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There are several controversies regarding the role of sex and gender in the pathophysiology and management of acute stroke. Assessing the role of sex, i.e., biological/pathophysiological factors, and gender, i.e., sociocultural factors, in isolation is often not possible since they are closely intertwined with each other. To complicate matters even more, the functional baseline status of women and men at the time of their first stroke is substantially different, whereby women have, on average, a poorer reported/ascertained baseline function compared to men. These differences in baseline variables account for a large part of the differences in post-stroke outcomes between women and men. Adjusting for these baseline differences is difficult, and in many cases, residual confounding cannot be excluded. Despite these obstacles, a better understanding of how patient sex and gender differences influence acute stroke and stroke care pathways is crucial to avoid biases and allow us to provide the best possible care for all acute stroke patients. Disregarding patient sex and gender on one hand and ignoring potential confounding factors in sex- and gender-stratified analyses on the other hand, may cause researchers to come to erroneous conclusions and physicians to provide suboptimal care. This review outlines sex- and gender-related factors in key aspects of acute stroke, including acute stroke epidemiology, diagnosis, access to care, treatment outcomes, and post-acute care. We also attempt to outline knowledge gaps, which deserve to be studied in further detail, and practical implications for physicians treating acute stroke patients in their daily practice.

Thrombolysis for acute ischemic stroke has predominantly been with alteplase for over a quarter of a century. In recent years, with trials showing evidence of higher rates of successful reperfusion, similar safety profile and efficacy of tenecteplase (TNK) as compared to alteplase, TNK has now emerged as another potential choice for thrombolysis in acute ischemic stroke. In this review, we will focus on these recent advances, aiming: (1) to provide a brief overview of thrombolysis in stroke; (2) to provide comparisons between alteplase and TNK for clinical, imaging, and safety outcomes; (3) to focus on key subgroups of interest to understand if there is an advantage of using TNK over alteplase or vice-versa, to review available evidence on role of TNK in intra-arterial thrombolysis, as bridging therapy and in mobile stroke units; and (4) to summarize what to expect in the near future from recently completed trials and propose areas for future research on this evolving topic. We present compelling data from several trials regarding the safety and efficacy of TNK in acute ischemic stroke along with completed yet unpublished trials that will help provide insight into these unanswered questions.

Introduction: Age is a predictor of functional outcome after acute ischemic stroke (AIS). Frailty increases with age and comorbidities, and imaging markers of brain-frailty (e.g. atrophy, small-vessel-disease) are associated with outcomes. However, the extent to which the association of age and 90-day outcome is mediated by brain-frailty is unknown. We explored this mediation in AIS patients receiving endovascular therapy (EVT), with a particular interest in neuroimaging. Methods: In this post-hoc analysis of the ESCAPE-NA1 trial, in which all patients underwent EVT, we assessed brain atrophy (subcortical/cortical), white-matter disease (periventricular/deep) and the number of lacunes and chronic infarctions. Structural equation modelling (SEM) was used to create 3 latent variables: “imaging-frailty” (above-mentioned markers), “clinical-frailty” (e.g. pre-stroke mRS, cardiovascular risk factors, cancer) and “total-frailty” (imaging + clinical markers). We created 3 models ( figure1) including each latent variable as a potential mediator of the association of age and 90-day outcome, adjusting for baseline ASPECTS, NIHSS, onset-to-puncture-time, nerinetide and alteplase. Results: Among 1,092 patients, the indirect effect of age on 90-day outcome, mediated by imaging-frailty, contributed 96% of the total effect(β=0.047;p=0.02), while the indirect effect through clinical-frailty accounted for only 21%(β=0.01;p=0.001) of the total effect. When including both frailty constructs, the indirect pathway accounted for 86% of the total effect(β=0.06;p Conclusions: Brian frailty mediates the association of age and 90-day outcome after EVT, with most of the effect mediated by imaging as opposed to clinical markers of frailty. This work underscores the importance of considering brain-frailty, as opposed to chronological age alone, in predicting post-stroke outcomes.

Background and Purpose: First pass effect (FPE), or effective reperfusion with a single pass of endovascular thrombectomy (EVT) for acute ischemic stroke (AIS), is strongly associated with good functional outcome (mRS≤2) and can aid in optimal device selection for EVT. We aim to investigate the arterial tortuosity from great vessel origin to the intracranial occlusion location and predict first pass effect, automatically by a novel neural network, on computed tomographic angiography (CTA). Materials and Methods: Patients with thin-slice (≤2.5 mm) neck CTA from the ESCAPE-NA1 trial (Efficacy and safety of nerinetide for the treatment of AIS) were included. Arterial centerlines from the aortic arch to the intracranial occlusion site were manually traced by three experienced readers on CTA. The centerlines were modeled and organized by tortuosity. A model based on graph neural network (GNN) was proposed to predict FPE on the processed data. Model performance was compared to manual annotations and traditional classification algorithms using diagnostic statistics. Results: 539 patients were included, with a 429/110 training/testing-ratio. FPE was observed in 136(31.7%, training set) and 35 (31.8%, testing set). The suggested model showed an overall good performance with an area under the receiver operating characteristic curve (AUC-ROC) of 0.66 (95% CI=0.65-0.67), precision of 0.46(17/37), sensitivity of 0.71(17/35), specificity of 0.61(55/75) and accuracy of 0.65(72/110), whereas the manually annotated features with traditional classification methods had an AUC-ROC of 0.54 (95%CI=0.53, 0.55), precision of 0.42(8/19), sensitivity of 0.23(8/35), specificity of 0.85(64/75) and accuracy of 0.65(72/110). Conclusion: An automated model for FPE prediction on CTA had better performance and higher sensitivity as compared to manual annotations and traditional machine learning algorithms, suggesting that it could be used in routine clinical practice prior to EVT.

Introduction: Brain-selective hypothermia is a promising neuroprotectant in acute ischemic stroke. However, a non-invasive bedside method to monitor brain temperature during cooling is lacking. We tested the feasibility and accuracy of measuring brain temperature non-invasively using sensors designed to monitor core body temperature. Methods: In this prospective single-center study, 20 patients with large or medium vessel occlusion strokes were enrolled. Patients underwent a 3T MR spectroscopy imaging (MRSI, the reference standard) and zero heat flux (ZHF) core temperature sensor measurements (3M TM Bair Hugger TM ) within 12-72 hours from admission. Two ZHF sensors were placed on each side of the forehead on the side of stroke and contralateral side and the temperatures were checked before and after MRSI. A 2x2x2 cm voxel was centered on the infarct and matching contralateral location using diffusion weighted imaging. Brain temperature on MRSI was calculated using the relative chemical shifts of water and N-acetyl aspartate. Temperature measurements of the ZHF sensors were compared to MRSI measurements. Results: The brain temperature of stroke and contralateral sides were similar using MRSI or using ZHF sensors when each modality was compared to itself by hemisphere (all p>0.05). However, there was a significant difference for the ipsilateral side: median (SD) temperatures using MRSI was 36.0°C (1.8) vs 36.8°C (0.5) for sensor measurement. Bland-Altman plots showed that 95% of the observations fell within upper and lower limits of agreement of -2.1 to +3.7°C while 61% of observations fell within an agreement limit of +/- 1°C. There was an indication of an overall higher temperature measurements using the ZHF sensors compared to MRSI (Figure 1). Conclusions: More studies are needed to validate the use of ZHF thermometry in ischemic stroke including studies implementing hypothermia. Figure 1. Boxplot of stroke side MRSI compared to zero-heat-flux sensors.

Endovascular therapy (EVT) is an effective treatment for ischemic stroke due to large vessel occlusion (LVO). Unlike intravenous thrombolysis, EVT enables visualization of the restoration of blood flow, also known as successful reperfusion in real time. However, until successful reperfusion is achieved, the survival of the ischemic brain is mainly dependent on blood flow from the leptomeningeal collaterals (LMC). It plays a critical role in maintaining tissue perfusion after LVO via pre-existing channels between the arborizing pial small arteries or arterioles overlying the cerebral hemispheres. In the ischemic territory where the physiologic cerebral autoregulation is impaired and the pial arteries are maximally dilated within their capacity, the direction and amount of LMC perfusion rely on the systemic perfusion, which can be estimated by measuring blood pressure (BP). After the EVT procedure, treatment focuses on mitigating the risk of hemorrhagic transformation, potentially via BP reduction. Thus, BP management may be a key component of acute care for patients with LVO stroke. However, the guidelines on BP management during and after EVT are limited, mostly due to the scarcity of high-level evidence on this issue. In this review, we aim to summarize the anatomical and physiological characteristics of LMC to maintain cerebral perfusion after acute LVO, along with a landscape summary of the literature on BP management in endovascular treatment. The objective of this review is to describe the mechanistic association between systemic BP and collateral perfusion after LVO and thus provide clinical and research perspectives on this topic.

Background and purpose: Endovascular treatment (EVT) is a powerful treatment for large vessel occlusion (LVO) stroke if reperfusion can be achieved, while in cases with failed reperfusion, EVT may cause harm, as procedure-related complications may occur. We hypothesized that EVT with failed recanalization does not result in worse outcomes compared to best medical management and compared clinical outcomes of LVO stroke patients who underwent EVT with failed reperfusion to those who were treated with best medical management. Methods: We included patients with failed reperfusion from the control (EVT-only) arm of the ESCAPE-NA1 trial and the EVT arm of the ESCAPE trial and patients of the ESCAPE control arm who were treated with best medical management. Failed reperfusion following EVT was defined as modified thrombolysis in cerebral infarction score 0–2a. Proportions of good outcome (modified Rankin scale 0–2) were compared between patients who did and did not undergo EVT, and adjusted effect size estimates for EVT on outcomes were obtained. Results: We included 260 patients (110 failed EVT and 150 non-EVT patients). Proportions of good outcome were 38/110 (34.6%) with failed EVT vs.43/147 (29.3%) without EVT (adjusted odds ratio[aOR]: 1.48 [95%CI: 0.81–2.68]). Mortality and proportions of sICH in the failed EVT group vs. patients treated with best medical management were 26/110 (23.6%) vs. 28/147 (19.1%), aOR: 1.12 (95%CI: 0.56–2.24), and 7/110 (6.4%) vs. 4/150 (2.7%), aOR: 2.34 (95%CI: 0.00–22.97). Conclusion: Clinical outcomes of EVT patients with failed reperfusion did not differ significantly from patients treated with best medical management.

Background and Purpose: Quantitating the effect of intravenous alteplase on the technical outcome of early recanalization of large vessel occlusions aids understanding. We report the prevalence of early recanalization in patients with stroke because of large vessel occlusion treated with and without intravenous alteplase and endovascular thrombectomy, and its association with clinical outcome. Methods: Patients with acute ischemic stroke with large vessel occlusion from the ESCAPE trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times Trial) were included in this post hoc analysis. Outcomes of interest were the prevalence of early recanalization (1) and good outcome (2), defined as modified Rankin Scale score of 0 to 2 at 90 days. Results: Among 147 patients who did not receive endovascular thrombectomy, early recanalization occurred in 4/30 (13.3%) patients without and 48/117 (41.0%) patients with intravenous alteplase (adjusted risk ratios, 3.2 [95% CI, 1.2–8.1]). Good outcome was achieved by 34/116 (29.3%) of patients who received intravenous alteplase versus 10/29 (34.5%) who did not receive alteplase (adjusted risk ratios, 1.0 [95% CI, 0.6–1.5) and by 20/52 (38.5%) patients with versus 24/93 (25.8%) without early recanalization (adjusted risk ratios, 1.9 [95% CI, 1.2–2.9]). Conclusions: Early recanalization was confirmed as a strong predictor of good outcome in patients who did not undergo endovascular thrombectomy and was improved with intravenous alteplase, yet a majority of patients (59.0%) did not achieve early reperfusion. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01778335.

The AcT trial (Alteplase Compared to Tenecteplase) compares alteplase or tenecteplase for patients with acute ischemic stroke. All eligible patients are enrolled by deferral of consent. Although the use of deferral of consent in the AcT trial meets the requirements of Canadian policy, we sought to provide a more explicit and rigorous approach to the justification of deferral of consent organized around 3 questions. Ultimately, the approach we outline here could become the foundation for a general justification for deferral of consent.

Background: 90-day home-time, the number of days a patient is back at their premorbid living situation without an increase in level of care in the first 90 days post stroke, is routinely collected in administrative data. We evaluated the prediction of 90-day home-time using machine learning modelling in patients undergoing endovascular treatment (EVT). Methods: We used the QuICR provincial stroke registry and administrative data from Southern Alberta from Jan 2015-Dec 2019 to identify patients who underwent EVT. Imaging data were scored by 2-physician consensus. The primary outcome was 90 day home-time, which has a highly non-normal distribution with excess zero’s. We modelled using generalized boosting machine model with Gaussian distribution. Contribution of different covariates to hometime was determined using partial dependence plots. Results: We identified 659 EVT patients from Jan 2015 to Dec 2019 treated in Calgary, Alberta. Overall,median predicted 90d home-time was 41days (IQR 5.5 to 77.8) with good model accuracy (Root mean square error 6.96). Holding other covariates constant, factors predicting lower 90d-hometime were diabetes mellitus(-14.1d), hypertension (-7d), low baseline ASPECTS (≤5) (-5.6d) and symptomatic intracerebral hemorrhage (sICH) on follow up scan (-13.8d). There was a consistent improvement in the predicted home-time over the last 5 years. There was no meaningful difference in predicted 90d-home-time by age, baseline NIHSS, sex, atrial fibrillation, occlusion site, tandem occlusion, thrombolysis, or successful reperfusion (Figure 1) Conclusions: Predicting 90-d hometime using boosting machine learning modelling is useful to assess complex relationships between predictors and home-time. Hypertension, diabetes, low ASPECTS and sICH were predictors of lower 90-d home-time in this registry.

Introduction: First-pass effect (FPE), i.e., achieving reperfusion with a single thrombectomy device pass, is associated with better clinical outcomes in patients with acute stroke. FPE is therefore increasingly being used as a marker of device and procedural efficacy. We evaluated the ability of thrombus-based radiomics models to predict FPE in patients undergoing endovascular thrombectomy (EVT) and compare performance to experts and non-radiomics thrombus characteristics. Methods: Patients with thin-slice non-contrast CT and CT angiography from The Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke (ESCAPE-NA1) trial were included. Thrombi were manually segmented on all images. Data was randomly split into a derivation set that included a training and a validation subset and an independent test set. Radiomics features were extracted from the derivation data set. Three expert stroke physicians reviewed baseline imaging and clinical data for the test set. The machine learning (ML) models were compared to the three experts in predicting the primary outcome (FPE) in the test set using area under the receiver operating characteristic curves (AUC-ROC). Results: A total of 554 patients with available thin-slice images comprised of a derivation set (training subset [n=388, 70%]), validation subset [n=55, 10%]), and a test set (n=111, 20%). FPE was seen in 31.8% in the derivation set and 31.5 % in the test set. AUC of the best radiomics model was 0.74 (95% CI: 0.64, 0.84), which was higher than the mean AUC of the three experts 0.60 (95% CI: 0.50, 0.71) ( P =0.009). Specificity of radiomics was better than the mean specificity of the three experts, 46 of 76 (60%) vs. 35 of 76 (46.4%), P =0.004, whereas sensitivity was not significantly different between radiomics (28 of 35 [79%]) and experts (27 of 35 [77%]). Moreover, radiomics features performed better than non-radiomics features such as thrombus volume and permeability measurements in predicting FPE ( P Conclusion: A radiomics-based ML model of thrombus characteristics on non-contrast CT and CT angiography performs better than experts and non-radiomics image characteristics in predicting FPE in patients with acute stroke treated with EVT.

Background: The outcome in stroke patients with ASPECTS of ≤5 who undergo Endovascular Thrombectomy(EVT) in Large Vessel Occlusion (LVO) is uncertain. We used machine learning models to predict 90-day home-time in these patients. Methods: We used the QuICR provincial stroke registry and administrative data from Southern Alberta to identify patients who underwent EVT from Jan 2015-Dec 2019. Imaging data were scored by 2-physician consensus. The primary outcome was the predicted 90-day home-time(number of days a patient is back at their premorbid living situation without an increase in level of care within 90 days of the stroke) using generalized boosting machine model with Gaussian distribution. Covariate contribution to hometime was determined using partial dependence plots. Results: Of 659 EVT patients, 82(12%) had baseline ASPECTS ≤5(mean age 69.8y, 44.6% females, 93% good-moderate collaterals, M1 occlusion(64.1%). Overall, patients with low ASPECTS had lower median predicted home-time by 2.8d. Holding other covariates constant, factors predicting lower 90d-home-time were diabetes mellitus(-14d), hypertension(-7d), and symptomatic intracerebral hemorrhage (sICH) on follow up scan(-14d). Home-time decreased with increasing age in both low and non-low ASPECTS groups, but the difference was larger in older age groups (Figure). There was no meaningful difference in predicted 90d-home-time by sex, atrial fibrillation, baseline NIHSS, occlusion site, tandem lesion, thrombolysis, or successful reperfusion. Conclusions: Among patients with low ASPECTS who underwent EVT, hypertension, diabetes and sICH predicted lower 90-d home-time. .

Introduction: Leptomeningeal collaterals help maintain cerebral perfusion after the large vessel occlusion (LVO), potentially regulated by systemic blood pressure (BP). We hypothesized that the association between BP and endovascular treatment (EVT) outcomes would differ by the baseline perfusions status and before and after recanalization. Method: From a prospective registry, we identified anterior circulation LVO patients who received EVT ≤24 hours after their onset, had baseline perfusion, and achieved post-EVT mTICI ≥2b. BPs were measured from arrival at 5-minute intervals in the ER and during the procedure. Systolic BPs (SBP) up to 24 hours after EVT were summarized as dropmax (the maximal decrement over two consecutive measurements), incmax (the maximal increment), mean, coefficient of variation, and standard deviation. Baseline perfusion images were quantified using Olea Sphere. Infarct proportion was defined as the volume of final infarct on DWI within the volume of Tmax>6 sec. Significant hemorrhage included PH2 or HBC class 3. 3-month mRS was prospectively collected. Result: A total of 388 LVO patients were included. Mean SBP at arrival was 153 ± 42 mm Hg; the average count of BP measurements was 47 ± 17 per patient.In the adequate baseline perfusion group, i.e., hypoperfusion intensity ratio (HIR) Conclusion: Association between BP and patient outcomes differs by baseline perfusion status and before and after recanalization. BP management during the peri-EVT period may therefore need to be individualized.

Objective Prognostic scores help in predicting mortality and functional outcome post intracerebral hemorrhage (ICH). We aimed to validate the ICH and ICH-GS scores in a cohort of Indian patients with ICH and observe the impact of any surgical intervention on prognostication. Methods This was an ambispective observational study of primary ICH cases enrolled between January 2014 and April 2018. Observed mortality on ICH and ICH GS scores for the entire cohort and individually for the medically and surgically managed patients was compared to the published mortality in the original derivation cohorts. Results 617 patients, (464 retrospective and 153 prospective) of ICH were included. In hospital mortality and 30-day mortality was 28.7% and 28.5% respectively. There was a significant association of increasing mortality with increasing ICH and ICH-GS scores. Area under receiver operating characteristic curve for 30-day mortality was 75.9% and 74.1% for ICH and ICH-GS scores respectively. However, mortality observed at individual scores was significantly less than previously reported. Among the surgically intervened patients (n = 265), both the expected mortality at baseline and discriminative ability of ICH and ICH-GS scores for 30-day mortality was significantly reduced following surgical intervention (ROC in surgically intervened groups: 59.9 (52.6-67.2) and 63(56-70) for ICH and ICH-GS scores respectively). Conclusions Although ICH and ICH-GS scores are valid in Indian population, mortality at individual scores is lower than previously reported. Mortality prediction using ICH and ICH GS scores is significantly modified by surgical interventions. Thus, newer prognostic tools which incorporate surgical intervention need to be developed and validated in future.

PURPOSE Cortical vein opacification is not routinely assessed in patients presenting with acute ischemic stroke (AIS), and the value of temporal assessment of venous outflow is not known. We evaluated the utility of assessing cortical venous drainage over time using multiphase CT angiography (mCTA). METHODS Cortical venous drainage was assessed in patients from the Precise and Rapid Assessment of Collaterals Using Multi-Phase CTA in the Triage of Patients With Acute Ischemic Stroke for IA Therapy prospective multicenter cohort study of patients with symptoms of AIS with ICA and/or middle cerebral artery occlusion on baseline mCTA. Opacification of vein of Labbe, sphenoparietal sinus, superficial middle cerebral vein, and vein of Trolard of the affected hemisphere was graded as no (0), partial (1), or full (2) opacification in each mCTA phase. The venous opacification scores for each phase were added to generate a total venous score (TVS) (range 0-24). Primary outcome was 90-day modified Rankin score. Repeated measures analysis was used to assess the effect of phase timing on venous score on outcome. RESULTS Of 432 patients, 284 (65.7%) had proximal arterial occlusions. Median venous opacification score per phase (range 0-8) was 3 (IQR 1-6) in the first phase and increased in the second and third phases [median (IQR): 6 (5-8) and 8 (6-8), respectively] of the mCTA. In a multivariable analysis adjusting for age, baseline National Institutes of Health Stroke Scale, and Alberta stroke program early CT score, a significant association between TVS and 90-day mRS was noted ([adjusted cOR for TVS 6-11: 0.16 (95% CI 0.05-0.51); TVS 12-17: 0.18 (95% CI 0.06-0.57); TVS 18-24: 0.20 (0.06-0.63)]. Repeated measures analysis of venous scores from all three phases showed a significant effect of time/phase on TVS (p

Background: Time from imaging to establishing reperfusion is a major influencer of clinical outcomes and over the years thrombectomy techniques have evolved rapidly. This has led to improvements in achieving fast and complete reperfusion. We analyzed the impact of various intra-procedural techniques and tools on the speed of reperfusion and correlated procedural duration with probability of achieving good clinical outcomes. Methods: We analyzed intra-procedural time metrics and examined factors leading to delays during EVT. The relationship between outcome (mRS Scale) and procedural time from arterial puncture to time of achieving mTICI 2b-3 First Reperfusion (FRE) was modeled using logistic regression. Results: The various procedural time metrics are summarized in Figure 1. Every 10-minute increase in FRE time reduced the probability of achieving functional independence(90-day modified Rankin Scale 0-2) by 6.7% (P=0.021, adjusted). The medianFRE timewas 25min (IQR 17-39) and was significantly longer in patients with tandem occlusions(median 34min, p 0.0005). General anesthesia vs procedural sedation vs no sedation use did not significantly alter the FRE time (p = 0.1453). The use of BGC (54.2%) was nominally longer FRE (median 26min “IQR 18-38” vs 23ming, “IQR 16-38”; p 0.095)while the use of contact aspiration (n=213) vs retrievable stents (n=676) as the first approach was associated with a shorter FRE time (21min “IQR 14-35” vs 26 min “IQR18-40”, p =0.001). Conclusions: Puncture to first reperfusion time is a significant predictor of clinical outcome in theESCAPE-NA1 trial. Various procedural and anatomical factors influence this timemetric. Figure: Intra-Procedural workflow time metrics expressed in medians and 90th percentiles. The cumulative times are calculated for each major milestone in the procedure for upto three attempts. First reperfusion duration where TICI 2b was achieved is shown in comparison to other procedural time metrics.

Purpose: We assessed whether balloon guide catheter (BGC) use during endovascular thrombectomy (EVT) influences procedural and clinical outcomes in the ESCAPE-NA1 trial. Methods: ESCAPE-NA1 was an international multicenter trial that randomized large vessel occlusion stroke patients who underwent endovascular thrombectomy (EVT) to receive Nerinetide vs. placebo. Information on EVT techniques and devices was extracted from angiographic images and procedure report forms. Effect estimates of BGC use on angiographic and clinical outcomes were obtained with logistic regression with adjustment for age, ASPECTS, baseline NIHSS, occlusion site, alteplase and study drug treatment. Results: Detailed information on EVT devices and technique was available for 891/1105 (80.6%) patients. A BGC was used in 599/891 patients (67.2%). BGC use was most common with a retrievable stent use (with or without distal access catheter) as the first-line approach (in 252/266 cases [94.7%] vs. combined approach (both aspiration and SR): 288/414 [69.6%], vs. contact aspiration: 37/159 cases [23.3%]). Overall, eTICI 2b/3 rates with vs. without BGC did not differ significantly (525/598 [87.8%] vs. 260/292 [89.0%]), but eTICI 2c/3 rates were significantly higher when a BGC was used (304/598 [50.8%] vs. 126/292 [43.2%], adjusted OR 1.39 [95%CI 1.05 - 1.9]). Good outcomes (mRS 0-2) were not associated with BGC use (adjusted OR 1.07 [95%CI 0.78 - 1.48]). Conclusion: BGC use was associated with a greater proportion of near-complete reperfusion, while there was no significant association with clinical outcomes.

Background: The degree of cortical venous opacification could reflect the degree of ischemia in tandem occlusions strokes. We assessed the association between asymmetric cortical vein opacification and outcome among patients with acute ischemic stroke and tandem occlusion. Methods: ESCAPE NA1 was a multicenter randomized-controlled trial comparing medical treatments nerinetide vs. placebo in patients with acute ischemic stroke and large vessel occlusion who underwent EVT. Tandem carotid occlusion was defined as complete occlusion of the ICA on catheter angiography. We assessed cortical venous opacification on baseline CTA using the COVES score (Jansen, et al. Radiology 2019, ranging from 0-6 with lower numbers indicating poor cortical venous filling, and dichotomized to 0 vs. 1-6). The influence of cortical venous opacification on functional outcome was analyzed using regression modelling with adjustment for age, baseline NIHSS and ASPECTS, thrombolysis and treatment allocation. Results: We assessed 115 patients with tandem occlusion. Median COVES score was 2 (IQR 1-3) with 9 patients (8%) scoring 0 (complete absence of cortical venous filling). Patients with COVES 0 were less likely to have good leptomeningeal collaterals (good collaterals: COVES 0: 0/9 (0%) vs. COVES 1-6: 19/102 (18%), p = 0.007). Patients with COVES 0 were less likely to achieve good outcome (mRS 0-2, COVES 0: 3/9 patients (33%) vs. COVES 1-6: 79/106 (74%), p=0.016). Cortical venous filling was significantly associated with good functional outcome on univariable analysis (OR 5.9, 95%CI 1.4 - 25.0), and after adjustment for baseline variables (OR 8.6, 95%CI 1.4 - 51.0). Cervical carotid angioplasty and/or stenting did not modify functional outcome after adjustment for COVES score. Conclusion: Impaired venous drainage is a marker of poor pial collaterals and is associated with poorer outcome in tandem occlusion patients.

Background: We evaluated technical aspects of stent retriever use and its relation to reperfusion in ESCAPE NA1 trial. Methods: ESCAPE-NA1 was a multicenter, international randomized trial assessing the efficacy of nerinetide in ischemic stroke patients who underwent EVT within 12h from onset. The following stent retriever characteristics were evaluated: stent retriever length, diameter, thrombus position in relation to stent retriever - proximal, middle or distal third, bypass effect during stent retriever deployment (Figure 1), and stent retriever placement in the anterior or posterior MCA trunk (in M1 occlusions). Primary outcome was reperfusion grade and the unit of analysis was stent retriever attempt. Results: Data from 1062 patients were evaluated. Angiographic data for up to three passes were analyzed as only 8.9% of patients required >3 passes. Stent retriever was used in 1241 passes in 808 patients. The occlusion sites were terminal ICA (14.9%), M1 MCA (58.7%), M2 MCA (23.7%), other (2.1%). A successful reperfusion attempt (mTICI 2b-3) was associated with the presence of bypass effect (OR 1.7; 95%CI 1.07-2.72), and positioning of stent retriever so the thrombus was in the proximal and middle third of stent retriever (OR 2.06; 95%CI 1.24-3.40 and OR 1.92; 95%CI 1.16-3.15, respectively). The position of the thrombus in the middle third of stent retriever was a significant predictor of bypass effect (OR 2.71; 95%CI 1.61-4.58). Stent retriever length, diameter, or choice of MCA trunk did not predict successful attempts, Table 1. Conclusion: Bypass effect and positioning of stent retriever so the thrombus was in proximal 2/3rds are predictors of successful reperfusion attempts.

Introduction: Infarct in new territory (INT) is a known complication of endovascular therapy. We assessed the prevalence, predictors and clinical relevance of INT Methods: We included patients from the ESCAPE-NA1: a multicenter, international randomized study that assessed the efficacy of intravenous nerinetide in patients with acute ischemic stroke who underwent EVT within 12 hours from onset. All imaging was re-evaluated, and INT was defined by presence of infarct in new vascular territory, outside the baseline target occlusion(s) on follow up CT and MRI. INT’s were classified by maximum diameter (20mm) and location. Results: Of 1099 analyzed patients in ESCAPE NA1, 107 had INT (9.7%, mean age 67 years, 51.4% females). There were no differences at baseline in those with vs without INT. Most INTs (75.7%) were angiographically occult and 41(38.3%) were > 20mm. The most common INT territory was the ACA alone or in combination with MCA/PCA (30.3%). The presence of emboli in new territory angiographically was significantly associated with INT (OR 16.39, 95%CI 8.14-33.09). Alteplase use, balloon guide catheter use, nerinetide and initial occlusion site did not predict INT. INT patients had higher final median infarct volumes compared to non-INT (44.5cc vs 23.3cc, P20mm) were associated with poor clinical outcome compared to INT ( Conclusion: Infarcts in new territory are common and are associated with poor outcome.

Objective: To determine the prevalence of non-stenotic carotid plaques ( Methods: Data was analyzed from the STRATIS registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke)—a prospective, nonrandomized study of patients undergoing thrombectomy with the Solitaire device. Prevalence of non-stenotic carotid plaques, ipsilateral and contralateral to the stroke was compared in patients with ESUS and cardioembolic strokes. Plaque features were further compared within both subgroups between patients with and without ipsilateral stroke. Uni- and multivariable logistic regression was performed to determine associations between non-stenotic carotid plaque, plaque characteristics, and ipsilateral stroke in both subgroups. Results: Of the 946 patients in the database, 226 patients with cardioembolic stroke (median age, 72 years) and 141 patients with ESUS (median age, 69 years) were included in the analysis.The prevalence of non-stenotic carotid plaque in the cardioembolic and ESUS subgroups was 33/226 (14.6%) and 32/141(22.7%) respectively. Bilateral non-stenotic carotid plaques were seen in 10/226(4.4%) cardioembolic and 13/141(9.2%) ESUS patients. Non-stenotic carotid plaques were significantly associated with ipsilateral strokes in cardioembolic stroke (aOR,1.91 [95% CI,1.15-3.18]) and in ESUS (aOR,1.69 [95% CI, 1.05-2.73]). Plaque irregularity, plaque hypodensity and increasing plaque thickness were significantly associated with ipsilateral stroke, only in the ESUS subgroup. Conclusion: Non-stenotic carotid plaques were significantly associated with ipsilateral stroke in cardioembolic and ESUS subgroups and there was increased association of hypodense plaque, increasing plaque thickness and plaque irregularity with ipsilateral stroke in the ESUS subgroup, suggesting these plaques could be a potential cause of stroke in these patient subgroups.

Purpose: In this post-hoc analysis of the ESCAPE-NA1 trial, we investigated the prevalence of deep grey matter infarcts and their influence on clinical outcome. Methods: Infarcts on 24 hour follow up imaging (non contrast head CT or diffusion-weighted MRI) were categorized as predominantly deep grey matter infarcts (caudate and/or lentiform nucleus infarcts with sparing of the superficial grey matter and white matter) vs. other infarcts. Total infarct volume was manually segmented in all patients. When MRI follow-up was available, deep grey matter and grey matter infarct volumes were segmented separately. Multivariable logistic regression with adjustment for key minimization variables and by infarct volume was used to assess the association of predominantly deep grey matter infarcts and good outcome. Results: Of the 1026 included patients, 316 (30.8%) had predominantly deep grey matter infarcts. Cumulative proportions of good outcome for overall, grey matter, deep grey matter, and superficial grey matter infarct volumes are shown in the figure. Good outcomes were more frequently achieved in patients with predominantly deep grey matter infarcts (239/316 [75.6%] vs. 374/704 [53.1%]). Deep infarcts were tightly correlated with infarct volume (Pearson rho -0.35) and in multivariable analysis deep grey matter infarcts were predictive of outcome overall; when examined in volume percentiles, there was no effect of deep infarct location. Conclusion: Predominantly deep grey matter infarcts are associated with good outcomes. Deep grey matter infarct location favorable prognosis is associated with small overall infarct size.

Purpose: We investigated the prevalence and prognostic impact on outcome of any intracranial hemorrhage, hemorrhage morphology, type and volume in acute ischemic stroke patients undergoing mechanical thrombectomy. Methods: Prevalence of intracranial hemorrhage, hemorrhage type, morphology and volume was determined on 24h follow-up imaging (non contrast head CT or gradient-echo/susceptibility-weighted MRI). Proportions of good outcome (mRS 0-2 at 90 days) were reported for patients with vs. without any intracranial hemorrhage. Multivariable logistic regression with adjustment for key minimization variables and total infarct volume was performed to obtain adjusted effect size estimates for hemorrhage type and volume on good outcome. Results: Hemorrhage on follow up-imaging was seen in 372/1097 (33.9%) patients, among them 126 (33.9%) with hemorrhagic infarction (HI) type 1, 108 (29.0%) with HI-2, 72 /19.4%) with parenchymal hematoma (PH) type 1, 37 (10.0) with PH2, 8 (2.2%) with remote PH and 21 (5.7%) with extra-parenchymal/intraventricular hemorrhage. Good outcomes were less often achieved by patients with hemorrhage on follow-up imaging (164/369 [44.4%] vs. 500/720 [69.4%]). Any type of intracranial hemorrhage was strongly associated with decreased chances of good outcome ( adj OR 0.62 [CI 95 0.44 - 0.87]). The effect of hemorrhage was driven by both PH hemorrhage sub-type [PH-1 ( adj OR 0.39 [CI 95 0.21 - 0.72]), PH-2 ( adj OR 0.15 [CI 95 0.05 - 0.50])] and extra-parenchymal/intraventricular hemorrhage ( adj OR 0.60 (0.20-1.78) Petechial hemorrhages (HI-1 and HI-2) were not associated with poorer outcomes. Hemorrhage volume ( adj OR 0.97 [CI 95 0.05 - 0.99] per ml increase) was significantly associated with decreased chances of good outcome. Conclusion: Presence of any hemorrhage on follow-up imaging was seen in one third of patients and strongly associated with decreased chances of good outcome.

Introduction: Emboli in new territory (ENT) are known potential complication of endovascular thrombectomy. We explored their incidence and predictors in ESCAPE-NA-1 trial. Methods: We included patients from the ESCAPE-NA1: a multicenter, international randomized study that assessed the efficacy of intravenous nerinetide in patients with acute ischemic stroke who underwent EVT within 12 hours from onset. All the imaging was reassessed, and ENT was defined as angiographic evidence of emboli in vascular territories other than the MCA, which was not present in the initial CT angiogram. We collected details of management and its influence on outcomes. Results: We analyzed 1095 patients from the ESCAPE NA1. ENT occurred in 40 patients (3.6%, mean age 69.5 years, 50% females). There were no significant differences at baseline in groups with and without ENT. Most common ENT site was ACA (38,95%). Thrombolysis, use of balloon guide catheter, nerinetide treatment, and initial occlusion site did not predict ENT. Seven ENTs (17.5%) were pursued with endovascular therapy: retrievable stents in 6 patients and intra-arterial thrombolysis in 1 patient. Patients with ENT had longer total arterial puncture to first reperfusion times (65 vs 40.5 minutes, P Conclusion: The incidence of ENT was low in ESCAPE NA1 trial but associated with poorer clinical outcomes.

Background: We evaluated clinical outcome in relation to the degree of reperfusion in ESCAPE-NA1 trial. Methods: ESCAPE-NA1 was a multicenter, international randomized trial assessing the efficacy of nerinetide in ischemic stroke patients who underwent EVT within 12h from onset. Independent clinical outcome [90-days modified Rankin Scale (mRS) 0-2], excellent clinical outcome (90-days mRS 0-1), isolated subarachnoid hemorrhage with no parenchymal hemorrhage (iSAH) or symptomatic hemorrhage (sICH) on follow-up imaging, and death were compared between a treatment group and control group with respect to the level of reperfusion defined as mTICI. Univariable and multivariable logistic regression analyses were performed. Results: Data from 1090 patients were assessed. The occlusion locations were terminal ICA (18.3%), M1 MCA (61.8%,) M2 MCA (15.1%), other - e.g. M3 (3.7%). Final mTICI 0-1 was achieved in 5.5% of patients, mTICI 2a in 7.5%, mTICI 2b in 40.8%, mTICI 2c in 26.6% and mTICI 3 in 19.5%. Isolated SAH was present in 1.7% and sICH in 3%. There was no significant difference between the nerinetide and control groups in the reperfusion grade, presence of iSAH or sICH, or in clinical outcome. Odds of independent outcomes (mRS 0-2) and odds of excellent outcome (mRS 0-1) were significantly increasing with each improved reperfusion grade, Table 1. Sixty percent of patients with final mTICI 2b, 70% with mTICI 2c and 69% with mTICI 3 achieved good clinical outcome in comparison to 30% of patients with mTICI 0-2a. The incidence of iSAH was significantly lower in the NA1 arm (OR 0.28, 95%CI: 0.09-0.86, p=.027) adjusting for reperfusion status. Conclusion: Degrees of better reperfusion are strongly associated with better outcomes and reduced mortality. mTICI 2c-3 reperfusion should be a standard goal of EVT.

Background: The optimal treatment for stroke patients with tandem cervical carotid occlusion is debated. We analyzed the treatment strategies and outcomes of tandem occlusion patients in the ESCAPE NA1 trial. Methods: ESCAPE NA1 was a multicenter international randomized trial of nerinetide vs. placebo in patients with acute ischemic stroke who underwent EVT. We defined tandem occlusions as complete occlusion of the cervical ICA on catheter angiography. The influence of tandem occlusions on outcome was analyzed using regression modeling with adjustment for age, sex, baseline NIHSS and ASPECTS, occlusion location, thrombolysis and treatment allocation. Results: 115 of 1105 patients (10.4%) had tandem occlusions. 73/115 tandem patients (66.0%) received treatment for the cervical occlusion: 21.9% were stented before thrombectomy, 68.5% were stented after thrombectomy, and 8.2% had angioplasty alone. Successful reperfusion was significantly higher in patients who had thrombectomy first followed by carotid treatment (eTICI 2b-3: 40/40 (100.0%)) or carotid angioplasty before and cervical stent after intracranial thrombectomy (9/10 (90.0%)) compared to carotid intervention before intracranial thrombectomy: (19/23 (82.1%), p=0.016). 90-day mRS 0-2 was achieved in 82/115 patients (71.3%) with tandem occlusions (treated occlusions: 74.0%, untreated: 66.7%) compared to 579/981 (59.5%) patients without tandem occlusions. In adjusted analysis, tandem occlusion was not predictive of outcome. In the subgroup of tandem patients, cervical stent-treatment was nominally associated with better outcomes (OR 2.2, 95% CI 0.5 - 9.2). Conclusion: Cervical carotid stenting may improve outcomes for EVT patients with tandem occlusions, but these results are limited by the sample size and non-randomized selection of patients for stenting.

Non-stenotic (50%) carotid plaques have recently been recognized as a potential source of stroke. This meta-analysis aims to summarize the prevalence of non-stenotic carotid plaques in stroke patients in general and in patients with embolic stroke of undetermined source in particular.We performed a comprehensive systematic review of the literature and meta-analysis on acute ischemic stroke patients in whom carotid imaging was performed using the MEDLINE, Embase and Cochrane database, including studies published up to December 2019. Keywords were "stroke", "transient ischemic attack", "carotid", "plaque", "atherosclerosis" and "disease". Included studies had ≥10 patients with acute ischemic stroke and reported the prevalence of non-stenotic (50%%stenosis) carotid plaques detected on any imaging modality.We included forty-five studies (n = 18304 patients, 48.4% males, mean age 63.6 years) in our meta-analysis. Imaging modalities used were ultrasound (n = 26 studies), CT-angiography (n = 7), magnetic resonance-imaging (n = 8) and catheter angiography (n = 4). The overall prevalence of non-stenotic carotid plaques was 51% (95% CI: 43 - 59). 10 studies included mainly patients with embolic stroke of undetermined source (50% of all patients). The pooled prevalence of non-stenotic carotid plaques in these studies was 55% (95% CI: 42 - 68). 23 studies explicitly reported ipsilateral non-stenotic carotid plaques, the pooled prevalence of which was 51% (95% CI: 45 - 59).In this meta-analysis, non-stenotic carotid plaques were present in more than 50% of all acute ischemic stroke patients, with a slightly higher prevalence in ESUS patients. Given the potential role of non-stenotic carotid plaques in stroke etiology, particularly in ESUS, further research should aim to identify criteria that predict the stroke risk associated with non-stenotic carotid plaques.

Background and Purpose— Embolic stroke of undetermined source (ESUS) constitutes a large proportion of acute ischemic stroke. It is crucial to identify possible stroke etiologies in this patient subgroup to individually tailor secondary stroke prevention strategies. This study aimed to assess the prevalence of carotid plaques causing Methods— Patients from INTERRSeCT—a multicenter prospective study of patients with acute ischemic stroke—were included in this study if their stroke etiology was not large artery atherosclerosis (>50% stenosis), and neck computed tomography angiography was obtained. Degree of stenosis ( Results— Four hundred forty-six patients were included in the study (median age, 73 years; 218 men), 138 of which were ESUS patients (median age, 70 years; 61 men). Nonstenotic carotid plaques (with P =0.004). Nonstenotic carotid plaques were significantly associated with ipsilateral strokes (adjusted odds ratio, 1.83 [95% CI, 1.05–3.18]). Conclusions— In patients with ESUS, nonstenotic carotid plaques were significantly more common on the side of the ischemic stroke, suggesting that these plaques could be a potential stroke etiology in patients in whom the ischemic stroke is classified currently as ESUS.

Background and Objectives Ischemic stroke (IS) and coronary artery disease (CAD) share common risk factors and one may be the harbinger of the other. We aimed to study prevalence of symptomatic and asymptomatic CAD in a cohort of consecutive patients with IS and assess its relationship with intracranial and extracranial large artery cerebrovascular disease (LAD). Methods All consecutive eligible IS and Transient Ischemic Attack (TIA) patients were recruited into the study. Both clinically suspected and asymptomatic patients (N = 259) underwent myocardial Stress-rest Gated Technetium-99m (Tc99m) MIBI Myocardial Perfusion SPECT scan performed on a dual head SPECT-CT to estimate evidence of myocardial ischemia. Results Three hundred patients completed the study. Forty one patients were previously diagnosed cases of definitive CAD. Twelve patients were clinically suspected to have CAD and 247 patients were asymptomatic. Among these, 12 patients (4.81%) had a positive SPECT. The overall prevalence of CAD was 17.67% (n = 53). Presence of diabetes was an independent predictor of CAD (OR 1.98, 95% CI 1.07-3.67. P .02). No significant association was found between the presence of LAD and CAD in all subgroup comparisons. However, there was a suggestion of higher LAD among patients with known CAD compared with others. Conclusions CAD is prevalent in patients with ischemic stroke. No definitive relationship was found between CAD and intracranial or extracranial LAD. Population based stratification tools are needed to further assess the need to detect subclinical CAD in patients with stroke.