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Background: Whereas the beneficial effect of antiplatelet therapy for recurrent stroke prevention has been well established, uncertainties remain regarding the optimal antithrombotic regimen for recently symptomatic carotid stenosis. We sought to explore the approaches of stroke physicians to antithrombotic management of patients with symptomatic carotid stenosis. Methods: We employed a qualitative descriptive methodology to explore the decision-making approaches and opinions of physicians regarding antithrombotic regimens for symptomatic carotid stenosis. We conducted semi-structured interviews with a purposive sample of 22 stroke physicians (11 neurologists, 3 geriatricians, 5 interventional-neuroradiologists, and 3 neurosurgeons) from 16 centers on four continents to discuss symptomatic carotid stenosis management. We then conducted thematic analysis on the transcripts. Results: Important themes revealed from our analysis included limitations of existing clinical trial evidence, competing surgeon versus neurologist/internist preferences, and the choice of antiplatelet therapy while awaiting revascularization. There was a greater concern for adverse events while using multiple antiplatelet agents (e.g., dual-antiplatelet therapy (DAPT)) in patients undergoing carotid endarterectomy compared to carotid artery stenting. Regional variations included more frequent use of single antiplatelet agents among European participants. Areas of uncertainty included antithrombotic management if already on an antiplatelet agent, implications of nonstenotic features of carotid disease, the role of newer antiplatelet agents or anticoagulants, platelet aggregation testing, and timing of DAPT. Conclusion: Our qualitative findings can help physicians critically examine the rationale underlying their own antithrombotic approaches to symptomatic carotid stenosis. Future clinical trials may wish to accommodate identified variations in practice patterns and areas of uncertainty to better inform clinical 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.

Background: The CHANCE-2 study compared 3 weeks of aspirin–ticagrelor to aspirin–clopidogrel in CYP2C19 loss-of-function (LOF) allele carriers following a transient ischemic attack (TIA)/minor stroke and demonstrated a modestly lower risk of stroke recurrence with aspirin–ticagrelor. This stroke protection was largely for minor stroke and came at an increased risk of bleeding. The cost-effectiveness of implementing testing for LOF allele status to personalize antiplatelet regimen for secondary stroke prevention after a TIA/minor stroke in the Canadian health care context is unknown. Methods: Cost-effectiveness analysis using a decision-analytic Markov cohort model with a lifetime horizon was performed to determine the costs and health benefits of testing for LOF allele status compared with no testing (current standard of care). The population of interest was patients living in Canada who suffered a TIA/minor stroke. Outcomes of interest were life-years gained (LYG), quality-adjusted life years (QALY) gained, costs (reported in 2022 Canadian dollars), and the incremental cost-effectiveness ratio (ICER). We adopted the perspective of the Federal, Provincial, and Territorial Ministries of Health and used a 1.5% annual discount rate. Sensitivity analyses were performed to assess uncertainty. Results: Compared to standard of care, LOF allele testing leads to 0.14 LYG (undiscounted), 0.12 QALYs gained (undiscounted), and additional lifetime costs of CAD$432 (discounted) per patient. The ICER of the LOF allele testing strategy is CAD$4310 per QALY gained compared with standard of care. The probabilistic sensitivity analyses demonstrated that LOF allele testing was cost-effective in more than 99.99% of simulations using a willingness-to-pay threshold of CAD$50,000 per QALY. Conclusion: Based on available evidence, testing for LOF allele followed by short duration 3 weeks of aspirin–ticagrelor compared to standard-of-care aspirin–clopidogrel can lead to prolonged life and improved quality of life and can be considered very cost-effective when compared with other well-accepted technologies in health and medicine.

BackgroundThe Alteplase compared to Tenecteplase (AcT) randomized controlled trial (RCT) showed that tenecteplase is non-inferior to alteplase in treating acute ischemic stroke within 4.5 hours of symptom onset. The effect of time to treatment on clinical outcomes with alteplase is well known, however the nature of this relationship is yet to be described with tenecteplase. We assessed whether the association of time to thrombolysis treatment with clinical outcomes in patients with acute ischemic stroke differs by whether they receive intravenous tenecteplase versus alteplase.MethodsPatients included were from AcT, a pragmatic, registry linked, phase 3 RCT comparing intravenous tenecteplase to alteplase in patients with acute ischemic stroke. Eligible patients were >18 years old, with disabling neurological deficits, presenting within 4·5 hours of symptom onset, and eligible for thrombolysis. Primary outcome was modified Rankin scale(mRS) 0-1 at 90 days. Safety outcomes included 24-hour symptomatic intracerebral hemorrhage (sICH) and 90-day mortality rates. Mixed effects logistic regression was used to assess a)the association of stroke symptom onset to needle time (ONT), b)door (hospital arrival) to needle time(DNT) with outcomes and c)if these associations were modified by type of thrombolytic administered (tenecteplase vs. alteplase), after adjusting for age, sex, baseline stroke severity and site of intracranial occlusion.ResultsOf the 1538 patients included in this analysis, 1146(74.5%)[591: tenecteplase, 555 alteplase] presented within 3 hours vs. 392 (25.5%)[196: TNK, 196 alteplase] who presented within 3-4.5 hours of symptom onset. Baseline patient characteristics in the 0-3 hour versus 3-4.5-hour time window were similar, except patients in the 3-to-4.5-hour window had lower median baseline NIHSS (10 vs 7 respectively) and lower proportion of patients with large vessel occlusion on baseline CT Angiography (26.9% vs 18.7% respectively). Type of thrombolytic agent (tenecteplase vs. alteplase) did not modify the association between ONT(pinteraction= 0.161) or DNT(pinteraction= 0.972) and primary clinical outcome. Irrespective of the thrombolytic agent used, each 30-min reduction in ONT was associated with a 1.8% increase while every 10 min reduction in DNT was associated with a 0.2% increase in the probability of achieving 90-day mRS 0-1 respectively.ConclusionThe effect of time to tenecteplase administration on clinical outcomes is like that of alteplase, with faster administration resulting in better clinical outcomes.Key points:QuestionIn patients with acute ischemic stroke, does the effect of time to thrombolysis on clinical outcomes differ with tenecteplase vs. alteplase administration?FindingsIn this analysis from the alteplase compared to tenecteplase (AcT) trial, a pragmatic, registry linked, phase 3 randomized controlled trial, each 30-min reduction in stroke onset to thrombolysis start time was associated with a 1.8% increase in the probability of achieving excellent functional outcome, which means that for every 30-minute reduction in onset to needle time two more of a 100 people achieved an excellent outcome. This effect was not modified by type of thrombolytic used (alteplase versus tenecteplase)MeaningThe effect of time to tenecteplase administration on clinical outcomes is like that of alteplase, with faster administration resulting in better clinical outcomes.

Background We recently developed a novel machine learning‐based algorithm using multiphase computed tomography angiography (mCTA) to generate perfusion maps of the brain, similar to computed tomography perfusion (CTP) (ie, multiphase CTA perfusion [mCTAp]). Here, we aim to validate the clinical utility of mCTAp in detection of brain ischemia and its side, extent, and location. Methods In this prospective multi‐reader‐multi‐case analysis, we included baseline images: mCTAp ( StrokeSENS ‐algorithm) and CTP (4D; GE Healthcare) from 121 randomly selected patients whose scans were not part of algorithm‐development. After excluding 2/121 scans because of poor image‐quality, 3 experienced radiologists read time to maximum, and relative cerebral blood flow‐maps generated by the test (mCTAp) and reference (CTP) modality. The 2 reading sessions were separated by 5 days although the reading order was randomized. Core laboratory imaging assessments – that used non contrast computed tomography, mCTA, and CTP – were considered as ground‐truth. A mixed‐effects statistical model with “reader” as random effects variable was used to calculate the area under the curve (with 95% CI), sensitivity, and specificity for both modalities (mCTAp/CTP) for ischemia detection, affected side, and occlusion location. The time required for interpretation and inter‐rater variability in assessments were compared across the 2 modalities. Results Area under the curves (95% CI) for detecting ischemia using mCTAp and CTP were 0.85 (95% CI, 0.8–0.9) and 0.84 (0.8–0.9) respectively ( P =0.43). Area under the curves for the affected side were 0.94 (0.92–0.97) and 0.96 (0.94–0.98) ( P =0.69), respectively; for detecting large vessel occlusion were 0.84 (0.8–0.9) and 0.86 (0.8–0.9), ( P =0.31), respectively; M2‐or‐distal occlusion were 0.79 (0.73–0.84) and 0.88 (0.83–0.92) ( P =0.22), respectively, for anterior cerebral artery‐occlusion 0.82 (0.66–0.98) and 0.93 (0.82–1.00) ( P =0.15), respectively, and for posterior cerebral artery‐occlusions 0.9 (0.8–1) and 0.99 (0.98–0.99) ( P =0.01), respectively. The median (interquartile range [IQR]) time for image interpretation was 62 seconds (IQR, 46–78) and 59 seconds (IQR, 42–69) for mCTAp and CTP, respectively, ( P =0.15). Fleiss` Kappa‐values for inter‐rater reliability in detecting ischemia were 0.5 and 0.8 for mCTAp and CTP, respectively. Conclusion mCTAp shows similar performance and interpretation times compared to CTP in assisting readers to detect brain ischemia, affected side, and occlusion location, but mainly as it relates to proximal vessel occlusions. The proposed tool still needs further refinement for distal vessel occlusions. Nonetheless, mCTAp is a promising tool as it allows for acquisition of brain perfusion maps with lower radiation exposure, acquisition time, and contrast dose compared with additional CTP.

Background and purpose Previous studies suggest that mechanisms and outcomes in patients with COVID-19-associated stroke differ from those in patients with non-COVID-19-associated strokes, but there is limited comparative evidence focusing on these populations. The aim of this study, therefore, was to determine if a significant association exists between COVID-19 status with revascularization and functional outcomes following thrombectomy for large vessel occlusion (LVO), after adjustment for potential confounding factors. Methods A cross-sectional, international multicenter retrospective study was conducted in consecutively admitted COVID-19 patients with concomitant acute LVO, compared to a control group without COVID-19. Data collected included age, gender, comorbidities, clinical characteristics, details of the involved vessels, procedural technique, and various outcomes. A multivariable-adjusted analysis was conducted. Results In this cohort of 697 patients with acute LVO, 302 had COVID-19 while 395 patients did not. There was a significant difference (p < 0.001) in the mean age (in years) and gender of patients, with younger patients and more males in the COVID-19 group. In terms of favorable revascularization (modified Thrombolysis in Cerebral Infarction [mTICI] grade 3), COVID-19 was associated with lower odds of complete revascularization (odds ratio 0.33, 95% confidence interval [CI] 0.23-0.48; p < 0.001), which persisted on multivariable modeling with adjustment for other predictors (adjusted odds ratio 0.30, 95% CI 0.12-0.77; p = 0.012). Moreover, endovascular complications, in-hospital mortality, and length of hospital stay were significantly higher among COVID-19 patients (p < 0.001). Conclusion COVID-19 was an independent predictor of incomplete revascularization and poor functional outcome in patients with stroke due to LVO. Furthermore, COVID-19 patients with LVO were more often younger and had higher morbidity/mortality rates.

Background The relationship between duration of transient neurological events and presence of diffusion‐weighted lesions by symptom type is unclear. Methods and Results This was a substudy of SpecTRA (Spectrometry for Transient Ischemic Attack Rapid Assessment), a multicenter prospective cohort of patients with minor ischemic cerebrovascular events or stroke mimics at academic emergency departments in Canada. For this study we included patients with resolved symptoms and determined the presence of diffusion‐weighted imaging (DWI) lesion on magnetic resonance imaging within 7 days. Using logistic regression, we evaluated the association between symptom duration and DWI lesion, assessing for interaction with symptom type (focal only versus nonfocal/mixed), and adjusting for age, sex, education, comorbidities, and systolic blood pressure. Of 658 patients included, a DWI lesion was present in 232 (35.1%). There was a significant interaction between symptom duration and symptom type. For those with focal‐only symptoms, there was a continuous increase in DWI probability up to 24 hours in duration (ranging from ≈40% to 80% probability). In stratified analyses, the increase in probability of DWI lesion with increased duration of focal symptoms was seen in women but not men. For those with nonfocal or mixed symptoms, predicted probability of DWI lesion was ≈35% and was greater in men, but did not increase with longer duration. Conclusions Increased duration of neurological deficits is associated with greater probability of DWI lesion in those with focal symptoms only. For individuals with nonfocal or mixed symptoms, about one‐third had DWI lesions, but the probability did not increase with duration. These results may be important to improve risk stratification of transient neurological events.

Introduction: Mechanical thrombectomy (MT) is a highly safe and effective standard of care for acute ischemic strokes with large vessel occlusion. However, timely access to MT is extremely limited on a global scale, with vast disparities in access between countries. MT2020+, a global non-profit initiative of SVIN, aimed to create a semi-quantitative global MT access barrier score (MTABS) to objectively measure the barriers impeding the implementation of treatment worldwide. Methods: Four independent investigators performed an in-depth systematic literature review using the peer review of electronic search strategies. Barriers to access were identified and categorized into 3 groups: information and diagnostic, physical, and financial. An international expert panel was created and scored each attribute using a modified Delphi process with the assistance of consultants from the University of Calgary W21C. A 1-9-point scale was used, with 1 being not at all important and 9 being extremely important. A meeting was held for the attributes that require deliberation. After an agreement, a list of attributes for access was elaborated. Next, a ranking of importance and individual weighting was done. We assigned a presence of or lack of an attribute a numerical value (1 for yes, 0 for no) and multiply by its weight to determine a final score. Results: After an initial screening of 2864 abstracts, 121 studies were included in the final systematic review. A total of 34 possible attributes that are barriers to access were identified. After the modified Delphi process, 26 individual attributes were selected. The MTABS was made with possible results from 0-62 points, with higher scores meaning higher barriers to access to MT. Conclusions: The global MTABS represents the first tool to quantify barriers to MT access worldwide. Its implementation will objectively measure the magnitude and identify key barriers to guide regional public health interventions to improve MT workflow and access.

Introduction: Mechanical thrombectomy (MT) is a highly safe and effective standard of care for acute ischemic strokes with large vessel occlusion. However, timely access to MT is extremely limited on a global scale, with vast disparities in access between countries. MT2020+, a global non-profit initiative of SVIN, aimed to create a semi-quantitative global MT access barrier score (MTABS) to objectively measure the barriers impeding the implementation of treatment worldwide. Methods: Four independent investigators performed an in-depth systematic literature review using the peer review of electronic search strategies. Barriers to access were identified and categorized into 3 groups: information and diagnostic, physical, and financial. An international expert panel was created and scored each attribute using a modified Delphi process with the assistance of consultants from the University of Calgary W21C. A 1-9-point scale was used, with 1 being not at all important and 9 being extremely important. A meeting was held for the attributes that require deliberation. After an agreement, a list of attributes for access was elaborated. Next, a ranking of importance and individual weighting was done. We assigned a presence of or lack of an attribute a numerical value (1 for yes, 0 for no) and multiply by its weight to determine a final score. Results: After an initial screening of 2864 abstracts, 121 studies were included in the final systematic review. A total of 34 possible attributes that are barriers to access were identified. After the modified Delphi process, 26 individual attributes were selected. The MTABS was made with possible results from 0-62 points, with higher scores meaning higher barriers to access to MT. Conclusions: The global MTABS represents the first tool to quantify barriers to MT access worldwide. Its implementation will objectively measure the magnitude and identify key barriers to guide regional public health interventions to improve MT workflow and access.

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.

Background:Cervico-cephalic arterial dissections (CeAD) are an important cause of stroke in young patients. This study aimed to determine the frequency and predictors of recanalization in spontaneous CeAD and to study the effect of recanalization on functional outcomes.Methods:We identified patients presenting with acute ischemic stroke secondary to CeAD from the CT angiography (CTA) database of the Calgary Stroke Program. Dissections were diagnosed based on standard clinical and imaging findings. At the discretion of treating stroke Neurologists, the patients were either treated with single antiplatelet or dual antiplatelet or triple therapy. Follow-up imaging with CTA, magnetic resonance imaging, and DSA was completed, and a Modified Rankin scale (mRS) was performed to determine the outcome.Results:Fifty-six patients with CeAdD were studied. Thirty-four patients (18 VAD; vertebral artery dissection and 16 CAD; carotid artery dissection) were followed up for recanalization. Complete recanalization was observed in 27 subjects; 13 patients with VAD recanalized in comparison to 14 with CAD (p = 0.40). All non-recanalized patients had hypertension. A good clinical outcome (mRS ≤ 2) was observed in 47 patients. Interestingly, the likelihood of a good neurological outcome was not influenced by recanalization status. There was no difference in clinical outcome for different sites in VAD, whereas patients with intracranial CAD had severe strokes (NIHSS > 21).Conclusions:CeAD has good recanalization rates and neurological outcomes, with recanalization seen even in vessels with initial complete occlusion. The presence of hypertension may influence recanalization. The efficacy of dual antiplatelets and heparin for early recanalization needs to be assessed in future clinical trials.

Background and Purpose: Sex-related differences exist in many aspects of acute stroke and were mainly investigated in the early time window with conflicting results. However, data regarding sex disparities in late presenters are scarce. Therefore, we sought to investigate differences in outcomes between women and men treated with endovascular treatment in the late time window. Methods: Analyses were based on the SOLSTICE Consortium (Selection of Late-Window Stroke for Thrombectomy by Imaging Collateral Extent), which was an individual-patient level analysis of seven trials and registries. Baseline characteristics, 90-day functional independence (modified Rankin Scale score ≤2), mortality, and symptomatic intracranial hemorrhage were compared between women and men. Effect of sex on the association of age and successful reperfusion (final Thrombolysis in Cerebral Infarction 2b–3) with outcomes was assessed using multivariable logistic regression adjusted for age, National Institutes of Health Stroke Scale score, Alberta Stroke Program Early CT Score, time from onset to puncture, occlusion location, intravenous thrombolysis, and successful reperfusion, with interaction terms. Results: Among 608 patients treated with endovascular treatment, 50.5% were women. Women were older than men (median age of 72 versus 68 years, P =0.02) and had a lower prevalence of tandem occlusions (14.0% versus 22.9%, P =0.005). Workflow times were similar between sexes. Adjusted outcomes did not differ between women and men. Functional independence at 90 days was achieved by 127 out of 292 women (43.5%) and 135 out of 291 men (46.4%). Mortality at 90 days (54 [18.5%] versus 48 [16.5%]) and symptomatic intracranial hemorrhage (37 [13.3%] versus 33 [11.6%]) were similar between women and men. There was no sex-by-age interaction on functional outcomes. However, men had higher likelihood of mortality ( P interaction =0.003) and symptomatic intracranial hemorrhage ( P interaction =0.017) with advancing age. Sex did not influence the relation between successful reperfusion and outcomes. Conclusions: In this multicenter analysis of late patients treated with endovascular treatment, sex was not associated with functional outcome. However, sex influenced the association between age and safety outcomes, with men experiencing worse outcomes with advancing age.

Successful reperfusion determines the treatment effect of endovascular thrombectomy. We evaluated stent-retriever characteristics and their relation to reperfusion in the ESCAPE-NA1 trial.Independent re-scoring of reperfusion grade for each attempt was conducted. The following characteristics were evaluated: stent-retriever length and diameter, thrombus position within stent-retriever, bypass effect, deployment in the superior or inferior MCA trunk, use of balloon guide catheter and distal access catheter. Primary outcome was successful reperfusion defined as expanded thrombolysis in cerebral infarction (eTICI) 2b-3 per attempt. The secondary outcome was successful reperfusion eTICI 2b-3 after the first attempt. Separate regression models for each stent-retriever characteristic and an exploratory multivariable modeling to test the impact of all characteristics on successful reperfusion were built.Of 1105 patients in the trial, 809 with the stent-retriever use (1241 attempts) were included in the primary analysis. The stent-retriever was used as the first-line approach in 751 attempts. A successful attempt was associated with thrombus position within the proximal or middle third of the stent (OR 2.06; 95% CI: 1.24-3.40 and OR 1.92; 95% CI: 1.16-3.15 compared to the distal third respectively) and with bypass effect (OR 1.7; 95% CI: 1.07-2.72). Thrombus position within the proximal or middle third (OR 2.80; 95% CI: 1.47-5.35 and OR 2.05; 95% CI: 1.09-3.84, respectively) was associated with first-pass eTICI 2b-3 reperfusion. In the exploratory analysis accounting for all characteristics, bypass effect was the only independent predictor of eTICI 2b-3 reperfusion (OR 1.95; 95% CI: 1.10-3.46).The presence of bypass effect and thrombus positioning within the proximal and middle third of the stent-retriever were strongly associated with successful reperfusion.

Trials examining the benefit of thrombectomy in anterior circulation proximal large vessel occlusion stroke have enrolled patients considered to have salvageable brain tissue, who were randomly assigned beyond 6 h and (depending on study protocol) up to 24 h from time last seen well. We aimed to estimate the benefit of thrombectomy overall and in prespecified subgroups through individual patient data meta-analysis.We did a systematic review and individual patient data meta-analysis between Jan 1, 2010, and March 1, 2021, of randomised controlled trials of endovascular stroke therapy. In the Analysis Of Pooled Data From Randomized Studies Of Thrombectomy More Than 6 Hours After Last Known Well (AURORA) collaboration, the primary outcome was disability on the modified Rankin Scale (mRS) at 90 days, analysed by ordinal logistic regression. Key safety outcomes were symptomatic intracerebral haemorrhage and mortality within 90 days.Patient level data from 505 individuals (n=266 intervention, n=239 control; mean age 68·6 years [SD 13·7], 259 [51·3%] women) were included from six trials that met inclusion criteria of 17 screened published randomised trials. Primary outcome analysis showed a benefit of thrombectomy with an unadjusted common odds ratio (OR) of 2·42 (95% CI 1·76-3·33; p0·0001) and an adjusted common OR (for age, gender, baseline stroke severity, extent of infarction on baseline head CT, and time from onset to random assignment) of 2·54 (1·83-3·54; p0·0001). Thrombectomy was associated with higher rates of independence in activities of daily living (mRS 0-2) than best medical therapy alone (122 [45·9%] of 266 vs 46 [19·3%] of 238; p0·0001). No significant difference between intervention and control groups was found when analysing either 90-day mortality (44 [16·5%] of 266 vs 46 [19·3%] of 238) or symptomatic intracerebral haemorrhage (14 [5·3%] of 266 vs eight [3·3%] of 239). No heterogeneity of treatment effect was noted across subgroups defined by age, gender, baseline stroke severity, vessel occlusion site, baseline Alberta Stroke Program Early CT Score, and mode of presentation; treatment effect was stronger in patients randomly assigned within 12-24 h (common OR 5·86 [95% CI 3·14-10·94]) than those randomly assigned within 6-12 h (1·76 [1·18-2·62]; pThese findings strengthen the evidence for benefit of endovascular thrombectomy in patients with evidence of reversible cerebral ischaemia across the 6-24 h time window and are relevant to clinical practice. Our findings suggest that in these patients, thrombectomy should not be withheld on the basis of mode of presentation or of the point in time of presentation within the 6-24 h time window.Stryker Neurovascular.

Background and purpose Accurate and reliable detection of medium-vessel occlusions is important to establish the diagnosis of acute ischemic stroke and initiate appropriate treatment with intravenous thrombolysis or endovascular thrombectomy. However, medium-vessel occlusions are often challenging to detect, especially for unexperienced readers. We aimed to evaluate the accuracy and interrater agreement of the detection of medium-vessel occlusions using single-phase and multiphase CTA. Materials and methods Single-phase and multiphase CTA of 120 patients with acute ischemic stroke (20 with no occlusion, 44 with large-vessel occlusion, and 56 with medium-vessel occlusion in the anterior and posterior circulation) were assessed by 3 readers with varying levels of experience (session 1: single-phase CTA; session 2: multiphase CTA). Interrater agreement for occlusion type (large-vessel occlusion versus medium-vessel occlusion versus no occlusion) and for detailed occlusion sites was calculated using the Fleiss κ with 95% confidence intervals. Accuracy for the detection of medium-vessel occlusions was calculated for each reader using classification tables. Results Interrater agreement for occlusion type was moderate for single-phase CTA (κ = 0.58; 95% CI, 0.56-0.62) and almost perfect for multiphase CTA (κ = 0.81; 95% CI, 0.78-0.83). Interrater agreement for detailed occlusion sites was moderate for single-phase CTA (κ = 0.55; 95% CI, 0.53-0.56) and substantial for multiphase CTA (κ = 0.71; 95% CI, 0.67-0.74). On single-phase CTA, readers 1, 2, and 3 classified 33/56 (59%), 34/56 (61%), and 32/56 (57%) correctly as medium-vessel occlusions. On multiphase CTA, 48/56 (86%), 50/56 (89%), and 50/56 (89%) medium-vessel occlusions were classified correctly. Conclusions Interrater agreement for medium-vessel occlusions is moderate when using single-phase CTA and almost perfect with multiphase CTA. Detection accuracy is substantially higher with multiphase CTA compared with single-phase CTA, suggesting that multiphase CTA might be a valuable tool for assessment of medium-vessel occlusion stroke.

Infarct lesion volume (ILV) may serve as an imaging biomarker for clinical outcomes in the early post-treatment stage in patients with acute ischemic stroke. The aim of this study was to evaluate the inter- and intra-rater reliability of manual segmentation of ILV on follow-up non-contrast CT (NCCT) scans. Fifty patients from the Prove-IT study were randomly selected for this analysis. Three raters manually segmented ILV on 24-h NCCT scans, slice by slice, three times. The reference standard for ILV was generated by the Simultaneous Truth And Performance Level estimation (STAPLE) algorithm. Intra- and inter-rater reliability was evaluated, using metrics of intraclass correlation coefficient (ICC) regarding lesion volume and the Dice similarity coefficient (DSC). Median age of the 50 subjects included was 74.5 years (interquartile range [IQR] 67–80), 54% were women, median baseline National Institutes of Health Stroke Scale was 18 (IQR 11–22), median baseline ASPECTS was 9 (IQR 6–10). The mean reference standard ILV was 92.5 ml (standard deviation (SD) ± 100.9 ml). The manually segmented ILV ranged from 88.2 ± 91.5 to 135.5 ± 119.9 ml (means referring to the variation between readers, SD within readers). Inter-rater ICC was 0.83 (95%CI: 0.76–0.88); intra-rater ICC ranged from 0.85 (95%CI: 0.72–0.92) to 0.95 (95%CI: 0.91–0.97). The mean DSC among the three readers ranged from 65.5 ± 22.9 to 76.4 ± 17.1% and the mean overall DSC was 72.8 ± 23.0%. Manual ILV measurements on follow-up CT scans are reliable to measure the radiological outcome despite some variability.

Background and ObjectivesNew imaging techniques have advanced our ability to capture thrombus characteristics and burden in real time. An improved understanding of recanalization rates with thrombolysis and endovascular thrombectomy based on thrombus characteristics has spurred interest in new therapies for acute stroke.Methods and ResultsThis article reviews the biochemical, structural, and imaging characteristics of intracranial thrombi in acute ischemic stroke; the relationship between thrombus composition and response to lytic and endovascular therapies; and current and future directions for improving outcomes in patients with acute stroke based on thrombus characteristics.DiscussionThrombus composition, size, location, and timing from stroke onset correlate with imaging findings in acute ischemic stroke and are associated with clinical outcome. Further research across multiple domains could assist in better applying our knowledge of thrombi to patient selection and individualization of acute therapies.

BACKGROUND Strokes are a longstanding complication of acute type A aortic dissection (ATAAD) repair. Understanding the neuroanatomy, mechanism, and severity of stroke will facilitate efforts to improve prediction, prevention, and treatment strategies. METHODS Retrospective review of patients who sustained stroke from a consecutive series of patients undergoing ATAAD repair. Neuroimaging was interpreted by two stroke neurologists blinded to clinical results. Severity of stroke was assessed by the National Institutes of Health Stroke Scale (NIHSS). Residual disability at 30 days was assessed using the modified Rankin Scale (mRS). RESULTS Twenty percent (38/189) of patients undergoing repair for ATAAD had stroke (unilateral 58%, bi-hemispheric 42% [p = .33]). All strokes were ischemic. No significant lateralization (right vs. left) was noted with unilateral strokes (26% vs. 32%, p = .67). Etiology of stroke was embolic (58%), hypoperfusion (26%), mixed (11%), and unknown (5%). There were no intraoperative variables that correlated with the neuroanatomy or mechanism of stroke. Preoperative carotid dissection was seen in 40% (n = 15), while postoperatively 10% (n = 4) sustained intracranial large vessel occlusion (LVO). Strokes were moderate or severe (NIHSS ≥ 9) in 97% of cases, with 66% incidence of moderate residual disability (mRS ≥ 3) at 1 month postoperatively. CONCLUSIONS Strokes associated with ATAAD are severe at presentation resulting in significant disability. One in 10 strokes is due to LVO and potentially amenable to endovascular treatment. Heterogeneity in both location and etiology of stroke makes prevention challenging. Future trials may evaluate the role of early neuroimaging and simultaneous treatment of stroke given advancements in endovascular therapy.

Background: Age and infarct volume are strong predictors of outcome in patients with ischemic stroke who underwent endovascular therapy (EVT). We aimed to investigate the impact of ischemic core volume (ICV) on stroke outcome after EVT in elderly. Methods: Using the HERMES (Highly Effective Reperfusion Using Multiple Endovascular Devices) collaboration, a patient-level meta-analysis of 7 randomized trials in which patients were enrolled from December 2010 to April 2015) dataset, we categorized patients into those aged Results: A total of 899 patients who had baseline ICV data, 247 patients aged ≥75 years, of which 118 were randomized in the EVT arm. Patients aged ≥75 years required smaller ICV to achieve mRS score ≤3 than those aged P Conclusions: Baseline ICV has an impact on stroke outcome after EVT in the elderly, but elderly patients with large ICV may still benefit from EVT if near-complete or complete reperfusion is achieved. Young patients seem to benefit from EVT regardless of ICV status.

Medium vessel occlusions (MeVOs) can be challenging to detect on imaging. Multiphase computed tomography angiography (mCTA) has been shown to improve large vessel occlusion (LVO) detection and endovascular treatment (EVT) selection. The aims of this study were to determine if mCTA-derived tissue maps can (1) accurately detect MeVOs and (2) predict infarction on 24-h follow-up imaging with comparable accuracy to CT perfusion (CTP). Two readers assessed mCTA tissue maps of 116 ischemic stroke patients (58 MeVOs, 58 non-MeVOs) and determined by consensus: (1) MeVO (yes/no) and (2) occlusion site, blinded to clinical or imaging data. Sensitivity, specificity, and area under the curve (AUC) for MeVO detection were estimated in comparison to reference standards of (1) expert readings of baseline mCTA and (2) CTP maps. Volumetric and spatial agreement between mCTA- and CTP-predicted infarcts was assessed using concordance/intraclass correlation and Dice coefficients. Interrater agreement for MeVO detection on mCTA tissue maps was estimated with Cohen’s kappa. MeVO detection from mCTA-derived tissue maps had a sensitivity of 91% (95% CI: 80–97), specificity of 82% (95% CI: 70–90), and AUC of 0.87 (95% CI: 0.80–0.93) compared to expert reads of baseline mCTA. Interrater reliability was good (0.72, 95% CI: 0.60–0.85). Compared to CTP maps, sensitivity was 87% (95% CI: 75–95), specificity was 78% (95%CI: 65–88), and AUC was 0.83 (95% CI: 0.76–0.90). The mean difference between mCTA- and CTP-predicted final infarct volume was 4.8 mL (limits of agreement: − 58.5 to 68.1) with a Dice coefficient of 33.5%. mCTA tissue maps can be used to reliably detect MeVO stroke and predict tissue fate.

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 Intracranial hemorrhage is a known complication after endovascular treatment in patients with acute ischemic stroke due to large vessel occlusion, but the association between radiologic hemorrhage severity and outcome is controversial. Purpose To investigate the prevalence and impact on outcome of intracranial hemorrhage and hemorrhage severity after endovascular stroke treatment. Materials and Methods The Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke (ESCAPE-NA1) trial enrolled participants with acute large vessel occlusion stroke who underwent endovascular treatment from March 1, 2017, to August 12, 2019. Evidence of any intracranial hemorrhage, hemorrhage multiplicity, and radiologic severity, according to the Heidelberg classification (hemorrhagic infarction type 1 [HI1], hemorrhagic infarction type 2 [HI2], parenchymal hematoma type 1 [PH1], and parenchymal hematoma type 2 [PH2]) was assessed at CT or MRI 24 hours after endovascular treatment. Good functional outcome, defined as a modified Rankin score of 0-2 at 90 days, was compared between participants with intracranial hemorrhage and those without intracranial hemorrhage at follow-up imaging and between hemorrhage subtypes. Poisson regression was performed to obtain adjusted effect size estimates for the presence of any intracranial hemorrhage and hemorrhage subtypes at good functional outcome. Results Of 1097 evaluated participants (mean age, 69 years ± 14 [standard deviation]; 551 men), any degree of intracranial hemorrhage was observed in 372 (34%). Good outcomes were less often achieved among participants with hemorrhage than among those without hemorrhage at follow-up imaging (164 of 372 participants [44%] vs 500 of 720 [69%], respectively; P < .01). After adjusting for baseline variables and infarct volume, intracranial hemorrhage was not associated with decreased chances of good outcome (adjusted risk ratio [RR] = 0.91 [95% CI: 0.82, 1.02], P = .10), but there was a graded relationship of radiologic hemorrhage severity and outcomes, whereby PH1 (RR = 0.77 [95% CI: 0.61, 0.97], P = .03) and PH2 (RR = 0.41 [95% CI: 0.21, 0.81], P = .01) were associated with decreased chances of good outcome. Conclusion Any degree of intracranial hemorrhage after endovascular treatment was seen in one-third of participants. A graded association existed between radiologic hemorrhage severity and outcome. Hemorrhagic infarction was not associated with outcome, whereas parenchymal hematoma was strongly associated with poor outcome, independent of infarct volume. © RSNA, 2021 Clinical trial registration no. NCT01778335 Online supplemental material is available for this article.

Background Intravenous thrombolysis with alteplase is widely used in patients with acute ischemic stroke presenting early after symptom onset. Recent phase II trials have suggested that intravenous tenecteplase may be safer and associated with higher early reperfusion rates as compared with alteplase. This study investigates whether intravenous tenecteplase is noninferior to intravenous alteplase for the treatment of acute ischemic stroke. Methods This is a pragmatic, registry‐linked, prospective, randomized (1:1) controlled, open‐label parallel group clinical trial (AcT [Alteplase Compared to Tenecteplase in Patients With Acute Ischemic Stroke]) with blinded end point assessment of 1600 patients to test if intravenous tenecteplase (0.25 mg/kg body weight, maximum dose 25 mg) is noninferior to intravenous alteplase (0.9 mg/kg body weight; maximum dose, 90 mg) in patients with acute ischemic stroke eligible for intravenous thrombolysis in clinical routine. Patients are recruited from comprehensive and primary stroke centers and enrolled using deferral of consent. The proposed sample has at least 90% power with a noninferiority margin of 5%, assuming incidence of the 90‐day modified Rankin Scale score of 0 to 1 is 38% in the tenecteplase and 35% in the alteplase groups, and a loss to follow‐up rate Results The blinded primary end point is the proportion of subjects achieving a 90‐day modified Rankin Scale score of 0 to 1. Key safety outcomes include 24‐hour symptomatic intracerebral hemorrhage and 90‐day all‐cause mortality. All serious adverse events within a 24‐hour period will be reported and coded using the Medical Dictionary for Regulatory Activities. Outcomes are collected either centrally (primary, key secondary, and safety end points) or through ongoing Canadian stroke registries. The primary analysis is a simple unadjusted comparison of proportions. Conclusions Results from the trial will provide real‐world evidence of the effectiveness of intravenous tenecteplase versus alteplase in patients with acute ischemic stroke presenting early after stroke onset.

Background: Subgroup analyses are widely used to evaluate the heterogeneity of treatment effects in randomized clinical trials. However, there is a limited investigation of the quality of prespecified and reported subgroup analyses in stroke trials. This study evaluated the credibility of subgroup analyses in stroke trials. Methods and analysis: We searched Medline/PubMed, Embase, the Cochrane Central Register of Controlled Trials, and the Web of Science from inception to 24 March 2021. Three reviewers screened, extracted, and analyzed the data from the publications. Primary publications of stroke trials that reported at least one subgroup effect and had published corresponding study protocols were included. The Instrument for Assessing the Credibility of Effect Modification Analyses (ICEMAN) was used to examine the quality of the subgroup effects reported, with each subgroup effect assigned a credibility rating ranging from very low to high. Subgroup effects with two or more “definitely no” responses received a low credibility rating. The risk of bias was assessed using the Cochrane Risk-of-Bias tool for randomized trials version 2. Results: Seventy-four articles met the inclusion criteria and reported a combined total of 647 subgroup effects. The median sample size was 1264 (interquartile range (IQR): 380–3876), and the median number of subgroups prespecified in the protocol was 6 (IQR: 2–10). Sixty-one (82%) studies used the univariate test of interaction. Of the total 647 subgroup effects reported in these studies, 319 (49%) were reported in acute stroke trials, while 423 (65%) had low credibility. Conclusion: The quality of subgroup analysis reporting in stroke trials remains poor. More effort is needed to train trialists on the best methods for designing and performing subgroup analyses, and how to report the results. Trial registration number: We prospectively registered the review with International Prospective Register for Systematic Reviews (registration number: CRD42020223133)

Background The effect of infarct pattern on functional outcome in acute ischemic stroke is incompletely understood. Purpose To investigate the association of qualitative and quantitative infarct variables at 24-hour follow-up noncontrast CT and diffusion-weighted MRI with 90-day clinical outcome. Materials and Methods The Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke, or ESCAPE-NA1, randomized controlled trial enrolled patients with large-vessel-occlusion stroke undergoing mechanical thrombectomy from March 1, 2017, to August 12, 2019. In this post hoc analysis of the trial, qualitative infarct variables (predominantly gray [vs gray and white] matter involvement, corticospinal tract involvement, infarct structure [scattered vs territorial]) and total infarct volume were assessed at 24-hour follow-up noncontrast CT or diffusion-weighted MRI. White and gray matter infarct volumes were assessed in patients by using follow-up diffusion-weighted MRI. Infarct variables were compared between patients with and those without good outcome, defined as a modified Rankin Scale score of 0-2 at 90 days. The association of infarct variables with good outcome was determined with use of multivariable logistic regression. Separate regression models were used to report effect size estimates with adjustment for total infarct volume. Results Qualitative infarct variables were assessed in 1026 patients (mean age ± standard deviation, 69 years ± 13; 522 men) and quantitative infarct variables were assessed in a subgroup of 358 of 1026 patients (mean age, 67 years ± 13; 190 women). Patients with gray and white matter involvement (odds ratio [OR] after multivariable adjustment, 0.19; 95% CI: 0.14, 0.25; P < .001), corticospinal tract involvement (OR after multivariable adjustment, 0.06; 95% CI: 0.04, 0.10; P < .001), and territorial infarcts (OR after multivariable adjustment, 0.22; 95% CI: 0.14, 0.32; P < .001) were less likely to achieve good outcome, independent of total infarct volume. Conclusion Infarct confinement to the gray matter, corticospinal tract sparing, and scattered infarct structure at 24-hour noncontrast CT and diffusion-weighted MRI were highly predictive of good 90-day clinical outcome, independent of total infarct volume. Clinical trial registration no. NCT02930018 © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Mossa-Basha in this issue.

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 Identification of therapies to prevent severe COVID-19 remains a priority. We sought to determine whether hydroxychloroquine treatment for outpatients with SARS-CoV-2 infection could prevent hospitalization, mechanical ventilation or death. Methods This randomized controlled trial was conducted in Alberta during the first wave of the COVID-19 pandemic without direct contact with participants. Community-dwelling individuals with confirmed SARS-CoV-2 infection (by reverse transcription polymerase chain reaction [RT-PCR] viral ribonucleic acid test) within the previous 4 days, and symptom onset within the previous 12 days, were randomly assigned to oral hydroxychloroquine or matching placebo for 5 days. Enrolment began Apr. 15, 2020. The primary outcome was the composite of hospitalization, invasive mechanical ventilation or death within 30 days. Secondary outcomes included symptom duration and disposition at 30 days. Safety outcomes, such as serious adverse events and mortality, were also ascertained. Outcomes were determined by telephone follow-up and administrative data. Results Among 4919 individuals with a positive RT-PCR test, 148 (10.2% of a planned 1446 patients) were randomly assigned, 111 to hydroxychloroquine and 37 to placebo. Of the 148 participants, 24 (16.2%) did not start the study drug. Four participants in the hydroxychloroquine group met the primary outcome (4 hospitalizations, 0 mechanical ventilation, 4 survived to 30 days) and none in the placebo group. Hydroxychloroquine did not reduce symptom duration (hazard ratio 0.77, 95% confidence interval 0.49-1.21). Recruitment was paused on May 22, 2020, when a since-retracted publication raised concerns about the safety of hydroxychloroquine for hospitalized patients with COVID-19. Although we had not identified concerns in a safety review, enrolment was slower than expected among those eligible for the study, and cases within the community were decreasing. Recruitment goals were deemed to be unattainable and the trial was not resumed, resulting in a study underpowered to assess the effect of treatment with hydroxychloroquine and safety. Interpretation There was no evidence that hydroxychloroquine reduced symptom duration or prevented severe outcomes among outpatients with proven COVID-19, but the early termination of our study meant that it was underpowered. Trial registration ClinicalTrials.gov, no. NCT04329611.

Background and Purpose: Endovascular thrombectomy (EVT) reduces 90-day disability in patients following acute ischemic stroke due to large vessel occlusion. Patient-reported outcome measures after EVT, such as health-related quality of life and specific functional domains, are less well described. Methods: We report outcomes on the EuroQol-5D (EQ-5D) from the ESCAPE (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times) randomized controlled trial at 90 days after stroke. Death was assigned an index value of 0 for EQ-5D. We used quantile regression to evaluate the association between EVT and EQ-5D index scores and logistic regression for the association between EVT and symptom-free status among 90-day survivors for each EQ-5D dimension (self-care, usual activities, mobility, pain/discomfort, and anxiety/depression), assessing for modification by age or sex and adjusting for baseline factors including stroke severity, affected hemisphere, and receipt of alteplase. Lastly, the association between severe disability at 90 days and EQ-5D was evaluated with assessment for modification by EVT, age, and sex. Results: There were 165 patients randomized to EVT and 150 patients randomized to control. Median EQ-5D was significantly higher for those who received EVT compared with best medical management (0.80 versus 0.60; P Conclusions: Patients treated with EVT report substantially improved health-related quality of life, with relatively greater impact in older individuals and observed benefit across multiple dimensions.

Background and Purpose: Fast infarct progression in acute ischemic stroke has a severe impact on patient prognosis and benefit of endovascular thrombectomy. In this post hoc analysis of the ESCAPE trial (Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke), we identified acute ischemic stroke patients with rapid infarct growth and investigated their baseline clinical and imaging characteristics. Methods: Control arm patients were included if they had follow-up imaging at 2-8 hours without substantial recanalization, and if their baseline Alberta Stroke Program Early CT Score was ≥9. Fast infarct progression was defined as Alberta Stroke Program Early CT Score decay ≥3 points from baseline to 2- to 8-hour follow-up imaging. Clinical and imaging baseline characteristics were compared between fast progressors and other patients, and occlusion site and collateral flow patterns were assessed in detail. Results: Fast infarct progression occurred in 15 of 43 included patients (34.9%). Fast progressors had worse collaterals (poor in 3/15 [20%] versus 0/28 patients, P =0.021) and more carotid-T or -L occlusions (8/15 [53.4%] versus 3/28[10.7%], P =0.021). In 8 out of 15 (53.3%), occlusion site and circle of Willis configuration prevented collateral flow via the anterior or posterior cerebral artery. Conclusions: Most patients with fast infarct progression had terminal carotid occlusions and impaired collateral flow via the anterior or posterior cerebral artery, indicating that occlusion location and intracranial vascular anatomy are relevant for infarct progression.

Background and Purpose Multiphase computed tomographic angiography (mCTA) provides time variant images of pial vasculature supplying brain in patients with acute ischemic stroke (AIS). To develop a machine learning (ML) technique to predict tissue perfusion and infarction from mCTA source images.Methods 284 patients with AIS were included from the Precise and Rapid assessment of collaterals using multi-phase CTA in the triage of patients with acute ischemic stroke for Intra-artery Therapy (Prove-IT) study. All patients had non-contrast computed tomography, mCTA, and computed tomographic perfusion (CTP) at baseline and follow-up magnetic resonance imaging/non-contrast-enhanced computed tomography. Of the 284 patient images, 140 patient images were randomly selected to train and validate three ML models to predict a pre-defined Tmax thresholded perfusion abnormality, core and penumbra on CTP. The remaining 144 patient images were used to test the ML models. The predicted perfusion, core and penumbra lesions from ML models were compared to CTP perfusion lesion and to follow-up infarct using Bland-Altman plots, concordance correlation coefficient (CCC), intra-class correlation coefficient (ICC), and Dice similarity coefficient.Results Mean difference between the mCTA predicted perfusion volume and CTP perfusion volume was 4.6 mL (limit of agreement [LoA], –53 to 62.1 mL; P=0.56; CCC 0.63 [95% confidence interval [CI], 0.53 to 0.71; P