including retrospective NIHSS score (range 0 - 42) based on clinical findings at initial presentation. Descriptive statistics for NIHSS were estimated by study year, demographics, and medical history. Data regarding mortality was obtained from the National Death Index. The Contal and O’Quigley method based on a modified log-rank test statistic was used to determine cut-points of the NIHSS score associated with 30-day mortality, and hazard ratios were obtained from Cox models with adjustment for sex, race, and age. Results: In 2005, 2010, and 2015 there were 1704, 1818 and 1852 ischemic stroke events with 30-day mortality rates of 10.5%, 9.6% and 9.0%, respectively. Optimal cut-points of NIHSS 16 were identified. Across all 3 periods, 3431 (84.5%) cases had NIHSS 0-8, 352 (8.7%) had NIHSS 9-16 and 274 (6.8%) >16. Kaplan Meier Survival Curves for the 3 NIHSS groups are shown in the Figure. Strokes with NIHSS >16 at initial presentation were associated with a 15-fold (HR with 95% CI: 13, 19) increase in the risk of death at 30-days compared to those with NIHSS Discussion: NIH Stroke Scale scores are a reliable predictor of mortality, with higher NIHSS scores having higher risk of death. The cut points reported identify subgroups of stroke patients with dramatically different prognoses. Future studies should assess if this excess mortality risk among severe strokes persists after the more widespread implementation of thrombectomy beyond 2015.

Background: Previous studies spanning the 1990s-2010s have inconsistently identified a decline in 30-day stroke case-fatality rate (CFR), and little is known about trends in longer term stroke CFR over that period. We studied temporal trends in 30-day and 5-year CFRs in the well-defined Greater Cincinnati/Norther Kentucky (GCNK) stroke population. Methods: The NIH-funded GCNK Stroke Study is a population-based study conducted in a 5-county region that is representative of the USA in terms of Black race, income, and education. The study ascertained all strokes in 1993/4, 1999, 2005, 2010, and 2015 using well-validated methods. All stroke subtypes were included: ischemic strokes (IS), intracerebral hemorrhages (ICH), and subarachnoid hemorrhages (SAHs). Deaths were identified via the National Death Index. Cox proportional hazards models were used to assess all-cause fatality, by subtype, to examine temporal trends adjusting for age, sex, and race. Results: A total of 10372 stroke cases were ascertained over the five study periods (8428 IS, 443 SAH, and 1501 ICH). IS patients did not demonstrate a decline in 30-day CFRs over time, but did show a nonsignificant decrease in 5-year CFR. Among IS patients, female sex was associated with a lower 5-year CFR, whereas Black individuals had a lower 30-day CFR but a higher 5-year CFR. For ICH, there was a small increase in both 30-day and 5-year CFR in later study periods, although this did not reach significance in all years. SAH showed a lower 30-day CFR over time but no change in 5-year CFR. Older age was associated with a higher 30-day and 5-year CFR in all subtypes. Discussion: Despite widespread advances in post-stroke care, adjusted 5-year CFR has not clearly improved for any stroke subtype and may have slightly worsened for ICH. 30-day CFR has shown a modest improvement among SAH patients. Future studies should investigate why Black individuals with IS experience lower early CFR but a higher late CFR.

Background: Accurate identification of stroke by EMS is necessary for triage and pre-notification within stroke systems of care. Our objective was to describe disparities in the documentation of stroke as the patient’s chief complaint (CC) by EMS in a large population-based stroke study. Methods: We included physician-adjudicated strokes and TIAs occurring among adults ≥18 years old in 2015 in the GCNKSS study population, based in a 5-county area of Southern Ohio/Northern Kentucky. Strokes in which EMS was not used and events occurring in the hospital, during EMS transport, at an unknown location, or outside the study region were excluded. The documented CC by EMS (stroke/CVA, MI, seizure, fall, weakness/numbness, headache, or other) were compared between race/sex subgroups. Sequential multivariable logistic regression was performed to identify associations between race, sex, and social determinants of health with an EMS-documented stroke CC. Social determinants included living arrangement and census tract social deprivation index (SDI). Results: A total of 1451 stroke/TIA events were included. White women had the highest proportion of EMS-documented stroke CCs (56%), more than Black women (48%), White men (45%), and Black men (42%), (p=0.02). Black race was inversely associated with an EMS-documented stroke CC in initial models but was collinear with SDI and no longer significant when SDI was included. In the full model, age, previous stroke, and living with others were associated with an EMS-documented stroke CC, while SDI and CAD were inversely associated with EMS-documented stroke CCs. (Table) Conclusion: Patients living in census tracts characterized by social deprivation were less likely to have EMS-documented stroke CCs, suggesting differences in either patient or EMS recognition of stroke. Further work is needed to explore potential confounders including EMS protocols and to improve identification of stroke by patients and EMS providers.

Introduction: Hemoglobin concentrations and diffusion weighted imaging (DWI) lesions are separately known to be associated with poor intracerebral hemorrhage (ICH) outcomes. Though hemoglobin concentrations are related to both hypoxia and thrombosis at their extremes, it is unknown whether hemoglobin concentrations relate to DWI lesions after ICH. Methods: Spontaneous, supratentorial ICH patients with available baseline hemoglobin and hospitalized MRI data enrolled into a multicenter cohort study between 2010-2016 were analyzed. Baseline hemoglobin was assessed as both a continuous variable (g/dL) and categorical variable (/=15 g/dL). Primary analyses assessed relationships of baseline hemoglobin with MRI DWI lesions. Secondary analyses assessed independent relationships of hemoglobin and DWI lesions with poor 3-month outcomes (modified Rankin Scale [mRS] 4-6). Separate multivariable regression models assessed these relationships after adjusting for relevant covariates. Results: Of 917 ICH patients analyzed, the mean baseline hemoglobin was 13.8 g/dL (+/-1.9), 60% were deep ICH, and DWI lesions were identified in 27% of the cohort. In our primary analyses, increased hemoglobin, defined as a continuous variable, was associated with DWI lesions (adjusted OR 1.21, 95% CI: 1.07-1.37) after adjusting for sex, race, ICH severity, time to MRI, and blood pressure treatment change. In secondary analyses, DWI lesions were associated with poor 3-month outcomes (adjusted OR 1.83, 95% CI: 1.24-2.69) adjusting for similar covariates. We identified associations of low hemoglobin categories, when referenced to hemoglobin 13 to /=15 g/dL) with poor outcomes were smaller and imprecise (adjusted OR 1.39, 95% CI: 0.89-2.17). Conclusions: We identified novel relationships between higher baseline hemoglobin concentrations and DWI lesions in ICH patients. Further studies are required to clarify the role of hemoglobin concentrations on both cerebral small vessel disease pathophysiology and ICH outcomes.

Background: Intracerebral hemorrhage is the most severe stroke subtype, and extension of blood into the ventricles (IVH) is associated with increased morbidity and mortality. The mechanisms that contribute to poor clinical outcomes are unclear. We set out to establish a novel IVH mouse model for the purpose of measuring motor and cognitive function in acute and chronic stages. Methods: Mice underwent either an autologous blood (40ul; IVH) or normal saline (40 ul; SHAM) injection into a lateral ventricle. Motor function was tested in an open field automated locomotion test at 3- and 7-days post-surgery, and weekly thereafter until 90 days after injection. Anxiety-like behavior was measured using Elevated Plus Maze at 14, 30- and 120-days post injection, and cognitive function was tested using Barnes Maze 30 days post injection. Neuroinflammation was assessed utilizing Iba1+ for activated microglia and GFAP+ immunoreactivity for reactive astrocytes. Adult neurogenesis was assessed at the subventricular and subgranular zones using tamoxifen treated nestin-creER-Ai9-tdTomato mice that were harvested at 30 days post injection. Results: MRI revealed blood in the ventricles up to 7 days post injection; confirmed via histology. Hydrocephalus occurred in the IVH, but not SHAM group (p = 0.04). There was no difference in cognitive function or anxiety-like behavior at any time point post injection. At 30 days, mild astrocyte reactivity was noted near the lateral ventricular wall in the IVH, but not SHAM group. There was no difference in reactive astrocytes between the IVH and SHAM groups in the hippocampus or cortex or newly born immature neurons. Conclusion: While global neuroinflammation was not detected in our novel mouse model of pure IVH, local inflammation continued out to 30 days post IVH. This long-term activation was not accompanied by cognitive deficits, suggesting that the model does not emulate clinical findings, but supports study of local inflammation after IVH.

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:There are significant racial disparities in stroke in the United States, with Black individuals having a higher risk of incident stroke even when adjusted for traditional stroke risk factors. It is unknown whether Black individuals are also at a higher risk of recurrent stroke.Methods:Over an 18-month period spanning 2014-2015, we ascertained index stroke cases within the Greater Cincinnati/Northern Kentucky population of 1.3 million. We then followed all patients for 3 years and determined the risk of recurrence. Multivariable survival analysis was performed to determine the effect of Black race on recurrence.Results:There were 3816 patients with index stroke/TIA events in our study period, and 476 patients had a recurrent event within three years. The Kaplan-Meier estimate of 3-year recurrence rate was 15.4%. Age- and sex-adjusted stroke recurrence rate was higher in Black individuals (HR 1.34, 95% CI 1.1-1.6; p=0.003); however, when adjusted for traditional stroke risk factors including hypertension, diabetes, smoking status, age, and left ventricular hypertrophy, the association between Black race and recurrence was significantly attenuated and became nonsignificant (HR 1.1, 95% CI 0.9-1.36, p=0.32). At younger ages, Black race was more strongly associated with recurrence and this effect may not be fully attenuated by traditional stroke risk factors.Conclusions:Recurrent stroke was more common among Black individuals, but the magnitude of the racial difference was substantially attenuated and became nonsignificant when adjusted for traditional stroke risk factors. Interventions targeting these risk factors could reduce disparities in stroke recurrence.

Background and Purpose: To determine whether obstructive sleep apnea (OSA) is associated with intracerebral hemorrhage (ICH) risk, we assessed premorbid OSA exposure of patients with nontraumatic ICH and matched controls. Methods: Ethnic/Racial Variations of Intracerebral Hemorrhage is a multicenter, case-control study evaluating risk factors for ICH that recruited 3000 cases with ICH and 3000 controls. OSA status was ascertained using the Berlin Questionnaire as a surrogate for premorbid OSA. We performed logistic regression analyses to evaluate the association between OSA and ICH. Results: Two thousand and sixty-four (71%) cases and 1516 (52%) controls were classified as having OSA by the Berlin Questionnaire. Cases with OSA were significantly more likely to be male and have hypertension, heart disease, hyperlipidemia, and higher body mass index compared with those without OSA. OSA was more common among cases compared with controls (71% versus 52%, odds ratio, 2.28 [95% CI, 2.05–2.55]). In a multivariable logistic regression model, OSA was associated with increased risk for ICH (odds ratio, 1.47 [95% CI, 1.29–1.67]). Conclusions: OSA is a risk factor for ICH.

Introduction The risk of intracerebral haemorrhage (ICH) associated with hypertension (HTN) is well documented. While the prevalence of HTN increases with age, the greatest odds ratio (OR) for HTN as a risk for ischemic stroke is at an early age. We sought to evaluate if the risk for ICH from HTN was higher in the youngest patients of each race. Patients and methods The Ethnic/Racial Variations of ICH (ERICH) study is a prospective multicenter case-control study of ICH among whites, blacks, and Hispanics. Participants were divided into age groups based on race-specific quartiles. Cases in each race/age group were compared to controls using logistic regression (i.e., cases and controls unmatched). The probability of ICH among cases and controls for each race were compared against independent variables of HTN, quartile of age and interaction of quartile and age also using logistic regression. Results Overall, 2033 non-lobar ICH cases and 2060 controls, and 913 lobar ICH cases with 927 controls were included. ORs were highest in the youngest age quartile for non-lobar haemorrhage for blacks and Hispanics and highest in the youngest quartile for lobar haemorrhage for all races. The formal test of interaction between age and HTN was significant in all races for all locations with the exception of lobar ICH in whites (p = 0.2935). Discussion Hypertension is a strong independent risk factor for ICH irrespective of location among persons of younger age, consistent with the hypothesis that first exposure to HTN is a particularly sensitive time for all locations of ICH.

Background and Purpose: In intracerebral hemorrhage (ICH), preexisting cognitive impairment has been identified as a risk factor for increased mortality and morbidity. However, previous studies examined predominantly White populations; therefore, the prevalence and effect of preICH cognitive impairment has not been studied in a multiethnic cohort. This limits the generalizability of previous findings. We sought to investigate the role of preexisting cognitive impairment in a multiethnic population on short-term mortality and functional outcomes after ICH. Methods: Patients with ICH were prospectively enrolled as cases for the GERFHS III (Genetic and Environmental Risk Factors for Hemorrhagic Stroke) Study and the Ethnic/Racial Variations of ICH (ERICH) Study. Cognitive impairment before ICH was defined as positive history of dementia or treatment with donepezil, galantamine, memantine, or rivastigmine on chart abstraction or baseline interview. Specific outcomes—modified Rankin Scale score at 3 months (0–2 versus ≥3), Barthel Index score ( Results: Of the 3537 cases of ICH, 304 patients had cognitive impairment predating ICH. Cognitively impaired subjects were more likely to experience withdrawal of care during hospitalization, and for survivors, greater disability (modified Rankin Scale score of ≥3) and lower Barthel scores after ICH. After propensity score matching, preexisting cognitive impairment was associated with a lower modified Rankin Scale at 3 months in the White, Black, and Hispanic subgroups. Conclusions: Preexisting cognitive impairment was associated with loss of independence 3-month post-ICH, when matching for risk factors of cognitive impairment, in the White, Black, and Hispanic subgroups. This suggests that preexisting cognitive impairment has a negative effect in obtaining functional independence following ICH, irrespective of race/ethnicity.

Background In patients with spontaneous intracerebral hemorrhage (ICH), pre-hospital markers of disease severity might be useful to potentially triage patients to undergo early interventions. Objective Here, we tested whether loss of consciousness (LOC) at the onset of ICH is associated with intraventricular hemorrhage (IVH) on brain computed tomography (CT). Methods Among 3000 ICH cases from ERICH (Ethnic/Racial Variations of Intracerebral Hemorrhage study, NS069763), we included patients with complete ICH/IVH volumetric CT measurements and excluded those with seizures at ICH onset. Trained investigators extracted data from medical charts. Mental status at symptom onset (categorized as alert/oriented, alert/confused, drowsy/somnolent, coma/unresponsive/posturing) and 3-month disability (modified Rankin score, mRS) were assessed through standardized interviews of participants or dedicated proxies. We used logistic regression and mediation analysis to assess relationships between LOC, IVH, and unfavorable outcome (mRS 4–6). Results Two thousand seven hundred and twenty-four patients met inclusion criteria. Median admission Glasgow Coma Score was 15 (interquartile range 11–15). 46% had IVH on admission or follow-up CT. Patients with LOC (mental status: coma/unresponsive, n = 352) compared to those without LOC (all other mental status, n = 2372) were younger (60 vs. 62 years, p = 0.005) and had greater IVH frequency (77 vs. 41%, p p p p Conclusion LOC at ICH onset may be a useful pre-hospital marker to identify patients at risk of having or developing IVH.

INTRODUCTION: We sought to determine the feasibility and validity of estimating post-stroke outcomes using information available in the electronic medical record (EMR) through comparison with outcomes obtained from telephone interviews. METHODS: The Greater Cincinnati Northern Kentucky Stroke Study is a retrospective population-based epidemiology study that ascertains hospitalized strokes in the study region. As a sub-study, we identified all ischemic stroke patients who presented to a system of 4 hospitals during the study period 1/1/2015–12/31/2015 and were discharged alive. Enrolled subjects (or proxies for cognitively-disabled patients) were contacted by telephone at 3 and 6 months post-stroke to determine current place of residence and two functional outcomes—the modified Rankin Score (mRS) and the EuroQol (EQ-5D). Concurrently, the lead study coordinator, blinded to the telephone assessment outcomes, reviewed all available EMRs to estimate outcome status. Agreement between outcomes estimated from the EMR with “gold-standard” data obtained from telephone interviews was analyzed using the kappa statistic or interclass correlation (ICC), as appropriate. For each outcome, EMR-determined results were evaluated for added value beyond the information readily available from the stroke hospital stay. RESULTS: Of 381 ischemic strokes identified, 294 (median [IQR] age 70 [60–79] years, 4% black, 52% female) were interviewed post-stroke. Agreement between EMR and telephone for 3-month residence was very good (kappa=0.84, 95% CI 0.74–0.94), good for mRS (weighted kappa=0.75, 95% CI 0.70–0.80), and good for EQ-5D (ICC=0.74, 95% CI 0.68–0.79). Similar results were observed at 6 months post stroke. At both 3 and 6 months post stroke, EMR-determined outcomes added value in predicting the gold standard telephone results beyond the information available from the stroke hospitalization; the added fraction of new information ranged from 0.25 to 0.59. CONCLUSIONS: Determining place of residence, mRS, and EQ-5D outcomes derived from information recorded in the EMR post-stroke, without patient contact, is feasible and has good agreement with data obtained from direct contact. However, we note that the level of agreement for mRS and EQ-5D was higher for proxy interviews and that the EMR often reflects health care providers’ judgments that tend to overestimate disability and underestimate quality of life.

BackgroundIntracerebral hemorrhage (ICH), the most fatal form of stroke, has an estimated heritability of 29%. Applying a meta-scoring approach, we developed a genomic risk score for ICH and determined its predictive power in comparison to standard clinical risk factors.MethodsUsing a meta-analytic approach, we combined genome-wide association data from individuals of European ancestry for ICH and ICH-related traits in a meta-genomic risk score (metaGRS) consisting of 2.6 million variants. We tested associations with ICH and the predictive performance of the metaGRS in addition to clinical risk factors in a held-out validation dataset (842 cases and 796 controls). Furthermore, we tested associations with risk of incident ICH in the population-based UK Biobank cohort (486,784 individuals, 1,526 events, median follow-up 11.3 years).ResultsOne SD increment in the metaGRS was significantly associated with 45% higher odds for ICH (OR 1.45; 95%CI: 1.30-1.63) in age- and sex-adjusted models and 31% higher odds for ICH (OR: 1.31, 95%CI: 1.16-1.48) in models further adjusted for clinical risk factors. The metaGRS identified individuals with almost 5-fold higher odds for ICH in the top score percentile (OR: 4.83, 95%CI: 1.56-21.2). Predictive models for ICH incorporating the metaGRS in addition to clinical predictors showed superior performance compared with clinical risk factors alone (c-index: 0.695 vs. 0.686). The metaGRS showed similar associations for both lobar and non-lobar ICH, which were independent of the known APOE risk locus for lobar ICH. In the UK Biobank, the metaGRS was associated with higher risk of incident ICH (HR: 1.15, 95%CI: 1.09-1.21). The associations were significant within both a relatively high-risk population of users of antithrombotic medications, as well as among a relatively low-risk population with a good control of vascular risk factors and no use of anticoagulants.ConclusionsWe developed and validated a genomic risk score that predicts lifetime risk of ICH beyond established clinical risk factors among individuals of European ancestry. Whether implementation of the score in risk prognostication models for high-risk populations, such as patients under antithrombotic treatment, could improve clinical decision making should be explored in future studies.

ObjectiveTo test the hypothesis that thrombogenic atrial cardiopathy may be relevant to stroke-related racial disparities, we compared atrial cardiopathy phenotypes between Black vs White patients with ischemic stroke.MethodsWe assessed markers of atrial cardiopathy in the Greater Cincinnati/Northern Kentucky Stroke Study, a study of stroke incidence in a population of 1.3 million. We obtained ECGs and reports of echocardiograms performed during evaluation of stroke during the 2010/2015 study periods. Patients with atrial fibrillation (AF) or flutter (AFL) were excluded. Investigators blinded to patients' characteristics measured P-wave terminal force in ECG lead V1 (PTFV1), a marker of left atrial fibrosis and impaired interatrial conduction, and abstracted left atrial diameter from echocardiogram reports. Linear regression was used to examine the association between race and atrial cardiopathy markers after adjustment for demographics, body mass index, and vascular comorbidities.ResultsAmong 3,426 ischemic stroke cases in Black or White patients without AF/AFL, 2,391 had a left atrial diameter measurement (mean, 3.65 ± 0.70 cm). Black race was associated with smaller left atrial diameter in unadjusted (β coefficient, −0.11; 95% confidence interval [CI], −0.17 to −0.05) and adjusted (β, −0.15; 95% CI, −0.21 to −0.09) models. PTFV1 measurements were available in 3,209 patients (mean, 3,434 ± 2,525 μV*ms). Black race was associated with greater PTFV1 in unadjusted (β, 1.59; 95% CI, 1.21–1.97) and adjusted (β, 1.45; 95% CI, 1.00–1.80) models.ConclusionsWe found systematic Black–White racial differences in left atrial structure and pathophysiology in a population-based sample of patients with ischemic stroke.Classification of EvidenceThis study provides Class II evidence that atrial cardiopathy phenotypes differ in Black people with acute stroke compared to White people.

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.

Background and Purpose— Selective serotonin reuptake inhibitors (SSRIs) have a well-established association with bleeding complications and conflicting reports on outcome after stroke. We sought to evaluate whether pre–intracerebral hemorrhage (ICH) SSRI use increased ICH risk and post-ICH SSRI use improved ICH outcome. Methods— Through post hoc analysis of the ERICH study (Ethnic/Racial Variations of Intracerebral Hemorrhage), SSRI use was categorized into no use, pre-ICH only, pre- and post-ICH use (termed “continuous”), and post-ICH only (termed “new”). Using multivariable modeling, associations were sought between pre-ICH SSRI use and ICH risk in the case-control set, and associations between post-ICH SSRI use and 3-month outcome were analyzed in the ICH case set. Exploratory analyses sought to assess influence of race/ethnicity in models. Results— The final study cohort consisted of 2287 ICH cases and 2895 controls. Pre-ICH SSRI use was not associated with ICH risk (odds ratio, 0.824 [95% CI, 0.632–1.074]) nor potentiation of ICH risk with anticoagulant or antiplatelet use. New post-ICH SSRI use was associated with unfavorable modified Rankin Scale score at 3 months after ICH (odds ratio, 1.673 [95% CI, 1.162–2.408]; P =0.006) in multivariable analyses. Additional propensity score analysis indicated a similar trend but did not reach statistical significance ( P =0.107). When stratified by race/ethnicity, multivariable modeling demonstrated reduced ICH risk with pre-ICH SSRI use in Hispanics (odds ratio, 0.513 [95% CI, 0.301–0.875]; P =0.014), but not non-Hispanic whites or blacks, and no associations between post-ICH SSRI use and 3-month outcome in any racial/ethnic group. Conclusions— In a large multiethnic cohort, pre-ICH SSRI use was not associated with increased ICH risk, but post-ICH SSRI use was associated with unfavorable 3-month neurological outcome after ICH. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01202864.

Background and Purpose— Volumes of hemorrhage and perihematomal edema (PHE) are well-established biomarkers of primary and secondary injury, respectively, in spontaneous intracerebral hemorrhage. An automated imaging pipeline capable of accurately and rapidly quantifying these biomarkers would facilitate large cohort studies evaluating underlying mechanisms of injury. Methods— Regions of hemorrhage and PHE were manually delineated on computed tomography scans of patients enrolled in 2 intracerebral hemorrhage studies. Manual ground-truth masks from the first cohort were used to train a fully convolutional neural network to segment images into hemorrhage and PHE. The primary outcome was automated-versus-human concordance in hemorrhage and PHE volumes. The secondary outcome was voxel-by-voxel overlap of segmentations, quantified by the Dice similarity coefficient (DSC). Algorithm performance was validated on 84 scans from the second study. Results— Two hundred twenty-four scans from 124 patients with supratentorial intracerebral hemorrhage were used for algorithm derivation. Median volumes were 18 mL (interquartile range, 8–43) for hemorrhage and 12 mL (interquartile range, 5–30) for PHE. Concordance was excellent (0.96) for automated quantification of hemorrhage and good (0.81) for PHE, with DSC of 0.90 (interquartile range, 0.85–0.93) and 0.54 (0.39–0.65), respectively. External validation confirmed algorithm accuracy for hemorrhage (concordance 0.98, DSC 0.90) and PHE (concordance 0.90, DSC 0.55). This was comparable with the consistency observed between 2 human raters (DSC 0.90 for hemorrhage, 0.57 for PHE). Conclusions— We have developed a deep learning-based imaging algorithm capable of accurately measuring hemorrhage and PHE volumes. Rapid and consistent automated biomarker quantification may accelerate powerful and precise studies of disease biology in large cohorts of intracerebral hemorrhage patients.

ObjectivesWe investigated the predictors of functional outcome in young patients enrolled in a multiethnic study of intracerebral hemorrhage (ICH).MethodsThe Ethnic/Racial Variations in Intracerebral Hemorrhage (ERICH) study is a prospective multicenter study of ICH among adult (age ≥18 years) non-Hispanic white, non-Hispanic black, and Hispanic participants. The study recruited 1,000 participants per racial/ethnic group. The present study utilized the subset of ERICH participants aged ResultsOf the 3,000 patients with ICH enrolled in ERICH, 418 were studied (mean age 43 years, 69% male), of whom 48 (12%) were white, 173 (41%) were black, and 197 (47%) were Hispanic. For supratentorial ICH, black participants (odds ratio [OR], 0.42; p = 0.046) and Hispanic participants (OR, 0.34; p = 0.01) had better outcomes than white participants after adjustment for other factors associated with poor outcome: age, baseline disability, admission blood pressure, admission Glasgow Coma Scale score, ICH volume, deep ICH location, and intraventricular extension.ConclusionsIn young patients with supratentorial ICH, black and Hispanic race/ethnicity is associated with better functional outcomes, compared with white race. Additional studies are needed to identify the biological and social mediators of this association.

Background: We report contemporary trends in nationwide incidence of intracerebral hemorrhage (ICH) across demographic and regional strata over a 15-year period. Methods: Utilizing the Nationwide Inpatient Sample (2004–2018) and US Census Bureau data, we calculated ICH incidence rates for age, race/ethnicity, sex, and hospital region sub-cohorts across 5 consecutive 3-year periods (2004–2006 to 2016–2018). We fit Poisson and log binomial regression models to evaluate demographic and regional differences in ICH incidence and trends in prevalence of hypertension and past/current anticoagulant use among hospitalized ICH patients. Results: Overall, the annual incidence rate (95% CI) of ICH per 100 000 was 23.15 (23.10–23.20). The 3-year incidence of ICH (per 100 000) increased from 62.79 in 2004 to 2006 to 78.86 in 2016 to 2018 (adjusted incidence rate ratio, CI: 1.11 [1.02–1.20]), coinciding with increased 3-year prevalence of hypertension and anticoagulant use among hospitalized ICH patients (adjusted risk ratio, CI: hypertension—1.16 [1.15–1.17]; anticoagulant use—2.30 [2.14–2.47]). We found a significant age-time interaction, whereby ICH incidence increased significantly faster among those aged 18 to 44 years (adjusted incidence rate ratio, CI: 1.10 [1.05–1.14]) and 45 to 64 years (adjusted incidence rate ratio, CI: 1.08 [1.03–1.13]), relative to those aged ≥75 years. Conclusions: Rising ICH incidence among young and middle-aged Americans warrants ICH prevention strategies targeting these economically productive age groups.

Background: In acute stroke, reducing delays between symptom onset and treatment can improve outcomes. While in-hospital delays have been successfully reduced, pre-hospital delays have persisted. Public health campaigns have attempted to reduce these delays by increasing stroke symptom awareness, but it is unknown whether these efforts have improved the percentage of patients presenting early after symptom onset. Methods: We performed an analysis of the Greater Cincinnati/Northern Kentucky Stroke Study, a population-based study of all stroke patients in a large geographic area. We looked at the 2010 and 2015 study years. All stroke cases (ischemic and hemorrhagic) presenting to the 16 regional EDs were included. We examined the time between symptom onset and ED arrival times, dichotomized into ≤3.5 hours and >3.5 hours. In cases without a clear onset, estimates were derived using wake-up or last known well times. Comparisons were made using multivariable logistic regression. Results: Among 4633 total stroke patients, 1359 patients presented early (29%). Results of the multivariable analysis are shown in the Table . There was no improvement the rate of early presentation in 2015 (aOR 1.01, 95% CI 0.89-1.16). EMS utilization, night arrival, higher NIHSS scores, and better premorbid function were associated with early arrival. Patients who lived alone were less likely to arrive early. Conclusion: We found no evidence for improvement in the rate of early presentation over the years studied. Work is needed to address other barriers to early hospital arrival, including underutilization of EMS.

Introduction: Stroke is a major cause of balance and walking impairment and is on the rise. The most widely used walking impairment measure is the 10-meter walk test (10-mWT), which provides information about walking speed but does not inform about walking kinematics or neuromuscular control. Objective: Herein, we evaluate single support center of pressure distance (SS CoP Dist), a kinematic measure of dynamic postural control and walking stability, as a complementary measure of walking impairment. We hypothesize that SS CoP Dist will be closely associated with baseline walking speed, and will improve with Backward Locomotor Treadmill Training (BLTT). Methods: Thirty-six chronic stroke survivors with residual walking impairment, based on 10-mWT speed [ mild >0.8 m/s (n =7); moderate 0.4-0.8m/s (n =18); and severe Results: At baseline, there was a weak to moderate positive relationship between walking speed and SS CoP Dist (R 2 paretic = 0.22, p = 0.0036; R 2 Nonparetic = 0.44, p < 0.0001). Following BLTT, SS COP Dist increased (more stable) in the mild and moderate groups [mild paretic ( p = 0.0039)/mild Nonparetic ( p = 0.0034) , moderate paretic ( p = 0.0360)/ moderate Nonparetic ( p = 0.0087)], with improved interlimb symmetry in the mild group. In contrast, no significant improvement in SS CoP Dist was seen in participants with severe walking impairment ( p = 0.3830). Training-related changes in walking speed were strongly correlated with change in SS CoP Dist (R 2 Nonparetic = 0.54, p = 0.0007). Conclusion: Our preliminary findings suggest that SS CoP Dist compliments walking speed for characterizing walking severity and response to training in chronic stroke survivors. In addition, BLTT significantly improved SS CoP Dist in mild-moderately impaired stroke survivors but not in survivors with severe walking impairment. Future well-powered, prospective studies with BLTT and other training paradigms are needed to validate these findings.

Background: Acute ischemic stroke (AIS) is a leading cause of disability worldwide, with up to 30% of cases preceded by transient ischemic attack (TIA). Urgent evaluation of TIA symptoms is recommended to reduce risk of stroke, but not all patients with TIA symptoms seek evaluation. Our goal was to assess temporal trends in the demographics of such patients. Methods: Using the Greater Cincinnati/Northern Kentucky Stroke Study (GCNKSS) for years 2005, 2010, and 2015, we selected patients with a diagnosis of AIS using ICD-9/10 codes in adults ≥18yrs of age presenting to the ED. We identified patients who had a preceding TIA based on symptoms within 60 days of presentation, as judged by an adjudicating physician. Demographics, histories, and proportion of patients with TIA were compared across study years using Wilcoxon rank sum test or chi-square test. Results: We identified 5977 patients presenting with AIS across three epochs. Of these 207 (3%) had prior suspected TIA and did not seek immediate medical attention; 56/1790 (3%) in 2005, 62/1993 (3%) in 2010, and 70/2194 (3%) in 2015 (p-value=0.99). Patients with suspected TIA had increasing rates of previously diagnosed HLD and DM over the three time periods. No other risk factors or demographics showed a change over time. Known HTN was consistently prevalent across epochs (Table 2). Conclusion: Over the three epochs, 3% of AIS patients consistently did not seek emergent medical attention for a recent preceding TIA. A substantial proportion of these patients were increasingly already diagnosed with DM and HLD over the study periods, and the majority were persistently diagnosed with HTN. This is an opportune cohort for future targeted outreach.

Background: Intracerebral hemorrhage (ICH) patients may appear disabled despite intact cortical spinal tracts (CST). ICH lesions may also vary in volume and location relative to the CST with differential impacts on motor outcome. In this study, we evaluated whether diffusion tensor imaging (DTI) integrity of CST fiber tracking associates with mobility three months post ICH. Methods: The Recovery and Outcomes from StrokE (ROSE) Study is a prospective, multi-center study of ICH serially assessed with motor, cognitive, and functional outcomes and MRI/DTI. Outcome data were collected by hospital chart review and interview/exam. Acute MRI images were analyzed by a central neuroimaging core for ICH location, size, intraventricular hemorrhage, and fractional anisotropy (FA) derived from DTI of the CST. Mobility was assessed at 3-month follow-up using the Barthel Mobility Index. We computed single variable logistic regression analyses (outcome = Barthel mobility at 3 months). We also computed a stepwise logistic model, with and without age, sex, and race, including variables that met P Results: There were 76 ICH patients with DTI FA data available for analysis; 61 with complete data for the multivariate model. Poor mobility after ICH (N = 21; 27.6%) was associated with ICH volume, presence of IVH, Glasgow coma score, ipsilesional CST FA, ipsilesional CP FA and CP FA asymmetry index (Table 1). The multivariate model that adjusted for age, sex, and race identified ipsilesional CP FA, admission GCS and presence of IVH as associated with poor mobility at 3 months; notably, log ICH volume was not associated after controlling for CST injury (Table 1). Conclusions: The presence of IVH and the GCS score at baseline were associated with poor mobility. In addition, the CP FA asymmetry index was independently associated with poor mobility even after accounting for log ICH volume, suggesting that DTI is informative of outcome beyond classic ICH outcome predictors.

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: Disparities in acute ischemic stroke (IS) care due to patients’ pre-stroke disabilities remain understudied. Using the Greater Cincinnati Northern Kentucky (GCNK) Stroke Study, we aimed to understand the differences in acute stroke presentation and care according to patients’ pre-stroke functional status. Methods: We ascertained all hospitalized IS patients ≥18 years old presenting to emergency departments in the GCNK region in 2015 using ICD-9 430-436; ICD-10 I60-I67, G45-G46; all cases were physician-reviewed. Trained nurses ascertained pre-stroke functional status from the medical record. Acute IS presentation, time metrics, and treatment were compared between patients with pre-stroke mRS 0-1 vs ≥2 using Wilcoxon rank-sum or chi-square tests. Logistic regression was used to evaluate the association between pre-stroke mRS and intravenous thrombolysis (IVT) and endovascular treatment adjusting for age, presenting NIHSS, time to presentation, and baseline anticoagulation use. Results: Of 2191 patients with IS, 1134 had a pre-stroke mRS ≥2. Patients in the latter group were older, more likely be female, had higher rates of medical comorbidities, had higher presenting NIHSS (3[1-8] vs 2[1-5], p Conclusions: Acute IS patients with pre-stroke disability presented later, with more severe strokes, and were less likely to receive reperfusion treatments. Further research into factors driving acute stroke medical decision-making for patients with a pre-stroke disability is needed to ensure optimal acute neurovascular care for all IS patients across the nation and worldwide.

Background: Antithrombotic medications (AT) are often withheld before procedures to reduce risk of bleeding. In 2005, members of our team reported that 5.2% of ischemic strokes were associated with the withdrawal of AT in the preceding 60 days. Subsequently, new medications, including DOACs, have become widely used. Given changing prescription and practice patterns we sought to compare rates of stroke in the setting of antithrombotic withdrawal in 2010 and 2015. Methods: The GCNKSS is a population-based stroke study from the Greater Cincinnati region. In 2005, 2010, and 2015, we captured all strokes in the Greater Cincinnati/Northern Kentucky 5 county area by screening ICD9 codes 430-436 and ICD10 (2015) codes I60-I68, and G45-46. Study nurses abstracted all cases and physicians adjudicated each event. Data regarding the withdrawal of AT and timing were captured. 2005 data was included as a reference. Fisher’s exact test was used to examine differences by years. Results: In 2010 and 2015, 4768 cases of ischemic stroke were identified. Across the study periods, those that were on AT at time of stroke versus those who stopped AT Conclusions: The withdrawal of AT is associated with 228 (4.8%) of ischemic strokes within 60 days in our study population. These rates remain consistent across our study periods. This highlights that despite new agents, stroke in the setting of AT withdrawal remains consistent and the decision to stop AT must be carefully considered.

Introduction: Disparities exist in acute ischemic stroke care according to patients’ pre-stroke functional status. However, the effects of baseline disability on the presentation and care of patients with intracerebral hemorrhage (ICH) are unknown. We aimed to understand this using the Greater Cincinnati Northern Kentucky (GCNK) Stroke Study. Methods: We ascertained all hospitalized ICH patients ≥18 years old in 2015 using ICD-9 430-436; ICD-10 I60-I67, G45-G46 GCNK) population; all cases were physician-reviewed. Per-stroke functional status was ascertained by medical record review. Baseline NIHSS, Glasgow coma scale (GCS), imaging modalities (CT/MRI), in-hospital rehabilitative therapies (rate and frequency), initiation of antihypertensive treatment, and discharge disposition between patients with pre-ICH mRS 0-1 vs ≥2 were compared using Wilcoxon rank-sum or chi-square tests. Logistic regression was used to evaluate the association between pre-stroke mRS and in-hospital therapy, post-discharge therapy, and ICH workup adjusting for age, Glasgow score, insurance status, and ICH location. Results: Of 350 patients with ICH, 187 (53%) had a pre-ICH mRS ≥2. Compared to those with pre-stroke mRS 0-1, these patients had more severe clinical presentation as measured by NIHSS and GCS (table). Among patients who were not made comfort care, no association between pre-ICH mRS and performance of inpatient MRI or in-hospital and post-discharge rehabilitative therapies was found in adjusted analyses. Conclusions: Patients with pre-ICH mRS >2 were made comfort care at a higher rate, but for those not made comfort care there were no post-ICH disparities of care seen in the 2015 GCNK population-based cohort of 350 patients.

Background: Prior studies have demonstrated a rising incidence of infective endocarditis related stroke (IERS) in the US due to the opioid epidemic. The Greater Cincinnati/Northern Kentucky (GCNK) region has one of the highest opioid abuse rates in the nation. A modern epidemiologic description is necessary to understand the impact of the opioid epidemic on the clinical phenotype of IERS. Methods: Using the GCNK Stroke Study, all patients hospitalized with IERS in 2005, 2010, and 2015 were abstracted and physician reviewed. IERS was defined as an acute stroke clinically attributed to infective endocarditis in patients meeting modified Duke Criteria for possible or definite endocarditis. Comparison between years were by chi-square or Fisher’s exact test for categorical variables; ANOVA or Kruskal-Wallis test for numerical variables. Cochran-Armitage test was used to examine trend. Secondary analysis compared characteristics between intravenous drug users (IVDU) and non-IVDU. Results: A total of 54 patients with IERS were identified in 2005, 2010, and 2015. Over the period, there was a significant decline in hypertension (91.7% in 2005, 36.0% in 2015; p=0.0005) and increase in IVDU (8.3% in 2005, 44.0% in 2015; p=0.02). They trended towards increased white race, younger age, and fewer vascular risk factors. Compared to non-IVDU, IVDU were significantly younger (41.1±14.1vs 63.1±14.3 years; p Conclusion: From 2005 to 2015, IERS was increasingly associated with IVDU and an absence of hypertension. These trends likely reflect the demographics of the opioid epidemic, which has affected younger patients with less comorbidities.

Background: The evidence of association between Intracerebral Hemorrhage (ICH) outcomes and hypercholesterolemia (HC) is equivocal. We provide nationwide estimates of ICH in-hospital mortality (IHM) among patients with HC, across race/ethnicity subgroups. Methods: In a pooled cross-sectional analysis of adult (≥ 18 years) primary ICH patients in the National Inpatient Sample (2004 - 2018), we used ICD 9 / 10 codes to identify patients with HC. We fit survey design multivariable logistic regression models to provide nationwide estimates of the association between IHM and HC as adjusted odds ratio (aOR) and 95% confidence interval (CI). Results: Among a total of 803,230 ICH hospitalizations, we identified 56,635 HC ICH patients. HC patients, compared to patients with no hypercholesterolemia (NHC), were older (72.3 vs. 68.7 years), had higher proportional (%) burden of diabetes (35.8 vs. 26.4), hypertension (90.0 vs. 80.9), obesity (9.2 vs. 8.0), atrial fibrillation (22.1 vs. 19.3) and past / current use of anticoagulation (11.9 vs. 9.8). However, HC patients (vs. NHC) were less likely to have extreme loss of function (21.4 vs. 28.7) or receive invasive treatment, including extra-ventricular drain (5.2 vs. 7.6), invasive ventilation (5.7 vs. 7.9), tracheostomy (2.4 vs. 4.2) and gastric tube placement (6.0 vs. 8.5). Overall, and non-Hispanic whites (NHW), non-Hispanic black and Hispanic, HC patients (vs. NHC) had lower IHM (aOR, CI for overall effect: 0.85, 0.81 - 0.90) (Figure 1). The HC - IHM association was significantly modified by age among NHW, whereby the likelihood of IHM among HC (vs. NHC) significantly increased with advancing age (aOR, CI: 1.01, 1.00 - 1.02) (Figure 2). Conclusion: HC is associated with lower ICH severity and IHM, albeit with significant race/ethnic variations. Further evaluation of potential role of genetic, environmental and treatment factors, across race/ethnicity sub-groups, in the relationship between HC and ICH outcomes is warranted.

Background: Elevated cardiac troponin (cTn) levels are frequently encountered after intracerebral hemorrhage (ICH). In small cohorts, increased cTn was associated with in-hospital mortality. This study investigated the factors associated with elevated cTn in ICH cases and its relationship with outcome. Methods: We examined maximum cTn levels within 48 hours of hospital arrival in subjects enrolled in the Ethnic Racial Variations of Intracerebral Hemorrhage (ERICH) study. ERICH is a multi-center prospective study designed to examine ethnic variations in the risk, presentation, and outcomes of ICH. Elevated troponins were defined as cTn>0.1 mg/dL. Poor outcome was defined as modified Rankin Scale (mRS)≥3 at 3 months. We used logistic regression analysis with backward elimination to identify factors associated with elevated cTn levels and their relationship with poor outcome. The model included baseline demographics and clinical characteristics with at least weak association at baseline (p Results: Of the 2061 included in the analysis, 39% were females and 177 (9.4%) had elevated cTn levels. The sample was 31% white, 33% Hispanic, and 36% black. In univariate analysis, blacks, prior use of opioids or marijuana, low Glasgow coma scale (GCS) on admission, and presence of intraventricular hemorrhage (IVH) were associated with elevated cTn (p3 at 3 months (OR=2.17, 95% CI 1.43-3.30). Conclusion: Elevated cardiac troponin was associated with worse 3 month outcome independent of ICH severity. Surprisingly, sympathomimetic drug use was not associated with peak troponin while opiate and marijuana use were. Our results suggest the need to understand why blacks may have a greater susceptibility to myocardial injury after ICH.

Introduction: Ischemic lesions seen on diffusion weighted imaging (DWI) are associated with worsened outcomes after intracerebral hemorrhage (ICH) and are thought to arise due to microvascular damage. While hyperglycemia and diabetes mellitus contribute to small vessel disease, it is not known if these factors contribute to the development of DWI lesions and associated outcomes after ICH. Hypothesis: Indicators of diabetes/hyperglycemia will be associated with the development of DWI lesions and poor outcomes after ICH Methods: 1123 patients with MRI data from the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study were included. Predictors with p Results: In univariate analysis, no measure of diabetes or hyperglycemia (medical history of diabetes, insulin or non-insulin antidiabetic medication use, blood glucose obtained by emergency medical services, blood glucose on admission, fasting blood glucose, or hemoglobin A1c) was associated with the development of DWI lesions (p>0.05). Blood glucose on admission was incorporated into the initial multivariable model (p3) showed that history of diabetes (p Conclusions: While diabetes and hyperglycemia are associated with worsened outcomes after ICH, this relationship is unexpectedly not mediated by microinfarcts despite their association with cerebral small vessel disease.

Background: Anticoagulant-associated intracerebral hemorrhage (AA-ICH) quintupled in the Greater Cincinnati/Northern Kentucky (GC/NK) region from 1988 to 1999 in association with increasing warfarin use. Direct-acting oral anticoagulants (DOACs), available in 2010, have evidence of less bleeding risk, while atrial fibrillation detection rates have increased. We sought to determine if rates of AA-ICH continued to increase in the last decade within a large, bi-racial population. Methods: We identified all patients, 20 years or older, hospitalized with first-ever intracerebral hemorrhage (ICH) in GC/NK region in 1993/4, 1999, 2005, 2010 and 2015. AA-ICH was defined as ICH in patients prescribed warfarin, heparin or low molecular weight heparin, or a DOAC at the time of their ICH. Incidence rates were age-, sex- and race-adjusted to the 2010 US population. Change over time was tested using regression. All-cause case fatality was adjusted for age, sex and race and trend over time evaluated using a general linear model. Results: There was no significant change over time in the incidence rate for total ICH or AA-ICH from 1993 through 2015 (Table). As compared to ICH patients without anticoagulant use, patients with AA-ICH were more likely to be older, white, have hypertension, diabetes mellitus, hyperlipidemia, prior ischemic stroke and atrial fibrillation, but less likely to smoke. The age-, sex- and race-adjusted 30-day case fatality for ICH overall and AA-ICH also did not change significantly from 1993/4 to 2015 (Table). Warfarin utilization increased in our ICH population from 1993/4 (7.6%) to 2005 (17.7%), then decreased through 2015 (11.8%/DOAC 6.4%); p Conclusion: Despite increased incidence rates of AA-ICH in the late 1980s to 1990s, we observed no overall change in incidence or case-fatality rate from AA-ICH over the full 20-year period despite higher rates of atrial fibrillation detection which may be explained by higher rates of DOAC (vs warfarin) use.

Introduction: Endovascular (EVT) eligibility estimates using population-based, NIH-funded Greater Cincinnati Northern Kentucky (GCNK) Stroke Study 2010 data have been reported. Given the evolving EVT landscape, we present updated estimates of annual EVT eligibility using the 2015 GCNK epidemiological data and extrapolate to the 2021 US census. We project the potential increase in eligible patients in the US for each possible expanded indication with a randomized trial currently planned/underway. Methods: We ascertained all hospitalized AIS patients ≥18 years old in 2015 using ICD-9 430-436; ICD-10 I60-I67, G45-G46 within GCNK population; all cases were physician-reviewed. Patients presenting within 0-5 hrs of last known well (LKW) were considered EVT eligible if they had a pre-stroke mRS1 (for 0-5 hrs) or ≥2 (for 5-23 hrs), or larger core. Estimates of vessel occlusion and favorable imaging were applied based on literature review and expert opinions. The derived estimates were age, race and sex-adjusted to the 2015 US adult population and extrapolated to 2021 population. Results: Among the 1.3 million total (1.05m adult) GCNK population in 2015, 2741 adults had an ischemic stroke and 2176 had data available for this analysis. A total of 1978 presented within 23 hrs of LKW, and 1233 within 0-5 hrs of LKW. Further results are outlined in the figure. Conclusions: It is estimated 18,484 adult patients in the US in 2021 meet strict EVT eligibility criteria. An estimated 15,699 patients with low NIHSS, 9621 with unfavorable imaging, and 28,107 with pre-stroke disability may become eligible for EVT in the future annually. US stroke systems should be optimized to handle all EVT-eligible stroke patients both now and in the future.

Background: Posterior circulation strokes (PCS) make up 20% of all strokes, yet there is poor understanding of what factors contribute to poor clinical outcomes. We investigated clinical and demographic characteristics associated with poor clinical outcomes in PCS using a population-based biracial cohort. Methods: Greater Cincinnati Northern Kentucky Stroke Study (GSNKSS) 2010 and 2015 data was utilized to identify 1842 patients who were >20 years old with MRI-proven PCS. Eligible patients were then stratified based on functional outcomes (modified Rankin Scale/= 3, with >= 3 considered poor) according to demographics, stroke risk factors, tPA treatment, stroke location, and stroke mechanism. A multivariable logistic model was used to identify the predictors for poor functional outcomes. Results: Age, higher NIHSS, higher baseline mRS, hypertension, temporal, thalamus, and brainstem location, and cardioembolic mechanism were associated with poor clinical outcomes (Table). After multivariable analysis, age, higher NIHSS, higher baseline mRS, hypertension, temporal, thalamus, and brainstem location, and cardioembolic mechanism remained associated with poor outcomes. Conclusion: Understanding these factors associated with poor prognosis after posterior circulation stroke will allow for better prognostication and family counseling.