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Background and Objectives: We aimed to develop a novel computed tomography angiography (CTA)-based grading system to quantify the severity of aortic arch disease and compare the detection of aortic arch atherosclerosis (AAAthero) on routinely acquired arch-to-vertex CTA against transesophageal echocardiogram (TEE) among patients with cryptogenic ischemic stroke. Methods: A systematic literature review was conducted to develop a computed tomography (CT)-based AAAthero grading system. CTA was compared against TEE for detecting AAAthero. The severity of arch atherosclerosis was scored based on a 5-point grading system. Patients with cryptogenic stroke who underwent both CTA and TEE were included in the derivation cohort to assess the sensitivity and specificity of CTA compared to TEE. The CT-based grading system for aortic plaques was then applied to an independent cohort of patients with cryptogenic stroke. Results: Three studies were identified in a systematic review, and 141 patients were included in the derivation cohort. AAAthero was detected in 29 patients (20.6%) and 28 patients (19.9%) on TEE and CTA, respectively. The sensitivity of CTA to detect any atherosclerosis was 76%, which increased to 100% to detect moderate to severe disease. The specificity was 95% for any atherosclerosis and 100% for moderate to severe arch disease. Seven patients with AAAthero on TEE had normal CTA, but mild arch disease. Meanwhile, six patients with CTA and negative TEE had plaques on the arch's transverse segment. Conclusions: Routinely acquired arch-to-vertex CTA provides an accurate, noninvasive alternative to TEE for detecting AAAthero, especially in clinically relevant moderate to severe arch disease. Keywords: Arch-to-vertex CT angiogram, atherosclerotic aortic arch disease, ischemic stroke, transesophageal echocardiography, Author(s): Ankur Wadhwa (corresponding author) [1,2]; Ravinder-Jeet Singh [3]; Mohammed Almekhlafi [4]; Bijoy K Menon [4]; Poornima N Nambiar [5]; Arun Kathuveetil [5]; Santhosh Kannath [5]; Manik Chhabra [6]; PN [...]

Background: Early ischemic changes on baseline imaging are commonly evaluated for acute stroke decision-making and prognostication. Aims: We assess the association of early ischemic changes on clinical outcomes and whether it differs between intravenous tenecteplase and Alteplase. Methods: Data are from the phase 3, Alteplase compared to Tenecteplase (AcT) trial. Subjects with anterior circulation stroke were included. Early ischemic changes were assessed using the Alberta Stroke Program Early CT score (ASPECTS). Efficacy outcomes included modified Rankin scale (mRS) 0–1, mRS 0–2, and ordinal mRS at 90 days. Safety outcomes included 24-h symptomatic intracerebral hemorrhage (sICH), any hemorrhage on follow-up scan, and 90-day mortality rate. Mixed-effects logistic regression was used to assess the association of ASPECTS (continuous and categorical (0–4 vs 5–7 vs 8–10)) with outcomes and if these associations were modified by thrombolytic type after adjusting for age, sex, and baseline stroke severity. Results: Of the 1577 patients in the trial, 901 patients (56.3%; median age 75 years (IQR 65–84), 50.8% females, median National Institute of Health Stroke Scale (NIHSS) 14 (IQR 17–19)) with anterior circulation stroke were included. mRS 0–1 at 90 days was achieved in 1/14 (0.3%), 43/160 (14.7%), and 252/726 (85.1%) in the ASPECTS 0–4, 5–7, and 8–10 groups respectively. Every one-point decrease in ASPECTS was associated with 2.7% and 1.9% decrease in chances of mRS 0–1 and mRS 0–2 at 90 days, respectively, and 1.9% chances of increase in mortality at 90 days. Subgroup analysis in endovascular thrombectomy (EVT)-treated population showed similar results. Thrombolytic type did not modify this association between ASPECTS and 90-day mRS 0–1 (P-interaction 0.75). There was no significant interaction by thrombolytic type with any other outcomes. Conclusion: Similar to prior studies, we found that every one-point decrease in ASPECTS was associated with poorer clinical and safety outcomes. This effect did not differ between alteplase and tenecteplase. Data access statement: Data shall made available on reasonable request from the PI (BMM). [ABSTRACT FROM AUTHOR]

Background: In the ESCAPE-NA1 trial, treatment with nerinetide, an eicosapeptide that interferes with post-synaptic density protein 95, was associated with improved functional outcome among patients with acute ischaemic stroke due to large vessel occlusion undergoing endovascular thrombectomy without co-treatment with an intravenous thrombolytic agent. There was no benefit when intravenous thrombolytic agent co-treatment was used. We sought to confirm the clinical benefit of nerinetide in the absence of previous intravenous thrombolytic drug treatment., Methods: In this multicentre, randomised, double-blind, placebo-controlled study, done in 77 centres in Canada (16), the USA (16), Germany (21), Italy (four), the Netherlands (three), Norway (four), Switzerland (three), Australia (eight), and Singapore (two), we enrolled patients with acute ischaemic stroke due to anterior circulation large vessel occlusion within 12 h from onset. Eligible patients were aged 18 years or older with a disabling ischaemic stroke at the time of randomisation (baseline National Institutes of Health Stroke Scale [NIHSS] score >5), who had been functioning independently in the community (Barthel Index score >90) before the stroke, had Alberta Stroke Program Early CT Score (ASPECTS) greater than 4, and who were not treated with a plasminogen activator. Patients were randomly allocated (1:1) to receive intravenous infusion of nerinetide in a single dose of 2·6 mg/kg, up to a maximum dose of 270 mg, based upon estimated or actual weight (if known) or saline placebo using a real-time, dynamic, internet-based, stratified randomised minimisation procedure. All patients underwent endovascular thrombectomy. The primary outcome was a favourable functional outcome 90 days from randomisation, defined as a modified Rankin Scale (mRS) score of 0-2. The analysis was by intention to treat and adjusted for time from stroke onset to randomisation (≤4·5 h [yes or no]), age, sex, baseline NIHSS score, occlusion location, time from qualifying imaging to randomisation, baseline ASPECTS, and region. Secondary outcomes were measures of mortality, worsening of stroke, improved functional independence, and measures of neurological disability. This trial is registered with ClinicalTrials.gov, NCT04462536., Findings: From Dec 6, 2020, to Jan 31, 2023, 850 patients were assigned to receive nerinetide (n=454) or placebo (n=396). 206 (45%) participants in the nerinetide group and 181 (46%) participants in the placebo group achieved an mRS score of 0-2 at 90 days (odds ratio 0·97, 95% CI 0·72-1·30; p=0·82). Serious adverse events occurred equally between groups., Interpretation: While nerinetide did not improve outcomes in patients with acute ischaemic stroke, it was not associated with excess adverse events. Further study is needed to identify the ideal timing of treatment and the sub-population of stroke patients who might benefit from treatment combined with current reperfusion therapies., Funding: Canadian Institutes for Health Research and NoNO., Competing Interests: Declaration of interests AHA reports an unrestricted grant from Boehringer-Ingelheim for the TenCRAOS trial. DJG reports share ownership in NoNO. MAA reports Advisory Board membership for Fluid Biomed and Palmera Medical. NA reports salary support from the American Heart Association for her role as section editor in Stroke and from the Florida Stroke Registry. JMC reports grants from Bayer and AstraZeneca and is a co-founder and shareholder of TrianecT. AMD reports a grant from Medtronic, DSMC membership for the WE TRUST study (sponsored by Phillips), DSMC chairman for the LT 3001-203 and LT3001-205 studies (sponsored by Lumosa), and board chairmanship for the Canadian Stroke Consortium (non-profit sector). DWJD reports grants from Stryker Neurovascular, Medtronic, Cerenovus, Penumbra, and Thrombolytic Science, DSMC chairmanship for the ACT-Global and LATE-MT studies, and past chairmanship of the CONTRAST Consortium. AE reports board membership of the Norwegian Stroke Organization. TSF reports payment for advisory board roles for Bayer, Novartis, HLS Therapeutics, and AstraZeneca and board membership for Destine Health and the Vancouver General Hospital–University of British Columbia Foundation. SF reports consulting fees and honoria from Microvention, Rapid Medical,and Stryker Neurovascular. DG reports grants from Microvention and consulting fees from Navigantis. MG reports grants from Medtronic and Cerenovus; consulting fees from Microvention, Stryker Neurovascular, Medronic, Mentice, Phillips, and Penumbra; and stock ownership in Circle Neurovascular. JG reports consulting fees from Medtronic and Johnson & Johnson/Cerenovus. AEH reports grants from GE Healthcare and Viz.ai, consulting fees or honoraria from Medtronic, Microvention, Stryker Neurovascular, Penumbra, Cerevonus, Xcath, Imperative Care, Perfuze, Route 92, Genentech, GE Healthcare, Scientia, Balt, Viz.ai, Insera Therapeutics, Proximie, NovaSignal, and Vesalio, DSMC membership for the COMMAND study, and is the past-president of the Society of Vascular and Interventional Neurology. KJH reports share ownership in NoNO. VH reports grants and consulting fees from Wallaby/Phenox. MDH reports grants from NoNO and Canadian Institutes of Health Research (CIHR) which directly supported the ESCAPE-NEXT study, past grants from NoNO, Medtronic, Boehringer-Ingelheim, CIHR, and Heart & Stroke Foundation; consulting fees from Sun Pharma and Brainsgate, patents licensed to Circle Neurovascular, DSMC charimanship for the DUMAS and Oncover Hiltonel trials, DSMC membership for the ARTESIA, BRAIN-AF and LAAOS-4 trials, stock ownership in Circle Neurovascular, and is the current president of the Canadian Neurological Sciences Federation (non-profit sector). MH reports consulting fees or honoraria from Balt, Medtronic, Stryker Neurovascular, Microvention, Phenox, Cerenovus, Siemens, and Rapid Medical. MEK reports consulting fees from Medtronic and Penumbra and stock or stock options from Basecamp Vascular, Radical Catheter Technology, and Endostream. TL reports grants from Cerus, Stryker Neurovascular, and Phenox and DSMC membership in the CLOT OUT study. NL reports consulting fees from Medtronic and honoraria from Medtronic, Penumbra, Balt, Cerenovus, Microvention, and Stryker Neurovascular. JLM reports advisory board membership for the SECRET study and board membership for the Canadian Stroke Consortium (non-profit sector). BKM reports grants for the CIHR. MM reports consulting fees from Stryker Neurovascular. MP reports grants from German Research Foundation and honoraria from Merck. SP reports grants from BMS/Pfizer, Boehringer-Ingelheim, Danichi-Sankyo, EU, German Federal Joint Committee Innovation Fund, German Federal Ministry of Education of Research, Helena Laboratories, and Werfen; consulting fees from Alexion, AstraZeneca, Daichi-Sankyo, and Werfen; and honoraria from Alexion, Bayer, Boehringer-Ingelheim, BMS/Pfizer, and Portola. AYP reports grants from Brain Canada, Heart & Stroke Foundation Canada, and CIHR, honoraria from Roche Canada, safety committee chairmanship for the ACT trial, and fellowship certification committee chairmanship for the Canadian Stroke Consortium (non-profit sector). M-NP reports grants from Swiss National Science Foundation, Bangerter-Rhyner Stiftung, Stryker Neurovascular, Phenox, Medtronic, Penumbra, and Siemens Healthineers and honoraria from Stryker Neurovascular, Medtronic, Pneumbra, Acandis, and Siemens Healthineers. ASP reports DSMC membership for Cerevasc and Keep, stock or stock options in NTI, Galaxy, Agile, and Perfuse, and a consultancy role for Cerenovus, Agile, Arsenal, Route 92, Stryker Neurovascular, Rapid, and Spryte. MR reports grants from the National Institutes of Health (NIH). RHS reports grants from the NIH, CIHR, and Ontario Brain Institute, DSMC membership for Hoffman La Roche, and stock or stock options in FollowMD. JWT reports consulting fees from Medtronic, Stryker Neurovascular, and Qure.ai. MT reports stock and CEO role in NoNO. PJvD reports consulting fees from Stryker Neurovascular, Phillips, Medtronic, and Siemens. WvZ reports consulting fees or honoraria from Phillips, Bayer, Stryker Neurovascular, Medtronic, Nico Lab, Cerenovus, and DSMC membership in the WeTrust, Athena, and InExtremis trials. MW reports grants from Ab medica, Acandis, Cerenovus, Kaneka Pharmaceuticals, Medtronic, Microvention, Phenox, Siemens Healthcare, and Stryker Neurovascular, consulting fees from Stryker Neurovascular, honoraria from Bracco Imaging, Medtronic, Siemens Healthcare, and Stryker Neurovascular. LLLY reports grants from National Medical Research Council (Singapore) and the Ministry of Education, advisory board membership for AstraZeneca, vice-president role for the Society of Neurointerventional Surgery, stock or stock options in Cereflo and medical advisor roles for Sunbird-bio, Cortirio, and See-mode. All other authors declare no competing interests., (Copyright © 2025 The Author(s). Published by Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. Published by Elsevier Ltd.. All rights reserved.)

Background: Intravenous (IV) tenecteplase is increasingly being used in lieu of alteplase for acute ischemic stroke. We sought to study the influence of IV tenecteplase versus IV alteplase on the efficacy of first line thrombectomy strategy., Methods: This was a secondary analysis of the Alteplase versus Tenecteplase (AcT) trial. We included anterior and posterior circulation stroke patients in whom a thrombectomy was attempted. We compared outcomes for stent retriever as first line strategy versus contact aspiration alone, and interactions with thrombolysis type. We examined angiographic outcomes (extended final thrombolysis in cerebral infarction (eTICI) 2c-3 after first-pass, eTICI 2b-3 and eTICI 2 c-3 on final angiography), and clinical and safety outcomes. Mixed effect regression analyses with interaction terms were performed. All outcomes were assessed and analyzed by blinded adjudicators., Results: Among 506 patients who received thrombectomy, 435 were included (222 (51.0%) IV tenecteplase, 213 (49.0%) IV alteplase). A stent retriever was used as the first line endovascular thrombectomy (EVT) approach in 288 (66.2%), and aspiration in 147 (33.8%) patients. There was no difference in rates of final eTICI 2c-3 between groups (57.0% with stent retriever vs 61.9% with aspiration; P=0.35). There was, however, a significant interaction (P=0.02) between thrombolysis type and first line EVT strategy for final eTICI 2c-3, where tenecteplase was associated with higher odds of final eTICI 2c-3 with aspiration (adjusted OR (aOR) 2.29, 95% CI 1.10 to 4.75), but not with stent retriever (aOR 0.63, 95% CI 0.38 to 1.04). No significant interaction between thrombolysis and first line strategy was found for the other angiographic, clinical or safety outcomes., Conclusion: IV tenecteplase before EVT may enhance reperfusion with first line aspiration., Trial Registration Number: NCT03889249., Competing Interests: Competing interests: BKM has stock options in Circle NVI and has consulted for Biogen, Roche, and Boehringer Ingelheim. LC received payments by Servier, and consulting fees from Ischaemavie RAPID, Circle NV, and CMPA. MDH has received consulting fees from Sun Pharma and Brainsgate, and has stock options in Circle NVI. TS has received consulting fees from Circle NVI. RHS has stock options in FollowMD, and gets salary support for research from the Heart and Stroke Foundation of Canada, Sandra Black Center for Brain Resilience and Recovery, and Ontario Brain Institute., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Carotid web (CaW) is a risk factor for ischemic stroke, mainly in young patients with stroke of undetermined etiology. Its detection is challenging, especially among non-experienced physicians., Methods: We included patients with CaW from six international trials and registries of patients with acute ischemic stroke. Identification and manual segmentations of CaW were performed by three trained radiologists. We designed a two-stage segmentation strategy based on a convolutional neural network (CNN). At the first stage, the two carotid arteries were segmented using a U-shaped CNN. At the second stage, the segmentation of the CaW was first confined to the vicinity of the carotid arteries. Then, the carotid bifurcation region was localized by the proposed carotid bifurcation localization algorithm followed by another U-shaped CNN. A volume threshold based on the derived CaW manual segmentation statistics was then used to determine whether or not CaW was present., Results: We included 58 patients (median (IQR) age 59 (50-75) years, 60% women). The Dice similarity coefficient and 95th percentile Hausdorff distance between manually segmented CaW and the algorithm segmented CaW were 63.20±19.03% and 1.19±0.9 mm, respectively. Using a volume threshold of 5 mm 3 , binary classification detection metrics for CaW on a single artery were as follows: accuracy: 92.2% (95% CI 87.93% to 96.55%), precision: 94.83% (95% CI 88.68% to 100.00%), sensitivity: 90.16% (95% CI 82.16% to 96.97%), specificity: 94.55% (95% CI 88.0% to 100.0%), F1 measure: 0.9244 (95% CI 0.8679 to 0.9692), area under the curve: 0.9235 (95%CI 0.8726 to 0.9688)., Conclusions: The proposed two-stage method enables reliable segmentation and detection of CaW from head and neck CT angiography., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)