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OBJECTIVE: To evaluate whether patients discharged to home after an emergency department (ED) visit for headache face a heightened short-term risk of stroke. BACKGROUND: Stroke hospitalizations that occur soon after ED visits for headache complaints may reflect diagnostic error. METHODS: We conducted a retrospective cohort study using statewide administrative claims data for all ED visits and admissions at nonfederal hospitals in Florida 2005–2018 and New York 2005–2016. Using standard International Classification of Diseases (ICD) codes, we identified adult patients discharged to home from the ED (treat-and-release visit) with a benign headache diagnosis (cohort of interest) as well as those with a diagnosis of renal colic or back pain (negative controls). The primary study outcome was hospitalization within 30 days for stroke (ischemic or hemorrhagic) defined using validated ICD codes. We assess the relationship between index ED visit discharge diagnosis and stroke hospitalization adjusting for patient demographics and vascular comorbidities. RESULTS: We identified 1,502,831 patients with an ED treat-and-release headache visit; mean age was 41 (standard deviation: 17) years and 1,044,520 (70%) were female. A total of 2150 (0.14%) patients with headache were hospitalized for stroke within 30 days. In adjusted analysis, stroke risk was higher after headache compared to renal colic (hazard ratio [HR]: 2.69; 95% confidence interval [CI]: 2.29–3.16) or back pain (HR: 4.0; 95% CI: 3.74–4.3). In the subgroup of 26,714 (1.78%) patients with headache who received brain magnetic resonance imaging at index ED visit, stroke risk was only slightly elevated compared to renal colic (HR: 1.47; 95% CI: 1.22–1.78) or back pain (HR: 1.49; 95% CI: 1.24–1.80). CONCLUSION: Approximately 1 in 700 patients discharged to home from the ED with a headache diagnosis had a stroke in the following month. Stroke risk was three to four times higher after an ED visit for headache compared to renal colic or back pain.

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.

Background: There are limited data about the epidemiology and secondary stroke prevention strategies used for patients with depressed left ventricular ejection fraction (LVEF) and sinus rhythm following an acute ischemic stroke (AIS). We sought to describe the prevalence of LVEF ≤40% and sinus rhythm among patients with AIS and antithrombotic treatment practice in a multi-center cohort from 2002 to 2018. Methods: This was a multi-center, retrospective cohort study comprised of patients with AIS hospitalized in the Greater Cincinnati Northern Kentucky Stroke Study and 4 academic, hospital-based cohorts in the United States. A 1-stage meta-analysis of proportions was undertaken to calculate a pooled prevalence. Univariate analyses and an adjusted multivariable logistic regression model were performed to identify demographic, clinical, and echocardiographic characteristics associated with being prescribed an anticoagulant upon AIS hospitalization discharge. Results: Among 14 338 patients with AIS with documented LVEF during the stroke hospitalization, the weighted pooled prevalence of LVEF ≤40% and sinus rhythm was 5.0% (95% CI, 4.1–6.0%; I 2 , 84.4%). Of 524 patients with no cardiac thrombus and no prior indication for anticoagulant who survived postdischarge, 200 (38%) were discharged on anticoagulant, 289 (55%) were discharged on antiplatelet therapy only, and 35 (7%) on neither. There was heterogeneity by site in the proportion discharged with an anticoagulant (22% to 45%, P 8 (odds ratio, 2.0 [95% CI, 1.1–3.8]) were significant, independent predictors of being discharged with an anticoagulant in an adjusted analysis. Conclusions: Nearly 5% of patients with AIS have a depressed LVEF and are in sinus rhythm. There is significant variation in the clinical practice of antithrombotic therapy prescription by site and stroke severity. Given this clinical equipoise, further study is needed to define optimal antithrombotic treatment regimens for secondary stroke prevention in this patient population.

This cohort study evaluates the mortality and functional outcome in patients with spontaneous intracerebral hemorrhage who received intraventricular alteplase vs those who received saline., Key Points Question Is intraventricular thrombolysis in patients with spontaneous intracerebral hemorrhage (ICH) and intraventricular hemorrhage (IVH) associated with reduced parenchymal ICH volume? Findings In this cohort study of 454 patients with ICH and IVH who were enrolled in a randomized clinical trial, intraventricular alteplase use was associated with a small reduction in the parenchymal ICH volume. However, no association was found between a change in parenchymal ICH volume and death or major disability. Meaning Findings of this study suggest that further exploration of the role of intraventricular thrombolysis in reducing parenchymal ICH volumes and potentially improving outcomes is warranted in patients with a moderate to large ICH with IVH and those with a thalamic ICH., Importance Intraventricular thrombolysis reduces intraventricular hemorrhage (IVH) volume in patients with spontaneous intracerebral hemorrhage (ICH), but it is unclear if a similar association with parenchymal ICH volume exists. Objective To evaluate the association between intraventricular alteplase use and ICH volume as well as the association between a change in parenchymal ICH volume and long-term functional outcomes. Design, Setting, and Participants This cohort study was a post hoc exploratory analysis of data from the Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage phase 3 randomized clinical trial with blinded outcome assessments. Between September 1, 2009, and January 31, 2015, patients with ICH and IVH were randomized to receive either intraventricular alteplase or normal saline via an external ventricular drain. Participants with primary IVH were excluded. Data analyses were performed between January 1 and June 30, 2021. Exposure Randomization to receive intraventricular alteplase. Main Outcomes and Measures The primary outcome was the change in parenchymal ICH volume between the hematoma stability and end-of-treatment computed tomography scans. Secondary outcomes were a modified Rankin Scale score higher than 3 and mortality, both of which were assessed at 6 months. The association between alteplase and change in parenchymal ICH volume was assessed using multiple linear regression, whereas the associations between change in parenchymal ICH volume and 6-month outcomes were assessed using multiple logistic regression. Prespecified subgroup analyses were performed for baseline IVH volume, admission ICH volume, and ICH location. Results A total of 454 patients (254 men [55.9%]; mean [SD] age, 59 [11] years) were included in the study. Of these patients, 230 (50.7%) were randomized to receive alteplase and 224 (49.3%) to receive normal saline. The alteplase group had a greater mean (SD) reduction in parenchymal ICH volume compared with the saline group (1.8 [0.2] mL vs 0.4 [0.1] mL; P

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.

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

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.

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.

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 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.

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.

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 Black individuals in the United States experience higher rates of ischemic stroke than other racial groups but have lower rates of clinically apparent atrial fibrillation ( AF ). It is unclear whether blacks truly have less AF or simply more undiagnosed AF . Methods and Results We performed a retrospective cohort study using inpatient and outpatient claims from 2009 to 2015 for a 5% nationally representative sample of Medicare beneficiaries. We included patients aged ≥66 years with at least 1 documented Current Procedural Terminology code for interrogation of an implantable pacemaker, cardioverter‐defibrillator, or loop recorder and no documented history of AF , atrial flutter, or stroke before their first device interrogation. Kaplan–Meier statistics and Cox proportional hazards models were used to examine the association between black race and the composite outcome of AF or atrial flutter while adjusting for age, sex, and vascular risk factors. Among 47 417 eligible patients, the annual incidence of AF /atrial flutter was 12.2 (95% CI , 11.5–13.1) per 100 person‐years among blacks and 17.6 (95% CI , 17.4–17.9) per 100 person‐years among non‐black beneficiaries. After adjustment for confounders, black beneficiaries faced a lower hazard of AF /atrial flutter than non‐black beneficiaries (hazard ratio, 0.75; 95% CI , 0.70–0.80). Despite the lower risk of AF , black patients faced a higher hazard of ischemic stroke (hazard ratio, 1.37; 95% CI , 1.22–1.53). Conclusions Among Medicare beneficiaries with implanted cardiac devices capable of detecting atrial rhythm, black patients had a lower incidence of AF despite a higher burden of vascular risk factors and a higher risk of stroke.

Objective: We evaluated the ability of genetic and serological testing to diagnose clinically relevant thrombophilias in young adults with ischemic stroke. Methods: We performed a retrospective cohort study of patients aged 18-65 years diagnosed with acute ischemic stroke at a comprehensive stroke center between 2011 and 2015 with laboratory testing for thrombophilia. The primary outcome was any positive thrombophilia screening test. The secondary outcome was a change in clinical management based on thrombophilia testing results. Logistic regression was used to assess whether the prespecified risk factors of age, sex, prior venous thromboembolism, family history of stroke, stroke subtype, and presence of patent foramen ovale were associated with outcomes. Results: Among 196 young ischemic stroke patients, at least 1 positive thrombophilia test was identified in 85 patients (43%; 95% CI, 36%-51%) and 16 (8%; 95% CI, 5%-13%) had a resultant change in management. Among 111 patients with cryptogenic strokes, 49 (44%) had an abnormal thrombophilia test and 9 (8%) had a change in management. After excluding cases of isolated hyperhomocysteinemia or methylenetetrahydrofolate reductase or Factor V Leiden gene mutation heterozygosity, the proportion of patients with an abnormal thrombophilia screen decreased to 24%. Prespecified risk factors were not significantly associated with positive thrombophilia testing or a change in management. Conclusions: Two-of-five young patients with ischemic stroke who underwent thrombophilia screening at our institution had at least 1 positive test but only one-in-twelve had a resultant change in clinical management. Neither cryptogenic stroke subtype nor other studied clinical factors were associated with a prothrombotic state.

Background and Purpose— It is unclear whether atrial fibrillation/flutter (AF) newly diagnosed after ischemic stroke represents a preexisting risk factor that led to stroke, an arrhythmia triggered by poststroke autonomic dysfunction, or an incidental finding. Methods— We compared AF incidence after hospitalizations for ischemic stroke, hemorrhagic stroke, and nonstroke conditions using inpatient and outpatient claims between 2008 and 2015 from a nationally representative 5% sample of Medicare beneficiaries. We used validated International Classification of Diseases, Ninth Revision, Clinical Modification ( ICD-9-CM ) codes to identify AF-free patients hospitalized with ischemic or hemorrhagic stroke and matched them in a 1:1 ratio by age, sex, race, calendar year, vascular risk factors, and Charlson comorbidities. We then matched the combined stroke cohort in a 1:1 ratio to patients hospitalized for nonstroke diagnoses. We used survival statistics and Cox regression to compare postdischarge AF incidence among groups. Results— We matched 2580 patients with ischemic stroke, 2580 with hemorrhagic stroke, and 5160 patients with other conditions. The annual postdischarge AF incidence was 3.4% (95% CI, 3.1%–3.7%) after ischemic stroke, 2.2% (95% CI, 1.9%–2.4%) after hemorrhagic stroke, and 2.9% (95% CI, 2.6%–3.1%) after nonstroke hospitalization. Ischemic stroke was associated with a somewhat higher risk of AF than hemorrhagic stroke (hazard ratio, 1.5; 95% CI, 1.3–1.8) or nonstroke conditions (hazard ratio, 1.2; 95% CI, 1.1–1.3). The latter association attenuated in sensitivity analyses limiting the outcome to AF diagnoses made by cardiologists (hazard ratio, 1.1; 95% CI, 0.8–1.5) or limiting the outcome to a minimum of 2 AF claims on separate dates (hazard ratio, 1.2; 95% CI, 1.0–1.5; P =0.09). Conclusions— New diagnoses of AF were more common after hospitalization for ischemic stroke than after hospitalization for hemorrhagic stroke or nonstroke conditions, but all hospitalized patients had a substantial incidence of new AF diagnoses after discharge and differences were attenuated when using more stringent definitions.

Background and Purpose— Case reports suggest that unruptured intracranial aneurysms may serve as a nidus for thrombus formation and downstream embolic stroke. However, few data exist to support an association between unruptured aneurysms and ischemic stroke. Methods— We conducted a within-subjects case-control study of acute ischemic stroke patients prospectively enrolled in the Cornell Acute Stroke Academic Registry who had magnetic resonance imaging of the brain and arterial imaging of the head within 14 days of admission. Reviewers blinded to the study hypothesis ascertained the presence of aneurysms from the neuroradiologist’s clinical report of the arterial imaging findings. McNemar test for paired data was used to compare the prevalence of unruptured aneurysms ipsilateral versus contralateral to the side of anterior circulation infarcts. Aneurysms of the anterior communicating artery or in the posterior circulation were not counted in the analysis. Results— Among 2116 patients registered in the Cornell Acute Stroke Academic Registry during 2011 to 2016, 1541 met our inclusion criteria, of whom 176 (11.4%; 95% CI, 9.8–13.0%) had an intracranial aneurysm. The prevalence of aneurysms did not differ on the side ipsilateral versus contralateral to the infarction (risk ratio [RR], 1.2; 95% CI, 0.9–1.5). There was no significant association between aneurysms and ipsilateral stroke in secondary analyses of the 1244 patients with stroke in a single anterior circulation territory (RR, 1.2; 95% CI, 0.8–1.9), the 619 patients with cryptogenic stroke (RR, 1.4; 95% CI, 0.9–2.0), or the 485 patients with cryptogenic stroke in a single anterior circulation territory (RR, 1.7; 95% CI, 0.8–3.3). Results were unchanged when counting only aneurysms >3 mm (RR, 1.2; 95% CI, 0.8–1.9) or 5 mm in diameter (RR, 1.2; 95% CI, 0.9–1.5). Conclusions— Contrary to our hypothesis, we found no significant association between unruptured intracranial aneurysms and ipsilateral ischemic stroke.

Objective Seizures can be provoked by systemic diseases associated with metabolic derangements, but the association between liver disease and seizures remains unclear. 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. The primary exposure variable was cirrhosis, and the secondary exposure was mild, noncirrhotic liver disease. The primary outcome was seizure, and the secondary outcome was status epilepticus. Diagnoses were ascertained using validated International Classification of Diseases, Ninth Edition, Clinical Modification codes. Survival statistics were used to calculate incidence rates, and Cox proportional hazards models were used to examine the association between exposures and outcomes while adjusting for seizure risk factors. Results Among 1 782 402 beneficiaries, we identified 10 393 (0.6%) beneficiaries with cirrhosis and 19 557 (1.1%) with mild, noncirrhotic liver disease. Individuals with liver disease were older and had more seizure risk factors than those without liver disease. Over 4.6 ± 2.2 years of follow-up, 49 843 (2.8%) individuals were diagnosed with seizures and 25 patients (0.001%) were diagnosed with status epilepticus. Cirrhosis was not associated with seizures (hazard ratio [HR] = 1.1, 95% confidence interval [CI] = 1.0-1.3), but there was an association with status epilepticus (HR = 1.9, 95% CI = 1.3-2.8). Mild liver disease was not associated with a higher risk of seizures (HR = 0.8, 95% CI = 0.6-0.9) or status epilepticus (HR = 1.1, 95% CI = 0.7-1.5). Significance In a large, population-based cohort, we found an association between cirrhosis and status epilepticus, but no overall association between liver disease and seizures.

Background and Purpose: The significance of transient neurological attack (TNA) symptoms is unclear. We sought to determine the risk of ischemic stroke after discharge from the emergency department (ED) with a diagnosis consistent with symptoms of TNA. Methods: Using administrative claims data, we identified patients discharged from EDs in New York between 2006 and 2012 with a primary discharge diagnosis of a TNA symptom, defined as altered mental status, generalized weakness, and sensory changes. The primary outcome was ischemic stroke. We used Kaplan-Meier survival statistics to calculate cumulative rates, and Cox regression to compare stroke risk after TNA versus after transient ischemic attack (TIA; positive control) or renal colic (negative control) while adjusting for demographics and vascular risk factors. Results: Of 499 369 patients diagnosed with a TNA symptom and discharged from the ED, 7756 were hospitalized for ischemic stroke over a period of 4.7 (±1.9) years. At 90 days, the cumulative stroke rate was 0.29% (95% confidence interval [CI]: 0.28%-0.31%) after TNA symptoms versus 2.08% (95% CI: 1.89%-2.28%) after TIA and 0.03% (95% CI: 0.02%-0.04%) after renal colic. The hazard ratio (HR) of stroke was higher after TNA than after renal colic (HR: 2.13; 95% CI: 1.90-2.40) but significantly lower than after TIA (HR: 0.47; 95% CI: 0.44-0.50). Compared to TIA, TNA was less strongly associated with stroke among patients under 60 years of age compared to those over 60. Conclusions: Patients discharged from the ED with TNA symptoms faced a higher risk of ischemic stroke than patients with renal colic, but the magnitude of stroke risk was low, particularly compared to TIA.

Background and Purpose— The safety and efficacy of restarting anticoagulation therapy after intracranial hemorrhage (ICH) remain unclear. We performed a systematic review and meta-analysis to summarize the associations of anticoagulation resumption with the subsequent risk of ICH recurrence and thromboembolism. Methods— We searched published medical literature to identify cohort studies involving adults with anticoagulation-associated ICH. Our predictor variable was resumption of anticoagulation. Outcome measures were thromboembolic events (stroke and myocardial infarction) and recurrence of ICH. After assessing study heterogeneity and publication bias, we performed a meta-analysis using random-effects models to assess the strength of association between anticoagulation resumption and our outcomes. Results— Eight studies were eligible for inclusion in the meta-analysis, with 5306 ICH patients. Almost all studies evaluated anticoagulation with vitamin K antagonists. Reinitiation of anticoagulation was associated with a significantly lower risk of thromboembolic complications (pooled relative risk, 0.34; 95% confidence interval, 0.25–0.45; Q =5.12, P for heterogeneity=0.28). There was no evidence of increased risk of recurrent ICH after reinstatement of anticoagulation therapy, although there was significant heterogeneity among included studies (pooled relative risk, 1.01; 95% confidence interval, 0.58–1.77; Q =24.68, P for heterogeneity Conclusions— In observational studies, reinstitution of anticoagulation after ICH was associated with a lower risk of thromboembolic complications and a similar risk of ICH recurrence. Randomized clinical trials are needed to determine the true risk–benefit profile of anticoagulation resumption after ICH.

Background and Purpose— Cerebral vein thrombosis (CVT) is a type of venous thromboembolism. Whether the risk of pulmonary embolism (PE) after CVT is similar to the risk after deep venous thrombosis (DVT) is unknown. Methods— We performed a retrospective cohort study using administrative data from all emergency department visits and hospitalizations in California, New York, and Florida from 2005 to 2013. We identified patients with CVT or DVT and the outcome of PE using previously validated International Classification of Diseases, Ninth Revision, Clinical Modification codes. Kaplan–Meier survival statistics and Cox proportional hazards models were used to compare the risk of PE after CVT versus PE after DVT. Results— We identified 4754 patients with CVT and 241 276 with DVT. During a mean follow-up of 3.4 (±2.4) years, 138 patients with CVT and 23 063 with DVT developed PE. CVT patients were younger, more often female, and had fewer risk factors for thromboembolism than patients with DVT. During the index hospitalization, the rate of PE was 1.4% (95% confidence interval [CI], 1.1%–1.8%) in patients with CVT and 6.6% (95% CI, 6.5%–6.7%) in patients with DVT. By 5 years, the cumulative rate of PE after CVT was 3.4% (95% CI, 2.9%–4.0%) compared with 10.9% (95% CI, 10.8%–11.0%; P Conclusion— The risk of PE after CVT was significantly lower than the risk after DVT. Among patients with CVT, the greatest risk for PE was during the index hospitalization.

Background Single-center studies suggest that patients with cancer have similar outcomes after intracerebral hemorrhage (ICH) compared to patients without cancer. However, these studies were limited by small sample sizes and high rates of intratumoral hemorrhage. Our hypothesis was that systemic cancer patients without brain involvement fare worse after ICH than patients without cancer. Methods We identified all patients diagnosed with spontaneous ICH from 2002 to 2011 in the Nationwide Inpatient Sample. Our predictor variable was systemic cancer. Our primary outcome was discharge disposition, dichotomized into favorable discharge (home/self-care or rehabilitation) or unfavorable discharge (nursing facility, hospice, or death). We used logistic regression to compare outcomes and performed secondary analyses by cancer subtype (i.e., nonmetastatic solid tumors, nonmetastatic hematologic tumors, and metastatic solid or hematologic tumors). Results Among 597,046 identified ICH patients, 22,394 (3.8%) had systemic cancer. Stroke risk factors such as hypertension and diabetes were more common in patients without cancer, whereas anticoagulant use and higher Charlson comorbidity scores were more common among cancer patients. In multivariate logistic regression analysis adjusted for demographics, comorbidities, and hospital-level characteristics, patients with cancer had higher odds of death (OR 1.62, 95% CI 1.56-1.69) and lower odds of favorable discharge (OR .59, 95% CI .56-.63) than patients without cancer. Among cancer groups, patients with nonmetastatic hematologic tumors and those with metastatic disease fared the worst. Conclusions Patients with systemic cancer have higher mortality and less favorable discharge outcomes after ICH than patients without cancer. Cancer subtype may influence outcomes after ICH.

Background and Purpose: Providers vary in their thresholds for obtaining blood cultures in patients with ischemic stroke or transient ischemic attack (TIA). We assessed the rate of missed diagnoses of infective endocarditis (IE) in patients discharged with stroke or TIA before blood culture results could have been available. Methods: Using administrative claims data, we performed a retrospective cohort study of all patients discharged from nonfederal California emergency departments or acute care hospitals from 2005 through 2011 with stroke ( International Classification of Diseases, Ninth Revision, Clinical Modification [ ICD-9-CM] codes 433.x1, 434.x1, or 436 in any position) or TIA ( ICD-9-CM code 435 in the primary diagnosis position). We excluded patients with a length of stay >2 days to focus on those discharged before conclusive blood culture results could have been available. Our outcome was hospitalization within 14 days with a new diagnosis of IE ( ICD-9-CM codes 391.1 or 421.x in any position). Results: Among 173 966 eligible patients, 24 were subsequently hospitalized for IE—a readmission rate of 1.4 per 10 000 (95% confidence interval [CI], 0.8-1.9 per 10 000). Multiple logistic regression identified the following potential associations with readmission: prosthetic valve: odds ratio (OR), 15.8 (95% CI, 1.9-129.0); other valvular disease: OR, 1.5 (95% CI, 0.2-10.8); urinary tract infection: OR, 3.5 (95% CI, 1.0-12.3; P = .05). Conclusions: In patients with acute cerebral ischemia discharged before blood culture results could have been available, the rate of subsequent IE was negligible. These findings argue against the liberal use of blood cultures for the routine evaluation of stroke or TIA.