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Background Nerinetide treatment was associated with better clinical outcomes among patients with stroke undergoing endovascular treatment who were not treated with concurrent alteplase in the randomized ESCAPE‐NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke) trial. In patients receiving alteplase, no such effect was seen due to an inactivation of nerinetide by plasmin – the product of tissue plasminogen activation. We hypothesized that improved outcomes in the no‐alteplase patients were associated with reduced infarct growth, a radiological correlate of improved stroke outcomes. Methods Data are from the no‐alteplase stratum of the ESCAPE‐NA1 trial. Patients who underwent computer tomography perfusion (CTP) as part of routine clinical care were included. Admission CTP source data were processed using RAPID software. Infarct core at baseline was defined as areas of relative cerebral blood flow

Background The optimal management of patients with symptomatic isolated internal carotid artery (ICA) occlusion is unknown. We aimed to assess whether endovascular treatment (EVT) compared with standard medical care was associated with improved functional outcomes in patients with acute symptomatic isolated intracranial ICA occlusion without involvement of the middle or anterior cerebral artery, that is, ICA‐I occlusion. Additionally, we aimed to compare ICA‐I with ICA‐L/T occlusion, which involves themiddle and anterior cerebral artery, respectively. Methods We analyzed data from the highly effective reperfusion evaluated in multiple endovascular stroke trials (HERMES) collaboration, which performed an individual patient data meta‐analysis of 7 randomized controlled trials conducted between 2010 and 2017 assessing the benefit of EVT compared to medical management in patients with anterior circulation large vessel occlusion. We assessed the association between EVT and 90‐day good functional outcome (modified Rankin scale scores 0–2), National Institutes of Health Stroke Scale scores at 24 hours, symptomatic intracranial hemorrhage rates and mortality in patients with ICA‐I and ICA‐L/T occlusion. Results We included 442 patients with intracranial ICA occlusion, of whom 38 (8.6%) had ICA‐I occlusion. In the ICA‐I group, the median age [interquartile range] was 69.5 [61.7–79.5] years, 42.1% were male, and median baseline National Institutes of Health Stroke Scale was 17 [15–20]. Compared with standard medical care alone, EVT resulted in higher good outcome rates in patients with ICA‐I (42.9% versus 25%; P=0.296) and ICA‐L/T occlusion (32.5% versus 14.4%; P

Background First‐pass effect (FPE), that is, achieving reperfusion with a single thrombectomy device pass, is associated with better clinical outcomes in patients with acute stroke. FPE is therefore increasingly used as a marker of device and procedural efficacy. We aimed to evaluate the ability of thrombus‐based radiomics models to predict FPE in patients undergoing endovascular thrombectomy and compare performance with experts and nonradiomics thrombus characteristics. Methods Patients with thin‐slice noncontrast computed tomography and computed tomography angiography from the ESCAPE‐NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke) trial were included. Thrombi were manually segmented on all images. Data were 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 set. The machine learning models were compared with 3 expert stroke physicians in predicting FPE in the test set using area under the receiver operating characteristic curves. Results Thin‐slice images of 554 patients were divided into a derivation set (training [n=388] and validation [n=55]) and a test set (n=111). A radiomics model using the combination of noncontrast computed tomography, computed tomography angiography, and noncontrast computed tomography–computed tomography angiography difference achieved the highest performance (area under the curve, 0.74 [95% CI, 0.64–0.84]) for prediction of FPE. This was higher than the mean area under the curve of the 3 experts (0.62 [95% CI, 0.53–0.71], P=0.01 for difference in area under the curves). The radiomics model also performed better than nonradiomics‐based thrombus features such as volume and permeability measurements in predicting FPE (P

Background Patients with white matter disease (WMD) – a key marker of cerebral small vessel disease – may have less brain reserve to cope with ischemic injury. The relationship of WMD to functional recovery after endovascular thrombectomy is uncertain. We aim to explore the association between WMD and functional outcome, assessed at multiple time‐points postendovascular thrombectomy. Methods In this post hoc analysis, we analyzed noncontrast computed tomography‐imaging from the ESCAPE‐NA1 (Safety and Efficacy of Nerinetide [NA‐1] in Subjects Undergoing Endovascular Thrombectomy for Stroke) trial and assessed WMD by using the total Fazekas‐score (score range: 0–6). The primary outcome was repeated measurements of the modified Rankin scale (mRS) scores (i.e., day‐5/discharge, day‐30, and day‐90). Secondary outcome measures were the ordinal‐mRS at 90‐days, 90‐day‐mRS0–2, and 90‐day‐mortality. Mixed‐linear and binary/ordinal logistic regressions were performed, adjusting for age, sex, baseline National Institutes of Health Stroke Scale, cortical atrophy, chronic infarctions, stroke laterality, follow‐up infarct volume, and alteplase–nerinetide interaction. Sensitivity analyses were done including only those patients for whom magnetic resonance imaging was available. Results We included 1102 patients with noncontrast computed tomography (median age 71, interquartile range: 61–80; median National Institutes of Health Stroke Scale 17, interquartile range: 12–21). The median total Fazekas‐score was 1(interquartile range: 0–2). Out of 1202 patients, 566 had follow‐up magnetic resonance imaging. We observed heterogeneity in functional recovery with varying degrees of WMD‐burden (P

Introduction Endovascular therapy (EVT) is the standard‐of‐care for large vessel occlusion stroke; however, timely access to treatment is still limited for a large proportion of the population. Telerobotic EVT has the potential to decrease time to treatment and expand existing networks of care to more rural populations. It is currently unclear how its implementation would impact existing stroke networks. Methods Conditional probability models were generated to predict the probability of excellent outcome (modified Rankin Scale 0–1 at 90 days post stroke) for patients with suspected large vessel occlusion (LVO). A baseline stroke network was created for California using existing intravenous thrombolysis (IVT) centers and comprehensive stroke centers (CSCs) capable of IVT and EVT. Optimal transport decisions and catchment areas were generated for the baseline model and three hypothetical scenarios through conversion of IVT centers at various distances from a CSC into centers capable of Telerobotic EVT [i.e. hospitals ≥ 15 and < 50 miles from a CSC were converted (Scenario 1), ≥ 50 and < 100 miles (Scenario 2), and ≥ 100 miles (Scenario 3)]. Catchment areas were calculated for each scenario using varied robotic procedural delay times and success rates. Results In the baseline model, 51 hospitals were designated as CSCs and 142 hospitals were designated IVT centers. Conversion of IVT centers into Telerobotic EVT centers decreased median travel time for LVO patients in all three scenarios. The estimated number of robotically treated LVOs per year in Scenarios 1, 2, and 3 were 2172, 740, and 212, respectively. Scenario 1 (15‐50 miles) was the most sensitive to robotic time delay and success rate, but all three scenarios were more sensitive to decreases in procedural success rate compared to time delay. Conclusions Telerobotic EVT has the potential to improve care for stroke patients outside of major urban centers. Compared to procedural time delays in robotic EVT, a decrease in procedural success rate would not be well tolerated. This modeling analysis can inform system planning for the potential advent of remote EVT care.

Introduction The current neurovascular research funding environment is highly competitive, stifling collaboration and hindering progress. Further, specific groups of researchers/research topics are disproportionately affected, resulting in inequity in the funding process. These include early‐career researchers, women, and researchers from low‐middle income countries. Certain conditions, e.g., rare, stroke‐related diseases are due to their low prevalence not suitable for clinical trials, and therefore even less likely to receive funding. Currently, there is no easy way for people working on such topics to come together and collaborate. To address this problem, a novel internet‐based platform, Collavidence (www.collavidence.com), was designed. The idea is to complement current systems of neurovascular research collaboration and funding for more inclusive, efficient, and impactful research results. The aim of this study is to present the initial performance of the platform in achieving this goal. Methods Analytics on pre‐defined user‐, project‐, and interaction‐based metrics will be performed to describe the level of platform engagement in the initial months following launch. These include the number of users and projects posted, the amount of funding accumulated, the proportion of successfully funded projects, and the iterative improvement of the proposals. Further, the relative engagement of early‐career, female researchers, and researchers from low‐middle‐income countries will be assessed. Results A qualitative assessment of the value of the overall platform, the process of iterative review, and possibilities for collaboration will be presented. Further, trends in platform engagement during the initial 3 months, including the relative distribution of specific user demographics to assess the platform’s success in encouraging equity, diversity, and inclusion, will be presented. Conclusions This study will assess the feasibility and initial success of Collavidence as a unique platform for neurovascular research collaboration and funding.

Background Current stroke guidelines recommend advanced imaging (computed tomography [CT] perfusion or magnetic resonance imaging) prior to endovascular therapy (EVT) in patients with late presentation of large vessel occlusion. Adherence to guidelines may be constrained by resources or timely access to imaging. We sought to understand the factors which influence late window imaging selection for EVT candidates with large vessel occlusion. Methods We conducted an international survey from January to May 2022. The questions aimed to identify advanced imaging and treatment decisions based on access to imaging, time delays, and simulated patient scenarios. Results There were 3000 invited participants and 1506 respondents, the majority (89.6%) from comprehensive stroke centers in high‐income countries. Neurointerventionalists comprised 31.8% and noninterventionalists 68.2% of respondents. Overall, 70.7% reported routine use of advanced imaging for late EVT selection, and 63.6% reported its usage in every case. There was greater availability of advanced imaging in comprehensive stroke centers versus primary stroke centers (67.0% versus 33.7%; P

Background Although the association between cortical venous opacification (VO) and clinical outcomes has been shown in previous studies, little is known about the relationship between parenchymal hemorrhage (PH) and VO in patients with acute stroke. We aimed to determine whether cortical VO assessed on computed tomography angiography correlates with the risk of PH following endovascular treatment. Methods This is a post hoc analysis of the ESCAPE NA‐1 (Efficacy and Safety of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke) trial. Control‐arm patients with adequate venous assessment on computed tomography angiography were included. Any PH and symptomatic intracranial hemorrhage were compared between patients with poor VO (cortical vein opacification score

Background The best management of basilar artery occlusion (BAO) remains uncertain. The BASICS (Basilar Artery International Cooperation Study) and the BEST (Basilar Artery Occlusion Endovascular Intervention Versus Standard Medical Treatment) trials reported neutral results. We sought to understand physicians’ approaches to BAOs and whether further BAO randomized controlled trials were warranted. Methods We conducted an online international survey from January to March 2022 to stroke neurologists and neurointerventionalists. Survey questions were designed to examine clinical and imaging parameters under which clinicians would offer (or rescind) a patient with BAO to endovascular therapy (EVT) or best medical management versus enrollment into a randomized clinical trial. Results Of >3002 invited participants, 1245 responded (41.4% response rate) from 73 countries, including 54.7% stroke neurologists and 43.6% neurointerventionalists. More than 95% of respondents would offer EVT to patients with BAO, albeit in various clinical circumstances. There were 70.0% of respondents who indicated that the BASICS and BEST trials did not change their practice. Only 22.1% of respondents would perform EVT according to anterior circulation occlusion criteria. The selection of patients for BAO EVT by clinical severity, timing, and imaging modality differed according to geography, specialty, and country income level. Over 80% of respondents agreed that further randomized clinical trials for BAO were warranted. Moreover, 45.6% of respondents indicated they would find it acceptable to enroll all trial‐eligible patients into the medical arm of a BAO trial, whereas 26.3% would not enroll. Conclusion Most stroke physicians continue to believe in the efficacy of EVT in selected patients with BAO in spite of BEST and BASICS. There is no consensus on which selection criteria to use, and few clinicians would use anterior circulation occlusion criteria for BAOs. Further randomized clinical trials for BAO are warranted.

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.

The benefit of acute ischemic stroke (AIS) treatment is highly time dependent. Although studies on workflow improvement in AIS are increasingly gaining attention, there is a lack of consensus and consistency regarding the definition, measurement, and reporting of AIS workflow times. We discuss the challenges related to defining and measuring workflow times in AIS and propose a basic set of time intervals that should be reported in AIS workflow studies. We particularly focus on patients undergoing mechanical thrombectomy. Importantly, endovascular treatment workflow times should always be reported in conjunction with reperfusion quality because one is not informative without the other. We further suggest standardized reporting of workflow times that includes the 90th percentile in addition to medians and interquartile ranges, means, and SDs. The proposed methodology serves as a framework for AIS studies and aids further discussion on workflow‐related AIS research.

Background A heterogeneous patient population receives endovascular treatment (EVT) for acute ischemic stroke caused by proximal large‐vessel occlusion every day. We aimed to conduct a population‐based study of EVT in the province of Alberta, Canada, to understand the effectiveness in a complete population and how the magnitude of effect differs from the artificial world of clinical trials. Methods and Results Within a 3‐year period (April 2015 to March 2018), 576 patients fit the inclusion criteria of our study and constituted the EVT group of our analysis. The medical treatment group of the ESCAPE (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT [Computed Tomography] to Recanalization Times) trial had 150 patients. Thus, our total sample size was 726. We captured outcomes in clinical routine using administrative data and a linked database method. Primary outcome of our study was home‐time. Home‐time refers to the number of days that the patient was back at premorbid living situation without increase in level of care within 90 days of index stroke event. Median age of patients was 70 years (interquartile range, 59–81 years), and 47.8% were women. Median National Institutes of Health Stroke Scale score was 17 (interquartile range, 13–20). EVT was associated with an increased 90‐day home‐time by an average of 8.5 days compared with medical treatment alone using Cragg hurdle regression (P=0.009). Age and higher National Institutes of Health Stroke Scale score were associated with decreased 90‐day home‐time (both P

BackgroundExamination of linked data on patient outcomes and cost of care may help identify areas where stroke care can be improved. We report on the association between variations in stroke severity, patient outcomes, cost, and treatment patterns observed over the acute hospital stay and through the 12‐month follow‐up for subjects receiving endovascular therapy compared to intravenous tissue plasminogen activator alone in the IMS (Interventional Management of Stroke) III Trial. Methods and ResultsProspective data collected for a prespecified economic analysis of the trial were used. Data included hospital billing records for the initial stroke admission and subsequent detailed resource use after the acute hospitalization collected at 3, 6, 9, and 12 months. Cost of follow‐up care varied 6‐fold for patients in the lowest (0–1) and highest (20+) National Institutes of Health Stroke Scale category at 5 days, and by modified Rankin Scale at 3 months. The kind of resources used postdischarge also varied between treatment groups. Incremental short‐term cost‐effectiveness ratios varied greatly when treatments were compared for patient subgroups. Patient subgroups predefined by stroke severity had incremental cost‐effectiveness ratios of $97 303/quality‐adjusted life year (severe stroke) and $3 187 805/quality‐adjusted life year (moderately severe stroke). ConclusionsDetailed economic and resource utilization data from IMS III provide powerful evidence for the large effect that patient outcome has on the economic value of medical and endovascular reperfusion therapies. These data can be used to inform process improvements for stroke care and to estimate the cost‐effectiveness of endovascular therapy in the US health system for stroke intervention trials. Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Registration number: NCT00359424.