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Background and Purpose: Data are lacking on the long-term risk of hip fracture among patients with ischemic stroke. A better understanding of the contemporary incidence of hip fracture after ischemic stroke could benefit patient care by promoting strategies to prevent this disabling complication in stroke survivors. Methods: We performed a retrospective cohort study using inpatient and outpatient claims between 2008 and 2015 from a nationally representative 5% sample of Medicare beneficiaries. We included patients ≥66 years of age who were hospitalized with acute ischemic stroke, defined through a validated diagnostic code algorithm. We excluded patients who had a prior or concurrent hip fracture diagnosis at the time of ischemic stroke. The primary outcome was hip fracture requiring hospitalization. Survival statistics were used to calculate crude incidence rates, and the Kaplan-Meier method was used to calculate cumulative rates. Results: Among the 1 772 550 beneficiaries in our sample, 60 099 were diagnosed with an acute ischemic stroke without prior or concomitant hip fracture. During 4.5 (±2.2) years of follow-up, the incidence of hip fracture was 1.6 (95% confidence interval [CI]: 1.5-1.6) per 100 person-years in patients with acute ischemic stroke versus 0.6 (95% CI: 0.6-0.6) per 100 person-years in patients without acute ischemic stroke. The cumulative 5-year rate of hip fracture was 7.6% (95% CI: 7.2%-8.0%) among patients with acute ischemic stroke versus 2.8% (95% CI: 2.8%-2.9%) among the remaining Medicare beneficiaries. Conclusion: We found that among elderly Medicare beneficiaries with acute ischemic stroke, nearly 1 in 12 developed a hip fracture over the next 5 years.

Background Retrospective studies have reported an association between cancer and arterial thromboembolic event (ATE) risk. Objectives We sought to confirm this in a prospective cohort with adjudicated outcomes. Methods We evaluated participants enrolled in the REGARDS (REasons for Geographic and Racial Differences in Stroke) study with Medicare coverage for 365 days before their baseline visit (2003-2007). Medicare claims were used to identify new cancer diagnoses during follow-up. Using incidence-density sampling, participants who developed cancer were matched by age, sex, race, and education 1:4 to control participants who had not developed cancer. Participants were prospectively followed through 2015 for an expert-adjudicated ATE, defined as acute myocardial infarction or ischemic stroke. Cox regression was performed to evaluate the association between incident cancer and subsequent ATE. Results In this analysis, 836 REGARDS participants with incident cancer were matched to 3339 control participants without cancer. In the 30 days after cancer diagnosis, 0.60% (n = 5) of the participants had an ATE; most of these events occurred near the time of cancer diagnosis. After adjustment for demographics, geographic region, and cardiovascular risk factors, compared to the noncancer controls, participants with incident cancer had an increased risk of ATE in the first 30 days after diagnosis (hazard ratio, 5.8; 95% confidence interval, 2.1-15.9). There was no association between cancer diagnosis and ATE beyond 30 days. Cancers with known metastases and types considered high risk for venous thromboembolism had the strongest associations with ATE. Conclusions Incident cancer is associated with an increased short-term risk of ATE independent of vascular risk factors.

Background: The short-term risk of ischemic stroke in patients with left ventricular (LV) thrombus identified via delayed-enhancement cardiac magnetic resonance (DE-CMR) imaging is uncertain. Methods: We performed a retrospective cohort study of patients who underwent DE-CMR for evaluation of LV systolic dysfunction at NewYork-Presbyterian Hospital/Weill Cornell between 2007 and 2016. We identified all hospitalized patients who had DE-CMR evidence of LV thrombus, and as controls, all hospitalized patients who had no DE-CMR evidence of LV thrombus; 2 control patients were randomly selected for each patient with LV thrombus. Our primary outcome was ischemic stroke prior to hospital discharge. Additionally, we compared the risk of stroke among patients with: (1) no LV thrombus, (2) LV thrombus by DE-CMR but not by echocardiography, and (3) LV thrombus by both DE-CMR and echocardiography. Results: We identified 33 patients with LV thrombus and 66 patients without LV thrombus on DE-CMR. Of the 33 patients with LV thrombus on DE-CMR, 13 had echocardiographic evidence of thrombus. Ischemic stroke occurred in 3 of 33 (9.1%; 95% CI, 1.9%-24.3%) patients with LV thrombus on DE-CMR. Ischemic stroke occurred in 0 of 66 (0%; 95% CI, 0%-5.4%) patients without LV thrombus on DE-CMR, 1 of 20 (5.0%; 95% CI, .1%-24.9%) patients with thrombus on DE-CMR but not echocardiogram, and 2 of 13 (15.4%; 95% CI, 1.9%-45.4%) patients with thrombus on both DE-CMR and echocardiogram (P value for comparison among groups, .02). Conclusions: We found a 9% short-term risk of ischemic stroke in patients with LV thrombus detected on DE-CMR.

Cancer patients face an increased risk of arterial thromboembolism; however, it is uncertain when this excess risk begins. This study evaluated the risk of arterial thromboembolism before cancer diagnosis. Using the population-based Surveillance Epidemiology and End Results-Medicare linked dataset, we identified 374 331 patients ≥67 years of age with a new primary diagnosis of breast, lung, prostate, colorectal, bladder, uterine, pancreatic, gastric cancer, or non-Hodgkin lymphoma from 2005 through 2013. Cancer patients were individually matched by demographics and comorbidities to Medicare beneficiaries without cancer, who served as controls. Validated diagnosis codes were used to identify arterial thromboembolic events, defined as a composite of myocardial infarction or ischemic stroke. The Mantel-Haenszel estimator was used to compare risks of arterial thromboembolic events between cancer and noncancer groups during 30-day periods in the 360 days before date of cancer diagnosis. From 360 to 151 days before cancer diagnosis, the 30-day interval risks of arterial thromboembolic events were similar between cancer patients and matched controls. From 150 to 1 day before cancer diagnosis, the interval 30-day risks of arterial thromboembolic events were higher in cancer patients vs matched controls, progressively increasing as the cancer diagnosis date approached and peaking during the 30 days immediately before cancer diagnosis, when 2313 (0.62%) cancer patients were diagnosed with an arterial thromboembolic event vs 413 (0.11%) controls (odds ratio, 5.63; 95% confidence interval, 5.07-6.25). In conclusion, the risk of arterial thromboembolic events begins to increase 150 days before the date of cancer diagnosis in older persons and peaks in the 30 days before.

Background: In 2013, investigators from A Randomized Trial of Unruptured Brain Arteriovenous Malformations (AVM; ARUBA) reported that interventions to obliterate unruptured AVMs caused more morbidity and mortality than medical management. Objective: We sought to determine whether interventions for unruptured AVM decreased after publication of ARUBA results. Methods: We used the Nationwide Readmissions Database to assess trends in interventional AVM management in patients ≥18 years of age from 2010 through 2015. Unruptured brain AVMs were identified using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code 747.81 and excluding any patient with a diagnosis of intracranial hemorrhage. Our primary outcome was interventional AVM treatment, identified using ICD-9-CM procedure codes for surgical resection, endovascular therapy, and stereotactic radiosurgery. Join-point regression was used to assess trends in the incidence of interventional AVM management among adults from 2010 through 2015. Results: There was no significant U.S. population level change in unruptured brain AVM intervention rates before versus after ARUBA (p = 0.59), with the incidence of AVM intervention ranging from 8.0 to 9.2 per 10 million U.S. residents before the trial publication to 7.7–8.3 per 10 million afterwards. Conclusions: In a nationally representative sample, we found no change in rates of interventional unruptured AVM management after publication of the ARUBA trial results.

Background and Purpose Risk factors for hemorrhagic transformation of ischemic stroke after mechanical thrombectomy (MT) are not well established. We conducted a study to determine if prominent angiographic cerebral vascularity following recanalization with thrombectomy (angiographic blush) is associated with hemorrhagic transformation. Methods Using the Cornell AcutE Stroke Academic Registry, we identified stroke patients who had thrombectomy and achieved recanalization of anterior circulation large-vessel occlusion between 2012 and 2015. The exposure variable was presence of angiographic blush after recanalization, defined as capillary blush with or without early venous drainage. The primary outcome was volume of hemorrhagic transformation on brain imaging after thrombectomy, as determined by semiautomated volumetric analysis on computed tomography or magnetic resonance imaging among those adjudicated to have hemorrhagic conversion by neuroradiology investigators blinded to angiography results. Using a doubly robust estimator with propensity scores and outcome regression adjusting for demographics and known risk factors for hemorrhagic transformation, we evaluated whether angiographic blush after recanalization is associated with an increased volume of hemorrhagic transformation. Results Among 48 eligible patients, 31 (64.6%) had angiographic blush and 26 (54.2%) had radiographic hemorrhagic transformation (mean volume, 7.6 ml). Patients with angiographic blush averaged lower thrombolysis in cerebral infarction scores and more often received intravenous thrombolysis. In adjusted analysis, angiographic blush was associated with an increased volume of hemorrhagic transformation: mean volume, 10.3ml (95% CI, 3.7-16.9 ml) with blush versus 1.8ml (95% Confidence Interval (CII = Confidence Interval), 0.1-3.4 ml) without (P = .01). Conclusions Presence of angiographic blush after MT was independently associated with the volume of hemorrhagic transformation.

Cancer patients with acute ischemic stroke (AIS) are high-risk for recurrent thromboembolic events (RTE). Currently, no risk stratification model exists to predict RTE in this population. We tested the hypothesis that the Khorana score, a validated risk model for predicting venous thromboembolism in cancer patients, can effectively classify RTE risk in cancer patients with AIS. We retrospectively identified adults with active solid or hematological cancer diagnosed with AIS at a tertiary-care cancer center from 2005 to 2010. The Khorana score at the time of index stroke was calculated. The primary outcome was arterial or venous RTE. Cox regression was used to evaluate the association of the Khorana score and its individual components with RTE. Harrell’s c-statistic was used to calculate the score’s discriminatory ability. Among 263 AIS patients, median survival was 84 days (IQR 24–149 days) and 90 (34%) had RTE. The median Khorana score was 2 (IQR 1–2, range 0–5). Cumulative rate of RTE was 28% among patients who scored 0, 36% with scores of 1–2, and 32% with scores of 3–6. The overall Khorana score was marginally associated with RTE (HR, 1.14; 95% CI, 1.02–1.28). Of its individual components, only leukocytosis was associated with RTE (HR adjusted for other components, 1.45; 95% CI 1.11–1.90). The score’s c-statistic for predicting RTE was 0.57. In this study, the Khorana score had poor discriminatory ability for predicting RTE in cancer patients with AIS. Future research is needed to identify better methods for predicting RTE in this high-risk population.

Thrombophilia testing is frequently performed after an ischemic stroke, particularly when cryptogenic. However, there is minimal evidence supporting a significant association between most conditions assessed through thrombophilia testing and ischemic stroke, and the rationale for thrombophilia testing in many clinical situations remains uncertain. In this topical review, we review and contextualize the existing data on the risks, predictors, and outcomes of thrombophilic conditions in patients with ischemic stroke. We report that inherited thrombophilias have an uncertain relationship with ischemic stroke. Conversely, antiphospholipid syndrome, an acquired immune-mediated thrombophilia, seems to be a strong risk factor for arterial thromboembolic events, including ischemic stroke, and especially among young patients. Our findings suggest that certain circumstances may warrant targeted thrombophilia testing, such as stroke in the young, cryptogenic stroke, and high estrogen states. Future prospective studies should investigate the utility and cost effectiveness of thrombophilia testing in various stroke settings, including among patients with patent foramen ovale; as well as the optimal secondary stroke prevention regimen in patients with confirmed thrombophilia, particularly if no other potential stroke mechanism is identified.

Background: Recent clinical trials have established the efficacy of endovascular stroke therapy and intravenous thrombolysis using advanced imaging, particularly computed tomography perfusion (CTP). The availability and utilization of CTP for patients and hospitals that treat acute ischemic stroke (AIS), however, is uncertain. Methods: We performed a retrospective cross-sectional analysis using 2 complementary Medicare datasets, full sample Texas and 5% national fee-for-service data from 2014 to 2017. AIS cases were identified using International Classification of Diseases , Ninth Revision and International Classification of Diseases , Tenth Revision coding criteria. Imaging utilization performed in the initial evaluation of patients with AIS was derived using Current Procedural Terminology codes from professional claims. Primary outcomes were utilization of imaging in AIS cases and the change in utilization over time. Hospitals were defined as imaging modality–performing if they submitted at least 1 claim for that modality per calendar year. The National Medicare dataset was used to validate state-level findings, and a local hospital-level cohort was used to validate the claims-based approach. Results: Among 50 797 AIS cases in the Texas Medicare fee-for-service cohort, 64% were evaluated with noncontrast head CT, 17% with CT angiography, 3% with CTP, and 33% with magnetic resonance imaging. CTP utilization was greater in patients treated with endovascular stroke therapy (17%) and intravenous thrombolysis (9%). CT angiography (4%/y) and CTP (1%/y) utilization increased over the study period. These findings were validated in the National dataset. Among hospitals in the Texas cohort, 100% were noncontrast head CT–performing, 77% CT angiography–performing, and 14% CTP-performing in 2017. Most AIS cases (69%) were evaluated at non-CTP–performing hospitals. CTP-performing hospitals were clustered in urban areas, whereas large regions of the state lacked immediate access. Conclusions: In state-wide and national Medicare fee-for-service cohorts, CTP utilization in patients with AIS was low, and most patients were evaluated at non-CTP–performing hospitals. These findings support the need for alternative means of screening for AIS recanalization therapies.

Introduction: Black Americans face a higher risk of recurrent stroke than White Americans, and the reasons are unclear. Smoking after stroke is associated with a higher risk of recurrence. We investigated whether there are racial disparities in smoking cessation among stroke survivors in the United States. Methods: We performed a cross-sectional analysis of data from the Centers for Disease Control and Prevention Behavioral Risk Factor Surveillance System, an annual, nationally representative health survey. Respondents are asked about medical conditions and health-related behaviors. We pooled data from 2013-2018, during which race and ethnicity were uniformly reported. We included respondents with prior stroke and any smoking history. The exposure was self-reported race, and the outcome was smoking cessation. We calculated the quit ratio, defined as the proportion of former smokers among ever smokers; this is a standard measure in population-based studies of smoking cessation. Survey procedures were used to estimate frequencies and summarize quit ratios by race. Multiple logistic regression was used to assess the association of Black race with smoking cessation, as compared to White race, while adjusting for age, gender, Hispanic ethnicity, education, income, health insurance, and the number of smoking-related health conditions (heart disease, lung disease, cancer) that may prompt cessation. Results: Among 4,374,011 Americans with a history of stroke and any smoking, the median age was 67 years (IQR, 58-76), and 45.7% were women; 15.4% were Black, 74.8% were White, and 9.8% reported other race. The crude quit ratio was 51.4% (95% CI, 49.0-53.7) in Black and 63.2% (95% CI, 62.4-64.1) in White stroke survivors. In unadjusted analyses, Black stroke survivors were less likely to have quit smoking than White stroke survivors (OR, 0.61; 95% CI, 0.55-0.68). This remained the case after accounting for differences in demographics and smoking-related comorbidities (OR, 0.85; 95% CI, 0.74-0.98). Conclusion: In this nationwide study, Black stroke survivors had lower smoking quit rates than White stroke survivors, even after accounting for group differences. Expanding access to smoking-cessation interventions may reduce disparities in recurrent stroke.

Introduction: Influenza-like illness (ILI) is associated with an increased short-term risk of ischemic stroke. Whether ILI is associated with an increased short-term risk of hemorrhagic stroke remains uncertain. Hypothesis: We hypothesized that ILI would be associated with a heightened risk of hemorrhagic stroke. Methods: We performed a case-crossover analysis utilizing administrative claims data from all emergency department visits and acute care hospitalizations from 2006-2015 in NY and 2005-2015 in FL. We used previously validated International Classification of Disease, Ninth Revision, Clinical Modification codes (ICD-9-CM) to identify patients with ILI and hemorrhagic stroke. Hemorrhagic stroke was defined as the composite of nontraumatic intracranial hemorrhage, nontraumatic subarachnoid hemorrhage, and nontraumatic subdural hemorrhage. We compared the risk of hemorrhagic stroke in successive 30-day periods after ILI versus the corresponding 30-day period one year earlier. We used McNemar test for matched data to calculate the absolute risk increases. Results: We identified 2,838,178 patients with ILI. The absolute increase in hemorrhagic stroke risk was 0.02% (95% confidene interval [CI], 0.02-0.03%) in the thirty days post ILI compared with the same period one year earlier (OR, 3.7; 95% CI, 3.2-4.3). The absolute increase in hemorrhagic stroke risk decreased over successive 30-day periods after ILI and was no longer significant after 180 days post ILI (Figure). Our results were similar when we evaluated the risk of hemorrhagic stroke subtypes separately. Conclusions: ILI is associated with a heightened short-term risk of hemorrhagic stroke. Further studies are warranted to evaluate mechanisms of how infection and/or inflammation lead to a heightened risk of hemorrhagic stroke.

Introduction: Aortic stenosis (AS) is known to cause mechanical degradation of von Willebrand factor, resulting in an increased risk of gastrointestinal bleeding, also known as Heyde syndrome. We hypothesized that AS is also associated with an increased risk of nontraumatic intracerebral hemorrhage (ICH). Methods: We performed a retrospective cohort study of Medicare beneficiaries using a 5% sample of inpatient and outpatient claims from1/1/2008-9/30/2015. Based on prior validation, we ascertained AS based on at least one inpatient or two outpatient claims with ICD-9-CM diagnosis code 395.0 in any position. ICH was identified through a validated ICD-9-CM diagnosis code algorithm. We used survival statistics to determine incidence rates and Cox proportional hazard analyses to examine associations. In prespecified models, we controlled for age, gender, race, bleeding risk (HAS-BLED and ATRIA scores), and common indications for antithrombotic treatment (atrial fibrillation, coronary artery disease, peripheral vascular disease, venous thromboembolism). Results: Among 1,785,836 Medicare beneficiaries, the mean age was 73.5 years (SD, 7.7) and 57.0% were women. AS was diagnosed in 6,157 (0.34%) patients. During a mean of 4.7 years (SD, 2.2) of follow-up, 28,309 (1.6%) were hospitalized with ICH. The incidence of ICH was 5.9 (95% CI, 4.9-7.2) per 1,000 person-years in those with AS compared to 3.4 (95% CI, 3.4-3.4) per 1,000 person-years in those without. After adjustment for demographics, AS was associated with an increased risk of ICH (HR, 1.31; 95% CI, 1.09-1.59). This association was not statistically significant after adjusting additionally for HAS-BLED score components (HR 1.15, 95% CI 0.95-1.39) or ATRIA score components (HR 1.18, 95% CI 0.98-1.43). Effect sizes were further attenuated after adjusting for indications for antithrombotic drugs in addition to the HAS-BLED score (HR, 0.90; 95% CI, 0.74-1.09) and ATRIA score (HR, 0.90; 95% CI, 0.73-1.08). Conclusions: Medicare beneficiaries with AS faced an elevated risk of ICH. However, comorbid conditions that require the use of antithrombotic drugs accounted for the observed association, making an independent association between AS and ICH unlikely.

Introduction: Reductions in hospital visits for stroke have been seen during the COVID-19 pandemic, partly reflecting perceived risks of in-hospital care. We recently implemented an evidence-based protocol for outpatient rapid evaluation of transient and minor, non-disabling stroke symptoms for patients seeking care 24 hours after symptom onset. We present our early experience through the pandemic. Methods: We conducted a retrospective review of patients evaluated in the RESCUE-TIA ( R apid E valuation of minor S troke and C erebrovasc U lar E vents including TIA ) clinic from December 2019-August 2020. The clinic sees patients with TIA symptoms or with fixed, non-disabling deficits seeking care > 24 hours after symptom onset. We introduced telemedicine in March 2020. Magnetic resonance brain and vascular imaging is available within 24 hours of visit. We summarized patient characteristics and quality data with standard descriptive statistics. Results: A total of 21 patients were seen in the RESCUE-TIA clinic, including 15 patients during the height of the pandemic in NY; 67% were seen by telemedicine. The median age was 75 years (interquartile range [IQR], 61-82), and 71% were women. The median NIH Stroke Score for patients with minor stroke was 0 (IQR, 0-1), and the median ABCD 2 score for TIA patients was 3 (IQR, 2-3). Median time from symptom onset to evaluation was 3 days (IQR, 2.5-17.5). Median time from evaluation to laboratory diagnostics was 8 hours (IQR, 2-21), and to completion of imaging was 1 day (IQR, 0-5). Outpatient telemetry commenced in a median of 5 days (IQR, 1-9), and echocardiography was completed in a median of 8 days (IQR, 0-10). One patient was referred to the emergency room for a carotid occlusion. Final diagnoses were TIA (n=12), ischemic stroke (n=5), transient global amnesia (n=2), migraine (n=1), and non-aneurysmal, distal subarachnoid hemorrhage (n=1). Secondary prevention was initiated or optimized in 94% of TIA and stroke patients. Recurrent TIA occurred in 1 patient after 67 days, and ischemic stroke occurred in 1 patient 55 days after TIA. Conclusion: Timely outpatient evaluation of patients with recent TIA and minor, non-disabling stroke is feasible and may be useful during the pandemic, especially during emergency room crowding.

Introduction: Patients with acute ischemic stroke (AIS) are generally vulnerable to subsequent infection, but there are few population-based data on the risk of herpes zoster infection after AIS. We tested the hypothesis that AIS is associated with an increased risk of zoster. Methods: We performed a retrospective cohort study using statewide administrative claims data from all emergency department (ED) visits and admissions at nonfederal hospitals in Florida from 2005 to 2015 and New York from 2006 to 2015. These Healthcare Cost and Utilization Project data are well suited for longitudinal analyses of acute care utilization. The primary exposure was AIS, and the outcome was subsequent zoster; diagnoses were ascertained using validated ICD-9-CM codes. We excluded people with zoster before AIS. Survival statistics were used to calculate incidence rates, and Cox proportional hazards analysis was used to determine the association between AIS and subsequent ED visit or admission with zoster. In addition to demographics and comorbidities, models were adjusted for conditions associated with zoster (cancer and HIV/AIDS). In a secondary analysis, we limited the population to people under 50 years old, because current guidelines recommend zoster vaccination for only those at least 50 years old. Results: Among 19,675,854 beneficiaries, 421,940 (2.1%) had AIS; their mean age was 70.8 (SD, 14.5) years. Follow-up duration was a mean of 4.1 (SD, 3.0) years. The incidence of zoster was 4.1 per 1000 patient-years in those with AIS and 2.1 per 1000 patient-years in those without. After AIS, the median time to zoster was 1.7 years (IQR, 0.4-4.1). In unadjusted models, patients with AIS had a two-fold higher risk of zoster (HR, 2.1; 95% CI, 2.0-2.1). AIS remained associated with zoster after adjusting for cardiopulmonary comorbidities and risk factors, medical comorbidities, tobacco and alcohol use, cancer, and HIV/AIDS (HR, 1.34; 95% CI, 1.30-1.39). This association was also observed in people under 50 years old (HR, 1.55; 95% CI, 1.31-1.84). Conclusions: AIS is associated with an increased risk of subsequent ED and inpatient visit with zoster infection. Preventive strategies, including with currently available vaccinations, should be investigated.

Introduction: One-tenth of patients with stroke have cancer. We previously identified mRNA profiles differentiating patients with stroke and cancer, stroke only, and cancer only. In this study, we investigated mRNA and microRNA (miRNA) transcriptomes to identify potential miRNA regulators that underlie the observed mRNA changes. Methods: We prospectively enrolled 4 groups of subjects at 3 centers from 2009-2020. This analysis included 41 subjects with ischemic stroke plus cancer, 42 subjects with ischemic stroke only, 28 subjects with cancer only, and 30 vascular risk factor controls. Stroke-only and cancer-only subjects were matched to stroke-plus-cancer subjects by age, sex, and cancer type. We performed miRNA and mRNA sequencing on blood drawn 72-120 hours after stroke. ANCOVA estimated differential expression of miRNA and mRNA between groups (FDR p1.2). Analyses were adjusted for time from stroke onset, sex, age, vascular risk factors and batch. Results: We identified differential expression in 36 miRNA and 264 corresponding mRNA targets between the stroke-plus-cancer and stroke-only groups after accounting for cancer-only expression (Fig 1). Immune and coagulation pathways, including complement, platelet glycoproteins, TGF-β, and mTOR signaling, were overrepresented in stroke-plus-cancer vs stroke-only subjects. T cell, B cell and platelet precursor-specific genes were also overrepresented in stroke-plus-cancer subjects. When compared to other groups, stroke-plus-cancer subjects had 230 unique mRNA encoding for transcriptional regulators, including those involving splicing, epigenetics, and mediator complex genes bridging transcription factors and RNA transcriptional machinery. Conclusion: Patients with stroke and cancer had distinct signatures of miRNA and target mRNA compared to stroke patients without cancer, supporting the hypothesis that cancer-related stroke is a unique subgroup of ischemic stroke.

Background and Purpose: Emerging data suggest an increased risk of arterial ischemic events after intracerebral hemorrhage (ICH), but their impact on ICH outcomes is unclear. This study aimed to evaluate the risk of death among ICH survivors with and without an incident arterial ischemic event. Methods: We performed a retrospective cohort study using claims data from Medicare beneficiaries with a non-traumatic ICH from January 2008 to October 2015. Our exposure was an arterial ischemic event, defined as a composite of acute ischemic stroke or myocardial infarction (MI), identified using validated ICD-9-CM diagnosis codes. The outcome was death. After excluding ischemic events and deaths in the first 30 days after ICH discharge to prevent carryover of diagnosis codes from the initial hospitalization, we used marginal structural models to analyze the risk of death among ICH patients with and without an arterial ischemic event, after adjusting for demographics and vascular comorbidities as time-varying covariates. In secondary analyses, we studied the mortality risk separately after an ischemic stroke and MI. Results: Among 8,222 Medicare beneficiaries with an ICH, 2,371 (28.8%) had an arterial ischemic event. During a median follow up time of 2.0 years (interquartile range, 0.8-3.8), the cumulative mortality rate was 7.0% (95% confidence interval [CI], 6.5-7.5%) in patients with an arterial ischemic event and 4.0% (95% CI, 3.8-4.2%) in patients without an arterial ischemic event. In the marginal structural model, the occurrence of an arterial ischemic event was associated with an increased risk of death (hazard ratio [HR], 1.6; 95% confidence interval [CI], 1.5- 1.7). In secondary analyses, the mortality risk was elevated after both an ischemic stroke (HR, 1.5; 95% CI, 1.4-1.6), and a MI (HR, 2.6; 95% CI, 2.1-3.2). Conclusions: In a large population-based cohort, we found that elderly patients who survived an ICH had an increased risk of death after a subsequent ischemic stroke or MI. Careful exploration of secondary cardiovascular and stroke prevention strategies may be warranted in these patients.

Background and Purpose: Non-traumatic subarachnoid hemorrhage (SAH) is associated with poor long-term functional outcomes, but the risk of ischemic stroke among SAH survivors is poorly understood. Methods: We performed a retrospective cohort study using claims data from Medicare beneficiaries from 2008-2015. The exposure was a diagnosis of SAH, while the outcome was an acute ischemic stroke. The exposure and outcomes were identified using previously validated ICD-9-CM diagnosis codes. We excluded patients with prevalent ischemic stroke at the time of SAH diagnosis and those which occurred in the first 90 days after SAH discharge to avoid inclusion of stroke occurring as a medical or procedural complication of SAH. We used Cox regression adjusting for demographics and stroke risk factors to evaluate the association between SAH and long-term risk of ischemic stroke. Results: Among 1.3 million Medicare beneficiaries, 3,171 (0.18%) were diagnosed with non-traumatic SAH. During a median follow-up of 5.3 years (interquartile range [IQR], 2.7- 6.7), the cumulative incidence of ischemic stroke was 92 per 1,000 patients per year among patients with SAH, and 21 per 1,000 patients per year in those without SAH. In multivariable Cox regression analysis, SAH was associated with an increased risk of ischemic stroke (hazard ratio, 2.6; 95% confidence interval, 2.4-2.8) as compared to beneficiaries without SAH. Conclusions: In a large, heterogeneous national cohort of elderly patients, we found that survivors of SAH had more than double the long-term risk of ischemic stroke as compared to those without SAH. SAH survivors should be closely monitored and risk stratified for ischemic stroke.

Introduction: Acute ischemic stroke (AIS) may be the first sign of occult cancer. We aimed to better define the incidence of cancer in the year after AIS and to identify clinical factors associated with new cancer diagnoses. Methods: This was a retrospective cohort study using data from the Cornell Acute Stroke Academic Registry (CAESAR) on patients hospitalized at our center with AIS from 2011-2015. Patients with history of cancer were excluded. Through automated electronic data capture and manual abstraction of inpatient and outpatient medical records, we collected data on patients’ demographics, comorbidities, presentation, radiographic characteristics, stroke subtype, and clinical outcomes. Patients were followed for 1 year after the index AIS for a new diagnosis of pathologically-confirmed cancer. Cox hazards regression adjusting for the competing risk of death was used to evaluate associations between clinical factors and incident cancer. Factors significantly associated in multivariable analysis were entered into a risk stratification score, and this score’s discriminatory ability was evaluated by Harrell’s C-statistic. Results: After excluding 253 patients with history of cancer, this analysis included 963 patients with AIS. During a mean follow-up of 222 days, 16 patients (1.7%; 95% CI, 1.0-2.7%) were diagnosed with cancer. The most common cancers were lung (n=7) and leukemia (n=4) and the median time to cancer diagnosis was 13 days (IQR, 7-194 days). Among patients with cryptogenic stroke, the 1-year cancer incidence rate was 1.7% (95% CI, 0.6-3.7%). Clinical factors associated with incident cancer in multivariable analysis were venous thromboembolism during the AIS hospitalization (HR, 12.5; 95% CI, 3.3-47.0), unexplained weight loss within 6 months (HR 11.7; 95% CI, 3.3-42.0), and three-territory acute infarcts (HR, 4.1, 95% CI, 1.3-13.4). These factors were used to create a clinical score that had a C-statistic of 0.7 (95% CI, 0.5-0.8). Conclusions: In a large urban cohort of AIS, the estimated 1-year incidence of first-ever cancer was 1.7%. Unexplained weight loss, concomitant venous thromboembolism, and three-territory acute infarction pattern may serve as clues to occult cancer with AIS.

Background: Emerging data indicates an increased risk for cerebrovascular events with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and highlights the potential impact of coronavirus disease (COVID-19) on the management and outcomes of acute stroke. We conducted a systematic review and meta-analysis to evaluate the aforementioned considerations. Methods: We performed a meta-analysis of observational cohort studies reporting on the occurrence and/or outcomes of patients with cerebrovascular events in association with their SARS-CoV-2 infection status. We used a random-effects model. Summary estimates were reported as odds ratios (ORs) and corresponding 95% confidence intervals (95%CI). Results: We identified 16 cohort studies including 44,004 patients. Among patients with SARS-CoV-2, 1.3% (95%CI: 0.9-1.8%; I 2 =88%) were hospitalized for cerebrovascular events, 1.2% (95%CI: 0.8-1.5%; I 2 =85%) for ischemic stroke, and 0.2% (95%CI: 0.1-0.4%; I 2 =69%) for hemorrhagic stroke. Compared to non-infected contemporary or historical controls, patients with SARS-CoV-2 infection had increased odds of ischemic stroke (OR=3.58, 95%CI: 1.43-8.92; I 2 =43%) and cryptogenic stroke (OR=3.98, 95%CI: 1.62-9.77; I 2 =0%). Odds for in-hospital mortality were higher among SARS-CoV-2 stroke patients compared to non-infected contemporary or historical stroke patients (OR=5.60, 95%CI: 3.19-9.80; I 2 =45%). SARS-CoV-2 infection status was not associated to the likelihood of receiving intravenous thrombolysis (OR=1.42, 95%CI: 0.65-3.10; I 2 =0%) or endovascular thrombectomy (OR=0.78, 95%CI: 0.35-1.74; I 2 =0%) among hospitalized ischemic stroke patients during the COVID-19 pandemic. Diabetes mellitus was found to be more prevalent among SARS-CoV-2 stroke patients compared to non-infected contemporary or historical controls (OR=1.39, 95%CI: 1.04-1.86; I 2 =0%). Conclusion: SARS-CoV-2 appears to be associated with an increased risk of ischemic stroke, particularly the cryptogenic subtype. SARS-CoV-2 infection in stroke substantially increases the mortality risk.

Introduction: Chronic liver disease is associated with aberrant hemostasis, resulting in an increased risk of clotting and bleeding. We hypothesized that liver fibrosis, a manifestation of progressive chronic liver disease, is associated with stroke among people who have been subjected to the hemostatic stress of surgery. Methods: We conducted a retrospective, multicenter cohort study using data from 680 hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program (NSQIP), a prospective registry of 30-day outcomes. Quality measures, such as stroke, have been validated and have 95% inter-observer agreement. We included adults who underwent major surgery, except neurosurgery, from 2005-2016. The exposure was the Aspartate aminotransferase to Platelet Ratio Index (APRI) liver fibrosis score, calculated from preoperative aspartate aminotransferase and platelet count. The primary outcome was incident stroke, reported by NSQIP as a composite of ischemic and hemorrhagic stroke. We used multivariable Cox proportional hazards models to assess the relationship between APRI and incident stroke, adjusting for demographics, comorbidities, and surgical characteristics (surgical type and American Society of Anesthesiologists preoperative fitness classification). In a sensitivity analysis, we also adjusted for preoperative platelet count and coagulation indices. Results: Among 2,729,995 patients, the mean age was 57 (SD, 17) years and 58% were women. A total of 6,886 patients had stroke within 30 days (0.25%). In unadjusted analyses, a 1-point increase in APRI was associated with a 3% increased risk of stroke (HR, 1.03; 95% CI, 1.02-1.03). The association remained significant in models adjusted for comorbidities and surgical characteristics (HR, 1.02; 95% CI, 1.01-1.03). Sensitivity analyses also adjusted for platelet count and coagulation indices were consistent (HR, 1.03; 95% CI, 1.01-1.04). Conclusions: A liver fibrosis score calculated from routine preoperative laboratory data was independently, albeit modestly, associated with an increased risk of stroke within 30 days after surgery. Whether preoperative assessment of liver disease markers has clinical utility requires investigation.

Introduction: Patients with stroke face an increased risk of contracting influenza and herpes zoster. We compared vaccination rates in stroke survivors versus the general United States population. Methods: We performed a cross-sectional analysis of data from the Centers for Disease Control and Prevention (CDC) Behavioral Risk Factor Surveillance System, which is an annual, nationally representative, health survey. Respondents are asked about medical conditions and care. We used the most recent years with complete data for influenza (2018) and zoster (2017). We utilized survey procedures to estimate CDC-recommended vaccination rates for influenza (annual vaccination for all) and zoster (one-time vaccination for those at least 50 years old). Multiple logistic regression was used to compare the odds of vaccination in those with and without prior stroke, while adjusting for demographics (including income and health insurance) and comorbidities that may influence vaccination rates (obesity, diabetes, heart disease, cancer, pulmonary disease, and smoking). Results: In 2018, 8,254,136 (3.4%; 95% CI, 3.3-3.5) Americans were stroke survivors. The influenza vaccination rate was 44.4% (95% CI, 42.8-46.2) in stroke survivors and 32.8% (95% CI, 32.5-33.1) otherwise. In unadjusted models, stroke survivors were more likely to have had an influenza vaccination in the past year than those without stroke (OR, 1.6; 95% CI, 1.5-1.8). In 2017, 5,839,186 (5.7%; 95% CI, 5.5-5.9) Americans over 50 years old (i.e., eligible for zoster vaccination) were stroke survivors. The zoster vaccination rate was 30.3% (95% CI, 28.8-32.0) in stroke survivors and 27.6% (95% CI, 27.3-28.0) in those without prior stroke. Stroke survivors were more likely to have had zoster vaccination than those without stroke (OR, 1.14; 95% CI, 1.06-1.23). However, after accounting for demographics and comorbidities, stroke survivors were not more likely to be vaccinated for influenza (OR, 1.01; 95% CI, 0.93-1.10) or zoster (OR, 1.00; 95% CI, 0.90-1.12). Conclusion: Stroke survivors were not vaccinated at higher rates than expected based on demographics and comorbidities, and absolute vaccination rates were low, especially for zoster. Efforts to increase vaccination after stroke may be needed.

Background: Cervical artery dissection (CAD) often affects young, otherwise healthy people. Few data exist on whether patients with CAD face an increased vulnerability to aortic dissection. Herein we tested the hypothesis that CAD is associated with an increased risk of aortic dissection. Methods: We performed a retrospective cohort study using statewide administrative claims data from all Emergency Department visits and admissions at nonfederal hospitals in Florida from 2005 to 2015 and New York from 2006 to 2015. We used previously validated International Classification of Disease, Ninth Revision, Clinical Modification codes (ICD-9-CM) to identify patients with CAD and aortic dissection. Patients with prevalent aortic dissection were excluded. Our exposure variable was CAD and the outcome was incident aortic dissection after discharge from CAD hospitalization. Survival statistics were used to calculate incidence rates and Cox proportional hazards analysis was used to determine the association between CAD and aortic dissection while adjusting for demographics and vascular risk factors. In a secondary analysis, we excluded patients who had a traumatic CAD, defined as having concomitant ICD-9-CM codes for head or neck trauma at the time of CAD. Results: Among 19,715,114 patients, 4,537 (0.02%) had a CAD. The mean age of patients with CAD was 52.3±16.4 years. During 4.2±3.1 years of follow up, 16,571 patients were diagnosed with an aortic dissection (0.08%). The incidence of aortic dissection was 2.5 (95% CI, 1.7-3.7) per 1,000 patients per year in those with CAD versus 0.2 (95% CI, 0.2-0.2) per 1,000 patients per year in those without CAD. After adjustment for demographics and vascular risk factors, we found that CAD was associated with subsequent aortic dissection (HR 3.0, 95% CI, 2.1-4.5). Our results were similar in a secondary analysis excluding patients with traumatic CAD (HR 3.3, 95% CI, 2.2-4.8). Conclusions: In a large population-based cohort, we found that CAD was associated with a 3-fold increased risk of aortic dissection. Future studies should evaluate the utility of performing screening aortic imaging in patients with CAD.

Background and Purpose: Cardiac amyloidosis is increasingly recognized as an important cause of heart failure. Given the paucity of data on cerebrovascular complications of cardiac amyloidosis, we evaluated whether cardiac amyloidosis is associated with ischemic stroke. Methods: We performed a retrospective cohort study of Medicare beneficiaries using a 5% sample of inpatient and outpatient claims from January 1, 2008 through October 1, 2015. We identified patients with cardiac amyloidosis using International Classification of Diseases, 9th Revision, Clinical Modification ( ICD-9-CM ) code 277.3x in combination with a diagnosis code for heart failure or cardiomyopathy. The primary outcome was ischemic stroke, identified by a previously validated ICD-9-CM code algorithm. We used survival statistics to determine incidence rates. Cox proportional hazard analysis, adjusted for demographics, vascular risk factors, and the Elixhauser comorbidity index, was used to study the risk of ischemic stroke. Results: Among 1.8 million beneficiaries with mean follow-up of 4.6 years (standard deviation ±2.2), 454 (0.03%) had a diagnosis of cardiac amyloidosis. Patients with cardiac amyloidosis were older (78.1±7.4 versus 73.4±7.7 years) and had a greater comorbidity burden than those without the diagnosis. A total of 63,627 (3.6%) developed an ischemic stroke in the entire cohort. The incidence of ischemic stroke was 47 per 1,000 patients per year in those with cardiac amyloidosis compared to 7.8 per 1,000 patients per year in those without cardiac amyloidosis. In the adjusted Cox regression analysis, cardiac amyloidosis was associated with an increased risk of ischemic stroke (HR, 2.4; 95% confidence interval, 1.6-3.6). Conclusions: In a large heterogenous cohort of elderly patients, cardiac amyloidosis was associated with a 2.5-fold heightened risk of ischemic stroke.

International audience; Objective: Emerging data indicate an increased risk of cerebrovascular events with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and highlight the potential impact of coronavirus disease (COVID-19) on the management and outcomes of acute stroke. We conducted a systematic review and meta-analysis to evaluate the aforementioned considerations.Methods: We performed a meta-analysis of observational cohort studies reporting on the occurrence and/or outcomes of patients with cerebrovascular events in association with their SARS-CoV-2 infection status. We used a random-effects model. Summary estimates were reported as odds ratios (ORs) and corresponding 95% confidence intervals (CIs).Results: We identified 18 cohort studies including 67,845 patients. Among patients with SARS-CoV-2, 1.3% (95% CI = 0.9-1.6%, I2 = 87%) were hospitalized for cerebrovascular events, 1.1% (95% CI = 0.8-1.3%, I2 = 85%) for ischemic stroke, and 0.2% (95% CI = 0.1-0.3%, I2 = 64%) for hemorrhagic stroke. Compared to noninfected contemporary or historical controls, patients with SARS-CoV-2 infection had increased odds of ischemic stroke (OR = 3.58, 95% CI = 1.43-8.92, I2 = 43%) and cryptogenic stroke (OR = 3.98, 95% CI = 1.62-9.77, I2 = 0%). Diabetes mellitus was found to be more prevalent among SARS-CoV-2 stroke patients compared to noninfected historical controls (OR = 1.39, 95% CI = 1.00-1.94, I2 = 0%). SARS-CoV-2 infection status was not associated with the likelihood of receiving intravenous thrombolysis (OR = 1.42, 95% CI = 0.65-3.10, I2 = 0%) or endovascular thrombectomy (OR = 0.78, 95% CI = 0.35-1.74, I2 = 0%) among hospitalized ischemic stroke patients during the COVID-19 pandemic. Odds of in-hospital mortality were higher among SARS-CoV-2 stroke patients compared to noninfected contemporary or historical stroke patients (OR = 5.60, 95% CI = 3.19-9.80, I2 = 45%).Interpretation: SARS-CoV-2 appears to be associated with an increased risk of ischemic stroke, and potentially cryptogenic stroke in particular. It may also be related to an increased mortality risk. ANN NEUROL 2021;89:380-388.

One-quarter to one-third of ischemic strokes have no established mechanism after standard diagnostic evaluation and are classified as embolic stroke of undetermined source (ESUS). Failure of randomized trials to demonstrate a benefit of direct oral anticoagulants over aspirin for the treatment of ESUS as a single homogeneous entity has led to renewed interest by stroke experts to divide ESUS into subgroups. Emerging data suggest that active cancer, which is present in 5% to 10% of patients with ESUS, is a distinct and important subgroup of ESUS with unique clinical characteristics, underlying pathophysiologies, and treatment and prognostic considerations. Furthermore, the prevalence of cancer-related ESUS is expected to increase as patients with cancer, even those with distant metastases, survive longer due to improvements in cancer treatments. In this topical review, we examine the epidemiological link between ESUS and cancer, the clinical features and potential mechanistic underpinnings of ESUS with cancer (with a focus on novel biomarkers and their relationship to recurrent stroke and other thromboembolic events), and the potential treatment strategies for cancer-related ESUS. We include a critical appraisal of existing data and ongoing or planned clinical trials of different antithrombotic approaches. As cancer-related ESUS is a dynamic disease with variable course, we recommend close collaboration between neurologists and oncologists to develop individualized management plans.

Importance It is uncertain whether coronavirus disease 2019 (COVID-19) is associated with a higher risk of ischemic stroke than would be expected from a viral respiratory infection. Objective To compare the rate of ischemic stroke between patients with COVID-19 and patients with influenza, a respiratory viral illness previously associated with stroke. Design, Setting, and Participants This retrospective cohort study was conducted at 2 academic hospitals in New York City, New York, and included adult patients with emergency department visits or hospitalizations with COVID-19 from March 4, 2020, through May 2, 2020. The comparison cohort included adults with emergency department visits or hospitalizations with influenza A/B from January 1, 2016, through May 31, 2018 (spanning moderate and severe influenza seasons). Exposures COVID-19 infection confirmed by evidence of severe acute respiratory syndrome coronavirus 2 in the nasopharynx by polymerase chain reaction and laboratory-confirmed influenza A/B. Main Outcomes and Measures A panel of neurologists adjudicated the primary outcome of acute ischemic stroke and its clinical characteristics, mechanisms, and outcomes. We used logistic regression to compare the proportion of patients with COVID-19 with ischemic stroke vs the proportion among patients with influenza. Results Among 1916 patients with emergency department visits or hospitalizations with COVID-19, 31 (1.6%; 95% CI, 1.1%-2.3%) had an acute ischemic stroke. The median age of patients with stroke was 69 years (interquartile range, 66-78 years); 18 (58%) were men. Stroke was the reason for hospital presentation in 8 cases (26%). In comparison, 3 of 1486 patients with influenza (0.2%; 95% CI, 0.0%-0.6%) had an acute ischemic stroke. After adjustment for age, sex, and race, the likelihood of stroke was higher with COVID-19 infection than with influenza infection (odds ratio, 7.6; 95% CI, 2.3-25.2). The association persisted across sensitivity analyses adjusting for vascular risk factors, viral symptomatology, and intensive care unit admission. Conclusions and Relevance In this retrospective cohort study from 2 New York City academic hospitals, approximately 1.6% of adults with COVID-19 who visited the emergency department or were hospitalized experienced ischemic stroke, a higher rate of stroke compared with a cohort of patients with influenza. Additional studies are needed to confirm these findings and to investigate possible thrombotic mechanisms associated with COVID-19.

BackgroundPrior studies on rupture risk of brain arteriovenous malformations (AVMs) in women undergoing pregnancy and delivery have reported conflicting findings, but also have not accounted for AVM morphology and heterogeneity. Here, we assess the association between pregnancy and the risk of intracranial hemorrhage (ICH) in women with AVMs using a cohort-crossover design in which each woman serves as her own control.MethodsWomen who underwent pregnancy and delivery were identified using DRG codes from the Healthcare Cost and Utilization Project State Inpatient Databases for California (2005–2011), Florida (2005–2014), and New York (2005–2014). The presence of AVM and ICH was determined using ICD 9 codes. Pregnancy was defined as the 40 weeks prior to delivery, and postpartum as 12 weeks after. We defined a non-exposure control period as a 52-week period prior to pregnancy. The relative risks of ICH during pregnancy were compared against the non-exposure period using conditional Poisson regression.ResultsAmong 4 022 811 women identified with an eligible delivery hospitalization (median age, 28 years; 7.3% with gestational diabetes; 4.5% with preeclampsia/eclampsia), 568 (0.014%) had an AVM. The rates of ICH during pregnancy and puerperium were 6355.4 (95% CI 4279.4 to 8431.5) and 14.4 (95% CI 13.3 to 15.6) per 100 000 person-years for women with and without AVM, respectively. In cohort-crossover analysis, in women with AVMs the risk of ICH increased 3.27-fold (RR, 95% CI 1.67 to 6.43) during pregnancy and puerperium compared with a non-pregnant period.ConclusionsAmong women with AVM, pregnancy and puerperium were associated with a greater than 3-fold risk of ICH.

Objective To report four patients with coronavirus disease 2019 (COVID-19) who developed posterior reversible encephalopathy syndrome (PRES). Methods Patient data was abstracted from medical records at Weill Cornell Medical Center. Results Four patients with SARS-CoV-2 infection and PRES were identified. The patients' ages ranged from 64 to 74 years, and two were women. All four patients were admitted to the hospital with acute respiratory distress syndrome requiring intensive care unit admission and mechanical ventilation. PRES was diagnosed after persistent confusion, lethargy, new focal neurological deficits, or seizures were noted, with evidence of seizures on electroencephalogram for two of the patients. Imaging confirmed the presence of cerebral vasogenic edema. All four patients had elevated blood pressure and renal injury in the days preceding PRES diagnosis, as well as evidence of systemic inflammation and systemic hypercoagulability. Symptoms of PRES improved with blood pressure control. Conclusions Our four cases demonstrate the occurrence of PRES in critically-ill patients with COVID-19. PRES should be considered in the differential for acute neurological deficits and seizures in this setting., Highlights • We report four patients with COVID-19 COVID 19 who developed posterior reversible encephalopathy syndrome (PRES). • PRES was diagnosed in the context of persistent confusion, lethargy, focal neurologic deficits and seizure. • All patients had acute hypertension, renal injury,evidence of systemic inflammation and hypercoagulability. • PRES should be considered in patients with neurological symptoms and COVID-19 to ensure early treatment.

Background and Purpose: One-fifth of ischemic strokes are embolic strokes of undetermined source (ESUS). Their theoretical causes can be classified as cardioembolic versus noncardioembolic. This distinction has important implications, but the categories’ proportions are unknown. Methods: Using data from the Cornell Acute Stroke Academic Registry, we trained a machine-learning algorithm to distinguish cardioembolic versus non-cardioembolic strokes, then applied the algorithm to ESUS cases to determine the predicted proportion with an occult cardioembolic source. A panel of neurologists adjudicated stroke etiologies using standard criteria. We trained a machine learning classifier using data on demographics, comorbidities, vitals, laboratory results, and echocardiograms. An ensemble predictive method including L1 regularization, gradient-boosted decision tree ensemble (XGBoost), random forests, and multivariate adaptive splines was used. Random search and cross-validation were used to tune hyperparameters. Model performance was assessed using cross-validation among cases of known etiology. We applied the final algorithm to an independent set of ESUS cases to determine the predicted mechanism (cardioembolic or not). To assess our classifier’s validity, we correlated the predicted probability of a cardioembolic source with the eventual post-ESUS diagnosis of atrial fibrillation. Results: Among 1083 strokes with known etiologies, our classifier distinguished cardioembolic versus noncardioembolic cases with excellent accuracy (area under the curve, 0.85). Applied to 580 ESUS cases, the classifier predicted that 44% (95% credibility interval, 39%–49%) resulted from cardiac embolism. Individual ESUS patients’ predicted likelihood of cardiac embolism was associated with eventual atrial fibrillation detection (OR per 10% increase, 1.27 [95% CI, 1.03–1.57]; c-statistic, 0.68 [95% CI, 0.58–0.78]). ESUS patients with high predicted probability of cardiac embolism were older and had more coronary and peripheral vascular disease, lower ejection fractions, larger left atria, lower blood pressures, and higher creatinine levels. Conclusions: A machine learning estimator that distinguished known cardioembolic versus noncardioembolic strokes indirectly estimated that 44% of ESUS cases were cardioembolic.

ObjectiveTo test the hypothesis that the prevalence of cervical artery dissection remains constant across age groups, we evaluated the relationship between age and cervical artery dissection in patients with stroke using a nationally representative sample from the United States.MethodsWe used inpatient claims data included in the 2012–2015 releases of the National Inpatient Sample (NIS). We used validated ICD-9-CM codes to identify adults hospitalized with ischemic stroke and a concomitant diagnosis of carotid or vertebral artery dissection. Survey weights provided by the NIS and population estimates from the US census were used to calculate nationally representative estimates. The χ2 test for trend was used to compare the prevalence of concomitant dissection among stroke hospitalizations across patient subgroups defined by age. Poisson regression and the Wald test for trend were used to evaluate whether the prevalence of hospitalizations for stroke and concomitant dissection per million person-years varied by age groups.ResultsThere were 17,320 (95% confidence interval [CI], 15,614–19,026) hospitalizations involving ischemic stroke and a concomitant dissection. The prevalence of dissection among stroke hospitalizations decreased across 10-year age groups from 7.2% (95% CI, 6.2%–8.1%) among persons younger than 30 years to 0.2% (95% CI, 0.1%–0.2%) among persons older than 80 years (p value for trend p value for trend ConclusionIn a nationally representative sample, the prevalence of hospitalizations for dissection-related stroke increased with age.

Key Points Question How does the risk of acute ischemic stroke compare between patients with Covid-19 and patients with influenza (a respiratory virus previously linked to stroke)? Findings In this large retrospective cohort study conducted at two academic hospitals in New York City, patients with emergency department visits and hospitalizations with Covid-19 were approximately seven times as likely to have an acute ischemic stroke as compared to patients with emergency department visits or hospitalizations with influenza. Meaning Patients with Covid-19 are at heightened risk for acute ischemic stroke as compared to patients with influenza. Importance Case series without control groups suggest that Covid-19 may cause ischemic stroke, but whether Covid-19 is associated with a higher risk of ischemic stroke than would be expected from a viral respiratory infection is uncertain. Objective To compare the rate of ischemic stroke between patients with Covid-19 and patients with influenza, a respiratory viral illness previously linked to stroke. Design A retrospective cohort study. Setting Two academic hospitals in New York City. Participants We included adult patients with emergency department visits or hospitalizations with Covid-19 from March 4, 2020 through May 2, 2020. Our comparison cohort included adult patients with emergency department visits or hospitalizations with influenza A or B from January 1, 2016 through May 31, 2018 (calendar years spanning moderate and severe influenza seasons). Exposures Covid-19 infection confirmed by evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the nasopharynx by polymerase chain reaction, and laboratory-confirmed influenza A or B. Main Outcomes and Measures A panel of neurologists adjudicated the primary outcome of acute ischemic stroke and its clinical characteristics, etiological mechanisms, and outcomes. We used logistic regression to compare the proportion of Covid-19 patients with ischemic stroke versus the proportion among patients with influenza. Results Among 2,132 patients with emergency department visits or hospitalizations with Covid-19, 31 patients (1.5%; 95% confidence interval [CI], 1.0%-2.1%) had an acute ischemic stroke. The median age of patients with stroke was 69 years (interquartile range, 66-78) and 58% were men. Stroke was the reason for hospital presentation in 8 (26%) cases. For our comparison cohort, we identified 1,516 patients with influenza, of whom 0.2% (95% CI, 0.0-0.6%) had an acute ischemic stroke. After adjustment for age, sex, and race, the likelihood of stroke was significantly higher with Covid-19 than with influenza infection (odds ratio, 7.5; 95% CI, 2.3-24.9). Conclusions and Relevance Approximately 1.5% of patients with emergency department visits or hospitalizations with Covid-19 experienced ischemic stroke, a rate 7.5-fold higher than in patients with influenza. Future studies should investigate the thrombotic mechanisms in Covid-19 in order to determine optimal strategies to prevent disabling complications like ischemic stroke.

Background and Purpose— Cervicocephalic artery dissection is an important cause of stroke. The clinical presentation of dissection can resemble that of benign neurological conditions leading to delayed or missed diagnosis. Methods— We performed a retrospective cohort study using statewide administrative claims data from all Emergency Department visits and admissions at nonfederal hospitals in Florida from 2005 to 2015 and New York from 2006 to 2015. Using validated International Classification of Diseases, Ninth Revision, CM codes , we identified adult patients hospitalized for cervicocephalic artery dissection. We defined probable misdiagnosis of dissection as having an Emergency Department treat-and-release visit for symptoms or signs of dissection, including headache, neck pain, and focal neurological deficits in the 14 days before dissection diagnosis. Multivariable logistic regression was used to compare adverse clinical outcomes in patients with and without probable misdiagnosis. Results— Among 7090 patients diagnosed with a dissection (mean age 52.7 years, 44.9% women), 218 (3.1% [95% CI, 2.7%–3.5%]) had a preceding probable Emergency Department misdiagnosis. After adjustment for demographics and vascular risk factors, there were no differences in rates of stroke (odds ratio, 0.82 [95% CI, 0.62–1.09]) or in-hospital death (odds ratio, 0.26 [95% CI, 0.07–1.08]) between dissection patients with and without a probable misdiagnosis at index hospitalization. Conclusions— We found that ≈1 in 30 dissection patients was probably misdiagnosed in the 2 weeks before their diagnosis.

Background To investigate the rates, predictors, and outcomes of prolonged mechanical ventilation (≥ 96 h) following endovascular treatment (EVT) of ischemic stroke. Methods Hospitalizations with acute ischemic stroke and EVT were identified using validated codes in the National Inpatient Sample (2010–2015). The primary outcome was prolonged mechanical ventilation defined as ventilation ≥ 96 consecutive hours. We compared hospitalizations involving prolonged ventilation following EVT with those that did not involve prolonged ventilation. Propensity score matching was used to adjust for differences between groups. Clinical predictors of prolonged ventilation were assessed using multivariable conditional logistic regression analyses. Results Among the 34,184 hospitalizations with EVT, 5087 (14.9%) required prolonged mechanical ventilation. There was a decline in overall intubation and prolonged ventilation during the study period. On multivariable analysis, history of heart failure [OR 1.28 (95% CI 1.05–1.57)] and diabetes [OR 1.22 (95% CI 1–1.50)] was independent predictors of prolonged ventilation following EVT. In a sensitivity analysis of anterior circulation stroke only, heart failure [OR 1.3 (95% CI 1.10–1.61)], diabetes [OR 1.25 (95% CI 1.01–1.57)], and chronic lung disease [OR 1.31 (95% CI 1.03–1.66)] were independent predictors of prolonged ventilation. The weighted proportions of in-hospital mortality, post-procedural shock, acute renal failure, and intracerebral hemorrhage were higher in the prolonged ventilation group. Conclusions Among a nationally representative sample of hospitalizations, nearly one-in-six patients had prolonged mechanical ventilation after EVT. Heart failure and diabetes were significantly associated with prolonged mechanical ventilation following EVT. Prolonged ventilation was associated with significant increase in in-hospital mortality and morbidity. Electronic supplementary material The online version of this article (10.1007/s12028-020-01125-9) contains supplementary material, which is available to authorized users.

Background and Purpose: We sought to determine the proportion of patients with ischemic stroke evaluated by vascular neurologists in the United States. Methods: Using 2009 to 2015 claims from a 5% nationally representative sample of Medicare beneficiaries, we identified patients ≥65 years of age who were hospitalized for ischemic stroke. We ascertained the proportion of patients evaluated during the hospitalization or within 90 days of discharge by nonvascular and vascular neurologists. We assessed the relationship between county-level socioeconomic status and the likelihood of neurologist evaluation and between neurologist evaluation and diagnostic testing. Results: Among 66 989 patients with ischemic stroke, 37 820 (56.5%) were evaluated by a nonvascular neurologist and 11 700 (17.5%) by a board-certified vascular neurologist. Across increasing quartiles of county socioeconomic advantage, the proportion of patients evaluated by a vascular neurologist was 12.2%, 16.5%, 19.8%, and 23.0%. Relative to evaluation by a nonvascular neurologist, evaluation by a vascular neurologist was associated with a higher likelihood of postdischarge heart rhythm monitoring (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.6-1.9), echocardiography (OR, 1.4; 95% CI, 1.3-1.4), cervical vessel imaging (OR, 1.3; 95% CI, 1.2-1.3), and intracranial vessel imaging (OR, 2.1; 95% CI, 2.0-2.2). Conclusions: In a nationally representative cohort of Medicare beneficiaries, we found that about three quarters of patients with ischemic stroke were evaluated by a neurologist, and about one-sixth were evaluated by a vascular neurologist. Patients who were evaluated by a vascular neurologist were significantly more likely to undergo diagnostic testing.

Background Sex differences have been found in stroke risk factors, incidence, treatment, and outcomes. There are conflicting data on whether diagnostic evaluation for stroke may differ between men and women. Methods and Results We performed a retrospective cohort study using inpatient and outpatient claims between 2008 and 2016 from a nationally representative 5% sample of Medicare beneficiaries. We included patients ≥65 years old and hospitalized with ischemic stroke, defined by International Classification of Diseases, Ninth Revision, Clinical Modification ( ICD ‐9‐ CM ) and ICD ‐10‐ CM diagnosis codes. Logistic regression was used to determine the association between female sex and the odds of diagnostic testing and specialist evaluation, adjusted for age, race, and number of Charlson comorbidities. Among 78 822 patients with acute ischemic stroke, 58.3% (95% CI , 57.9–58.6%) were women. Female sex was associated with decreased odds of intracranial vessel imaging (odds ratio [ OR ]: 0.94; 95% CI , 0.91–0.97), extracranial vessel imaging ( OR: 0.89; 95% CI , 0.86–0.92), heart‐rhythm monitoring ( OR: 0.92; 95% CI , 0.87–0.98), echocardiography ( OR: 0.92; 95% CI , 0.89–0.95), evaluation by a neurologist ( OR: 0.94; 95% CI , 0.91–0.97), and evaluation by a vascular neurologist ( OR: 0.94; 95% CI , 0.90–0.97), after adjustment for age, race, and comorbidities. These findings were unchanged in separate sensitivity analyses excluding patients who died during the index hospitalization or were discharged to hospice and excluding patients with atrial fibrillation diagnosed before their index stroke. Conclusions In a nationally representative cohort of Medicare beneficiaries, we found that women with acute ischemic stroke were less likely to be evaluated by stroke specialists and less likely to undergo standard diagnostic testing compared with men.

Background and Purpose: Pregnancy is a risk factor for stroke. The mechanisms of stroke in pregnancy have not been well established. Cervical artery dissection may be one such mechanism, but it is unclear whether pregnancy is a risk factor for cervical artery dissection. Methods: We performed a cohort-crossover analysis using administrative claims data from all hospitalizations and emergency department visits involving nonfederal acute care hospitals in NY and FL between 2005-2015. We identified women ≥12 years old who were hospitalized for labor and delivery. Our outcome was cervical artery dissection, defined as carotid or vertebral artery dissection. We defined the period of risk as 6 months antepartum through 3 months postpartum. We compared each patient’s risk of dissection during this time period versus the corresponding 270-day period exactly 1 year later. Conditional Poisson models with robust standard errors were used to calculate incidence risk ratios (IRRs). Results: We identified 4,193,417 pregnancies among 3,061,413 women during our study period. There were 52 cases of cervical artery dissection during the peripartum period and 24 cases during the control period 1 year later. The incidence of cervical artery dissection was 12 (95% CI, 10-17) per million pregnancies versus 6 (95% CI, 4-9) per million patients during the control period 1 year later (IRR, 2.2; 95% CI, 1.3-3.5). Our findings were similar when we limited our outcome to cervical artery dissections complicated by ischemic stroke (IRR, 2.3; 95% CI, 1.1-5.1). Secondary analyses suggested that the heightened risk occurred in the peripartum and postpartum period (IRR,5.5; 95% CI, 2.6-11.7), not the antepartum period (IRR, 0.5; 95% CI, 0.2-1.2). Conclusions: In a large, population-based sample of women, pregnancy was associated with an increased risk of cervical artery dissection. This increased risk appeared to be limited to the peripartum and postpartum period.

Introduction: Recent national utilization and in-hospital outcomes of stenting for intracranial atherosclerosis following emergent or elective hospitalizations are not well-established. Methods: Using validated codes, we identified all hospitalizations with stenting for intracranial atherosclerosis in the National Inpatient Sample (NIS) from 2010-2016. The primary outcome was in-hospital mortality. Poor outcome was defined as death or discharge to skilled nursing facility. We used multivariable models adjusting for relevant demographic, hospital and clinical variables to examine outcomes among hospitalizations with elective or non-elective procedures. We used NIS sampling weights to calculate utilization patterns and clinical outcomes across time. Results: A total of 4,733 eligible hospitalizations with intracranial stenting were identified during the study period (21% elective admissions). An abrupt decline in intracranial stenting was observed in the 3 rd quarter of 2011 after publication of the SAMMPRIS trial. After 2011, there were steadily increasing rates of hyperacute intracranial stenting combined with mechanical thrombectomy whereas elective intracranial stenting trended downward. In-hospital mortality for non-elective stenting was unchanged across the study period, whereas in-hospital mortality for elective intracranial stenting declined significantly. In multivariable models, age (OR, 1.1), female sex (OR, 1.64) and concomitant thrombectomy (OR, 1.95) were associated with poor outcome in the non-elective stenting cohort, whereas black race (OR, 2.1) and atrial fibrillation (OR, 3.61) were independent predictors for poor outcome in the elective stenting cohort (all p < 0.05). Conclusion: Elective hospitalizations for intracranial stenting accounted for approximately one-fifth of all procedures for intracranial atherosclerosis in the U.S. and were associated with improving outcomes from 2010 to 2016. Figure: Intracranial stenting utilization patterns for intracranial atherosclerosis in US (2010-2016).

Background: Liver disease has been associated with cardiac structural abnormalities and atrial fibrillation. We hypothesized that advanced liver fibrosis - commonly subclinical in the general population - is associated with cardioembolic stroke subtype. Secondarily, we hypothesized an association with cryptogenic stroke, based on its suspected embolic etiology. Methods: Among patients prospectively enrolled in the Cornell AcutE Stroke Academic Registry (CAESAR) from 2011-2016, we selected patients who had liver function tests within 7 days of admission. We calculated each patient’s Fibrosis-4 score, a validated, non-invasive liver fibrosis score derived from age, transaminase values, and platelet count. The primary exposure was advanced liver fibrosis, defined using a validated threshold of > 3.25; these patients were compared to patients without liver fibrosis. The primary outcome was cardioembolic stroke subtype, adjudicated using TOAST classification. The secondary outcome was cryptogenic subtype. We used logistic regression to separately evaluate the association between advanced liver fibrosis and these stroke subtypes, as compared to non-cardioembolic stroke. Models were adjusted for demographics, atrial fibrillation, hypertension, diabetes, dyslipidemia, coronary artery disease, congestive heart failure, peripheral vascular disease, and chronic kidney disease. Results: Among 1,586 ischemic stroke patients in our study, the mean age was 71 (SD, 15) years, and 50% were women. Overall, 18% had liver fibrosis; 34% and 27% of strokes were cardioembolic and cryptogenic, respectively. Advanced liver fibrosis was associated with cardioembolic stroke after adjusting for demographics and vascular risk factors (odds ratio [OR], 3.8; 95% confidence interval [CI], 2.1-6.9) compared to patients without liver fibrosis. There was a significant, albeit attenuated, association with cryptogenic stroke (OR, 1.9; 95% CI, 1.0-3.4). Conclusion: Advanced liver fibrosis is associated with cardioembolic stroke and, to a lesser degree, cryptogenic stroke. Whether liver fibrosis is a marker or independent causal factor of cardioembolism is to be determined.

Introduction: Transesophageal echocardiography (TEE) is often used as an adjunct to transthoracic echocardiography (TTE) to identify sources of cardiac embolism after ischemic stroke and transient ischemic attack (TIA). Unlike TTE, TEE is invasive and may lead to aspiration. Few data exist on the risk of respiratory complications after TEE in patients with stroke and TIA. Methods: We performed a retrospective cohort study using inpatient and outpatient claims data between 2008 through 2016 from a 5% sample of Medicare beneficiaries. We included patients ≥65 years old and hospitalized with acute ischemic stroke or TIA, defined by validated ICD-9 and ICD-10 diagnosis codes. CPT codes and ICD procedure codes were used to ascertain whether TEE, endotracheal intubation, mechanical ventilation, intravenous thrombolysis, or mechanical thrombectomy were performed during the stroke/TIA hospitalization. The exposure was TEE, modeled as a time-varying covariate, and the outcome was acute respiratory failure, defined as endotracheal intubation and/or mechanical ventilation. Patients were censored at hospital discharge or 21 days from admission. Cox proportional hazards regression was used to adjust for age, race, Charlson comorbidities, diagnosis of stroke versus TIA, thrombolysis, and thrombectomy. Results: Of 103,072 patients included during the study period, 72,981 (70.8%) had a diagnosis of ischemic stroke and 30,091 (29.2%) had a diagnosis of TIA. A total of 5,096 (4.9%) underwent TEE. The cumulative rate of respiratory failure at 21 days was higher after TEE (13.1%; 95% CI, 8.8-19.2%) than in patients without TEE (9.7%; 95% CI, 8.7-10.9%). After adjustment for potential confounders, TEE was associated with an increased risk of intubation (HR, 1.6; 95% CI, 1.3-2.0). This association was present when we assessed TIA patients only (HR, 2.7; 95% CI, 1.1-6.8). Conclusions: In a large cohort of Medicare beneficiaries, we found that TEE was associated with an increased risk of respiratory failure in patients with ischemic stroke or TIA.

Introduction: Thrombophilias are a known cause of acute ischemic stroke (AIS) in the young. We hypothesized that thrombophilias would be associated with an increased burden of chronic cerebrovascular disease in these patients. Methods: We included patients enrolled in the prospective Cornell AcutE Stroke Academic Registry (CAESAR) who were 18-65 years of age, diagnosed with AIS by brain MRI between 2011-2015, and had thrombophilia testing within 6 months of their stroke. The exposure variable was thrombophilia, defined as at least one positive thrombophilia test according to standard criteria. The primary outcome was the total Age-Related White Matter Changes (ARWMC) score (0-15). Secondary outcomes were the Fazekas score (0-3) and the number of chronic small vessel (subcortical) cerebral infarcts. Outcomes were determined by a single radiologist blinded to thrombophilia status using clinically-performed brain MRIs at the time of index stroke. Doubly robust estimator analyses were used to test the association between an underlying thrombophilia and outcomes. Models were adjusted for age, gender, race, and vascular risk factors. Results: Among 177 patients meeting eligibility criteria, mean age was 47 (SD, 10) years and 50% were women. Thrombophilia was detected in 77 patients (44%). The mean total ARWMC score, Fazekas score, and number of chronic small vessel infarcts were 1.90 (SD, 1.74), 0.91 (SD, 0.69), and 0.16 (SD, 0.63) in patients with thrombophilia and 2.16 (SD, 1.64), 1.07 (SD, 0.69) and 0.35 (SD, 0.81) in patients without thrombophilia. In multivariable analyses, there was no difference in the total ARWMC score (mean difference -0.05, 95% CI -0.43 to 0.33, p=0.80) or Fazekas score (mean difference -0.05, 95% CI -0.21 to 0.11, p=0.52) between patients with thrombophilia and those without. However, in multivariable analyses, the number of chronic infarcts (mean difference -0.22, 95% CI -0.42 to -0.01, p=0.01) was lower in patients with thrombophilia than in those without. Conclusions: In a single-center study of young adults with AIS, underlying thrombophilia was not associated with white matter disease burden. However, contrary to our hypothesis, it was inversely associated with the number of chronic small vessel infarcts.

Introduction: To study the risk of arterial ischemic events after non-traumatic subdural hemorrhage (SDH). Methods: We performed a retrospective cohort study using inpatient and outpatient claims data from 2008-2015 from a nationally representative 5% sample of Medicare beneficiaries. The exposure was diagnosis of SDH. Our primary outcome was an arterial ischemic event defined as a composite of acute ischemic stroke and acute myocardial infarction (MI). Secondary outcomes were ischemic stroke alone and MI alone. We used validated ICD-9-CM diagnosis codes to identify our predictor and outcomes. We excluded patients who had an arterial ischemic event prior to SDH diagnosis. Using Cox regression and corresponding survival probabilities, adjusted for demographics and vascular comorbidities, we computed the hazard ratio (HR) in each 4-week interval after discharge for SDH. We performed secondary analyses stratified by strong indications for antithrombotic therapy (composite of atrial fibrillation, peripheral vascular disease, valvular heart disease and venous thromboembolism). Results: Among 1.7 million Medicare beneficiaries, 2,939 were diagnosed with SDH. Compared to patients without SDH, those with SDH were more often older, male, and had more vascular risk factors. In the 4 weeks after SDH, patients’ risk of an arterial ischemic event was substantially increased (HR, 4.2; 95% CI, 2.2-6.7). There was no association between SDH diagnosis and arterial ischemic event risk beyond 4 weeks. In secondary analysis, during the 4 weeks after SDH, patients’ risk of ischemic stroke was increased (HR, 5.6; 95% CI, 3.6-9.7) but not their risk of MI (HR, 0.8, 95% CI, 0.2-1.7). Patients with strong indications for antithrombotic therapy had similarly increased risks for arterial ischemic events as compared to patients in the primary analysis; patients without strong indications for antithrombotic did not demonstrate an increased risk for arterial ischemic events. Conclusions: Among Medicare beneficiaries, we found a heightened risk of arterial ischemic events, particularly ischemic stroke, in the four weeks after SDH. This increased risk may be driven by withholding of antithrombotic therapy after SDH diagnosis.

Background: Active smoking after stroke is associated with worse outcomes. Since several smoking cessation drugs have become available during the last two decades, we sought to determine whether the rate of active smoking among stroke survivors has decreased. Methods: We performed a trends analysis using cross-sectional data from all nine available consecutive cycles of the continuous phase of the National Health and Nutrition Examination Survey from 1999 to 2016. Participants in each cycle were asked about their medical history and health-related behaviors. We included participants 20 years of age and older who answered questions regarding smoking. Patients with prior stroke were identified based on self-report, which has been validated against expert chart review. Active smoking was defined based on self-report. We used multivariable logistic regression methods for survey data to assess for trends in active smoking among all participants and those with prior stroke. Models were adjusted for demographics. Results: We included 49,440 participants in our analysis, of whom 1,921 (2.7%) reported a prior stroke. The mean age of stroke survivors was 64.8 (standard error, 0.5) years, and 57% were women. The average prevalence of active smoking over 1999-2016 was 22.2% for the whole sample and 24.3% among stroke survivors. In the overall population, the adjusted prevalence of active smoking decreased over the study period (odds ratio [OR] per cycle, 0.96; 95% confidence interval [CI], 0.94-0.97). The rate did not decrease among stroke survivors (OR, 1.01; 95% CI, 0.93-1.09) (Fig). Conclusion: Despite the availability of several effective smoking cessation therapies, the rate of active smoking among stroke survivors has not decreased in the past two decades. Effective strategies for smoking cessation for secondary stroke prevention are needed.

Introduction: Thoracic aorta surgery carries a risk of perioperative stroke, but the long-term incidence of stroke after the perioperative period in these patients remains unclear. We therefore assessed the long-term risk of stroke in patients who underwent thoracic aorta repair. Methods: We performed a retrospective cohort study using 2008-2015 claims data from a nationally representative 5% sample of Medicare beneficiaries. Our exposure of interest was thoracic aorta surgery, defined using ICD-9-CM hospital procedure codes for endovascular graft implantation (39.73) or surgical resection and replacement (38.45). Our primary outcome was ischemic stroke, defined using previously validated ICD-9-CM diagnosis codes. Patients with stroke during the index surgical hospitalization were excluded, since our focus was on long-term stroke risk after the perioperative period . Cox proportional hazards analysis was used to examine the association between thoracic aorta surgery and stroke risk after adjustment for demographics and vascular risk factors. Given a clear violation of the proportional hazards assumption, we calculated period-specific risk estimates. Results: Among 1,751,719 beneficiaries (mean age 73 ±8 years), 1,402 underwent thoracic aorta repair. During 4.6 ±2.2 years of follow-up, 62,702 patients were diagnosed with ischemic stroke. The incidence of stroke was 1.24% (95% CI, 0.93-1.66%) per year after thoracic aorta repair compared to 0.77% (95% CI, 0.76-0.78%) per year in patients without thoracic aorta surgery. In adjusted models, there was an increased risk of stroke in the first 120 days after discharge from thoracic aorta surgery (HR, 2.1; 95% CI, 1.2-3.7), but no heightened risk was seen beyond 120 days after discharge from surgery (HR, 0.7; 95% CI, 0.5-1.0). Conclusions: In a large sample of Medicare beneficiaries, thoracic aorta surgery was associated with an increased risk of ischemic stroke in the first 120 days after hospital discharge, but there was no excess risk beyond that time point.

Introduction About one-fourth of ischaemic strokes are classified as embolic strokes of undetermined source. Lambl’s excrescences are commonly seen on cardiac valves, and data are limited on whether they may be a source of embolization. We examined the relationship between Lambl’s excrescences and embolic stroke of undetermined source. Patients and Methods We performed a case-control study of patients in the Cornell AcutE Stroke Academic Registry. Stroke aetiologies were adjudicated using the Trial of Org 10172 in Acute Stroke Treatment and embolic stroke of undetermined source criteria. We included patients with acute ischaemic stroke between 2011 and 2016 who underwent transthoracic or transoesophageal echocardiography within six months of hospitalisation. Cases were embolic stroke of undetermined source patients and controls were patients with an identified, non-cardioembolic stroke aetiology (i.e. small- or large-vessel strokes). Multiple logistic regression was used to evaluate the association between Lambl’s excrescences and embolic stroke of undetermined source after adjustment for demographics, comorbidities and mode of echocardiography. Results A total of 923 patients met the criteria for this analysis, including 530 with embolic stroke of undetermined source and 393 with small- or large-vessel strokes. Lambl’s excrescences were identified in 47 (8.9%) patients with embolic stroke of undetermined source and 11 (2.8%) patients with small- or large-artery strokes, but the majority (54/58) of Lambl’s excrescences were visualised on transoesophageal echocardiogram and embolic stroke of undetermined source patients were more likely to undergo transoesophageal echocardiogram. After adjustment for demographics, comorbidities and mode of echocardiography, we found no association between the presence of Lambl’s excrescences and embolic stroke of undetermined source (odds ratio 0.9; 95% confidence interval 0.4–2.3). Conclusion We found no association between Lambl’s excrescences and embolic stroke of undetermined source. These results do not support the hypothesis that Lambl’s excrescences are an occult cause of embolic stroke of undetermined source.

Background and Purpose— Cirrhosis—clinically overt, advanced liver disease—is associated with an increased risk of hemorrhagic stroke and poor stroke outcomes. We sought to investigate whether subclinical liver disease, specifically liver fibrosis, is associated with clinical and radiological outcomes in patients with primary intracerebral hemorrhage. Methods— We performed a retrospective cohort study using data from the Virtual International Stroke Trials Archive–Intracerebral Hemorrhage. We included adult patients with primary intracerebral hemorrhage presenting within 6 hours of symptom onset. We calculated 3 validated fibrosis indices—Aspartate Aminotransferase–Platelet Ratio Index, Fibrosis-4 score, and Nonalcoholic Fatty Liver Disease Fibrosis Score—and modeled them as continuous exposure variables. Primary outcomes were admission hematoma volume and hematoma expansion. Secondary outcomes were mortality, and the composite of major disability or death, at 90 days. We used linear and logistic regression models adjusted for previously established risk factors. Results— Among 432 patients with intracerebral hemorrhage, the mean Aspartate Aminotransferase–Platelet Ratio Index, Fibrosis-4, and Nonalcoholic Fatty Liver Disease Fibrosis Score values on admission reflected intermediate probabilities of fibrosis, whereas standard hepatic assays and coagulation parameters were largely normal. After adjusting for potential confounders, Aspartate Aminotransferase–Platelet Ratio Index was associated with hematoma volume (β, 0.20 [95% CI, 0.04–0.36]), hematoma expansion (odds ratio, 1.6 [95% CI, 1.1–2.3]), and mortality (odds ratio, 1.8 [95% CI, 1.1–2.7]). Fibrosis-4 was also associated with hematoma volume (β, 0.27 [95% CI, 0.07–0.47]), hematoma expansion (odds ratio, 1.9 [95% CI, 1.2–3.0]), and mortality (odds ratio, 2.0 [95% CI, 1.1–3.6]). Nonalcoholic Fatty Liver Disease Fibrosis Score was not associated with any outcome. Indices were not associated with the composite of major disability or death. Conclusions— In patients with largely normal liver chemistries, 2 liver fibrosis indices were associated with admission hematoma volume, hematoma expansion, and mortality after intracerebral hemorrhage.

Background and Purpose— Observational data suggest that antiplatelet therapy after intracerebral hemorrhage (ICH) alleviates thromboembolic risk without increasing the risk of recurrent ICH. Given the paucity of data on the relationship between antiplatelet therapy after ICH and functional outcomes, we aimed to study this association in a multicenter cohort. Methods— We meta-analyzed data from (1) the Massachusetts General Hospital ICH registry (n=1854), (2) the Virtual International Stroke Trials Archive database (n=762), and (3) the Yale stroke registry (n=185). Our exposure was antiplatelet therapy after ICH, which was modeled as a time-varying covariate. Our primary outcomes were all-cause mortality and a composite of major disability or death (modified Rankin Scale score 4–6). We used Cox proportional regression analyses to estimate the hazard ratio of death or poor functional outcome as a function of antiplatelet therapy and random-effects meta-analysis to pool the estimated HRs across studies. Additional analyses stratified by hematoma location (lobar and deep ICH) were performed. Results— We included a total of 2801 ICH patients, of whom 288 (10.3%) were started on antiplatelet medications after ICH. Median times to antiplatelet therapy ranged from 7 to 39 days. Antiplatelet therapy after ICH was not associated with mortality (hazard ratio, 0.85; 95% CI, 0.66–1.09), or death or major disability (hazard ratio, 0.83; 95% CI, 0.59–1.16) compared with patients not started on antiplatelet therapy. Similar results were obtained in additional analyses stratified by hematoma location. Conclusions— Antiplatelet therapy after ICH appeared safe and was not associated with all-cause mortality or functional outcome, regardless of hematoma location. Randomized clinical trials are needed to determine the effects and harms of antiplatelet therapy after ICH.

Introduction: Evidence of visceral infarction is often found in patients with acute ischemic stroke. It remains uncertain whether there exists a relationship between visceral infarction and functional outcomes among patients with stroke. Objective: The aim of this study was to evaluate whether evidence of visceral infarction is associated with functional outcomes among patients with stroke. Methods: Among patients with acute ischemic stroke enrolled in the Cornell AcutE Stroke Academic Registry (CAESAR) from 2011 through 2016, we included those with a contrast-enhanced abdominal computed tomographic scan within 1 year of admission. Our outcome was ambulatory status at discharge from acute stroke hospitalization, categorized as walking without assistance, walking with assistance, and unable to walk. We used ordinal logistic regression to examine the association between visceral infarction and discharge ambulatory status after adjustment for demographics, stroke risk factors, stroke severity (NIH Stroke Scale), and stroke subtype. Results: Among 2,116 ischemic stroke patients registered in CAESAR from 2011 to 2016, 259 had contrast-enhanced abdominal computed tomographic imaging, of whom 48 (19%) had evidence of visceral infarction. After adjustment for demographics, stroke risk factors, stroke severity, and stroke subtype, the presence of visceral infarction was associated with a worse ambulatory status at discharge (global OR for better ambulatory status, 0.4; 95% CI, 0.2–1.0, p = 0.046). Conclusions: We found that the presence of visceral infarction was associated with poor functional outcomes at the time of hospital discharge. These findings suggest that such findings are not necessarily benign and are at the least a marker of poor outcomes.

Background and Purpose— Carotid artery plaque with Methods— We included patients enrolled in the Cornell Acute Stroke Academic Registry from 2011 to 2015 who had anterior circulation infarction, magnetic resonance imaging of the brain, and magnetic resonance angiography of the neck. High-risk plaque was identified by intraplaque hemorrhage ascertained from routine neck magnetic resonance angiography studies using validated methods. Infarct location was determined from diffusion-weighted imaging. Intraplaque hemorrhage and infarct location were assessed separately in a blinded fashion by a neuroradiologist. We used the McNemar test for matched data to compare the prevalence of intraplaque hemorrhage ipsilateral versus contralateral to brain infarction. We reclassified stroke subtypes by including large-artery atherosclerosis as a cause if there was intraplaque hemorrhage ipsilateral to brain infarction, regardless of the degree of stenosis. Results— Among the 1721 acute ischemic stroke patients registered in the Cornell Acute Stroke Academic Registry from 2011 to 2015, 579 were eligible for this analysis. High-risk plaque was more common ipsilateral versus contralateral to brain infarction in large-artery atherosclerotic (risk ratio [RR], 3.7 [95% CI, 2.2–6.1]), cryptogenic (RR, 2.1 [95% CI, 1.4–3.1]), and cardioembolic strokes (RR, 1.7 [95% CI, 1.1–2.4]). There were nonsignificant ipsilateral-contralateral differences in high-risk plaque among lacunar strokes (RR, 1.2 [95% CI, 0.4–3.5]) and strokes of other determined cause (RR, 1.5 [95% CI, 0.7–3.3]). After accounting for ipsilateral high-risk plaque, 88 (15.2%) patients were reclassified: 38 (22.6%) cardioembolic to multiple potential etiologies, 6 (8.5%) lacunar to multiple, 3 (15.8%) other determined cause to multiple, and 41 (20.8%) cryptogenic to large-artery atherosclerosis. Conclusions— High-risk carotid plaque was more prevalent ipsilateral to brain infarction across several ischemic stroke subtypes. Accounting for such plaques may reclassify the etiologies of up to 15% of cases in our sample.

Background Mobile stroke units ( MSU s) reduce time to intravenous thrombolysis in acute ischemic stroke. Whether this advantage exists in densely populated urban areas with many proximate hospitals is unclear. Methods and Results We evaluated patients from the METRONOME (Metropolitan New York Mobile Stroke) registry with suspected acute ischemic stroke who were transported by a bi‐institutional MSU operating in Manhattan, New York, from October 2016 to September 2017. The comparison group included patients transported to our hospitals via conventional ambulance for acute ischemic stroke during the same hours of MSU operation (Monday to Friday, 9 am to 5 pm) . Our exposure was MSU care, and our primary outcome was dispatch‐to‐thrombolysis time. We estimated mean differences in the primary outcome between both groups, adjusting for clinical, demographic, and geographic factors, including numbers of nearby designated stroke centers and population density. We identified 66 patients treated or transported by MSU and 19 patients transported by conventional ambulance. Patients receiving MSU care had significantly shorter dispatch‐to‐thrombolysis time than patients receiving conventional care (mean: 61.2 versus 91.6 minutes; P =0.001). Compared with patients receiving conventional care, patients receiving MSU care were significantly more likely to be picked up closer to a higher mean number of designated stroke centers in a 2.0‐mile radius (4.8 versus 2.7, P =0.002). In multivariable analysis, MSU care was associated with a mean decrease in dispatch‐to‐thrombolysis time of 29.7 minutes (95% CI , 6.9–52.5) compared with conventional care. Conclusions In a densely populated urban area with a high number of intermediary stroke centers, MSU care was associated with substantially quicker time to thrombolysis compared with conventional ambulance care.

Background Thromboembolism from nonstenosing carotid plaques may be an underrecognized cause of embolic strokes of undetermined source ( ESUS ). We evaluated the association between features of nonstenosing atherosclerotic plaque on computed tomographic angiography and ESUS . Methods and Results We identified consecutive acute ischemic stroke patients from 2011 to 2015 who had unilateral anterior territory infarction on brain magnetic resonance imaging and a neck computed tomographic angiography. We included ESUS cases and as controls, cardioembolic strokes. Patients with ≥50% internal carotid artery atherosclerotic stenosis ipsilateral to the stroke were excluded from this analysis. Reviewers blinded to infarct location and stroke cause retrospectively evaluated computed tomographic angiography studies for specific plaque features including thickness of the total, soft, and calcified plaque; presence of ulceration; and perivascular fat attenuation. Paired t tests and McNemar's test for paired data were used to compare plaque features ipsilateral versus contralateral to the side of infarction. Ninety‐one patients with ESUS or cardioembolic stroke were included in this study. Total plaque thickness was greater on the infarcted side (2.1±2.0 mm) than the contralateral side (1.2±1.5 mm) ( P =0.006) among ESUS cases, but not among cardioembolic cases (1.9±1.6 mm versus 1.8±1.6 mm) ( P =0.32). Conclusions Among ESUS cases, total plaque thickness was greater ipsilateral to the side of infarction than on the contralateral, stroke‐free side. No such side‐to‐side differences were apparent in cardioembolic strokes. Our findings suggest that nonstenosing large‐artery atherosclerotic plaques represent one underlying mechanism of ESUS .