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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 and Purpose Intracranial arterial stenosis (ICAS)-related stroke occurs due to three primary mechanisms with distinct infarct patterns: (1) borderzone infarcts (BZI) due to impaired distal perfusion, (2) territorial infarcts due to distal plaque/thrombus embolization, and (3) plaque progression occluding perforators. The objective of the systematic review is to determine whether BZI secondary to ICAS is associated with a higher risk of recurrent stroke or neurological deterioration.Methods As part of this registered systematic review (CRD42021265230), a comprehensive search was performed to identify relevant papers and conference abstracts (with ≥20 patients) reporting initial infarct patterns and recurrence rates in patients with symptomatic ICAS. Subgroup analyses were performed for studies including any BZI versus isolated BZI and those excluding posterior circulation stroke. The study outcome included neurological deterioration or recurrent stroke during follow-up. For all outcome events, corresponding risk ratios (RRs) and 95% confidence intervals (95% CI) were calculated.Results A literature search yielded 4,478 records with 32 selected during the title/abstract triage for full text; 11 met inclusion criteria and 8 studies were included in the analysis (n=1,219 patients; 341 with BZI). The meta-analysis demonstrated that the RR of outcome in the BZI group compared to the no BZI group was 2.10 (95% CI 1.52–2.90). Limiting the analysis to studies including any BZI, the RR was 2.10 (95% CI 1.38–3.18). For isolated BZI, RR was 2.59 (95% CI 1.24–5.41). RR was 2.96 (95% CI 1.71–5.12) for studies only including anterior circulation stroke patients.Conclusion This systematic review and meta-analysis suggests that the presence of BZI secondary to ICAS may be an imaging biomarker that predicts neurological deterioration and/or stroke recurrence.

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.

Advances in acute ischemic stroke (AIS) treatment have been contingent on innovations in neuroimaging. Neuroimaging plays a pivotal role in the diagnosis and prognosis of ischemic stroke and large vessel occlusion, enabling triage decisions in the emergent care of the stroke patient. Current imaging protocols for acute stroke are dependent on the available resources and clinicians’ preferences and experiences. In addition, differential application of neuroimaging in medical decision-making, and the rapidly growing evidence to support varying paradigms have outpaced guideline-based recommendations for selecting patients to receive intravenous or endovascular treatment. In this review, we aimed to discuss the various imaging modalities and approaches used in the diagnosis and treatment of AIS.

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.

Guidelines recommend a confirmed diagnosis of atrial fibrillation (AF) to initiate oral anticoagulation in cryptogenic stroke (CS) patients. However, the intermittent nature of AF can make detection challenging with intermittent short-term cardiac monitoring.The purpose of this retrospective cohort study was to examine post-CS utilization of cardiac monitoring and associated clinical outcomes.Adults with incident hospitalization for CS were identified in the Optum® claims database and assessed for cardiac monitoring received poststroke. Patient were stratified into those with a long-term insertable cardiac monitor (ICM) vs external cardiac monitor (ECM) only. The timing of ICM placement poststroke was treated as a time-dependent covariate. The clinical outcomes of interest were time to AF diagnosis, oral anticoagulation usage, and all-cause mortality.A total of 12,994 patients met selection criteria for the analysis, of whom 1949 (15%) received an ICM and 11,045 (85%) received ECM only. In those who had received an ECM as their first monitoring modality, only 4.4% moved on to receive an ICM for longer-term monitoring. Use of ECM before ICM was associated with a longer time to AF diagnosis (median 336 vs 194 days). Compared to those with ECM only, ICM patients had a significantly lower rate of death (hazard ratio [HR] 0.70;In a real-world study of CS patients, prolonged cardiac monitoring was associated with higher rates of AF detection and treatment, and higher odds of survival.

BackgroundIn 2017 the CDC issued an alert that, after decades of consistent decline, the stroke death rate levelled off in 2013, particularly in younger individuals and without clear origin. The objective of this analysis is to understand whether social determinants of health have influenced trends in stroke mortality.MethodsWe performed a longitudinal analysis of county-level ischemic and hemorrhagic stroke death rate per 100,000 adults, from 1999-2018 using a Bayesian spatiotemporally smoothed CDC dataset stratified by age [35-64 (younger) and ≥65 (older)] and then by county-level social determinants of health. We report stroke death rate by county and the percentage change in stroke death rate in 2014-18 compared to 2009-13.ResultsWe included data from 3,082 counties for younger individuals and 3,019 counties for older individuals. The stroke death rate began to increase for younger individuals in 2013 (pDiscussionImprovements in the United States’ stroke death rate are slowing and even reversing in younger individuals and many US counties. County-level increases in stroke death rate were associated with distinct social determinants of health for younger versus older individuals. These findings may inform targeted public health strategies.

Background and PurposeThe relationship between the degree and location of vertebrobasilar stenosis and QMRA distal-flow status is uncertain. Our aim was to investigate the relationship between QMRA distal-flow status with degree and location of vertebrobasilar stenosis.MethodsWe retrospectively reviewed patients who presented with acute ischemic stroke, had neurovascular imaging demonstrating ≥50% stenosis of extracranial or intracranial vertebral or basilar arteries, and QMRA performed within one year of stroke, between 2009 and 2021. Standardized methods were used to measure the degree of stenosis and to dichotomize vertebrobasilar distal-flow status. Patients were grouped based on the involved artery and the location and severity of disease. P-values were calculated using chi-squared analysis and Fisher exact test with statistical significance defined as p ResultsSixty-nine patients met study inclusion, consisting of 31 with low distal-flow and 38 with normal distal-flow states. Low distal-flow states were found exclusively in patients with severe stenosis or occlusion; however, severe stenosis or occlusion was poorly predictive of distal-flow status as nearly half of these patients had normal flow states (47%). Bilateral vertebral disease was significantly associated with low distal-flow states compared to patients with unilateral vertebral (70.8% versus 14.3%; p = 0.01), isolated basilar (70.8% versus 28.6%; p = 0.01), or mixed (71.4% versus 47.1%; p = 0.01) disease.ConclusionsSevere stenosis of ≥70% may mark the minimal threshold required to cause hemodynamic insufficiency in the posterior circulation, but nearly half of these patients may remain hemodynamically sufficient. The presence of bilateral vertebral stenosis resulted in a five-fold increase in the probability of QMRA low distal-flow status compared to unilateral vertebral disease. Our findings may have implications for the design of future treatment trials of endovascular versus medical management that may use hemodynamic markers as inclusion criteria.

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.

The past decade has seen significant advances in stroke prevention. These advances include new antithrombotic agents, new options for dyslipidemia treatment, and novel techniques for surgical stroke prevention. In addition, there is greater recognition of the benefits of multifaceted interventions, including the role of physical activity and dietary modification. Despite these advances, the aging of the population and the high prevalence of key vascular risk factors pose challenges to reducing the burden of stroke. Using a cause-based framework, current approaches to prevention of cardioembolic, cryptogenic, atherosclerotic, and small vessel disease stroke are outlined in this paper. Special emphasis is given to recent trials of antithrombotic agents, including studies that have tested combination treatments and responses according to genetic factors.

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

Progression of white matter hyperintensities (WMHs), a radiographic marker of cerebral small vessel disease, occurs with uncontrolled conventional cerebrovascular risk factors. Less certain, however, is the influence of dyslipidemia and the impact of 3-hydroxy-3-methylglutaryl-coenzyme-A reductase inhibitors (statins) on WMH progression. The goal of this study was to evaluate the influence of statins on the progression of WMH over a 4-year interval.We performed a post hoc analysis of the SPRINT-MIND database on those with serial volumetric WMH data. WMH progression was calculated as the difference in WMH volume between the 2 scans and then segmented into tertiles due to rightward skew. We defined statin usage as no therapy (0% of visits), partial therapy (1% to 99% of visits) or full therapy (100% of visits) as logged during study visits. Analysis of variance and χ2 tests were used for continuous and categorical variables with adjustments made for variables known to influence WMH development.A total of 425 individuals were included in this study: 53% without statins use, 27% partial use, and 20% full use. Demographic characteristics and baseline WMH volumes were similar among the cohort. Those with full statin use were significantly more likely to be in the top tertile of WMH progression (adjusted odds ratio: 2.30, 95% confidence interval: 1.11-4.77, P=0.025), despite improvement in dyslipidemia.SPRINT-MIND participants prescribed a statin were nearly 2.5 times more likely to be within the top tertile of WMH progression over 4 years, despite adjustment for synergistic risk factors and improvement in low-density lipoprotein.

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.

Background and ObjectivesProlonged poststroke cardiac rhythm monitoring (PCM) reveals a substantial proportion of patients with ischemic stroke (IS) with atrial fibrillation (AF) not detected by conventional rhythm monitoring strategies. We evaluated the association between PCM and the institution of stroke preventive strategies and stroke recurrence.MethodsWe searched MEDLINE and SCOPUS databases to identify studies reporting stroke recurrence rates in patients with history of recent IS or TIA receiving PCM compared with patients receiving conventional cardiac rhythm monitoring. Pairwise meta-analyses were performed under the random effects model. To explore for differences between the monitoring strategies, we combined direct and indirect evidence for any given pair of monitoring devices assessed within a randomized controlled trial (RCT).ResultsWe included 8 studies (5 RCTs, 3 observational; 2,994 patients). Patients receiving PCM after their index event had a higher rate of AF detection and anticoagulant initiation in RCTs (risk ratio [RR] 3.91, 95% CI 2.54–6.03; RR 2.16, 95% CI 1.66–2.80, respectively) and observational studies (RR 2.06, 95% CI 1.57–2.70; RR 2.01, 95% CI 1.43–2.83, respectively). PCM was associated with a lower risk of recurrent stroke during follow-up in observational studies (RR 0.29, 95% CI 0.15–0.59), but not in RCTs (RR 0.72, 95% CI 0.49–1.07). In indirect analyses of RCTs, the likelihood of AF detection and anticoagulation initiation was higher for implantable loop recorders compared with Holter monitors and external loop recorders.DiscussionPCM after an IS or TIA can lead to higher rates of AF detection and anticoagulant initiation. There is no solid RCT evidence supporting that PCM may be associated with lower stroke recurrence risk.

Background There are multiple tools available to visualize the retinal and choroidal vasculature of the posterior globe. However, there are currently no reliable in vivo imaging techniques that can visualize the entire retrobulbar course of the retinal and ciliary vessels. Purpose To identify and characterize the central retinal artery (CRA) using cone-beam CT (CBCT) images obtained as part of diagnostic cerebral angiography. Materials and Methods In this retrospective study, patients with catheter DSA performed between October 2019 and October 2020 were included if CBCT angiography included the orbit in the field of view. The CBCT angiography data sets were postprocessed with a small field-of-view volume centered in the posterior globe to a maximum resolution of 0.2 mm. The following were evaluated: CRA origin, CRA course, CRA point of penetration into the optic nerve sheath, bifurcation of the CRA at the papilla, visualization of anatomic variants, and visualization of the central retinal vein. Descriptive statistical analysis was performed. Results Twenty-one patients with 24 visualized orbits were included in the analysis (mean age, 55 years ± 15; 14 women). Indications for angiography were as follows: diagnostic angiography (n = 8), aneurysm treatment (n = 6), or other (n = 7). The CRA was identified in all orbits; the origin, course, point of penetration of the CRA into the optic nerve sheath, and termination in the papilla were visualized in all orbits. The average length of the intraneural segment was 10.6 mm (range, 7-18 mm). The central retinal vein was identified in six of 24 orbits. Conclusion Cone-beam CT, performed during diagnostic angiography, consistently demonstrated the in vivo central retinal artery, demonstrating excellent potential for multiple diagnostic and therapeutic applications. © RSNA, 2021 Online supplemental material is available for this article.

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.