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Introduction: It is well established that reduced door-to-needle (DTN) time leads to improved outcomes in acute ischemic stroke. Rhode Island Hospital is a Comprehensive Stroke Center focused on improving outcomes by seeking novel methods to improve the DTN to below the institutional goal of a median of < 30 minutes. Methods: We sought to reduce DTN time by the following methods: 1) Addition of an electronic DTN Timer appearing in the Electronic Medical Record (EMR) to improve situational awareness of elapsed time in Code Strokes in real time (Figure). 2) Creation of a multidisciplinary Thrombolysis Focus Group to analyze data and improve processes. 3) Increased awareness of metric exclusion criteria and ease of processes for providers to document exclusions. 4) Concurrent review of each thrombolysis case with direct provider feedback and opportunity to appropriately document and clarify delays. 5) Creation of a thrombolysis Time-Out process. Results: The median DTN for the pre-implementation period of January 2020 to August 2021 was 40.3 minutes compared to 35.8 min for the post-implantation period of September 2021 to June 2022. Additionally, the percent of thrombolysis cases meeting the institutional goal of under 30 minutes improved from 22.6% to 29.8% percent (Figure) and when exclusions were applied, this percentage improved from 29.8% to 49.4% (Figure). Conclusion: Novel measures to reduce the DTN time in acute stroke thrombolysis can positively impact both the door-to-needle time and percent of cases under the institutional DTN time goal. Figure 1.

Recent studies have failed to reveal benefit of anticoagulation over antiplatelet therapy in the prevention of recurrent stroke in Embolic Stroke of Undetermined Source (ESUS) patients. This is attributed to significant heterogeneity in underlying mechanisms of ESUS. Atrial fibrillation (AF) is a potential cause of ESUS, and evaluating left atrial (LA) function by measuring LA strain by speckle tracking echocardiography (STE) is an emerging technique to assess LA biomechanics. Our study investigates the relationship between LA strain and AF detection in ESUS patients. We included hospitalized patients with ESUS subtype who underwent STE. LA function by assessing three phases of LA strain (reservoir, conduit and contractile) were retrospectively quantified and evaluated. Several patients were discharged with mobile cardiac telemetry that was retrospectively reviewed for AF detection. Descriptive statistical methods and both unadjusted and adjusted regression models were used. Among 325 ESUS patients, mean age was 66.5±15.0, 49% were male, 49% had outpatient cardiac monitoring, and 25% had AF detected. LA reservoir (25.17±13.4 vs 32.43±18.13), LA contractile (11.95±9.66 vs 16.67±10.94) and LA conduit (13.08±6.47 vs 17.20±12.21) strains were significantly lower in patients with AF detected compared to patients without AF detected. In the unadjusted binary logistic regression analysis, patients with AF detected had significantly lower LA reservoir (OR 0.967, 95% CI 0.941-0.994), LA contractile (OR 0.957, 95% CI 0.918-0.997) and LA conduit (OR 0.961, 95% CI 0.925-0.998) strains. This significance was lost after adjusting for age. Our study demonstrates that reduced LA strain is associated with subsequent detection of AF in ESUS patients. We believe that routine LA strain measurement can aid clinicians in identifying ESUS patients with high AF prevalence and thereby appropriately target patients for anticoagulation therapy to prevent subsequent strokes.

Introduction: Prior systematic reviews have focused on a comparison of efficacy endpoints between tenecteplase (TNK) and alteplase. The objectives of this study are to determine whether the rate of treatment complications differs between patients treated with the two agents. Methods: This systematic review (CRD42022303835) was performed according to PRISMA guidelines. We included prospective, interventional studies and prospective and retrospective observational studies. We searched MEDLINE, the Cochrane Central Register of Controlled Trials, Embase, Web of Science and the ClinicalTrials.gov registry from inception through June 3 rd 2022. The primary endpoint was symptomatic intracranial hemorrhage (sICH) and secondary endpoints included any ICH, mortality, angioedema, gastrointestinal hemorrhage and other extracranial hemorrhage. We performed separate random effects meta analyses for each endpoint. Evidence was synthesized as relative risks, comparing subjects exposed to TNK versus alteplase as well as absolute risks in those treated with TNK. Results: Of 2,226 records identified, 26 were eligible for inclusion including 7,921 patients. Seventeen studies included alteplase as a comparator group and 10 were non-comparative. The relative risk of sICH in patients treated with TNK compared with alteplase was 0.93 (95% CI: 0.68-1.28). Across those treated with low, medium and high doses of TNK, the relative risks were 0.78 (95% CI: 0.22-2.82), 0.84 (95% CI: 0.58-1.20) and 2.31 (0.69-7.75) respectively. The unadjusted rate of sICH, including comparative and non-comparative studies, was 1%, 2% and 4% within the low, medium and high dose groups. Discussion: To-date, this is the most comprehensive systematic review examining relative complications of TNK and alteplase. The rate of treatment harms is broadly comparable between those treated with the two agents. We present evidence that the rate of sICH may be increased in those treated with higher doses of TNK.

Introduction: Embolic stroke of undetermined source (ESUS) is suspected to be primarily of cardioembolic origin with ongoing trials evaluating cardiac biomarkers to confirm or refute this theory. Presently, it is unclear whether left ventricular ejection fraction (LVEF) is a contributor to ESUS and whether LVEF influences identification of atrial fibrillation (AF) on mobile telemetry. We hypothesized that lower LVEF is associated with the ESUS stroke subtype and higher likelihood of capturing AF. Methods: We retrospectively obtained data through the Comprehensive Stroke Program at Rhode Island Hospital. Those included were adults diagnosed with ESUS on discharge defined as an emboliform ischemic infarct, LVEF >30%, no ipsilateral stenoses > 50%, and cardiac telemetry for at least two weeks without contributory dysrhythmia. Data was compared with a non-cardioembolic (NCE) ischemic stroke population. A transthoracic echocardiogram was performed while hospitalized and interpreted by a cardiologist. A subset of those with ESUS completed cardiac monitoring whose data was retrospectively reviewed. LVEF was categorized as 30 - 54%, 55 - 65%, and > 65%. Standard descriptive and logistic regression analyses adjusted for age were used for statistical interpretation. Results: We identified 677 participants (ESUS: 324, NCE: 353); mean age was 66 years and 55% were male. In adjusted models, there was an association between ESUS subtype and LVEF 30 - 54% (vs. LVEF >65%) OR 2.51, 95%CI 1.27 - 4.95, p = 0.008 and LVEF 55 - 65% (vs. LVEF > 65%) OR 1.38, 95%CI 0.97 - 1.97, p = 0.077. With LVEF treated as a continuous variable, every 5% increase in LVEF lowered the likelihood of an ESUS subtype diagnosis (OR 0.85 95% CI 0.76-0.94 p=0.002). Those with a LVEF of 30 - 54% or LVEF > 65% had a lower rate of AF detection than patients with LVEF 55 - 65% (OR 0.37, 95%CI 0.16 - 0.85, p = 0.019) on prolonged monitoring. Conclusions: ESUS subtype was more common with lower LVEF. AF detection was lower amongst the lowest and highest LVEF ESUS subtype groups. This suggests that both LVEF and AF separately contribute to ESUS. Studies are needed to confirm our findings and improve stroke prevention strategies in patients with low LVEF and ESUS.

Introduction: Anticoagulation therapy are commonly interrupted in patients with atrial fibrillation (AF) for elective procedures. However, risk factors of subsequent stroke during the periprocedural period is uncertain. We performed a nationwide analysis to evaluate risk factors for acute ischemic stroke (AIS) readmission in patients with AF admitted for elective procedure. Methods: Using the Healthcare Cost and Utilization Project (HCUP) Nationwide Readmission Database, we included electively admitted adult patients, who had AF diagnosis and procedural Diagnosis-related group code from 2016 to 2019. AF, AIS and other diagnosis were identified based on standard ICD-10 CM codes. Patients who had history of stroke or stroke during the index admission were excluded. We constructed a Cox regression model to determine hazard ratios (HR) of demographic, clinical factors and procedural type associated with AIS readmission. Results: Of the 1,048,422 patients with AF admitted for elective procedure, the mean age was 71.5 and 39.1% were female, and 1625 (0.15%) had AIS readmission within 30 days of discharge. In the adjusted Cox regression model, age (adjusted HR 1.05, 95% CI 1.04-1.06, P < 0.001), female sex (aHR 1.22, 95% CI 1.05-1.41, P = 0.009), cancer (aHR 1.45, 95% CI 1.89-1.76, P < 0.001), congestive heart failure (aHR 1.22, 95% CI 1.03-1.44, P = 0.021), diabetes (aHR 1.33, 95% CI 1.14-1.55, P < 0.001), neurological surgery (aHR 2.27, 95% CI 1.69-3.06, P < 0.001), cardiovascular surgery (aHR 1.59, 95% CI 1.32-1.91, P < 0.001). Furthermore, higher CHADS 2 VASC 2 score (aHR 1.29 by one point, 95% CI 1.22-1.37, P < 0.001) were associated with AIS readmission. Conclusion: AF patients with higher CHADS 2 VASC 2 score and those undergoing cardiac or neurological surgeries are at higher risk of perioperative stroke. Studies are needed to tailor anticoagulation management during the perioperative time to reduce perioperative AIS risk in such patients.

Introduction: Small subcortical infarcts, synonymous in the literature with lacunar or small vessel disease infarcts, occur in roughly a quarter of all ischemic stroke. While the use of alteplase and other thrombolytics is well known to improve outcomes for acute ischemic stroke, the role of thrombolytics in the acute management of this infarct subtype is not entirely proven. We hypothesized that the use of alteplase in the hyperacute management of small vessel infarcts improved long-term outcomes. Methods: We performed a post-hoc analysis of the Stroke Hyperglycemia Insulin Network Effort (SHINE) dataset. We included only those with an etiologic diagnosis of lacunar stroke. The primary exposure was guideline-based administration of alteplase. The primary outcome was 90-day functional outcome by mRS 0 - 2 (good) versus 3 - 6 (poor). Insulin treatment arms were combined as no differential treatment effect was demonstrated in the original SHINE publication. Standard descriptive and logistic regression analysis, adjusted for age, arrival blood glucose, and NIH Stroke Scale, were used for data interpretation. Results: We included 258 SHINE participants who were diagnosed with a lacunar infarct: mean age 65 ± 13 years, 53% (138/258) were men, and 57.7% (150/258) received alteplase. Demographic data including age, sex, and presenting variables including NIH Stroke Scale score, systolic blood pressure, and blood glucose levels did not differ between those who received alteplase and those who did not. Those who received alteplase were more likely to be within the good outcome group (OR 1.89, 95%CI 1.03 - 3.47, p = 0.039). Conclusion: The administration of intravenous alteplase for reported lacunar stroke increased the likelihood of a good outcome by nearly 2-fold. Lacunar infarcts, a radiographic outcome of small subcortical infarcts, are unique in pathogenesis compared to cardioembolic and large-artery atheromatous disease. Despite these differences, our findings support the use of acute thrombolytic therapy within this patient population. Future studies are needed to assess the response between small subcortical infarcts subtypes (e.g. branch atheromatous disease, subcortical microembolism, lipohyalinosis) and acute reperfusion therapy.

Introduction: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is hallmarked by a mutation in the NOTCH3 receptor resulting in impaired cerebrovascular autoregulation with subsequent vessel fragility and progressive accumulation of cerebral small vessel disease (CSVD). Antiplatelet medications are commonly prescribed for secondary stroke prevention though this is of unknown therapeutic benefit in preventing acute ischemic stroke (AIS). We aimed to identify whether antiplatelet therapy reduced incidence of AIS in those with reported CADASIL. Methods: Data was collected through the TriNetX Research Network database. Those included were adults with the ICD-10 code (I67.850) for CADASIL. The primary outcome was the validated ICD-10 code for AIS (I63) which were linked with hospital admission encounters. Demographic data and medication use was recorded. The primary exposure was use of an antiplatelet medication for at least 1 month prior to admission for AIS. Standard descriptive and regression analyses were used. Results: Our cohort included 455 individuals: mean age 57±14 years, 36% being female and with similar rates of vascular risk factors between the groups. The antiplatelet cohort was older (antiplatelet: 61 ± 12 yrs vs. unexposed: 57±14 yrs, p = 0.034) and included 40 (8.8%) participants. Rate of AIS trended higher in the antiplatelet group but was not significantly different (antiplatelet: 23%, 9/40 vs. unexposed: 14%, 60/415; p=0.18). Age adjusted logistic regression showed higher odds of AIS (OR 1.62, 95%CI 0.73 - 3.60, p = 0.23). Conclusions: In this hypothesis generating study, our data suggests that antiplatelet use did not significantly impact incidence of AIS. It is unclear if the likelihood findings are related to the natural history of the disease, though this model accounted for differences in age. Further studies are needed to improve power for robust statistical analysis to confirm or refute our findings.

Background: Intracranial arterial stenosis (ICAS) can cause stroke by different mechanisms: perforator disease, artery to artery embolism, and impaired flow. There is limited data exists on the utility of perfusion imaging in patients with ICAS. We aim to determine associations between perfusion delay volume and 90-day recurrence in patients with anterior circulation ICAS. Methods: This is a two-center study of symptomatic anterior circulation ICAS involving the left M1 or ICA who underwent perfusion imaging (MRP or CTP). The primary predictor was hypoperfusion mismatch volume HPV (T max delay volume - core volume) using Tmax>4 sec or Tmax>6 sec thresholds. The outcome was recurrent cerebrovascular events (RCVE) defined as new or worsening neurological symptoms due to confirmed or suspected new infarct or infarct extension. We used Youden’s index to define the optimal cut-point of Tmax4 and Tmax6 mismatch for predicting recurrent stroke. We fit time-to-event models for RCVE with HPV at dichotomized cut-points, both as a univariate analysis and after adjusting for co-variates. Results: 50 patients met the inclusion criteria and 30% had RCVE. The median T max 4 HPV in mL was higher in patients with vs. without RCVE (121 vs. 19, p < 0.001) and the median T max 6 HPV in mL was higher in patients with vs. without RCVE (33 vs. 0, p = 0.004). We found an association between Tmax> 4 sec hypoperfusion volume (AUC 0.79, p =0.012) and max>6 sec hypoperfusion volume (AUC 0.75, p = 0.008) with RCVE. For Tmax 4 the cut-point was at 94 mL and for Tmax6 the cut-point was at 10 mL. Recurrent stroke was higher in those with vs. without Tmax>4 sec ≥94 mL delay (66.7% vs. 14.3%, (p6 sec≥10 mL delay (68.8% vs. 11.8%, p4 sec HPV ≥ 94 mL was 5.0 (95% CI 1.5-16.4) and that of Tmax>6 sec HPV > 8 ml was 11.3 (95% CI 3.7-116.8). Conclusion: In this two-center study, hypoperfusion delay volume is associated with early recurrence in patients with symptomatic ICAS. Studies are needed to validate our findings and to test endovascular reperfusion in the subset of patients with symptomatic ICAS and perfusion delay.

Background: Two early basilar artery occlusion (BAO) randomized controlled trials did not establish superiority of endovascular thrombectomy (EVT) over medical management. While many providers continue to recommend EVT for acute BAO, perceptions of equipoise in randomizing patients with BAO to medical management may differ between clinician specialties. Methods: We conducted an international survey (1/1/22-3/31/22) regarding management strategies in acute BAO prior to the announcement of 2 trials indicating superiority of EVT, and compared responses between interventionalists (INT) and non-interventionalists (nINT). Selection practices for routine EVT based on neuroimaging and clinical features were compared between the two groups using descriptive statistics. Results: Among the 1245 respondents (nINT=702), INT more commonly believed that EVT was superior to medical management in acute BAO (98.5% vs. 95.1%, p0.05), although nINT more commonly preferred perfusion imaging (24.2% vs. 19.7%, p=0.04). Among respondents who indicated they would randomize to medical management, INT were more likely to randomize when the NIHSS was ≥10 (15.9% vs. 6.9%, p Conclusions: Following the publication of two neutral clinical trials in BAO EVT, most stroke providers believed EVT to be superior to medical management in carefully selected patients, with most indicating they would not randomize a patient to medical treatment. There were small differences in preference of advanced neuroimaging, although these preferences were unsupported by clinical trial data.

Introduction: Cervical artery dissection (CAD) is a common cause of stroke in the young and carries a high risk of early recurrence. We aim to compare the characteristics of patients from a real-world cohort to those from prior randomized controlled trials. Methods: We pooled data from consecutive patients with a diagnosis of spontaneous CAD treated at a comprehensive stroke center who were followed for at least 90 days. We excluded patients with traumatic dissection and those with primary intracranial hemorrhage in the setting of trauma or dissection. We compared the baseline characteristics and stroke recurrence rates in our cohort to the TREAT-CAD (2021) and CADISS (2019) trials. We report recurrence rates in patients treated with single antiplatelet (SAPT), dual antiplatelet (DAPT), and anticoagulation (AC). Results: 80 patients with CAD met our inclusion criteria. Our study sample characteristics differ from TREAT-CAD and CADISS, with our cohort more likely to have hypertension and diabetes but less likely to have a smoking history. The rate of recurrent stroke at 90 days was numerically higher in our patient cohort (6.3%) compared to TREAT-CAD (3.6%) and CADISS (1.6%). The rates of recurrent stroke were 8.6% (3/35) with SAPT, 4.2% (1/24) with DAPT, and 5% (1/20) with AC strategies. Conclusions: Characteristics of a real-world CAD population differ from those enrolled in clinical trials with an overall higher rate of recurrent stroke but comparable rates among patients treated with DAPT and AC. The ongoing STOP-CAD study will compare DAPT to AC with a substantially larger number of patients, with an estimated projection of at least 3000 patients in a multi-center international cohort.

Introduction: Previous studies have failed to show an interaction between known atrial fibrillation (AF) and treatment effect of endovascular thrombectomy (EVT) performed within 6 hours of time last known well. However, it is not known if these findings apply to patients treated beyond 6 hours. The objective of the present study is to determine if a known diagnosis of AF exhibits effect modification on the association between treatment (EVT vs. medical therapy) and outcomes in patients >6 hours from time last known well. Methods: We performed a post hoc analysis of the DEFUSE-3 trial investigating the functional outcomes in study participants stratified by AF status. Our primary endpoint was functional outcome as measured by the modified Rankin Scale (mRS) score. We constructed an ordinal logistic regression model to determine the association between EVT/medical therapy and mRS in subgroups by AF status. Secondary endpoints include functional independence (mRS 0-2 vs. 3-6), final infarct volume, sICH, and mortality, examined via binary logistic or linear regression. We fit treatment modality*AF interaction terms. Results: Among 182 participants, 62 had AF (34 randomized to EVT) and 120 did not have AF (58 randomized to EVT). Patients with AF were older (median: 76.5 vs 66.5), presented with a higher NIHSS (median: 17 vs 16), and received IV tPA less frequently (4.8% vs. 12.5%). In patients with AF, the odds of a one-point improvement in mRS in EVT vs. medical therapy were 4.56 (95% CI: 1.79-12.17), while in patients without AF, the odds were 2.42 (95% CI: 1.27-4.67). We found no significant interaction between AF and EVT for the primary or secondary endpoints. Conclusion: Our study did not show a significant interaction between AF status and EVT, with the caveat that the study may be underpowered to detect such an effect. The trend for greater treatment effect should be evaluated in larger studies.

Background: The proper imaging modality for use in the selection of patients for endovascular thrombectomy (EVT) presenting in the late window remains controversial, despite current guidelines advocating the use of advanced imaging in this population. We sought to understand if clinicians with different specialty training differ in their approach to patient selection for EVT in the late time window. Methods: We conducted an international survey of stroke and neurointerventional clinicians between January and May 2022 with questions focusing on imaging and treatment decisions of large vessel occlusion (LVO) patients presenting in the late window. Interventional neurologists, interventional neuroradiologists, and endovascular neurosurgeons were defined as interventionists whereas all other specialties were defined as non-interventionists. The non-interventionist group was defined by all other specialties of the respondents: stroke neurologist, neuroradiologist, emergency medicine physician, trainee (fellows and residents) and others. Results: Of 3000 invited to participate, 1506 (1027 non-interventionists, 478 interventionists, 1 declined to specify) physicians completed the study. Interventionist respondents were more likely to proceed directly to EVT (39.5% vs. 19.5%; p < 0.0001) compared to non-interventionist respondents in patients with favorable ASPECTS (Alberta Stroke Program Early CT Score). Despite no difference in access to advanced imaging, interventionists were more likely to prefer CT/CTA alone (34.8% vs. 21.0%) and less likely to prefer CT/CTA/CTP (39.1% vs. 52.4%) for patient selection (p < 0.0001). When faced with uncertainty, non-interventionists were more likely to follow clinical guidelines (45.1% vs. 30.2%) while interventionists were more likely to follow their assessment of evidence (38.7% vs. 27.0%) (p < 0.0001). Conclusion: Interventionists were less likely to use advanced imaging techniques in selecting LVO patients presenting in the late window and more likely to base their decisions on their assessment of evidence rather than published guidelines. These results reflect gaps between interventionists and non-interventionists reliance on clinical guidelines, the limits of available evidence, and clinician belief in the utility of advanced imaging.

© 2023 American Society of Neuroimaging., Background and purpose: Two early basilar artery occlusion (BAO) randomized controlled trials did not establish the superiority of endovascular thrombectomy (EVT) over medical management. While many providers continue to recommend EVT for acute BAO, perceptions of equipoise in randomizing patients with BAO to EVT versus medical management may differ between clinician specialties. Methods: We conducted an international survey (January 18, 2022 to March 31, 2022) regarding management strategies in acute BAO prior to the announcement of two trials indicating the superiority of EVT, and compared responses between interventionalists (INTs) and non-interventionalists (nINTs). Selection practices for routine EVT and perceptions of equipoise regarding randomizing to medical management based on neuroimaging and clinical features were compared between the two groups using descriptive statistics. Results: Among the 1245 respondents (nINTs = 702), INTs more commonly believed that EVT was superior to medical management in acute BAO (98.5% vs. 95.1%, p < .01). A similar proportion of INTs and nINTs responded that they would not randomize a patient with BAO to EVT (29.4% vs. 26.7%), or that they would only under specific clinical circumstances (p = .45). Among respondents who would recommend EVT for BAO, there was no difference in the maximum prestroke disability, minimum stroke severity, or infarct burden on computed tomography between the two groups (p > .05), although nINTs more commonly preferred perfusion imaging (24.2% vs. 19.7%, p = .04). Among respondents who indicated they would randomize to medical management, INTs were more likely to randomize when the National Institutes of Health Stroke Scale was ≥10 (15.9% vs. 6.9%, p < .01). Conclusions: Following the publication of two neutral clinical trials in BAO EVT, most stroke providers believed EVT to be superior to medical management in carefully selected patients, with most indicating they would not randomize a BAO patient to medical treatment. There were small differences in preference for advanced neuroimaging for patient selection, although these preferences were unsupported by clinical trial data at the time of the survey.

Background: The aim of this study was to determine the effect of smoking status on subsequent stroke risk in patients with minor ischemic stroke or TIA and to determine whether smoking modifies the effect of clopidogrel-based DAPT on subsequent stroke risk. Methods: This was a post-hoc analysis of the Platelet Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial, which had a 90-day follow-up period. We used multivariable Cox regression and subgroup interaction analysis to determine the effect of smoking on the risk of subsequent ischemic stroke and major hemorrhage, respectively. Results: Data from 4877 participants enrolled in the POINT trial were analyzed. Among these, 1004 were current smokers and 3873 were non-smokers at the time of index event. Smoking was associated with a non-significant trend toward an increased risk of subsequent ischemic stroke during follow up (adjusted HR, 1.31 (95% CI, 0.97–1.78), p = 0.076). The effect of clopidogrel on ischemic stroke did not differ between non-smokers (HR, 0.74 (95% CI, 0.56–0.98), p = 0.03) and smokers (HR, 0.63 (95% CI, 0.37–1.05), p = 0.078), p for interaction = 0.572. Similarly, the effect of clopidogrel on major hemorrhage did not differ between non-smokers (hazard ratio, 1.67 (95% CI, 0.40–7.00), p = 0.481) and smokers (HR, 2.59 (95% CI, 1.08–6.21), p = 0.032), p for interaction = 0.613. Conclusions: In this post-hoc analysis of the POINT trial we found that the effect of clopidogrel on reducing subsequent ischemic stroke as well as risk of major hemorrhage did not depend on smoking status, indicating that smokers benefit to a similar degree from DAPT as non-smokers.

Background: It is unknown if race/ethnicity modifies the response to blood pressure (BP) lowering treatment after intracerebral hemorrhage (ICH). We aimed to examine the race/ethnicity differences in the response to BP lowering treatment after ICH. Methods: This is a post hoc analysis of the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-2) trial. The primary outcome is good outcome, defined as 90-day modified Rankin Scale 0–3. The primary predictor is race/ethnicity for which we included non-Hispanic categories of White, Black, Asian, and the category of Hispanic. We fit adjusted logistic regression models with the predictor of race/ethnicity and models with the interaction term of treatment*race/ethnicity. Results: We included a total of 953 patients in our analysis (White = 213, Black = 112, Asian = 554, and Hispanic = 74). In the models with the interaction between race/ethnicity and treatment, we found that White patients assigned to the intensive treatment arm had lower predicted probability of good outcome than those assigned to the standard treatment arm (Model 1: 56.2% vs. 68.1%, p = .027; Model 2: 53.4% vs. 68.3%, p = .009). When divided into White and non-White groups, intensive treatment was associated with higher odds of serious adverse events in White group but not in the non-White group. In addition, there was an association between intensive treatment and higher risk of hematoma expansion in White patients and lower risk of hematoma expansion in non-White patients. Conclusions: In the ATACH-2, there was an interaction between race/ethnicity and response to BP lowering treatment after ICH, with White patients having an association between intensive blood pressure reduction and worse outcome.

Supplemental Digital Content is available in the text., In the spring of 2021, reports of rare and unusual venous thrombosis in association with the ChAdOx1 and Ad26.COV2.S adenovirus-based coronavirus vaccines led to a brief suspension of their use by several countries. Thromboses in the cerebral and splanchnic veins among patients vaccinated in the preceding 4 weeks were described in 17 patients out of 7.98 million recipients of the Ad26.COV2.S vaccine (with 3 fatalities related to cerebral vein thrombosis) and 169 cases of cerebral vein thrombosis among 35 million ChAdOx1 recipients. Events were associated with thrombocytopenia and anti-PF4 (antibodies directed against platelet factor 4), leading to the designation vaccine-induced immune thrombotic thrombocytopenia. Unlike the related heparin-induced thrombotic thrombocytopenia, with an estimated incidence of

Background and Aims: Although intravenous thrombolysis (IVT) represents standard-of-care treatment for acute ischemic stroke (AIS) in eligible adult patients, definitive evidence-based guidelines and randomized clinical trial data evaluating its safety and efficacy in the pediatric population remain absent from the literature. We aimed to evaluate the utilization and outcomes of IVT for the treatment of pediatric AIS using a large national registry. Methods: Weighted hospitalizations for pediatric (Results: Among 13,901 pediatric AIS patients, 270 (1.9%) were treated with IVT monotherapy (median age 12.8 years). IVT-treated patients developed any intracranial hemorrhage (ICH) at a rate of 5.6% (n = 15), and 71.9% (n = 194) experienced favorable functional outcomes at discharge (to home or to acute rehabilitation). Following propensity-score adjustment for age, acute stroke severity, infarct location, and etiological/comorbid conditions, IVT was not associated with an increased risk of any ICH (5.6% vs 5.4%, p = 0.931; adjusted odds ratio (aOR) = 1.01, 95% confidence interval (CI) = 0.48–2.14, p = 0.971), nor with favorable functional outcome (71.9% vs 74.5%, p = 0.489; aOR = 0.88, 95% CI = 0.60–1.29, p = 0.511) in comparison with other medical therapy. Conclusions: Twenty years of population-level data in the United States demonstrate that pediatric AIS patients treated with IVT experienced high rates of favorable outcomes without an increased risk of hemorrhagic transformation.

Anticoagulation substantially reduces the risk of stroke in patients with atrial fibrillation (AF). However, recent studies have shown that up to 22%–36% of patients on anticoagulation will suffer an ischaemic stroke (IS). In this narrative review, we provide an overview of risk factors, mechanisms, management of acute IS and strategies for secondary prevention for patients with AF with stroke despite oral anticoagulation. For this paper, we reviewed available literature from important studies (randomised clinical trials, meta-analyses, reviews and case series) on patients with IS despite anticoagulation. We focused on recent studies that examined safety and efficacy of acute stroke treatments and evaluation and management strategies for secondary prevention. The literature review suggests that patients with AF with IS despite anticoagulation are a heterogeneous group with several possible mechanisms, which may include reduced or non-adherence to anticoagulation, competing non-cardioembolic stroke aetiologies or cardioembolic mechanisms separate from AF. The identification of one or more possible mechanisms of stroke despite anticoagulation may allow for a more targeted and individualised approach for secondary prevention. There are limited data to guide management in such patients, and strategies to prevent recurrent strokes include strict risk factor control and therapies targeting the most likely stroke mechanism. In cases where AF is suspected to be the culprit, clinical trials are needed to test the safety and efficacy of left atrial appendage occlusion plus anticoagulation versus continued anticoagulation alone.

Background and Purpose: In patients with acute large vessel occlusion, the natural history of penumbral tissue based on perfusion time-to-maximum (T max ) delay is not well established in relation to late-window endovascular thrombectomy. In this study, we sought to evaluate penumbra consumption rates for T max delays in patients with large vessel occlusion evaluated between 6 and 16 hours from last known normal. Methods: This is a post hoc analysis of the DEFUSE 3 trial (The Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke), which included patients with an acute ischemic stroke due to anterior circulation occlusion within 6 to 16 hours of last known normal. The primary outcome is percentage penumbra consumption, defined as (24-hour magnetic resonance imaging infarct volume–baseline core infarct volume)/(T max 6 or 10 s volume–baseline core volume). We stratified the cohort into 4 categories based on treatment modality and Thrombolysis in Cerebral Infarction (TICI score; untreated, TICI 0-2a, TICI 2b, and TICI3) and calculated penumbral consumption rates in each category. Results: We included 141 patients, among whom 68 were untreated. In the untreated versus TICI 3 patients, a median (interquartile range) of 53.7% (21.2%–87.7%) versus 5.3% (1.1%–14.6%) of penumbral tissue was consumed based on T max >6 s ( P max >10 s, we saw a difference of 165.4% (interquartile range, 56.1%–479.8%) versus 25.7% (interquartile range, 3.2%–72.1%; P max >6 s ( P =0.52) or T max >10 s ( P =0.92). Conclusions: Among extended window endovascular thrombectomy patients, T max >10-s mismatch volume may comprise large volumes of salvageable tissue, whereas nearly half the T max >6-s mismatch volume may remain viable in untreated patients at 24 hours.

Background and Purpose: The National Institutes of Health Stroke Scale (NIHSS) measured at an early time point is an appealing surrogate marker for long-term functional outcome of stroke patients treated with endovascular therapy. However, definitions and analytical methods for an early NIHSS-based outcome measure that optimize power and precision in clinical studies are not well-established. Methods: In this post-hoc analysis of our prospective observational study that enrolled endovascular therapy-treated patients at 12 comprehensive stroke centers across the US, we compared the ability of 24-hour NIHSS, ΔNIHSS (baseline minus 24-hour NIHSS), and percentage change (NIHSS×100/baseline NIHSS), analyzed as continuous and dichotomous measures, to predict 90-day modified Rankin Scale (mRS) using logistic regression (adjusted for age, baseline NIHSS, glucose, hypertension, Alberta Stroke Program Early CT Score, time to recanalization, recanalization status, and intravenous thrombolysis) and Spearman ρ. Results: Of 485 patients in the BEST (Blood Pressure After Endovascular Stroke Therapy) cohort, 446 (92%) with 90-day follow-up data were included. An absolute 24-hour NIHSS, adjusted for baseline in multivariable modeling, had the highest predictive power of all definitions evaluated (aR 2 0.368 and adjusted odds ratio 0.79 [0.75–0.84], P 2 0.444 and adjusted odds ratio 0.84 [0.8–0.86] for ordinal mRS). For predicting mRS score of 0–2 with a cut point, the second most efficient approach, the optimal threshold for 24-hour NIHSS score was ≤7 (sensitivity 80.1%, specificity 80.4%; adjusted odds ratio 12.5 [7.14–20], P P Conclusions: Twenty-four–hour NIHSS, adjusted for baseline, was the strongest predictor of both dichotomous and ordinal 90-day mRS outcomes for endovascular therapy-treated patients. A dichotomous 24-hour NIHSS score of ≤7 was the second-best predictor. Although ΔNIHSS, continuous and dichotomized at ≥4, predicted 90-day outcomes, absolute 24-hour NIHSS definitions performed better.

BACKGROUND Studies demonstrate an association between visit-to-visit blood pressure variability (BPV) and cardiovascular events and death. We aimed to determine the long-term cardiovascular and mortality effects of BPV in midlife in participants with and without cardiovascular risk factors. METHODS This is a post-hoc analysis of the Atherosclerosis Risk in the Community study. Long-term BPV was derived utilizing mean systolic blood pressure at Visits 1–4 (Visit 1: 1987–1989, Visit 2: 1990–1992, Visit 3: 1993–1995, Visit 4: 1996–1998). The primary outcome was mortality from Visit 4 to 2016 and secondary outcome was cardiovascular events (fatal coronary heart disease, myocardial infarction, cardiac procedure, or stroke). We fit Cox proportional hazards models and also performed the analysis in a subgroup of cardiovascular disease-free patients without prior stroke, myocardial infarction, congestive heart failure, hypertension, or diabetes. RESULTS We included 9,578 participants. The mean age at the beginning of follow-up was 62.9 ± 5.7 years, and mean follow-up was 14.2 ± 4.5 years. During follow-up, 3,712 (38.8%) participants died and 1,721 (n = 8,771, 19.6%) had cardiovascular events. For every SD higher in systolic residual SD (range 0–60.5 mm Hg, SD = 5.6 mm Hg), the hazard ratio for death was 1.09 (95% confidence interval [CI] 1.05–1.12) and for cardiovascular events was 1.00 (95% CI 0.95–1.05). In cardiovascular disease-free participants (n = 4,452), the corresponding hazard ratio for death was 1.12 (95% CI 1.03–1.21) and for cardiovascular events was 1.01 (95% CI 0.89–1.14). CONCLUSION Long-term BPV during midlife is an independent predictor of later life mortality but not cardiovascular events.

BACKGROUND AND PURPOSE There is a relative paucity of data regarding long-term outcomes and treatment-related complications in women of childbearing age with cerebral venous sinus thrombosis (CVST). We sought to determine whether outcomes differ in women of childbearing age with versus without postpartum CVST. METHODS We retrospectively analysed 373 non-pregnant females of childbearing age (18-45 years) included in the multicenter observational Anticoagulation in the Treatment of Cerebral Venous Thrombosis study (ACTION-CVT). Comparisons were made between postpartum (first 12 weeks from delivery, n=38 [10.2%]) versus non-postpartum women (n=335 [89.8%]). The primary outcomes of interest were one-year risk of all-cause death, venous thromboembolism (VTE) recurrence, and major hemorrhage (i.e., new or worsening intracranial hemorrhage or major extracranial hemorrhage). Secondary outcomes were the discharge disposition and modified Rankin Scale (mRS) score at discharge and 90 days. RESULTS Postpartum status was associated with greater risk of seizures (42.1% versus 20.9%, p=0.003), venous infarction (47.4% versus 29.5%, p=0.025), intracranial hemorrhage (55.3% versus 36.1%, p=0.022), and requirement for neurosurgical treatment (13.2% versus 3.6%, p=0.021). There was no significant association with one year all cause death (N=373 HR=1.35, 95%-CI=0.15-11.87, p=0.784), VTE recurrence (N=373, HR=1.27, 95%-CI=0.45-3.59, p=0.648), major hemorrhage (N=373, HR=1.36, 95%-CI=0.46-4.0, p=0.581) as well as excellent (mRS[0-1]: OR=1.58, 95%-CI=0.4-7.1, p=0.554) and good (mRS[0-2]: OR=0.92, 95%-CI=0.2-4.27, p=0.918) 90-day mRS. Results were similar after adjustment for potential confounders. CONCLUSIONS Although CVST in the 12-week postpartum period was more frequently associated with early complications, 90-day functional disability and one-year outcomes were similar to women with CVST unrelated to pregnancy.

Intracranial stenosis (ICAS) is a common cause of stroke worldwide and patients with symptomatic ICAS exhibit a high rate of recurrence, particularly in the early period after the initial event. In this study, we aimed to study the association between borderzone infarct and recurrent ischemic stroke in patients hospitalized with symptomatic ICAS.This is a retrospective single center study that included patients hospitalized with acute ischemic stroke in the setting of intracranial stenosis (50% or more and an acute ischemic stroke in the territory supplied by the stenosed artery) over a 32-month period. We excluded patients who did not receive a brain MRI or did not have an infarct on brain imaging. The primary predictor is infarct pattern (any borderzone vs. no borderzone infarct) and the primary outcome was recurrent cerebrovascular events (RCVE) within 90 days. We used unadjusted, and age and sex adjusted logistic regression models to determine associations between infarct pattern and RCVE at 90-days.Among 99 patients who met the inclusion criteria (4 tandem), the mean age was 70.1 ± 11.2 years and 41.4% were women; 43 had borderzone infarcts and 19 had RCVE. In adjusted binary logistic regression analysis, borderzone infarct was associated with increased risk of RCVE (adjusted OR 4.00 95% CI 1.33-11.99, p=0.013). The association between borderzone infarction and RCVE was not different among anterior circulation ICAD (adjusted HR 2.85 95% CI 0.64-12.76, p=0.172) vs. posterior circulation ICAD (adjusted HR 6.69 95% CI 1.06-42.11, p=0.043), p-value for interaction = 0.592.In real world post-SAMMPRIS medically treated patients with ICAD, the borderzone infarct pattern was associated with 90-day RCVE. Borderzone infarcts are likely a surrogate marker of impaired distal blood flow, highlighting the importance of targeting stroke mechanisms and developing alternative treatment strategies for high-risk cohorts.

Limited data exists evaluating predictors of long-term outcomes after hospitalization for COVID-19.We conducted a prospective, longitudinal cohort study of patients hospitalized for COVID-19. The following outcomes were collected at 6 and 12-months post-diagnosis: disability using the modified Rankin Scale (mRS), activities of daily living assessed with the Barthel Index, cognition assessed with the telephone Montreal Cognitive Assessment (t-MoCA), Neuro-QoL batteries for anxiety, depression, fatigue and sleep, and post-acute symptoms of COVID-19. Predictors of these outcomes, including demographics, pre-COVID-19 comorbidities, index COVID-19 hospitalization metrics, and life stressors, were evaluated using multivariable logistic regression.Of 790 COVID-19 patients who survived hospitalization, 451(57%) completed 6-month (N = 383) and/or 12-month (N = 242) follow-up, and 77/451 (17%) died between discharge and 12-month follow-up. Significant life stressors were reported in 121/239 (51%) at 12-months. In multivariable analyses, life stressors including financial insecurity, food insecurity, death of a close contact and new disability were the strongest independent predictors of worse mRS, Barthel Index, depression, fatigue, and sleep scores, and prolonged symptoms, with adjusted odds ratios ranging from 2.5 to 20.8. Other predictors of poor outcome included older age (associated with worse mRS, Barthel, t-MoCA, depression scores), baseline disability (associated with worse mRS, fatigue, Barthel scores), female sex (associated with worse Barthel, anxiety scores) and index COVID-19 severity (associated with worse Barthel index, prolonged symptoms).Life stressors contribute substantially to worse functional, cognitive and neuropsychiatric outcomes 12-months after COVID-19 hospitalization. Other predictors of poor outcome include older age, female sex, baseline disability and severity of index COVID-19.

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

Objective Patients with developmental disabilities (DD) are frequently excluded from acute ischemic stroke (AIS) randomized control trials. We sought to evaluate the impact of having DD on this patient cohort Methods The National Inpatient Sample was analyzed to explore the impact of AIS and treatment on discharge dispositions in patients with DD. Clinical characteristics, treatments, and outcomes were compared to fully-abled patients with AIS. Results 1,605,723 patients with AIS were identified from 2010–2019, of whom 4094 (0.30%) had a DD. AIS patients with DD were younger (60.31 vs 70.93 years, p Conclusion AIS patients with DD were less likely to receive tPA and EVT compared to fully-abled patients. Individuals with DD had higher mortality and worse discharge disposition. There was no significant difference in post-EVT outcomes between fully-abled patients and patients with developmental disabilities. In the absence of prospective clinical trials, population based cross-sectional analyses such as the present study provide valuable clinical insight.

Background and ObjectiveLittle is known about trajectories of recovery 12 months after hospitalization for severe COVID-19.MethodsWe conducted a prospective, longitudinal cohort study of patients with and without neurologic complications during index hospitalization for COVID-19 from March 10, 2020, to May 20, 2020. Phone follow-up batteries were performed at 6 and 12 months after COVID-19 onset. The primary 12-month outcome was the modified Rankin Scale (mRS) score comparing patients with or without neurologic complications using multivariable ordinal analysis. Secondary outcomes included activities of daily living (Barthel Index), telephone Montreal Cognitive Assessment (t-MoCA), and Quality of Life in Neurologic Disorders (Neuro-QoL) batteries for anxiety, depression, fatigue, and sleep. Changes in outcome scores from 6 to 12 months were compared using nonparametric paired-samples sign test.ResultsTwelve-month follow-up was completed in 242 patients (median age 65 years, 64% male, 34% intubated during hospitalization) and 174 completed both 6- and 12-month follow-up. At 12 months, 197/227 (87%) had ≥1 abnormal metric: mRS >0 (75%), Barthel Index p = 0.037). Significant improvements in outcome trajectories from 6 to 12 months were observed in t-MoCA scores (56% improved, median difference 1 point; p = 0.002) and Neuro-QoL anxiety scores (45% improved; p = 0.003). Nonsignificant improvements occurred in fatigue, sleep, and depression scores in 48%, 48%, and 38% of patients, respectively. Barthel Index and mRS scores remained unchanged between 6 and 12 months in >50% of patients.DiscussionAt 12 months after hospitalization for severe COVID-19, 87% of patients had ongoing abnormalities in functional, cognitive, or Neuro-QoL metrics and abnormal cognition persisted in 50% of patients without a history of dementia/cognitive abnormality. Only fatigue severity differed significantly between patients with or without neurologic complications during index hospitalization. However, significant improvements in cognitive (t-MoCA) and anxiety (Neuro-QoL) scores occurred in 56% and 45% of patients, respectively, between 6 and 12 months. These results may not be generalizable to those with mild or moderate COVID-19.

ObjectiveTo investigate the aetiology, subsequent preventive strategies and outcomes of stroke despite anticoagulation in patients with atrial fibrillation (AF).MethodsWe analysed consecutive patients with AF with an index imaging-proven ischaemic stroke despite vitamin K-antagonist (VKA) or direct oral anticoagulant (DOAC) treatment across 11 stroke centres. We classified stroke aetiology as: (i) competing stroke mechanism other than AF-related cardioembolism; (ii) insufficient anticoagulation (non-adherence or low anticoagulant activity measured with drug-specific assays); or, (iii) AF-related cardioembolism despite sufficient anticoagulation. We investigated subsequent preventive strategies with regard to the primary (composite of recurrent ischaemic stroke, intracranial haemorrhage, death) and secondary endpoint (recurrent ischaemic stroke) within 3 months after index stroke.ResultsAmong 2946 patients (median age 81 years; 48% women; 43% VKA, 57% DOAC), stroke aetiology was competing mechanism in 713 patients (24%), insufficient anticoagulation in 934 (32%) and cardioembolism despite sufficient anticoagulation in 1299 (44%). We found high rates of the primary (27% of patients; completeness 91.6%) and secondary endpoint (4.6%; completeness 88.5%). Only DOAC (vs VKA) treatment after index stroke showed lower odds for both endpoints (primary: adjusted OR (aOR) (95% CI) 0.49 (0.32 to 0.73); secondary: 0.44 (0.24 to 0.80)), but not switching between different DOAC types. Adding antiplatelets showed higher odds for both endpoints (primary: aOR (95% CI) 1.99 (1.25 to 3.15); secondary: 2.66 (1.40 to 5.04)). Only few patients (1%) received left atrial appendage occlusion as additional preventive strategy.ConclusionsStroke despite anticoagulation comprises heterogeneous aetiologies and cardioembolism despite sufficient anticoagulation is most common. While DOAC were associated with better outcomes than VKA, adding antiplatelets was linked to worse outcomes in these high-risk patients. Our findings indicate that individualised and novel preventive strategies beyond the currently available anticoagulants are needed.Trial registration numberISRCTN48292829.

Background Infarction of the medulla has been associated with prolongation of the QTc, severe arrhythmia, and sudden cardiac death, yet the precise anatomical substrate remains uncertain. Aims We sought to determine the possible anatomical structures relating to QTc-prolongation in patients with acute medullary infarction. Methods We included 12 subjects with acute ischemic medullary infarction on brain MRI, who presented within 4.5 h from the last known well time, with a 90-day follow-up. For an unbiased lesion analysis, medullary infarcts were manually outlined on diffusion weighted MRI and co-registered with an anatomical atlas. Results Nine out of 12 had QTc-prolongation. Qualitative and semi-quantitative comparisons were made between infarct location and QTc-prolongation. Among patients with QTc-prolongation, the greatest degree of congruence of the infarct location was over the dorsal vagal nucleus (DVN, 8 out of 9). There was a significant correlation between the number of sections showing infarction of the DVN and presence of QTc-prolongation (r = .582, p = .047). Among patients without QTc-prolongation, the maximum lesion overlap included the medial aspect of the gigantocelluar reticular nucleus of the reticular formation. Conclusion We found that the DVN is a key anatomical substrate related to QTc-prolongation. Further studies with more patients and high-resolution, volumetric MRI are needed to confirm our findings.

Background and purposeA subset of ischaemic stroke patients with atrial fibrillation (AF) have ischaemic stroke despite anticoagulation. We sought to determine the association between prestroke anticoagulant therapy and recurrent ischaemic events and symptomatic intracranial haemorrhage (sICH).MethodsWe included consecutive patients with acute ischaemic stroke and AF from the Initiation of Anticoagulation after Cardioembolic stroke (IAC) study from eight comprehensive stroke centres in the USA. We compared recurrent ischaemic events and delayed sICH risk using adjusted Cox regression analyses between patients who were prescribed anticoagulation (ACp) versus patients who were naïve to anticoagulation therapy prior to the ischaemic stroke (anticoagulation naïve).ResultsAmong 2084 patients in IAC, 1518 had prior anticoagulation status recorded and were followed for 90 days. In adjusted Cox hazard models, ACp was associated with some evidence of a higher risk higher risk of 90-day recurrent ischaemic events only in the fully adjusted model (adjusted HR 1.50, 95% CI 0.99 to 2.28, p=0.058) but not increased risk of 90-day sICH (adjusted HR 1.08, 95% CI 0.46 to 2.51, p=0.862). In addition, switching anticoagulation class was not associated with reduced risk of recurrent ischaemic events (adjusted HR 0.41, 95% CI 0.12 to 1.33, p=0.136) nor sICH (adjusted HR 1.47, 95% CI 0.29 to 7.50, p=0.641).ConclusionAF patients with ischaemic stroke despite anticoagulation may have higher recurrent ischaemic event risk compared with anticoagulation-naïve patients. This suggests differing underlying pathomechanisms requiring different stroke prevention measures and identifying these mechanisms may improve secondary prevention strategies.

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.

Background Toxic metabolic encephalopathy (TME) has been reported in 7–31% of hospitalized patients with coronavirus disease 2019 (COVID-19); however, some reports include sedation-related delirium and few data exist on the etiology of TME. We aimed to identify the prevalence, etiologies, and mortality rates associated with TME in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients. Methods We conducted a retrospective, multicenter, observational cohort study among patients with reverse transcriptase–polymerase chain reaction-confirmed SARS-CoV-2 infection hospitalized at four New York City hospitals in the same health network between March 1, 2020, and May 20, 2020. TME was diagnosed in patients with altered mental status off sedation or after an adequate sedation washout. Patients with structural brain disease, seizures, or primary neurological diagnoses were excluded. The coprimary outcomes were the prevalence of TME stratified by etiology and in-hospital mortality (excluding comfort care only patients) assessed by using a multivariable time-dependent Cox proportional hazards models with adjustment for age, race, sex, intubation, intensive care unit requirement, Sequential Organ Failure Assessment scores, hospital location, and date of admission. Results Among 4491 patients with COVID-19, 559 (12%) were diagnosed with TME, of whom 435 of 559 (78%) developed encephalopathy immediately prior to hospital admission. The most common etiologies were septic encephalopathy (n = 247 of 559 [62%]), hypoxic-ischemic encephalopathy (HIE) (n = 331 of 559 [59%]), and uremia (n = 156 of 559 [28%]). Multiple etiologies were present in 435 (78%) patients. Compared with those without TME (n = 3932), patients with TME were older (76 vs. 62 years), had dementia (27% vs. 3%) or psychiatric history (20% vs. 10%), were more often intubated (37% vs. 20%), had a longer hospital length of stay (7.9 vs. 6.0 days), and were less often discharged home (25% vs. 66% [all P

Perfusion imaging can risk stratify patients with symptomatic intracranial stenosis. We aim to determine the association between perfusion delay and length of hospital stay (LOS) in symptomatic middle cerebral artery (MCA) stenosis patients.This is a retrospective study of consecutive patients admitted to a comprehensive stroke center over 5 years with ischemic stroke or transient ischemic attack (TIA) within 7 days of symptom onset due to MCA stenosis (50-99%) and underwent perfusion imaging. Patients were divided into three groups: mismatch volume ≥ 15 cc based on T max6 second delay, T max 4-6 second delay, and4 second delay. The outcome was LOS, both as a continuous variable and categorical (≥7 days [prolonged LOS] vs.7 days). We used adjusted regression analyses to determine the association between perfusion categories and LOS.One hundred and seventy eight of 194 patients met the inclusion criteria. After adjusting for age and NIHSS, T max6 second mismatch was associated with prolonged LOS (OR 2.94 95% CI 1.06-8.18; P = .039), but T max 4-6 second was not (OR 1.45 95% CI .46-4.58, P = .528). We found similar associations when LOS was a continuous variable for T max6 second (β coefficient = 2.01, 95% CI .05-3.97, P = .044) and T max 4-6 second (β coefficient = 1.24, 95% CI -.85 to 3.34, P = .244).In patients with symptomatic MCA stenosis, T max6 second perfusion delay is associated with prolonged LOS. Prospective studies are needed to validate our findings.

BackgroundIntracerebral hemorrhage (ICH) occurs in ~20%–30% of stroke patients undergoing endovascular therapy (EVT). However, there is conflicting evidence regarding the effect of asymptomatic ICH (aICH) on post-EVT outcomes. We sought to evaluate the effect of aICH on immediate and 90-day post-EVT neurological outcomes.MethodsIn this post-hoc analysis of the multicenter, prospective Blood Pressure after Endovascular Therapy (BEST) study we identified subjects with ICH following EVT. This population was divided into no ICH, aICH, and symptomatic ICH (sICH). Associations with 90-day modified Rankin Scale (mRS) dichotomized by functional independence (0–2 vs 3–6) and early neurological recovery (ENR) were determined using univariate/multivariate logistic regression models.ResultsOf 485 patients enrolled in BEST, 446 had 90-day follow-up data available. 92 (20.6%) developed aICH, and 18 (4%) developed sICH. Compared with those without ICH, aICH was not associated with worse 90-day outcome or lower ENR (OR 0.84 [0.53–1.35], P=0.55, aOR 0.84 [0.48–1.44], P=0.53 for 90-day mRS 0–2; OR 0.77 [0.48–1.23], P=0.34, aOR 0.72 [0.43–1.22] for ENR). aICH was not associated with 90-day outcome or ENR in patients with mTICI ≥2 b (OR 0.78 [0.48–1.26], P=0.33 for 90-day mRS 0–2; OR 0.89 [0.69–1.12], P=0.15 for ENR). A higher proportion of patients with aICH had mTICI ≥2 b than those without ICH (97%vs 87%, P=0.01).ConclusionsaICH was not associated with worse outcomes in patients with large-vessel stroke treated with EVT. aICH was more frequent in patients with successful recanalization. Further validation of our findings in large cohort studies of EVT-treated patients is warranted.

Background: We assessed cost–effectiveness of insertable cardiac monitors (ICMs) in a US cryptogenic stroke population. Materials & methods: We modelled lifetime costs and quality-adjusted life years for three monitoring strategies post cryptogenic stroke: ICM starting immediately, ICM starting after Holter monitoring (delayed ICM) and standard of care involving intermittent ECG and Holter monitoring. Patient characteristics and detection efficacy were based on the CRYSTAL-AF trial. AF detection altered the modelled anticoagulation therapy and subsequent stroke and bleed risks. Results & conclusion: Immediate ICM was found to be cost-effective versus standard of care and cost-saving versus delayed ICM. Results were robust to sensitivity analyses. ICMs are a cost-effective diagnostic tool for the prevention of recurrent stroke in a US cryptogenic stroke population.

Background In the post-Carotid Occlusion Surgery Study (COSS) era, multiple reviews suggested subset groups of patients as potential candidates for superficial temporal artery to middle cerebral artery (STA-MCA) bypass. Among them are patients with recurrent strokes despite optimal medical therapy. There is a paucity of data on the outcome of bypass in these specific patients. Objective To examine the safety and efficacy of direct STA-MCA bypass in patients with nonmoyamoya, symptomatic steno-occlusive disease with impaired distal perfusion, who failed optimal medical management or endovascular treatment. Methods A retrospective review was performed to identify patients with cerebrovascular steno-occlusive disease who underwent bypass after symptomatic recurrent or rapidly progressive strokes, despite optimal conservative or endovascular treatment. Results A total of 8 patients (mean age 60 ± 6 yr) underwent direct or combined direct/indirect STA-MCA bypass between 2016 and 2019. All anastomoses were patent. One bypass carried slow flow. There were no procedure-related permanent deficits. One patient developed seizures which were controlled by medications. A total of 7 out of 8 patients were stable or improved clinically at last follow-up (mean 27.3 ± 13.8 mo) without recurrent strokes. One patient did not recover from their presenting stroke, experienced severe bilateral strokes 4 mo postoperatively, and subsequently expired. Modified Rankin Scale (mRS) improved in 6 patients (75%), remained stable in 1 patient (12.5%), and deteriorated in 1 (12.5%). Good long-term functional outcome was achieved in 5 patients (63%, mRS ≤ 2). Conclusion Patients with symptomatic, hypoperfused steno-occlusive disease who fail optimal medical or endovascular treatment may benefit from cerebral revascularization. Direct or combined STA-MCA bypass was safe and provided favorable outcomes in this small series.

The carotid web is a proposed stroke mechanism that may underlie cryptogenic stroke, particularly in younger patients without vascular risk factors. The web appears as a shelf-like projection into the lumen of the proximal cervical internal carotid artery without evidence of calcification. It is pathologically defined as intimal fibromuscular dysplasia. Altered haemodynamics distal to the web cause flow stagnation and remote embolisation of fibrin-based clots. It is best demonstrated and diagnosed on CT angiography (CTA) of the neck because of its ability to resolve calcium and create multiplanar reconstructions. Although they can be readily visualised on CTA, carotid webs may be missed or misinterpreted because they do not typically cause haemodynamically significant stenosis and can mimic arterial dissection, non-calcified atherosclerotic plaque and intraluminal thrombus. Options for management include antiplatelet therapy, carotid endarterectomy and carotid artery stenting. Modern management strategies for cryptogenic stroke include long-term cardiac monitoring, further investigation for structural cardiac disease and a diagnostic workup for arterial hypercoagulability, however, these strategies are not likely to capture the possibility of a carotid web. Carotid webs should be suspected in a young patient presenting with recurrent unihemispheric strokes particularly when conventional vascular risk factors are not present.

Background: In patients with atrial fibrillation who suffered an ischemic stroke while on treatment with nonvitamin K antagonist oral anticoagulants, rates and determinants of recurrent ischemic events and major bleedings remain uncertain. Methods: This prospective multicenter observational study aimed to estimate the rates of ischemic and bleeding events and their determinants in the follow-up of consecutive patients with atrial fibrillation who suffered an acute cerebrovascular ischemic event while on nonvitamin K antagonist oral anticoagulant treatment. Afterwards, we compared the estimated risks of ischemic and bleeding events between the patients in whom anticoagulant therapy was changed to those who continued the original treatment. Results: After a mean follow-up time of 15.0±10.9 months, 192 out of 1240 patients (15.5%) had 207 ischemic or bleeding events corresponding to an annual rate of 13.4%. Among the events, 111 were ischemic strokes, 15 systemic embolisms, 24 intracranial bleedings, and 57 major extracranial bleedings. Predictive factors of recurrent ischemic events (strokes and systemic embolisms) included CHA 2 DS 2 -VASc score after the index event (odds ratio [OR], 1.2 [95% CI, 1.0–1.3] for each point increase; P =0.05) and hypertension (OR, 2.3 [95% CI, 1.0–5.1]; P =0.04). Predictive factors of bleeding events (intracranial and major extracranial bleedings) included age (OR, 1.1 [95% CI, 1.0–1.2] for each year increase; P =0.002), history of major bleeding (OR, 6.9 [95% CI, 3.4–14.2]; P =0.0001) and the concomitant administration of an antiplatelet agent (OR, 2.8 [95% CI, 1.4–5.5]; P =0.003). Rates of ischemic and bleeding events were no different in patients who changed or not changed the original nonvitamin K antagonist oral anticoagulants treatment (OR, 1.2 [95% CI, 0.8–1.7]). Conclusions: Patients suffering a stroke despite being on nonvitamin K antagonist oral anticoagulant therapy are at high risk of recurrent ischemic stroke and bleeding. In these patients, further research is needed to improve secondary prevention by investigating the mechanisms of recurrent ischemic stroke and bleeding.

Background: Treatment of uncontrolled arterial hypertension reduces the risk of cerebral small vessel disease (CSVD) progression, although it is unclear whether this reduction occurs due to blood pressure control or class-specific pleiotropic effects, such as improved beat-to-beat arterial pressure variability with calcium channel blockers. The goal of this study was to investigate the influence of antihypertensive medication class, particularly with calcium channel blocker, on accumulation of white matter hyperintensities (WMH), a radiographic marker of CSVD, within a cohort with well-controlled hypertension. Methods: We completed an observational cohort analysis of the SPRINT-MIND trial (Systolic Blood Pressure Trial Memory and Cognition in Decreased Hypertension), a large randomized controlled trial of participants who completed a baseline and 4-year follow-up brain magnetic resonance image with volumetric WMH data. Antihypertensive medication data were recorded at follow-up visits between the magnetic resonance images. A percentage of follow-up time participants were prescribed each of the 11 classes of antihypertensive was then derived. Progression of CSVD was calculated as the difference in WMH volume between 2 scans and, to address skew, dichotomized into a top tertile of the distribution compared with the remaining. Results: Among 448 individuals, vascular risk profiles were similar across WMH progression subgroups except age (70.1±7.9 versus 65.7±7.3 years; P P =0.039). Seventy-two (48.3%) of the top tertile cohort and 177 (59.2%) of the remaining cohort were in the intensive blood pressure arm. Those within the top tertile of progression had a mean WMH progression of 4.7±4.3 mL compared with 0.13±1.0 mL ( P P =0.011) and dihydropyridine calcium channel blockers (odds ratio, 0.39 [95% CI, 0.19–0.80]; P =0.011) was associated with less WMH progression, although dihydropyridine calcium channel blockers lost significance when WMH was treated as a continuous variable. Conclusions: Among participants of SPRINT-MIND trial, angiotensin-converting enzyme inhibitor was most consistently associated with less WMH progression independent of blood pressure control and age.

Background: Conflicting data exists surrounding whether or not the effect of clopidogrel on risk reduction of cardiovascular outcomes, including stroke, is more pronounced in smokers. The aim of this study was to determine the effect of smoking status on subsequent stroke risk in all patients with minor ischemic stroke or TIA, as well as subgroups that may be particularly impacted by an effect, and determine whether smoking improves the effect of clopidogrel treatment on subsequent stroke risk reduction. Subgroup analysis included those of older age, black race, and female gender, as these groups may have higher risk of clopidogrel non-response and subsequently poor outcomes. Methods: This was a post-hoc analysis of the Platelet Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial. The POINT trial compared clopidogrel plus aspirin (DAPT) to aspirin alone for prevention of recurrent stroke, myocardial infarction, or vascular death within 3 months of a high-risk TIA or minor ischemic stroke. We used multivariable cox-regression models to determine the effect of smoking on the efficacy of DAPT in reducing the risk of subsequent ischemic stroke in all patients and prespecified subgroups stratified based on age, sex, race, and diabetes. We also performed interaction analyses to determine whether the effect of clopidogrel on subsequent ischemic stroke differed with respect to smoking status. Results: Data from 4,877 participants enrolled in the POINT trial were analyzed. Among these, 1,004 were current smokers and 3,873 were non-smokers. Smoking was associated with a non-significantly increased risk of recurrent ischemic stroke during follow up (hazard ratio, 1.31 [95% CI, 0.97 - 1.78], P=0.076). The effect of clopidogrel on ischemic stroke was not significantly different in non-smokers (hazard ratio, 0.74 [95% CI, 0.56 - 0.98], P=0.03) compared to smokers (adjusted hazard ratio, 0.63 [95% CI, 0.37 - 1.05], P=0.078), P for interaction = 0.572. In addition, the effect of clopidogrel on major hemorrhage was not significantly different in current smokers (hazard ratio, 2.59 [95% CI, 1.08 - 6.21], P=0.032) compared to non-smokers (hazard ratio, 1.67 [95% CI, 0.40 - 7.00], P=0.481), P for interaction = 0.613. This finding was maintained across different subgroups: males, females, blacks, whites, those with and without diabetes, and those aged < 60 and ≥ 60 years. Conclusions: Cigarette smoking was associated with a non-significantly higher risk of subsequent ischemic stroke and smoking did not modify the effect of clopidogrel-based dual antiplatelet therapy on subsequent ischemic stroke risk reduction, even in the subgroups of stratified based on age, sex, race, and diabetes, where greater likelihood of effect was theorized. Every effort should be made to encourage tobacco dependence treatment and cessation in patients with minor ischemic stroke and TIA.

Background Recent studies have noted concern for increased thromboembolic events in the setting of Coronavirus Disease 2019 (COVID-19). Cerebral venous sinus thrombosis (CVST) is a form of thromboembolism that has been observed as a neuro-ophthalmologic complication of COVID-19. Methods Review of the scientific literature. Results In this article, we report an overview of CVST epidemiology, clinical presentation, diagnostics, disease pathophysiology, and management in the setting of COVID-19. Conclusion CVST is an uncommon thromboembolic event with variable phenotypes and multiple etiologies. Neurologic complications can be severe, including significant visual deficits and death. Current observations suggest that the risk of CVST may be profoundly impacted by this novel COVID-19 pandemic, thus prompting increased attention to disease presentation, pathogenesis, and management.

ObjectiveTo determine the prevalence and associated mortality of well-defined neurologic diagnoses among patients with coronavirus disease 2019 (COVID-19), we prospectively followed hospitalized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–positive patients and recorded new neurologic disorders and hospital outcomes.MethodsWe conducted a prospective, multicenter, observational study of consecutive hospitalized adults in the New York City metropolitan area with laboratory-confirmed SARS-CoV-2 infection. The prevalence of new neurologic disorders (as diagnosed by a neurologist) was recorded and in-hospital mortality and discharge disposition were compared between patients with COVID-19 with and without neurologic disorders.ResultsOf 4,491 patients with COVID-19 hospitalized during the study timeframe, 606 (13.5%) developed a new neurologic disorder in a median of 2 days from COVID-19 symptom onset. The most common diagnoses were toxic/metabolic encephalopathy (6.8%), seizure (1.6%), stroke (1.9%), and hypoxic/ischemic injury (1.4%). No patient had meningitis/encephalitis or myelopathy/myelitis referable to SARS-CoV-2 infection and 18/18 CSF specimens were reverse transcriptase PCR negative for SARS-CoV-2. Patients with neurologic disorders were more often older, male, white, hypertensive, diabetic, intubated, and had higher sequential organ failure assessment (SOFA) scores (all p < 0.05). After adjusting for age, sex, SOFA scores, intubation, history, medical complications, medications, and comfort care status, patients with COVID-19 with neurologic disorders had increased risk of in-hospital mortality (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.17–1.62, p < 0.001) and decreased likelihood of discharge home (HR 0.72, 95% CI 0.63–0.85, p < 0.001).ConclusionsNeurologic disorders were detected in 13.5% of patients with COVID-19 and were associated with increased risk of in-hospital mortality and decreased likelihood of discharge home. Many observed neurologic disorders may be sequelae of severe systemic illness.

Background Standard urine sampling and testing techniques do not mitigate against detection of colonization, resulting in false positive catheter-associated urinary tract infections (CAUTI). We aimed to evaluate whether a novel protocol for urine sampling and testing reduces rates of CAUTI. Methods A preintervention and postintervention study with a contemporaneous control group was conducted at 2 campuses (test and control) of the same academic medical center. The test campus implemented a protocol requiring urinary catheter removal prior to urine sampling from a new catheter or sterile straight catheterization, along with urine bacteria and pyuria screening prior to culture. Primary outcomes were test campus CAUTI rates, compared between each 9-month pre- and postintervention epoch. Secondary outcomes included the percent reductions in CAUTI rates, compared between the test campus and a propensity score–matched cohort at the control campus. Results A total of 7991 patients from the test campus were included in the primary analysis, and 4264 were included in the propensity score–matched secondary analysis. In the primary analysis, the number of CAUTI cases per 1000 patients was reduced by 77% (6.6 to 1.5), the number of CAUTI cases per 1000 catheter days was reduced by 63% (5.9 to 2.2), and the number of urinary catheter days per patient was reduced by 37% (1.1 to 0.69; all P values ≤ .001). In the propensity score–matched analysis, the number of CAUTI cases per 1000 patients was reduced by 82% at the test campus, versus 57% at the control campus; the number of CAUTI cases per 1000 catheter days declined by 68% versus 57%, respectively; and the number of urinary catheter days per patient decreased by 44% versus 1%, respectively (all P values Conclusions Protocolized urine sampling and testing aimed at minimizing contamination by colonization was associated with significantly reduced CAUTI infection rates and urinary catheter days.

BACKGROUND: Anticoagulation increases the risk of intracerebral hemorrhage (ICH) in patients with cerebral amyloid angiopathy (CAA), so the management of stroke-risk in patients with both atrial fibrillation (AF) and CAA is controversial. Advances in left atrial appendage closure (LAAC) techniques provide a stroke-risk-reduction option which avoids long-term oral anticoagulation (OAC). We aimed to evaluate the safety of this intervention in patients with CAA. METHODS: This is an observational cohort study of patients with severe CAA (with or without ICH) and AF who were treated with LAA closure. The Watchman™ and Amulet® LAAC devices, Lariat procedure or open surgical closure of the LAA were all considered acceptable means of closure. Patients with symptomatic ICH and those naive to anticoagulation were placed on clopidogrel and/or aspirin for 6 weeks after the procedure; patients who previously tolerated anticoagulation remained on warfarin or a DOAC for 6 weeks post-procedure. All antiplatelet and anticoagulation therapy was discontinued after confirmation of LAAC. All patients had aggressively optimized blood pressure and fall precautions in addition to surgical intervention. Safety, tolerability, stroke and hemorrhage rates were documented. OUTCOME: Twenty-six patients with a mean CHA(2)DS(2)-VASc score of 4.6 were treated, 13 with a history of symptomatic lobar hemorrhage and 13 without. All patients who completed LAAC tolerated device implantation. There were no documented ischemic strokes or symptomatic ICH during the 30 days after device implantation. Patients were followed for an average of 25 months. One patient who underwent LARIAT LAAC had an ischemic stroke in follow-up, but recovered well; there were no other thromboemboli in this cohort. CONCLUSIONS: This cohort study provides evidence that LAAC appears to be a safe and tolerable treatment to reduce stroke risk in patients with CAA. Because of the small size of the cohort and relatively short follow-up, the efficacy for stroke and ICH prevention is not conclusive, but the preliminary results are encouraging. LAA closure may be a good alternative to anticoagulation in patients with CAA and atrial fibrillation.

Supplemental Digital Content is available in the text., Objective: To determine the prevalence of D-dimer elevation in coronavirus disease 2019 (COVID-19) hospitalization, trajectory of D-dimer levels during hospitalization, and its association with clinical outcomes. Approach and Results: Consecutive adults admitted to a large New York City hospital system with a positive polymerase chain reaction test for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) between March 1, 2020 and April 8, 2020 were identified. Elevated D-dimer was defined by the laboratory-specific upper limit of normal (>230 ng/mL). Outcomes included critical illness (intensive care, mechanical ventilation, discharge to hospice, or death), thrombotic events, acute kidney injury, and death during admission. Among 2377 adults hospitalized with COVID-19 and ≥1 D-dimer measurement, 1823 (76%) had elevated D-dimer at presentation. Patients with elevated presenting baseline D-dimer were more likely than those with normal D-dimer to have critical illness (43.9% versus 18.5%; adjusted odds ratio, 2.4 [95% CI, 1.9–3.1]; P2000 ng/mL had the highest risk of critical illness (66%), thrombotic event (37.8%), acute kidney injury (58.3%), and death (47%). Conclusions: Abnormal D-dimer was frequently observed at admission with COVID-19 and was associated with higher incidence of critical illness, thrombotic events, acute kidney injury, and death. The optimal management of patients with elevated D-dimer in COVID-19 requires further study.

Introduction The aim of this study in patients with acute posterior ischaemic stroke (PS) and atrial fibrillation (AF) was to evaluate (1) the risks of recurrent ischaemic event and severe bleeding and (2) these risks in relation with oral anticoagulant therapy (OAT) and its timing. Materials and Methods Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of stroke recurrence, transient ischaemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke. Results A total of 2470 patients were available for the analysis: 473 (19.1%) with PS and 1997 (80.9%) with AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39–2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16–1.80). Discussion our findings suggest that, when deciding the time to initiate oral anticoagulation, the location of stroke, either anterior or posterior, does not predict the risk of outcome events. Conclusions Patients with PS or AS and AF appear to have similar risks of ischaemic or haemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT.

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.

IntroductionPredictors of long-term ischaemic and haemorrhagic complications in atrial fibrillation (AF) have been studied, but there are limited data on predictors of early ischaemic and haemorrhagic complications after AF-associated ischaemic stroke. We sought to determine these predictors.MethodsThe Initiation of Anticoagulation after Cardioembolic stroke study is a multicentre retrospective study across that pooled data from consecutive patients with ischaemic stroke in the setting of AF from stroke registries across eight comprehensive stroke centres in the USA. The coprimary outcomes were recurrent ischaemic event (stroke/TIA/systemic arterial embolism) and delayed symptomatic intracranial haemorrhage (d-sICH) within 90 days. We performed univariate analyses and Cox regression analyses including important predictors on univariate analyses to determine independent predictors of early ischaemic events (stroke/TIA/systemic embolism) and d-sICH.ResultsOut of 2084 patients, 1520 patients qualified; 104 patients (6.8%) had recurrent ischaemic events and 23 patients (1.5%) had d-sICH within 90 days from the index event. In Cox regression models, factors associated with a trend for recurrent ischaemic events were prior stroke or transient ischemic attack (TIA) (HR 1.42, 95% CI 0.96 to 2.10) and ipsilateral arterial stenosis with 50%–99% narrowing (HR 1.54, 95% CI 0.98 to 2.43). Those associated with sICH were male sex (HR 2.68, 95% CI 1.06 to 6.83), history of hyperlipidaemia (HR 2.91, 95% CI 1.08 to 7.84) and early haemorrhagic transformation (HR 5.35, 95% CI 2.22 to 12.92).ConclusionIn patients with ischaemic stroke and AF, predictors of d-sICH are different than those of recurrent ischaemic events; therefore, recognising these predictors may help inform early stroke versus d-sICH prevention strategies.

Background and Purpose— The first of the 2 NINDS (National Institute of Neurological Disorders and Stroke) Study trials did not show a significant increase in early neurological improvement, defined as National Institutes of Health Stroke Scale (NIHSS) improvement by ≥4, with alteplase treatment. We hypothesized that early neurological improvement defined as a percentage change in NIHSS (percent change NIHSS) at 24 hours is superior to other definitions in predicting 3-month functional outcomes and using this definition there would be treatment benefit of alteplase over placebo at 24 hours. Methods— We analyzed the NINDS rt-PA Stroke Study (Parts 1 and 2) trial data. Percent change NIHSS was defined as ([admission NIHSS score−24-hour NIHSS score]×100/admission NIHSS score] and delta NIHSS as (admission NIHSS score−24-hour NIHSS score). We compared early neurological improvement using these definitions between alteplase versus placebo patients. We also used receiver operating characteristic curve to determine the predictive association of early neurological improvement with excellent 3-month functional outcomes (Barthel Index score of 95–100 and modified Rankin Scale score of 0–1), good 3-month functional outcome (modified Rankin Scale score of 0–2), and 3-month infarct volume. Results— There was a significantly greater improvement in the 24-hour median percent change NIHSS among patients treated with alteplase compared with the placebo group (28% versus 15%; P =0.045) but not median delta NIHSS (3 versus 2; P =0.471). Receiver operating characteristic curve comparison showed that percent change NIHSS (ROC percent ) was better than delta NIHSS (ROC delta ) and admission NIHSS (ROC admission ) with regards to excellent 3-month Barthel Index (ROC percent , 0.83; ROC delta , 0.76; ROC admission , 0.75), excellent 3-month modified Rankin Scale (ROC percent , 0.83; ROC delta , 0.74; ROC admission , 0.78), and good 3-month modified Rankin Scale (ROC percent , 0.83; ROC delta , 0.76; ROC admission , 0.78). Conclusions— In the NINDS rt-PA trial, alteplase was associated with a significant percent change improvement in NIHSS at 24 hours. Percent change in NIHSS may be a better surrogate marker of thrombolytic activity and 3-month outcomes.