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Background: Continued smoking after stroke is associated with a high risk of stroke recurrence and other cardiovascular disease. We sought to comprehensively understand the epidemiology of smoking cessation in stroke survivors in the United States. Furthermore, we compared smoking cessation in stroke and cancer survivors because cancer is another smoking-related condition in which smoking cessation is prioritized. 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. Using pooled data from 2013 to 2019, we identified stroke and cancer survivors with a history of smoking. We used survey procedures to estimate frequencies and summarize quit ratios with attention to demographic and geographic (state-wise and rural-urban) factors for stroke survivors. The quit ratio is conventionally defined as the proportion of ever smokers who have quit. Then, we used multivariable logistic regression to compare quit ratios in stroke and cancer survivors while adjusting for demographics and smoking-related comorbidities. Results: Among 4 434 604 Americans with a history of stroke and smoking, the median age was 68 years (interquartile range, 59–76), and 45.4% were women. The overall quit ratio was 60.8% (95% CI, 60.1%–61.6%). Quit ratios varied by age group, sex, race and ethnicity, and several geographic factors. There was marked geographic variation in quit ratios, ranging from 48.3% in Kentucky to 71.5% in California. Furthermore, compared with cancer survivors, stroke survivors were less likely to have quit smoking (odds ratio, 0.72 [95% CI, 0.67–0.79]) after accounting for differences in demographics and smoking-related comorbidities. Conclusions: There were considerable demographic and geographic disparities in smoking quit ratios in stroke survivors, who were less likely to have quit smoking than cancer survivors. A targeted initiative is needed to improve smoking cessation for stroke survivors.

Background and Purpose: Coronavirus disease 2019 (COVID-19) may be associated with increased risk for ischemic stroke. We present prevalence and characteristics of strokes in patients with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection enrolled in the American Heart Association COVID-19 Cardiovascular Disease Registry. Methods: In this quality improvement registry study, we examined demographic, baseline clinical characteristics, and in-hospital outcomes among hospitalized COVID-19 patients. The primary outcomes were ischemic stroke or transient ischemic attack (TIA) and in-hospital death. Results: Among 21 073 patients with COVID-19 admitted at 107 hospitals between January 29, 2020, and November 23, 2020, 160 (0.75%) experienced acute ischemic stroke/TIA (55.3% of all acute strokes) and 129 (0.61%) had other types of stroke. Among nonischemic strokes, there were 44 (15.2%) intracerebral hemorrhages, 33 (11.4%) subarachnoid hemorrhages, 21 (7.3%) epidural/subdural hemorrhages, 2 (0.7%) cerebral venous sinus thromboses, and 24 (8.3%) strokes not otherwise classified. Asians and non-Hispanic Blacks were overrepresented among ischemic stroke/TIA patients compared with their overall representation in the registry, but adjusted odds of stroke did not vary by race. Median time from COVID-19 symptom onset to ischemic stroke was 11.5 days (interquartile range, 17.8); median National Institutes of Health Stroke Scale score was 11 (interquartile range, 17). COVID-19 patients with acute ischemic stroke/TIA had higher prevalence of hypertension, diabetes, and atrial fibrillation compared with those without stroke. Intensive care unit admission and mechanical ventilation were associated with higher odds of acute ischemic stroke/TIA, but older age was not a predictor. In adjusted models, acute ischemic stroke/TIA was not associated with in-hospital mortality. Conclusions: Ischemic stroke risk did not vary by race. In contrast to the association between older age and death from COVID-19, ischemic stroke risk was the highest among middle-aged adults after adjusting for comorbidities and illness severity, suggesting a potential mechanism for ischemic stroke in COVID-19 independent of age-related atherosclerotic pathways.

Background Mobile stroke units (MSUs) are ambulances with staff and a computed tomographic scanner that may enable faster treatment with tissue plasminogen activator (t-PA) than standard m...

Objective The objective of this study was to examine the pathophysiology of ischemic stroke with cancer. Methods We conducted a prospective cross-sectional study from 2016 to 2020 at 2 hospitals. We enrolled 3 groups of 50 adult participants each. The main group included patients with active solid tumor cancer and acute ischemic stroke. The control groups included patients with acute ischemic stroke only or active cancer only. The patients with stroke-only and patients with cancer-only were matched to the patients with cancer-plus-stroke by age, sex, and cancer type, if applicable. The outcomes were prespecified hematological biomarkers and transcranial Doppler microemboli detection. Hematological biomarkers included markers of coagulation (D-dimer and thrombin-antithrombin), platelet function (P-selectin), and endothelial integrity (thrombomodulin, soluble intercellular adhesion molecule-1 [sICAM-1], and soluble vascular cell adhesion molecule-1 [sVCAM-1]). Hematological biomarkers were compared between groups using the Kruskal-Wallis and Wilcoxon Rank-Sum tests. In multivariable linear regression models, we adjusted for race, number of stroke risk factors, smoking, stroke severity, and antithrombotic use. Transcranial Doppler microemboli presence was compared between groups using chi-square tests. Results Levels of all study biomarkers were different between groups. In univariate between-group comparisons, patients with cancer-plus-stroke had higher levels of D-dimer, sICAM-1, sVCAM-1, and thrombomodulin than both control groups; higher levels of thrombin-antithrombin than patients with cancer-only; and higher levels of P-selectin than patients with stroke-only. Findings were similar in multivariable analyses. Transcranial Doppler microemboli were detected in 32% of patients with cancer-plus-stroke, 16% of patients with stroke-only, and 6% of patients with cancer-only (p = 0.005). Interpretation Patients with cancer-related stroke have higher markers of coagulation, platelet, and endothelial dysfunction, and more circulating microemboli, than matched controls. ANN NEUROL 2021;90:159-169.

ObjectiveTo estimate the incidence of hospitalization for reversible cerebral vasoconstriction syndrome (RCVS), we identified RCVS-related hospital admissions across 11 US states in 2016.MethodsWe tested the validity of ICD-10 code I67.841 in 79 patients with hospital admissions for RCVS or other cerebrovascular diseases at 1 academic and 1 community hospital. After determining that this code had a sensitivity of 100% (95% confidence interval [CI], 82%–100%) and a specificity of 90% (95% CI, 79%–96%), we applied it to administrative data from the Healthcare Cost and Utilization Project on all hospital admissions across 11 states. Age- and sex-standardized RCVS incidence was calculated using census data. Descriptive statistics were used to analyze associated diagnoses.ResultsAcross 5,067,250 hospital admissions in our administrative data, we identified 222 patients with a discharge diagnosis of RCVS in 2016. The estimated annual age- and sex-standardized incidence of RCVS hospitalization was 2.7 (95% CI, 2.4–3.1) cases per million adults. Many patients had concomitant neurologic diagnoses, including subarachnoid hemorrhage (37%), ischemic stroke (16%), and intracerebral hemorrhage (10%). In the 90 days before the index admission, 97 patients had an emergency department (ED) visit and 34 patients a hospital admission, most commonly for neurologic, psychiatric, and pregnancy-related diagnoses. Following discharge from the RCVS hospital admission, 58 patients had an ED visit and 31 had a hospital admission, most commonly for neurologic diagnoses.ConclusionsUsing population-wide data, we estimated the age- and sex-standardized incidence of hospitalization for RCVS in US adults as approximately 3 per million per year.

The grim circumstances of the COVID-19 pandemic have highlighted the need to refine and adapt stroke systems of care. Patients’ care-seeking behaviors have changed due to perceived risks of in-hospital treatment during the pandemic. In response to these challenges, we optimized a recently implemented, novel outpatient approach for the evaluation and management of minor stroke and transient ischemic attack, entitled RESCUE-TIA. This modified approach incorporated telemedicine visits and remote testing, and proved valuable during the pandemic. In this review article, we provide the evidence-based rationale for our approach, describe its operationalization, and provide data from our initial experience.

Cerebrovascular complications among critically ill patients with COVID-19 have yet to be fully characterized. In this retrospective case series from a single academic tertiary care referral center in New York City, we present 12 patients with ischemic or hemorrhagic strokes that were found on imaging after a period of prolonged sedation in the setting of COVID-19 pneumonia. This series demonstrates a pattern of cerebrovascular events clinically masked by deep sedation required for management of COVID-19 related acute respiratory distress syndrome (ARDS). Of the 12 patients included, 10 had ischemic stroke, 4 of which had hemorrhagic conversion, and 2 had primary intracerebral hemorrhage. Ten patients were on therapeutic anticoagulation prior to discovery of their stroke, and the remainder received intermediate dose anticoagulation (in a range between prophylactic and therapeutic levels). Additional studies are needed to further characterize the counterbalancing risks of ischemic and hemorrhagic stroke, as well as the optimal management of this patient population.

ObjectiveTo evaluate the relationship between prior antiplatelet therapy (APT) and outcomes after primary intracerebral haemorrhage (ICH), and assess if it varies by haematoma location.MethodsWe pooled individual patient data from the Virtual International Stroke Trials Archive-ICH trials dataset, Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage III trial and the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation Phase III trial. The exposure was APT preceding ICH diagnosis. The primary outcome was haematoma expansion at 72 hours. Secondary outcomes were admission haematoma volume, all-cause mortality, death or major disability (modified Rankin Scale (mRS) score ≥4) and shift in mRS distribution. Mixed-effects models were used to assess the relationship between APT and outcomes. Secondary analyses were stratified by ICH location and study cohort.ResultsAmong 1420 patients with ICH, there were 782 (55.1%) lobar and 596 (42.0%) deep haemorrhages. APT was reported in 284 (20.0%) patients. In adjusted regression models, prior APT was not associated with haematoma expansion (OR, 0.97; 95% CI 0.60 to 1.57), major disability or death (OR, 1.05; 95% CI 0.61 to 1.63), all-cause mortality (OR, 0.89; 95% CI 0.47 to 1.85), admission haematoma volume (beta, −0.17; SE, 0.09; p=0.07) and shift in mRS (p=0.43). In secondary analyses, APT was associated with admission haematoma volume in lobar ICH (beta, 0.25; SE, 0.12; p=0.03), but there was no relationship with other ICH outcomes when stratified by haematoma location or study cohort.ConclusionsIn a large heterogeneous cohort of patients with ICH, prior APT was not associated with haematoma expansion or functional outcomes after ICH, regardless of haematoma location. APT was associated with admission haematoma volumes in lobar ICH.

Objective We wanted to determine whether pregnancy is associated with cervical artery dissection. Methods We performed a case-control study using claims data from all nonfederal emergency departments and acute care hospitals in New York and Florida between 2005 and 2015. Cases were women 12-42 years of age hospitalized with cervical artery dissection, defined using validated diagnosis codes for carotid/vertebral artery dissection. Controls were women 12-42 years of age with a primary diagnosis of renal colic. Cases and controls were matched 1:1 on age, race, insurance, income, state, and visit year. The exposure variable was pregnancy, defined as labor and delivery within 90 days before or 6 months after the index visit. Logistic regression was used to compare the odds of pregnancy between cases and controls. We performed a secondary cohort-crossover study comparing the risk of cervical artery dissection during pregnancy versus the same time period 1 year later. Results Pregnancy was twice as common among 826 women with cervical artery dissection compared with the 826 matched controls with renal colic (odds ratio, 2.5; 95% confidence interval [CI], 1.3-4.7). In our secondary analysis, pregnancy was associated with a higher risk of cervical artery dissection (incidence rate ratio [IRR], 2.2; 95% CI, 1.3-3.5), with the heightened risk limited to the postpartum period (IRR, 5.5; 95% CI, 2.6-11.7). Interpretation Pregnancy, specifically the postpartum period, was associated with hospitalization for cervical artery dissection. Although these findings might in part reflect ascertainment bias, our results suggest that arterial dissection is one mechanism by which pregnancy can lead to stroke. ANN NEUROL 2020;88:596-602.

Background and Purpose— Patients who continue to smoke after a stroke face a higher risk of recurrent stroke. While several effective drugs for smoking cessation became available over the past 2 decades, whether active smoking has decreased among stroke survivors is unknown. We, therefore, evaluated trends in active smoking among stroke survivors during this period. Methods— We performed trends analyses using cross-sectional data collected every 1 to 2 years from 2 US health surveys spanning 1999 to 2018. In the National Health and Nutrition Examination Survey (NHANES) and the Behavioral Risk Factor Surveillance System (BRFSS) survey, participants were asked about prior stroke and active tobacco smoking. In NHANES, serum cotinine levels were available as a secondary measure of active smoking. We used multivariable logistic regression models for survey data to assess trends in active smoking among participants with and without prior stroke. Results— Among 49 375 participants in NHANES during 1999 to 2016 and 3 621 741 participants in BRFSS during 2011 to 2018, the prevalence of stroke was ≈3%. The overall prevalence of active smoking among stroke survivors was 24% in NHANES and 23% in BRFSS. Among individuals without prior stroke, the odds of smoking decreased over time in both NHANES (odds ratio, 0.95 per 2 years [95% CI, 0.93–0.96]) and BRFSS (odds ratio, 0.96 per year [95% CI, 0.96–0.96]). In contrast, there was no decrease in smoking among stroke survivors in NHANES (odds ratio, 1.00 [95% CI, 0.93–1.07]) or BRFSS (odds ratio, 0.99 [95% CI, 0.98–1.004]). Results were consistent in secondary analysis using biochemical ascertainment of active smoking in NHANES and in sensitivity analyses accounting for potential demographic changes in stroke epidemiology. Conclusions— In contrast to the general population, the prevalence of active smoking among stroke survivors has not decreased during the past 2 decades.

Background and Purpose— The risk of arterial ischemic events after subdural hemorrhage (SDH) is poorly understood. This study aimed to evaluate the risk of acute ischemic stroke and myocardial infarction among patients with and without nontraumatic SDH. Methods— We performed a retrospective cohort study using claims data from 2008 through 2014 from a nationally representative sample of Medicare beneficiaries. The exposure was nontraumatic SDH. Our primary outcome was an arterial ischemic event, a composite of acute ischemic stroke and acute myocardial infarction. Secondary outcomes were ischemic stroke alone and myocardial infarction alone. We used validated International Classification of Diseases , Ninth Revision , Clinical Modification diagnosis codes to identify our predictor and outcomes. Using Cox regression and corresponding survival probabilities, adjusted for demographics and vascular comorbidities, we computed the hazard ratio in 4-week intervals after SDH discharge. 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, 2939 were diagnosed with SDH. In the 4 weeks after SDH, patients’ risk of an arterial ischemic event was substantially increased (hazard ratio, 3.6 [95% CI, 1.9–5.5]). There was no association between SDH diagnosis and arterial ischemic events beyond 4 weeks. In secondary analysis, during the 4 weeks after SDH, patients’ risk of ischemic stroke was increased (hazard ratio, 4.2 [95% CI, 2.1–7.3]) but their risk of myocardial infarction was not (hazard ratio, 0.8 [95% CI, 0.2–1.7]). Patients with strong indications for antithrombotic therapy had increased risks for arterial ischemic events similar to patients in the primary analysis, but those without such indications did not demonstrate an increased risk for arterial ischemic events. Conclusions— Among Medicare beneficiaries, we found a heightened risk of arterial ischemic events driven by an increased risk of ischemic stroke, in the 4 weeks after nontraumatic SDH. This increased risk may be due to interruption of antithrombotic therapy after SDH diagnosis.

Background and Purpose— The risk of arterial ischemic events after intracerebral hemorrhage (ICH) is poorly understood given the lack of a control group in prior studies. This study aimed to evaluate the risk of acute ischemic stroke and myocardial infarction (MI) among patients with and without ICH. Methods— We performed a retrospective cohort study using claims data from Medicare beneficiaries from 2008 to 2014. Our exposure was acute ICH, identified using validated International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes. Our primary outcome was a composite of acute ischemic stroke and MI, whereas secondary outcomes were ischemic stroke alone and MI alone. We used Cox regression analysis to compute hazard ratios during 1-month intervals after ICH. Sensitivity analyses entailed exclusion of patients with atrial fibrillation and valvular heart disease. Results— Among 1 760 439 Medicare beneficiaries, 5924 had ICH. The 1-year cumulative incidence of an arterial ischemic event was 5.7% (95% CI, 4.8–6.8) in patients with ICH and 1.8% (95% CI, 1.7–1.9) in patients without ICH. After adjusting for potential confounders, the risk of an arterial ischemic event remained significantly increased for the first 6 months after ICH and was especially high in the first month (hazard ratio, 6.7 [95% CI, 5.0–8.6]). In secondary analysis, the risk of ischemic stroke was increased in the first 6 months after ICH (hazard ratio, 6.1 [95% CI, 3.5–9.3]) but the risk of MI was not (hazard ratio, 1.6 [95% CI, 0.3–2.9]). In sensitivity analyses excluding patients with atrial fibrillation and valvular heart disease, the association between ICH and arterial ischemic events was similar to that of the primary analysis. Conclusions— In a large population-based cohort, we found that elderly patients with ICH had a substantially increased risk of ischemic stroke in the first 6 months after diagnosis. Further exploration of this risk is needed to determine optimal secondary prevention strategies for these patients.

Background and Purpose— Comorbid cancer is common in patients with acute ischemic stroke (AIS). As blood mRNA profiles can distinguish AIS mechanisms, we hypothesized that cancer-related AIS would have a distinctive gene expression profile. Methods— We evaluated 4 groups of 10 subjects prospectively enrolled at 3 centers from 2009 to 2018. This included the group of interest with active solid tumor cancer and AIS and 3 control groups with active cancer only, AIS only, or vascular risk factors only. Subjects in the AIS-only and cancer-only groups were matched to subjects in the cancer-stroke group by age, sex, and cancer type (if applicable). Subjects in the vascular risk factor group were matched to subjects in the cancer-stroke and stroke-only groups by age, sex, and vascular risk factors. Blood was drawn 72 to 120 hours after stroke. Total RNA was processed using 3′ mRNA sequencing. ANOVA and Fisher least significant difference contrast methods were used to estimate differential gene expression between groups. Results— In the cancer-stroke group, 50% of strokes were cryptogenic. All groups had differentially expressed genes that could distinguish among them. Comparing the cancer-stroke group to the stroke-only group and after accounting for cancer-only genes, 438 genes were differentially expressed, including upregulation of multiple genes/pathways implicated in autophagy signaling, immunity/inflammation, and gene regulation, including IL (interleukin)-1, interferon, relaxin, mammalian target of rapamycin signaling, SQSTMI1 (sequestosome-1), and CREB1 (cAMP response element binding protein-1). Conclusions— This study provides evidence for a distinctive molecular signature in blood mRNA expression profiles of patients with cancer-related AIS. Future studies should evaluate whether blood mRNA can predict detection of occult cancer in patients with AIS. Clinical Trial Registration— URL: https://clinicaltrials.gov . Unique identifier: NCT02604667.

Background: It is important to understand the risk for in-hospital mortality of adults hospitalized with acute coronavirus disease 2019 (COVID-19) infection with a history of heart failure (HF). Methods: We examined patients hospitalized with COVID-19 infection from January 1, 2020 to July 22, 2020, from 88 centers across the US participating in the American Heart Association’s COVID-19 Cardiovascular Disease registry. The primary exposure was history of HF and the primary outcome was in-hospital mortality. To examine the association between history of HF and in-hospital mortality, we conducted multivariable modified Poisson regression models that included sociodemographics and comorbid conditions. We also examined HF subtypes based on left ventricular ejection fraction in the prior year, when available. Results: Among 8920 patients hospitalized with COVID-19, mean age was 61.4±17.5 years and 55.5% were men. History of HF was present in 979 (11%) patients. In-hospital mortality occurred in 31.6% of patients with history of HF, and 16.9% in patients without a history of HF. In a fully adjusted model, history of HF was associated with increased risk for in-hospital mortality (relative risk: 1.16 [95% CI, 1.03–1.30]). Among 335 patients with left ventricular ejection fraction, heart failure with reduced ejection fraction was significantly associated with in-hospital mortality in a fully adjusted model (heart failure with reduced ejection fraction relative risk: 1.40 [95% CI, 1.10–1.79]; heart failure with mid-range ejection fraction relative risk: 1.06 [95% CI, 0.65–1.73]; heart failure with preserved ejection fraction relative risk, 1.06 [95% CI, 0.84–1.33]). Conclusions: Risk for in-hospital mortality was substantial among adults with history of HF, in large part due to age and comorbid conditions. History of heart failure with reduced ejection fraction may confer especially elevated risk. This population thus merits prioritization for the COVID-19 vaccine.

Supplemental Digital Content is available in the text., Background and Purpose: We systematically evaluated the impact of the coronavirus 2019 (COVID-19) pandemic on stroke care across the world. Methods: Observational studies comparing characteristics, acute treatment delivery, or hospitalization outcomes between patients with stroke admitted during the COVID-19 pandemic and those admitted before the pandemic were identified by Medline, Scopus, and Embase databases search. Random-effects meta-analyses were conducted for all outcomes. Results: We identified 46 studies including 129 491 patients. Patients admitted with stroke during the COVID-19 pandemic were found to be younger (mean difference, −1.19 [95% CI, −2.05 to −0.32]; I2=70%) and more frequently male (odds ratio, 1.11 [95% CI, 1.01–1.22]; I2=54%) compared with patients admitted with stroke in the prepandemic era. Patients admitted with stroke during the COVID-19 pandemic, also, had higher baseline National Institutes of Health Stroke Scale scores (mean difference, 0.55 [95% CI, 0.12–0.98]; I2=90%), higher probability for large vessel occlusion presence (odds ratio, 1.63 [95% CI, 1.07–2.48]; I2=49%) and higher risk for in-hospital mortality (odds ratio, 1.26 [95% CI, 1.05–1.52]; I2=55%). Patients with acute ischemic stroke admitted during the COVID-19 pandemic had higher probability of receiving endovascular thrombectomy treatment (odds ratio, 1.24 [95% CI, 1.05–1.47]; I2=40%). No difference in the rates of intravenous thrombolysis administration or difference in time metrics regarding onset to treatment time for intravenous thrombolysis and onset to groin puncture time for endovascular thrombectomy were detected. Conclusions: The present systematic review and meta-analysis indicates an increased prevalence of younger patients, more severe strokes attributed to large vessel occlusion, and higher endovascular treatment rates during the COVID-19 pandemic. Patients admitted with stroke during the COVID-19 pandemic had higher in-hospital mortality. These findings need to be interpreted with caution in view of discrepant reports and heterogeneity being present across studies.

Introduction: 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. Objectives: The aim of this study was to evaluate the risk of ischemic stroke among survivors of SAH. Methods: We performed a retrospective cohort study using claims data from Medicare beneficiaries from 2008 to 2015. The exposure was a diagnosis of SAH, while the outcome was an acute ischemic stroke, both identified using previously validated ICD-9-CM diagnosis codes. We used Cox regression analysis adjusting for demographics and stroke risk factors to evaluate the association between SAH and long-term risk of ischemic stroke. Results: Among 1.7 million Medicare beneficiaries, 912 were hospitalized with non-traumatic SAH. During a median follow-up of 5.2 years (IQR, 2.7–6.7), the cumulative incidence of ischemic stroke was 22 per 1,000 patients per year among patients with SAH, and 7 per 1,000 patients per year in those without SAH. In adjusted Cox models, SAH was associated with an increased risk of ischemic stroke (HR, 2.0; 95% confidence interval, 1.4–2.8) as compared to beneficiaries without SAH. Similar results were obtained in sensitivity analyses, when treating death as a competing risk (sub HR, 3.0; 95% CI, 2.8–3.3) and after excluding ischemic stroke within 30 days of SAH discharge (HR, 1.5; 95% CI, 1.1–2.3). Conclusions: In a large, heterogeneous national cohort of elderly patients, survivors of SAH had double the long-term risk of ischemic stroke. SAH survivors should be closely monitored and risk stratified for ischemic stroke.

Background and Purpose: The impact of arterial ischemic events after intracerebral hemorrhage (ICH) on 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, a composite of acute ischemic stroke or myocardial infarction (MI), identified using validated ICD-9-CM diagnosis codes. The outcome was mortality. We used marginal structural models to analyze the risk of death among ICH patients with and without an arterial ischemic event, after adjusting for confounders as time-varying covariates. Results: Among 8,804 Medicare beneficiaries with ICH, 2,371 (26.9%) had an arterial ischemic event. During a median follow-up time of 1.9 years (interquartile range, 0.7-3.9), ICH patients with an arterial ischemic event had a mortality rate of 21.7 (95% confidence interval [CI], 20.4-23.0) per 100 person-years compared to a rate of 15.0 (95% CI, 14.4-15.6) per 100 person-years in those without. In the marginal structural model, an arterial ischemic event was associated with an increased risk of death (hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.6-1.9). In secondary analyses, the mortality risk was elevated after an ischemic stroke (HR, 1.7; 95% CI, 1.5-1.8), and MI (HR, 3.0; 95% CI, 2.4-3.8). Conclusions: We found that elderly patients who survived an ICH had an increased risk of death after a subsequent ischemic stroke or MI.

Background and Purpose: Mechanical thrombectomy helps prevent disability in patients with acute ischemic stroke involving occlusion of a large cerebral vessel. Thrombectomy requires procedural expertise and not all hospitals have the staff to perform this intervention. Few population-wide data exist regarding access to mechanical thrombectomy. Methods: We examined access to thrombectomy for ischemic stroke using discharge data from calendar years 2016 to 2018 from all nonfederal emergency departments and acute care hospitals across 11 US states encompassing 80 million residents. Facilities were classified as hubs if they performed mechanical thrombectomy, gateways if they transferred patients who ultimately underwent mechanical thrombectomy, and gaps otherwise. We used standard descriptive statistics and unadjusted logistic regression models in our primary analyses. Results: Among 205 681 patients with ischemic stroke, 100 139 (48.7% [95% CI, 48.5%–48.9%]) initially received care at a thrombectomy hub, 72 534 (35.3% [95% CI, 35.1%–35.5%]) at a thrombectomy gateway, and 33 008 (16.0% [95% CI, 15.9%–16.2%]) at a thrombectomy gap. Patients who initially received care at thrombectomy gateways were substantially less likely to ultimately undergo thrombectomy than patients who initially received care at thrombectomy hubs (odds ratio, 0.27 [95% CI, 0.25–0.28]). Rural patients had particularly limited access: 27.7% (95% CI, 26.9%–28.6%) of such patients initially received care at hubs versus 69.5% (95% CI, 69.1%–69.9%) of urban patients. For 93.8% (95% CI, 93.6%–94.0%) of patients with stroke at gateways, their initial facility was capable of delivering intravenous thrombolysis, compared with 76.3% (95% CI, 75.8%–76.7%) of patients at gaps. Our findings were unchanged in models adjusted for demographics and comorbidities and persisted across multiple sensitivity analyses, including analyses adjusting for estimated stroke severity. Conclusions: We found that a substantial proportion of patients with ischemic stroke across the United States lacked access to thrombectomy even after accounting for interhospital transfers. US systems of stroke care require further development to optimize thrombectomy access.

Objective To determine whether cerebrovascular risk factors are associated with subsequent diagnoses of Parkinson disease, and whether these associations are similar in magnitude to those with subsequent diagnoses of Alzheimer disease. Methods This was a retrospective cohort study using claims data from a 5% random sample of Medicare beneficiaries from 2008 to 2015. The exposures were stroke, atrial fibrillation, coronary disease, hyperlipidemia, hypertension, sleep apnea, diabetes mellitus, heart failure, peripheral vascular disease, chronic kidney disease, chronic obstructive pulmonary disease, valvular heart disease, tobacco use, and alcohol abuse. The primary outcome was a new diagnosis of idiopathic Parkinson disease. The secondary outcome was a new diagnosis of Alzheimer disease. Marginal structural Cox models adjusting for time-dependent confounding were used to characterize the association between exposures and outcomes. We also evaluated the association between cerebrovascular risk factors and subsequent renal colic (negative control). Results Among 1,035,536 Medicare beneficiaries followed for a mean of 5.2 years, 15,531 (1.5%) participants were diagnosed with Parkinson disease and 81,974 (7.9%) were diagnosed with Alzheimer disease. Most evaluated cerebrovascular risk factors, including prior stroke (hazard ratio = 1.55; 95% confidence interval = 1.39-1.72), were associated with the subsequent diagnosis of Parkinson disease. The magnitudes of these associations were similar, but attenuated, to the associations between cerebrovascular risk factors and Alzheimer disease. Confirming the validity of our analytical model, most cerebrovascular risk factors were not associated with the subsequent diagnosis of renal colic. Interpretation Cerebrovascular risk factors are associated with Parkinson disease, an effect comparable to their association with Alzheimer disease. ANN NEUROL 2019;86:572-581.

Objective Atrial cardiopathy without atrial fibrillation (AF) may be a potential cardiac source of embolic strokes of undetermined source (ESUS). Atrial volume is a feature of atrial cardiopathy, but the relationship between atrial volume and ESUS remains unclear. Methods We compared left atrial volume among ischemic stroke subtypes in the Cornell Acute Stroke Academic Registry (CAESAR), which includes all patients with acute ischemic stroke at our hospital since 2011. Stroke subtype was determined by neurologists per the TOAST classification and consensus ESUS definition. Left atrial volume index (LAVI) was obtained directly from our echocardiography image system (Xcelera, Philips Healthcare). We used t‐tests and analysis of variance for unadjusted comparisons and targeted minimum loss‐based estimation for comparisons adjusted for demographics and comorbidities. Results Among 2116 patients in CAESAR from 2011 to 2016, 1293 had LAVI measurements. LAVI varied across subtypes (P

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.