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BACKGROUND: Nimodipine improves outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, the impact of alternative dosing strategies on outcome remains unclear. METHODS: We performed a retrospective cohort study of consecutive patients admitted with aSAH to an academic referral center from 2016 to 2019. Patients with a confirmed aneurysm cause who received nimodipine were included; patients who died or had withdrawal of life-sustaining treatment within 24 hours of admission were excluded. Univariable and multivariable modified Poisson regression models were used to identify predictors of using modified nimodipine dosing (30 mg every 2 hours) versus standard dosing (60 mg every 4 hours). Inverse probability weighted and modified Poisson regression models were used to estimate adjusted risk ratios (RRs) for outcome measures, with poor outcome defined as modified Rankin Scale score 4–6 at 3 months. RESULTS: We identified 175 patients with aSAH who met eligibility criteria (mean [SD] age = 57 [13.2] years, 62% female, 73% White); 49% (n = 86) received modified nimodipine dosing. A modified dose was used more frequently in women (RR 2.08, 95% confidence interval [CI] 1.11–3.89, P = 0.02), patients with vasospasm (RR 3.47, 95% CI 1.84–6.51, P < 0.001), and patients who required vasopressors (RR 1.73, 95% CI 1.3–2.32, P < 0.001). Modified dosing was not associated with poor functional outcome (inverse probability weighted RR 1.1, 95% CI 0.8–1.4, P = 0.65). CONCLUSIONS: Modified dosing of nimodipine is well tolerated and may not be associated with worse functional outcome. Prospective studies are needed to better assess the relationship between nimodipine dosing and outcomes in patients with aSAH.

Background and ObjectivesAndexanet alfa was recently approved as a reversal agent for the factor Xa inhibitors (FXais) apixaban and rivaroxaban, but its impact on long-term outcomes in FXai-associated intracerebral hemorrhage (ICH) is unknown. We aimed to explore potential clinical implications of andexanet alfa in FXai-associated ICH in this simulation study.MethodsWe simulated potential downstream implications of andexanet alfa across a range of possible hemostatic effects using data from a single center that treats FXai-associated ICH with prothrombin complex concentrate (PCC). We determined baseline probabilities of inadequate hemostasis across patients taking FXai and those not taking FXai via multivariable regression models and then determined the probabilities of unfavorable 3-month outcome (modified Rankin Scale score 4–6) using models comprising established predictors and each patient's calculated probability of inadequate hemostasis. We applied bootstrapping with model parameters from this derivation cohort to simulate a range of hemostatic improvements and corresponding outcomes and then calculated absolute risk reduction (relative to PCC) and projected number needed to treat (NNT) to prevent 1 unfavorable outcome.ResultsTraining models using real-world patients (n = 603 total, 55 on FXai) had good accuracy in predicting inadequate hemostasis (area under the curve [AUC] 0.78) and unfavorable outcome (AUC 0.78). Inadequate hemostasis was strongly associated with unfavorable outcome (odds ratio 4.5, 95% confidence interval [CI] 2.0–9.9) and occurred in 11.4% of patients taking FXai. Across simulated patients taking FXai comparable to those in A Study in Participants With Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of Factor Xa Inhibitors (ANNEXA-4) study, predicted absolute risk reduction of unfavorable outcome was 4.9% (95% CI 1.3%–7.8%) when the probability of inadequate hemostasis was reduced by 33% and 7.4% (95% CI 2.0%–11.9%) at 50% reduction, translating to projected NNT of 21 (cumulative cost $519,750) and 14 ($346,500), respectively.DiscussionEven optimistic simulated hemostatic effects suggest that the costs and potential benefits of andexanet alfa should be carefully considered. Placebo-controlled randomized trials are needed before its use can definitively be recommended.

Background An increasing white blood cell (WBC) count in early course of aneurysmal subarachnoid hemorrhage (SAH) can indicate a systemic inflammatory state triggered by the initial insult. We sought to determine the significance of the early WBC trend as a potential predictor of outcomes. Methods We analyzed a cohort of consecutive patients with aneurysmal SAH. The WBC values in first 5 days of admission, plus relevant clinical and imaging data, and modified Rankin Scale (mRS) at 3 months after hospital discharge were retrieved and analyzed. Favorable outcome was defined as mRS 0–3. The association between WBC counts and outcomes including mRS and delayed cerebral ischemia (DCI) was determined using binary logistic regression models. We used receiver operating characteristic curve analysis to assess accuracy of WBC in predicting outcomes. Results We included 167 patients in final analysis. Mean age was 56.4 (standard deviation [SD] 14.8) years, and 65% (109) of patients were female. Peak WBC was greater in patients with poor functional outcome (mean 17 × 109 cells/L, SD 6.4 vs. 13.5 × 109 cells/L SD 4.7). Combining peak WBC with modified Fisher scale slightly increased accuracy in predicting DCI (area under the curve 0.670, 95% confidence interval 0.586–0.755) compared with each component alone. Conclusions WBC count in the early course of SAH may have prognostic values in predicting DCI and functional outcome. WBC count monitoring may be used in conjunction with other clinical and radiographic tools to stratify patients with SAH into high- and low-risk groups to tailor neuromonitoring and treatment strategies.

Anemia has been linked to delayed cerebral ischemia (DCI) and worse outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, the association of hemoglobin (Hb) trend and outcomes is not well studied. We investigated predictors of Hb trend and its association with outcomes in patients with aSAH. Our hypothesis was that a negative Hb trend is associated with poorer outcomes independent of Hb values.We conducted a retrospective study of a prospectively collected cohort of consecutive patients with aSAH who were admitted to an academic center (2016-2021). We tested the association of Hb trend and values with measures including DCI and poor functional outcome defined as modified Rankin scale 4-6 at 3 months after discharge. Multiple linear regression analysis was used to identify factors associated with Hb difference from admission to discharge.We included 310 patients with confirmed aneurysmal etiology (mean age 57 years, SD13.6; 62 % female). Greater Hb decrement from admission to discharge was independently associated with higher likelihood of both DCI (OR 1.28 per 1 g/dl decrease in Hb, 95 % CI 1.08-1.47; p = 0.003) and poor functional outcome (OR 1.27 per 1 g/dl decrease in Hb, 1.03-1.53; p = 0.026) independent of any absolute Hb values. Predictors of Hb decrement from admission to discharge were hospital length of stay, Hunt and Hess grades, female sex and age.Greater Hb decrement can be associated with higher likelihood of DCI and poor functional outcome in aSAH. More evidence is needed to use Hb trend to guide transfusion threshold in aSAH patients.

Background and Purpose Venous thromboembolism (VTE) is a life-threatening complication of stroke. We evaluated nationwide rates and risk factors for hospital readmissions with VTE after an intracerebral hemorrhage (ICH) or acute ischemic stroke (AIS) hospitalization.Methods Using the Healthcare Cost and Utilization Project (HCUP) Nationwide Readmission Database, we included patients with a principal discharge diagnosis of ICH or AIS from 2016 to 2019. Patients who had VTE diagnosis or history of VTE during the index admission were excluded. We performed Cox regression models to determine factors associated with VTE readmission, compared rates between AIS and ICH and developed post-stroke VTE risk score. We estimated VTE readmission rates per day over a 90-day time window post-discharge using linear splines.Results Of the total 1,459,865 patients with stroke, readmission with VTE as the principal diagnosis within 90 days occurred in 0.26% (3,407/1,330,584) AIS and 0.65% (843/129,281) ICH patients. The rate of VTE readmission decreased within first 4–6 weeks (P

Background and Purpose: Clinical trials on stroke prevention in patients with atrial fibrillation have consistently shown clinical benefit from either warfarin or non–vitamin K antagonist oral anticoagulants (NOACs). NOAC-treated patients have consistently reported to be at lower risk for intracerebral hemorrhage (ICH) than warfarin-treated patients. The aims of this prospective, multicenter, multinational, unmatched, case-control study were (1) to investigate for risk factors that could predict ICH occurring in patients with atrial fibrillation during NOAC treatment and (2) to evaluate the role of CHA 2 DS 2 -VASc and HAS-BLED scores in the same setting. Methods: Cases were consecutive patients with atrial fibrillation who had ICH during NOAC treatment. Controls were consecutive patients with atrial fibrillation who did not have ICH during NOAC treatment. As within the CHA 2 DS 2 -VASc and HAS-BLED scores there are some risk factors in common, several multivariable logistic regression models were performed to identify independent prespecified predictors for ICH events. Results: Four hundred nineteen cases (mean age, 78.8±8.1 years) and 1526 controls (mean age, 76.0±10.3 years) were included in the study. From the different models performed, independent predictors of ICH were increasing age, concomitant use of antiplatelet agents, active malignancy, high risk of fall, hyperlipidemia, low clearance of creatinine, peripheral artery disease, and white matter changes. Low doses of NOACs (given according to label or not) and congestive heart failure were inversely associated with the risk of ICH. HAS-BLED and CHA 2 DS 2 -VASc scores performed poorly in predicting ICH with areas under the curves of 0.496 (95% CI, 0.468–0.525) and 0.530 (95% CI, 0.500–0.560), respectively. Conclusions: Several risk factors were associated to ICH in patients treated with NOACs for stroke prevention but not HAS-BLED and CHA 2 DS 2 -VASc scores.

Delayed cerebral ischemia (DCI) and poor functional outcome are common complications in patients who suffer from aneurysmal subarachnoid hemorrhage (aSAH). It has been proposed that pre-admission beta-blocker therapy may lower cerebral vasospasm (cVSP) risk after aSAH; however, this association with other antihypertensives is unknown. We sought to determine the association between antihypertensives and clinical outcomes in aSAH patients.We performed a retrospective study on a prospectively collected cohort of consecutive patients with aSAH who were admitted to an academic center from 2016 to 2021. Association between pre-admission use of antihypertensives and patient outcomes was determined. Primary outcomes included DCI and poor functional outcome at 3 months after discharge defined as modified Rankin scale [mRS] 4-6. The secondary outcome was cVSP identified using transcranial Doppler (TCD).The cohort consisted of 306 aSAH patients with mean age 57.1 (SD 13.6) years with 187 females (61 %). Although pre-admission use of beta-blockers (OR 0.40, 95 % CI 0.21-80, p = 0.02), calcium channel blockers (OR 0.43, 95 % CI 0.19-0.93, p = 0.035), and thiazide (OR 0.31, 95 % CI 0.11-0.86, p = 0.025) were associated with lower risk of cVSP in univariate analysis, we did not find any association in a multivariate model after adjusting for age. There was no association between any class of antihypertensives and DCI or functional outcome.Pre-admission use of antihypertensive agents may affect TCD findings, however, none of them appear to be independently associated with DCI or functional outcome. Larger prospective studies are needed to establish any potential association.

Although seizures are common in prehospital settings, standardized emergency medical services (EMS) treatment algorithms do not exist nationally. We examined nationwide variability in status epilepticus treatment by analyzing 33 publicly available statewide EMS protocols. All adult protocols recommend intravenous benzodiazepines (midazolam, n = 33; lorazepam, n = 23; diazepam, n = 24), 30 recommend intramuscular benzodiazepines (midazolam, n = 30; lorazepam, n = 8; diazepam, n = 3), and 27 recommend intranasal benzodiazepines (midazolam, n = 27; lorazepam, n = 3); pediatric protocols also frequently recommend rectal diazepam (n = 14). Recommended dosages vary widely, and first- and second-line agents are designated in only 18 and 2 states, respectively. Given this degree of variability, standardized national EMS guidelines are needed. ANN NEUROL 2021;89:604-609.

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.

Introduction: Neutrophil-to-lymphocyte ratio (NLR) is a marker of acute inflammation after brain injury. We sought to evaluate the relationship between NLR at admission and 3-month outcome in patients with spontaneous intracerebral hemorrhage (ICH). Methods: We pooled individual level data from 2 prospective ICH cohorts, the Acute Brain Injury Biorepository at Yale and Brown ICH registry. We included patients with ICH who had available NLR at admission (exposure of interest) and 3-month modified Rankin Scale (mRS). The primary endpoint was poor outcome at 3-months, defined as mRS 4-6. In each cohort, we fit multivariable logistic regression models to test for association between NLR (natural log transformed and quartiles) and 3-month mRS. Multivariable models were adjusted for sex and components of the ICH score. We then pooled study-specific results using a random-effects (with inverse variance-weighting) meta-analysis. Results: 592 patients from Brown (69 years [SD 14], 47% female), and 107 patients from Yale (67 years [SD 14], 49% female) were included in the analysis. In the Brown cohort, average ICH volume was 9 cc and 64% of patients had lobar ICH. In the Yale cohort, ICH volume was 10.7 cc and 51% of patients had a lobar ICH. The NLR at admission was 8.21 [SD 9.39] in the Brown cohort and 6.98 [SD 11.35] in the Yale cohort (p=0.230). In the Brown cohort, NLR was associated with poor 3-month outcome in unadjusted (OR 1.28, 95% CI 1.06-1.54, p = 0.01) and adjusted analyses (OR 1.27, 95% CI 1.03-1.57, p = 0.03). In the Yale cohort, NLR yielded similar results in unadjusted (OR 1.80, 95% CI 1.11-2.92, p = 0.02) and adjusted analyses, although not statistically significant (OR 1.90, 95% 0.64-5.63, p = 0.24). Random effect models showed a consistent association in both unadjusted (OR 1.41; 95% CI, 1.04-1.90; p = 0.025; heterogeneity I 2 =40%; Q=1.67, p=0.2) and adjusted analyses (OR 1.29; 95% CI, 1.05-1.59; p=0.016; heterogeneity I 2 =68%; Q=0.49, p=0.48). Compared to the lowest quartile, the highest quartile of NLR had a 20% increase in the odds of having a poor outcome at 3 months (p=0.03). Conclusions: In a pooled study of two prospective cohorts, NLR was associated with poor functional outcome at 3 months. Future studies are needed to further evaluate NLR as a prognostic marker.

Background: Delirium is an acute cognitive disturbance frequently characterized by abnormal levels of motor activity and sleep-wake cycle disruption. However, the degree to which delirium affects activity patterns in the acute period after stroke is unclear. We aimed to examine these patterns in a cohort of patients with intracerebral hemorrhage (ICH). Methods: We enrolled 40 patients with supratentorial ICH and hemiparesis who had daily delirium assessments performed by expert clinicians. Continuous measurements of activity were captured using bilateral wrist actigraphs for the duration of each patient’s admission. Activity data were collected in 1-minute intervals, with “rest” intervals defined as periods with zero activity recorded. We compared differences in activity based on delirium status across multiple time intervals using linear regression models adjusted for age, ICH severity, and mechanical ventilation. Results: There were 312 total days of actigraphy monitoring, of which 233 (75%) were rated as days with delirium; 85% of patients (34/40) experienced delirium during their hospitalization. In multivariable analyses, delirium days were associated with 66.3 (95% CI 9.4-123.2) fewer total minutes of rest, including 6.1% (95% CI 2.3-9.9%) fewer minutes of rest during daytime periods (06:00-21:59) and 9.2% (95% CI 3.3-15.0%) fewer minutes of rest during nocturnal periods (22:00-5:59). In separate analyses for individual hourly intervals, delirium days were associated with significantly higher levels of activity across multiple consecutive time intervals, including 05:00-09:00 and 17:00-03:00. In subgroup analyses, hyperactive or mixed delirium was associated with fewer total daily minutes of rest compared to hypoactive delirium, along with lower proportions of time at rest during both daytime and nocturnal periods (4.3% [95% CI 0.5-8.0%] and 6.5% [95% CI 0.9-12.1%] lower, respectively). Conclusion: Post-stroke delirium is associated with less rest and higher overall levels of activity, especially during nocturnal periods and in patients with hyperactive or mixed delirium.

Background: Delirium occurs frequently in patients with stroke but is often underrecognized. We aimed to develop a novel delirium screening tool designed specifically for stroke patients, and to test its feasibility and accuracy in a pilot study. Methods: We designed an easy-to-use 5-point instrument called the Fluctuating Mental Status Evaluation (FMSE) and tested it in a cohort of patients with intracerebral hemorrhage (ICH) who had daily delirium assessments throughout their admission. Expert ratings were performed by an attending neurointensivist or behavioral neurologist each afternoon using DSM-5 criteria, and were derived from bedside assessments and clinical data from the preceding 24 hours. Paired FMSE assessments were performed by patients’ clinical nurses after brief training on the use of the tool. Nursing assessments were aggregated over 24-hour periods (including day and night shifts), and accuracy of the FMSE was analyzed on both a per-assessment day and per-patient basis. Results: Among the 40 enrolled patients (mean age 71.1±12.2, median initial NIHSS score 16.5 [IQR 12-20]), 34 experienced delirium during their hospitalization. There were 306 total coma-free days with paired assessments, of which 208 (68%) were rated as days with delirium. Compared to expert ratings, an FMSE score ≥1 had 86% sensitivity and 74% specificity on a per-day basis, while a score ≥2 had 68% sensitivity and 83% specificity. On a per-patient basis, a score ≥1 at any point during admission had 97% sensitivity and 67% specificity in identifying patients who experienced delirium, while a score ≥2 had 94% sensitivity and 67% specificity. Conclusion: The FMSE is a feasible delirium screening tool in ICH patients, with high real-world sensitivity and specificity. Based on these results, we plan to validate the tool in a larger, more diverse cohort of stroke patients, using score cutoffs of ≥1 as “possible” delirium and ≥2 as “probable” delirium.

White matter hyperintensity (WMH) is an abnormal T2 signal in the deep and subcortical white matter visualized on MRI associated with hypertension, cerebrovascular disease, and aging. The Fazekas (Fz) scoring system is a commonly used qualitative tool to assess the severity of WMH. While studies have compared Fazekas scores to other scoring methods, the comparison of Fazekas scores and volume of WMH using current semiautomated volumetric techniques has not been studied.We reviewed MRI studies acquired at our institution between 2015 and 2017. Relative WMH was scored by one author trained in Fazekas scoring. A board certified neuroradiologist scored them independently for confirmation. Manual segmentations of WMH were completed using 3D Slicer 4.9. A 3D model was formed to quantify WMH in milliliters (mL). ANOVA tests were performed to determine the association of Fazekas scores with corresponding WMH volumes.Among the 198 patients in our study, WMH were visualized in 163 (Fz1: n=66; Fz2: n=49; Fz3: n=48). WMH volumes significantly differed according to Fazekas score (F = 141.1, p0.001), with increasing WMHV associated with higher Fazekas scores: Fz1, range 0.1-8.3 mL (mean 3.7, SD 2.3); Fz2, range 6.0-17.7 mL (mean 10.8, SD 3.1); Fz3, range 14.2-77.2 mL (mean 35.2, SD 17.9); and Fz3 (excluding 11 outliers above 50 mL), 14.2-47.0 mL (mean 27.1, SD 8.9).Fazekas scores correspond with distinct ranges of WMH volume with relatively little overlap, but scores based on volumes are more efficacious. A modified Fazekas from 0-4 should be considered.

Cerebral vasospasm (cVSP) is a common complication in aneurysmal subarachnoid hemorrhage (aSAH) and is associated with worse outcomes. However, clinical significance of asymptomatic cVSP is poorly understood. We sought to determine the association of asymptomatic cVSP with functional outcome and hospital length of stay (LOS).We performed a retrospective study of a prospectively collected cohort of patients with aSAH who survived hospitalization at an academic center between 2016 and 2021. We defined cVSP based on transcranial Doppler criteria. Multivariate logistic and multiple linear regression analyses were used to determine the association of asymptomatic cVSP with poor functional outcome (defined as modified Rankin scale 3-6 at 3 months after discharge) and hospital length of stay (LOS).The cohort consisted of 201 aSAH patients with a mean age 54.9 years (SD 13.6) and 60% were female. One hundred nine patients (54%) experienced cVSP, of whom 43 patients (39%) were asymptomatic. Patients with asymptomatic cVSP were younger (mean 50.5 years [SD 10.6] vs 61 years [SD12.5]; p 0.001) and had longer ICU LOS (median 13 days [IQR12-20] vs median 12 days [IQR9-15], p = 0.018) compared to those without cVSP. However, after adjusting with other variables asymptomatic cVSP was not associated with longer ICU or hospital LOS. Asymptomatic cVSP was not associated with poor outcome either (p = 0.14).Asymptomatic cVSP, which was more common in younger patients, was neither associated with poor functional outcome nor hospital LOS. Larger prospective studies are needed to assess the significance of asymptomatic cVSP on long-term outcomes.

IntroductionAtraumatic convexity subarachnoid hemorrhage is a subtype of spontaneous subarachnoid hemorrhage that often presents a diagnostic challenge. Common etiologies include cerebral amyloid angiopathy, vasculopathies, and coagulopathy; however, aneurysm is rare. Given the broad differential of causes of convexity subarachnoid hemorrhage, we assessed the diagnostic yield of common tests and propose a testing strategy.MethodsWe performed a single-center retrospective study on consecutive patients with atraumatic convexity subarachnoid hemorrhage over a 2-year period. We obtained and reviewed each patient’s imaging and characterized the frequency with which each test ultimately diagnosed the cause. Additionally, we discuss clinical features of patients with convexity subarachnoid hemorrhage with respect to the mechanism of hemorrhage.ResultsWe identified 70 patients over the study period (mean (SD) age 64.70 (16.9) years, 35.7% men), of whom 58 patients (82%) had a brain MRI, 57 (81%) had non-invasive vessel imaging, and 27 (38.5%) underwent catheter-based angiography. Diagnoses were made using only non-invasive imaging modalities in 40 patients (57%), while catheter-based angiography confirmed the diagnosis in nine patients (13%). Further clinical history and laboratory testing yielded a diagnosis in an additional 17 patients (24%), while the cause remained unknown in four patients (6%).ConclusionThe etiology of convexity subarachnoid hemorrhage may be diagnosed in most cases via non-invasive imaging and a thorough clinical history. However, catheter angiography should be strongly considered when non-invasive imaging fails to reveal the diagnosis or to better characterize a vascular malformation. Larger prospective studies are needed to validate this algorithm.

Background and Purpose: Patients with ischemic stroke of cardioembolic origin are at risk of visceral (renal or splenic) infarction. We hypothesized that serum troponin level at time of ischemic stroke would be associated with presence of visceral infarction. Methods: Data were abstracted from a single center prospective stroke database over 18 months and included all patients with ischemic stroke who underwent contrast-enhanced computerized tomography (CT) of the abdomen and pelvis for clinical purposes within 1 year of stroke. The primary predictor was troponin concentration ≥.1ng/mL. The primary outcome was visceral infarct (renal and/or splenic) on CT abdomen and pelvis. Univariate and multivariable logistic regression models were used to estimate the odds ratio and 95% confidence intervals (OR, 95% CI) for the association of troponin with visceral infarction. Results: Of 1233 patients with ischemic stroke, 259 patients had a qualifying visceral CT. Serum troponin level on admission was measured in 237 of 259 patients (93.3%) and 41 of 237 (17.3%) had positive troponin. There were 25 patients with visceral infarcts: 16 renal, 7 splenic, and 2 both. In univariate models, patients with a positive troponin level (versus negative) were more likely to have visceral infarcts (39.1% [9/23] versus 15.0% [32/214], P = .008) and this association persisted in multivariable models (adjusted OR 3.83; 95% CI 1.42-10.31, P = .006). Conclusions: In ischemic stroke patients, elevated serum troponin levels may help identify patients with visceral infarcts. This suggests that troponin in the acute stroke setting is a biomarker of embolic risk. Larger studies with systematic visceral imaging are needed to confirm our findings.

BackgroundThe aetiology of wall motion abnormalities (WMA) in patients with ischaemic stroke is unclear. We hypothesised that WMAs on transthoracic echocardiography (TTE) in the setting of ischaemic stroke mostly reflect pre-existing coronary heart disease rather than simply an isolated neurocardiogenic phenomenon.MethodsData were retrospectively abstracted from a prospective ischaemic stroke database over 18 months and included patients with ischaemic stroke who underwent a TTE. Coronary artery disease was defined as history of myocardial infarction (MI), coronary intervention or ECG evidence of prior MI. The presence (vs absence) of WMA was abstracted. Multivariable logistic regression was used to determine the association between coronary artery disease and WMA in models adjusting for potential confounders.ResultsWe identified 1044 patients who met inclusion criteria; 139 (13.3%, 95% CI 11.2% to 15.4%) had evidence of WMA of whom only 23 (16.6%, 95% CI 10.4% to 22.8%) had no history of heart disease or ECG evidence of prior MI. Among these 23 patients, 12 had a follow-up TTE after the stroke and WMA persisted in 92.7% (11/12) of patients. In fully adjusted models, factors associated with WMA were older age (OR per year increase 1.03, 95% 1.01 to 1.05, p=0.009), congestive heart failure (OR 4.44, 95% CI 2.39 to 8.33, pConclusionIn patients with ischaemic stroke, WMA on TTE may reflect underlying cardiac disease and further cardiac evaluation may be considered.

Background: Central retinal artery occlusion (CRAO) causes sudden, irreversible blindness and is a form of acute ischemic stroke. In this study, we sought to determine the proportion of patients in whom atrial fibrillation (AF) is detected by extended cardiac monitoring after CRAO. Methods: We performed a retrospective, observational cohort study using data from the Optum deidentified electronic health record of 30.8 million people cross-referenced with the Medtronic CareLink database of 2.7 million people with cardiac monitoring devices in situ. We enrolled patients in 3 groups: (1) CRAO, (2) cerebral ischemic stroke, and (3) age-, sex-, and comorbidity-matched controls. The primary end point was the detection of new AF (defined as ≥2 minutes of AF detected on a cardiac monitoring device). Results: We reviewed 884 431 patient records in common between the two databases to identify 100 patients with CRAO, 6559 with ischemic stroke, and 1000 matched controls. After CRAO, the cumulative incidence of new AF at 2 years was 49.6% (95% CI, 37.4%–61.7%). Patients with CRAO had a higher rate of AF than controls (hazard ratio, 1.64 [95% CI, 1.17–2.31]) and a comparable rate to patients with stroke (hazard ratio, 1.01 [95% CI, 0.75–1.36]). CRAO was associated with a higher incidence of new stroke compared with matched controls (hazard ratio, 2.85 [95% CI, 1.29–6.29]). Conclusions: The rate of AF detection after CRAO is higher than that seen in age-, sex-, and comorbidity-matched controls and comparable to that seen after ischemic cerebral stroke. Paroxysmal AF should be considered as part of the differential etiology of CRAO, and those patients may benefit from long-term cardiac monitoring.

Background: Prior studies identified an increased risk of hematoma expansion (HE) in patients with spontaneous intracerebral hemorrhage (ICH) and lower admission hemoglobin (Hgb) levels. We aimed to externally validate these findings in a separate cohort of ICH patients. Methods: We performed an observational cohort study on consecutive patients with ICH admitted to a Comprehensive Stroke Center over 2 years, using data from an institutional ICH registry. We excluded patients with secondary, non-spontaneous ICH etiologies, as well as patients who arrived >24 hours from symptom onset. Data on HE (defined as an increase of >33% or >6 mL) and 3-month outcomes were prospectively collected, while admission laboratory values were retrospectively abstracted. We compared admission Hgb, INR, and platelet count (Plt) between patients with and without HE, then determined associations between Hgb, HE, and unfavorable 3-month outcomes (modified Rankin Scale 4-6) after adjusting for established ICH predictors, any anticoagulant use, and laboratory markers of coagulopathy with multivariable logistic regression analysis. Results: Of 375 patients, mean age was 73.6 [SD 13.5], 50% (n=187) were male, 85% (n=317) were white, and 19% (n=71) had HE. Admission Hgb values were similar in patients with and without HE (mean [SD] 13.1 [1.8] g/dl vs. 13.1 [1.9] g/dl, p=0.98), as were INR values (median [IQR] 1.1 [1-1.3] vs. 1.1 [1.0-1.2], p=0.15), although patients with HE had modestly lower Plt (median [IQR] 181 [155-230] x 10 9 /l vs. 207 [170-253] x 10 9 /l, p=0.02). In our multivariable models, Hgb was not associated with HE (OR 0.97, 95% CI 0.83-1.12), but odds of unfavorable 3-month outcome increased with lower Hgb levels (OR 0.81 per 1 g/dL Hgb, 95% CI 0.68-0.96). Conclusion: Our study did not confirm prior associations between Hgb and HE, suggesting that if Hgb is implicated in HE, its effects are likely modest. However, Hgb may mediate outcomes in ICH patients via alternative mechanisms.

Background: Socioeconomic status (SES) has been associated with intracerebral hemorrhage (ICH) incidence, but its impact on ICH-related features and outcomes is unclear. Methods: We performed a single-center cohort study on consecutive ICH patients admitted over 2 years. Demographics, ICH characteristics, and outcomes were prospectively collected, while SES-related data were retrospectively abstracted. We classified SES quartiles using census estimates of median household incomes corresponding to patients’ home ZIP codes, then categorized patients as “lower SES” if their ZIP code was in the lowest SES quartile, if they were uninsured, or had Medicaid as their source of insurance. We compared ICH characteristics between patients with lower vs. higher SES, then determined associations between lower SES and unfavorable 3-month outcome (modified Rankin Scale 4-6) using multivariable logistic regression. Results: Of 665 patients, 31% (n=207) were categorized as lower SES. Patients with lower SES were significantly younger (mean [SD] 64.7 [16.1] vs. 73.1 [14.2] years, p Conclusions: Differences in ICH features may be driven by pre-morbid healthcare disparities in lower SES patients. Although their younger age and shorter time to presentation may have mitigated the deleterious effects of comorbidities on long-term outcomes, these factors may also belie a greater loss of quality-adjusted life years from ICH-related disability.

Background: Urgent blood pressure (BP) control is a mainstay of acute intracerebral hemorrhage (ICH) treatment, but the relationship between time to BP control and clinical outcomes is unclear. Methods: We performed a single-center observational cohort study on consecutive patients with ICH who were hypertensive on hospital arrival over a 2-year period. We defined time-to-BP-control as the time from initial hospital arrival to first BP recorded below our institutionally mandated goal (systolic BP [SBP] 200 mmHg, hypertensive ICH etiology, and anticoagulation-related ICH. Results: Among 330 patients in our cohort, mean arrival SBP was 191±131 mmHg and mean time-to-BP-control was 2.3±1.5 hours. On univariate analysis, patients without HE had longer time-to-BP-control than those with HE (mean 2.5 vs. 2.1 hours, p=0.02). This was confirmed in multivariable models, where longer time-to-BP-control was associated with a lower likelihood of HE (OR 0.81 per hour, 95% CI 0.66-0.98), and was not associated with 3-month outcome (OR 0.99 per hour, 95% CI 0.81-1.21). Results were similar in subgroup analyses of patients with arrival SBP >200 mmHg and hypertensive ICH etiology. However, in those with anticoagulation-related ICH, longer time-to-BP-control was associated with a higher likelihood of unfavorable 3-month outcome (OR 2.02 per hour, 95% CI 1.13-3.61). Conclusion: Earlier BP control may not improve outcomes in all ICH patients, though some subgroups, such as those with anticoagulation-related ICH, may derive greater benefit from earlier treatment.

Background: Andexanet alfa was recently approved as a reversal agent for the Factor Xa inhibitors (FXai) apixaban and rivaroxaban, but its impact on long-term outcomes in FXai-associated intracerebral hemorrhage (ICH) is unknown. Methods: We performed a simulation study to determine the potential clinical implications of andexanet alfa across a range of possible hemostatic effects using data from a single-center cohort of ICH patients who did not receive the drug. We used this data to determine the baseline probability of insufficient hemostatic efficacy (IHE) across patients with and without FXai use via k-fold cross-validated multivariable regression models, which we aggregated into an IHE propensity score. We then determined the probability of unfavorable 3-month outcome (modified Rankin Scale 4-6) using a model comprised of established clinical predictors and IHE propensity. We applied model parameters from this derivation cohort to simulate a range of IHE reductions and corresponding outcomes, which we used to calculate absolute risk reduction (ARR) and projected number needed to treat (NNT) to prevent one unfavorable outcome. Results: Training models using a real-world ICH cohort (n=604 total; 55 FXai patients) had good accuracy in predicting IHE (AUC 0.78) and unfavorable outcome (AUC 0.82). IHE was strongly associated with unfavorable outcome (OR 6.7, 95% CI 3.8-11.8) and occurred in 11.4% of FXai patients. Predicted ARR of unfavorable outcome was 5% (95% CI 3-8%) at one-third reduction of IHE and 8% (95% CI = 4-13%) at 50% IHE reduction, translating to a projected NNT of 20 (cumulative treatment cost $495,000) and 13 ($321,750), respectively. Conclusion: Even optimistic simulated hemostatic effects suggest that the costs and potential benefits of andexanet alfa should be carefully considered, and placebo-controlled randomized trials are needed before its use can definitively be recommended.

Background: Acute dizziness can present diagnostic challenges for emergency department (ED) clinicians because of the potential for an underlying cerebrovascular cause. Although various strategies may aid in diagnosing cases caused by stroke, it is unclear whether dizziness due to intracerebral hemorrhage (ICH) is associated with delays in diagnostic imaging. Methods: We performed a single center cohort study on consecutive ICH patients admitted over 2 years. We retrospectively abstracted initial reported symptoms and aggregated patients with dizziness, vertigo, lightheadedness, or nausea under the category of dizziness-related symptoms. After excluding patients with ED intubation due to potential procedural delays, we calculated time from initial ED arrival to first computed tomography (CT) scan. Using linear regression, we determined associations between dizziness-related symptoms and ED-to-CT time after adjusting for demographics and time from symptom onset, with additional analyses considering the presence of typical stroke symptoms and cerebellar ICH. Results: Of 427 patients, 110 (26%) presented with dizziness-related symptoms and 36 (8%) had cerebellar ICH. In univariate analyses, patients with dizziness-related symptoms had longer ED-to-CT times than other patients (median [IQR] 51 [21-144] vs. 32 [14-92] min, p=0.007), as did those with cerebellar ICH (71 [27-182] min). In our primary adjusted model, dizziness-related symptoms were associated with longer ED-to-CT times (+26 min [95% CI 6-46]). This imaging delay was further compounded in a subgroup analysis of patients without typical stroke symptoms (+45 min [95% CI 7-84], and in a separate model considering patients with cerebellar ICH (+48 min [95% CI 17-80]). Conclusions: Dizziness-related symptoms are associated with delayed diagnostic imaging in patients with ICH, which suggests the need for increased early awareness and urgency in these cases.

Background: Opioids are often used as analgesics in patients with subarachnoid hemorrhage, but their use in the setting of intracerebral hemorrhage (ICH) is not well described. We aimed to determine risk factors for opioid use in both the acute and post-discharge settings in patients with ICH. Methods: We analyzed data from a single-center cohort of consecutive ICH patients admitted over two years. Demographics and ICH-related characteristics were prospectively collected as part of an institutional ICH registry, while pre-morbid, in-hospital, and post-discharge medications were retrospectively abstracted from medication administration records and physician documentation. After excluding patients who received end-of-life care, we used multivariable regression models adjusted for pre-morbid opioid use to determine demographic and ICH-related risk factors for in-hospital and post-discharge opioid use. Results: Of 468 patients in our cohort, 15% (n=70) had pre-morbid opioid use, 53% (n=248) had in-hospital opioid use, and 12% (n=53) of survivors had opioids prescribed at discharge. The most commonly used in-hospital opioids were fentanyl (38% of patients), oxycodone (30%), morphine (26%), and hydromorphone (7%). Patients who received in-hospital opioids were significantly younger (mean 62.7 vs. 74.0 years, p Conclusion: Inpatient opioid use in ICH patients is common, with risk factors that may be mechanistically connected to headache pathophysiology. However, the lower frequency of post-discharge opioid prescriptions may be reassuring given the prevalence of opioid dependence nationwide.

Objectives Opioids are frequently used for analgesia in patients with acute subarachnoid hemorrhage (SAH) due to a high prevalence of headache and neck pain. However, it is unclear if this practice may pose a risk for opioid dependence, as long-term opioid use in this population remains unknown. We sought to determine the prevalence of opioid use in SAH survivors, and to identify potential risk factors for opioid utilization. Methods We analyzed a cohort of consecutive patients admitted with non-traumatic and suspected aneurysmal SAH to an academic referral center. We included patients who survived hospitalization and excluded those who were not opioid-naive. Potential risk factors for opioid prescription at discharge, 3 and 12 months post-discharge were assessed. Results Of 240 SAH patients who met our inclusion criteria (mean age 58.4 years [SD 14.8], 58% women), 233 (97%) received opioids during hospitalization and 152 (63%) received opioid prescription at discharge. Twenty-eight patients (12%) still continued to use opioids at 3 months post-discharge, and 13 patients (6%) at 12-month follow up. Although patients with poor Hunt and Hess grades (odds ratio 0.19, 95% CI 0.06–0.57) and those with intraventricular hemorrhage (odds ratio 0.38, 95% CI 0.18–0.87) were less likely to receive opioid prescriptions at discharge, we did not find significant differences between patients who had long-term opioid use and those who did not. Conclusion Opioids are regularly used in both the acute SAH setting and immediately after discharge. A considerable number of patients also continue to use opioids in the long-term. Opioid-sparing pain control strategies should be explored in the future.

Hypertension is a known risk factor for intracerebral hemorrhage (ICH), but it is unclear whether blood pressure (BP) at hospital arrival can be used to distinguish hypertensive ICH from non-hypertensive etiologies.We performed a single-center cohort study using data from consecutive ICH patients over 12 months. ICH characteristics including etiology were prospectively adjudicated by two attending neurologists. Using adjusted linear regression models, we compared first recorded systolic BPs (SBP) and mean arterial pressures (MAP) in patients with hypertensive vs. other ICH etiologies. We then used area under the ROC curve (AUC) analysis to determine the accuracy of admission BP in differentiating between hypertensive and non-hypertensive ICH.Of 311 patients in our cohort (mean age 70.6 ± 15.6, 50% male, 83% white), the most frequent ICH etiologies were hypertension (50%) and cerebral amyloid angiopathy (CAA; 22%). Mean SBP and MAP for patients with hypertensive ICH was 175.1 ± 32.9 mmHg and 120.4 ± 22.9 mmHg, respectively, compared to 156.4 ± 28.0 mmHg and 109.6 ± 20.3 mmHg in non-hypertensive ICH (p .001). Adjusted models showed that hypertensive ICH patients had higher BPs than those with CAA (mean SBP difference 10.7 mmHg [95% CI 0.8-20.5]; mean MAP difference 8.1 mmHg [1.1-15.0]) and especially patients with other non-CAA causes (mean SBP difference 23.9 mmHg [15.3-32.4]; mean MAP difference 14.5 mmHg [8.5-20.6]). However, on a patient-level, arrival BP did not reliably discriminate between hypertensive and non-hypertensive etiologies (AUC 0.660 [0.599-0.720]).Arrival BP differs between hypertensive and non-hypertensive ICH but should not be used as a primary determinant of etiology, as hypertension may be implicated in various subtypes of ICH.

Background: There is limited data on predictors of sICH in patients who underwent mechanical thrombectomy. In this study, we aim to determine those predictors with external validation. Methods: We evaluated mechanical thrombectomy in a derivation cohort of patients at a comprehensive stroke center over a 30-month period. sICH was defined using the European Cooperative Acute Stroke Study III. We compared clinical and radiographic characteristics between patients with and without sICH to identify independent predictors of sICH with p Results: We identified 578 patients with acute ischemic stroke who received thrombectomy, 19 had sICH (3.3%). Predictive factors of sICH were: Thrombolysis in cerebral ischemia score, Alberta stroke program early computed tomography score (ASPECTS), and Glucose level, and using these predictors, we derived the weighted TAG score which was associated with sICH in the derivation (OR per unit increase 1.98, 95% CI 1.48-2.66, AUC=0.79) and validation (OR per unit increase 1.48, 95% CI 1.22-1.79, AUC=0.69) cohorts. Conclusion: High TAG scores are associated with sICH in patients receiving mechanical thrombectomy. Larger studies are needed to validate this scoring system and test strategies to reduce sICH risk and make thrombectomy safer in patients with elevated TAG scores.

Background: Delays in medical care are known to be associated with worse outcomes in ischemic stroke, but outcomes in patients with intracerebral hemorrhage (ICH) and delayed presentation are unclear. We aimed to determine factors associated with prolonged delays from ICH symptom onset to hospital presentation and implications for long-term outcomes. Methods: We performed a single-center cohort study using data from consecutive ICH patients over 12 months. ICH characteristics and outcomes were prospectively collected, while time of symptom onset (or last-known-well) and emergency department arrival were retrospectively abstracted. We calculated time-to-arrival and defined prolonged delay as >24 hours. Using multivariable logistic regression, we determined factors associated with prolonged delays to presentation, then determined associations with unfavorable 3-month outcomes (modified Rankin Scale [mRS] 4-6) after adjusting for demographics and ICH severity. Results: Of 299 patients with out-of-hospital ICH, 21% (n=62) presented >24 hours from symptom onset; median time-to-arrival was 5.5 hours (IQR 1.2-17.8). There were not significant differences in age (mean 71.9±14.0 vs. 70.4±16.0, p=0.50), sex (48% vs. 50% male, p=0.80), race (89% vs. 82% white, p=0.22), or ICH size (mean 15.5±23.2 vs. 20.5±27.4cc, p=0.19) between patients presenting >24 hours and Conclusions: Outcomes in ICH patients with prolonged delays to presentation differ from those who present earlier. ICH severity in such patients may not be accurately captured by established predictors, and prognostication models should therefore account for inherent survivorship bias.

Introduction: Clinical outcomes in patients with acute basilar occlusion (BAO) vary widely; several prognostic scores based on noninvasive imaging have been proposed. We aimed to compare the predictive value of several noninvasive neuroimaging scores in patients with BAO. Methods: We performed a single-center retrospective cohort study including all patients with acute BAO from 2015-2019. Using available clinical radiographic data, we calculated the following scores based on computed tomography (CT) and CT angiogram: Goyal posterior communicating artery score, posterior circulation collateral score, Basilar Artery on Computed Tomography Angiography (BATMAN) score, pc-ASPECTS score, and pons-midbrain index. We also calculated the following scores based on diffusion-weighted (DWI) magnetic resonance imaging (MRI): Bern DWI score, MRI pc-ASPECTS, and pons-midbrain index on DWI. We then used logistic regression with area under the ROC curve analysis to determine the accuracy of each score in predicting favorable 3-month outcome (modified Rankin Scale 0-2). Results: Of 39 patients in our cohort, 92.3% underwent endovascular treatment (n=36) and 35.8% (n=14) had a favorable 3-month outcome. The Bern DWI score (AUC 0.790, 95% CI 0.619-0.960), pc-ASPECTS on MRI (AUC 0.880, 95% CI 0.601-0.958), and pons-midbrain index on MRI (AUC 0.764, 95% CI 0.594-0.934) accurately predicted 3-month outcome when analyzed as raw scores (Figure 1).: Conclusion: MRI scores more strongly predict outcome in BAO as compared to CTA collateral scores. Larger prospective studies are needed to confirm our findings.

Background: Delirium occurs frequently in patients with intracerebral hemorrhage (ICH), though its pathogenesis may be multifactorial. Given the potential role of systemic stressors in delirium, we aimed to explore differences in commonly measured markers of physiologic stress between delirious and non-delirious ICH patients. Methods: We performed a single-center cohort study using data from consecutive non-comatose ICH patients over 12 months. ICH and patient characteristics were prospectively collected, and the presence of delirium at any point during hospitalization was diagnosed based on DSM-5 criteria. We retrospectively abstracted admission laboratory values and selected three common markers of physiologic stress for comparison: neutrophil-lymphocyte ratio (NLR), troponin, and glucose. Using multivariable models adjusted for demographics, relevant comorbidities, and ICH severity, we determined associations between delirium and the following: NLR, using linear regression; elevated troponin (>0.05 ng/mL), using binary logistic regression; and elevated glucose (categorized as 130-180 or >180 mg/dL), using ordered logistic regression. Results: Of 284 ICH patients in our cohort, 55% (n=157) had delirium. Patients with delirium were not significantly older than non-delirious patients (mean age 71.7±16.2 vs. 68.3±15.1, p=0.07), but had larger ICH volumes (mean 23.3±24.6 vs. 7.0±10.6 cc, p Conclusions: Delirium after ICH is independently associated with elevated serum markers of physiologic stress, suggesting that systemic factors may be implicated in delirium pathogenesis.

Introduction: Spontaneous intracerebral hemorrhage (ICH) most commonly arises due to primary etiologies such as hypertensive or cerebral amyloid angiopathy (CAA), but may also occur due to underlying secondary causes such as vascular malformations or intracranial neoplasms. However, focal mass effect may potentially obscure underlying lesions on neuroimaging performed during the acute phase of ICH, and follow-up imaging is often recommended. We sought to determine the yield of interval magnetic resonance imaging (MRI) in identifying cryptogenic ICH etiologies. Methods: We performed a single-center descriptive cohort study of consecutive patients enrolled in an institutional ICH registry over 12 months. ICH features including etiology and acute neuroimaging were prospectively adjudicated, while planned interval follow-up imaging was retrospectively reviewed. We determined the frequency of newly-discovered findings on interval MRI, and classified new findings according to whether or not they contributed meaningfully to patient management. Results: There were 241 ICH patients in our cohort who survived to discharge and did not have MRI-incompatible devices; 44 had planned follow-up imaging and 33 ultimately completed a follow-up MRI. Mean interval between initial and follow-up MRI was 61 (±34) days. New findings were identified in 33% of follow-up cases (11/33), with changes in patient management occurring in 12% (4/33). Age (59.4 vs. 61.5, p=0.74), sex (45% vs. 45% male, p>0.99), and secondary ICH score (median 3 [IQR 2-3] vs. 3 [1-4], p=0.87) were not significantly different between patients who had new findings and those who did not. New findings included cavernoma (n=4; 1 underwent resection), CAA-related changes (n=3), intracranial malignancy (n=2; 1 transitioned to hospice care, 1 led to cancer workup), new embolic stroke (n=1, underwent extended cardiac monitoring), and demyelination (n=1). Conclusions: Interval MRI aided in diagnosing ICH etiology in one-third of patients who received one, though few cases led to direct actionable changes in patient management.

Introduction: Central retinal artery occlusion (CRAO) is a form of ischemic stroke and necessitates a comprehensive workup, including for cardioembolic sources such as atrial fibrillation (AF). However, the incidence of new AF diagnosed after CRAO is unknown. We aimed to examine the incidence of new, cardiac device-detected AF after CRAO in a large population-based cohort. Methods: Using patient-level data from the Optum® de-identified EHR dataset (2007-2017) linked with Medtronic implantable cardiac device data, we identified patients that had a diagnosis-code corresponding to CRAO and no known history of AF, and who also had either a device in-situ at the time of CRAO or implanted ≤1 year post-CRAO with continuous AF monitoring data available. AF incidence was defined as ≥2 minutes of device-detected AF in a day. Results: Of 467,167 patients screened, 246/433 (56.8%) with CRAO had no history of AF, of whom 39 had an eligible implantable cardiac device (mean age 66.7±14.8, 41.0% female). Prevalence of vascular risk factors was high (hypertension, 71.8%; hyperlipidemia, 61.5%; coronary artery disease, 46.2%). Within 3 months, 7.7% of these patients (n=3) had device-detected AF. At 36 months, 33.3% of patients (n=13). The maximum daily AF burden post CRAO ranged from 2 minutes to 24 hours with a mean of 390±530 minutes. Of the patients with device-detected AF, 9 were found by an implantable cardiac monitor and 4 by pacemaker or defibrillator. Discussion: The rate of long-term AF detection after CRAO was high in patients with implanted cardiac devices, and appears comparable with rates seen after cryptogenic ischemic stroke and in other high-risk populations. Our findings warrant future prospective studies not limited by selection bias.

Background: White matter hyperintensity (WMH), also known as leukoaraiosis, is commonly visualized as abnormal T2 signal in the deep and subcortical white matter on Magnetic Resonance Imaging (MRI). It is also commonly associated with aging, diabetes, hypertension and cerebrovascular disease. The Fazekas (F) scoring system is a subjective tool commonly used to assess WMH, but no volumetric analysis has been published showing how the scores correspond to true quantities of white matter disease. Methods: MRIs performed on inpatients and outpatients at our tertiary care institution between 2015 and 2017 were reviewed and their relative WMH was scored by one author trained in using the Fazekas scale. Using 3D Slicer 4.9, manual segmentations of WMH were completed and a 3D model was created to quantify the amount of WMH. Univariate analysis and ANOVA tests were run to determine the association of each Fazekas score with volume of WMH. Results: Among the 198 patients in our study (53% female), 163 had WMH (F1 n=66, F2 n=49, F3 n=48). Ranges of WMH in each group were 0.1-8.3 mL in Fazekas 1 (mean = 3.7, SD = 2.3), 6.0-17.7 mL in Fazekas 2 (mean = 10.8, SD = 3.1), and 14.2-77.2 mL in Fazekas 3 (mean = 35.2, SD = 17.9); if 11 outliers above 50 mL were excluded, the range for Fazekas 3 was 14.2-47.0 mL (mean = 27.1, SD = 8.9). When comparing data between groups, both the comparison between F1+2 (t-value = 14.1, p Conclusion: When accurately trained in assigning Fazekas scores to patient’s WMH, each of the scores appears to represent an approximate range of distinct volumes for WMH. Studies have shown that the presence and extent of WMH is a predictor for future development of stroke. These results should be validated in subsequent studies.

Background: Intracerebral hemorrhage (ICH) often carries cardiac implications, and serum troponin has been suggested as a predictive biomarker for patients with ICH and other stroke subtypes. We aimed to determine whether previously described associations between troponin and worse outcomes in ICH patients varied based on the presence of atrial fibrillation (AF). Methods: We performed a single-center cohort study using data from consecutive ICH patients admitted over 12 months. ICH characteristics and 3-month outcomes were prospectively collected, while admission troponin levels were retrospectively abstracted. We performed ordinal and binary logistic regression to determine associations between elevated troponins (>0.05 ng/mL) and 3-month outcomes (using the modified Rankin Scale [mRS]), with multivariable models adjusted for relevant demographics, ICH severity, and comorbidities including AF, anticoagulation use, coronary artery disease (CAD), and chronic kidney disease (CKD). An interaction variable combining elevated troponin and AF was also included in our models. Results: Of 261 ICH patients with troponin measured on admission, 17% (n=44) had elevated troponins. Patients with elevated troponins were not significantly older than patients with normal troponin levels (mean age 74.8±13.6 vs. 70.4±15.4, p=0.08), but were more likely to have AF (36% vs. 21%, p=0.03), CAD (32% vs. 15%, p=0.007), and CKD (16% vs. 5%, p=0.006); ICH size, location, and other predictors were not significantly different between groups. In adjusted models, neither elevated troponin nor AF were independently associated with worse outcomes. However, the interaction between the two was significant (p=0.003), and the presence of elevated admission troponin in the context of AF was significantly associated with worse outcomes (ordinal: common OR 9.8 [95% CI 2.0-47.8]; binary (mRS 4-6): OR 14.4 [95% CI 1.9-106.4]). Conclusions: Troponin may be a useful predictive biomarker in ICH patients with underlying AF, potentially signaling higher levels of cardiac and systemic stress in patients with lower cardiac reserve.

Introduction: The detection of atrial fibrillation (AF) is a crucial component of ischemic stroke secondary prevention. Inpatient cardiac telemetry is part of the structured inpatient workup for ischemic stroke but the yield of telemetry is unknown when ipsilateral, hemodynamically-significant large artery atherosclerosis is identified at the time of initial presentation. Methods: We performed a single-center, retrospective, cohort study utilizing data from an institutional quality improvement database. We identified consecutive patients with acute ischemic stroke presenting between July 2015 and September 2017. We included patients with hemodynamically-significant (>50%) large artery stenosis in the arterial territory subserving the region of infarct. We excluded patients with a known history of AF. We determined the yield of an electrocardiogram, inpatient telemetry and outpatient cardiac event monitoring in detecting new AF. Groups with and without AF were compared using unpaired student’s T-test for continuous variables and Chi 2 test for categorical variables. Results: We identified 1435 patients presenting to our institution during the study period of whom 209 (14.6%) met inclusion criteria. Patients were aged 69.37±12.6 years and 33% were female. Of these patients, 19 (9.1%) were found to have new AF during their hospitalization and a further 2 (1%) were found to have AF on extended cardiac monitoring. Thirty seven patients had 30-day cardiac monitoring performed after hospitalization and the yield on this was 5.4% for the detection of AF. Patients with AF were older (76.29±11.31 years vs. 68.60±12.58 years, p=0.008) and had higher rates of hypertension (94% vs. 75%, p=0.04) and hyperlipidemia (72% vs. 52%, p=0.09). In all patients, anticoagulation was planned after the discovery of AF. Discussion: Inpatient cardiac telemetry detects new atrial fibrillation in 9.1% of patients known to have hemodynamically-significant large artery disease at the time of initial presentation. The yield of further outpatient cardiac monitoring is lower (5%). This hypothesis-generating study is limited by its retrospective nature and the potential for selection bias.

Background: Predictors of alteplase associated symptomatic intracranial hemorrhage (sICH) have been identified but there are very limited data on predictors of delayed sICH (> 24 hours from infusion). We hypothesize that asymptomatic hemorrhage on 24 hour brain imaging predicts delayed sICH and that delaying antithrombotic treatment in these patients reduces this risk. Methods: This is a retrospective analysis of a prospective quality improvement database of a comprehensive stroke center. We included all patients with a discharge diagnosis of ischemic stroke who received alteplase. Patients with sICH occurring within 24 hours from alteplase and those whose code status was changed to comfort measures only were excluded. Delayed sICH was defined as any hemorrhage causing neurological deterioration. We compared baseline characteristics, asymptomatic hemorrhage on 24 hour brain imaging, and median time to initiating antithrombotic therapy between patients with and without delayed sICH. Results: Among 606 patients who met our inclusion criteria; mean age was 70 years and 52% were men; 23.8% had asymptomatic hemorrhage on 24 hour brain imaging (CT or MRI) and 12 patients (2%) had delayed sICH. Aspirin was the most common initial antithrombotic (91.2%) followed by plavix (2.6%), and others (3.8%). After adjusting for confounders, asymptomatic hemorrhage on 24 hour brain imaging was associated with increased odds of delayed sICH (OR 5.5, 95% CI 1.52 - 19.87, p = 0.009) but the median time (days) to starting antithrombotic therapy did not differ between those with asymptomatic hemorrhage who developed delayed sICH vs. those who did not [2 (3) vs. 3 (5), p = 0.447). Conclusion: Delayed sICH in patients receiving alteplase is uncommon and asymptomatic hemorrhage is a strong predictor. Delaying initiation of antithrombotic treatment in patients with asymptomatic hemorrhage on 24 hour imaging was not associated with reduced delayed sICH risk. It is possible that other factors such as reperfusion and blood brain barrier disruption are more important determinants of delayed sICH risk as opposed to timing of antithrombotic therapy initiation.

ObjectiveTo determine the impact of delirium on withdrawal of life-sustaining treatment (WLST) after intracerebral hemorrhage (ICH) in the context of established predictors of poor outcome, using data from an institutional ICH registry.MethodsWe performed a single-center cohort study on consecutive patients with ICH admitted over 12 months. ICH features were prospectively adjudicated, and WLST and corresponding hospital day were recorded retrospectively. Patients were categorized using DSM-5 criteria as never delirious, ever delirious (either on admission or later during hospitalization), or persistently comatose. We determined the impact of delirium on WLST using Cox regression models adjusted for demographics and ICH predictors (including Glasgow Coma Scale score), then used logistic regression with receiver operating characteristic curve analysis to compare the accuracy of ICH score–based models with and without delirium category in predicting WLST.ResultsOf 311 patients (mean age 70.6 ± 15.6, median ICH score 1 [interquartile range 1–2]), 50% had delirium. WLST occurred in 26%, and median time to WLST was 1 day (0–6). WLST was more frequent in patients who developed delirium (adjusted hazard ratio 8.9 [95% confidence interval (CI) 2.1–37.6]), with high rates of WLST in both early (occurring ≤24 hours from admission) and later delirium groups. An ICH score-based model was strongly predictive of WLST (area under the curve [AUC] 0.902 [95% CI 0.863–0.941]), and the addition of delirium category further improved the model's accuracy (AUC 0.936 [95% CI 0.909–0.962], p = 0.004).ConclusionDelirium is associated with WLST after ICH regardless of when it occurs. Further study on the impact of delirium on clinician and surrogate decision-making is warranted.

Background Many factors may potentially complicate the stroke recovery process, including persistently impaired level of consciousness (LOC)—whether from residual stroke effects or from superimposed delirium. We aimed to determine the degree to which impaired LOC at hospital discharge is associated with outcomes after ischemic stroke. Methods We conducted a single-center retrospective cohort study using prospectively-collected data from 2015 to 2017, collecting total NIHSS-LOC score at discharge as well as subscores for responsiveness (LOC-R), orientation questions (LOC-Q), and command-following (LOC-C). We determined associations between LOC scores and 3-month outcome using logistic regression, with discharge location (skilled nursing facility [SNF] vs. inpatient rehabilitation) representing a pre-specified secondary outcome. Results We identified 1003 consecutive patients with ischemic stroke who survived to discharge, of whom 32% had any LOC score > 0. Total LOC score at discharge was associated with unfavorable 3-month outcome (OR 4.9 [95% CI 2.4–9.8] for LOC = 1; OR 8.0 [2.7–23.9] for LOC = 2–3; OR 6.3 [2.1–18.5] for LOC = 4–5; all patients with LOC = 6–7 had poor outcomes), as were subscores for LOC-R (OR 5.3 [1.3–21.2] for LOC-R = 1; all patients with LOC-R = 2–3 had poor outcomes) and LOC-Q (OR 4.1 [2.1–8.3] for LOC-Q = 1; OR 4.9 [1.8–13.5] for LOC-Q = 2). Total LOC score (OR 2.6 [1.3–5.3] for LOC = 1; OR 3.1 [1.2–8.2] for LOC = 2–3) and LOC-Q (OR 3.3 [1.6–6.6] for LOC-Q = 1; OR 3.4 [1.3–9.0] for LOC-Q = 2) were also associated with discharge to SNF rather than to inpatient rehabilitation. Conclusions The presence of impaired consciousness or disorientation at discharge is associated with markedly worse outcomes after ischemic stroke. Further studies are necessary to determine the separate effects of residual stroke-related LOC changes and those caused by superimposed delirium.

Background and Purpose— We sought to determine the long-term risk of seizures after stroke according to age, sex, race, and stroke subtype. Methods— We performed a retrospective cohort study using administrative claims from 2 complementary patient data sets. First, we analyzed data from all emergency department visits and hospitalizations in California, Florida, and New York from 2005 to 2013. Second, we evaluated inpatient and outpatient claims from a nationally representative 5% random sample of Medicare beneficiaries. Our cohort consisted of all adults at the time of acute stroke hospitalization without a prior history of seizures. Our outcome was seizure occurring after hospital discharge for stroke. Poisson regression and demographic data were used to calculate age-, sex-, and race-standardized incidence rate ratios (IRR). Results— Among 777 276 patients in the multistate cohort, the annual incidence of seizures was 1.68% (95% confidence interval [CI], 1.67%–1.70%) after stroke versus 0.15% (95% CI, 0.15%–0.15%) among the general population (IRR, 7.3; 95% CI, 7.3–7.4). By 8 years, the cumulative rate of any emergency department visit or hospitalization for seizure was 9.27% (95% CI, 9.16%–9.38%) after stroke versus 1.21% (95% CI, 1.21%–1.22%) in the general population. Stroke was more strongly associated with a subsequent seizure among patients Conclusions— Almost 10% of patients with stroke will develop seizures within a decade. Hemorrhagic stroke, nonwhite race, and younger age seem to confer the greatest risk of developing seizures.

BACKGROUND: Agitation is common after subarachnoid hemorrhage (SAH) and may be independently associated with outcomes. We sought to determine whether the duration of agitation and fluctuating consciousness were also associated with outcomes in patients with SAH. METHODS: We identified all patients with positive Richmond Agitation Sedation Scale (RASS) scores from a prospective observational cohort of patients with SAH from 2011–2015. Total duration of agitation was extrapolated for each patient using available RASS scores, and 24-hour mean and standard deviation (SD) of RASS scores were calculated for each patient. We also calculated each patient’s duration of substantial fluctuation of consciousness, defined as the number of days with 24-hour RASS SD >1. Patients were stratified by 3-month outcome using the modified Rankin Scale (mRS), and associations with outcome were assessed via logistic regression. RESULTS: There were 98 patients with at least one positive RASS score, with median total duration of agitation 8 hours (interquartile range [IQR] 4–18), and median duration of substantially fluctuating consciousness 2 days (IQR 1–3). Unfavorable 3-month outcome was significantly associated with a longer duration of fluctuating consciousness (odds ratio [OR] per day, 1.51; 95% confidence interval [CI], 1.04–2.20; p=0.031), but a briefer duration of agitation (OR per hour, 0.94; 95% CI, 0.89–0.99; p=0.031). CONCLUSION: Though a longer duration of fluctuating consciousness was associated with worse outcomes in our cohort, total duration of agitation was not, and may have had the opposite effect. Our findings should therefore challenge the intensity with which agitation is often treated in SAH patients.

Background and Purpose— Elevated cardiac troponin is a marker of cardiac disease and has been recently shown to be associated with embolic stroke risk. We hypothesize that early elevated troponin levels in the acute stroke setting are more prevalent in patients with embolic stroke subtypes (cardioembolic and embolic stroke of unknown source) as opposed to noncardioembolic subtypes (large-vessel disease, small-vessel disease, and other). Methods— We abstracted data from our prospective ischemic stroke database and included all patients with ischemic stroke during an 18-month period. Per our laboratory, we defined positive troponin as ≥0.1 ng/mL and intermediate as ≥0.06 ng/mL and Results— We identified 1234 patients, of whom 1129 had admission troponin levels available; 10.0% (113/1129) of these had a positive troponin. In fully adjusted models, there was an association between troponin positivity and embolic stroke of unknown source subtype (adjusted odds ratio, 4.46; 95% confidence interval, 1.03–7.97; P =0.003) and cardioembolic stroke subtype (odds ratio, 5.00; 95% confidence interval, 1.83–13.63; P =0.002). Conclusions— We found that early positive troponin after ischemic stroke may be independently associated with a cardiac embolic source. Future studies are needed to confirm our findings using high-sensitivity troponin assays and to test optimal secondary prevention strategies in patients with embolic stroke of unknown source and positive troponin.

Background and Purpose— Protease/antiprotease imbalance is implicated in the pathogenesis of emphysema and may also lead to vessel wall weakening, aneurysm development, and rupture. However, it is unclear whether emphysema is associated with cerebral and aortic aneurysm rupture. Methods— We performed a retrospective cohort study using outpatient and inpatient claims data from 2008 to 2014 from a nationally representative sample of Medicare beneficiaries ≥66 years of age. Our predictor variable was emphysema, and our outcome was hospitalization for either aneurysmal subarachnoid hemorrhage or a ruptured aortic aneurysm. All predictors and outcomes were defined using previously reported International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code algorithms. Survival statistics and Cox regression were used to compare risk between patients with and without emphysema. Results— We identified 1 670 915 patients, of whom 133 972 had a diagnosis of emphysema. During a mean follow-up period of 4.3 (±1.9) years, we identified 4835 cases of aneurysm rupture, 433 of which occurred in patients with emphysema. The annual incidence of aneurysm rupture was 6.5 (95% CI, 6.4–6.8) per 10 000 in patients without emphysema and 14.6 (95% CI, 13.3–16.0) per 10 000 in patients with emphysema. After adjustment for demographics and known risk factors for aneurysmal disease, emphysema was independently associated with aneurysm rupture (hazard ratio, 1.7; 95% CI, 1.5–1.9). Emphysema was associated with both aneurysmal subarachnoid hemorrhage (hazard ratio, 1.5; 95% CI, 1.3–1.7) and ruptured aortic aneurysm (hazard ratio, 2.3; 95% CI, 1.9–2.8). Conclusions— Patients with emphysema face an increased risk of developing subarachnoid hemorrhage and aortic aneurysm rupture, potentially consistent with shared pathways in pathogenesis.

Objectives Routine implementation of protocol-driven stroke “codes” results in timelier and more effective acute stroke management. However, it is unclear if patient demographics contribute to disparities in stroke code activation. We aimed to explore these demographic factors in a retrospective cohort study of patients with intracerebral hemorrhage (ICH). Materials and Methods We identified consecutive patients with non-traumatic ICH who presented directly to our Comprehensive Stroke Center over 2 years and collected data on demographics, clinical features, and stroke code activation. We used multivariable logistic regression to examine differences in stroke code activation based on patient demographics while adjusting for initial clinical features (NIH Stroke Scale, FAST [facial drooping, arm weakness, speech difficulties] vs. non-FAST symptoms, time from last-known-well [LKW], and systolic blood pressure [SBP]). Results Among 265 patients, 68% (n=179) had a stroke code activation. Stroke codes occurred less frequently in women (62%) than men (72%) and in non-white (57%) vs. white patients (70%). Non-stroke code patients were less likely to have FAST symptoms (37% vs. 87%) and had lower initial SBP (mean±SD 159.3±34.2 vs. 176.0±31.9 mmHg) than stroke code patients. In our primary multivariable models, neither age nor race were associated with stroke code activation. However, women were significantly less likely to have stroke codes than men (OR 0.49 [95% CI 0.24-0.98]), as were non-FAST symptoms (OR 0.11 [95% CI 0.05-0.22]). Conclusions Our data suggest gender disparities in emergency stroke care that should prompt further investigations into potential systemic biases. Increased awareness of atypical stroke symptoms is also warranted.

This cross-sectional study characterizes prehospital large vessel occlusion transport algorithms across the US.

Objectives Hunt and Hess (HH) and World Federation of Neurological Surgeons (WFNS) grades are commonly used to report clinical severity of aneurysmal subarachnoid hemorrhage (aSAH). We sought to determine the impact of early neurological changes and the timing of clinical grade assignment on the prognostication accuracy. Methods We retrospectively reviewed a cohort of consecutive patients with aSAH who were admitted to an academic center. Patients with confirmed aneurysmal cause were included. Relevant clinical data including daily clinical grades, imaging data and functional outcome were analyzed. Favorable outcome was defined as mRS 0 to 3. Early neurological improvement (ENI) and early neurological deterioration (END) were respectively defined as any improvement or deterioration of HH grades from hospital day 1 to the earliest time from hospital day 2 to 5. Results Of 310 patients, 24% experienced early neurological changes from hospital day 1 to 3. For each point increase in HH grades from day 1 to day 3, the odds ratio for worse outcome was 2.57 (95% CI [1.74-3.79]) and for each point decrease in HH grades from day 1 to day 3, the odds ratio for worse outcome was 0.28 (95% CI [0.17-0.47]). Receiver Operating Characteristic curve analysis revealed that clinical grades on day 3 had higher accuracy in predicting worse outcome than clinical grades on day 1. Conclusion Early changes in neurological status can alter trajectory of hospital course and functional outcome. The prognostic accuracy of the clinical grades from hospital day 3 is significantly greater than those on admission.