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Large vessel occlusion stroke due to underlying intracranial atherosclerotic disease (ICAD-LVO) is prevalent in 10 to 30% of LVOs depending on patient factors such as vascular risk factors, race and ethnicity, and age. Patients with ICAD-LVO derive similar functional outcome benefit from endovascular thrombectomy as other mechanisms of LVO, but up to half of ICAD-LVO patients reocclude after revascularization. Therefore, early identification and treatment planning for ICAD-LVO are important given the unique considerations before, during, and after endovascular thrombectomy. In this review of ICAD-LVO, we propose a multistep approach to ICAD-LVO identification, pretreatment and endovascular thrombectomy considerations, adjunctive medications, and medical management. There have been no large-scale randomized controlled trials dedicated to studying ICAD-LVO, therefore this review focuses on observational studies.

Occlusive and nonocclusive cervicocephalic thrombi can be encountered during neurovascular imaging in patients with acute ischemic stroke. Radiographic and morphological characteristics on basic and advanced imaging modalities can be important clues towards determination of pathomechanism and the choice of acute and subacute treatment modalities. The aim of this review article is to evaluate the epidemiology, radiographic properties, histologic clot composition of cervicocephalic arterial thrombi, and its response to various medical and endovascular therapy modalities. Future studies are needed to derive and validate a classification system for extracranial and intracranial partially occlusive thrombi to enable further testing of various stroke treatment and prevention strategies in these patients.

Background: Prior systematic reviews have compared the efficacy of intravenous tenecteplase and alteplase in acute ischemic stroke, assigning their relative complications as a secondary objective. The objective of the present study is to determine whether the risk of treatment complications differs between patients treated with either agent. Methods: We performed a systematic review including interventional studies and prospective and retrospective, observational studies enrolling adult patients treated with intravenous tenecteplase for ischemic stroke (both comparative and noncomparative with alteplase). We searched MEDLINE, Embase, the Cochrane Library, Web of Science, and the www.ClinicalTrials.gov registry from inception through June 3, 2022. The primary outcome was symptomatic intracranial hemorrhage, and secondary outcomes included any intracranial hemorrhage, angioedema, gastrointestinal hemorrhage, other extracranial hemorrhage, and mortality. We performed random effects meta-analyses where appropriate. Evidence was synthesized as relative risks, comparing risks in patients exposed to tenecteplase versus alteplase and absolute risks in patients treated with tenecteplase. Results: Of 2226 records identified, 25 full-text articles (reporting 26 studies of 7913 patients) were included. Sixteen studies included alteplase as a comparator, and 10 were noncomparative. The relative risk of symptomatic intracranial hemorrhage in patients treated with tenecteplase compared with alteplase in the 16 comparative studies was 0.89 ([95% CI, 0.65–1.23]; I 2 =0%). Among patients treated with low dose (2 =0%), 0.77 ([95% CI, 0.53–1.14]; I 2 =0%), and 2.31 ([95% CI, 0.69–7.75]; I 2 =40%), respectively. The pooled risk of symptomatic intracranial hemorrhage in tenecteplase-treated patients, including comparative and noncomparative studies, was 0.99% ([95% CI, 0%–3.49%]; I 2 =0%, 7 studies), 1.69% ([95% CI, 1.14%–2.32%]; I 2 =1%, 23 studies), and 4.19% ([95% CI, 1.92%–7.11%]; I 2 =52%, 5 studies) within the low-, medium-, and high-dose groups. The risks of any intracranial hemorrhage, mortality, and other studied outcomes were comparable between the 2 agents. Conclusions: Across medium- and low-dose tiers, the risks of complications were generally comparable between those treated with tenecteplase versus alteplase for acute ischemic stroke.

Background: Cigarette smoking is a known risk factor for cardiovascular disease, including ischemic stroke. The literature regarding the rate of persistent smoking after acute ischemic stroke and its effect on subsequent cardiovascular events is scarce. With this study, we aimed to report the rate of persistent smoking after ischemic stroke and the association between smoking status and major cardiovascular outcomes. Methods: This is a post-hoc analysis of the SPS3 trial (Secondary Prevention of Small Subcortical Strokes). Patients were divided into 4 groups based on smoking status at trial enrollment: (1) never smokers, (2) former smokers, (3) smokers who quit at 3 months, and (4) persistent smokers. The primary outcome is a major adverse cardiovascular events composite of stroke (ischemic and hemorrhagic), myocardial infarction, and mortality. Outcomes were adjudicated after month 3 of enrollment until an outcome event or the end of study follow-up. Results: A total of 2874 patients were included in the study. Of the total cohort, 570 patients (20%) were smokers at enrollment, of whom 408 (71.5%) patients continued to smoke and 162 (28.4%) quit smoking by 3 months. The major adverse cardiovascular events outcome occurred in 18.4%, 12.4%, 16.2%, and 14.4%, respectively, in persistent smokers, smokers who quit, prior smokers, and never smokers. In a model adjusted for age, sex, race, ethnicity, education, employment status, history of hypertension, diabetes, hyperlipidemia, myocardial infarction, and intensive blood pressure randomization arm, the risk of major adverse cardiovascular events, and death were higher in the persistent smokers compared with never smokers (HR for major adverse cardiovascular events: 1.56 [95% CI, 1.16–2.09]; HR for death: 2.0 [95% CI, 2.18–3.12]). The risk of stroke, and MI did not differ according to smoking status Conclusions: Compared with never smoking, persistent smoking after acute ischemic stroke was associated with an increased risk of cardiovascular events and death. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00059306.

Background: High level evidence for direct oral anticoagulants (DOACs) in patients with cerebral venous thrombosis is lacking. We performed a systematic review and meta-analysis to assess the efficacy and safety of DOACs versus vitamin K antagonists in patients with cerebral venous thrombosis. Methods: This systematic review was registered in PROSPERO (CRD42021228800). We searched MEDLINE (via Ovid), EMBASE, CINAHL, and the Web of Science Core Collection between January 1, 2007 and Feb 22, 2022. Search terms included a combination of keywords and controlled vocabulary terms for cerebral venous thrombosis, vitamin K antagonists/warfarin, and DOACs. We included both randomized and nonrandomized studies that compared vitamin K antagonists and DOACs in 5 or more patients with cerebral venous thrombosis. Where studies were sufficiently similar, we performed meta-analyses for efficacy (recurrent venous thromboembolism and complete recanalization) and safety (major hemorrhage) outcomes, using relative risks (RRs). Results: Out of 10 665 records identified, we screened 254 as potentially eligible. Nineteen studies (16 observational studies [n=1735] and 3 randomized controlled trials [n=215]) met the inclusion criteria. All 3 randomized controlled trials had some concerns, and all 16 observational studies had at least moderate risk of bias. When compared with vitamin K antagonist treatment, DOAC had comparable risks of recurrent venous thromboembolism (relative risk [RR], 0.85 [95% CI, 0.52–1.37], I 2 =0%), major hemorrhage (RR, 0.70 [95% CI, 0.40–1.21], I 2 =0%), intracranial hemorrhage (RR, 0.58 [95% CI, 0.30–1.12]; I 2 =0%), death (RR, 1.14 [95% CI, 0.54–2.43], I 2 =1%), and complete venous recanalization (RR, 0.98 [95% CI, 0.87–1.11]; I 2 =0%). Conclusions: This systematic review and meta-analysis suggest that in patients with cerebral venous thrombosis, DOACs, and warfarin may have comparable efficacy and safety. Given the limitations of the studies included (low number of randomized controlled trials, modest total sample size, rare outcome events), our findings should be interpreted with caution pending confirmation by ongoing randomized controlled trials and large, prospective, observational studies.

Background: There is a paucity of nationally representative data regarding the impact of COVID-19 on acute ischemic stroke (AIS) outcome. Methods: We created a cross-sectional cohort of nationally weighted National Inpatient Sample nonelective hospital discharges aged ≥18 years with a diagnosis of ischemic stroke from 2016 to 2020. The outcome was in-hospital mortality and exposure was COVID-19 status. To understand the effect of COVID-19 on AIS severity, we report National Institutes of Health Stroke Scale by exposure status. In a final analysis, we used a nationally weighted logistic regression and marginal effects to compare April to December 2020 to the same period in 2019 to understand how the pandemic modified the effect of race and ethnicity and median household income on in-hospital AIS mortality. Results: We observed significantly higher AIS mortality in 2020 than prior years (2020 versus 2016-19, 7.3% versus 6.3%, P P P =0.001). Comparing April to December 2020 to 2019, the adjusted risk of in-hospital AIS mortality was most notably increased in Hispanics (2020 versus 2019: 9.2% versus 5.8%, P P Conclusions: In-hospital stroke mortality increased in 2020 in the United States because of comorbid AIS and COVID-19, which had higher stroke severity. The increase in AIS mortality during April-December 2020 was significantly more pronounced in Hispanics and those in the lowest quartile of household income.

Background: The “1-3-6-12-day rule” for starting direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation after acute ischemic stroke or transient ischemic attack recommends timings that may be later than used in clinical practice. We investigated more practical optimal timing of DOAC initiation according to stroke severity. Methods: The combined data of prospective registries in Japan, Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-nonvalvular atrial fibrillation (September 2011 to March 2014) and RELAXED (February 2014 to April 2016) were used. Patients were divided into transient ischemic attack and 3 stroke subgroups by the National Institutes of Health Stroke Scale score: mild (0–7), moderate (8–15), and severe (≥16). The early treatment group was defined as patients starting DOACs earlier than the median initiation day in each subgroup. Outcomes included a composite of recurrent stroke or systemic embolism, ischemic stroke, and severe bleeding within 90 days. Six European prospective registries were used for validation. Results: In the 1797 derivation cohort patients, DOACs were started at median 2 days after transient ischemic attack and 3, 4, and 5 days after mild, moderate, and severe strokes, respectively. Stroke or systemic embolism was less common in Early Group (n=785)—initiating DOACS within 1, 2, 3, and 4 days, respectively—than Late Group (n=1012) (1.9% versus 3.9%; adjusted hazard ratio, 0.50 [95% CI, 0.27–0.89]), as was ischemic stroke (1.7% versus 3.2%, 0.54 [0.27–0.999]). Major bleeding was similarly common in the 2 groups (0.8% versus 1.0%). On validation, both ischemic stroke (2.4% versus 2.2%) and intracranial hemorrhage (0.2% versus 0.6%) were similarly common in Early (n=547) and Late (n=1483) Groups defined using derivation data. Conclusions: In Japanese and European populations, early DOAC initiation within 1, 2, 3, or 4 days according to stroke severity seemed to be feasible to decrease the risk of recurrent stroke or systemic embolism and no increase in major bleeding. These findings support ongoing randomized trials to better establish the optimal timing of DOAC initiation.

Background: Evidence regarding the utilization and outcomes of endovascular thrombectomy (EVT) for pediatric ischemic stroke is limited, and justification for its use is largely based on extrapolation from clinical benefits observed in adults. Methods: Weighted discharge data from the National Inpatient Sample were queried to identify pediatric patients with ischemic stroke ( Results: Among 7365 pediatric patients with ischemic stroke identified, 190 (2.6%) were treated with EVT. Utilization significantly increased in the post-EVT clinical trial era (2016–2019; 1.7% versus 4.0%; P P P =0.830; adjusted hazard ratio, 1.01 [95% CI, 0.51–2.03]; P =0.972 for unfavorable outcome). Among patients with baseline National Institutes of Health Stroke Scale score >11 (75th percentile of scores in cohort), EVT-treated patients trended toward higher rates of favorable functional outcomes compared with those treated medically only (71.4% versus 55.6%; P =0.146). In a subcohort assessment of EVT-treated patients, those administered preceding thrombolytic therapy (n=79, 41.6%) trended toward higher rates of favorable functional outcomes (63.3% versus 49.5%; P =0.060). Conclusions: This cross-sectional evaluation of the clinical course and short-term outcomes of pediatric patients with ischemic stroke treated with EVT demonstrates that EVT is likely a safe modality which confers high rates of favorable functional outcomes.

Introduction: Data on predictors of early stroke recurrence in patients with symptomatic intracranial atherosclerotic disease (sICAD) is limited. We hypothesized that hypoperfusion delay predicts stroke recurrence within 90-days. Methods: We retrospectively collected all patients hospitalized with anterior circulation sICAD over 3 years (April 2019-April 2022) at a comprehensive stroke center. We collected demographics, clinical risk factors, radiological variables, and treatment strategies. Patients with an indication for anticoagulation such as atrial fibrillation and those with intracranial stenting or angioplasty were excluded. The outcome (verified by two independent reviewers) was recurrent stroke within 90 days in the affected artery. We assessed factors associated with stroke recurrence. We measured the effect of hypoperfusion delay volume on stroke recurrence using Cox-regression models. Results: Out of 131 sICAD hospitalizations during the study period, 66 involved the middle cerebral artery (MCA) M1 segment or intracranial internal carotid artery (ICA) and 44 patients met the inclusion criteria. The mean age was 71 years and 41% were women; 75% were treated with best medical management (dual antiplatelet therapy/high intensity statin therapy); and 75% had baseline perfusion imaging performed. Over 90 days, 11/44 (25%) patients had recurrent stroke. Factors associated with recurrence stroke were no best medical management (15.2% vs. 54.5%, p = 0.02), hypoperfusion Tmax>4 sec mismatch volume (p = 0.003), and hypoperfusion delay Tmax>6 sec mismatch volume (p=0.01). Using Youden’s cutoff for Tmax>4 sec mismatch (13 mL) and for Tmax>6 sec mismatch (5 mL), the risk of recurrent stroke at 90 days in separate models was higher in patients with Tmax>4 sec delay mismatch volume > 13 mL (HR 11.98 95% CI 1.48-96.96 p=0.02) and Tmax>6 sec mismatch volume > 5 mL (HR 4.37 95% CI 1.02-18.82, p=0.048). Effect size of the associations did not meaningfully change after adjusting for best medical management. Conclusion: Hypoperfusion delay is associated with an increased recurrent stroke risk within 90 days in patients with sICAD, despite best medical management. Validation by large prospective studies is warranted.

Background: While optimizing medical treatment contributed to the low recurrence risk seen in SAMMPRIS medical arm, other factors such as delayed enrollment may have contributed to this low event rate. In this study, we aim to determine the 30-day recurrence risk in a real-world setting in patients with symptomatic intracranial atherosclerosis. Methods: We used a stroke registry of a comprehensive stroke center to identify hospitalized patients with acute ischemic stroke in the setting of symptomatic intracranial atherosclerosis of the ICA, M1, vertebral, or basilar with 50-99% luminal narrowing. We excluded patients with a clear indication for anticoagulation and those who received endovascular treatment. The outcome was recurrent stroke attributed to the affected artery within 30-days. We used adjusted Cox regression models to identify factors associated with increased recurrence risk. Results: Among 131 symptomatic 50-99% intracranial stenosis hospitalizations over 3 years, 66 patients met the inclusion criteria. The mean age was 71.9 years and 51.5% were men; 75.8% were treated with best medical management (dual antiplatelet therapy/high intensity stain therapy). Over 30-day follow-up, 21.2 % had recurrent stroke, 57.1% (8/14) occurred within first 7 days. The recurrence risk was similar to another real world ICAD cohort, and higher than that seen in SAMMPRIS (Figure). While maximal medical treatment was the only factor associated with a lower rate of recurrence (OR 0.32 95% CI 0.09-1.12, p = 0.075), the recurrence rate in patients treated with maximal medical therapy (16.0%, 95% CI 8.1-29.3%) and those SAMMPRIS eligible (17.6%, 95% CI 7.9-34.9%) remained elevated. Conclusions: In patients with symptomatic ICAS, the real-world recurrence is higher than that seen in clinical trials, despite optimally using the same medical treatment strategies. This may suggest that the low risk of recurrence achieved in clinical trials may not apply to real world practice.

Introduction: Diastolic dysfunction, particularly with elevated left ventricle filling pressure (LVFP) is known to be a strong independent predictor of all-cause mortality and major cardiac events. There is limited data on the role of diastolic function in ischemic stroke. We hypothesize that diastolic dysfunction with elevated LVFP is more likely to be present in patients with Embolic stroke of undetermined source (ESUS) compared to non-cardioembolic stroke and is associated with AF on cardiac monitoring in the ESUS group. Methods: This is a single center retrospective study that included adult patients with a diagnosis of acute ischemic stroke from 2014 to 2016. We excluded patients with confirmed cardioembolic stroke and those with indeterminate diastolic function. ESUS was defined as no ipsilateral stenoses ≥ 50%, cardiac telemetry for at least two weeks without evidence of atrial fibrillation or atrial flutter, and a LVEF ≥ 30%. A transthoracic echocardiogram was performed and interpreted by cardiologists. Baseline patient characteristics and clinical variables were compared among patients with and without diastolic dysfunction. Potential associations between diastolic dysfunction, ESUS and AF detection in ESUS patients were assessed using logistic regression. Results: There were 509 patients, the mean age was 64.19, 54.81% were male, and 146 had LVFP data. Diastolic dysfunction overall was not associated with ESUS (adjusted OR 1.44, 95% CI 0.91-2.28, p = 0.125) or AF detection on cardiac monitoring (adjusted OR 1.87, 95% CI 0.75-4.70, p = 0.183). However, diastolic dysfunction and elevated LVFP was associated with ESUS subtype (adjusted OR 2.26, 95% CI 1.03-4.93, p = 0.041) and AF detection on cardiac monitoring (adjusted OR 3.58, 95% CI 1.07-12.01, p = 0.039). Conclusion: Our study suggests that diastolic dysfunction with elevated LVFP is associated with ESUS stroke subtype and AF detection on cardiac monitoring. Therefore, the presence of diastolic dysfunction with elevated LVFP may identify a population of stroke patients more likely to have ESUS, particularly in the setting of occult AF. Studies are needed to confirm our findings and test the safety and efficacy of anticoagulation in patients with ESUS and diastolic dysfunction with elevated LVFP.

Background: Intracranial dural arteriovenous fistulae (DAVF) are uncommon vascular anomalies with a reported incidence of 0.2 per 100,000 person years. An association between cerebral venous thrombosis (CVT) and DAVF has been reported; however, the direction of causality between the two remains uncertain. We aimed to identify the incidence and predictors of development of DAVF among patients with CVT. Methods: This is a post-hoc analysis of Anticoagulation in the Treatment of Cerebral Venous Thrombosis (ACTION-CVT), a multicenter retrospective study comparing outcomes of CVT patients treated with warfarin versus direct oral anticoagulants (DOACs) from 2015 to 2020. Patients were included in this analysis if they did not have DAVF on initial imaging and had follow-up vascular imaging during the study. Clinical, imaging, and anticoagulation characteristics of patients who developed DAVF were compared to those who did not. Stepwise binary logistic regression including important variables (achieving p Results: A total of 751 patients (median age 43, 66% female) met inclusion criteria of whom 13 (1.7%) developed DAVF with an estimated rate of 2.40 per 100 patient years. Patients with DAVF were less likely to have headache at presentation (53.8% vs 79.3%, p=0.037), but more likely to have no venous recanalization on follow-up imaging (46.2% vs 14.8%, p=0.008), baseline cortical vein thrombosis (15.4% vs 2.7%, p=0.053), and received warfarin (vs. DOACs) as initial oral anticoagulant (84.6% vs 58.7%, p=0.085) but the latter two missed the statistical significance threshold. In stepwise binary logistic regression analysis, cortical vein thrombosis (OR 7.98, 95% CI 1.40-45.35, p=0.02) and lack of venous recanalization (OR 4.93, 95% CI 1.48-16.39, p=0.01) were associated with development of DAVF. Conclusion: In this large multicenter study of CVT, the incidence of DAVF development was higher than the previously reported rate in the general population. The presence of cortical vein thrombosis and lack of venous recanalization were associated with increased risk of development of DAVF.

Introduction: Cervical artery dissection (CAD) is a well-recognized cause of acute ischemic stroke, especially in young adults, accounting for up to 20-25% of all cases. Several studies reported an incidence between 2.5-5 per 100,000 in the general population. However, the actual incidence may be higher as many patients remain asymptomatic. Even though CAD is one of the leading causes of ischemic stroke, there is a lack of consensus in management. Our study surveyed practicing clinicians involved in the management of CAD to characterize current practice trends and provide a foundation for future research. Methods: An online case-based questionnaire with 11 questions regarding the management of cervical artery dissection was developed and piloted internally with 12 Mayo Clinic cerebrovascular neurologist/neurosurgeons. The survey was finalized, and initially sent to the STOP-CAD study group. We then sent the survey to practicing vascular neurologists across different academic institutions. Surveys were sent to 126 unique individuals. Results: A total of 42 clinicians completed the questionnaires. The response rate was 33% (42/126). Aspirin antiplatelet monotherapy was seen as the most appropriate therapy for asymptomatic CAD (81% [34/42]). Anticoagulation was the treatment of choice for cases with CAD and concomitant intraluminal thrombus (74% [31/42]). Most (74% [31/42]) of the participants recommended repeat imaging at three months. However, no consistent response regarding the type of antithrombotic agent for symptomatic CAD without intramural thrombus or cases with pseudoaneurysm. There was marked variability regarding the duration of antithrombotic therapy, ranging from three months to life-long treatment. Conclusion: Marked variability was seen in the management of CAD, especially regarding the choice of antithrombotic agent in symptomatic and complicated (stenosis or pseudoaneurysm) cases and the duration of such therapy, which reflects the lack of definitive clinical trial data. Ongoing research is needed to better guide the optimal management of these patients.

Introduction: Trials have shown that WATCHMAN left atrial appendage closure (LAAC) for stroke is noninferior to oral anticoagulation (OAC) for stroke prevention in patients with atrial fibrillation (AF). Since the approval of WATCHMAN, real world clinical outcome of LAAC is still limited. We performed a state wide analysis to evaluate clinical outcomes for AF patients undergo LAAC. Methods: Using the Healthcare Cost and Utilization Project (HCUP) State Inpatient Database, we included New York state adult patients, who had AF diagnosis with and without LAAC procedure from 2011 to 2017. Patients who had acute ischemic stroke (AIS) or history of AIS prior or during index admission were excluded. AF, AIS and other diagnosis were identified based on standard ICD-9 CM and ICD-10 CM codes. We compared rates of AIS, intracranial hemorrhage (ICH) and death between patients with and without LAAC. We also constructed a Cox regression model to determine hazard ratios (HR) of LAAC associated with each outcome. Results: Of the 627,972 patients with AF admitted, the mean age was 75.8 and 33.1% were female, and 773 (0.1%) underwent LAAC. AIS readmission occurred in 0.030% of AF patients without LAAC while it occurred in 0.012% of patients underwent LAAC. In the Cox regression model, LAAC had similar AIS readmission (HR 0.84, 95% CI 0.44-1.62, P = 0.602) and ICH readmission (HR 1.688, 95% CI 0.63-4.50, P = 0.296), but LAAC was associated with less death (HR 0.295, 95% CI 0.20-0.43, P < 0.001). These outcomes remained the same despite adjustment with common risk factors and insurance type, or adjustment with CHADS 2 VASC 2 scores. In sensitivity analysis, after restricting to patients that had ICH prior to index admission, LAAC again had similar AIS readmission (HR 1.884, 95% CI 0.26-13.46, P = 0.528) compared to non-LAAC group but still marginally associated with less death (HR 0.289, 95% CI 0.07-1.16, P = 0.080). Conclusion: In New York state, AF patients underwent LAAC procedural are less likely to have death during follow up despite adjustment of common risk factors or CHADS 2 VASC 2 score, while AIS and ICH readmission appears to be similar. However, given potential underlying confounding by treatment indication, these findings need confirmation by ongoing randomized control trials.

Background: Individuals with diabetes mellitus are prone to neurologic complications from prolonged hyperglycemia. While the effects of hyperglycemia are well documented, aggressive correction of systemic glucose levels may have deleterious effects. We aimed to identify whether diabetic treatment goals influenced the progression of white matter hyperintensities (WMH) burden in a meaningful way in a cohort of known diabetics. We hypothesized that more aggressive treatment would yield less WMH progression. Methods: We included individuals enrolled in the ACCORD-MIND trial who had a baseline and 40-month follow-up MRI with volumetric quantification of WMH in mL. The primary outcome was WMH progression, defined as the baseline adjusted difference in WMH between the two scans. The exposure was the interaction between a microvascular outcome (ACCORD composite of photocoagulation or vitrectomy for retinopathy, acute renal failure, ESRD/dialysis, or serum creatinine ≥3.3 mg/dL) and glucose treatment arm (standard therapy with target A1c 7-7.9 or intensive therapy with target A1c 6-6.9). We fit a linear regression model adjusted for baseline age, sex, race/ethnicity, history of cardiovascular disease including stroke, Hgb A1c, and mean systolic blood pressure between the MRIs. Results: We included 502 individuals (mean age 62.7±5.7 years, 46.2% female, 67.9% White), of which 29 had a microvascular outcome and 229 were randomized to the intensive glucose arm. The interaction between microvascular outcome*glucose arm was highly significant (p=0.009). In individuals without a microvascular outcome, WMH progression was not significantly different in the intensive vs. standard glucose arm (difference of 0.3 mL, 95% CI -0.2, 0.7; p=0.299), but in those with a microvascular outcome there was 2.6 mL more WMH progression in the intensive than standard glucose arm (95% CI 0.9-4.4; p=0.003). Conclusion: Although hypothesis-generating, these results suggest that in diabetic individuals with microvascular disease, intensive glucose lowering may have a harmful effect on WMH progression. Our data is similar to other findings amongst the ACCORD trial suggesting intensive glucose control may not be benign in all diabetics.

Introduction: Sulfonylurea medications may reduce cerebral edema following ischemic stroke. Prior retrospective studies evaluated the impact of pre-stroke sulfonylurea exposure on outcome metrics yielding inconclusive results and have not provided results based on stroke subtype. We hypothesize that exposure to pre-stroke sulfonylureas would have a better outcome than unexposed regardless of stroke etiology. Methods: We performed a post-hoc analysis of the Stroke Hyperglycemia Insulin Network Effort (SHINE) dataset. Only those with pre-enrollment diabetes mellitus were included. The primary exposure was pre-stroke sulfonylurea usage. The primary outcome was 90-day functional outcome by mRS 0 - 2 (good) versus 3 - 6 (poor). Ischemic stroke was categorized as lacunar or non-lacunar. Standard descriptive and logistic regression analyses were used for data interpretation. Results: A total of 919 individuals met inclusion criteria: mean age 65 years, 58% male, 256 (28%) being sulfonylurea exposed. Lacunar stroke was diagnosed in 220 (24%) of the cohort. Pre-stroke sulfonylurea exposure was reported in 256 participants (lacunar: 59 vs. non-lacunar: 197, p = 0.69). Amongst the whole cohort, exposed individuals were more likely to have a poor outcome (OR 1.7, 95%CI 1.25 - 2.32, p = Conclusion: Patients with pre-stroke sulfonylurea exposure were more likely to have a poor outcome at 90 days. Current trials investigating sulfonylurea infusion for cerebral edema, though these data suggest chronic oral administration may mitigate this response. Limitations exist including potential unaccounted differences amongst the cohort. This is a hypothesis generating study with future studies needed expand and corroborate our findings.

Introduction: White matter hyperintensity (WMH) is a neuroimaging manifestation of cerebrovascular disease that is associated with vascular risk factors and the development of cognitive impairment and stroke. Estimating atherosclerotic cardiovascular disease (ASCVD) risk is a method of measuring the extent of vascular risk for a given individual and, thus, there exists a potential link between ASCVD risk and WMH volume. Methods: We included participants in the SPRINT MIND study who underwent a research MRI with volumetric quantification of the burden of WMH in mL. We report the WMH burden by categories of 10-year ASCVD risk using the Pooled Cohort Equations CV Risk (2014 edition). The ASCVD categories include low (0-5%), borderline (5-7.49%), intermediate (7.5-19.9%), and high (>20%). We used a violin plot to show the results graphically and also report the medians and IQR. As a secondary outcome we report WMH progression, which is the difference in WMH burden between the baseline MRI and a follow-up MRI performed 48 months later. Results: We included 727 individuals, of which 22 (3.0%) were low, 46 (6.3%) were borderline, 370 (50.9%) were intermediate, and 289 (39.8%) were high ASCVD risk. The median (IQR) WMH burden was 1.6 mL (0.9-2.9) in the low, 1.7 mL (1.1-3.0) in the borderline, 2.7 mL (1.4-5.1) in the intermediate, and 4.7 mL (2.5-10.7) in the high ASCVD risk group (p Conclusions: There is a positive association between ASCVD risk and WMH volume and progression. ASCVD risk, which can be assessed through demographic and clinical variables, may be a useful predictor of the volume of WMH, which is traditionally obtained through an MRI scan.

Background and Purpose: Recanalization after cerebral venous thrombosis (CVT) is poorly understood. We aimed to investigate predictors and timing of recanalization in a large, international cohort of patients with CVT. Materials and Methods: We used data from the multicenter, international, AntiCoagulaTION in the Treatment of Cerebral Venous Thrombosis (ACTION-CVT) study of consecutive patients with confirmed CVT from 01/2015 to 12/2020. Our analysis included patients that had undergone repeat venous neuroimaging more than 30 days after initiation of anticoagulation treatment. Pre-specified variables were included in univariate and multivariable analyses to identify independent predictors of failure to recanalize. We also examined improvement in recanalization at clinically-relevant time points ( Results: Among the 551 patients (mean age, 44.4 ± 16.2 years, 66% women) that met inclusion criteria, 486 (88.2%) had complete or partial, and 65 (11.8%) had no recanalization. In multivariable analysis, older age (OR, 1.05; 95% CI, 1.03 - 1.07), male sex (OR, 0.44; 95% CI, 0.24 - 0.80), and lack of parenchymal changes on baseline imaging (OR, 0.53; 95% CI, 0.29 - 0.96) were associated with no recanalization. The majority of improvement in recanalization (71.1%) occurred before 3 months from initial diagnosis. A high percentage of complete recanalization (59.0%) took place within the first 3 months after diagnosis. Discussion: Older age, male sex, and lack of parenchymal changes were associated with no recanalization after CVT. The majority of improvement in recanalization and complete recanalization occurred early in the disease course.

Background: Although prior research has investigated the association of race/ethnicity with stroke severity, the cohorts were not nationally representative or stroke severity was put into categories (i.e, mild to severe). Methods: We performed an analysis of adult hospital discharges in the National Inpatient Sample 2016-2019 with a primary diagnosis of ischemic stroke (I63*) and an admission NIH Stroke Scale (NIHSS). We treat NIHSS as an interval variable because the 43 levels (0-42) approximate an interval variable and prior simulations have demonstrated that it does not inflate the type I error. We fit linear regression models to NIHSS with the predictor or self-reported race/ethnicity (White, Black, Hispanic, other). Model 1 is unadjusted, model 2 is adjusted for age and sex, model 3 is further adjusted for atrial fibrillation, diabetes, congestive heart failure, and hypertension, and model 4 is further adjusted for income quartile by zip code and primary payor. Results: We included 138,680 stroke discharges with a mean NIHSS of 6.7±7.3. The cohort was 68.8% White, 17.2% Black, 8.0% Hispanic, and 6.0% other. In unadjusted analysis, White discharges have a significantly lower NIHSS than other race/ethnicity (Figure 1). After sequential adjustments, Black discharges consistently have the most severe stroke severity, which is ~1 NIHSS point higher than White discharges (p Conclusion: In a large, contemporary, and nationally representative sample of acute ischemic stroke patients, we show an association between non-White race/ethnicity and higher stroke severity. These results require further validation, but are concerning for a potentially underappreciated health disparity in ischemic stroke.

Introduction: Stroke secondary to intracranial atherosclerosis (ICAD) results in three distinct infarct patterns: (a) border zone infarcts (BZI) due to impaired distal perfusion (b) territorial infarcts due to distal plaque/thrombus embolization, and (c) perforator infarcts due to plaque progression. Previous studies indicate higher stroke recurrence in ICAD patients with BZI. Methods: This registered systematic review (CRD42021265230) comprised Medline and Web of Science search from inception to March 2022 for keywords (Intracranial Atherosclerosis OR Intracranial Stenosis) AND (Border zone OR Infarct Pattern) to identify papers and conference abstracts reporting initial infarct patterns and recurrence rates in patients with symptomatic ICAD. Sensitivity analyses were performed for studies including any BZI vs isolated BZI and those excluding posterior circulation strokes. The study outcome included neurological deterioration and/or stroke recurrence. For all outcome events, corresponding risk ratios (RR) and 95% confidence intervals (CI) were calculated. Risk of bias assessments will be presented. Results: Literature search yielded 4478 studies,11 met inclusion criteria (n=1315 patients, 354 with BZI, weighted proportions summarized in figure). The meta-analysis of these studies with moderate heterogeneity (I 2 =38.7%) demonstrated that RR of outcomes in BZI group compared to non-BZI group was 2.10 (95% CI 1.52-2.90). Limiting analysis to studies including any BZI, RR (and 95% CI) was 2.32 (1.58-3.40), and 3.25 (2.09-5.07) for studies only including anterior circulation strokes with low heterogeneity for both (I 2 =0%). A non-significantly high outcome rate was seen with isolated BZI (RR 2.29, 95% CI 0.94-5.62) but with moderate heterogeneity across studies (I 2 =70.25%). Conclusion: We demonstrate the presence of BZI secondary to symptomatic ICAD can be imaging biomarker to predict neurological deterioration and/or stroke recurrence.

Introduction: Up to 25% of strokes are recognized upon awakening. Recent studies have demonstrated that a “tissue clock” rather than a time clock can be used to identify patients who may benefit from intravenous thrombolytics (IVT) beyond 4.5 hours from last known well (LKW). Consistent access to hyperacute MRI limits many centers from treating wake-up stroke patients. We created a formal protocol of clinical and imaging criteria to standardize evaluation and management of wake-up strokes. Methods: This retrospective, observational study reviewed consecutive patients admitted to our Comprehensive Stroke Center who qualified for the wake-up protocol between February 2022 and June 2022. The implemented protocol, based on clinical trials’ inclusion criteria, is comprised of the following: 1) arrival within 12 hours from LKW and within 4.5 hours from symptom discovery; 2) high suspicion for acute ischemic stroke; 3) no contraindication to MRI; 4) NIHSS of at least 4; 5) baseline mRS 0-3; 6) no absolute contraindications to IVT. For patients meeting above inclusion criteria, emergent MRI with perfusion was performed. Diffusion-FLAIR mismatch (signal intensity ratio) and diffusion-perfusion mismatch were reviewed to determine thrombolysis eligibility by a trained neuroradiologist or vascular neurologist. Results: Ten patients qualified for the wake-up protocol in the first five months of protocol implementation. Median NIHSS was 7, median LKW to arrival time was 8 hours, and median door to MRI time was 72.5 minutes. A final diagnosis of ischemic stroke was made in 80% of these cases. Overall, 50% were eligible for IVT based on our criteria, and 30% received thrombolysis. Median door to needle time was 92 minutes (range 75-117). There were no symptomatic intracranial hemorrhages. All patients treated with IVT were discharged home with no to minimal residual deficits with mRS 0-1 and median NIHSS at discharge of 2 (range 0-4). Conclusion: A formal protocol for wake-up stroke management allowed a streamlined approach to expand the number of IVT-eligible cases. Continued efforts are needed to improve door to needle times in such cases and to follow clinical courses of treated patients.

Introduction: Management of anterior circulation emergent large vessel occlusion with tandem carotid occlusion (TCO) remains a challenge during mechanical thrombectomy (MT). To day, there is no consensus regarding emergent carotid stenting (ECS) in the setting of MT with TCO. We aimed to compare the outcomes of ECS versus conservative management (MT alone) among patients with TCO. Methods: Data from the Stroke Thrombectomy and Aneurysm Registry between 2010 and 2022 was interrogated. Only patients with concomitant occlusions of cervical carotid and proximal ipsilateral intracranial segments of the ICA or MCA were included in the analyses. We compared baseline, procedural charecteristics, successful reperfusion (mTICI 2b-3), favorable 90-day good outcomes (mRS 0-2), intravenous tPA administration and symptomatic ICH between patients who did or did not undergo ECS. Multivariate regression was performed adjusting for variables of clinical importance. Propensity score matching for IV tPA use was performed to explore its safety with stenting. Results: Among 9812 thrombectomy patients, 688 patients had TCO; 132 underwent emergent stenting and 444 had MT alone. Patients who did not undergo ECS had a higher prevalence of atrial fibrillation (33.9% Vs 9.2%, P Conclusion: ECS during MT for TCO appears to be safe and is associated with better clinical and angiographic outcomes compared to conservative management.

Background: Elevated systolic blood pressure (SBP) has been linked to pre-procedural rebleeding risk and poor outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, the relationship between blood pressure parameters including mean arterial pressure (MAP) with rebleeding both prior to and during aneurysm securement remains unclear. This study seeks to determine the association between BP parameters and rebleeding events and outcomes in patients with aSAH. Design/Methods: We performed a retrospective analysis of a prospectively collected cohort of consecutive patients with aSAH admitted to an academic center between July 2016 and March 2021. All BP parameters, which were recorded on an hourly basis from admission, were reviewed. Per our institutional protocol, the SBP target is Results: The cohort included 295 patients (mean age 57 years [SD 13.4], 61% female, 87% received endovascular treatments, 13% surgical clipping). Two or more consecutive SBP values >140 were seen in 41% and >160 in 15% of patients. Rebleeding prior or during securing aneurysms including intra-procedural bleeding occurred in 53 patients (18%). There was no association between either maximum recorded SBP (169.7 mmHg [36.2] vs. 166.9 [32.7], p=0.57) or MAP (121 mmHg [22.9] vs. 117.8 [22.9], p=0.42) and rebleeding. However, maximum recorded MAP was associated with poor outcome (OR 1.01 for 1 mmHg increase in MAP, 95% CI: 1.006-1.02, p=0.039). Conclusions: Elevated MAP peri-securement of a ruptured cerebral aneurysm can be associated with poor outcome. Multicenter prospective studies should further examine the association between MAP cut offs and outcomes to be considered in guidelines.

Introduction: Few clinical features have been associated with delayed diagnosis of cerebral venous thrombosis with variable impact of delay on patient outcomes. We therefore sought to use the data from a recent, multicenter study ACTION-CVT (Anticoagulation in the Treatment of CVT) to identify factors associated with delayed CVT diagnosis and evaluate the effect of delay on functional outcome. Methods: All ACTION-CVT patients with available data on date of neurological symptom onset and date of CVT diagnosis were included. Delayed diagnosis of CVT was defined as diagnosis occurring in the fourth (final) quartile of days from symptom onset. We also report the proportion of patients who were discharged from hospital or ED within 3 months prior to index CVT admission for any neurological symptom without being diagnosed with CVT. The primary study outcome was an excellent functional outcome at 90 days defined as modified Rankin Scale (mRS) ≤1. Secondary outcome was partial or complete CVT recanalization on last available venous imaging. Chi-squared and Student’s t-tests were used to identify variables associated with delayed diagnosis. Logistic regression was used to identify independent predictors of delayed diagnosis in CVT as well as the association of delay with outcomes. Results: We included 935 CVT patients in our analysis. Median time from symptom onset to diagnosis was 4 days (IQR: 1-10). Delayed CVT diagnosis occurred in 212 (23%) patients (median time to diagnosis >10 days). Out of 212 patients with delayed CVT diagnosis, 64 (30.2%) patients were discharged from hospital/ED in the 3 months prior to their index CVT admission. Headache symptoms were a predictor of delayed diagnosis (OR: 2.36 [1.26-4.42]; p Conclusion: In a large, multicenter cohort we found that CVT patients presenting with headache were at increased risk of delayed diagnosis, however, delayed diagnosis was not associated with adverse outcomes. CVT diagnosis should be considered in patients presenting with a new headache.

Introduction: Asymptomatic intracerebral hemorrhage (aICH) occurs in ~40% of acute ischemic stroke patients after endovascular thrombectomy (EVT). Unlike symptomatic ICH, which is undoubtedly associated with worse outcomes, studies evaluating the association of aICH on long-term outcomes have been inconclusive. We performed a systematic review and meta-analysis to evaluate the long-term effects of post-EVT aICH. Methods: The meta-analysis protocol was submitted to PROSPERO a priori. PubMed, SCOPUS and Web of Science were searched from inception through April 2022 using database-specific searches with combination of keywords and controlled vocabulary. After deduplication, two authors independently reviewed all abstracts. Included studies contained adult AIS patients undergoing EVT with follow-up imaging assessment of ICH reporting comparative outcomes according to aICH vs no ICH . Meta-analysis was performed using Cochrane Review Manager v5.4. Summary effects were estimated by a fixed-effects model to estimate summary odds ratio (OR) of the effect of aICH vs no ICH on primary outcomes of 90-day modified Rankin score 3-6 and mortality. Results: Systematic review yielded 278 studies; 52 abstracts were fully reviewed ; 8 studies fulfilled inclusion criteria (n=4701 patients total; 1562 with aICH). aICH was associated with 90-day mRS 3-6 (OR 2.11 [95% CI 1.85-2.40]; Figure 1A) and higher mortality (OR 1.66 [95% CI 1.41-1.96]; Figure 1B) compared to no ICH. There was insufficient evidence of difference in 90-day mRS 3-6 when studies were grouped according to Heidelberg (n=2 studies; OR 2.37 [95% CI 0.92, 6.12]) vs ECASS (n=5 studies; OR 2.07 [95%CI 1.62, 2.64]) criteria for ICH. Meta-regression analysis adjusting for covariates will be presented Conclusion: aICH is associated with worse 90-day functional outcomes and higher mortality. Further studies to evaluate the factors predicting aICH and treatments aimed at reducing its occurrence are warranted.

Background: The risk of ischemic stroke mortality increases with age, but the impact of stroke severity on this relationship has not been fully examined. Methods: We included adults in the National Inpatient Sample from 2016-2019 who had a primary discharge diagnosis of ischemic stroke (I63*) and a baseline NIH Stroke Scale (NIHSS). The primary outcome was in-hospital death. The exposure of age had left skew, so we transformed it into deciles. We fit a logistic regression model adjusted for sex, race/ethnicity, diabetes, atrial fibrillation, hypertension, thrombolytic therapy, and endovascular therapy. We report the predicted probability of the primary outcome with and without NIHSS and use structural equation modeling (SEM) to estimate the proportion of age’s effect on the primary outcome that is mediated by stroke severity. Results: We included 138,637 individuals, of which 3.5% died in-hospital. The proportion of in-hospital death and an NIHSS violinplot by decile of age are seen in Figure 1, both of which had a positive linear relationship. The AUC of the multivariable model without NIHSS was 0.70 and with NIHSS was 0.86 (p Conclusions: We found that elderly individuals in the United States have more severe stroke and higher stroke mortality, but the effect of age on stroke mortality is primarily mediated by elderly individuals having more severe stroke. Additional research is needed to better understand this novel finding.

Atrial fibrosis, a determinant of atrial cardiopathy, is seen more commonly in ESUS as compared to non-cardioembolic stroke patients and precedes changes in atrial dimension. We utilized speckle tracking echocardiography (STE) to identify atrial cardiopathy and to investigate the association between LA strain and ESUS compared to NCE stroke. Hospitalized patients with ESUS and NCE stroke subtypes who underwent in-hospital STE were included. Three phases of LA strain (reservoir, conduit, and contractile) were retrospectively calculated. Binary logistic regression analyses using LA strain as a continuous variable and as tertiles were performed to determine the association between different phases of LA strain and stroke subtypes (ESUS vs NCE). Among 680 total stroke patients, 355 were classified as NCE and 325 as ESUS. LA reservoir strain (36.3 ± 18.3 vs. 31.5 ± 17.8), LA contractile strain (17.4 ± 11.1 vs. 15.4 ± 10.4), and LA conduit strain (19.0 ± 11.9 vs. 16.7 ± 11.7) differed significantly between NCE and ESUS stroke subtypes. The fully adjusted binary logistic regression revealed that the lowest tertile of LA reservoir (OR 2.378, 95% CI 1.538-3.676), contractile (OR 1.555, 95% CI 1.032-2.342), and conduit strain (OR 2.009, 95% CI 1.293-3.124) was more likely to be associated with ESUS compared to NCE stroke. When using strain as continuous variables, LA reservoir (OR 0.987, 95% CI 0.977-0.997) and conduit strain (OR 0.980, 95% CI 0.965-0.996) were significantly reduced in ESUS compared to NCE. Our study demonstrates that reduced LA strain is more strongly associated with ESUS compared to NCE stroke subtype. We believe that atrial cardiopathy carries mechanistic significance and measuring LA strain may become a critical imaging biomarker in ESUS stroke prognostication.

Introduction: Percutaneous gastrostomy tubes are frequently required for patients with strokes due to dysphagia, malnutrition, and intestinal dysmotility. Though generally well tolerated, delayed detection of complications following percutaneous gastrostomy tube insertion (including dislodgement, infection and bleeding) can lead to increased morbidity and mortality. Methods: At a single academic tertiary hospital, a standardized protocol was instituted (September 2021) to enhance early detection and prevention of feeding tube complications on the neurology service, consisting predominantly of stroke patients. The protocol comprised of: 1) consistent documentation of feeding tube insertion by proceduralists, 2) universal abdominal binder application, 3) nursing driven delirium screening, 4) post procedural nursing assessment for high-risk feeding tube site changes, and 5) an escalation algorithm to address early complications. We compared rates of complications pre- (July 2020 - August 2021, 13 months) and post- (September 2021 - June 2022, 10 months) protocol implementation. Results: A total of 103 gastrostomy tube insertions were reviewed (64 pre and 39 post protocol implementation). Overall complication rates decreased from 12.5% (N = 8 of 64; 3 dislodgements, 3 infections, 2 insertion site bleeding) to 2.5% (N = 1 of 39; 1 dislodgment) following the intervention. Mortality from complications decreased from 1.6% to 0%. Conclusion: Complication rates of percutaneous gastrostomy tube placement may be reduced through implementation of standardized protocols on inpatient stroke patients. Further studies are warranted to assess its long-term effects and viability in other specialty services.

Background: An individual’s atherosclerotic burden is associated with the cumulative exposure to vascular risk factors across the lifespan. We used the ARIC study to identify trajectories of atherosclerotic cardiovascular disease (ASCVD) risk over time and to evaluate their association with risk of stroke and cognitive impairment. Methods: We included cardiovascular disease-free ARIC participants with low or borderline ASCVD risk at the baseline study visit (10-year ASCVD Risk Score Results: We included 3,470 ARIC participants. The four trajectories of ASCVD risk during follow-up are in Figure 1. The low and high increase trajectories comprised 46.5% and 7.0% of participants. Vascular risk factors such as hypertension, diabetes, hyperlipidemia, and obesity were more common in trajectories with higher ASCVD risk (Table 1). The rate of ARIC-adjudicated stroke during follow-up increased from 1.6% in the low trajectory to 4.6% in the high trajectory (p Conclusions: We found four main trajectories of ASCVD risk over 25 years of follow-up in individuals with baseline low or borderline ASCVD risk, which are associated with the risk of incident stroke and cognitive impairment. assessment.

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.

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 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 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: 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 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.

Introduction: The faster IV Alteplase and mechanical thrombectomy is initiated in acute ischemic stroke, the better the outcome. Delays can significantly impact times to treatment. A mechanism to communicate time targets to code stroke teams can play an important role in providing knowledge about time sensitive metrics. The utilization of the ASA Stroke Time Tracker tool was created to improve communication in a timely manner to stroke teams providing acute treatment. The emphasis is on the education of time targets to improve door to treatment times. Hypothesis: To explore whether the use of the American Stroke Association Time Tracker tool as a communication instrument is associated with improved DTN and DTD times in both direct and transfer patients. Methods: In March 2020 the application of the ASA time tracker tool was introduced. A retrospective review revealed that DTN times improved from 58.7% to 71.6 % for those receiving t-PA within 45 minutes or less during the period the tool was in use. To explore whether timely feedback using the Time Tracker tool was associated with improved DTD times, mechanical thrombectomy data including DTD was collected and communicated to stroke care teams in April 2021. Compilation of time sensitive metrics in the evaluation of DTN times continued through Q2 2021. A retrospective analysis was conducted. Results: For those who received IV Alteplase, the percentage of patients treated within 30 minutes continued to improve, 21.1% (Q3 2020) vs. 35.7% (Q2 2021). The percentage of patients treated within 45 minutes also improved from 71.8% (Q3 2020) to 80.0% (Q2 2021). In patients who received endovascular therapy during Quarter 3 2020, 56.1% met the advanced therapy AHA Elite Plus criteria of DTD within 60 minutes (transfer patients) OR within 90 minutes (direct admit). This improved to 73.1% patients in Quarter 2 2021, during the use of the tool. Conclusions: There is an association between use of the ASA Time Tracker tool and improved DTN and DTD times. Further study should include continued use of the tool to confirm an association between direct communication with Code Stroke teams and improved treatment times.

Introduction: Midlife hypertension is associated with an increased later-life ischemic stroke risk. However, temporal trends of blood pressure have not been fully explored. Methods: We performed a post hoc analysis of the ARIC study and included participants with four systolic blood pressures (SBP) at Visits 1-4 (1987-1999). Patients who had an ischemic stroke, died, or were lost to follow-up before 1999 were excluded from the analysis. We used group-based trajectory modeling to define six distinct SBP trajectories during Visits 1-4 (Figure 1). We report unadjusted and adjusted hazard ratios from Cox models fit to the primary outcome of ischemic stroke during follow-up from 1999-2017. We confirmed the proportional hazards assumptions of our models. Results: We included 9,689 participants, of which 758 (7.8%) had an ischemic stroke during follow-up. The mean±SD age at Visit 1 was 54±6 years and at Visit 4 was 63±6 years. The adjusted Cox models, Table 1, show the highest risk of ischemic stroke with increasing hypertension or stable severe hypertension. Comparing trajectories with similar baseline hypertension confirmed that increasing hypertension and stable severe hypertension had a higher risk than decreasing trajectories with the same starting point. Conclusion: Midlife blood pressure trajectory is associated with later-life ischemic stroke risk. Patients with hypertension who achieved a midlife reduction in systolic blood pressure were less likely to have a later-life stroke than those who did not.

Introduction: Hematoma expansion (HE) in patients with intracerebral hemorrhage (ICH) is a key predictor of poor prognosis and potentially amenable to treatment. Current clinical scoring models, radiological markers, and labs have limited ability to predict HE. This study aimed to create a more robust classification model to predict HE in patients with ICH using a deep learning algorithm, an artificial neural network (ANN). Methods: Data from the ATACH 2 trial (Antihypertensive Treatment of Acute Cerebral Hemorrhage) was utilized. Variables included in the models were chosen as per literature consensus on salient factors associated with HE and clinical expertise. HE was defined as increase in either >33% or 6mL in hematoma volume in the first 24 hours. A multi-layer feedforward ANN was trained using the back-propagation method to minimize the loss function with 5-fold cross validation. 80% of patients were used for training and 20% for testing. The ANN was compared to a logistic regression model (GLM). Given the imbalance in patients with HE, AUPRC (area under the precision-recall curve), recall and precision were calculated for the respective models. Results: Of the 963 patients in the study (mean age 62±13.0, 38.5% female), 31% had hematoma expansion. The median [interquartile range (IQR)] initial hematoma volume was 10.5mm 3 [5.16 - 20.25], median admission SBP [IQR] was 200 [184-217], median platelet count [IQR] was 213 [178-256], median INR [IQR] was 1.0 [0.9-1.0], and median admission GCS [IQR] was 15 [13-15]. The GLM model had AUPRC of 0.38 with recall of 0.60 and precision of 0.38 in the testing cohort. The ANN training model demonstrated AUPRC of 0.92 with recall of 0.72 with precision of 0.39 during testing. Initial ICH volume, platelets, INR, and GCS had the highest feature importance. Conclusion: We developed an ANN to predict HE in ICH patients performing with improved sensitivity and similar positive predictive value when compared to GLM. We support that ANN can capture complex associations between variables not attainable in classic regression models. This model may help identify patients at risk for HE who warrant careful monitoring and aggressive treatment upfront including those suitable for clinical trials for treatments.