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Transradial access has been described for mechanical thrombectomy in acute stroke, and proximal balloon occlusion has been shown to improve recanalization and outcomes. However, sheathed access requires a larger total catheter diameter at the access site. We aimed to characterize the safety of sheathless transradial balloon guide catheter use in acute stroke intervention.Consecutive patients who underwent sheathless right-sided transradial access for thrombectomy with a balloon guide catheter were identified in a prospectively collected dataset from 2019 to 2021. Demographics, procedure details, and short-term outcomes were collected and reported with descriptive statistics.A total of 48 patients (20 women) with a mean age of 72.3 years were identified. Of patients, 56.3% had occlusions in the left-sided circulation; 35 (72.9%) had M1 occlusions, 7 (14.6%) had M2 occlusions, and 6 (12.5%) had internal carotid artery occlusions. Tissue plasminogen activator was administered to 16 (33.3%) patients. Five (10.4%) patients underwent intraprocedural carotid stenting. The cohort had successful reperfusion after a median of 1 (interquartile range: 1, 2) pass. Median time from access to recanalization was 31 (interquartile range: 25, 53) minutes. A postprocedural Thrombolysis In Cerebral Infarction score of ≥2b was achieved in 46 (95.8%) patients. Five patients had wrist access site hematomas. All hematomas resolved with warm compresses, and no further intervention was required.Sheathless radial access using a balloon guide catheter may be safely performed for acute ischemic stroke with excellent radiographic outcomes. Further investigation is warranted to evaluate the comparative effectiveness of sheathless compared with sheathed transradial balloon guide access.

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

BACKGROUND AND PURPOSE: Infarct volume is an important predictor of clinical outcome in acute stroke. We hypothesized that the association of infarct volume and clinical outcome changes with the magnitude of infarct size. MATERIALS AND METHODS: Data were derived from the Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) trial, in which patients with acute stroke with large-vessel occlusion were randomized to endovascular treatment plus either nerinetide or a placebo. Infarct volume was manually segmented on 24-hour noncontrast CT or DWI. The relationship between infarct volume and good outcome, defined as mRS 0–2 at 90 days, was plotted. Patients were categorized on the basis of visual grouping at the curve shoulders of the infarct volume/outcome plot. The relationship between infarct volume and adjusted probability of good outcome was fitted with linear or polynomial functions as appropriate in each group. RESULTS: We included 1099 individuals in the study. Median infarct volume at 24 hours was 24.9 mL (interquartile range [IQR] = 6.6–92.2 mL). On the basis of the infarct volume/outcome plot, 4 infarct volume groups were defined (IQR = 0–15 mL, 15.1–70 mL, 70.1–200 mL, >200 mL). Proportions of good outcome in the 4 groups were 359/431 (83.3%), 219/337 (65.0%), 71/201 (35.3%), and 16/130 (12.3%), respectively. In small infarcts (IQR = 0–15 mL), no relationship with outcome was appreciated. In patients with intermediate infarct volume (IQR = 15–200 mL), there was progressive importance of volume as an outcome predictor. In infarcts of > 200 mL, outcomes were overall poor. CONCLUSIONS: The relationship between infarct volume and clinical outcome varies nonlinearly with the magnitude of infarct size. Infarct volume was linearly associated with decreased chances of achieving good outcome in patients with moderate-to-large infarcts, but not in those with small infarcts. In very large infarcts, a near-deterministic association with poor outcome was seen.

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.

There are few data on the prevalence and impact of isolated deep grey matter infarction in acute stroke. In this study, we aimed to investigate the prevalence of isolated deep grey matter infarcts and their impact on the outcome. Infarcts on 24-h follow-up imaging (non-contrast head CT or diffusion-weighted MRI) in the ESCAPE-NA1 trial were categorized into predominantly deep grey matter infarcts vs. infarcts involving additional territories (“other infarcts”). Total infarct volume was manually segmented. Baseline characteristics and proportions of good outcome (primary outcome, defined as modified Rankin Score [mRS] 0–2 at 90 days), excellent outcome (mRS 0–1) and mortality were compared between patients with and without predominantly deep grey matter infarcts. Multivariable logistic regression with adjustment for baseline variables and total infarct volume was used to determine a possible association of predominantly deep grey matter infarcts and clinical outcome. Predominantly deep grey matter infarcts were seen in 316/1026 patients (30.8%). Compared to other patients, their ASPECTS was higher, collateral status and reperfusion quality were better and time to treatment was shorter. Good outcome was seen in 239/316 (75.6%) with vs. 374/704 (53.1%) without predominantly deep grey matter infarcts. After adjusting for baseline variables and total infarct volume, predominantly deep grey matter infarcts were independently associated with excellent outcome (adjOR: 1.45 [CI95: 1.04–2.02]), but not with good outcome (adjOR: 1.24 [CI95: 0.86–1.80]) or mortality (adjOR: 0.73 [CI95:0.39–1.35]) Predominantly deep grey matter infarct patterns were seen in 1/3rd of patients and were significantly associated with increased chances of excellent outcome, independent of patient baseline status and infarct size.

BackgroundThe DAWN and DEFUSE-3 trials showed the benefit of endovascular treatment (EVT) in acute ischemic stroke patients presenting beyond 6 hours from last known well (LKW) and selected by perfusion imaging criteria. The ESCAPE NA1-trial selected patients based on non-contrast CT (NCCT) Alberta Stroke Program Early CT Score (ASPECTS) and multiphase CT angiography (CTA) collateral status. This study compares baseline characteristics, workflow, and outcomes in the EVT arms of DAWN and DEFUSE-3 with late-window patients from the EVT-only arm of ESCAPE-NA1.MethodsAggregate data on baseline characteristics, workflow, reperfusion quality, final infarct volume, and clinical outcomes (modified Rankin Score [mRS] at 90 days) in subjects enrolled in the DAWN and DEFUSE-3 EVT arms were compared with similar data from the ESCAPE-NA1 control arm (EVT-only arm) presenting beyond 6 hours from LKW using descriptive statistics.ResultsBaseline characteristics among late-window patients in the ESCAPE NA1 trial were similar to those in the DAWN and DEFUSE-3 EVT arms. Median time from LKW-to-puncture in subjects enrolled in the ESCAPE NA1 trial was 9 hrs (IQR: 7.5–11 hours) when compared with DAWN (n=107; 12.8 hours, IQR: 10.6–16.7 hours) and DEFUSE-3 (n=92; 11.5 hours, IQR: 9.2–12.8 hours). Median post-treatment infarct-volume was largest in the ESCAPE NA1-patients (47 mL [IQR: 19–146] vs median 8 mL [IQR: 0–48] in the DAWN group and 35 mL [IQR: 18–82] in DEFUSE-3), while % mRS 0–2 at 90 days were similar across the three trials (ESCAPE NA1: 50/111 [45%], DAWN: 52/107 [49%], DEFUSE-3: 41/92 [45%]).ConclusionPatients enrolled beyond 6 hours from LKW in the ESCAPE-NA1 trial based on NCCT-ASPECTS and mCTA had similar clinical outcomes when compared with patients selected by perfusion imaging in the DAWN and DEFUSE-3 trials.

CT angiography (CTA) is essential in acute stroke to detect emergent large vessel occlusions (ELVO) and must be interpreted by radiologists with and without subspecialized training. Additionally, grayscale inversion has been suggested to improve diagnostic accuracy in other radiology applications. This study examines diagnostic performance in ELVO detection between neuroradiologists, non-neuroradiologists, and radiology residents using standard and grayscale inversion viewing methods. A random, counterbalanced experimental design was used, where 18 radiologists with varying experiences interpreted the same patient images with and without grayscale inversion. Confirmed positive and negative ELVO cases were randomly ordered using a balanced design. Sensitivity, specificity, positive and negative predictive values as well as confidence, subjective assessment of image quality, time to ELVO detection, and overall interpretation time were examined between grayscale inversion (on/off) by experience level using generalized mixed modeling assuming a binary, negative binomial, and binomial distributions, respectively. All groups of radiologists had high sensitivity and specificity for ELVO detection (all > .94). Neuroradiologists were faster than non-neuroradiologists and residents in interpretation time, with a mean of 47 s to detect ELVO, as compared with 59 and 74 s, respectively. Residents were subjectively less confident than attending physicians. With respect to grayscale inversion, no differences were observed between groups with grayscale inversion vs. standard viewing for diagnostic performance (p = 0.30), detection time (p = .45), overall interpretation time (p = .97), and confidence (p = .20). Diagnostic performance in ELVO detection with CTA was high across all levels of radiologist training level. Grayscale inversion offered no significant detection advantage. • Stroke is an acute vascular syndrome that requires acute vascular imaging. • Proximal large vessel occlusions can be identified quickly and accurately by radiologists across all training levels. • Grayscale inversion demonstrated minimal detectable benefit in the detection of proximal large vessel occlusions.

Rationale Following endovascular treatment, poor clinical outcomes are more frequent if the initial infarct core or volume of irreversible brain damage is large. Clinical outcomes may be improved using neuroprotective agents that reduce stroke volume and improve recovery. Aim The aim of the REPERFUSE NA1 was to replicate the preclinical neuroprotection study that significantly reduced infarct volume in a primate model of ischemia reperfusion. Specifically, REPERFUSE NA1 will determine if administration of the neuroprotectant NA1 prior to endovascular therapy can significantly reduce early (Day 2 subtract Day 1 diffusion-weighted imaging volume) and delayed secondary infarct (90-day whole brain atrophy plus FLAIR volume—Day 1 diffusion-weighted imaging volume) growth, as measured by magnetic resonance imaging. Methods and design REPERFUSE-NA1 is a magnetic resonance imaging observational substudy of ESCAPE-NA1 (ClinicalTrialGov NCT02930018). A total of 150 acute stroke patients will be recruited (including 20% attrition) that have been randomized to either NA1 or placebo in the ESCAPE-NA1 trial. Study outcomes Primary—Early infarct growth measured using diffusion-weighted imaging will be at least 30% smaller in patients receiving NA1 compared to placebo. Secondary—Delayed secondary stroke injury at 90 days will be significantly reduced in patients receiving NA1 compared to placebo, as well as delayed secondary growth at 90 days. Conclusion REPERFUSE-NA1 will demonstrate the effect of NA1 neuroprotection on reducing the early and delayed stroke injury after reperfusion treatment.

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 AND PURPOSE: The role of collateral imaging in selecting patients for endovascular thrombectomy beyond 6 hours from onset has not been established. To assess the comparative utility of collateral imaging using multiphase CTA in selecting late window patients for EVT. MATERIALS AND METHODS: We used data from a prospective multicenter observational study in which all patients underwent imaging with multiphase CT angiography as well as CTP. Two blinded reviewers evaluated patients’ eligibility for endovascular thrombectomy using published collateral imaging (multiphase CTA) criteria compared with CTP using the selection criteria of the Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention with Trevo (DAWN) and Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 (DEFUSE-3) trials. CTP images were processed using automated commercial software. The outcomes of patients eligible for endovascular thrombectomy according to multiphase CTA, DAWN, or DEFUSE-3 criteria were compared using multivariable logistic regression modeling. Model characteristics were compared using the C-statistic for the receiver operating characteristic curve, the Akaike information criterion, and the Bayesian information criterion. RESULTS: Eighty-six patients presented beyond 6 hours from onset/last known well (median, 9.6 hours; interquartile range, 4.1 hours). Thirty-five patients (40.7%) received endovascular thrombectomy, of whom good functional outcome (90-day mRS, 0–2) was achieved in 16/35 (47%). Collateral-based imaging paradigms significantly modified the treatment effect of endovascular thrombectomy on 90-day mRS 0–2 (Pinteraction = .007). The multiphase CTA–based regression model best fit the data for the 90-day outcome (C-statistic, 0.86; 95% CI, 0.77–0.94) and was associated with the least information loss (Akaike information criterion, 95.7; Bayesian information criterion, 114.9) compared with CTP-based models. CONCLUSIONS: The collateral-based imaging paradigm using multiphase CTA compares well with CTP in selecting patients for endovascular thrombectomy in the late time window.

Background Statistical models to predict outcomes after endovascular therapy for acute ischemic stroke often incorporate baseline (pretreatment) variables only. We assessed the performance of stroke outcome prediction models for endovascular therapy in stroke in an iterative fashion using baseline, treatment‐related, and posttreatment variables. Methods Data from the ESCAPE‐NA1 (Safety and Efficacy of Nerinetide [NA‐1] in Subjects Undergoing Endovascular Thrombectomy for Stroke) trial were used to build 4 outcome prediction models using multivariable logistic regression: model 1 included baseline variables available before treatment decision making, model 2 included additional treatment‐related variables, model 3 additional posttreatment variables that become available early (within 24–48 hours), and model 4 later (beyond 48 hours) after endovascular therapy. The primary outcome was functional independence (90‐day Modified Rankin Scale score 0–2). Model performance was compared using the area under the receiver operating characteristic curve (AUC). Shapley values were used to determine marginal contributions of variables to outcome variance in the regression models. Results Among 1105 patients, functional independence was achieved by 666 (60.3%). When using baseline variables only (model 1), the AUC was 0.74 (95% CI, 0.71–0.77); this iteratively improved when treatment and posttreatment variables were added to the models (model 2: AUC, 0.77; 95% CI, 0.74–0.80; model 3: AUC, 0.80; 95% CI, 0.77–0.83; model 4: AUC, 0.82; 95% CI, 0.79–0.85). With baseline variables alone, 26% of patients who achieved functional independence were erroneously classified as not achieving functional independence. Even with the most comprehensive model, 19.8% of patients were misclassified as such. Patient age contributed most to outcome variance (Shapley value, 0.28), followed by severe adverse events including pneumonia (0.16) and intracranial hemorrhage at 24‐hours imaging (0.13). Conclusions A substantial contribution to outcomes after endovascular therapy comes from factors unrelated to currently collected baseline patient variables. One‐fifth of patients achieving functional independence were misclassified as not achieving independence, even with the most comprehensive model. Our findings suggest that the achievable accuracy of current outcome prediction models is limited, and caution should be used when applying them in clinical practice.

Key Points Question Why do some patients have poor outcomes despite small infarcts after endovascular therapy, while others with large infarcts fare better? Findings In this cohort study of 1091 patients who received endovascular therapy as part of a randomized clinical trial, discrepancies between infarct volume and functional outcome were associated with prespecified pretreatment factors, such as age, cancer, and vascular risk factors, as well as posttreatment factors, such as infarct in new territory, stroke progression, intracerebral hemorrhage, recurrent stroke, pneumonia, and heart failure. Models including these factors performed similar to those derived from stepwise regressions. Meaning In this study, discrepancies between outcome and infarct volume were associated with pretreatment and posttreatment factors, including complications related to index stroke evolution, secondary prevention, and quality of stroke unit care., This cohort study validates exploratory findings from the Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial regarding pretreatment, treatment, and posttreatment factors associated with discrepancies between follow-up infarct volume and 90-day functional outcome., Importance Some patients have poor outcomes despite small infarcts after endovascular therapy (EVT), while others with large infarcts do well. Understanding why these discrepancies occur may help to optimize EVT outcomes. Objective To validate exploratory findings from the Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial regarding pretreatment, treatment-related, and posttreatment factors associated with discrepancies between follow-up infarct volume (FIV) and 90-day functional outcome. Design, Setting, and Participants This cohort study is a post hoc analysis of the Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) trial, a double-blind, randomized, placebo-controlled, international, multicenter trial conducted from March 2017 to August 2019. Patients who participated in ESCAPE-NA1 and had available 90-day modified Rankin Scale (mRS) scores and 24-hour to 48-hour posttreatment follow-up parenchymal imaging were included. Exposures Small FIV (volume ≤25th percentile) and large FIV (volume ≥75th percentile) on 24-hour computed tomography/magnetic resonance imaging. Baseline factors, outcomes, treatments, and poststroke serious adverse events (SAEs) were compared between discrepant cases (ie, patients with 90-day mRS score ≥3 despite small FIV or those with mRS scores ≤2 despite large FIV) and nondiscrepant cases. Main Outcomes and Measures Area under the curve (AUC) and goodness of fit of prespecified logistic models, including pretreatment (eg, age, cancer, vascular risk factors) and treatment-related and posttreatment (eg, SAEs) factors, were compared with stepwise regression–derived models for ability to identify small FIV with higher mRS score and large FIV with lower mRS score. Results Among 1091 patients (median [IQR] age, 70.8 [60.8-79.8] years; 549 [49.7%] women; median [IQR] FIV, 24.9 mL [6.6-92.2 mL]), 42 of 287 patients (14.6%) with FIV of 7 mL or less (ie, ≤25th percentile) had an mRS score of at least 3; 65 of 275 patients (23.6%) with FIV of 92 mL or greater (ie, ≥75th percentile) had an mRS score of 2 or less. Prespecified models of pretreatment factors (ie, age, cancer, vascular risk factors) associated with low FIV and higher mRS score performed similarly to models selected by stepwise regression (AUC, 0.92 [95% CI, 0.89-0.95] vs 0.93 [95% CI, 0.90-0.95]; P = .42). SAEs, specifically infarct in new territory, recurrent stroke, pneumonia, and congestive heart failure, were associated with low FIV and higher mRS scores; stepwise models also identified 24-hour hemoglobin as treatment-related/posttreatment factor (AUC, 0.92 [95% CI, 0.90-0.95] vs 0.94 [95% CI, 0.91-0.96]; P = .14). Younger age was associated with high FIV and lower mRS score; stepwise models identified absence of diabetes and higher baseline hemoglobin as additional pretreatment factors (AUC, 0.76 [95% CI, 0.70-0.82] vs 0.77 [95% CI, 0.71-0.83]; P = .82). Absence of SAEs, especially stroke progression, symptomatic intracerebral hemorrhage, and pneumonia, was associated with high FIV and lower mRS score2; stepwise models also identified 24-hour hemoglobin level, glucose, and diastolic blood pressure as posttreatment factors associated with discrepant cases (AUC, 0.80 [95% CI, 0.74-0.87] vs 0.79 [95% CI, 0.72-0.86]; P = .92). Conclusions and Relevance In this study, discrepancies between functional outcome and post-EVT infarct volume were associated with differences in pretreatment factors, such as age and comorbidities, and posttreatment complications related to index stroke evolution, secondary prevention, and quality of stroke unit care. Besides preventing such complications, optimization of blood pressure, glucose levels, and hemoglobin levels are potentially modifiable factors meriting further study.

Introduction The carotid web is a compelling potential mechanism of embolic ischemic stroke. In this study, we aim to determine the prevalence of ipsilateral carotid web in a cohort of ischemic stroke patients and to perform a systematic review and meta-analysis of similar cohorts. Patients & methods We performed a retrospective, observational, cohort study of acute ischemic stroke patients admitted to a comprehensive stroke center from June 2012 to September 2017. Carotid web was defined on computed tomography angiography (CTA) as a thin shelf of non-calcified tissue immediately distal to the carotid bifurcation. We described the prevalence of carotid artery webs in our cohort, then performed a systematic review and meta-analysis of similar cohorts in the published literature. Results We identified 1,435 potentially eligible patients of whom 879 met criteria for inclusion in our analysis. An ipsilateral carotid web was detected in 4 out of 879 (0.45%) patients, of which 4/4 (1.6%) were in 244 patients with cryptogenic stroke and 3/4 were in 66 (4.5%) patients 2 = 66.1%). The relative risk (RR) of ipsilateral versus contralateral carotid web in all patients was 2.5 (95% CI 1.5–4.2, p = 0.0009) whereas in patients less than 60 with cryptogenic stroke it was 3.0 (95% CI 1.6–5.8, p = 0.0011). Discussion Carotid webs are more common in young patients with cryptogenic stroke than in other stroke subtypes. Future studies concerning the diagnosis and secondary prevention of stroke associated with carotid web should focus on this population.

BackgroundEndovascular therapy (EVT) for stroke improves outcomes but is time sensitive.ObjectiveTo compare times to treatment and outcomes between patients taken to the closest primary stroke center (PSC) with those triaged in the field to a more distant comprehensive stroke center (CSC).MethodsDuring the study, a portion of our region allowed field triage of patients who met severity criteria to a more distant CSC than the closest PSC. The remaining patients were transported to the closest PSC. We compared times to treatment and clinical outcomes between those two groups. Additionally, we performed a matched-pairs analysis of patients from both groups on stroke severity and distance to CSC.ResultsOver 2 years, 232 patients met inclusion criteria and were closest from the field to a PSC; 144 were taken to the closest PSC and 88 to the more distant CSC. The median additional transport time to the CSC was 7 min. Times from scene departure to alteplase and arterial puncture were faster in the direct group (50 vs 62 min; 93 vs 152 min; pConclusionsIn a densely populated setting, for patients with stroke who are EVT candidates and closest to a PSC from the field, triage to a slightly more distant CSC is associated with faster time to EVT, no delay to alteplase, and less disability at 90 days.

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

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

BackgroundDelays to endovascular therapy (EVT) for stroke may be mitigated with direct field triage to EVT centers. We sought to compare times to treatment over a 5.5 year span between two adjacent states, one with field triage and one without, served by a single comprehensive stroke center (CSC).MethodsDuring the study period, one of the two states implemented severity-based triage for suspected emergent large vessel occlusion, while in the other state, patients were transported to the closest hospital regardless of severity. We compared times to treatment and clinical outcomes between these two states. We also performed a matched pairs analysis, matching on date treated and distance from field to CSC.Results639 patients met the inclusion criteria, 407 in State 1 (with field triage) and 232 in State 2 (without field triage). In State 1, scene to EVT decreased 6% (or 8.13 min, p=0.0004) every year but no decrease was observed for State 2 (ConclusionsComparing adjacent states over time, the implementation of severity-based field triage significantly reduced time to EVT.

Background and Purpose— Interfacility transfers for thrombectomy in stroke patients with emergent large vessel occlusion (ELVO) are associated with longer treatment times and worse outcomes. In this series, we examined the association between Primary Stroke Center (PSC) door-in to door-out (DIDO) times and outcomes for confirmed ELVO stroke transfers and factors that may modify the interaction. Methods— We retrospectively identified 160 patients transferred to a single Comprehensive Stroke Center (CSC) with anterior circulation ELVO between July 1, 2015 and May 30, 2017. We included patients with acute occlusions of the internal carotid artery or proximal middle cerebral artery (M1 or M2 segments), with a National Institutes of Health Stroke Scale score of ≥6. Workflow metrics included time from onset to recanalization, PSC DIDO, interfacility transfer time, CSC arrival to arterial puncture, and arterial puncture to recanalization. Primary outcome measure was National Institutes of Health Stroke Scale at discharge and modified Rankin Scale (mRS) score at 90 days. Results— The median (Q1–Q3) age and National Institutes of Health Stroke Scale of the 130 ELVO transfers analyzed was 75 (64–84) and 17 (11–22). Intravenous alteplase was administered to 64% of patients. Regarding specific workflow metrics, median (Q1–Q3) times (in minutes) were 241 (199–332) for onset to recanalization, 85 (68–111) for PSC DIDO, 26 (17–32) for interfacility transport, 21 (16–39) for CSC door to arterial puncture, and 24 (15–35) for puncture to recanalization. Median discharge National Institutes of Health Stroke Scale score was 5 (2–16), and 46 (35%) patients had a favorable outcome at 90 days. Complete reperfusion (modified Thrombolysis in Cerebral Ischemia 2c/3) modified the deleterious association of DIDO on outcome. Conclusions— For patients diagnosed with ELVO at a PSC who are being transferred to a CSC for thrombectomy, longer DIDO times may have a deleterious effect on outcomes and may represent the single biggest modifiable factor in onset to recanalization time. PSCs should make efforts to decrease DIDO and routine use of DIDO as a performance measure is encouraged.

Background and purpose According to evidence-based clinical practice guidelines, patients presenting with disabling stroke symptoms should be treated with intravenous tissue plasminogen activator (IV tPA) within 4.5 h of time last known well. However, 25% of strokes are detected upon awakening (i.e., wake-up stroke [WUS]), which renders patients ineligible for IV tPA administered via time-based treatment algorithms, because it is impossible to establish a reliable time of symptom onset. We performed a systematic review and meta-analysis of the efficacy and safety of IV tPA compared with normal saline, placebo, or no treatment in patients with WUS using imaging-based treatment algorithms. Methods We searched MEDLINE, Web of Science, and Scopus between January 1, 2006 and April 30, 2020. We included controlled trials (randomized or nonrandomized), observational cohort studies (prospective or retrospective), and single-arm studies in which adults with WUS were administered IV tPA after magnetic resonance imaging (MRI)- or computed tomography (CT)-based imaging. Our primary outcome was recovery at 90 days (defined as a modified Rankin Scale [mRS] score of 0-2), and our secondary outcomes were symptomatic intracranial hemorrhage (sICH) within 36 h, mortality, and other adverse effects. Results We included 16 studies that enrolled a total of 14,017 patients. Most studies were conducted in Europe (37.5%) or North America (37.5%), and 1757 patients (12.5%) received IV tPA. All studies used MRI-based (five studies) or CT-based (10 studies) imaging selection, and one study used a combination of modalities. Sixty-one percent of patients receiving IV tPA achieved an mRS score of 0 to 2 at 90 days (95% confidence interval [CI]: 51%-70%, 12 studies), with a relative risk (RR) of 1.21 compared with patients not receiving IV tPA (95% CI: 1.01-1.46, four studies). Three percent of patients receiving IV tPA experienced sICH within 36 h (95% CI: 2.5%-4.1%; 16 studies), which is an RR of 4.00 compared with patients not receiving IV tPA (95% CI: 2.85-5.61, seven studies). Conclusions This systematic review and meta-analysis suggests that IV tPA is associated with a better functional outcome at 90 days despite the increased but acceptable risk of sICH. Based on these results, IV tPA should be offered as a treatment for WUS patients with favorable neuroimaging findings.

BackgroundThe optimal treatment and prognosis for stroke patients with tandem cervical carotid occlusion are unclear. We analyzed outcomes and treatment strategies of tandem occlusion patients in the ESCAPE-NA1 trial.MethodsESCAPE-NA1 was a multicenter international randomized trial of nerinetide versus placebo in 1105 patients with acute ischemic stroke who underwent endovascular treatment. We defined tandem occlusions as complete occlusion of the cervical internal carotid artery (ICA) on catheter angiography, in addition to a proximal ipsilateral intracranial large vessel occlusion. Baseline characteristics and outcome parameters were compared between patients with tandem occlusions versus those without, and between patients with tandem occlusion who underwent ICA stenting versus those who did not. The influence of tandem occlusions on functional outcome was analyzed using multivariable regression modeling.ResultsAmong 115/1105 patients (10.4%) with tandem occlusions, 62 (53.9%) received stenting for the cervical ICA occlusion. Of these, 46 (74.2%) were stented after and 16 (25.8%) before the intracranial thrombectomy. A modified Rankin Score (mRS) of 0–2 at 90 days was achieved in 82/115 patients (71.3%) with tandem occlusions compared with 579/981 (59.5%) patients without tandem occlusions. Tandem occlusion did not impact functional outcome in the adjusted analysis (OR 1.5, 95% CI 0.95 to 2.4). Among the subgroup of patients with tandem occlusion, cervical carotid stenting was not associated with different outcomes compared with no stenting (mRS 0–2: 75.8% vs 66.0%, adjusted OR 2.0, 95% CI 0.8 to 5.1).ConclusionsTandem cervical carotid occlusion in patients with acute large vessel stroke did not lower the odds of good functional outcome in our study. Functional outcomes were similar irrespective of the management of the cervical ICA occlusion (stenting vs not stenting).

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.

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: Twenty-five percent of strokes are detected upon awakening (‘wake-up strokes’; WUS) and are not amenable to thrombolytic therapy via existing time-based treatment approaches. We performed a systematic review and meta-analysis of the efficacy and safety of thrombolysis in patients with WUS using imaging-based selection algorithms. Methods: This systematic review was registered through PROSPERO (CRD42020151552). We searched PubMed, Web of Science, and Scopus between January 1, 2006 and April 30, 2020 for controlled trials and observational cohort studies (prospective or retrospective), in which adults with WUS were administered thrombolysis after MR- or CT-based imaging. Our primary outcome was recovery (mRS 0-2) at 90 days and our secondary outcome was symptomatic intracranial hemorrhage (sICH). We assessed risk of bias using the Cochrane Risk of Bias 2.0 and ROBINS-I tools. Results: We included 16 studies that enrolled a total of 14,017 patients. Sixty-one percent of patients receiving tPA achieved a functional recovery at 90 days (95% CI: 51% to 70%; 12 studies), with a relative risk (RR) of recovery of 1.21 compared with patients not receiving tPA (95% CI 1.01 to 1.46; 4 comparative studies). As shown in Figure 1, 3% of patients receiving tPA in the treated WUS stroke group experienced sICH, an RR of 4.0 (95% CI 2.85-5.61) compared with patients not receiving tPA. On meta-regression, advancing age was negatively associated with the RR of recovery (p Conclusions: In patients with WUS, thrombolysis is associated with functional recovery and with a low risk of sICH. This risk is comparable to the sICH rate from tPA-treatment of stroke utilizing the standard protocol timeframe (2.4% in ECASS III). Thrombolysis should be considered in the treatment of WUS in patients with favorable neuroimaging.

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.

Introduction: In patients with acute large vessel occlusion, the definition of penumbral tissue based on T max delay perfusion imaging is not well established in relation to late-window endovascular thrombectomy (EVT). In this study, we sought to evaluate penumbra consumption rates for T max delays in patients treated between 6 and 16 hours from last known normal. Methods: This is a secondary analysis of the DEFUSE-3 trial, which included patients with an acute ischemic stroke due to anterior circulation occlusion within 6-16 hours of last known normal. The primary outcome is percentage penumbra consumption defined as (24 hour infarct volume-core infarct volume)/(Tmax volume-baseline core volume). We stratified the cohort into 4 categories (untreated, TICI 0-2a, TICI 2b, and TICI3) and calculated penumbral consumption rates. Results: We included 143 patients, of which 66 were untreated, 16 had TICI 0-2a, 46 had TICI 2b, and 15 had TICI 3. In untreated patients, a median (IQR) of 48% (21% - 85%) of penumbral tissue was consumed based on Tmax6 as opposed to 160.6% (51% - 455.2%) of penumbral tissue based on Tmax10. On the contrary, in patients achieving TICI 3 reperfusion, a median (IQR) of 5.3% (1.1% - 14.6%) of penumbral tissue was consumed based on Tmax6 and 25.7% (3.2% - 72.1%) of penumbral tissue based on Tmax10. Conclusion: Contrary to prior studies, we show that at least 75% of penumbral tissue with Tmax > 10 sec delay can be salvaged with successful reperfusion and new generation devices. In untreated patients, since infarct expansion can occur beyond 24 hours, future studies with delayed brain imaging are needed to determine the optimal T max delay threshold that defines penumbral tissue in patients with proximal anterior circulation large vessel occlusion.

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.

Endovascular thrombectomy (EVT) has become standard of care for large vessel occlusion strokes but current guidelines exclude a large proportion of patients from this highly effective treatment. This review therefore focuses on expanding indications for EVT in several borderline indications such as patients in the extended time window, patients with extensive signs of infarction on admission imaging, elderly patients and patients with pre-existing deficits. It also discusses the current knowledge on intravenous thrombolysis as an adjunct to EVT and EVT as primary therapy for distal vessel occlusions, for tandem occlusions, for basilar artery occlusions and in pediatric patients. We provide clear recommendations based on current guidelines and further literature.

Background Large vessel occlusion (LVO) stroke is one of the most time-sensitive diagnoses in medicine and requires emergent endovascular therapy to reduce morbidity and mortality. Leveraging recent advances in deep learning may facilitate rapid detection and reduce time to treatment. Purpose To develop a convolutional neural network to detect LVOs at multiphase CT angiography. Materials and Methods This multicenter retrospective study evaluated 540 adults with CT angiography examinations for suspected acute ischemic stroke from February 2017 to June 2018. Examinations positive for LVO (n = 270) were confirmed by catheter angiography and LVO-negative examinations (n = 270) were confirmed through review of clinical and radiology reports. Preprocessing of the CT angiography examinations included vasculature segmentation and the creation of maximum intensity projection images to emphasize the contrast agent-enhanced vasculature. Seven experiments were performed by using combinations of the three phases (arterial, phase 1; peak venous, phase 2; and late venous, phase 3) of the CT angiography. Model performance was evaluated on the held-out test set. Metrics included area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Results The test set included 62 patients (mean age, 69.5 years; 48% women). Single-phase CT angiography achieved an AUC of 0.74 (95% confidence interval [CI]: 0.63, 0.85) with sensitivity of 77% (24 of 31; 95% CI: 59%, 89%) and specificity of 71% (22 of 31; 95% CI: 53%, 84%). Phases 1, 2, and 3 together achieved an AUC of 0.89 (95% CI: 0.81, 0.96), sensitivity of 100% (31 of 31; 95% CI: 99%, 100%), and specificity of 77% (24 of 31; 95% CI: 59%, 89%), a statistically significant improvement relative to single-phase CT angiography (P = .01). Likewise, phases 1 and 3 and phases 2 and 3 also demonstrated improved fit relative to single phase (P = .03). Conclusion This deep learning model was able to detect the presence of large vessel occlusion and its diagnostic performance was enhanced by using delayed phases at multiphase CT angiography examinations. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Ospel and Goyal in this issue.

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

Background: The current AHA/ASA guidelines recommend only offering mechanical thrombectomy (MT) to patients without pre-stroke disability. We aimed to compare outcomes of acute ischemic stroke patients with none-to-minimal (modified Rankin score, mRS, 0-1) and moderate (mRS 2-3) pre-stroke disability treated with MT. Methods: Consecutive adult patients undergoing MT for an anterior circulation stroke were prospectively identified at two comprehensive stroke centers from 2012-2018. Procedural and 90-day functional outcomes were compared among patients with pre-stroke mRS 0-1 and 2-3 using Chi-squared, logistic, and linear regression tests and were adjusted for prespecified covariates. Results: A total of 881 patients were included (mean age 70±16 years; 45% female) and 259 (29.4%) had moderate pre-stroke disability. Primary outcome of no accumulation of additional disability at 90 days was observed in 22.4% and 26.7% of patients with no-to-minimal and moderate pre-stroke disability, respectively (OR 1.27[0.88-1.81], p=0.2; adjusted OR 1.90[1.24, 2.94], p=0.004, Figure). Rate of symptomatic intracerebral hemorrhage (7.3% vs 6.2%, p=0.65), successful recanalization (86.7% vs 83.8%, p=0.33), and median length of hospital stay (5 vs 5 days, p=0.06) were not significantly different. Mean change in utility weighted mRS from baseline to 90 days was 0.35±0.35 in pre-stroke mRS 0-1 vs -0.38 ±0.32 in pre-stroke mRS 2-3, p=0.17. Death by 90-days was higher in patients with moderate pre-stroke disability (14.3% vs 40.3%, OR 4.06[2.82-5.86], p Interpretation: One-third of patients undergoing MT had a moderate pre-stroke disability. The odds of maintaining pre-stroke functional status at 90-days and procedural success rates were not different between patients with no-to-minimal and moderate pre-stroke disability. However, patients with pre-stroke disability were more likely to die by 90 days.

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