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Background: Posterior reversible encephalopathy syndrome (PRES) can cause short-term cerebrovascular complications, such as brain infarction and hemorrhage. We hypothesized that PRES is also associated with an increased long-term risk of stroke. Methods: We performed a retrospective cohort study in the United States using statewide all-payer claims data from 2016 to 2018 on all admissions to nonfederal hospitals in 11 states. Adults with PRES were compared with adults with renal colic (negative control) and transient ischemic attack (TIA; positive control). Any stroke and the secondary outcomes of ischemic and hemorrhagic stroke were ascertained using International Classification of Diseases, Tenth Revision, Clinical Modification codes . We excluded prevalent stroke. We used time-to-event statistics to calculate incidence rates and Cox proportional hazards analyses to evaluate the association between PRES and stroke, adjusting for demographics and stroke risk factors. In a sensitivity analysis, outcomes within 2 weeks of index admission were excluded. Results: We identified 1606 patients with PRES, 1192 with renal colic, and 38 216 with TIA. Patients with PRES had a mean age of 56±17 years; 72% were women. Over a median follow-up of 0.9 years, the stroke incidence per 100 person-years was 6.1 (95% CI, 5.0–7.4) after PRES, 1.0 (95% CI, 0.62–1.8) after renal colic, and 9.7 (95% CI, 9.4–10.0) after TIA. After statistical adjustment for patient characteristics and risk factors, patients with PRES had an elevated risk of stroke compared with renal colic (hazard ratio [HR], 2.3 [95% CI, 1.7–3.0]), but lower risk than patients with TIA (HR, 0.67 [95% CI, 0.54–0.82]). In secondary analyses, compared with TIA, PRES was associated with hemorrhagic stroke (HR, 2.0 [95% CI, 1.4–2.9]). PRES was associated with ischemic stroke when compared with renal colic (HR, 1.9 [95% CI, 1.4–2.7]) but not when compared with TIA (HR, 0.49 [95% CI, 0.38–0.63]). Results were similar with 2-week washout. Conclusions: Patients with PRES had an elevated risk of incident stroke.

Patients with cancer and acute ischemic stroke (AIS) face high rates of recurrent thromboembolism or death.To examine whether hematologic and embolic biomarkers soon after AIS are associated with subsequent adverse clinical outcomes.We prospectively enrolled 50 adults with active solid tumor cancer and AIS at two hospitals from 2016 to 2020. Blood was collected 72-120 h after stroke onset. A 30-min transcranial Doppler (TCD) microemboli detection study was performed. The exposure variables were hematologic markers of coagulation (D-dimer, thrombin-antithrombin), platelet (P-selectin), and endothelial activation (thrombomodulin, soluble intercellular adhesion molecule-1 [sICAM-1], soluble vascular cell adhesion molecule-1 [sVCAM-1]), and the presence of TCD microemboli. The primary outcome was a composite of recurrent arterial/venous thromboembolism or death. We used Cox regression to evaluate associations between biomarkers and subsequent outcomes.During an estimated median follow-up time of 48 days (IQR, 18-312), 43 (86%) participants developed recurrent thromboembolism or death, including 28 (56%) with recurrent thromboembolism, of which 13 were recurrent AIS (26%). In unadjusted analysis, D-dimer (HR 1.6; 95% CI 1.2-2.0), P-selectin (HR 1.9; 95% CI 1.4-2.7), sICAM-1 (HR 2.2; 95% CI 1.6-3.1), sVCAM-1 (HR 1.6; 95% CI 1.2-2.1), and microemboli (HR 2.2; 95% CI 1.1-4.5) were associated with the primary outcome, whereas thrombin-antithrombin and thrombomodulin were not. D-dimer was the only marker associated with recurrent AIS (HR 1.2; 95% CI 1.0-1.5). Results were generally consistent in analyses adjusted for important prognostic variables.Markers of hypercoagulability and embolic disease may be associated with adverse clinical outcomes in cancer-related stroke.

Background: Administrative data can be useful for stroke research but have historically lacked data on stroke severity. Hospitals increasingly report the National Institutes of Health Stroke Scale (NIHSS) score using an International Classification of Diseases , Tenth Revision ( ICD-10 ) diagnosis code, but this code’s validity remains unclear. Methods: We examined the concordance of ICD-10 NIHSS scores versus NIHSS scores recorded in CAESAR (Cornell Acute Stroke Academic Registry). We included all patients with acute ischemic stroke from October 1, 2015, when US hospitals transitioned to ICD-10 , through 2018, the latest year in our registry. The NIHSS score (range, 0–42) recorded in our registry served as the reference gold standard. ICD-10 NIHSS scores were derived from hospital discharge diagnosis code R29.7xx, with the latter 2 digits representing the NIHSS score. Multiple logistic regression was used to explore factors associated with availability of ICD-10 NIHSS scores. We used ANOVA to examine the proportion of variation ( R 2 ) in the true (registry) NIHSS score that was explained by the ICD-10 NIHSS score. Results: Among 1357 patients, 395 (29.1%) had an ICD-10 NIHSS score recorded. This proportion increased from 0% in 2015 to 46.5% in 2018. In a logistic regression model, only higher registry NIHSS score (odds ratio per point, 1.05 [95% CI, 1.03–1.07]) and cardioembolic stroke (odds ratio, 1.4 [95% CI, 1.0–2.0]) were associated with availability of the ICD-10 NIHSS score. In an ANOVA model, the ICD-10 NIHSS score explained almost all the variation in the registry NIHSS score ( R 2 =0.88). Fewer than 10% of patients had a large discordance (≥4 points) between their ICD-10 and registry NIHSS scores. Conclusions: When present, ICD-10 codes representing NIHSS scores had excellent agreement with NIHSS scores recorded in our stroke registry. However, ICD-10 NIHSS scores were often missing, especially in less severe strokes, limiting the reliability of these codes for risk adjustment.

Introduction: While well-established risk factors for cervical artery dissection include trauma and connective tissue disorders, many cases are considered “spontaneous.” Although the incidence of cervical artery dissection is greatest in the young, the prevalence increases with age, suggesting a potential role of vascular disease. In this study, we hypothesized that atherosclerosis may be a risk factor for cervical artery dissection. Methods: We performed a retrospective cohort study using administrative claims data from a 5% sample of Medicare beneficiaries between 2008 and 2018. The exposures of interest were vascular risk factors potentially associated with atherosclerosis including coronary artery disease, hyperlipidemia, hypertension, diabetes mellitus, heart failure, chronic kidney disease, chronic obstructive pulmonary disease, valvular heart disease, atrial fibrillation, tobacco use, and alcohol abuse. The primary outcome was a new diagnosis of cervical artery dissection. Marginal structural Cox models were used to characterize the association between the exposures and outcomes, adjusted for time-dependent confounding, age, sex, race/ethnicity, and prior stroke. Results: Among 2,256,826 eligible Medicare beneficiaries, 1,527 (0.07%) developed cervical artery dissection, with a mean age of 70.8, compared to 71.5 in those without cervical artery dissection. The following exposures were found to be significantly associated with the development of cervical artery dissection: coronary artery disease (1.81 [1.63-2.01]), hyperlipidemia (1.84 [1.61-2.11]), hypertension (2.04 [1.76-2.37]), diabetes mellitus (1.34 [1.21-1.49]), heart failure (1.44 [1.25-1.67]), chronic kidney disease (1.38 [1.20-1.59]), chronic obstructive pulmonary disease (1.3 [1.16-1.46]), valvular heart disease (1.81 [1.60-2.04]), atrial fibrillation (HR 1.75 [95% CI 1.54-1.98]), tobacco use (1.84 [1.57-2.15]), and alcohol abuse (1.84 [1.56-2.16]). Conclusion: In a large population-based cohort of older people, atherosclerotic risk factors were associated with subsequent cervical artery dissection. Further studies exploring the role of atherosclerosis in the development of cervical artery dissection are required.

Background: An estimated 40% of Americans will develop cancer in their lifetime, and most will require one or multiple surgeries for diagnosis and treatment. We sought to determine whether cancer is an independent risk factor for perioperative arterial ischemic events. Methods: We performed a retrospective cohort study of patients who had major inpatient or outpatient surgery registered in the National Surgical Quality Improvement Program (NSQIP) between 2006-2016. The study exposure was disseminated cancer. The study outcome was a perioperative arterial ischemic event, defined as an ischemic stroke or myocardial infarction within 30 days of surgery. Multivariable Cox regression was used to evaluate the association between the study exposure and outcome while adjusting for potential confounders. Various sensitivity analyses were conducted. Results: Among 5,609,675 NSQIP cases, 122,221 (2.2%) surgeries involved patients with disseminated cancer. Patients’ mean age was 56 years (SD, 17); 57% were women. The Kaplan-Meier 30-day perioperative arterial ischemic event rate was 0.96% (95% CI, 0.91-1.02%) among patients with disseminated cancer vs 0.48% (95% CI, 0.47-0.49%) among patients without disseminated cancer (HR, 2.0; 95% CI, 1.9-2.1) (Figure). In Cox regression analyses adjusting for demographics, functional status, comorbidities, surgical setting, anesthesia type, and relevant clinical factors, disseminated cancer remained associated with a perioperative arterial ischemic event (HR, 1.3; 95% CI, 1.2-1.4). This association persisted across analyses excluding neurosurgical and cardiac surgeries, restricting to elective surgeries, and restricting to patients with functional independence before surgery. Conclusions: In a large, nationwide, surgical registry, comorbid cancer was associated with an estimated 20-40% increased risk of perioperative arterial ischemic events.

Introduction: Cirrhosis is associated with an increased risk of hemorrhagic stroke (HS). Liver fibrosis, typically a silent condition, is antecedent to cirrhosis. We hypothesized that liver fibrosis is associated with an increased risk of HS. Further, because apolipoprotein E2 (ApoE2) and E4 (ApoE4) are associated with HS, and because liver-derived peripheral ApoE4 may disrupt endothelial integrity, we evaluated for effect modification by these isoforms. Methods: We performed a cohort analysis using the UK Biobank Study, which prospectively enrolled adults in 2007, with continuous follow-up. We excluded participants with prevalent HS or thrombocytopenia. Liver fibrosis was defined using the validated Fibrosis-4 score. The primary outcome, incident HS (intracerebral or subarachnoid hemorrhage), was captured in UK Biobank based on hospitalization and death registry data. We used Cox proportional hazards models to evaluate the association of liver fibrosis with HS while adjusting for HS risk factors (demographics, systolic blood pressure, hemoglobin A1c, total cholesterol, BMI, tobacco and alcohol use, antithrombotic use). Effect modification by ApoE2 and ApoE4 were evaluated using interaction terms and stratified analyses. Results: Among 453,251 included participants, the mean age was 57 years and 54% were women. Approximately 2% had liver fibrosis, 16% used antithrombotic agents, 29% were ApoE4 carriers, and 15% were ApoE2 carriers. In adjusted Cox models, liver fibrosis was associated with an increased risk of HS (HR, 2.17; 95% CI, 1.51-3.12) (Figure). This relationship appeared stronger in ApoE4 homozygotes (HR, 8.27; 95% CI, 2.30-29.73) than in others (HR, 2.18; 95% CI, 1.47-3.24) (P=0.05, interaction). ApoE4 carrier status, ApoE2 carrier status, and ApoE2 homozygosity did not modify this relationship (P>0.20, interactions). Conclusions: Liver fibrosis was associated with an increased risk of HS, possibly more so in ApoE4 homozygous persons.

Background: Intracerebral hemorrhage (ICH) is associated with an increased risk of ischemic stroke. Whether there are racial and ethnic disparities in the risk of ischemic stroke after ICH is poorly understood. Hypothesis: Non-Hispanic Black and Hispanic ICH patients have a higher risk of ischemic stroke compared to White ICH patients. Methods: We retrospectively analyzed data from the Healthcare Cost and Utilization Project on all hospitalizations at all nonfederal hospitals in Florida from 2005 to 2018 and New York from 2006 to 2016. We included patients with an ICH, and without a prior or concomitant diagnosis of ischemic stroke. ICH and ischemic stroke were ascertained using validated ICD-9-CM and ICD-10-CM codes. Using Cox proportional hazard models, we studied the relationship between race and risk of ischemic stroke, after adjustment of demographics and comorbidities. Results: We included 55,582 patients with ICH- 66% Non-Hispanic White, 19% Non-Hispanic Black, and 13% Hispanic. Black and Hispanic patients were younger and had a higher prevalence of cardiovascular comorbidities; however, atrial fibrillation was more prevalent among White patients. During a median follow up period of 3.6 years (IQR 0.7-7.2), an incident ischemic stroke occurred in 3,361 (9%) Non-Hispanic White, 1,308 (12%) Non-Hispanic Black, and 858 (12%) Hispanic patients (p Conclusions: Among patients with ICH, Non-Hispanic Black and Hispanic patients had a significantly higher risk of ischemic stroke compared to Non-Hispanic White patients.

Introduction: Syndromes of cerebrovascular dysregulation such as posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS) can be challenging to diagnose given their rarity and the need for advanced neuroimaging to diagnose them. We sought to measure the rate of potential PRES/RCVS misdiagnosis in the ED and identify features associated with misdiagnosis. Methods: We conducted a retrospective cohort study of patients with PRES/RCVS using deidentified administrative claims data from all nonfederal EDs and hospitals across 11 states from 2016-2018. To identify patients with PRES/RCVS, we used the previously validated ICD-10-CM codes I67.841 and I67.83. We defined patients with a probable misdiagnosis of PRES/RCVS as those with an ED visit resulting in discharge to home that occurred within the 14 days prior to their PRES/RCVS hospitalization. Only preceding ED visits where a non-specific neurological condition (e.g., headache, dizziness, numbness) was diagnosed were considered instances of probable ED misdiagnosis. Standard tests of comparison between patients with versus without probable misdiagnosis were used to identify patient-level and ED facility-level features associated with misdiagnosis. Results: We identified 4,633 patients hospitalized for PRES/RCVS; the majority (4,169; 90.0%) had PRES. A total of 210 patients (4.5%, 95% CI: 3.95-5.17) had at least one preceding ED visit with a probable misdiagnosis; these patients were younger (mean age 47.7 vs. 53.8 years; P Conclusion: Probable ED misdiagnosis occurred in nearly 1 of 20 cases of PRES/RCVS in a large, multistate cohort.

Introduction: We analyzed data regarding smoking cessation medication use after stroke/TIA in the United States. Methods: We performed a retrospective analysis using data from the Get With The Guidelines®-Stroke registry, which includes data for adult patients receiving acute care for stroke and TIA across the United States. Our outcome of interest was provision of cessation medication (nicotine replacement therapy [NRT], bupropion, varenicline) among patients who were active smokers at the time of stroke/TIA. We used unadjusted and multivariable regression models to explore factors associated with provision of cessation medications. We specifically evaluated whether event type (TIA and hemorrhagic stroke versus ischemic stroke) and burden of smoking-related cardiovascular conditions (≥1 versus 0) were associated with cessation medication provision. Results: Of 1,589,760 patients with stroke/TIA, 187,501 were smokers with available smoking treatment data. The mean age was 59.9 years (SD, 11.6); 42% were women. Most patients (97.7%) received some form of cessation intervention. As for specific treatments, 29.8% were provided cessation medication (NRT: 16.2%; varenicline or bupropion: 13.0%; multiple/other: 2.3%). The remaining 68.5% received counseling alone. In multivariable models, patients with hemorrhagic stroke (OR, 0.81; 95% CI, 0.76-0.86) and TIA (OR, 0.68; 95% CI, 0.64-0.73) had lower odds of receiving cessation medications than ischemic stroke patients. Cardiovascular disease burden was not associated with cessation medication provision (OR, 0.98; 95 CI, 0.94-1.02). However, multivariable models revealed demographic differences. Black (OR, 0.78; 95% CI, 0.74-0.82) and Asian (OR, 0.72; 95% CI, 0.58-0.87) patients had lower odds of receiving cessation medication, compared to White patients. Hispanic ethnicity was also associated with lower odds of cessation medication provision (OR, 0.65; 95% CI, 0.56-0.73). Conclusions: Approximately 30% of smokers were provided a smoking cessation medication during hospitalization. Compared to ischemic stroke, TIA and hemorrhagic stroke were associated with lower rates of smoking cessation medication provision, and racial and ethnic disparities were identified.

Secondary central nervous system lymphoma (SCNSL) is associated with poor prognosis and new therapeutic approaches are needed. The pivotal trial that led to US Food and Drug Administration (FDA) approval of axicabtagene ciloleucel excluded patients with SCNSL and human immunodeficiency virus. In this multi-institutional retrospective study, 14 SCNSL patients treated with axicabtagene ciloleucel, 3 of whom had human immunodeficiency virus, experienced rates of severe neurotoxicity and complete response of 32% and 58%, respectively. This is similar to rates observed in the pivotal ZUMA-1 trial that led to the approval of axi-cel at median follow-up of 5.9 months. Chimeric antigen receptor T-cell therapy is potentially a life-saving therapy for SCNSL patients and should not be withheld.

Background: Plasminogen activator inhibitor-1 (PAI-1), an inhibitor of fibrinolysis that is associated with adiposity, has been implicated in Alzheimer’s disease (AD) pathogenesis. However, whether circulating PAI-1 levels are altered during preclinical AD remains unclear. Objective: To measure plasma PAI-1 levels in cognitively normal cerebrospinal fluid (CSF) AD biomarker positive and biomarker negative participants and to examine the association of plasma PAI-1 levels with CSF AD biomarkers and Mini-Mental State Examination (MMSE) scores. Methods: In this cross-sectional study, plasma PAI-1 levels were measured in 155 cognitively normal (Clinical Dementia Rating, CDR 0) non-obese older adults. 29 men and 26 women were classified as preclinical AD by previously established CSF tau/Aβ42 criteria. All analyses were sex stratified due to reported sex differences in PAI-1 expression. Results: Plasma PAI-1 levels were associated with body mass index (BMI) but not age in men and women. In men, plasma PAI-1 levels and BMI were lower in preclinical AD compared to control. Plasma PAI-1 levels were positively associated with CSF amyloid-β42 (Aβ42) and CSF Aβ42/Aβ40 and negatively associated with CSF tau/Aβ42, while BMI was positively associated with CSF Aβ42 and negatively associated with CSF p-tau181 and CSF tau/Aβ42. In women, plasma PAI-1 levels and BMI were similar between preclinical AD and control and were not associated with CSF AD biomarkers. For men and women, plasma PAI-1 levels and BMI were not associated with MMSE scores. Conclusion: These findings suggest that there are significant sex differences in the systemic metabolic changes seen in the preclinical stage of AD.

This study uses data from the National Hospital Ambulatory Medical Care Survey to analyze adults with a neurological complaint as their reason for an emergency department visit.

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

We hypothesized that liver fibrosis is associated with worse cognitive performance and corresponding brain imaging changes.We examined the association of liver fibrosis with cognition and brain imaging parameters in the UK Biobank study. Liver fibrosis was assessed using the Fibrosis-4 (FIB-4) score. The primary cognitive outcome was the digit symbol substitution test (DSST); secondary outcomes were additional executive function/processing speed and memory tests. Imaging outcomes were hippocampal, total brain, and white matter hyperintensity (WMH) volumes.We included 105,313 participants with cognitive test data, and 41,982 with magnetic resonance imaging (MRI). In adjusted models, liver fibrosis was associated with worse performance on the DSST and tests of executive function but not memory. Liver fibrosis was associated with lower hippocampal and total brain volumes, without compelling association with WMH volume.Liver fibrosis is associated with worse performance on select cognitive tests and lower hippocampal and total brain volumes.It is increasingly recognized that chronic liver conditions impact brain health. We performed an analysis of data from the UK Biobank prospective cohort study. Liver fibrosis was associated with worse performance on executive function tests. Liver fibrosis was not associated with memory impairment. Liver fibrosis was associated with lower hippocampal and total brain volumes.

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.

Background and Purpose: With the surge of critically ill COVID-19 patients, neurology and neurosurgery residents and advanced practice providers (APPs) were deployed to intensive care units (ICU). These providers lacked relevant critical care training. We investigated whether a focused video-based learning curriculum could effectively teach high priority intensive care topics in this unprecedented setting to these neurology providers. Methods: Neurocritical care clinicians led a multidisciplinary team in developing a 2.5-hour lecture series covering the critical care management of COVID-19 patients. We examined whether provider confidence, stress, and knowledge base improved after viewing the lectures. Results: A total of 88 residents and APPs participated across 2 academic institutions. 64 participants (73%) had not spent time as an ICU provider. After viewing the lecture series, the proportion of providers who felt moderately, quite, or extremely confident increased from 11% to 72% (60% difference, 95% CI 49-72%) and the proportion of providers who felt nervous/stressed, very nervous/stressed, or extremely nervous/stressed decreased from 78% to 48% (38% difference, 95% CI 26-49%). Scores on knowledge base questions increased an average of 2.5 out of 12 points (SD 2.1; p < 0.001). Conclusion: A targeted, asynchronous curriculum on critical care COVID-19 management led to significantly increased confidence, decreased stress, and improved knowledge among resident trainees and APPs. This curriculum could serve as an effective didactic resource for neurology providers preparing for the COVID-19 ICU.

BackgroundThere is growing recognition of the role of chronic liver disease in brain health, but the impact of liver fibrosis on dementia risk was unclear. We evaluated the association between liver fibrosis and incident dementia using data from a large prospective cohort study.MethodsWe performed a cohort analysis using data from the UK Biobank study, which prospectively enrolled approximately 500,000 adults starting 2007 and continues to follow them. Liver fibrosis was defined using validated cutoffs of the Fibrosis-4 (FIB-4) liver fibrosis score. The primary outcome was incident dementia, ascertained using a validated approach based on participants’ hospital record and mortality data. Secondary outcomes were Alzheimer’s disease and vascular dementia. We excluded participants with prevalent dementia. We used Cox proportional hazards models to evaluate the association between liver fibrosis and incident dementia while adjusting for potential confounders. In additional models, the FIB-4 score was used as a continuous independent variable. Prespecified interaction analyses tested for effect modification by sex, metabolic syndrome, and apolipoprotein E4 carrier status.ResultsAmong 455,226 participants included in this analysis, the mean age was 56.5 years and 54% were women. Standard liver chemistries were largely in the normal range. However, 2.17% (95% CI, 2.13-2.22%) had liver fibrosis based on their FIB-4 score. The rate of dementia per 1,000 person-years was 1.76 (95% CI, 1.50-2.07) in participants with liver fibrosis and 0.52 (95% CI, 0.50-0.54) in those without. After adjusting for demographics, socioeconomic deprivation, educational attainment, metabolic syndrome, hypertension, diabetes, dyslipidemia, and tobacco and alcohol use, liver fibrosis was associated with an increased risk of dementia (HR, 1.52; 95% CI, 1.22-1.90). An independent association was also noted between FIB-4, treated as a continuous variable, and dementia (HR per unit, 1.29; 95% CI, 1.20-1.39). Effect modification by sex, metabolic syndrome, and apolipoprotein E4 carrier status was not seen.ConclusionLiver fibrosis in middle age was associated with an increased risk of incident dementia, independent of metabolic syndrome and shared risk factors. Liver fibrosis may be an underrecognized risk factor for dementia.

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.

To derive models that identify patients with COVID-19 at high risk for stroke.We used data from the AHA's Get With The Guidelines® COVID-19 Cardiovascular Disease Registry to generate models for predicting stroke risk among adults hospitalized with COVID-19 at 122 centers from March 2020-March 2021. To build our models, we used data on demographics, comorbidities, medications, and vital sign and laboratory values at admission. The outcome was a cerebrovascular event (stroke, TIA, or cerebral vein thrombosis). First, we used Cox regression with cross validation techniques to identify factors associated with the outcome in both univariable and multivariable analyses. Then, we assigned points for each variable based on corresponding coefficients to create a prediction score. Second, we used machine learning techniques to create risk estimators using all available covariates.Among 21,420 patients hospitalized with COVID-19, 312 (1.5%) had a cerebrovascular event. Using traditional Cox regression, we created/validated a COVID-19 stroke risk score with a C-statistic of 0.66 (95% CI, 0.60-0.72). The CANDLE score assigns 1 point each for prior cerebrovascular disease, afebrile temperature, no prior pulmonary disease, history of hypertension, leukocytosis, and elevated systolic blood pressure. CANDLE stratified risk of an acute cerebrovascular event according to low- (0-1: 0.2% risk), medium- (2-3: 1.1% risk), and high-risk (4-6: 2.1-3.0% risk) groups. Machine learning estimators had similar discriminatory performance as CANDLE: C-statistics, 0.63-0.69.We developed a practical clinical score, with similar performance to machine learning estimators, to help stratify stroke risk among patients hospitalized with COVID-19.

Introduction: When a stroke hospitalization follows soon after an Emergency Department (ED) treat-and-release visit for non-specific neurological complaints, a diagnostic error may have occurred. In this study, we sought to evaluate potential stroke misdiagnoses after ED treat-and-release headache visits. Methods: We conducted a retrospective cohort study using state-wide administrative claims data for all ED visits and admissions at nonfederal hospitals in Florida 2005-2018 and New York 2005-2016. Using standard ICD codes, we identified adult patients discharged home from the ED with a benign headache diagnosis (cohort of interest) as well as those with a diagnosis of back pain or renal colic (negative control cohorts). The primary study outcome was hospitalization within 30 days for stroke (ischemic or hemorrhagic), defined using validated ICD codes. We used Cox proportional hazards modeling to assess the relationship between the index ED visit reason and stroke hospitalization adjusting for demographics and vascular risk factors. Results: We identified 1,458,904 patients with an ED treat-and-release headache visit; mean age was 41 (SD: 17) and 70% were female. A total of 2,636 (0.18%) headache patients were hospitalized for stroke within 30 days. Stroke risk was higher among headache patients compared to patients diagnosed with renal colic (HR: 2.7; 95% CI, 2.3-3.1) or back pain (HR: 3.8; 95% CI, 3.6-4.1; Figure). Among patients Conclusion: Approximately 1 in 500 patients discharged home from the ED with a headache diagnosis had a stroke in the following month. Stroke risk was 3-4 times higher after an ED visit for headache compared to back pain or renal colic. There may be opportunities to reduce diagnostic error among patients with ED visits for headache, particularly for those

Introduction: Smoking cessation is an integral part of secondary prevention after stroke and TIA. Relapse after successful smoking cessation in this population is poorly understood. Methods: This is a retrospective cohort analysis of patients enrolled in the international Insulin Resistance Intervention After Stroke (IRIS) trial, which included 3,876 nondiabetic patients with ischemic stroke or TIA. In IRIS, patients were asked about smoking status at the time of the index event, at randomization, and annually thereafter for 5 years. For this analysis, we included patients who quit smoking by randomization. Patients with active smoking at any follow-up visit were categorized as relapsed. We used time-to-event analysis to estimate cumulative relapse rates. We used univariate Cox proportional hazards regression to assess possible predictors of relapse: demographics, index event type (stroke vs TIA), country of origin, cardiovascular comorbidities, and duration/intensity of smoking. Results: At the time of stroke/TIA, 1,072 patients were active smokers. By randomization, a median of 3 (IQR, 2-5) months later, 450 (42%) had quit smoking. The mean age of the 450 quitters was 58 years, and 35% were women. They had smoked a median of 20 (IQR, 10-25) cigarettes/day for a median of 40 (IQR, 34-46) years. Over a mean follow-up of 3.8 years, 156 patients relapsed. The 5-year cumulative relapse rate was 38% (95% CI, 34-43%), with 21% (95% CI, 18-25%) relapsing within 1 year (Figure). Age, sex, index event type, duration and intensity of smoking were not associated with relapse. However, patients at US sites (vs non-US sites) were more likely to relapse (HR, 1.46; 95% CI, 1.01-2.10), as were patients with more cardiovascular comorbidities (HR, 1.28; 95% CI, 1.05-1.55; for each additional condition). Conclusion: Stroke/TIA survivors with early smoking cessation have a high rate of relapse, highlighting a need to engage this at-risk population in sustained cessation interventions.

Introduction: We previously showed that patients with cancer and acute ischemic stroke (AIS) have higher markers of coagulation, platelet, and endothelial activation, and more circulating microemboli than patients with AIS and no cancer. Herein, we evaluate whether these markers are associated with clinical outcomes in patients with cancer and AIS. Methods: In the MOST-Cancer prospective study, we enrolled 50 adults with active solid-tumor cancer and AIS at 2 New York hospitals from 2016-2020. We collected blood from participants 72-120 hours after stroke onset. We performed a 30-minute transcranial Doppler (TCD) microemboli detection study a median of 4 days after stroke onset. The exposure variables were hematological markers of coagulation (D-dimer, thrombin-antithrombin), platelet (P-selectin), and endothelial activation (thrombomodulin, soluble intercellular adhesion molecule-1 [sICAM-1], soluble vascular cell adhesion molecule-1 [sVCAM-1]), and the presence of microemboli on TCD. The primary outcome was a composite of recurrent arterial or venous thromboembolism or death. The secondary outcome was recurrent AIS. We used Cox regression to evaluate individual associations between biomarkers and subsequent outcomes. Results: Median age was 69 years (IQR, 60-76) and 24 participants (48%) were women. The most common cancers were lung (28%) and pancreatic (22%); 86% of participants had distant metastases. During a mean follow-up of 278 days (SD, 367), 43 (86%) participants had the primary outcome of recurrent thromboembolism or death, including 28 (56%) who had recurrent thromboembolism, 13 who had recurrent AIS (26%), and 30 (60%) who died. D-dimer, P-selectin, sICAM-1, sVCAM-1, and microemboli were associated with the composite outcome (Table). Similar results were seen for recurrent AIS. Conclusion: Markers of hypercoagulability and embolic disease were associated with adverse clinical outcomes in cancer-related stroke.

Introduction: Posterior reversible encephalopathy syndrome (PRES) can cause brain infarction and hemorrhage in the acute phase. We hypothesized that PRES is also associated with an increased long-term risk of stroke. Methods: We performed a retrospective cohort study using statewide all-payer claims data from 2016-2018 for all admissions to nonfederal hospitals in 11 states. Adult patients with PRES were compared to patients with TIA (positive control) and renal colic (negative control), as done in prior studies. The primary outcome was any stroke, and secondary outcomes were ischemic and hemorrhagic stroke. Diagnoses were ascertained using ICD-10-CM codes. We excluded patients with stroke before and during index admissions for PRES and controls. We used Cox proportional hazards analyses to evaluate associations between PRES and stroke, adjusting for demographics, stroke risk factors, and factors associated with PRES (cancer, kidney disease, rheumatological disease). In a sensitivity analysis, stroke events within 4 weeks of index admissions were excluded. Results: We identified 3,086 patients with PRES, 85,189 with TIA, and 3,094 with renal colic. Patients with PRES (55±17 years) and renal colic (54±18 years) were younger than those with TIA (72±14 years). Median follow-up was 1.1 years and similar between groups. Stroke incidence was 3.2 per 100 person-years after PRES, 3.8 per 100 person-years after TIA, and 0.4 per 100 person-years after renal colic (Figure). After adjustment, patients with PRES had a similar stroke risk as patients with TIA (HR, 0.9; 95% CI, 0.8-1.2), and a higher stroke risk than patients with renal colic (HR, 2.6; 95% CI, 2.0-3.5). Compared to TIA, PRES had a higher risk of hemorrhagic stroke (HR, 2.9; 95% CI, 2.2-3.9) and a lower risk of ischemic stroke (HR, 0.7; 95% CI, 0.6-0.9). Results were similar with a 4-week washout period. Conclusions: PRES is associated with an increased risk of future stroke, specifically hemorrhagic stroke.

Introduction: Coronavirus Disease 2019 (COVID-19) is associated with an increased risk of stroke and worse stroke outcomes. A clinical score that can identify high-risk patients could enable closer monitoring and targeted preventative strategies. Methods: We used data from the AHA’s COVID-19 CVD Registry to create a clinical score to predict the risk of stroke among patients hospitalized with COVID-19. We included patients aged >18 years who were hospitalized with COVID-19 at 122 centers from March 2020-March 2021. To build our score, we used demographics, preexisting comorbidities, home medications, and vital sign and lab values at admission. The outcome was a cerebrovascular event, defined as any ischemic or hemorrhagic stroke, TIA, or cerebral vein thrombosis. We used two separate analytical approaches to build the score. First, we used Cox regression with cross validation techniques to identify factors associated with the outcome in both univariable (p Results: Among 21,420 patients hospitalized with COVID-19 (mean age 61 years, 54% men), 312 (1.5%) had a cerebrovascular event. Using traditional Cox regression, we created and internally validated a risk stratification score (CANDLE) (Fig) with a C-statistic of 0.66 (95% CI, 0.60-0.72). The machine learning estimator had similar discriminatory performance, with a C-statistic of 0.69 (95% CI, 0.65-0.72). For ischemic stroke or TIA, CANDLE’s C-statistic was 0.67 (95% 0.59-0.76). Conclusion: We developed an easy-to-use clinical score, with similar performance to a machine learning estimator, to help stratify stroke risk among patients hospitalized with COVID-19.

Introduction: Isolated amyloid deposition in the brain is associated with intracranial hemorrhage. Whether systemic amyloidosis also increases the risk of intracranial hemorrhage is unclear. Methods: We evaluated the association between systemic amyloidosis and intracranial hemorrhage using claims data from a 5% national sample of Medicare beneficiaries from 2008-2015. The primary outcome was non-traumatic intracranial hemorrhage, defined as a composite of intracerebral hemorrhage, subarachnoid hemorrhage, and subdural hemorrhage. Secondary outcome were each hemorrhage type assessed separately. The exposure and outcomes were identified using previously validated ICD-9-CM diagnosis codes. We used Cox regression analysis adjusting for demographics and vascular risk factors to evaluate the association between systemic amyloidosis and intracranial hemorrhage. We also examined the risk of hip fracture (negative control). In sensitivity analyses, we excluded patients with cardiac amyloidosis, a subset most likely to be on antithrombotic therapy. Results: Among 1.8 million Medicare beneficiaries, 924 were diagnosed with systemic amyloidosis. During a median follow-up of 5.3 years (IQR, 2.8- 6.7), the cumulative incidence of intracranial hemorrhage was 19 per 1,000 patients per year among patients with amyloidosis, and 2 per 1,000 patients per year in those without amyloidosis. In adjusted Cox models, systemic amyloidosis was associated with an increased risk of intracranial hemorrhage (HR, 4.3; 95% CI, 2.9-6.3). The association persisted in a sensitivity analysis after excluding beneficiaries with cardiac amyloidosis (HR, 8.0; 95% CI, 5.0-12.7). In secondary analyses, systemic amyloidosis was associated with intracerebral hemorrhage (HR, 5.6; 95% CI, 3.6-8.7), subarachnoid hemorrhage (HR, 14.7; 95% 9.0-24.0), and subdural hemorrhage (HR, 3.6; 95% 2.0-6.2). There was no association between systemic amyloidosis and hip fracture (HR, 0.9; 95% CI, 0.6-1.4). Conclusions: In a large, heterogeneous national cohort of elderly patients, a diagnosis of systemic amyloidosis was associated with a 4-fold increased risk of intracranial hemorrhage, including intracerebral, subarachnoid, and subdural hemorrhages.

Background: The postpartum state is associated with a heightened risk of thrombosis. The duration of heightened risk for postpartum cerebral venous thrombosis (CVT) is uncertain. Methods: Using claims data from the Healthcare Cost and Utilization Project (HCUP) from all emergency departments and acute care hospitalizations in Florida from 2005-2015 and New York from 2006-2015, we identified women aged ≥18 years old who were hospitalized for labor and delivery. CVT was ascertained using previously validated International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), diagnosis codes. For women with multiple labor-related hospitalizations during a single 40-week period, we excluded cases of false labor by identifying delivery as the latest hospitalization during that time. Patients with claims for CVT before their first recorded delivery, and women with a second delivery during the follow-up period were also excluded. We compared the likelihood of a first-ever recorded CVT during postpartum days 0-41 compared with the same period 1 year later. We repeated this crossover-cohort analysis for consecutive 6-weeks periods after delivery, as compared with the corresponding 6-week period 1 year later. We used McNemar's to calculate odds ratios for each 6-week interval. Results: Among the 1,406,447 women with a first recorded delivery, the risk of CVT was markedly higher within the 6 weeks after delivery than in the same period 1 year later (22 versus 3 CVTs per million deliveries). This corresponded to an absolute risk difference of 19 events per million (95% confidence interval [CI], 11-27) and an odds ratio of 10.0 (95% CI, 3.1-51.2). There was no significant increase in the risk of CVT during the period of 7 to 12 weeks after delivery as compared with the same period 1 year later with an absolute risk difference of 6.0 events (95% CI, 0-11) per million deliveries and an odds ratio of 3.0 (95% CI, 0.9-12.8). Conclusion: There appears to be a heightened risk of CVT for 6 weeks after delivery.

BACKGROUND AND PURPOSE: We examined the association of chronic liver disease with cognition and brain imaging markers of cognitive impairment using data from two large randomized controlled trials that included participants based on diabetes and hypertension, two common systemic risk factors for cognitive impairment and dementia. METHODS: We performed post hoc analyses using data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) and Systolic Blood Pressure Intervention Trial (SPRINT) studies, which included participants with diabetes and hypertension, respectively. Data were from the NHLBI Biologic Specimen and Data Repository Information Coordinating Center. In ACCORD, our measure of chronic liver disease was the Dallas Steatosis Index (DSI). In SPRINT, we used self-reported chronic liver disease. We used linear regression to evaluate the association between the measure of chronic liver disease and both baseline and longitudinal cognitive test performance and brain magnetic resonance imaging volume measurements. RESULTS: Among 2,969 diabetic participants in ACCORD, the mean age of participants was 62 years, 47% were women. The median DSI was 1.0 (IQR, 0.2–1.8); a DSI of 1.0 corresponds to approximately a >70% probability of having NAFLD. Among 2,890 hypertensive participants in SPRINT, the mean age was 68 years, and 37% were women, and 60 (2.1%) had chronic liver disease. There were no consistent associations between liver disease and cognitive performance or brain volumes at baseline or longitudinally after adjustment. CONCLUSION: Markers of chronic liver disease were not associated with cognitive impairment or related brain imaging markers among individuals with diabetes and hypertension.

ObjectiveTransesophageal echocardiography (TEE) is sometimes used to search for cardioembolic sources after ischemic stroke or transient ischemic attack (TIA). TEE visualizes some sources better than transthoracic echocardiography, but TEE is invasive and may cause aspiration. Few data exist on the risk of respiratory complications after TEE in patients who had stroke or TIA. Our objective was to determine whether TEE was associated with increased risk of respiratory failure in patients who had ischemic stroke or TIA.DesignThis is a retrospective cohort study using administrative data from inpatient and outpatient insurance claims collected by the US federal government’s Centers for Medicare and Medicaid Services.SettingHospitals and outpatient clinics throughout the USA.Participants99 081 patients ≥65 years old hospitalized for out-of-hospital ischemic stroke or TIA, defined by validated International Classification of Disease-9/10 diagnosis codes and present-on-admission codes, using claims data from 2008 to 2018 in a random 5% sample of Medicare beneficiaries.Main outcome measuresAcute respiratory failure, defined as endotracheal intubation and/or mechanical ventilation, starting on the first day after admission through 28 days afterward.ResultsOf 99 081 patients included in this analysis, 73 733 (74.4%) had an ischemic stroke and 25 348 (25.6%) a TIA. TEE was performed in 4677 (4.7%) patients and intubation and/or mechanical ventilation in 1403 (1.4%) patients. The 28-day cumulative risk of respiratory failure after TEE (1.4%; 95% CI 0.8% to 2.7%) was similar to that seen in those without TEE (1.4%; 95% CI 1.4% to 1.5%) (p=0.84). After adjustment for age, sex, race, Charlson comorbidities, diagnosis of stroke versus TIA, intravenous thrombolysis, and mechanical thrombectomy, TEE was not associated with an increased risk of respiratory failure (HR, 0.9; 95% CI 0.6 to 1.2).ConclusionsIn a cohort of older patients who had ischemic stroke or TIA, TEE was not associated with an increased risk of subsequent respiratory failure.

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.

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.

Background and ObjectivesTo study the relationship between the presence of cerebral microbleeds (CMBs) and acute hematoma characteristics among patients with primary intracerebral hemorrhage (ICH).MethodsWe pooled individual patient data from the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 (ATACH-2) trial and the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation phase 3 (MISTIE III) trial. We included individuals with a brain MRI scan. Exposure was the presence of a CMB. The coprimary outcomes were admission ICH volume and hematoma expansion. Mixed-effects linear and logistic regression models were used, with demographics and comorbid conditions considered fixed effects and the study cohort treated as a random effect. Additional analyses assessed the relationship between CMB topography and number and hematoma characteristics.ResultsOf the 1,499 patients with ICH enrolled in the parent trials, 466 (31.1%) were included in this analysis, and 231 (49.6%) patients had CMBs. In adjusted models, presence of CMBs was associated with smaller ICH volume (β = −0.26, 95% confidence interval [CI] −0.44 to −0.08) and lower odds of hematoma expansion (odds ratio 0.65, 95% CI 0.40–0.95; p = 0.04). The strength of association between CMBs and hematoma characteristics increased with increasing number of CMBs. The location of the CMBs and the severity of leukoaraiosis did not modify these results.DiscussionIn a pooled cohort of patients with ICH, our results are consistent with the hypothesis that more severe underlying small vessel disease, as represented by CMBs, leads to smaller baseline hematoma volumes and reduced hematoma expansion. Underlying cerebral small vessel disease may be of prognostic significance after ICH.Trial Registration InformationClinicalTrials.gov Identifier: NCT01176565 and NCT01827046.Classification of EvidenceThis study provides Class II evidence that the presence of microbleeds on MRI is associated with a smaller ICH volume at presentation and a lower rate of hematoma expansion on follow-up imaging.