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Introduction: No proven treatments exist for intracerebral hemorrhage (ICH). Carefully selected patients may benefit from surgery, and an international multicenter trial is ongoing. We sought to determine how many patients in a population-based ICH cohort would have been eligible for surgery using the Surgical Trial in Intracerebral Hemorrhage II (STICH II) criteria.Methods: We identified all patients aged > or =18 years residing in the five-county Greater Cincinnati region who were hospitalized with first-ever nontraumatic ICH in 2005. STICH II trial criteria were used to determine eligibility for treatment and reasons for exclusion.Results: During 2005, 286 ICH patients were identified (103 lobar, 126 deep cerebral, 23 brainstem, 28 cerebellar, and 6 IVH). Non-lobar hemorrhages are not eligible for STICH II. Among patients with lobar hemorrhage, 22 had no exclusions. The most common (not mutually exclusive) reasons for exclusion were volume <10 cc or >100 cc (n = 46) and presence of IVH (n = 27). No significant age, gender or racial differences existed between eligible and ineligible patients with lobar ICH. Only one (4.5%) of the 22 STICH II eligible patients in our population had surgery, compared with eight of 81 (9.9%) ineligible lobar ICH patients (P = 0.43). Mortality at 180 days in STICH II eligible patients was 36% vs. 49% for ineligible lobar ICH patients (P = 0.19).Conclusions: In this population-based ICH cohort, 7.7% (22 of 286) of ICH patients would have qualified for STICH II enrollment. Other treatment options need to be explored for most ICH patients. [ABSTRACT FROM AUTHOR]

Objective: Diabetes is a well known risk factor for stroke, but the impact of diabetes on stroke incidence rates is not known. This study uses a population-based study to describe the epidemiology of ischemic stroke in diabetic patients.Research Design and Methods: Hospitalized cases were ascertained by ICD-9 discharge codes, prospective screening of emergency department admission logs, and review of coroner's cases. A sampling scheme was used to ascertain cases in the out-of-hospital setting. All potential cases underwent detailed chart abstraction by study nurses followed by physician review. Diabetes-specific incidence rates, case fatality rates, and population-attributable risks were estimated.Results: Ischemic stroke patients with diabetes are younger, more likely to be African American, and more likely to have hypertension, myocardial infarction, and high cholesterol than nondiabetic patients. Age-specific incidence rates and rate ratios show that diabetes increases ischemic stroke incidence at all ages, but this risk is most prominent before age 55 in African Americans and before age 65 in whites. One-year case fatality rates after ischemic stroke are not different between those patients with and without diabetes.Conclusions: Given the "epidemic" of diabetes, with substantially increasing diabetes prevalence each year across all age- and race/ethnicity groups, the significance of diabetes as a risk factor for stroke is becoming more evident. Diabetes is clearly one of the most important risk factors for ischemic stroke, especially in those patients less than 65 years of age. We estimate that 37-42% of all ischemic strokes in both African Americans and whites are attributable to the effects of diabetes alone or in combination with hypertension. [ABSTRACT FROM AUTHOR]

Intracranial aneurysms (IAs) are usually asymptomatic with a low risk of rupture, but consequences of aneurysmal subarachnoid hemorrhage (aSAH) are severe. Identifying IAs at risk of rupture has important clinical and socio-economic consequences. The goal of this study was to assess the effect of patient and IA characteristics on the likelihood of IA being diagnosed incidentally versus ruptured. Patients were recruited at 21 international centers. Seven phenotypic patient characteristics and three IA characteristics were recorded. The analyzed cohort included 7992 patients. Multivariate analysis demonstrated that: (1) IA location is the strongest factor associated with IA rupture status at diagnosis; (2) Risk factor awareness (hypertension, smoking) increases the likelihood of being diagnosed with unruptured IA; (3) Patients with ruptured IAs in high-risk locations tend to be older, and their IAs are smaller; (4) Smokers with ruptured IAs tend to be younger, and their IAs are larger; (5) Female patients with ruptured IAs tend to be older, and their IAs are smaller; (6) IA size and age at rupture correlate. The assessment of associations regarding patient and IA characteristics with IA rupture allows us to refine IA disease models and provide data to develop risk instruments for clinicians to support personalized decision-making., Competing Interests: The authors declare no conflict of interest.

Objectives: Population-level estimates of the median intracerebral hemorrhage (ICH) volume would allow for the evaluation of clinical trial external validity and determination of temporal trends. We previously reported the median ICH volume in 1988. However, differences in risk factor management, neuroimaging, and demographics may have affected ICH volumes. The goal of this study is to determine the median volume of ICH within a population-based cross-sectional study, including whether it has changed over time., Methods: The Genetic and Environmental Risk Factors for Hemorrhagic Stroke study was a population-based study of ICH among residents of the Greater Cincinnati/Northern Kentucky region from 2008 through 2012. This study utilizes those data and compares with ICH cases from the same region in 1988. Initial computed tomography images of the head were reviewed, and ICH volumes were calculated using consistent methodology., Results: From 2008 through 2012, we identified 1117 cases of ICH. The median volume of ICH was 14.0 mL and was lower in black (11.6) than in white (15.5) patients. Median volumes of lobar and deep ICH were 28.8 mL and 9.8 mL, respectively. Median ICH volume changed significantly from 1988 to 2008-2012, with age-and-race-adjusted volume decreasing from 18.3 mL to 13.76 mL (p = 0.025)., Conclusions: Median volume of ICH was 13.76 mL, and this should be considered in clinical trial design. Median ICH volume has apparently decreased from 1988 to 2008-2012.

Introduction: Intracerebral hemorrhage (ICH) is the most severe subtype of stroke. Its mortality rate is high, and most survivors experience significant disability., Objective: To assess primary patient risk factors associated with mortality and neurologic disability 3 months after ICH in a large, racially and ethnically balanced cohort., Design, Setting, and Participants: This cohort study included participants from the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study, which prospectively recruited 1000 non-Hispanic White, 1000 non-Hispanic Black, and 1000 Hispanic patients with spontaneous ICH to study the epidemiological characteristics and genomics associated with ICH. Participants included those with uniform data collection and phenotype definitions, centralized neuroimaging review, and telephone follow-up at 3 months. Analyses were completed in November 2021., Exposures: Patient demographic and clinical characteristics as well as hospital event and imaging variables were examined, with characteristics meeting P < .20 considered candidates for a multivariate model. Elements included in the ICH score were specifically analyzed., Main Outcomes and Measures: Individual characteristics were screened for association with 3-month outcome of neurologic disability or mortality, as assessed by a modified Rankin Scale (mRS) score of 4 or greater vs 3 or less under a logistic regression model. A total of 25 characteristics were tested in the final model, which minimized the Akaike information criterion. Analyses were repeated removing individuals who had withdrawal of care., Results: A total of 2568 patients (mean [SD] age, 62.4 [14.7] years; 1069 [41.6%] women and 1499 [58.4%] men) had a 3-month outcome determination available, including death. The final logistic model had a significantly higher area under the receiver operating characteristics curve (C = 0.88) compared with ICH score alone (C = 0.76; P < .001). Among characteristics associated with neurologic disability and mortality were larger log ICH volume (OR, 2.74; 95% CI, 2.36-3.19; P < .001), older age (OR per 1-year increase, 1.04; 95% CI, 1.02-1.05; P < .001), pre-ICH mRS score (OR, 1.62; 95% CI, 1.41-1.87; P < .001), lobar location (OR, 0.22; 95% CI, 0.16-0.30; P < .001), and presence of infection (OR, 1.85; 95% CI, 1.42-2.41; P < .001)., Conclusions and Relevance: The findings of this cohort study validate ICH score elements and suggest additional baseline and interim patient characteristics were associated with variation in 3-month outcome.

Objectives: Intracerebral hemorrhage (ICH) has the highest morbidity and mortality rate of any stroke subtype and clinicians often administer prophylactic antiseizure medications (ASMs) as a means of preventing post-stroke seizures, particularly following lobar ICH. However, evidence for ASM efficacy in preventing seizures and reducing disability is lacking given limited randomized trials. Herein, we report analysis from a large prospective observational study that evaluates the effect of primary prophylactic ASM administration on seizure occurrence and disability following ICH., Materials and Methods: Primary analysis was performed on 1630 patients with ICH enrolled in the ERICH study. A propensity score for administration of prophylactic ASM was developed and patients were matched by the closest propensity score (difference < 0.1). McNemar's test was used to compare occurrence of in-hospital seizure and disability, defined by modified Rankin Score (mRS) ≥ 3 at 3 months post ICH., Results: Of the 815 matched pairs of patients treated with primary prophylactic ASM, there was no significant difference in seizure occurrence (p = 0.4631) or disability (p = 0.4653). Subset analysis of 280 matched pairs of patients with primary lobar ICH similarly revealed no significant difference in seizure occurrence (p = 0.1011) or disability (p = 1.00) between prophylactically treated and untreated patients., Conclusions: Although current guidelines do not recommend primary prophylactic ASM following ICH, clinical use remains widespread. Data from the ERICH study did not find an association between administering primary prophylactic ASM and preventing seizures or reducing disability following ICH, thus providing evidence to influence clinical practice and patient care., Competing Interests: Declaration of Competing Interest Dr. Moomaw is supported by U01NS069763. Dr. Sheth is supported by U24NS107215, U24NS107136, U01NS106513, R01NR018335, and AHA17CSA33550004; received research funding from Hyperfine, Bard, Novartis, and Biogen; received consulting fees from Zoll Medical Corporation; and holds equity in Alva Health and Astrocyte Pharmaceuticals Inc. Dr. Woo is supported by U01NS036695, T32NS047996, U01NS069763, and R01NS100417. The other authors report no conflicts or disclosures., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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.

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., Competing Interests: Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MLF is a co-founder and has ownership interest in Sense Diagnostics, Inc., a start-up company developing a non-invasive sensor intended to monitor ICH., (© European Stroke Organisation 2021.)

Objective: To 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., Methods: We 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 V 1 (PTFV 1 ), 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., Results: Among 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. PTFV 1 measurements were available in 3,209 patients (mean, 3,434 ± 2,525 μV*ms). Black race was associated with greater PTFV 1 in unadjusted (β, 1.59; 95% CI, 1.21-1.97) and adjusted (β, 1.45; 95% CI, 1.00-1.80) models., Conclusions: We found systematic Black-White racial differences in left atrial structure and pathophysiology in a population-based sample of patients with ischemic stroke., Classification of Evidence: This study provides Class II evidence that atrial cardiopathy phenotypes differ in Black people with acute stroke compared to White people., (© 2020 American Academy of Neurology.)

Background and Purpose: Acute ischemic stroke (AIS) patients may benefit from endovascular thrombectomy (EVT) up to 24 h since last known normal (LKN). Advanced imaging is required for patient selection. Small or rural hospitals may not have sufficient CT technician and radiology support to rapidly acquire and interpret images. We estimated transfer rates using non-contrast head CT and stroke severity to select patients to be transferred to larger centers for evaluation., Methods: We identified all AIS among residents of the study region in 2010. Only cases age ≥ 18 with baseline mRS 0-2 that presented to an ED were included. Among cases that presented between 6 and 24 h from LKN, those without evidence of acute infarct on head CT and with initial NIHSS ≥6 or ≥ 10 were identified., Results: Of 1359 AIS cases, 448 (33.0%) presented between 6 and 24 h, of which 383 (85.5%) showed no evidence of acute infarct on CT. Of cases with no acute infarct on CT, 89/383 (23.2%) had NIHSS ≥6, of which 66 (74.2%) initially presented to a hospital without thrombectomy capabilities; and 51/383 (13.3%) had NIHSS ≥10, of which 40 (78.4%) presented to a non-thrombectomy hospital., Conclusions: In our population, 40-66 AIS patients annually (0.8-1.3/week, or 3-5 patients/100,000 persons/year) may present to non-thrombectomy hospitals and need to be transferred using non-contrast CT and stroke severity as screening tools. Such an approach may sufficiently mitigate the impact of delays in treatment on outcomes, without overburdening the referring nor accepting hospitals., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: A previous study suggested that intracranial aneurysms are more likely to occur in the same arterial territory within families. We aimed to replicate this analysis in independent families and in a sample limited to intracranial aneurysms that ruptured., Methods: Among families with ≥2 first-degree relatives with intracranial aneurysms, we randomly matched index families to comparison families, and compared concordance in intracranial aneurysm territory between index and comparison families using a conditional logistic events/trials model. We analyzed three European cohorts separately, and pooled the results with those of the Familial Intracranial Aneurysm study by performing an inverse variance fixed effects meta-analysis. The main analysis included both unruptured and ruptured intracranial aneurysms, and a secondary analysis only ruptured intracranial aneurysms., Results: Among 70 Dutch, 142 Finnish, and 34 French families, concordance regarding intracranial aneurysm territory was higher within families than between families, although not statistically significant. Meta-analysis revealed higher concordance in territory within families overall (odds ratio [OR] 1.7, 95%CI 1.3-2.2) and for each separate territory except the anterior cerebral artery. In the analysis of ruptured intracranial aneurysms, overall territory concordance was higher within families than between families (OR 1.8; 95%CI 1.1-2.7) but the territory-specific analysis showed statistical significance only for the internal carotid artery territory., Conclusions: We confirmed that familial intracranial aneurysms are more likely to occur in the same arterial territory within families. Moreover, we found that ruptured aneurysms were also more likely to occur in the same arterial territory within families., Competing Interests: The authors have declared that no competing interests exist.

Background and Purpose: For survivors of oral anticoagulation therapy (OAT)-associated intracerebral hemorrhage (OAT-ICH) who are at high risk for thromboembolism, the benefits of OAT resumption must be weighed against increased risk of recurrent hemorrhagic stroke. The ε2/ε4 alleles of the apolipoprotein E ( APOE ) gene, MRI-defined cortical superficial siderosis, and cerebral microbleeds are the most potent risk factors for recurrent ICH. We sought to determine whether combining MRI markers and APOE genotype could have clinical impact by identifying ICH survivors in whom the risks of OAT resumption are highest., Methods: Joint analysis of data from 2 longitudinal cohort studies of OAT-ICH survivors: (1) MGH-ICH study (Massachusetts General Hospital ICH) and (2) longitudinal component of the ERICH study (Ethnic/Racial Variations of Intracerebral Hemorrhage). We evaluated whether MRI markers and APOE genotype predict ICH recurrence. We then developed and validated a combined APOE -MRI classification scheme to predict ICH recurrence, using Classification and Regression Tree analysis., Results: Cortical superficial siderosis, cerebral microbleed, and APOE ε2/ε4 variants were independently associated with ICH recurrence after OAT-ICH (all P <0.05). Combining APOE genotype and MRI data resulted in improved prediction of ICH recurrence (Harrell C: 0.79 versus 0.55 for clinical data alone, P =0.033). In the MGH (training) data set, CSS, cerebral microbleed, and APOE ε2/ε4 stratified likelihood of ICH recurrence into high-, medium-, and low-risk categories. In the ERICH (validation) data set, yearly ICH recurrence rates for high-, medium-, and low-risk individuals were 6.6%, 2.5%, and 0.9%, respectively, with overall area under the curve of 0.91 for prediction of recurrent ICH., Conclusions: Combining MRI and APOE genotype stratifies likelihood of ICH recurrence into high, medium, and low risk. If confirmed in prospective studies, this combined APOE -MRI classification scheme may prove useful for selecting individuals for OAT resumption after ICH.

Objective: We aimed to identify risk factors for seizures after intracerebral hemorrhage, and to validate the prognostic value of the previously reported CAVE score (0-4 points: cortical involvement, age <65, volume >10 mL, and early seizures within 7 days of hemorrhage)., Patients and Methods: Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) was a prospective study of spontaneous intracerebral hemorrhage. We included patients who did not have a prior history of seizure and survived to discharge. Univariate analysis and multiple logistic regression modeling were used to identify risk factors for seizure., Results: From 2010-2015, 3000 cases were recruited, and 2507 patients were included in this study. Seizures after hospital discharge developed in 77 patients 3.1 %). Patients with lobar (cortical) hemorrhage (OR 3.0, 95 % CI 1.8-5.0), larger hematoma volume (OR 1.5 per cm 3 , 95 % CI 1.2-2.0), and surgical evacuation of hematoma (OR 2.6, 95 % CI 1.4-4.8) had a higher risk of late seizure, and older patients had a lower risk (OR 0.88 per 5-year interval increase, 95 % CI 0.81-0.95). The CAVE score was highly associated with seizure development (OR 2.5 per unit score increase, 95 % CI 2.0-3.2, p < 0.0001). The CAVS score, substituting surgical evacuation for early seizure, increased the OR per unit score to 2.8 (95 % CI 2.2-3.5)., Conclusions: Lobar hemorrhage, larger hematoma volume, younger age, and surgical evacuation are strongly associated with the development of seizures. We validated the CAVE score in a multi-ethnic population, and found the CAVS score to have similar predictive value while representing the current practice of AED use., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Intraventricular hemorrhage (IVH) and white matter lesion (WML) severity are associated with higher rates of death and disability in intracerebral hemorrhage (ICH). A prior report identified an increased risk of IVH with greater WML burden but did not control for location of ICH. We sought to determine whether a higher degree of WML is associated with a higher risk of IVH after controlling for ICH location., Methods: Utilizing the patient population from 2 large ICH studies; the Genetic and Environmental Risk Factors for Hemorrhagic Stroke (GERFHS III) Study and the Ethnic/Racial Variations of Intracerebral Hemorrhage study, we graded WML using the Van Swieten Scale (0-1 for mild, 2 for moderate, and 3-4 for severe WML) and presence or absence of IVH in baseline CT scans. We used multivariable regression models to adjust for relevant covariates., Results: Among 3023 ICH patients, 1260 (41.7%) had presence of IVH. In patients with IVH, the proportion of severe WML (28.6%) was higher compared with patients without IVH (21.8%) (P < .0001). Multivariable analysis demonstrated that moderate-severe WML, deep ICH, and increasing ICH volume were independently associated with presence of IVH. We found an increased risk of IVH with moderate-severe WML (OR = 1.38; 95%Cl 1.03-1.86, P = .0328) in the subset of lobar hemorrhages., Conclusions: Moderate to severe WML is a risk for IVH. Even in lobar ICH hemorrhages, severe WML leads to an independent increased risk for ventricular rupture., (Published by Elsevier Inc.)

Background and Purpose- Sex differences in stroke incidence over time were previously reported from the GCNKSS (Greater Cincinnati/Northern Kentucky Stroke Study). We aimed to determine whether these differences continued through 2015 and whether they were driven by particular age groups. Methods- Within the GCNKSS population of 1.3 million, incident (first ever) strokes among residents ≥20 years of age were ascertained at all local hospitals during 5 periods: July 1993 to June 1994 and calendar years 1999, 2005, 2010, and 2015. Out-of-hospital cases were sampled. Sex-specific incidence rates per 100 000 were adjusted for age and race and standardized to the 2010 US Census. Trends over time by sex were compared (overall and age stratified). Sex-specific case fatality rates were also reported. Bonferroni corrections were applied for multiple comparisons. Results- Over the 5 study periods, there were 9733 incident strokes (56.3% women). For women, there were 229 (95% CI, 215-242) per 100 000 incident strokes in 1993/1994 and 174 (95% CI, 163-185) in 2015 ( P <0.05), compared with 282 (95% CI, 263-301) in 1993/1994 to 211 (95% CI, 198-225) in 2015 ( P <0.05) in men. Incidence rates decreased between the first and last study periods in both sexes for IS but not for intracerebral hemorrhage or subarachnoid hemorrhage. Significant decreases in stroke incidence occurred between the first and last study periods for both sexes in the 65- to 84-year age group and men only in the ≥85-year age group; stroke incidence increased for men only in the 20- to 44-year age group. Conclusions- Overall stroke incidence decreased from the early 1990s to 2015 for both sexes. Future studies should continue close surveillance of sex differences in the 20- to 44-year and ≥85-year age groups, and future stroke prevention strategies should target strokes in the young- and middle-age groups, as well as intracerebral hemorrhage.

Background and Purpose- Patients with intracerebral hemorrhage (ICH) and atrial fibrillation (AF) are at risk for ischemic events. While risk calculators (CHA 2 DS 2 -VASc and HAS-BLED) have been validated to assess risk for ischemic stroke and major bleeding in AF patients, decisions about anticoagulation must consider the net clinical benefit of anticoagulation. Furthermore, stroke and bleeding risk are highly correlated, making decisions more difficult. Methods- We examined patients in the GERFHS III study (Genetic and Environmental Risk Factors for Hemorrhagic Stroke)-a population-based retrospective study of spontaneous ICH patients without a structural or traumatic cause in the Greater Cincinnati/Northern Kentucky region between July 2008 and December 2012. CHA 2 DS 2 -VASc and HAS-B(L)ED (minus L because labile international normalized ratio was unavailable) scores were calculated for ICH patients with AF. Using a Markov state transition model, we estimated net clinical benefit of anticoagulation relative to no treatment in quality-adjusted life years (QALYs). We defined minimal clinically relevant benefit as 0.1 QALYs. Results- Among 1186 cases of spontaneous ICH, 95 cases had AF and met our survival criteria. Within 1 year, 8 of 95 (8%) would be expected to have a major bleeding event on anticoagulation, and 5 of 95 (5%) of patients would be expected to have an ischemic stroke off anticoagulation. Sixty-eight of 95 (71%) patients would have higher risk for major bleeding than for ischemic stroke. Anticoagulation with directly acting anticoagulants would result in no clinically significant gain or loss in 73%. Roughly 12% would gain >0.1 QALYs, and 15% would lose >0.1 QALYs. Among patients receiving aspirin, most have no significant net clinical benefit or loss. Overall, anticoagulation of the entire cohort would result in an aggregate loss of 0.92 QALYs. Conclusions- Our analysis suggests that universal anticoagulation after ICH would be associated with a net loss of QALY. Additional factors should be considered before anticoagulating patients with AF after ICH. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00930280.

Background and Purpose: Spontaneous supratentorial intracerebral hemorrhage (ICH) contributes disproportionately to stroke mortality, and randomized trials of surgical treatments for ICH have not shown benefit. Decompressive hemicraniectomy (DHC) improves functional outcome in patients with malignant middle cerebral artery ischemic stroke, but data in ICH patients is limited. We hypothesized that DHC would reduce in-hospital mortality and poor functional status (defined as modified Rankin scale ≥5) among survivors at 3 months, without increased complications., Methods: We performed a retrospective, case-control, propensity score matched study to determine whether hemicraniectomy affected outcome in patients with spontaneous supratentorial ICH. The propensity score consisted of variables associated with outcome or predictors of hemicraniectomy. Forty-three surgical patients were matched to 43 medically managed patients on ICH location, sex, and nearest neighbor matching. Three-month functional outcomes, in-hospital mortality, and in-hospital complications were measured., Results: In the medical management group, 72.1% of patients had poor outcome at 3 months compared with 37.2% who underwent hemicraniectomy (odds ratio 4.8, confidence interval 1.6-14). In-hospital mortality was 51.2% for medically managed patients and 16.3% for hemicraniectomy patients (odds ratio 8.5, confidence interval 2.0-36.8). There were no statistically significant differences in the occurrence of in-hospital complications., Conclusions: In our retrospective study of selected patients with spontaneous supratentorial ICH, DHC resulted in lower rate of in-hospital mortality and better 3-month functional status compared with medically managed patients. A randomized trial is necessary to evaluate DHC as a treatment for certain patients with spontaneous supratentorial ICH., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Measurement of quality of stroke care has become increasingly important, but data come mostly from programs in hospitals that choose to participate in certification programs, which may not be representative of the care provided in nonparticipating hospitals. The authors sought to determine differences in quality of care metric concordance for acute ischemic stroke among hospitals designated as a primary stroke center, comprehensive stroke center, and non-stroke center in a population-based epidemiologic study. Significant differences were found in both patient demographics and in concordance with guideline-based quality metrics. These differences may help inform quality improvement efforts across hospitals involved in certification as well as those that are not.

Background and Purpose- In this study, we aim to investigate the association of computed tomography-based markers of cerebral small vessel disease with functional outcome and recovery after intracerebral hemorrhage. Methods- Computed tomographic scans of patients in the ERICH study (Ethnic and Racial Variations of Intracerebral Hemorrhage) were evaluated for the extent of leukoaraiosis and cerebral atrophy using visual rating scales. Poor functional outcome was defined as a modified Rankin Scale (mRS) of ≥3. Multivariable logistic and linear regression models were used to explore the associations of cerebral small vessel disease imaging markers with poor functional outcome at discharge and, as a measure of recovery, change in mRS from discharge to 90 days poststroke. Results- After excluding in-hospital deaths, data from 2344 patients, 583 (24.9%) with good functional outcome (mRS of 0-2) at discharge and 1761 (75.1%) with poor functional outcome (mRS of 3-5) at discharge, were included. Increasing extent of leukoaraiosis ( P for trend, 0.01) and only severe (grade 4) global atrophy (odds ratio, 2.02; 95% CI, 1.22-3.39, P =0.007) were independently associated with poor functional outcome at discharge. Mean (SD) mRS change from discharge to 90-day follow-up was 0.57 (1.18). Increasing extent of leukoaraiosis ( P for trend, 0.002) and severe global atrophy (β [SE], -0.23 [0.115]; P =0.045) were independently associated with less improvement in mRS from discharge to 90 days poststroke. Conclusions- In intracerebral hemorrhage survivors, the extent of cerebral small vessel disease at the time of intracerebral hemorrhage is associated with poor functional outcome at hospital discharge and impaired functional recovery from discharge to 90 days poststroke.

Objective: Previously we reported that ischemic stroke incidence is declining over time for men but not women. We sought to describe temporal trends of sex differences in incidence of transient ischemic attack (TIA) within the same large, biracial population., Methods: Among the population of 1.3 million in the Greater Cincinnati Northern Kentucky Stroke Study (GCNKSS) region, TIAs among area residents (≥20 years old) were identified at all local hospitals. Out of hospital cases were ascertained using a sampling scheme. First-ever cases and first within each study period for a patient was included in incidence rates. All cases were physician-adjudicated. Incidence rates (during July 93-June 94 and calendar years 1999, 2005, and 2010) were calculated using the age-, race-, and sex-specific number of TIAs divided by the GCNKSS population in that group; rates were standardized to the 2010 U.S., Population: t Tests with Bonferroni correction were used to compare rates over time., Results: There were a total of 4746 TIA events; 53% were female, and 12% were black. In males, incidence decreased from 153 (95% confidence interval [CI] 139-167) per 100,000 in 1993/4 to 117 (95% CI 107-128) in 2010 (P < .05 for trend test) but was similar over time among females (107 (95% CI 97-116) to 102 (95%CI 94-111), P > .05)., Conclusions: Within the GCNKSS population, TIA incidence decreased significantly over time in males but not females, data which parallels trends in ischemic stroke in the GCNKSS over the same time period. Future research is needed to determine if these sex differences in incidence over time continue past 2010., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and Purpose- Clinical trials in spontaneous intracerebral hemorrhage (ICH) have used volume cutoffs as inclusion criteria to select populations in which the effects of interventions are likely to be the greatest. However, optimal volume cutoffs for predicting poor outcome in deep locations (thalamus versus basal ganglia) are unknown. Methods- We conducted a 2-phase study to determine ICH volume cutoffs for poor outcome (modified Rankin Scale score of 4-6) in the thalamus and basal ganglia. Cutoffs with optimal sensitivity and specificity for poor outcome were identified in the ERICH ([Ethnic/Racial Variations of ICH] study; derivation cohort) using receiver operating characteristic curves. The cutoffs were then validated in the ATACH-2 trial (Antihypertensive Treatment of Acute Cerebral Hemorrhage-2) by comparing the c-statistic of regression models for outcome (including dichotomized volume) in the validation cohort. Results- Of the 3000 patients enrolled in ERICH, 1564 (52%) had deep ICH, of whom 1305 (84%) had complete neuroimaging and outcome data (660 thalamic and 645 basal ganglia hemorrhages). Receiver operating characteristic curve analysis identified 8 mL in thalamic (area under the curve, 0.79; sensitivity, 73%; specificity, 78%) and 18 mL in basal ganglia ICH (area under the curve, 0.79; sensitivity, 70%; specificity, 83%) as optimal cutoffs for predicting poor outcome. The validation cohort included 834 (84%) patients with deep ICH and complete neuroimaging data enrolled in ATACH-2 (353 thalamic and 431 basal ganglia hemorrhages). In thalamic ICH, the c-statistic of the multivariable outcome model including dichotomized ICH volume was 0.80 (95% CI, 0.75-0.85) in the validation cohort. For basal ganglia ICH, the c-statistic was 0.81 (95% CI, 0.76-0.85) in the validation cohort. Conclusions- Optimal hematoma volume cutoffs for predicting poor outcome in deep ICH vary by the specific deep brain nucleus involved. Utilization of location-specific volume cutoffs may improve clinical trial design by targeting deep ICH patients that will obtain maximal benefit from candidate therapies.

Background: Patients with spontaneous intracerebral hemorrhage (ICH) are predisposed to venous thromboembolic (VTE) complications, such as deep vein thrombosis and pulmonary embolism., Objective: To evaluate, in a multicenter, retrospective cohort study, the rate of VTE complications in ICH patients during acute hospitalization, identify potential risk factors, and assess their association with functional outcome., Methods: We retrospectively analyzed prospectively collected data from 19 centers and 41 sites that participated in the Ethnic/Racial Variations of Intracerebral Hemorrhage study, from August 2010 to February 2016. We compared ICH patients with VTE complications to those without VTE complications. Statistical analyses were performed to determine predictors of VTE complications and poor outcome (modified Rankin Scale ≥ 4) at discharge and 3-mo follow-up., Results: Of the 2902 ICH patients who were eligible for analysis, 87 (3.0%) had VTE complications: 57 (2.0%) had only deep vein thrombosis, 19 (0.7%) had only pulmonary embolism, and 11 (0.4%) had both. In the multivariable logistic regression analysis, a prior history of VTE (odds ratio [OR] = 6.8; P < .0001), intubation (OR = 4.0; P < .0001), and presence of IVH (OR = 1.8; P = .0157) were independent predictors of VTE complications. After controlling for ICH volume and location, IVH, age, and presenting Glasgow Coma Scale, the occurrence of VTE complications was an independent predictor of poor outcome at discharge (OR = 2.9; P = .002) and 3-mo follow-up (OR = 2.1; P = .02)., Conclusion: Although VTE complications are uncommon after ICH, they are associated with significantly worse outcomes. Further studies will be needed to determine the optimal treatment regimen for the prevention and treatment of VTE complications in ICH patients., (Copyright © 2018 by the Congress of Neurological Surgeons.)

Importance: Genetic studies of intracerebral hemorrhage (ICH) have focused mainly on white participants, but genetic risk may vary or could be concealed by differing nongenetic coexposures in nonwhite populations. Transethnic analysis of risk may clarify the role of genetics in ICH risk across populations., Objective: To evaluate associations between established differences in ICH risk by race/ethnicity and the variability in the risks of apolipoprotein E (APOE) ε4 alleles, the most potent genetic risk factor for ICH., Design, Setting, and Participants: This case-control study of primary ICH meta-analyzed the association of APOE allele status on ICH risk, applying a 2-stage clustering approach based on race/ethnicity and stratified by a contributing study. A propensity score analysis was used to model the association of APOE with the burden of hypertension across race/ethnic groups. Primary ICH cases and controls were collected from 3 hospital- and population-based studies in the United States and 8 in European sites in the International Stroke Genetic Consortium. Participants were enrolled from January 1, 1999, to December 31, 2017. Participants with secondary causes of ICH were excluded from enrollment. Controls were regionally matched within each participating study., Main Outcomes and Measures: Clinical variables were systematically obtained from structured interviews within each site. APOE genotype was centrally determined for all studies., Results: In total, 13 124 participants (7153 [54.5%] male with a median [interquartile range] age of 66 [56-76] years) were included. In white participants, APOE ε2 (odds ratio [OR], 1.49; 95% CI, 1.24-1.80; P < .001) and APOE ε4 (OR, 1.51; 95% CI, 1.23-1.85; P < .001) were associated with lobar ICH risk; however, within self-identified Hispanic and black participants, no associations were found. After propensity score matching for hypertension burden, APOE ε4 was associated with lobar ICH risk among Hispanic (OR, 1.14; 95% CI, 1.03-1.28; P = .01) but not in black (OR, 1.02; 95% CI, 0.98-1.07; P = .25) participants. APOE ε2 and ε4 did not show an association with nonlobar ICH risk in any race/ethnicity., Conclusions and Relevance: APOE ε4 and ε2 alleles appear to affect lobar ICH risk variably by race/ethnicity, associations that are confirmed in white individuals but can be shown in Hispanic individuals only when the excess burden of hypertension is propensity score-matched; further studies are needed to explore the interactions between APOE alleles and environmental exposures that vary by race/ethnicity in representative populations at risk for ICH.

Background and Purpose: Patients with stroke can experience neurological deterioration in the prehospital setting. We evaluated patients with stroke to determine factors associated with prehospital neurological deterioration (PND)., Methods: Among the Greater Cincinnati/Northern Kentucky region (population ~1.3 million), we screened all 15 local hospitals' admissions from 2010 for acute stroke and included patients aged ≥20. The GCS was compared between emergency medical services (EMS) arrival and hospital arrival, with decrease ≥2 points considered PND. Data obtained retrospectively included demographics, medical history and medication use, stroke subtype (eg, ischaemic stroke (IS), intracerebral haemorrhage (ICH), subarachnoid haemorrhage (SAH)) and IS subtype (eg, small vessel, large vessel, cardioembolic), seizure at onset, time intervals between symptom onset, EMS arrival and hospital arrival, EMS level of training, and blood pressure and serum glucose on EMS arrival., Results: Of 2708 total patients who had a stroke, 1092 patients (median (IQR) age 74 (61-83) years; 56% women; 21% black) were analysed. PND occurred in 129 cases (12%), including 9% of IS, 24% of ICH and 16% of SAH. In multivariable analysis, black race, atrial fibrillation, haemorrhagic subtype and ALS level of transport were associated with PND., Conclusion: Haemorrhage and atrial fibrillation is associated with PND in stroke, and further investigation is needed to establish whether PND can be predicted. Further studies are also needed to assess whether preferential transport of patients with deterioration to hospitals equipped with higher levels of care is beneficial, identify why race is associated with deterioration and to test therapies targeting PND., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)