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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 Sex differences in stroke outcomes have been noted, but whether this extends to stroke recurrence is unclear. We examined sex differences in recurrent stroke using data from the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial. Patients and methods We assessed the risk of recurrent stroke in women compared to men using data from the POINT trial. Adults >18 years old were randomized within 12 hours of onset of minor ischemic stroke or transient ischemic attack (TIA), and followed for up to 90 days for ischemic stroke, our primary outcome. We used Cox proportional hazards model adjusted for demographics and stroke risk factors to evaluate the association between sex and stroke recurrence. We used interaction term testing and prespecified subgroup analyses to determine if the association between sex and recurrent stroke differed by age (60 years old), locale (US versus non-US), and index event type (stroke versus TIA). Last, we evaluated whether sex modified the effect of common stroke risk factors on stroke recurrence. Results Of 4,881 POINT trial participants with minor stroke or high-risk TIA, 2,195 (45%) were women. During the 90-day follow-up period, 267 ischemic strokes occurred; 121 were in women and 146 in men. The cumulative risk of recurrent ischemic stroke was not significantly different among women (5.76%; 95% CI, 4.84%–6.85%) compared to men (5.67%; 95% CI, 4.83%–6.63%). Women were not at a different risk of recurrent ischemic stroke compared to men (hazard ratio [HR], 1.02; 95% CI, 0.80–1.30) in unadjusted models or after adjusting for covariates. However, there was a significant interaction of age with sex (P=0.04). Among patients Discussion and Conclusion Among patients with minor stroke or TIA, the risk of recurrent ischemic stroke and the impact of common stroke risk factors did not differ between men and women.

Background and ObjectivesTo examine associations between indicators of estrogen exposure from women's reproductive history and brain MRI biomarkers of Alzheimer disease (AD) in midlife.MethodsWe evaluated 99 cognitively normal women 52 ± 6 years of age and 29 men 52 ± 7 years of age with reproductive history data, neuropsychological testing, and volumetric MRI scans. We used multiple regressions to examine associations among reproductive history indicators, voxel-wise gray matter volume (GMV), and memory and global cognition scores, adjusting for demographics and midlife health indicators. Exposure variables were menopause status, age at menarche, age at menopause, reproductive span, hysterectomy status, number of children and pregnancies, and use of menopause hormonal therapy (HT) and hormonal contraceptives (HC).ResultsAll menopausal groups exhibited lower GMV in AD-vulnerable regions compared to men, with perimenopausal and postmenopausal groups also exhibiting lower GMV in temporal cortex compared to the premenopausal group. Reproductive span, number of children and pregnancies, and use of HT and HC were positively associated with GMV, chiefly in temporal cortex, frontal cortex, and precuneus, independent of age, APOE ε4 status, and midlife health indicators. Although reproductive history indicators were not directly associated with cognitive measures, GMV in temporal regions was positively associated with memory and global cognition scores.DiscussionReproductive history events signaling more estrogen exposure such as premenopausal status, longer reproductive span, higher number of children, and use of HT and HC were associated with larger GMV in women in midlife. Further studies are needed to elucidate sex-specific biological pathways through which reproductive history influences cognitive aging and AD risk.

Upstream therapy of atrial remodeling may decrease atrial fibrillation and associated thromboembolism. We examined the impact of intensive BP lowering on ECG-defined left atrial abnormalities in the SPRINT. SPRINT was a randomized clinical trial comparing outcomes when a systolic BP of 4000 μV × ms. Secondary outcomes were regression of the left atrial abnormality and the change in PTFV1 from baseline across follow-up ECGs. Cox regression was used to examine the associations between treatment assignment and incident left atrial abnormality and its regression. We used linear mixed models to examine the changes in PTFV1. Of 9361 SPRINT participants, 7738 qualified for this analysis, of whom 5544 did not have baseline left atrial abnormalities. Intensive BP management was not associated with incident left atrial abnormality (HR, 0.96; 95% CI, 0.87-1.07) or regression of the baseline left atrial abnormality (HR, 1.09; 95% CI, 0.98-1.21). The change in PTFV1 from baseline through follow-up did not differ significantly between treatment groups (difference in μV × ms per year, 6; 95% CI, -67 to 79). Thus, among patients in a randomized clinical trial, we found no difference in the progression or regression of ECG-defined left atrial abnormalities with intensive BP management compared to standard BP management.

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.

ObjectiveTo test the hypothesis that silent myocardial infarction (MI) is a risk factor for ischemic stroke, we evaluated the association between silent MI and subsequent ischemic stroke in the Cardiovascular Health Study.MethodsThe Cardiovascular Health Study prospectively enrolled community-dwelling individuals ≥65 years of age. We included participants without prevalent stroke or baseline evidence of MI. Our exposures were silent and clinically apparent, overt MI. Silent MI was defined as new evidence of Q-wave MI, without clinical symptoms of MI, on ECGs performed during annual study visits from 1989 to 1999. The primary outcome was incident ischemic stroke. Secondary outcomes were ischemic stroke subtypes: nonlacunar, lacunar, and other/unknown. Cox proportional hazards analysis was used to model the association between time-varying MI status (silent, overt, or no MI) and stroke after adjustment for baseline demographics and vascular risk factors.ResultsAmong 4,224 participants, 362 (8.6%) had an incident silent MI, 421 (10.0%) an incident overt MI, and 377 (8.9%) an incident ischemic stroke during a median follow-up of 9.8 years. After adjustment for demographics and comorbidities, silent MI was independently associated with subsequent ischemic stroke (hazard ratio [HR], 1.51; 95% confidence interval [CI], 1.03–2.21). Overt MI was associated with ischemic stroke both in the short term (HR, 80; 95% CI, 53–119) and long term (HR, 1.60; 95% CI, 1.04–2.44). In secondary analyses, the association between silent MI and stroke was limited to nonlacunar ischemic stroke (HR, 2.40; 95% CI, 1.36–4.22).ConclusionIn a community-based sample, we found an association between silent MI and ischemic stroke.

Background: Atrial fibrillation (AF) is frequently reported as a complication of noncardiac surgery. It is unknown whether new-onset perioperative AF is associated with an increased risk of stroke and death beyond the perioperative period. We performed a systematic review and meta-analysis to assess the long-term risks of stroke and mortality associated with new-onset perioperative AF after noncardiac surgery. Methods: MEDLINE and EMBASE were searched from inception to March 2020 for studies reporting on the association between perioperative AF and the risk of stroke and death occurring beyond 30 days after noncardiac surgery. Reference screening, study selection, data extraction, and quality assessment were performed in duplicate. Data were pooled using inverse variance-weighted random-effects models and presented as risk ratios (RRs). Results: From 7344 citations, we included 31 studies (3,529,493 patients). The weighted mean incidence of perioperative AF was 0.7%. During a mean follow-up of 28.1 ± 9.4 months, perioperative AF was associated with an increased risk of stroke (1.5 vs 0.9 strokes per 100 patient-years; RR: 2.9, 95% confidence interval [CI]: 2.1-3.9, I2 = 78%). Perioperative AF was also associated with a significantly higher risk of all-cause mortality (21.0 vs 7.6 deaths per 100 patient-years; RR: 1.8, 95% CI: 1.5-2.2, I2 = 94%). The pooled adjusted hazard ratios for stroke and all-cause mortality were 1.9 (95% CI: 1.6-2.2, I2 = 31%) and 1.5 (95% CI: 1.3-1.7, I2 = 20%), respectively. Conclusions: Patients who had perioperative AF after noncardiac surgery had a higher long-term risk of stroke and mortality compared with patients who did not. Whether this risk is modifiable with oral anticoagulation therapy should be investigated. Résumé: Contexte: La fibrillation atriale (FA) est une arythmie fréquemment attribuée à une complication d’une chirurgie non cardiaque. On ne sait toutefois pas si l’apparition d’une FA périopératoire est associée à un risque accru d’accident vasculaire cérébral et de décès au-delà de la période périopératoire. Nous avons donc procédé à un examen et à une méta-analyse systématiques dans le but d’évaluer les risques à long terme d’accident vasculaire cérébral et de décès associés à l’apparition d’une FA périopératoire à la suite d’une chirurgie non cardiaque. Méthodologie: Des recherches ont été effectuées dans MEDLINE et EMBASE depuis leur création jusqu’à mars 2020 pour y relever les études signalant l’association entre la FA périopératoire et le risque d’accident vasculaire cérébral et de décès survenant au-delà de 30 jours à la suite d’une chirurgie non cardiaque. Le tri des références, la sélection des études, l’extraction des données et l’évaluation de la qualité ont été effectués en double. Les données ont été regroupées à l’aide de modèles à effets aléatoires pondérés par l’inverse de la variance et présentées sous forme de rapports de risques relatifs (RR). Résultats: Parmi 7 344 références, nous avons inclus 31 études (3 529 493 patients). L’incidence moyenne pondérée de FA périopératoire était de 0,7 %. Dans le cadre d’un suivi moyen de 28,1 ± 9,4 mois, la FA périopératoire était associée à un risque accru d’accident vasculaire cérébral (1,5 vs 0,9 accident vasculaire cérébral par 100 années-patients; RR de 2,9; intervalle de confiance [IC] à 95 %; de 2,1 à 3,9; I2 = 78 %). La FA périopératoire était également associée à un risque considérablement plus élevé de décès toutes causes confondues (21,0 vs 7,6 décès par 100 années-patients; RR de 1,8; IC à 95 %; de 1,5 à 2,2; I2 = 94 %). Les rapports de risques instantanés ajustés regroupés d’accident vasculaire cérébral et de décès toutes causes confondues étaient de 1,9 (IC à 95 %; de 1,6 à 2,2; I2 = 31 %) et de 1,5 (IC à 95 %; de 1,3 à 1,7; I2 = 20 %), respectivement. Conclusions: Les patients qui souffraient de FA périopératoire à la suite d’une chirurgie non cardiaque présentaient un risque accru à long terme d’accident vasculaire cérébral et de décès par rapport aux patients qui n’en souffraient pas. Il serait approprié d’examiner la possibilité de modifier ce risque par une anticoagulothérapie orale.

Background and Purpose: Recent studies suggest that alteration of the normal gut microbiome contributes to atherosclerotic burden and cardiovascular disease. While many gastrointestinal diseases are known to cause disruption of the normal gut microbiome in humans, the clinical impact of gastrointestinal diseases on subsequent cerebrovascular disease remains unknown. We conducted an exploratory analysis evaluating the relationship between gastrointestinal diseases and ischemic stroke. Methods: We performed a retrospective cohort study using claims between 2008 and 2015 from a nationally representative 5% sample of Medicare beneficiaries. We included only beneficiaries ≥66 years of age. We used previously validated diagnosis codes to ascertain our primary outcome of ischemic stroke. In an exploratory manner, we categorized gastrointestinal disorders by anatomic location, disease chronicity, and disease mechanism. We used Cox proportional hazards models to examine associations of gastrointestinal disorder categories and ischemic stroke with adjustment for demographics and established vascular risk factors. Results: Among a mean of 1 725 246 beneficiaries in each analysis, several categories of gastrointestinal disorders were associated with an increased risk of ischemic stroke after adjustment for established stroke risk factors. The most notable positive associations included disorders of the stomach (hazard ratio, 1.17 [95% CI, 1.15–1.19]) and functional (1.16 [95% CI, 1.15–1.17]), inflammatory (1.13 [95% CI, 1.12–1.15]), and infectious gastrointestinal disorders (1.13 [95% CI, 1.12–1.15]). In contrast, we found no associations with stroke for diseases of the anus and rectum (0.97 [95% CI, 0.94–1.00]) or neoplastic gastrointestinal disorders (0.97 [95% CI, 0.94–1.00]). Conclusions: In exploratory analyses, several categories of gastrointestinal disorders were associated with an increased risk of future ischemic stroke after adjustment for demographics and established stroke risk factors.

ObjectiveTo test the hypothesis that thrombogenic atrial cardiopathy may be relevant to stroke-related racial disparities, we compared atrial cardiopathy phenotypes between Black vs White patients with ischemic stroke.MethodsWe assessed markers of atrial cardiopathy in the Greater Cincinnati/Northern Kentucky Stroke Study, a study of stroke incidence in a population of 1.3 million. We obtained ECGs and reports of echocardiograms performed during evaluation of stroke during the 2010/2015 study periods. Patients with atrial fibrillation (AF) or flutter (AFL) were excluded. Investigators blinded to patients' characteristics measured P-wave terminal force in ECG lead V1 (PTFV1), a marker of left atrial fibrosis and impaired interatrial conduction, and abstracted left atrial diameter from echocardiogram reports. Linear regression was used to examine the association between race and atrial cardiopathy markers after adjustment for demographics, body mass index, and vascular comorbidities.ResultsAmong 3,426 ischemic stroke cases in Black or White patients without AF/AFL, 2,391 had a left atrial diameter measurement (mean, 3.65 ± 0.70 cm). Black race was associated with smaller left atrial diameter in unadjusted (β coefficient, −0.11; 95% confidence interval [CI], −0.17 to −0.05) and adjusted (β, −0.15; 95% CI, −0.21 to −0.09) models. PTFV1 measurements were available in 3,209 patients (mean, 3,434 ± 2,525 μV*ms). Black race was associated with greater PTFV1 in unadjusted (β, 1.59; 95% CI, 1.21–1.97) and adjusted (β, 1.45; 95% CI, 1.00–1.80) models.ConclusionsWe found systematic Black–White racial differences in left atrial structure and pathophysiology in a population-based sample of patients with ischemic stroke.Classification of EvidenceThis study provides Class II evidence that atrial cardiopathy phenotypes differ in Black people with acute stroke compared to White people.

Atrial fibrillation (AF) and stroke are inextricably connected, with classical Virchow pathophysiology explaining thromboembolism through blood stasis in the fibrillating left atrium. This conceptualization has been reinforced by the remarkable efficacy of oral anticoagulant (OAC) for stroke prevention in AF. A number of observations showing that the presence of AF is neither necessary nor sufficient for stroke, cast doubt on the causal role of AF as a villain in vascular brain injury (VBI). The requirement for additional risk factors before AF increases stroke risk; temporal disconnect of AF from a stroke in patients with no AF for months before stroke during continuous ECG monitoring but manifesting AF only after stroke; and increasing recognition of the role of atrial cardiomyopathy and atrial substrate in AF-related stroke, and also stroke without AF, have led to rethinking the pathogenetic model of cardioembolic stroke. This is quite separate from recognition that in AF, shared cardiovascular risk factors can lead both to non-embolic stroke, or emboli from the aorta and carotid arteries. Meanwhile, VBI is now expanded to include dementia and cognitive decline: research is required to see if reduced by OAC. A changed conceptual model with less focus on the arrhythmia, and more on atrial substrate/cardiomyopathy causing VBI both in the presence or absence of AF, is required to allow us to better prevent AF-related VBI. It could direct focus towards prevention of the atrial cardiomyopathy though much work is required to better define this entity before the balance between AF as villain or bystander can be determined.

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.

ObjectiveTo determine the leading causes of death in intracerebral hemorrhage (ICH) survivors, we used administrative data from 3 large US states to identify adult survivors of a first-time spontaneous ICH and track all hospital readmissions resulting in death.MethodsWe performed a longitudinal analysis of prospectively collected claims data from hospitalizations in California (2005–2011), New York (2005–2014), and Florida (2005–2014). Adult residents admitted with a nontraumatic ICH who survived to discharge were included. Patients were followed for a primary outcome of any readmission resulting in death. The cause of death was defined as the primary diagnosis assigned at discharge. Multivariable Cox proportional hazards and multinomial logistic regression were used to determine factors associated with the risk for and cause of death.ResultsOf 72,432 ICH survivors (mean age 68 years [SD 16], 48% female), 12,753 (18%) died during a median follow-up period of 4.0 years (interquartile range 2.3–6.3). The leading causes of death were infection (34%), recurrent intracranial hemorrhage (14%), cardiac disease (8%), respiratory failure (8%), and ischemic stroke (5%). Death in patients with atrial fibrillation (AF) was more likely to be caused by ischemic stroke (odds ratio [OR] 2.4, 95% confidence interval [CI] 1.9–2.9, p < 0.001) and less likely to be caused by recurrent intracranial hemorrhage (OR 0.7, 95% CI 0.6–0.8, p < 0.001) compared to patients without AF.ConclusionsInfection is the leading cause of death in all ICH survivors. Survivors with AF were at increased risk for death from ischemic stroke. These findings will help prioritize interventions aimed to improve long-term survival and recovery in ICH survivors.

ObjectiveTo determine whether race is associated with the development of epilepsy after subdural hematoma (SDH), we identified adult survivors of SDH in a statewide administrative dataset and followed them up for at least 1 year for revisits associated with epilepsy.MethodsWe performed a retrospective cohort study using claims data on all discharges from emergency departments (EDs) and hospitals in California. We identified adults (age ≥18 years) admitted from 2005 to 2011 with first-time traumatic and nontraumatic SDH. We used validated diagnosis codes to identify a primary outcome of ED or inpatient revisit for epilepsy. We used multivariable Cox regression for survival analysis to identify demographic and medical risk factors for epilepsy.ResultsWe identified 29,342 survivors of SDH (mean age 71.2 [SD 16.4] years, female sex 11,954 [41.1%]). Three thousand two hundred thirty (11.0%) patients had revisits to EDs or hospitals with a diagnosis of epilepsy during the study period. Black patients (n = 1,684 [5.7%]) had significantly increased risk compared to White patients (n = 16,945 [57.7%]; hazard ratio [HR] 1.45, 95% confidence interval [CI] 1.28–1.64, p < 0.001). Status epilepticus during the index SDH admission, although infrequent (n = 94 [0.3%]), was associated with a nearly 4-fold risk of epilepsy (HR 3.75, 95% CI 2.80–5.03, p < 0.001). Alcohol use, drug use, smoking, renal disease, and markers of injury severity (i.e., intubation, surgical intervention, length of stay, disposition other than home) were also associated with epilepsy (all p < 0.05).ConclusionsWe found an association between Black race and ED and hospital revisits for epilepsy after SDH, establishing the presence of a racial subgroup that is particularly vulnerable to post-SDH epileptogenesis.

BACKGROUND/OBJECTIVES: Liver disease is associated with altered serum osmolality, increased thrombin generation, and systemic inflammation, all of which may contribute to perihematomal edema (PHE) after intracerebral hemorrhage (ICH). We evaluated the association between a validated liver fibrosis index and PHE growth in a cohort of patients with primary ICH. METHODS: We performed a retrospective cohort study using data from the Virtual International Stroke Trials Archive-ICH. We included adult patients with primary ICH presenting within 6 hours of symptom onset. The exposure of interest was the Fibrosis-4 (FIB-4) score, a validated liver fibrosis index; this was modeled as a continuous variable. The primary outcome was absolute PHE growth over 96 hours. Secondary outcomes were absolute admission and 96-hour PHE volumes. We used multiple linear regression models adjusted for established determinants of PHE. In a secondary analysis, the FIB-4 score was modeled as a categorical variable to compare patients with versus without liver fibrosis. RESULTS: Among 354 patients with ICH, 8% had evidence of liver fibrosis based on a validated cut-off. The FIB-4 score was not associated with PHE growth in unadjusted (β, 0.03; 95% CI, −0.01–0.12) or adjusted models (β, 0.04; 95% CI, −0.03–0.13). In a secondary analysis treating FIB-4 as a categorical variable, patients with liver fibrosis did not have greater PHE growth than those without liver fibrosis. FIB-4 score was also not associated with absolute admission or 96-hour absolute PHE volumes. CONCLUSIONS: In a multicenter cohort of patients with primary intracerebral hemorrhage, a liver fibrosis score was not associated with PHE volume or growth.

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 Alpha-1 antitrypsin (AAT) is a potent anti-protease enzyme which may play a role in arterial wall stability. A variant of its encoding gene has been recently linked to ischemic stroke due to large artery atherosclerosis (LAA). We sought to explore potential relationships between ischemic stroke mechanisms, atherosclerosis burden and serum AAT levels. Methods We performed a prospective observational study of consecutive patients with acute ischemic stroke who were admitted to an academic comprehensive stroke center over a three-month period. Blood samples were collected within 24 h of hospital admission, and stroke subtype classification was determined based on modified TOAST criteria. Modified Woodcock scoring system was used to quantify calcification of major cervico-cranial arteries as a surrogate for atherosclerosis burden. Linear regression analysis was used to assess the association between serum AAT levels and calcification scores, both as continuous variables. Results Among eighteen patients met our inclusion criteria and were enrolled in our study, 10 patients (56%) were men; mean age was 66 (SD 12.5); median NIH stroke scale was 4 (IQR 9.5); 8 patients (44%) had stroke due to LAA. The median serum level of AAT was 140 mg/dl (IQR 41.7) for patients with LAA-related stroke, and 148.5 mg/dl (IQR 37.7) for patients with other stroke mechanisms (p = 0.26). Higher serum AAT levels was associated with lower modified Woodcock calcification scores. (p-value = 0.038) Conclusions Measurement of AAT levels in patients with acute stroke is feasible, and there may be associations between AAT levels and stroke mechanism that warrant further study in larger samples.

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.

Purpose of review This article discusses cryptogenic stroke and the results of recent randomized trials that can inform its evaluation and management. Recent findings Most cryptogenic strokes appear embolic, leading to the term embolic stroke of undetermined source. It was previously thought that embolic stroke of undetermined source was a single, therapeutically relevant entity, the underlying sources of which would respond to anticoagulant therapy; however, two large randomized trials found no benefit with anticoagulation compared to antiplatelet therapy for secondary stroke prevention after embolic stroke of undetermined source. A single antiplatelet drug remains the recommended long-term antithrombotic treatment for secondary stroke prevention in embolic stroke of undetermined source. However, three caveats should be considered with regard to cryptogenic stroke. First, those with minor stroke symptoms presenting early after onset should receive 3 weeks of dual antiplatelet therapy. Second, all patients with cryptogenic stroke should be monitored for atrial fibrillation. Third, patients 60 years of age or younger with a patent foramen ovale (PFO) should be carefully evaluated to determine whether the PFO may have caused the stroke and whether they might benefit from PFO closure. Summary More personalized strategies may soon be available to guide treatment of cryptogenic stroke. In the meantime, it is hoped that the application of recent findings from clinical trials will reduce stroke recurrence in this important population.

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.

ObjectiveTo estimate the risk of intracerebral hemorrhage (ICH) recurrence in a large, diverse, US-based population and to identify racial/ethnic and socioeconomic subgroups at higher risk.MethodsWe performed a longitudinal analysis of prospectively collected claims data from all hospitalizations in nonfederal California hospitals between 2005 and 2011. We used validated diagnosis codes to identify nontraumatic ICH and our primary outcome of recurrent ICH. California residents who survived to discharge were included. We used log-rank tests for unadjusted analyses of survival across racial/ethnic groups and multivariable Cox proportional hazards regression to determine factors associated with risk of recurrence after adjusting for potential confounders.ResultsWe identified 31,355 California residents with first-recorded ICH who survived to discharge, of whom 15,548 (50%) were white, 6,174 (20%) were Hispanic, 4,205 (14%) were Asian, and 2,772 (9%) were black. There were 1,330 recurrences (4.1%) over a median follow-up of 2.9 years (interquartile range 3.8). The 1-year recurrence rate was 3.0% (95% confidence interval [CI] 2.8%–3.2%). In multivariable analysis, black participants (hazard ratio [HR] 1.22; 95% CI 1.01–1.48; p = 0.04) and Asian participants (HR 1.29; 95% CI 1.10–1.50; p = 0.001) had a higher risk of recurrence than white participants. Private insurance was associated with a significant reduction in risk compared to patients with Medicare (HR 0.60; 95% CI 0.50–0.73; p < 0.001), with consistent estimates across racial/ethnic groups.ConclusionsBlack and Asian patients had a higher risk of ICH recurrence than white patients, whereas private insurance was associated with reduced risk compared to those with Medicare. Further research is needed to determine the drivers of these disparities.

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

The role of calcium in atherosclerosis is controversial and the relationship between vascular calcification and plaque vulnerability is not fully understood. Although calcifications are present in ≈50% to 60% of carotid plaques, their association with cerebrovascular ischemic events remains unclear. In this review, we summarize current understanding of carotid plaque calcification. We outline the role of calcium in atherosclerotic carotid disease by analyzing laboratory studies and histopathologic studies, as well as imaging findings to understand clinical implications of carotid artery calcifications. Differences in mechanism of calcium deposition express themselves into a wide range of calcification phenotypes in carotid plaques. Some patterns, such as rim calcification, are suggestive of plaques with inflammatory activity with leakage of the vasa vasourm and intraplaque hemorrhage. Other patterns such as dense, nodular calcifications may confer greater mechanical stability to the plaque and reduce the risk of embolization for a given degree of plaque size and luminal stenosis. Various distributions and patterns of carotid plaque calcification, often influenced by the underlying systemic pathological condition, have a different role in affecting plaque stability. Modern imaging techniques afford multiple approaches to assess geometry, pattern of distribution, size, and composition of carotid artery calcifications. Future investigations with these novel technologies will further improve our understanding of carotid artery calcification and will play an important role in understanding and minimizing stroke risk in patients with carotid plaques.

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.

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.

BackgroundThe prevalence, incidence and risk factors of atrial fibrillation (AF) in a large, geographically and ethnically diverse cohort in the United States have not been fully described.MethodsWe analyzed data from 173,099 participants of theAll of UsResearch Program recruited in the period 2017-2019, with 92,318 of them having electronic health records (EHR) data available, and 35,483 having completed a medical history survey. Presence of AF at baseline was identified from self-report and EHR records. Incident AF was obtained from EHR. Demographic, anthropometric and clinical risk factors were obtained from questionnaires, baseline physical measurements and EHR.ResultsAt enrollment, mean age was 52 years old (range 18-89). Females and males accounted for 61% and 39% respectively. Non-Hispanic Whites accounted for 67% of participants, with non-Hispanic Blacks, non-Hispanic Asians and Hispanics accounting for 26%, 4% and 3% of participants, respectively. Among 92,318 participants with available EHR data, 3,885 (4.2%) had AF at the time of study enrollment, while the corresponding figure among 35,483 with medical history data was 2,084 (5.9%). During a median follow-up of 16 months, 354 new cases of AF were identified among 88,433 eligible participants. Individuals who were older, male, non-Hispanic white, had higher body mass index, or a prior history of heart failure or coronary heart disease had higher prevalence and incidence of AF.ConclusionThe epidemiology of AF in theAll of UsResearch Program is similar to that reported in smaller studies with careful phenotyping, highlighting the value of this new resource for the study of AF and, potentially, other cardiovascular diseases.

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.

The objective of this study was to evaluate initial feasibility and improvement in the detection of calcified carotid arteries by including quantitative susceptibility mapping (QSM) in the carotid vessel wall multi-contrast MRI (mcMRI) protocol using CTA as the reference standard. In a pilot cohort of ten patients with significant carotid artery stenosis, calcified vessel detection by mcMRI achieved 64.7% sensitivity and 100% specificity. Adding QSM to mcMRI improved sensitivity to 100% while not affecting specificity.

Author(s): Nwabuobi, Lynda; Zhang, Cenai; Henchcliffe, Claire; Shah, Hiral; Sarva, Harini; Lee, Andrea; Kamel, Hooman | Abstract: BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has caused worse health outcomes among elderly populations with specific pre-existing medical conditions and chronic illnesses. There are limited data on health outcomes of hospitalized Parkinson's disease (PD) individuals infected with COVID-19.ObjectivesTo determine clinical characteristics and outcomes in hospitalized PD individuals infected with COVID-19.MethodsIndividuals admitted to NewYork-Presbyterian with a diagnosis of PD were retrospectively identified using an electronic medical record system. Clinical characteristics and mortality were abstracted.ResultsTwenty-five individuals with PD, mostly male (76%) with a median age of 82 years (IQR 73-88 years), were hospitalized for COVID-19 infection. A total of 80% of individuals had mid-stage to advanced PD (Hoehn and Yahr 3-5) and 80% were on symptomatic pharmacologic therapy, most commonly levodopa (72%). The most common comorbidities were hypertension (72%) and mild cognitive impairment or dementia (48%). A total of 44% and 12% of individuals presented with altered mental status and falls, respectively. Mortality rate was 32% compared to 26% for age-matched controls (Pn=n0.743). Individuals who died were more likely to have encephalopathy during their admission (88% vs. 35%; P l 0.03).ConclusionPD individuals who require hospitalization for COVID-19 infection are likely to be elderly, have mid-stage to advanced disease, and be on pharmacologic therapy. Hypertension and cognitive impairment are common comorbidities in these individuals and encephalopathy during hospitalization is associated with risk of death. Altered mental status and falls are clinical presentations of COVID-19 infection in PD that clinicians should be aware of. A diagnosis of PD is not a risk factor for COVID-19 mortality.

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.

IMPORTANCE: Patients with ischemic stroke attributed to large- or small-vessel disease are not considered at high risk for atrial fibrillation (AF), and the AF incidence rate in this population is unknown. OBJECTIVES: To determine whether long-term cardiac monitoring is more effective than usual care for AF detection in patients with stroke attributed to large- or small-vessel disease through 12 months of follow-up. DESIGN, SETTING, AND PARTICIPANTS: The STROKE-AF trial was a randomized (1:1), multicenter (33 sites in the US) clinical trial that enrolled 496 patients between April 2016 and July 2019, with primary end point follow-up through August 2020. Eligible patients were aged 60 years or older or aged 50 to 59 years with at least 1 additional stroke risk factor and had an index stroke attributed to large- or small-vessel disease within 10 days prior to insertable cardiac monitor (ICM) insertion. INTERVENTIONS: Patients randomized to the intervention group (n = 242) received ICM insertion within 10 days of the index stroke; patients in the control group (n = 250) received site-specific usual care consisting of external cardiac monitoring, such as 12-lead electrocardiograms, Holter monitoring, telemetry, or event recorders. MAIN OUTCOMES AND MEASURES: Incident AF lasting more than 30 seconds through 12 months. RESULTS: Among 492 patients who were randomized (mean [SD] age, 67.1 [9.4] years; 185 [37.6%] women), 417 (84.8%) completed 12 months of follow-up. The median (interquartile range) CHA(2)DS(2)-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischemic attack, vascular disease, age 65 to 74 years, sex category) score was 5 (4-6). AF detection at 12 months was significantly higher in the ICM group vs the control group (27 patients [12.1%] vs 4 patients [1.8%]; hazard ratio, 7.4 [95% CI, 2.6-21.3]; P

Cardiac thromboembolism attributed to atrial fibrillation (AF) is responsible for up to one-third of ischemic strokes. Stroke may be the first manifestation of previously undetected AF. Given the efficacy of oral anticoagulants in preventing AF-related ischemic strokes, strategies of searching for AF after a stroke using ECG monitoring followed by oral anticoagulation (OAC) treatment have been proposed to prevent recurrent cardioembolic strokes. This white paper by experts from the AF-SCREEN International Collaboration summarizes existing evidence and knowledge gaps on searching for AF after a stroke by using ECG monitoring. New AF can be detected by routine plus intensive ECG monitoring in approximately one-quarter of patients with ischemic stroke. It may be causal, a bystander, or neurogenically induced by the stroke. AF after a stroke is a risk factor for thromboembolism and a strong marker for atrial myopathy. After acute ischemic stroke, patients should undergo 72 hours of electrocardiographic monitoring to detect AF. The diagnosis requires an ECG of sufficient quality for confirmation by a health professional with ECG rhythm expertise. AF detection rate is a function of monitoring duration and quality of analysis, AF episode definition, interval from stroke to monitoring commencement, and patient characteristics including old age, certain ECG alterations, and stroke type. Markers of atrial myopathy (eg, imaging, atrial ectopy, natriuretic peptides) may increase AF yield from monitoring and could be used to guide patient selection for more intensive/prolonged poststroke ECG monitoring. Atrial myopathy without detected AF is not currently sufficient to initiate OAC. The concept of embolic stroke of unknown source is not proven to identify patients who have had a stroke benefitting from empiric OAC treatment. However, some embolic stroke of unknown source subgroups (eg, advanced age, atrial enlargement) might benefit more from non–vitamin K-dependent OAC therapy than aspirin. Fulfilling embolic stroke of unknown source criteria is an indication neither for empiric non–vitamin K-dependent OAC treatment nor for withholding prolonged ECG monitoring for AF. Clinically diagnosed AF after a stroke or a transient ischemic attack is associated with significantly increased risk of recurrent stroke or systemic embolism, in particular, with additional stroke risk factors, and requires OAC rather than antiplatelet therapy. The minimum subclinical AF duration required on ECG monitoring poststroke/transient ischemic attack to recommend OAC therapy is debated.

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.

Introduction Lipocalin-2 is an acute-phase protein with pleotropic functions that has been implicated in several diseases including Alzheimer's disease (AD). However, it is unknown if circulating lipocalin-2 levels are altered in the preclinical stage of AD, where AD pathology has accumulated but cognition remains relatively intact. Methods In this cross-sectional study, we used an immunoassay to measure plasma lipocalin-2 levels in cognitively normal (Clinical Dementia Rating 0) elderly individuals. 38 of 156 subjects were classified as preclinical AD by cerebrospinal fluid criteria. Results Plasma lipocalin-2 levels were higher in preclinical AD compared with control subjects and associated with cerebrospinal fluid amyloid-beta42 levels but not cerebrospinal fluid tau or phosphorylated-tau181 levels. Exploratory analyses revealed that plasma lipocalin-2 was associated with executive function but not episodic memory. Discussion Collectively, these results raise the possibility that circulating lipocalin-2 is involved early in AD pathogenesis and may represent an early blood biomarker of amyloid-beta pathology.

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.

Background and Purpose— The clinical utility of positron emission tomography (PET) imaging in evaluating carotid artery plaque vulnerability remains unclear. Two tracers of recent interest for carotid plaque imaging are 18 F-fluorodeoxyglucose ( 18 F-FDG) and 18 F-sodium fluoride ( 18 F-NaF). We performed a systematic review and meta-analysis evaluating the association between carotid artery 18 F-FDG or 18 F-NaF uptake and recent or future cerebral ischemic events. Methods— A systematic review of Ovid MEDLINE, Ovid EMBASE, and the Cochrane library was conducted from inception to December 2017 for articles evaluating PET tracer uptake in recently symptomatic versus asymptomatic carotid arteries, and articles evaluating carotid uptake in relation to future ischemic events. Cerebral ischemic events were defined as ipsilateral strokes, transient ischemic attacks, or amaurosis fugax. We quantitatively pooled studies by a random-effects model when 3 or more studies were amenable for analysis. We assessed the standardized mean difference between tracer uptake in the symptomatic versus asymptomatic carotid artery using Cohen’s d metric. Results— After screening 4144 unique articles, 13 prospective cohort studies assessing carotid artery 18 F-FDG uptake in patients with recent cerebral ischemia were eligible for review. Eleven cohorts of 290 subjects scanned with 18 F-FDG were eligible for meta-analysis. We found that carotid arteries ipsilateral to recent ischemic events had significantly higher 18 F-FDG uptake than asymptomatic arteries (Cohen’s d =0.492; CI=0.130–0.855; P =0.008) as well as significant heterogeneity (Cochran’s Q =31.5; P =0.0005; I 2 =68.3%). Meta-regression was not performed due to the limited number of studies in the analysis. Only 2 studies investigating 18 F-NaF PET imaging, and another 2 articles investigating ischemic event recurrence were found. Conclusions— Recent ipsilateral cerebral ischemia may be associated with increased carotid 18 F-FDG uptake on PET imaging regardless of degree of carotid stenosis, although significant heterogeneity was found, and these results should be interpreted with caution. Emerging evidence suggests a similar association may be present with 18 F-NaF plaque uptake. More studies are warranted to provide definitive conclusions on the utility of 18 F-FDG or 18 F-NaF in carotid plaque evaluation before investigating carotid PET as a diagnostic tool for cerebral ischemic events.

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

The Fifth Neurocritical Care Research Network (NCRN) Conference held in Boca Raton, Florida, in September of 2018 was devoted to challenging the current status quo and examining the role of the Neurocritical Care Society (NCS) in driving the science and research of neurocritical care. The aim of this in-person meeting was to set the agenda for the NCS’s Neurocritical Care Research Central, which is the overall research arm of the society. Prior to the meeting, all 103 participants received educational content (book and seminar) on the ‘Blue Ocean Strategy®,’ a concept from the business world which aims to identify undiscovered and uncontested market space, and to brainstorm innovative ideas and methods with which to address current challenges in neurocritical care research. Three five-member working groups met at least four times by teleconference prior to the in-person meeting to prepare answers to a set of questions using the Blue Ocean Strategy concept as a platform. At the Fifth NCRN Conference, these groups presented to a five-member jury and all attendees for open discussion. The jury then developed a set of recommendations for NCS to consider in order to move neurocritical care research forward. We have summarized the topics discussed at the conference and put forward recommendations for the future direction of the NCRN and neurocritical care research in general.

Background and Purpose— Although believed to be transient and self-limiting, new-onset perioperative/postoperative atrial fibrillation (POAF) might be a risk factor for stroke and mortality. We conducted a systematic review and meta-analysis to qualitatively and quantitatively evaluate the relationship of POAF with early and late risks of mortality and stroke. Methods— We searched Pubmed, EMBASE, and Cochrane Library (1966 through March 2018) to identify cohort studies that reported stroke and mortality associated with POAF. We computed a random-effects estimate based on the Mantel-Haenszel method. Odds ratios with 95% CI were used as a measure of the association between POAF and early (in-hospital or within 30 days of surgery) stroke and mortality, while hazard ratios (HR) were used for long-term outcomes. Results— Our analysis included 35 studies with 2 458 010 patients. Pooling the results from the random-effects model showed that POAF was associated with increased risks of early stroke (odds ratio, 1.62; 95% CI, 1.47–1.80), early mortality (odds ratios, 1.44; 95% CI, 1.11–1.88), long-term stroke (HR, 1.37; 95% CI, 1.07–1.77), and long-term mortality (HR, 1.37; 95% CI, 1.27–1.49). Analyses focusing on high-quality studies obtained similar results. In subgroup analyses, POAF was more strongly associated with stroke in patients undergoing noncardiac surgery (HR, 2.00; 95% CI, 1.70–2.35) than in patients undergoing cardiac surgery (HR, 1.20; 95% CI, 1.07–1.34). Conclusions— New-onset POAF is associated with an increased risk of stroke and mortality, both in the short-term and long-term. The best strategy to reduce stroke risk among these patients needs to be determined.

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.