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Background: Elevated blood pressure after endovascular thrombectomy (EVT) has been associated with an increased risk of hemorrhagic transformation and poor functional outcomes. However, the optimal hemodynamic management after EVT remains unknown, and the blood pressure course in the acute phase of ischemic stroke has not been well characterized. This study aimed to identify patient subgroups with distinct blood pressure trajectories after EVT and study their association with radiographic and functional outcomes. Methods: This multicenter retrospective cohort study included consecutive patients with anterior circulation large-vessel occlusion ischemic stroke who underwent EVT. Repeated time-stamped blood pressure data were recorded for the first 72 hours after thrombectomy. Latent variable mixture modeling was used to separate subjects into five groups with distinct postprocedural systolic blood pressure (SBP) trajectories. The primary outcome was functional status, measured on the modified Rankin Scale 90 days after stroke. Secondary outcomes included hemorrhagic transformation, symptomatic intracranial hemorrhage, and death. Results: Two thousand two hundred sixty-eight patients (mean age [±SD] 69±15, mean National Institutes of Health Stroke Scale 15±7) were included in the analysis. Five distinct SBP trajectories were observed: low (18%), moderate (37%), moderate-to-high (20%), high-to-moderate (18%), and high (6%). SBP trajectory group was independently associated with functional outcome at 90 days ( P P =0.0003 and adjusted odds ratio, 2.2 [95% CI, 1.5–3.2], P P =0.04). No significant association was found between trajectory group and hemorrhagic transformation. Conclusions: Patients with acute ischemic stroke demonstrate distinct SBP trajectories during the first 72 hours after EVT that have differing associations with functional outcome. These findings may help identify potential candidates for future blood pressure modulation trials.

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

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.

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.

Introduction: Stroke secondary to intracranial atherosclerosis (ICAD) results in three distinct infarct patterns: (a) border zone infarcts (BZI) due to impaired distal perfusion (b) territorial infarcts due to distal plaque/thrombus embolization, and (c) perforator infarcts due to plaque progression. Previous studies indicate higher stroke recurrence in ICAD patients with BZI. Methods: This registered systematic review (CRD42021265230) comprised Medline and Web of Science search from inception to March 2022 for keywords (Intracranial Atherosclerosis OR Intracranial Stenosis) AND (Border zone OR Infarct Pattern) to identify papers and conference abstracts reporting initial infarct patterns and recurrence rates in patients with symptomatic ICAD. Sensitivity analyses were performed for studies including any BZI vs isolated BZI and those excluding posterior circulation strokes. The study outcome included neurological deterioration and/or stroke recurrence. For all outcome events, corresponding risk ratios (RR) and 95% confidence intervals (CI) were calculated. Risk of bias assessments will be presented. Results: Literature search yielded 4478 studies,11 met inclusion criteria (n=1315 patients, 354 with BZI, weighted proportions summarized in figure). The meta-analysis of these studies with moderate heterogeneity (I 2 =38.7%) demonstrated that RR of outcomes in BZI group compared to non-BZI group was 2.10 (95% CI 1.52-2.90). Limiting analysis to studies including any BZI, RR (and 95% CI) was 2.32 (1.58-3.40), and 3.25 (2.09-5.07) for studies only including anterior circulation strokes with low heterogeneity for both (I 2 =0%). A non-significantly high outcome rate was seen with isolated BZI (RR 2.29, 95% CI 0.94-5.62) but with moderate heterogeneity across studies (I 2 =70.25%). Conclusion: We demonstrate the presence of BZI secondary to symptomatic ICAD can be imaging biomarker to predict neurological deterioration and/or stroke recurrence.

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.

Introduction: Asymptomatic intracerebral hemorrhage (aICH) occurs in ~40% of acute ischemic stroke patients after endovascular thrombectomy (EVT). Unlike symptomatic ICH, which is undoubtedly associated with worse outcomes, studies evaluating the association of aICH on long-term outcomes have been inconclusive. We performed a systematic review and meta-analysis to evaluate the long-term effects of post-EVT aICH. Methods: The meta-analysis protocol was submitted to PROSPERO a priori. PubMed, SCOPUS and Web of Science were searched from inception through April 2022 using database-specific searches with combination of keywords and controlled vocabulary. After deduplication, two authors independently reviewed all abstracts. Included studies contained adult AIS patients undergoing EVT with follow-up imaging assessment of ICH reporting comparative outcomes according to aICH vs no ICH . Meta-analysis was performed using Cochrane Review Manager v5.4. Summary effects were estimated by a fixed-effects model to estimate summary odds ratio (OR) of the effect of aICH vs no ICH on primary outcomes of 90-day modified Rankin score 3-6 and mortality. Results: Systematic review yielded 278 studies; 52 abstracts were fully reviewed ; 8 studies fulfilled inclusion criteria (n=4701 patients total; 1562 with aICH). aICH was associated with 90-day mRS 3-6 (OR 2.11 [95% CI 1.85-2.40]; Figure 1A) and higher mortality (OR 1.66 [95% CI 1.41-1.96]; Figure 1B) compared to no ICH. There was insufficient evidence of difference in 90-day mRS 3-6 when studies were grouped according to Heidelberg (n=2 studies; OR 2.37 [95% CI 0.92, 6.12]) vs ECASS (n=5 studies; OR 2.07 [95%CI 1.62, 2.64]) criteria for ICH. Meta-regression analysis adjusting for covariates will be presented Conclusion: aICH is associated with worse 90-day functional outcomes and higher mortality. Further studies to evaluate the factors predicting aICH and treatments aimed at reducing its occurrence are warranted.

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.

Background and Purpose Recent endovascular trials have spurred a paradigm shift toward routine use of CT perfusion (CTP) for decision-making in acute ischemic stroke. CTP use in the late window, however, remains under evaluation. Our objective was to assess the accuracy of CTP-predicted core in the late window. Methods In a retrospective review of our prospectively identified stroke registry at a single, comprehensive stroke center, we included patients with anterior large vessel occlusions presenting within the 6-24 h window who underwent baseline CTP evaluation and achieved TICI2b or TICI3 reperfusion on endovascular treatment. We recorded baseline CTP-predicted core volumes at relative cerebral blood flow (CBF) thresholds of Results Of the eligible patients, 134 met our inclusion criteria. Mean FIV was 39.5 (SD 49.6). Median CTP to reperfusion time was 93.5 min. Median absolute differences between CTP-predicted core and FIV were 14.7, 14.9, and 16.0 ml at Conclusion CTP cores in the 6–24 h period underestimate FIV, especially with larger infarcts. CTP-predicted core volumes in the late window show moderate positive correlation with FIV.

Background and Purpose: The National Institutes of Health Stroke Scale (NIHSS) measured at an early time point is an appealing surrogate marker for long-term functional outcome of stroke patients treated with endovascular therapy. However, definitions and analytical methods for an early NIHSS-based outcome measure that optimize power and precision in clinical studies are not well-established. Methods: In this post-hoc analysis of our prospective observational study that enrolled endovascular therapy-treated patients at 12 comprehensive stroke centers across the US, we compared the ability of 24-hour NIHSS, ΔNIHSS (baseline minus 24-hour NIHSS), and percentage change (NIHSS×100/baseline NIHSS), analyzed as continuous and dichotomous measures, to predict 90-day modified Rankin Scale (mRS) using logistic regression (adjusted for age, baseline NIHSS, glucose, hypertension, Alberta Stroke Program Early CT Score, time to recanalization, recanalization status, and intravenous thrombolysis) and Spearman ρ. Results: Of 485 patients in the BEST (Blood Pressure After Endovascular Stroke Therapy) cohort, 446 (92%) with 90-day follow-up data were included. An absolute 24-hour NIHSS, adjusted for baseline in multivariable modeling, had the highest predictive power of all definitions evaluated (aR 2 0.368 and adjusted odds ratio 0.79 [0.75–0.84], P 2 0.444 and adjusted odds ratio 0.84 [0.8–0.86] for ordinal mRS). For predicting mRS score of 0–2 with a cut point, the second most efficient approach, the optimal threshold for 24-hour NIHSS score was ≤7 (sensitivity 80.1%, specificity 80.4%; adjusted odds ratio 12.5 [7.14–20], P P Conclusions: Twenty-four–hour NIHSS, adjusted for baseline, was the strongest predictor of both dichotomous and ordinal 90-day mRS outcomes for endovascular therapy-treated patients. A dichotomous 24-hour NIHSS score of ≤7 was the second-best predictor. Although ΔNIHSS, continuous and dichotomized at ≥4, predicted 90-day outcomes, absolute 24-hour NIHSS definitions performed better.

Background and purposeA subset of ischaemic stroke patients with atrial fibrillation (AF) have ischaemic stroke despite anticoagulation. We sought to determine the association between prestroke anticoagulant therapy and recurrent ischaemic events and symptomatic intracranial haemorrhage (sICH).MethodsWe included consecutive patients with acute ischaemic stroke and AF from the Initiation of Anticoagulation after Cardioembolic stroke (IAC) study from eight comprehensive stroke centres in the USA. We compared recurrent ischaemic events and delayed sICH risk using adjusted Cox regression analyses between patients who were prescribed anticoagulation (ACp) versus patients who were naïve to anticoagulation therapy prior to the ischaemic stroke (anticoagulation naïve).ResultsAmong 2084 patients in IAC, 1518 had prior anticoagulation status recorded and were followed for 90 days. In adjusted Cox hazard models, ACp was associated with some evidence of a higher risk higher risk of 90-day recurrent ischaemic events only in the fully adjusted model (adjusted HR 1.50, 95% CI 0.99 to 2.28, p=0.058) but not increased risk of 90-day sICH (adjusted HR 1.08, 95% CI 0.46 to 2.51, p=0.862). In addition, switching anticoagulation class was not associated with reduced risk of recurrent ischaemic events (adjusted HR 0.41, 95% CI 0.12 to 1.33, p=0.136) nor sICH (adjusted HR 1.47, 95% CI 0.29 to 7.50, p=0.641).ConclusionAF patients with ischaemic stroke despite anticoagulation may have higher recurrent ischaemic event risk compared with anticoagulation-naïve patients. This suggests differing underlying pathomechanisms requiring different stroke prevention measures and identifying these mechanisms may improve secondary prevention strategies.

BackgroundIntracerebral hemorrhage (ICH) occurs in ~20%–30% of stroke patients undergoing endovascular therapy (EVT). However, there is conflicting evidence regarding the effect of asymptomatic ICH (aICH) on post-EVT outcomes. We sought to evaluate the effect of aICH on immediate and 90-day post-EVT neurological outcomes.MethodsIn this post-hoc analysis of the multicenter, prospective Blood Pressure after Endovascular Therapy (BEST) study we identified subjects with ICH following EVT. This population was divided into no ICH, aICH, and symptomatic ICH (sICH). Associations with 90-day modified Rankin Scale (mRS) dichotomized by functional independence (0–2 vs 3–6) and early neurological recovery (ENR) were determined using univariate/multivariate logistic regression models.ResultsOf 485 patients enrolled in BEST, 446 had 90-day follow-up data available. 92 (20.6%) developed aICH, and 18 (4%) developed sICH. Compared with those without ICH, aICH was not associated with worse 90-day outcome or lower ENR (OR 0.84 [0.53–1.35], P=0.55, aOR 0.84 [0.48–1.44], P=0.53 for 90-day mRS 0–2; OR 0.77 [0.48–1.23], P=0.34, aOR 0.72 [0.43–1.22] for ENR). aICH was not associated with 90-day outcome or ENR in patients with mTICI ≥2 b (OR 0.78 [0.48–1.26], P=0.33 for 90-day mRS 0–2; OR 0.89 [0.69–1.12], P=0.15 for ENR). A higher proportion of patients with aICH had mTICI ≥2 b than those without ICH (97%vs 87%, P=0.01).ConclusionsaICH was not associated with worse outcomes in patients with large-vessel stroke treated with EVT. aICH was more frequent in patients with successful recanalization. Further validation of our findings in large cohort studies of EVT-treated patients is warranted.

Background and Purpose: The Alberta Stroke Program Early Computed Tomography (CT) Score (ASPECTS) and CT perfusion (CTP) are commonly used to predict the ischemic core in acute ischemic strokes. CT angiography source images (CTA-SI) can also provide additional information to identify the extent of ischemia. Our objective was to investigate the correlation of noncontrast CT (NCCT) ASPECTS and CTA-SI ASPECTS with CTP core volumes. Methods: We utilized a single institutional, retrospective registry of consecutive patients with acute ischemic stroke with large vessel occlusion between May 2016 and May 2018. We graded ASPECTS both on baseline NCCT and CTA-SI and measured CTP core using automated RAPID software (cerebral blood flow Results: A total of 52 patients fit the inclusion criteria of large vessel occlusion in 6 to 24 hours and baseline imaging work up of NCCT, CTA, and CTP. The median age was 63 (interquartile range=53.5–75) and 38.46% were female. The median NCCT ASPECTS was 7 (interquartile range=6–9), CTA-SI ASPECTS was 5 (interquartile range=4–7), and CTP core was 14.5 mL (interquartile range=0–46 mL). There was a moderate correlation between NCCT ASPECTS and CTP core (r s =−0.55, P s =−0.50, P =0.0002). The optimal NCCT ASPECTS cutoff score to detect CTP core ≤70 mL was ≥6 (sensitivity, 0.84; specificity, 0.57; positive predictive value, 0.93; negative predictive value, 0.36) and the optimal CTA-SI ASPECTS was ≥5 (sensitivity, 0.76; specificity, 0.71; positive predictive value, 0.94; negative predictive value, 0.31). Conclusions: There was a moderate correlation between NCCT and CTA-SI ASPECTS in predicting CTP defined ischemic core in delayed time windows. Further studies are needed to determine if NCCT and CTA imaging could be used for image-based patient selection when CTP imaging is not available.

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.

High blood pressure (BP) is common after ischemic stroke and associated with a poor functional outcome and increased mortality. The conundrum then arises on whether to lower BP to improve outcome or whether this will worsen cerebral perfusion due to aberrant cerebral autoregulation. A number of large trials of BP lowering have failed to change outcome whether treatment was started prehospital in the community or hospital. Hence, nuances on how to manage high BP are likely, including whether different interventions are needed for different causes, the type and timing of the drug, how quickly BP is lowered, and the collateral effects of the drug, including on cerebral perfusion and platelets. Specific scenarios are also important, including when to lower BP before, during, and after intravenous thrombolysis and endovascular therapy/thrombectomy, when it may be necessary to raise BP, and when antihypertensive drugs taken before stroke should be restarted. This narrative review addresses these and other questions. Although further large trials are ongoing, it is increasingly likely that there is no simple answer. Different subgroups of patients may need to have their BP lowered (eg, before or after thrombolysis), left alone, or elevated.

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: Midlife hypertension is associated with an increased later-life ischemic stroke risk. However, temporal trends of blood pressure have not been fully explored. Methods: We performed a post hoc analysis of the ARIC study and included participants with four systolic blood pressures (SBP) at Visits 1-4 (1987-1999). Patients who had an ischemic stroke, died, or were lost to follow-up before 1999 were excluded from the analysis. We used group-based trajectory modeling to define six distinct SBP trajectories during Visits 1-4 (Figure 1). We report unadjusted and adjusted hazard ratios from Cox models fit to the primary outcome of ischemic stroke during follow-up from 1999-2017. We confirmed the proportional hazards assumptions of our models. Results: We included 9,689 participants, of which 758 (7.8%) had an ischemic stroke during follow-up. The mean±SD age at Visit 1 was 54±6 years and at Visit 4 was 63±6 years. The adjusted Cox models, Table 1, show the highest risk of ischemic stroke with increasing hypertension or stable severe hypertension. Comparing trajectories with similar baseline hypertension confirmed that increasing hypertension and stable severe hypertension had a higher risk than decreasing trajectories with the same starting point. Conclusion: Midlife blood pressure trajectory is associated with later-life ischemic stroke risk. Patients with hypertension who achieved a midlife reduction in systolic blood pressure were less likely to have a later-life stroke than those who did not.

Introduction: Stroke patients with a pre-existing disability are less likely to receive acute stroke treatments compared to those without a pre-existing disability. Using the Greater Cincinnati Northern Kentucky (GCNK) Stroke Study, we aimed to understand the disparities in inpatient and outpatient continuum of stroke care according to the patients’ pre-stroke functional status. Methods: We ascertained all hospitalized stroke patients ≥18 years old in year 2015 using ICD-9 430-436; ICD-10 I60-I67, G45-G46 within GCNK population; all cases were physician-reviewed. Per-stroke functional status was ascertained by trained research nurses during medical record review. We compared rates of in-hospital rehabilitative therapies, initiation of stroke prevention treatments, inpatient stroke workup (cardiac/vessel imaging), in-hospital and post-discharge rehabilitative therapies between ischemic stroke patients with pre-stroke modified Rankin score (mRS) 0-1 vs ≥2. Logistic regression was used to evaluate the association between pre-stroke mRS and these outcomes adjusting for age, presenting NIHSS, and insurance status. Results: Of 2476 patients with ischemic stroke in the GCNK population during 2015, 1326 (53%) had a pre-stroke mRS ≥2. Compared to those with pre-stroke mRS 0-1, these patients were less likely to receive complete stroke workup (aOR 0.86 [0.71-1.04]) and certain stroke prevention treatments (aOR 0.46[0.26-0.81], p Conclusions: Ischemic stroke patients with pre-stroke disability were less likely to receive complete in-hospital stroke workup and initiation of certain stroke preventive treatments. Further research into factors driving medical decision-making for stroke patients with a pre-stroke disability is urgently needed to ensure optimal continuum of stroke care.

Introduction: Direct oral anticoagulants (DOACs) have emerged as a potential anticoagulant therapy for patients with cerebral venous thrombosis (CVT). We conducted a systematic review and meta-analysis comparing DOACs versus vitamin K antagonists (VKAs) for treatment of CVT. Methods: We registered the review in PROSPERO (registration number CRD42021228800). We searched Medline, Embase, CINAHL, and the Web of Science Core Collection from January 1, 2007, to May 26, 2021. We included randomized controlled trials (RCTs) and non-randomized comparative studies (NRCSs) evaluating key outcomes for efficacy (recurrent venous thromboembolism [VTE] and complete recanalization) and safety (major hemorrhage). We assessed risk of bias using the Cochrane Risk of Bias Tool 2.0 (for RCTs) and the ROBINS-I tool (for NRCSs). Where studies were sufficiently similar, we performed meta-analyses using random-effects models. This review was funded by Brown Neurology. Results: Of 8213 identified records,10 studies (1 RCT and 9 NRCSs) with a total of 662 patients (33% DOAC and 67% VKAs) met the inclusion criteria. We will present our risk of bias assessment at the conference. DOACs and VKAs had comparable efficacy: recurrent VTE (risk ratio [RR] 1.00, 95% confidence interval [CI] 0.44-2.23; I 2 =0%; 10 studies) and complete recanalization (RR 1.00, 95% CI 0.77-1.28; I 2 =0%; 6 studies). DOAC and VKA also had comparable safety: major hemorrhage (RR 0.89, 95% CI 0.37-2.14; I 2 =0%; 9 studies). Conclusions: Studies comparing DOACs with VKAs in patients with CVT consist mostly of small, non-randomized, poorly controlled studies. While the two treatments appear comparable for major efficacy and safety outcomes, large, rigorously conducted studies, preferably randomized, are needed to overcome these limitations and permit development of clinical practice guidelines for the use of DOACs in patients with CVT.

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: Patients with symptomatic intracranial stenosis (ICAS) face elevated risks of recurrent cerebrovascular events (RCE) despite optimal medical therapy. Borderzone infarcts (BZI) indirectly correlate with impaired distal perfusion, a known mechanism of recurrence. Studies assessing associations between borderzone infarcts and recurrence rates are observational and have relatively small sample size. We therefore performed a meta-analysis of published studies investigating this association. Methods: We performed a Medline and Web of Science search using the key words (Intracranial Atherosclerosis OR Intracranial Stenosis) AND (Borderzone OR Infarct Pattern) to identify studies reporting associations between index infarct pattern and RCE, defined as recurrent ischemic stroke or neurological deterioration, or new infarct on follow up neuroimaging in patients with symptomatic ICAS. We included relevant papers and scientific abstracts with more than 20 patients included. For all outcome events we calculated the corresponding risk ratios (RRs) and 95% confidence intervals (95% CI). Results: We identified 178 studies using Web of Science and 384 studies using Medline with only 6 studies (591 patients) meeting our inclusion criteria (2 prospective and 4 retrospective). The weighted proportion of patients with BZI was 32.5% (28.7%-36.4%). During a follow-up period of 7-950 days, 33.1% (26.3%-40.5%) of patients with BZI had RCE and 63.6% (30.8%-89.1%) had new infarction on a 6-8 week follow up brain MRI. In meta-analysis, BZI was associated with increased rates of RCE (RR 2.40 95% CI 1.71-3.37) and new infarct(s) on follow up brain MRI (RR 2.55 95% CI 1.31-4.94). The findings were unchanged when the analysis was limited to 90-day RCE risks only (RR 2.22 95% 1.49-3.29). Conclusions: BZI are associated with over 2-fold increased risk of RCE and recurrent infarct in patients with symptomatic ICAS. Prospective studies are needed to validate these findings.

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.

Introduction: Stroke is the fifth leading cause of death in the US and a major cause of disability. Atrial fibrillation (AF) increases the risk of ischemic stroke fivefold. Cardioembolic stroke in patients with AF is associated with high mortality. The association of elevated cardiac troponin with mortality in patients with acute ischemic stroke has been studied previously; however, there is limited data in subgroups of ischemic stroke etiology. We sought to determine the association of troponin elevation at presentation with 90-day all-cause mortality in patients with acute ischemic stroke and AF. Methods: The I nitiation of A nticoagulation after C ardioembolic Stroke (IAC) study is a multicenter cohort drawn from eight US Stroke Centers. We included consecutive patients hospitalized with acute ischemic stroke and AF between 2015-2018, who had an initial baseline cardiac troponin I (bcTnI) obtained at presentation. The primary outcome was all-cause mortality at 90 days from stroke onset. We undertook multivariable logistic regression to determine the association between elevated bcTnl (≥0.1 ng/mL) and 90-day mortality. Results: Of the 2084 patients enrolled in IAC, 1889 patients had 90-day follow-up of which 1461 patients had bcTnI available. 239 of the included patients (16.4%) had an elevated bcTnl, and death within 90-days occurred in 323 patients (22.1%). Elevated bcTnI was associated with 90-day mortality in univariable analysis (49.4% vs 24.9%; OR 1.71, 95% CI 1.17-2.50, p Conclusion: In acute ischemic stroke patients with AF, elevated bcTnI was independently associated with 90-day all-cause mortality.

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: 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.

Background: Acute ischemic stroke (AIS) remains a leading cause of mortality and disability worldwide, with stroke etiology having an important role in work-up, management, and prognosis. The current AHA/ASA guidelines cite routine echocardiography as reasonable but not mandatory for the work-up of ischemic stroke. We sought to identify how often transthoracic echocardiogram (TTE) results would show a potentially treatment-altering finding. Methods: Using the Greater Cincinnati/Northern Kentucky Stroke Study (GCNKSS) for years 2005, 2010, and 2015, we selected patients with a new diagnosis of AIS using ICD-9/10 codes in adults ≥18yrs of age presenting to the emergency department and who had a TTE with stroke etiology of Cardioembolic, Small Vessel, or Large Vessel. All cases were physician reviewed and stroke etiology determined based on our epidemiologic criteria. Demographic information, medical history, electrocardiograms with atrial fibrillation (Afib), and TTE features were collected for each patient and compared across stroke etiology groups using Wilcoxon rank sum test and chi-square test, or Fisher’s exact test, as appropriate. Results: There were 5,490 patients presenting with AIS in the GCNKSS in 2005, 2010, and 2015 and 3,984 (73%) had a TTE performed. Of those with TTE, 2,422 (61%) had a presumed etiology of Small Vessel, Large Artery Atherosclerosis (LAA), or Cardioembolic (120 identified as “Other,” 1442 identified as “Undetermined”). Potential findings of TTE that could change management were 1% in Small Vessel, 2% in LAA, and 7% in Cardioembolic etiology strokes. Conclusion: In patients presenting with Small Vessel or LAA stroke etiologies, routine inpatient TTE rarely had management-changing findings. Future studies are needed in order to assess cost effective use of TTE in patients with established stroke etiology.

BACKGROUND: Anticoagulation increases the risk of intracerebral hemorrhage (ICH) in patients with cerebral amyloid angiopathy (CAA), so the management of stroke-risk in patients with both atrial fibrillation (AF) and CAA is controversial. Advances in left atrial appendage closure (LAAC) techniques provide a stroke-risk-reduction option which avoids long-term oral anticoagulation (OAC). We aimed to evaluate the safety of this intervention in patients with CAA. METHODS: This is an observational cohort study of patients with severe CAA (with or without ICH) and AF who were treated with LAA closure. The Watchman™ and Amulet® LAAC devices, Lariat procedure or open surgical closure of the LAA were all considered acceptable means of closure. Patients with symptomatic ICH and those naive to anticoagulation were placed on clopidogrel and/or aspirin for 6 weeks after the procedure; patients who previously tolerated anticoagulation remained on warfarin or a DOAC for 6 weeks post-procedure. All antiplatelet and anticoagulation therapy was discontinued after confirmation of LAAC. All patients had aggressively optimized blood pressure and fall precautions in addition to surgical intervention. Safety, tolerability, stroke and hemorrhage rates were documented. OUTCOME: Twenty-six patients with a mean CHA(2)DS(2)-VASc score of 4.6 were treated, 13 with a history of symptomatic lobar hemorrhage and 13 without. All patients who completed LAAC tolerated device implantation. There were no documented ischemic strokes or symptomatic ICH during the 30 days after device implantation. Patients were followed for an average of 25 months. One patient who underwent LARIAT LAAC had an ischemic stroke in follow-up, but recovered well; there were no other thromboemboli in this cohort. CONCLUSIONS: This cohort study provides evidence that LAAC appears to be a safe and tolerable treatment to reduce stroke risk in patients with CAA. Because of the small size of the cohort and relatively short follow-up, the efficacy for stroke and ICH prevention is not conclusive, but the preliminary results are encouraging. LAA closure may be a good alternative to anticoagulation in patients with CAA and atrial fibrillation.

IntroductionPredictors of long-term ischaemic and haemorrhagic complications in atrial fibrillation (AF) have been studied, but there are limited data on predictors of early ischaemic and haemorrhagic complications after AF-associated ischaemic stroke. We sought to determine these predictors.MethodsThe Initiation of Anticoagulation after Cardioembolic stroke study is a multicentre retrospective study across that pooled data from consecutive patients with ischaemic stroke in the setting of AF from stroke registries across eight comprehensive stroke centres in the USA. The coprimary outcomes were recurrent ischaemic event (stroke/TIA/systemic arterial embolism) and delayed symptomatic intracranial haemorrhage (d-sICH) within 90 days. We performed univariate analyses and Cox regression analyses including important predictors on univariate analyses to determine independent predictors of early ischaemic events (stroke/TIA/systemic embolism) and d-sICH.ResultsOut of 2084 patients, 1520 patients qualified; 104 patients (6.8%) had recurrent ischaemic events and 23 patients (1.5%) had d-sICH within 90 days from the index event. In Cox regression models, factors associated with a trend for recurrent ischaemic events were prior stroke or transient ischemic attack (TIA) (HR 1.42, 95% CI 0.96 to 2.10) and ipsilateral arterial stenosis with 50%–99% narrowing (HR 1.54, 95% CI 0.98 to 2.43). Those associated with sICH were male sex (HR 2.68, 95% CI 1.06 to 6.83), history of hyperlipidaemia (HR 2.91, 95% CI 1.08 to 7.84) and early haemorrhagic transformation (HR 5.35, 95% CI 2.22 to 12.92).ConclusionIn patients with ischaemic stroke and AF, predictors of d-sICH are different than those of recurrent ischaemic events; therefore, recognising these predictors may help inform early stroke versus d-sICH prevention strategies.

Background and Purpose— The first of the 2 NINDS (National Institute of Neurological Disorders and Stroke) Study trials did not show a significant increase in early neurological improvement, defined as National Institutes of Health Stroke Scale (NIHSS) improvement by ≥4, with alteplase treatment. We hypothesized that early neurological improvement defined as a percentage change in NIHSS (percent change NIHSS) at 24 hours is superior to other definitions in predicting 3-month functional outcomes and using this definition there would be treatment benefit of alteplase over placebo at 24 hours. Methods— We analyzed the NINDS rt-PA Stroke Study (Parts 1 and 2) trial data. Percent change NIHSS was defined as ([admission NIHSS score−24-hour NIHSS score]×100/admission NIHSS score] and delta NIHSS as (admission NIHSS score−24-hour NIHSS score). We compared early neurological improvement using these definitions between alteplase versus placebo patients. We also used receiver operating characteristic curve to determine the predictive association of early neurological improvement with excellent 3-month functional outcomes (Barthel Index score of 95–100 and modified Rankin Scale score of 0–1), good 3-month functional outcome (modified Rankin Scale score of 0–2), and 3-month infarct volume. Results— There was a significantly greater improvement in the 24-hour median percent change NIHSS among patients treated with alteplase compared with the placebo group (28% versus 15%; P =0.045) but not median delta NIHSS (3 versus 2; P =0.471). Receiver operating characteristic curve comparison showed that percent change NIHSS (ROC percent ) was better than delta NIHSS (ROC delta ) and admission NIHSS (ROC admission ) with regards to excellent 3-month Barthel Index (ROC percent , 0.83; ROC delta , 0.76; ROC admission , 0.75), excellent 3-month modified Rankin Scale (ROC percent , 0.83; ROC delta , 0.74; ROC admission , 0.78), and good 3-month modified Rankin Scale (ROC percent , 0.83; ROC delta , 0.76; ROC admission , 0.78). Conclusions— In the NINDS rt-PA trial, alteplase was associated with a significant percent change improvement in NIHSS at 24 hours. Percent change in NIHSS may be a better surrogate marker of thrombolytic activity and 3-month outcomes.

BACKGROUND AND PURPOSE: The increased severity of white matter disease is associated with worse outcomes and an increased rate of intracerebral hemorrhage in patients with ischemic stroke undergoing thrombolytic treatment. However, whether white matter disease is associated with outcomes in patients undergoing endovascular treatment remains unclear. MATERIALS AND METHODS: In this prespecified exploratory analysis of our prospective multi-institutional study that enrolled consecutive adult patients with anterior circulation ischemic stroke undergoing endovascular treatment from November 2017 to September 2018, we compared the following outcomes between patients with none-to-minimal (van Swieten score, 0–2) and moderate-to-severe (van Swieten score, 3–4) white matter disease using logistic regression: 90-day mRS 3–6, death, intracerebral hemorrhage, successful recanalization, and early neurologic recovery. RESULTS: Of the 485 patients enrolled in the Blood Pressure after Endovascular Stroke Therapy (BEST) study, 389 had white matter disease graded (50% women; median age, 68 years; range, 58–79 years). A van Swieten score of 3–4 (n = 74/389, 19%) was associated with a higher rate of 90-day mRS of 3–6 (45% versus 18%; adjusted OR, 2.73; 95% CI, 1.34–5.93; P = .008). Although the death rate was higher in patients with van Swieten scores of 3–4 (26% versus 15%), the adjusted likelihood was not significantly different (adjusted OR, 1.14; 95% CI, 0.56–2.26; P = .710). Ordered regression revealed a shift toward worse mRS scores with increasing van Swieten scores (adjusted common OR, 3.04; 95% CI, 1.93–4.84; P

Limited data exist evaluating the effect of blood pressure (BP) on clinical outcomes among patients with acute ischemic stroke with large vessel occlusion treated with mechanical thrombectomy (MT). We sought to evaluate the association of BP levels on clinical outcomes among patients with acute ischemic stroke with large vessel occlusion treated with MT. Studies were identified that reported the association of systolic BP (SBP) or diastolic BP levels before, during, or after MT on the outcomes of patients with acute ischemic stroke treated with MT. Unadjusted and adjusted analyses of studies reporting odds ratios (OR adj ) per 10 mm Hg BP increment were performed. Our analysis included 25 studies comprising 6474 patients. Higher pre-MT mean SBP ( P =0.008) and post-MT maximum SBP ( P =0.009) levels were observed in patients who died within 3 months. Patients with 3-month functional independence were noted to have lower pre-MT ( P P adj , 1.19 [95% CI,1.00–1.43]; I 2 =78%, P value for Cochran Q test: 0.001) and symptomatic intracranial hemorrhage (OR adj , 1.65 [95% CI, 1.11–2.44]; I 2 =0%, P value for Cochran Q test: 0.80), respectively. Increasing pre- and post-MT mean SBP levels were associated with lower odds of 3-month functional independence (OR adj , 0.86 [95% CI, 0.77–0.96]; I 2 =18%, P value for Cochran Q test: 0.30) and (OR adj , 0.80 [95% CI, 0.72–0.89]; I 2 =0%, P value for Cochran Q test: 0.51), respectively. In conclusion, elevated BP levels before and after MT are associated with adverse outcomes among patients with acute ischemic stroke with large vessel occlusion.

BackgroundTrials of endovascular thrombectomy (EVT) for acute stroke have excluded patients with pre-morbid disability. Observational studies may help inform consideration of EVT in this population. We aimed to assess the effectiveness and safety of EVT in patients with pre-morbid disability.MethodsAccording to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched MEDLINE and Embase for studies describing outcomes in patients with pre-morbid disability (modified Rankin Scale (mRS) 2–5), treated with EVT or medical management (MM). Random-effects meta-analysis was used to pool outcomes including 90-day return to baseline mRS, symptomatic intracerebral hemorrhage (sICH), and 90-day mortality.ResultsWe analyzed 14 studies of patients with pre-morbid disability (mRS 2–5, 1373 EVT and 253 MM). The rate of return to baseline mRS was 30.0% (95% CI 25.3% to 34.7%) in patients treated with EVT. Compared with medical therapy, EVT was associated with a higher likelihood of return to baseline mRS (OR 2.37, 95% CI 1.39 to 4.04) and a trend towards lower mortality (OR 0.68, 95% CI 0.46 to 1.02), with similar odds of sICH (OR 1.01, 95% CI 0.49 to 2.08). In studies comparing patients with versus without pre-morbid disability treated with EVT, similar results were found except that pre-morbid disability, when defined more strictly as mRS 3–5, was associated with mortality (OR 3.49, pConclusionIn eligible patients with pre-morbid disability, observational studies suggest that EVT carries a higher chance of return to baseline mRS compared with patients treated with MM or without pre-morbid disability, although with higher mortality than patients without pre-morbid disability. These findings argue against the routine exclusion of such patients from EVT and merit validation with randomized trials.

Background: It is unclear what factors clinicians consider when deciding about endovascular thrombectomy (EVT) in acute ischemic stroke patients with a pre-existing disability. We aimed to explore international practice patterns and preferences for EVT in patients with a pre-stroke disability, defined as a modified Rankin score (mRS) ≥ 2.Methods: Electronic survey link was sent to principal investigators of five major EVT trials and members of a professional interventional neurology society.Results: Of the 81 survey-responding clinicians, 57% were neuro-interventionalists and 33% were non-interventional stroke clinicians. Overall, 64.2% would never or almost never consider EVT for a patient with pre-stroke mRS of 4-5, and 49.3% would always or almost always offer EVT for a patient with pre-stroke mRS 2-3. Perceived benefit of EVT (89%) and severity of baseline disability (83.5%) were identified as the most important clinician-level and patient-level factors that influence EVT decisions in these patients.Conclusion: In this survey of 80 respondents, we found that EVT practice for patients with pre-stroke disability across the world is heterogenous and depends upon patient characteristics. Individual clinician opinions substantially alter EVT decisions in pre-stroke disabled patients.

Background Intravenous alteplase improves outcome after acute ischemic stroke without a benefit in 90‐day mortality. There are limited data on whether alteplase is associated with reduced mortality in patients with atrial fibrillation (AF)‐related ischemic stroke whose mortality rate is relatively high. We sought to determine the association of alteplase with hemorrhagic transformation and mortality in patients with AF. Methods and Results We retrospectively analyzed consecutive patients with acute ischemic stroke between 2015 and 2018 diagnosed with AF included in the IAC (Initiation of Anticoagulation After Cardioembolic Stroke) study, which pooled data from stroke registries at 8 comprehensive stroke centers across the United States. For our primary analysis, we included patients who did not undergo mechanical thrombectomy (MT), and secondary analyses included patients who underwent MT. We used binary logistic regression to determine whether alteplase use was associated with risk of hemorrhagic transformation and 90‐day mortality. There were 1889 patients (90.6%) who had 90‐day follow‐up data available for analyses and were included; 1367 patients (72.4%) did not receive MT, and 522 patients (27.6%) received MT. In our primary analyses we found that alteplase use was independently associated with an increased risk for hemorrhagic transformation (odds ratio [OR], 2.23; 95% CI, 1.57–3.17) but reduced risk of 90‐day mortality (OR, 0.58; 95% CI, 0.39–0.87). Among patients undergoing MT, alteplase use was not associated with a significant reduction in 90‐day mortality (OR, 0.68; 95% CI, 0.45–1.04). Conclusions Alteplase reduced 90‐day mortality of patients with acute ischemic stroke with AF not undergoing MT. Further study is required to assess the efficacy of alteplase in patients with AF undergoing MT.