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Abstract Determining acute ischemic stroke (AIS) etiology is fundamental to secondary stroke prevention efforts but can be diagnostically challenging. We trained and validated an automated classification tool, StrokeClassifier, using electronic health record (EHR) text from 2039 non-cryptogenic AIS patients at 2 academic hospitals to predict the 4-level outcome of stroke etiology adjudicated by agreement of at least 2 board-certified vascular neurologists’ review of the EHR. StrokeClassifier is an ensemble consensus meta-model of 9 machine learning classifiers applied to features extracted from discharge summary texts by natural language processing. StrokeClassifier was externally validated in 406 discharge summaries from the MIMIC-III dataset reviewed by a vascular neurologist to ascertain stroke etiology. Compared with vascular neurologists’ diagnoses, StrokeClassifier achieved the mean cross-validated accuracy of 0.74 and weighted F1 of 0.74 for multi-class classification. In MIMIC-III, its accuracy and weighted F1 were 0.70 and 0.71, respectively. In binary classification, the two metrics ranged from 0.77 to 0.96. The top 5 features contributing to stroke etiology prediction were atrial fibrillation, age, middle cerebral artery occlusion, internal carotid artery occlusion, and frontal stroke location. We designed a certainty heuristic to grade the confidence of StrokeClassifier’s diagnosis as non-cryptogenic by the degree of consensus among the 9 classifiers and applied it to 788 cryptogenic patients, reducing cryptogenic diagnoses from 25.2% to 7.2%. StrokeClassifier is a validated artificial intelligence tool that rivals the performance of vascular neurologists in classifying ischemic stroke etiology. With further training, StrokeClassifier may have downstream applications including its use as a clinical decision support system.

Background This study proposes a modification to the traditional Hunt and Hess (tHH) grading scale for prognostication in aneurysmal subarachnoid hemorrhage (aSAH), which differentiates the most severe‐grade patients based on the presence or absence of brainstem dysfunction [determined by Glasgow Coma Scale (GCS) scores 3‐5]. Methods Weighted aSAH hospitalizations were retrospectively identified in the National Inpatient Sample from 2015 to 2019 and were stratified by tHH and modified HH (mHH) grades. mHH grade 5 was defined as tHH grade 5 with GCS score 3–5, while mHH grade 4 comprised tHH grade 5 with GCS score 6–8 and tHH grade 4. HH grades 1–3 do not differ between the traditional and modified scales. Measures of diagnostic performance were compared for the primary study end point [poor outcome as determined by the previously validated NIS‐SAH Outcome Measure (NIS‐SOM), shown to have high concordance with modified Rankin Scale scores > 2]. External validation of the mHH was performed using data from a prospectively maintained aSAH registry. Results Among 6130 aSAH hospitalizations, 2245 (36%) were tHH grade 5. Seven hundred and eighty‐five (35%) of these had a GCS 3–5 and were designated as mHH grade 5. Poor outcomes were identified in 78% and 77% of grade 4 tHH and mHH, respectively, and in 83% and 95% of grade 5 tHH and mHH, respectively. In comparison with the tHH, the mHH achieved superior discrimination [c‐statistic 0.793 (95% CI 0.768, 0.818) versus 0.780 (95% CI 0.750, 0.807); DeLong p < 0.001] for poor outcome, as well as improved specificity (0.929 versus 0.304) and positive predictive value (PPV) (0.949 versus 0.827). External registry validation of the mHH demonstrated excellent discrimination [c‐statistic 0.835 (95% CI 0.801, 0.870)], with a specificity of 0.950 and PPV of 0.905. Conclusion The mHH achieved a favorable diagnostic performance profile using retrospective data and may aid in the prognostication of high‐severity patients with aSAH.

Background Data regarding the prevalence and phenotype of cognitive impairment in non-alcoholic fatty liver disease (NAFLD) are limited.Objective We assessed the prevalence and nature of cognitive deficits in people with NAFLD and assessed whether liver fibrosis, an important determinant of outcomes in NAFLD, is associated with worse cognitive performance.Methods We performed a prospective cross-sectional study. Patients with NAFLD underwent liver fibrosis assessment with transient elastography and the following assessments: Cognitive Change Index, Eight-Item Informant Interview to Differentiate Aging and Dementia Questionnaire (AD8), Montreal Cognitive Assessment (MoCA), EncephalApp minimal hepatic encephalopathy test and a limited National Institutes of Health Toolbox battery (Flanker Inhibitory Control and Attention Test, Pattern Comparison Test and Auditory Verbal Learning Test). We used multiple linear regression models to examine the association between liver fibrosis and cognitive measures while adjusting for relevant covariates.Results We included 69 participants with mean age 50.4 years (SD 14.4); 62% were women. The median liver stiffness was 5.0 kilopascals (IQR 4.0–6.9), and 25% had liver fibrosis (≥7.0 kilopascals). Cognitive deficits were common in people with NAFLD; 41% had subjective cognitive impairment, 13% had an AD8 >2, 32% had MoCA

Background Rates of dual antiplatelet therapy (DAPT) after high‐risk transient ischemic attack or minor ischemic stroke (TIAMIS) are suboptimal. We performed a cost‐effectiveness analysis to characterize the parameters of a quality improvement (QI) intervention designed to increase DAPT use after TIAMIS. Methods and Results We constructed a decision tree model that compared current national rates of DAPT use after TIAMIS with rates after implementing a theoretical QI intervention designed to increase appropriate DAPT use. The base case assumed that a QI intervention increased the rate of DAPT use to 65% from 45%. Costs (payer and societal) and outcomes (stroke, myocardial infarction, major bleed, or death) were modeled using a lifetime horizon. An incremental cost‐effectiveness ratio

Abstract Objective Patients with posterior reversible encephalopathy syndrome (PRES) can develop seizures during the acute phase. We sought to determine the long‐term risk of seizure after PRES. Methods We performed a retrospective cohort study using statewide all‐payer claims data from 2016–2018 from nonfederal hospitals in 11 US states. Adults admitted with PRES were compared to adults admitted with stroke, an acute cerebrovascular disorder associated with long‐term risk of seizure. The primary outcome was seizure diagnosed during an emergency room visit or hospital admission after the index hospitalization. The secondary outcome was status epilepticus. Diagnoses were determined using previously validated ICD‐10‐CM codes. Patients with seizure diagnoses before or during the index admission were excluded. We used Cox regression to evaluate the association of PRES with seizure, adjusting for demographics and potential confounders. Results We identified 2095 patients hospitalized with PRES and 341,809 with stroke. Median follow‐up was 0.9 years (IQR, 0.3–1.7) in the PRES group and 1.0 years (IQR, 0.4–1.8) in the stroke group. Crude seizure incidence per 100 person‐years was 9.5 after PRES and 2.5 after stroke. After adjustment for demographics and comorbidities, patients with PRES had a higher risk of seizure than patients with stroke (HR, 2.9; 95% CI, 2.6–3.4). Results were unchanged in a sensitivity analysis that applied a two‐week washout period to mitigate detection bias. A similar relationship was observed for the secondary outcome of status epilepticus. Interpretation PRES was associated with an increased long‐term risk of subsequent acute care utilization for seizure compared to stroke.

BackgroundLeft atrial volume index (LAVI) is one marker of atrial myopathy, which is increasingly being recognized as a cause of cardioembolic stroke even in the absence of atrial fibrillation. Cardiac embolism is associated with larger strokes than other stroke mechanisms. The purpose of this study was to examine the association between LAVI and total brain infarct volume in patients with ischemic stroke.MethodsThis was a retrospective study of 545 patients prospectively enrolled in the Cornell ActuE Stroke Academic Registry (CAESAR), which includes all acute ischemic stroke patients admitted to our hospital since 2011. LAVI measurements were obtained from our echocardiography image store system (Xclera, Philips Healthcare). Brain infarcts on diffusion-weighted images (DWI) were manually segmented and infarct volume was obtained on 3D Slicer. We used multiple linear regression models adjusted for age, sex, race, and vascular comorbidities including atrial fibrillation.ResultsAmong 2,945 CAESAR patients, 545 patients had both total infarct volume and LAVI measured. We found an association between LAVI and log-transformed total brain infarct volume in both unadjusted (β = 0.018; p = 0.002) and adjusted (β = 0.024; p = 0.001) models.ConclusionWe found that larger left atrial volume was associated with larger brain infarcts. This association was independent of known cardioembolic risk factors such as atrial fibrillation and heart failure. These findings support the concept that atrial myopathy may be a source of cardiac embolism even in the absence of traditionally recognized mechanisms such as atrial fibrillation.

Background Cerebrovascular dysregulation syndromes, posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS), are challenging to diagnose because they are rare and require advanced neuroimaging for confirmation. We sought to estimate PRES/RCVS misdiagnosis in the emergency department and its associated factors. Methods and Results We conducted a retrospective cohort study of PRES/RCVS patients using administrative claims data from 11 states (2016–2018). We defined patients with a probable PRES/RCVS misdiagnosis as those with an emergency department visit for a neurological symptom resulting in discharge to home that occurred ≤14 days before PRES/RCVS hospitalization. Proportions of patients with probable misdiagnosis were calculated, characteristics of patients with and without probable misdiagnosis were compared, and regression analyses adjusted for demographics and comorbidities were performed to identify factors affecting probable misdiagnosis. We identified 4633 patients with PRES/RCVS. A total of 210 patients (4.53% [95% CI, 3.97–5.17]) had a probable preceding emergency department misdiagnosis; these patients were younger (mean age, 48 versus 54 years; P

Abstract Background Pediatric spinal fusion may be associated with significant intraoperative blood loss, leading to complications from transfusion, hypoperfusion and coagulopathy. One emerging strategy to mediate these risks is by utilization of the anti-fibrinolytic agent tranexamic acid (TXA). However, concerns regarding potential adverse reactions, specifically postoperative seizures and thrombotic events, still exist. To assess these risks, we examined the perioperative morbidity of TXA use in a large national database. Methods Retrospective data from pediatric patients (age 18 years or younger), discharged between January 2013 to December 2015, who underwent primary or revision posterior spinal fusions, was collected from the Premier Perspective database (Premier, Charlotte, NC). Patients were stratified by TXA use and records were assessed for complications of new onset seizures, strokes, pulmonary embolisms (PE) or deep vein thromboses (DVT) occurring during the perioperative period. Results In this cohort of 2,633 pediatric patients undergoing posterior spinal fusions, most often to treat adolescent idiopathic scoliosis, 15% received TXA. Overall, adverse events were rare in this patient population. The incidence of seizure, stoke, PE, or DVT in the control group was 0.54% (95% CI, 0.31% to 0.94%) and not significantly different from the TXA group. There was no significant difference in the incidence of DVTs, and no incidences of stroke in either group. There were no new-onset seizures or PEs in patients who received TXA. Conclusions The use of TXA was not associated with an increased risk of adverse events including seizure, stroke, PE, and DVT. Our findings support the safety of TXA use in pediatric patients undergoing spinal fusion surgery.

Background Small spotty calcifications in the coronary arteries are associated with an increased risk of myocardial infarction. We examined the association between spotty calcifications near the carotid bifurcations and ipsilateral ischemic stroke in patients with

Background The duration and magnitude of increased stroke risk after a hospitalization for acute systolic heart failure (HF) remains uncertain. Methods and Results The authors performed a retrospective cohort study using claims (2008–2018) from a nationally representative 5% sample of Medicare beneficiaries aged ≥66 years. Cox regression models were fitted separately for the groups with and without acute systolic HF to examine its association with the incidence of ischemic stroke after adjustment for demographics, stroke risk factors, and Charlson comorbidities. Corresponding survival probabilities were used to compute the hazard ratio (HR) in each 30‐day interval after discharge. The authors stratified patients by the presence of atrial fibrillation (AF) before or during the hospitalization for acute systolic HF. Among 2 077 501 eligible beneficiaries, 94 641 were hospitalized with acute systolic HF. After adjusting for demographics, stroke risk factors, and Charlson comorbidities, the risk of ischemic stroke was highest in the first 30 days after discharge from an acute systolic HF hospitalization for patients with AF (HR, 2.4 [95% CI, 2.1–2.7]) and without AF (HR, 4.6 [95% CI, 4.0–5.3]). The risk of stroke remained elevated for 60 days in patients with AF (HR, 1.4 [95% CI, 1.2–1.6]) and was not significantly elevated afterward. The risk of stroke remained significantly elevated through 330 days in patients without AF (HR, 2.1 [95% CI, 1.7–2.7]) and was no longer significantly elevated afterward. Conclusions A hospitalization for acute systolic HF is associated with an increased risk of ischemic stroke up to 330 days in patients without concomitant AF.

Background Access to mechanical thrombectomy (MT) in the United States remains limited. Given potential staffing challenges, we hypothesized that access to thrombectomy would be worse off hours. Methods We used 2016 to 2018 all‐payer claims data from all nonfederal emergency departments and acute care hospitals across 11 US states encompassing 80 million residents. Using recorded arrival times, hospital presentation was classified as on hours if it fell between 8:00 a.m. and 6:00 p.m. on weekdays and as off hours otherwise. We examined the association between off‐hours arrival and MT using multiple adjusted logistic regression models. In a subset of patients with available National Institutes of Health Stroke Scale data, we performed a sensitivity analysis limited to patients who presented to a thrombectomy hub with a probable large‐vessel occlusion, defined as a documented National Institutes of Health Stroke Scale score ≥12, and underwent intravenous thrombolysis. Similar analyses were performed to assess MT odds during extreme off hours, defined as midnight to 6:00 a.m., compared to 8:00 a.m. to 2:00 p.m. Results Among 169 199 patients with ischemic stroke, the 82 784 (48.9%) who presented during off hours more often presented to thrombectomy hubs and teaching hospitals and more often received intravenous thrombolysis. Among 31 148 patients with documented National Institutes of Health Stroke Scale scores, those presenting off hours had higher scores (4 [interquartile range, 2–10] versus 2 [interquartile range, 1–9]; P

Abstract Recent evidence indicates that our understanding of the relationship between cardiac function and ischemic stroke remains incomplete. The Cardiovascular Health Study enrolled community-dwelling adults ≥ 65 years old. We included participants with speckle-tracking data from digitized baseline study echocardiograms. Exposures were left atrial reservoir strain (primary), left ventricular longitudinal strain, left ventricular early diastolic strain rate, septal e’ velocity, and lateral e’ velocity. The primary outcome was incident ischemic stroke. Cox proportional hazards models were adjusted for demographics, image quality, and risk factors including left ventricular ejection fraction and incident atrial fibrillation. Among 4,000 participants in our analysis, lower (worse) left atrial reservoir strain was associated with incident ischemic stroke (HR per SD absolute decrease, 1.14; 95% CI 1.04–25). All secondary exposure variables were significantly associated with the outcome. Left atrial reservoir strain was associated with cardioembolic stroke (HR per SD absolute decrease, 1.42; 95% CI 1.21–1.67) and cardioembolic stroke related to incident atrial fibrillation (HR per SD absolute decrease, 1.60; 1.32–1.95). Myocardial dysfunction that can ultimately lead to stroke may be identifiable at an early stage. This highlights opportunities to identify cerebrovascular risk earlier and improve stroke prevention via therapies for early myocardial dysfunction.