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While imaging has traditionally played a fundamental role in the selection of patients undergoing endovascular thrombectomy, recent thrombectomy trials involving patients with large ischemic strokes demonstrated a consistent benefit of endovascular thrombectomy across all imaging strata, suggesting that reperfusion benefit may exist independent of current imaging constructs. Although these findings attest to the uniformly beneficial effects of reperfusion, they also shed doubt on the accuracy and utility of our imaging modalities in defining reversible versus irreversible ischemia and challenge the premise of imaging-based selection. We aimed to review the histopathologic studies and clinical trials that have shaped our understanding of current imaging constructs aiming to outline the existing imaging-neuropathological gap that may be far wider than previously perceived., Competing Interests: Dr Liebeskind received compensation as a consultant for Medtronic, Stryker, Rapid Medical Ltd, Genentech, and Cerenovus. Dr Jovin has stock options in Viz.ai, StataDx, Basking, Route92, Methinks, Anaconda, FreeOx Biotech, Contego Medical, Inc, Gravity, and Kandu, received grants from Stryker Corporation and Medtronic USA, Inc; received compensation as a consultant from Contego Medical, Inc; and received compensation from Johnson & Johnson Cerenovus for data and safety monitoring services. The other authors report no conflicts.

Background: Acute ischemic stroke (AIS) from primary medium vessel occlusions (MeVO) is a prevalent condition associated with substantial morbidity and mortality. Despite the common use of mechanical thrombectomy (MT) in AIS, predictors of poor outcomes in MeVO remain poorly characterized., Methods: In this prospectively collected, retrospectively reviewed, multicenter, multinational study, data from the MAD-MT (Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy) registry were analyzed. The study included 1568 patients from 37 academic centers across North America, Asia, and Europe, treated with MT, with or without intravenous tissue plasminogen activator (IVtPA), between September 2017 and July 2021., Results: Among the 1568 patients, 347 (22.2%) experienced very poor outcomes (modified Rankin score (mRS), 5-6). Key predictors of poor outcomes were advanced age (odds ratio (OR): 1.03; 95% confidence interval (CI): 1.02 to 1.04; p < 0.001), higher baseline National Institutes of Health Stroke Scale (NIHSS) scores (OR: 1.07; 95% CI: 1.05 to 1.10; p < 0.001), pre-operative glucose levels (OR: 1.01; 95% CI: 1.00 to 1.02; p < 0.001), and a baseline mRS of 4 (OR: 2.69; 95% CI: 1.25 to 5.82; p = 0.011). The multivariable model demonstrated good predictive accuracy with an area under the receiver-operating characteristic (ROC) curve of 0.76., Conclusions: This study demonstrates that advanced age, higher NIHSS scores, elevated pre-stroke mRS, and pre-operative glucose levels significantly predict very poor outcomes in AIS-MeVO patients who received MT. These findings highlight the importance of a comprehensive risk assessment in primary MeVO patients for personalized treatment strategies. However, they also suggest a need for cautious patient selection for endovascular thrombectomy. Further prospective studies are needed to confirm these findings and explore targeted therapeutic interventions., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Regenhardt serves on a DSMB for a trial sponsored by Rapid Medical, serves as site PI for studies sponsored by Penumbra and Microvention, and receives stroke research grant funding from the National Institutes of Health, Society of Vascular and Interventional Neurology, and Heitman Stroke Foundation. Dr Guenego reports consultancy for Rapid Medical and Phenox, not directly related to the present work. Dr Clarençon reports conflicts of interest with Medtronic, Balt Extrusion (consultant), ClinSearch (core lab), Penumbra, Stryker (payment for reading), and Artedrone (Board); all not directly related to the present work. Dr Henninger received support from CDMRP/DoD W81XWH-19-PRARP-RPA and NINDS NS131756, during the conduct of the study. Dr Liebeskind is consultant as Imaging Core Lab to Cerenovus, Genentech, Medtronic, Stryker, and Rapid Medical. Dr Yeo reports Advisory work for AstraZeneca, substantial support from NMRC Singapore, and is a medical advisor for See-mode, Cortiro, and Sunbird Bio, with equity in Ceroflo. All unrelated to the present work. Dr Griessenauer reports a proctoring agreement with Medtronic and research funding by Penumbra. Dr Marnat reports conflicts of interest with Microvention Europe, Stryker Neurovascular, Balt (consulting), Medtronic, Johnson & Johnson, and Phenox (paid lectures), all not directly related to the present work. Dr Puri is a consultant for Medtronic Neurovascular, Stryker NeurovascularBalt, Q’Apel Medical, Cerenovus, Microvention, Imperative Care, Agile, Merit, CereVasc, and Arsenal Medical; he received research grants from NIH, Microvention, Cerenovus, Medtronic Neurovascular, and Stryker Neurovascular; and he holds stocks in InNeuroCo, Agile, Perfuze, Galaxy, and NTI. Dr Tjoumakaris is a consultant for Medtronic and Microvention (funds paid to institution, not personally). Dr Jabbour is a consultant for Medtronic, Microvention, and Cerus.

Background: The EXCELLENT registry aimed to evaluate the effectiveness of the EMBOTRAP Revascularization Device in an all-comer population in a real-world setting, with a focus on the composition of retrieved clots., Methods: EXCELLENT is a prospective, global registry of patients with acute ischemic stroke treated with EMBOTRAP as the first-line mechanical thrombectomy device conducted at 34 sites (25 sites contributing clot) from September 2018 to March 2021, utilizing core imaging and central histology laboratories blinded to clinical data, independent 90-day modified Rankin Scale assessment and Clinical Events Committee., Results: After screening 3799 patients, a total of 997 subjects (mean age, 70.0±14.2 years; 51.8% women; 19.7% non-White) were included. The first-pass modified Treatment in Cerebral Infarction (mTICI) ≥2b rate was 64.5% (623/966), first-pass mTICI ≥2c was 39.1% (378/966), and final mTICI ≥2b was 94.5% (931/985). A total of 427/912 (46.8%) patients achieved a 90-day modified Rankin Scale of 0 to 2 or ≤baseline. Embolization to a new territory occurred in 0.2% (2/984), and symptomatic intracranial hemorrhage at 24 hours in 1.6% (16/997). The 90-day mortality was 19.1% (175/918). Device- and/or procedure-related serious adverse events occurred in 5.9% (54/912) through 90 days. The mean RBC percentage of retrieved clots was 45.62±21.372. Among patients who achieved mTICI ≥2b with the first pass, 15.7% (52/331) and 9.7% (32/331), respectively, had RBC-poor (<25%) and RBC-rich (>75%) clots. Patients with no clot retrieved in any procedural pass had a lower percentage of hyperdense or susceptibility vessel sign on baseline imaging (58.9% versus 74.7%; P <0.001), pointing to a potential preprocedure indicator of challenging clot., Conclusions: The EXCELLENT registry informs real-world practices in mechanical thrombectomy and sheds light on the range of clots effectively retrieved by current technology. This is the first report of detailed patient characteristics where mechanical thrombectomy maneuvers failed to remove any clot material. Although the composition of nonretrievable clots cannot be assessed histologically, the results support the notion that no retrieval may be correlated with imaging findings suggesting clots lower in RBC., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03685578., Competing Interests: Dr Nogueira: consulting for Anaconda, Medtronic, Cerenovus, Genentech, Viz-AI, Stryker, Prolong Pharmaceuticals, Perfuze, Biogen, Shanghai Wallaby, Brainomix, Hybernia, RapidPulse, Imperative Care, Corindus, NeuroVasc Technologies, Vesalio, Cerebrotech, Phenox, Astrocyte, Ceretrieve, Philips; grants from Stryker, Cerenovus; data safety monitoring for Synchron; ownership/investment interest in Ceretrieve, Corindus, Brainomix, Perfuze, Truvic, Viz-AI, Reist, Q’Apel, Vesalio, Cerebrotech, Viseon, Piraeus, Brain4Care, Quantanosis-AI. Dr Andersson: consulting for Neuravi, Anaconda, Johnson & Johnson (J&J), Rapid Medical; ownership/investment interest in Ceroflo. Dr Haussen: consulting for Brainomix, Vesalio, Stryker, Poseydon, Chiesi, Cerenovus; ownership/investment interest in Viz-AI; data safety monitoring for Jacobs Institute. Dr Yoo: consulting for Philips, Nicolab, ZOLL Circulation, Vesalio, Rapid Medical; grants and consulting for J&J, Medtronic, Penumbra; grants from Stryker, Genentech; ownership/investment interest in Gravity, Galaxy Therapeutics, Insera, Nicolab; data safety monitoring for NIH; employment with HCA Healthcare; other services for AHA. Dr Hanel: consulting for Balt, MicroVention, Medtronic, Rapid Medical, Stryker, Phenox, Cerenovus, Q’Apel; ownership/investment interest in Cerebrotech, Three Rivers Medical, NTI, Endostream, BlinkTBI, RisT, InNeuroCo, Corindus, eLum, Scientia. Dr Zaidat: consulting for J&J; patent holder. Dr Hacke: consulting for J&J. Dr Jovin: consulting for Contego Medical; grants from Medtronic, Stryker; employment with Cooper University Healthcare; data safety monitoring for Cerenovus; ownership/investment interest in Anaconda, StataDx, Galaxy, Basking, Freeox Biotech, Kandu, Viz-AI, Route92, Gravity. Dr Fiehler: consulting for Stryker, Cerenovus, Penumbra, MicroVention, Roche, Tonbridge, Phenox, TG Medical, Medtronic, Acandis; ownership/investment interest in Vastrax, Eppdata, Tegus; employment with Eppdata. Dr De Meyer: travel support from J&J. Dr Brinjikji: consulting for Cerenovus, MicroVention, Medtronic, Balt, Imperative Care, MIVI; ownership interest in Piraeus, Nested Knowledge, MIVI; research funding from Cerenovus, Brainomix, NIH. Dr Doyle: grants from SFI, Cerenovus. Dr Kallmes: grants from MIVI, Cerenovus, Balt, Vesalio, Stryker, MicroVention, Insera, Medtronic, Brainomix; ownership/investment interest in Superior Medical Experts, Conway Medical, Piraeus, Monarch Biosciences, Marblehead, Nested Knowledge; patent holder. Dr Liebeskind: consulting for Cerenovus, Medtronic, Genentech, Stryker, Rapid Medical. Dr Virmani: grants from Endotronix, L&J Bio, W.L. Gore, Recombinetics, Transverse Medical, Profusa, Lutonix, MicroVention, Envision, Neovasc, Cerus EndoVascular, MedAlliance, Interface Biologics, Biotronik, Mercator MedSystems, Spectrawave, Cook Medical, SoundPipe, Ossio, Bolt Medical, CardioMech, Olympus, Spartan Micro, Intact Vascular, Inc, Whiteswell, Vascudyne, Imperative Care, Biotyx Medical, SMT, Innovative Medical Devices, Cardiovascular Solutions, Dexcom, Emboline, Cooper Health, Children’s National, Concept Medical, Filterlex, eLum Technologies, Protembis, Boston Scientific, Polares, MDS, CeloNova, UCSF Foundation, Croivalve, Canon, Terumo, BD Biosciences, Limflow, Renata, Vetex, Recor, Mayo Clinic, CSI, Ohio Health, UPMC, Regencor, Vesper, Ripple Therapeutics, Polyvascular, Invatin, Innovative Cardiovascular Solutions, TruLeaf, Coramaze, ProKidney, 480 Biomedical, Transmural Systems, Intershunt Technologies, Pi-Cardia, Lyra Therapeutics, Sanofi, Phenox, Qool Therapeutics, Chansu Vascular Technologies, Nyra Medical, Surmodics, Microport, Leducq Foundation, OrbusNeich, Cardiac Implants, Rush University, Edwards Lifesciences, Cardionomic, Restore Medical, Medanex, CRL, Lahav, Pulse Biosciences, Jacobs Institute, Nova Vascular, Nephronyx, Maywell, Innovalve, Elucid Bioimaging, Medtronic, Biosensors International Group, ShockWave Medical, Cardiawave, NIH, Occlutech; consulting for Terumo, Recor Medical, Sino Medical, Medtronic, Cook, W.L. Gore, CSI, Surmodics, CeloNova, Edwards Lifesciences, BARD, Xeltis; other services for Xeltis, Medtronic; employment with CVPath Institute. Dr Kokoszka: employment with Cerenovus. Dr Inoa: consulting for Siemens, Viz-AI, Medtronic, Cerenovus, MicroVention, Penumbra; grants from Medtronic; employment with Semmes Murphey Clinic. Dr Humphries: consulting for Cerenovus. Dr Jabbour: consulting for Medtronic. Dr François: consulting for iVascular. Dr Levy: consulting for Guidepoint, GLG Consulting, Clarion, StimMed, Mosaic; other services for Penumbra, Medtronic, MicroVention; ownership/investment interest in Imperative Care, StimMed, Three Rivers Medical, NeXtGen Biologics, Q’Apel, Claret Medical, Rapid Medical. Dr Dashti: consulting for MicroVention, J&J, Cerenovus. Dr Schirmer: consulting for Balt, Medtronic, Stryker, Viz-AI, MicroVention; grants from Route92, MicroVention, Penumbra, Cerenovus, Balt, MIVI, Medtronic; employment with Geisinger; other services for Werfen, Cerenovus, NIH, Stryker, Neurotechnology Investors; ownership interest in Reist. Dr Hussain: consulting for J&J. Dr De Leacy: consulting for J&J, Imperative Care, Stryker; ownership/investment interest in Vastrax, Q’Apel, Spartan Micro, Synchron, Endostream. Dr Puri: consulting for J&J, MicroVention, Merit Medical, Stryker, Medtronic, Balt. Dr Chitale: grants, consulting, and data safety monitoring for Medtronic; grants from J&J. Dr Siddiqui: consulting for Cerebrotech, Boston Scientific, Rapid Medical, Cordis, W.L. Gore, Peijia Medical, Corindus, StimMed, J&J, Viz-AI, Silk Road Medical, Piraeus, Medtronic, Penumbra, Hyperfine Operations, Cerenovus, Endostream, Minnetronix Neuro, Stryker, Canon Medical Systems, Integra LifeSciences, Imperative Care, Apellis, Amnis Therapeutics, Vassol, IRRAS, Cardinal Health 200, Q’Apel, InspireMD, MicroVention, Serenity Medical; grants from Brain Aneurysm Foundation, NIH; other services for Rapid Medical, MicroVention, MIVI, Medical University of South Carolina, Penumbra, Cerenovus, InspireMD, Medtronic; ownership/investment interest in Willow Medtech, Cognition Medical, Whisper Medical, Spinnaker, Sim & Cure, Hyperion, BlinkTBI, Surgical, Inc, Radical Catheter Technologies, Imperative Care, Code Zero Medical, E8, Truvic, Tulavi, Bend IT, Neurolutions, Q’Apel, Endostream, Cerebrotech, Instylla, Collavidence Medical, Sense Diagnostics, Neurotechnology Investors, Peijia Medical, Synchron, Viseon, Borvo, E8, Galaxy Therapeutics, Piraeus, Adona Medical, NeuroRadial Technologies, NextGen Biologics, Viz-AI, Three Rivers Medical, StimMed, Serenity Medical, Cerevatech, Cvaid, Silk Road Medical, PerFlow Medical, InspireMD, VICIS, QAS.ai, SongBird, Launch NY, Neurovascular Diagnostics, Vastrax, Cognition Medical, Integra LifeSciences, Medtronic; employment with University at Buffalo Neurosurgery, Jacobs Institute; patent holder. The other authors report no conflicts.

Background: Stroke remains a major health concern globally, with oral anticoagulants widely prescribed for stroke prevention. The efficacy and safety of mechanical thrombectomy (MT) in anticoagulated patients with distal medium vessel occlusions (DMVO) are not well understood., Methods: This retrospective analysis involved 1282 acute ischemic stroke (AIS) patients who underwent MT in 37 centers across North America, Asia, and Europe from September 2017 to July 2023. Data on demographics, clinical presentation, treatment specifics, and outcomes were collected. The primary outcomes were functional outcomes at 90 days post-MT, measured by modified Rankin Scale (mRS) scores. Secondary outcomes included reperfusion rates, mortality, and hemorrhagic complications., Results: Of the patients, 223 (34%) were on anticoagulation therapy. Anticoagulated patients were older (median age 78 vs 74 years; p  < 0.001) and had a higher prevalence of atrial fibrillation (77% vs 26%; p  < 0.001). Their baseline National Institutes of Health Stroke Scale (NIHSS) scores were also higher (median 12 vs 9; p  = 0.002). Before propensity score matching (PSM), anticoagulated patients had similar rates of favorable 90-day outcomes (mRS 0-1: 30% vs 37%, p  = 0.1; mRS 0-2: 47% vs 50%, p  = 0.41) but higher mortality (26% vs 17%, p  = 0.008). After PSM, there were no significant differences in outcomes between the two groups., Conclusion: Anticoagulated patients undergoing MT for AIS due to DMVO did not show significant differences in 90-day mRS outcomes, reperfusion, or hemorrhage compared to non-anticoagulated patients after adjustment for covariates., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Regenhardt serves on a DSMB for a trial sponsored by Rapid Medical, serves as site PI for studies sponsored by Penumbra and Microvention, and receives stroke research grant funding from the National Institutes of Health, Society of Vascular and Interventional Neurology, and Heitman Stroke Foundation.Dr. Guenego reports consultancy for Rapid Medical and Phenox, not directly related to the present work.Dr. Clarençon reports conflicts of interest with Medtronic, Balt Extrusion (consultant), ClinSearch (core lab), Penumbra, Stryker (payment for reading) and Artedrone (Board); all not directly related to the present work.Dr. Henninger received support from W81XWH-19-PRARP-RPA form the CDMRP/DoD, NS131756 and U24NS113844 from the NINDS, and NR020231 from the NINR and received compensation from Myrobalan, Inc. and General Dynamics during the conduct of this study unrelated to this work.Dr. Liebeskind is consultant as Imaging Core Lab to Cerenovus, Genentech, Medtronic, Stryker, Rapid Medical.Dr. Yeo reports Advisory work for AstraZeneca, Substantial support from NMRC Singapore and is a medical advisor for See-mode, Cortiro and Sunbird Bio, with equity in Ceroflo. All unrelated to the present work.Dr. Griessenauer reports a proctoring agreement with Medtronic and research funding by Penumbra.Dr. Marnat reports conflicts of interest with Microvention Europe, Stryker Neurovascular, Balt (consulting), Medtronic, Johnson & Johnson and Phenox (paid lectures), all not directly related to the present work.Dr. Puri is a consultant for Medtronic Neurovascular, Stryker NeurovascularBalt, Q’Apel Medical, Cerenovus, Microvention, Imperative Care, Agile, Merit, CereVasc and Arsenal Medical, he received research grants from NIH, Microvention, Cerenovus, Medtronic Neurovascular and Stryker Neurovascular, and holds stocks in InNeuroCo, Agile, Perfuze, Galaxy and NTI.Dr. Tjoumakaris is a consultant for Medtronic and Microvention (funds paid to institution, not personally).Dr. Jabbour is a consultant for Medtronic, Microvention and Cerus.

Background: Optimal anesthetic strategy for the endovascular treatment of stroke is still under debate. Despite scarce data concerning anesthetic management for medium and distal vessel occlusions (MeVOs) some centers empirically support a general anesthesia (GA) strategy in these patients., Methods: We conducted an international retrospective study of MeVO cases. A propensity score matching algorithm was used to mitigate potential differences across patients undergoing GA and conscious sedation (CS). Comparisons in clinical and safety outcomes were performed between the two study groups GA and CS. The favourable outcome was defined as a modified Rankin Scale (mRS) 0-2 at 90 days. Safety outcomes were 90-days mortality and symptomatic intracranial hemorrhage (sICH). Predictors of a favourable outcome and sICH were evaluated with backward logistic regression., Results: After propensity score matching 668 patients were included in the CS and 264 patients in the GA group. In the matched cohort, either strategy CS or GA resulted in similar rates of good functional outcomes (50.1% vs. 48.4%), and successful recanalization (89.4% vs. 90.2%). The GA group had higher rates of 90-day mortality (22.6% vs. 16.5%, p < 0.041) and sICH (4.2% vs. 0.9%, p = 0.001) compared to the CS group. Backward logistic regression did not identify GA vs CS as a predictor of good functional outcome (OR for GA vs CS = 0.95 (0.67-1.35)), but GA remained a significant predictor of sICH (OR = 5.32, 95% CI 1.92-14.72)., Conclusion: Anaesthetic strategy in MeVOs does not influence favorable outcomes or final successful recanalization rates, however, GA may be associated with an increased risk of sICH and mortality., Competing Interests: Conflict of interest R.W. Regenhardt serves on a DSMB for a trial sponsored by Rapid Medical, serves as site PI for studies sponsored by Penumbra and Microvention, and receives stroke research grant funding from the National Institutes of Health, Society of Vascular and Interventional Neurology, and Heitman Stroke Foundation. A. Guenego reports consultancy for Rapid Medical and Phenox, not directly related to the present work. F. Clarençon reports conflicts of interest with Medtronic, Balt Extrusion (consultant), ClinSearch (core lab), Penumbra, Stryker (payment for reading) and Artedrone (Board) ; all not directly related to the present work. N. Henninger received support from NINDS NS131756, during the conduct of the study. D.S. Liebeskind is consultant as Imaging Core Lab to Cerenovus, Genentech, Medtronic, Stryker, Rapid Medical. T.N. Nguyen reports advisory board with Idorsia. L.L.L. Yeo reports Advisory work for AstraZeneca, Substantial support from NMRC Singapore and is a medical advisor for See-mode, Cortiro and Sunbird Bio, with equity in Ceroflo. All unrelated to the present work. C.J. Griessenauer reports a proctoring agreement with Medtronic and research funding by Penumbra. G. Marnat reports conflicts of interest with Microvention Europe, Stryker Neurovascular, Balt (consulting), Medtronic, Johnson & Johnson and Phenox (paid lectures), all not directly related to the present work. I. Sibon reports conflict of interest with Medtronic, Sanofi, Bayer, Boehringer-Ingelheim, Novartis, Novo-nordisk, BMS-Pfizer (Board and paid lectures), all not directly related to the present work. V. Yedavalli is a consultant for RAPID (Ischemaview, Menlo Park, CA). A. Vagal is a consultant for Viz AI. She is also PI of the Imaging core lab for the ENDOLOW study funded by Cerenovus (monies go to the institution). A. Gopinathan reports conflicts of interest with Microvention, Stryker Neurovascular, Medtronic, BD, and Penumbra (paid lectures, workshops, and proctoring), all not directly related to the present work. R. A. Radu, V. Costalat, M. Romoli, B. Musmar, J.E. Siegler, S. Ghozy, J. Khalife, H. Salim, H. Shaikh, N. Adeeb, H.H. Cuellar-Saenz, A.J. Thomas, R. Kadirvel, M. Abdalkader, P. Klein, J.J. Heit, J.D. Bernstock, A.B. Patel, J.D. Rabinov, C.J. Stapleton, N.M. Cancelliere, T.R. Marotta, V. Mendes Pereira, K. El Naamani, A. Amllay, S.I. Tjoumakaris, P. Jabbour, L. Meyer, J. Fiehler, T.D. Faizy, H. Guerreiro, A. Dusart, F. Bellante, G. Forestier, A. Rouchaud, C. Mounayer, A.L. Kühn, A.S. Puri, C. Dyzmann, P.T. Kan, M. Colasurdo, J. Berge, X. Barreau, S. Nedelcu, T. Ota, S. Dofuku, B.Y. Tan, J.C. Martinez-Gutierrez, S. Salazar-Marioni, S. Sheth, L. Renieri, C. Capirossi, A. Mowla, L.M. Chervak, P. Khandelwal, A. Biswas, M. Elhorany, K. Premat, I. Valente, A. Pedicelli, A.M. Alexandre, J.P. Filipe, R. Varela, M. Quintero-Consuegra, N.R. Gonzalez, M.A. YMD, J. Jesser, C. Weyland, A. ter Schiphorst, P. Harker, Y. Aziz, B. Gory, C. Paul Stracke, C. Hecker, M. Killer-Oberpfalzer, C.-Y. Hsieh, I. Tancredi, R. Fahed, B. Lubicz, M.A. Essibayi, A. Baker, D. Altschul, L. Scarcia, E. Kalsoum and A.A. Dmytriw for the MAD-MT Consortium declare that they have no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Application of machine learning (ML) algorithms has shown promising results in estimating ischemic core volumes using non-contrast CT (NCCT)., Objective: To assess the performance of the e-Stroke Suite software (Brainomix) in assessing ischemic core volumes on NCCT compared with CT perfusion (CTP) in patients with acute ischemic stroke., Methods: In this retrospective multicenter study, patients with anterior circulation large vessel occlusions who underwent pretreatment NCCT and CTP, successful reperfusion (modified Thrombolysis in Cerbral Infarction ≥2b), and post-treatment MRI, were included from three stroke centers. Automated calculation of ischemic core volumes was obtained on NCCT scans using ML algorithm deployed by e-Stroke Suite and from CTP using Olea software (Olea Medical). Comparative analysis was performed between estimated core volumes on NCCT and CTP and against MRI calculated final infarct volume (FIV)., Results: A total of 111 patients were included. Estimated ischemic core volumes (mean±SD, mL) were 20.4±19.0 on NCCT and 19.9±18.6 on CTP, not significantly different (P=0.82). There was moderate (r=0.40) and significant (P<0.001) correlation between estimated core on NCCT and CTP. The mean difference between FIV and estimated core volume on NCCT and CTP was 29.9±34.6 mL and 29.6±35.0 mL, respectively (P=0.94). Correlations between FIV and estimated core volume were similar for NCCT (r=0.30, P=0.001) and CTP (r=0.36, P<0.001)., Conclusions: Results show that ML-based estimated ischemic core volumes on NCCT are comparable to those obtained from concurrent CTP in magnitude and in degree of correlation with MR-assessed FIV., Competing Interests: Competing interests: GPC: Stryker Neurovascular, MicroVention, Medtronic, Rapid Medical; JLS: Medtronic Cerenovus, Boehringer Ingelheim, NeuroVasc, Rapid Medical; DSL: Cerenovus, Genentech, Medtronic, Stryker, Olea; KN: Olea Medical, Brainomix; Achala Vagal: Viz AI., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Despite successful reperfusion after thrombectomy for large vessel occlusion (LVO) stroke, up to half of patients are dependent or dead at 3-month follow-up.The aim of the current study is to demonstrate safety and efficacy of administering adjunct intra-arterial (IA) tenecteplase in anterior circulation LVO patients who have achieved successful reperfusion defined as eTICI 2b50 to 3., Methods: ANGEL-TNK is a multicentre, open-label, assessor-blinded endpoint, prospective randomised, controlled trial that will enrol up to 256 patients. Patients who meet inclusion criteria with anterior circulation LVO stroke and successful reperfusion will be randomised to receive IA tenecteplase or best medical management at 1:1 ratio., Results: The primary endpoint is a 90-day excellent outcome defined as modified Rankin Scale (mRS) 0-1. The primary safety endpoint is symptomatic intracranial haemorrhage within 48 hours from randomisation. Secondary endpoints include 90-day ordinal mRS, mRS 0-2, mRS 0-3, all-cause mortality and any intracranial haemorrhage., Conclusion: In patients with anterior circulation LVO stroke, the ANGEL-TNK trial will inform whether adjunct IA tenecteplase administered after successful thrombectomy reperfusion improves patient outcomes., Trial Registration Number: NCT05624190., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Intracranial atherosclerotic disease (ICAD) is a major cause of stroke globally, with mechanisms presumed to be shared with atherosclerosis in other vascular regions. Due to the scarcity of relevant animal models, testing biological hypotheses specific to ICAD is challenging. We developed a workflow to create patient-specific models of the middle cerebral artery (MCA) from neuroimaging studies, such as CT angiography. These models, which can be endothelialized with human endothelial cells and subjected to flow forces, provide a reproducible ICAD model. Using imaging from the SAMMPRIS clinical trial, we validated this novel model. Computational fluid dynamics flow velocities correlated strongly with particle-derived flow, regardless of stenosis degree. Post-stenotic flow disruption varied with stenosis severity. Single-cell RNA-seq identified flow-dependent endothelial gene expression and specific endothelial subclusters in diseased MCA segments, including upregulated genes linked to atherosclerosis. Confocal microscopy revealed flow-dependent changes in endothelial cell proliferation and morphology in vessel segments related to stenosis. This platform, rooted in the specific anatomy of cerebral circulation, enables detailed modeling of ICAD lesions and pathways. Given the high stroke risk associated with ICAD and the lack of effective treatments, these experimental models are crucial for developing new ICAD-related stroke therapies., Competing Interests: Declarations Conflict of Interest The authors declare no competing interests., (© 2024. The Author(s).)

Background and Purpose: Intraarterial thrombolysis as an adjunct to mechanical thrombectomy is increasingly being considered to enhance reperfusion in acute ischemic stroke patients. Intraarterial thrombolysis may increase the risk of post-thrombectomy intracerebral hemorrhage (ICH) in certain patient subgroups., Methods: We analyzed acute ischemic stroke patients treated with mechanical thrombectomy in a multicenter registry. The occurrence of any (asymptomatic and symptomatic) post-thrombectomy ICH was ascertained using standard definition requiring serial neurological examinations and computed tomographic scans acquired within 48 hours of the thrombectomy. We determined the risk of ICH in subgroups defined by clinical characteristics and the use of intravenous (IV) thrombolysis., Results: A total of 146 (7.5%) patients received intraarterial thrombolysis among 1953 acute ischemic stroke patients who underwent mechanical thrombectomy. The proportion of patients who developed any ICH was 26 (17.8%) and 510 (28.2%) among patients who were and were not treated with intraarterial thrombolysis, respectively (p = .006). The proportion of patients who developed symptomatic ICH was 4 (2.7%) and 30 (1.7%) among patients who were and were not treated with intraarterial thrombolysis, respectively (p = .34). Among patients who received IV thrombolysis (n = 1042), the proportion of patients who developed any ICH was 9 (16.7%) and 294 (30.7%) among patients who were and were not treated with intraarterial thrombolysis, respectively (p = .028). The risk was not different in strata defined by age, gender, location of occlusion, preprocedure National Institutes of Health Stroke Scale score, time interval between symptom onset and thrombectomy, Alberta Stroke Program Early CT Score, systolic blood pressure, and serum glucose concentrations., Conclusions: In patients undergoing mechanical thrombectomy, the risk of any ICH and symptomatic ICH was not increased with intraarterial thrombolysis, including in those who had already received IV thrombolytics., (© 2024 American Society of Neuroimaging.)

Objective: Ischemic stroke is a significant cause of disability and death worldwide. Randomized clinical trials (RCTs) are important in changing guidelines and treatment strategies. This study aimed to analyze the progress of RCTs in ischemic stroke and to guide future research directions., Methods: Ischemic stroke-related RCT articles were identified in six high-impact medical journals using the Web of Science Core Collection database. Google Scholar was used to check whether relevant articles were included in the guidelines. The characteristics of these articles were analyzed and future research hotspots were predicted., Results: 389 relevant articles were included in the analysis. The number of articles increased rapidly from 1972 to 2022, from 5 (1.3%; 1972-1982) to 208 (53.5%; 2013-2022) articles. 338 (86.9%) articles were included in relevant guidelines. According to corresponding author location, Europe was the source of the highest number of publications (183; 47.0%), followed by the Americas (152; 39.1%) and the Western Pacific (54; 13.9%). The number of publications steadily increased over time in the USA, England, Canada, Australia, Germany, and France, and surged in China and Spain, especially in the last 5 years. In recent years, endovascular therapy has accounted for the majority of ischemic stroke-related RCT articles., Conclusions: Numerous RCTs related to ischemic stroke have been conducted in recent decades, and both the number of articles and their contribution to guideline updates are increasing. Also, a shift in research topics was observed. However, great regional imbalances in this research exist, calling for more research to be conducted in specific regions to promote the generalizability of trial conclusions., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Introduction: Intracranial artery calcification (ICAC) is a common finding on computed tomography (CT) in patients presenting with large vessel occlusion acute ischemic stroke (LVO-AIS) and could serve as a useful biomarker of intracranial atherosclerosis and altered intracranial vessel pliability in patients undergoing endovascular thrombectomy (EVT)., Methods: This was a retrospective cohort study analyzing consecutive patients undergoing CT head prior to EVT between 2016 and 2020. Extent of ICAC proximal to the target vessel was scored using a validated grading scale examining thickness and circumferential extent of calcifications. The relationship between 3 levels of ICAC burden and procedural, clinical, and safety outcomes was analyzed., Results: Among 86 patients meeting inclusion criteria, ICAC of any degree was present in 72.1 %. Median ICAC score was 3 [IQR 0-4]. There was a U-shaped association between ICAC score and successful reperfusion: 90.9 %, 65.7 %, and 94.4 % in the low, intermediate, and high ICAC score groups, respectively (p = 0.008). Use of rescue intervention, most often angioplasty and stenting, was greatest in the high ICAC score group: 3.0 % vs. 5.7 % vs. 22.2 % (p = 0.05). Functional independence at 90 days did not differ significantly among groups (41.7 % vs. 31.0 % vs. 15.4 %, p = 0.26), nor did rates of symptomatic intracranial hemorrhage (15.2 % vs. 14.3 % vs. 16.7 %, p = 0.97)., Conclusions: ICAC is seen on CT in nearly three-quarters of patients with LVO-AIS. Extent of ICAC has a U-shaped association with successful reperfusion, in part due to more frequent use of rescue interventions in patients with extensive ICAC., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: David S. Liebeskind reports a relationship with Cerenovus that includes: consulting or advisory. David S. Liebeskind reports a relationship with Genentech that includes: consulting or advisory. David S. Liebeskind reports a relationship with Medtronic that includes: consulting or advisory. David S. Liebeskind reports a relationship with Stryker that includes: consulting or advisory. David S. Liebeskind reports a relationship with Rapid Medical that includes: consulting or advisory. Geoffrey P. Colby reports a relationship with Stryker Neurovascular that includes: consulting or advisory. Geoffrey P. Colby reports a relationship with Medtronic that includes: consulting or advisory. Geoffrey P. Colby reports a relationship with MicroVention Inc that includes: consulting or advisory. Geoffrey P. Colby reports a relationship with Cerenovus that includes: consulting or advisory. Geoffrey P. Colby reports a relationship with Rapid Medical that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Despite the proven effectiveness of endovascular therapy (EVT) in acute ischemic strokes (AIS) involving anterior circulation large vessel occlusions, isolated posterior cerebral artery (PCA) occlusions (iPCAo) remain underexplored in clinical trials. This study investigates the comparative effectiveness and safety of EVT against medical management (MM) in patients with iPCAo., Methods: This multinational, multicenter propensity score-weighted study analyzed data from the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry, involving 37 centers across North America, Asia, and Europe. We included iPCAo patients treated with either EVT or MM. The primary outcome was the modified Rankin Scale (mRS) at 90 days, with secondary outcomes including functional independence, mortality, and safety profiles such as hemorrhagic complications., Results: A total of 177 patients were analyzed (88 MM and 89 EVT). EVT showed a statistically significant improvement in 90-day mRS scores (OR = 0.55, 95% CI = 0.30-1.00, p  = 0.048), functional independence (OR = 2.52, 95% CI = 1.02-6.20, p  = 0.045), and a reduction in 90-day mortality (OR = 0.12, 95% CI = 0.03-0.54, p  = 0.006) compared to MM. Hemorrhagic complications were not significantly different between the groups., Conclusion: EVT for iPCAo is associated with better neurological outcomes and lower mortality compared to MM, without an increased risk of hemorrhagic complications. Nevertheless, these results should be interpreted with caution due to the study's observational design. The findings are hypothesis-generating and highlight the need for future randomized controlled trials to confirm these observations and establish definitive treatment guidelines for this patient population., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Regenhardt serves on a DSMB for a trial sponsored by Rapid Medical, serves as site PI for studies sponsored by Penumbra and Microvention, and receives stroke research grant funding from the National Institutes of Health, Society of Vascular and Interventional Neurology, and Heitman Stroke Foundation. Dr. Guenego reports consultancy for Rapid Medical and Phenox, not directly related to the present work. Dr. Clarençon reports conflicts of interest with Medtronic, Balt Extrusion (consultant), ClinSearch (core lab), Penumbra, Stryker (payment for reading), and Artedrone (Board); all not directly related to the present work. Dr. Henninger received support from W81XWH-19-PRARP-RPA form the CDMRP/DoD, NS131756 and U24NS113844 from the NINDS, and NR020231 from the NINR and received compensation from Myrobalan, Inc. and General Dynamics during the conduct of this study unrelated to this work. Dr. Liebeskind is consultant as Imaging Core Lab to Cerenovus, Genentech, Medtronic, Stryker, Rapid Medical. Dr. Yeo reports Advisory work for AstraZeneca, Substantial support from NMRC Singapore and is a medical advisor for See-mode, Cortiro, and Sunbird Bio, with equity in Ceroflo. All unrelated to the present work. Dr. Griessenauer reports a proctoring agreement with Medtronic and research funding by Penumbra. Dr. Marnat reports conflicts of interest with Microvention Europe, Stryker Neurovascular, Balt (consulting), Medtronic, Johnson & Johnson, and Phenox (paid lectures), all not directly related to the present work. Dr. Puri is a consultant for Medtronic Neurovascular, Stryker NeurovascularBalt, Q’Apel Medical, Cerenovus, Microvention, Imperative Care, Agile, Merit, CereVasc, and Arsenal Medical, he received research grants from NIH, Microvention, Cerenovus, Medtronic Neurovascular, and Stryker Neurovascular, and holds stocks in InNeuroCo, Agile, Perfuze, Galaxy, and NTI. Dr. Tjoumakaris is a consultant for Medtronic and Microvention (funds paid to institution, not personally). Dr. Jabbour is a consultant for Medtronic, Microvention, and Cerus.

Background: The Tigertriever device offers a unique feature that enables gradual control of the radial expansion. We sought to evaluate the safety and efficacy of the Tigertriever device in patients with large vessel occlusion (LVO) and underlying intracranial atherosclerotic disease (ICAD). The patients were part of the TIGER trial., Methods: The presence of underlying ICAD was determined by a core imaging laboratory using CT angiography and digital subtraction angiography. The primary outcomes included successful reperfusion, puncture to reperfusion time, and complications associated with the use of the Tigertriever device. Patients underwent mechanical thrombectomy with the Tigertriever device for up to three passes, and alternative devices were employed for subsequent passes., Results: A total of 160 patients were enrolled in the TIGER trial, and 32 patients had ICAD. Among the patients with ICAD, 78% achieved successful reperfusion within three passes of the Tigertriever device, without requiring rescue therapy. Additionally, a first pass effect was observed in 46.8%. The median time from puncture to reperfusion was 22 minutes. There were no device-related complications. The National Institutes of Health Stroke Scale (NIHSS) score at 24 hours was significantly reduced, from an average of 17 at baseline to 8. At the 3 month follow-up, 50% of patients achieved a modified Rankin Scale score of ≤2., Conclusion: Endovascular therapy (EVT) with the Tigertriever device for LVO in patients with underlying ICAD is effective and safe. When compared with historical data from other devices employed in similar cases, we observed a high rate of successful reperfusion, along with a shorter puncture to reperfusion time., Competing Interests: Competing interests: Dr Samaniego is a consultant for Rapid Medical., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Previous randomized clinical trials did not demonstrate the superiority of endovascular stenting over aggressive medical management for patients with symptomatic intracranial atherosclerotic stenosis (sICAS). However, balloon angioplasty has not been investigated in a randomized clinical trial., Objective: To determine whether balloon angioplasty plus aggressive medical management is superior to aggressive medical management alone for patients with sICAS., Design, Setting, and Participants: A randomized, open-label, blinded end point clinical trial at 31 centers across China. Eligible patients aged 35 to 80 years with sICAS defined as recent transient ischemic attack (<90 days) or ischemic stroke (14-90 days) before enrollment attributed to a 70% to 99% atherosclerotic stenosis of a major intracranial artery receiving treatment with at least 1 antithrombotic drug and/or standard risk factor management were recruited between November 8, 2018, and April 2, 2022 (final follow-up: April 3, 2023)., Interventions: Submaximal balloon angioplasty plus aggressive medical management (n = 249) or aggressive medical management alone (n = 252). Aggressive medical management included dual antiplatelet therapy for the first 90 days and risk factor control., Main Outcomes and Measures: The primary outcome was a composite of any stroke or death within 30 days after enrollment or after balloon angioplasty of the qualifying lesion or any ischemic stroke in the qualifying artery territory or revascularization of the qualifying artery after 30 days through 12 months after enrollment., Results: Among 512 randomized patients, 501 were confirmed eligible (mean age, 58.0 years; 158 [31.5%] women) and completed the trial. The incidence of the primary outcome was lower in the balloon angioplasty group than the medical management group (4.4% vs 13.5%; hazard ratio, 0.32 [95% CI, 0.16-0.63]; P < .001). The respective rates of any stroke or all-cause death within 30 days were 3.2% and 1.6%. Beyond 30 days through 1 year after enrollment, the rates of any ischemic stroke in the qualifying artery territory were 0.4% and 7.5%, respectively, and revascularization of the qualifying artery occurred in 1.2% and 8.3%, respectively. The rate of symptomatic intracranial hemorrhage in the balloon angioplasty and medical management groups was 1.2% and 0.4%, respectively. In the balloon angioplasty group, procedural complications occurred in 17.4% of patients and arterial dissection occurred in 14.5% of patients., Conclusions and Relevance: In patients with sICAS, balloon angioplasty plus aggressive medical management, compared with aggressive medical management alone, statistically significantly lowered the risk of a composite outcome of any stroke or death within 30 days or an ischemic stroke or revascularization of the qualifying artery after 30 days through 12 months. The findings suggest that balloon angioplasty plus aggressive medical management may be an effective treatment for sICAS, although the risk of stroke or death within 30 days of balloon angioplasty should be considered in clinical practice., Trial Registration: ClinicalTrials.gov Identifier: NCT03703635.

Background Clinical outcome prediction based on acute-phase ischemic stroke data is valuable for planning health care resources, designing clinical trials, and setting patient expectations. Existing methods require individualized features and often involve manually engineered, time-consuming postprocessing activities. Purpose To predict the 90-day modified Rankin Scale (mRS) score with a deep learning (DL) model fusing noncontrast-enhanced CT (NCCT) and clinical information from the acute phase of stroke. Materials and Methods This retrospective study included data from six patient datasets from four multicenter trials and two registries. The DL-based imaging and clinical model was trained by using NCCT data obtained 1-7 days after baseline imaging and clinical data (age; sex; baseline and 24-hour National Institutes of Health Stroke Scale scores; and history of hypertension, diabetes, and atrial fibrillation). This model was compared with models based on either NCCT or clinical information alone. Model-specific mRS score prediction accuracy, mRS score accuracy within 1 point of the actual mRS score, mean absolute error (MAE), and performance in identifying unfavorable outcomes (mRS score, >2) were evaluated. Results A total of 1335 patients (median age, 71 years; IQR, 60-80 years; 674 female patients) were included for model development and testing through sixfold cross validation, with distributions of 979, 133, and 223 patients across training, validation, and test sets in each of the six cross-validation folds, respectively. The fused model achieved an MAE of 0.94 (95% CI: 0.89, 0.98) for predicting the specific mRS score, outperforming the imaging-only (MAE, 1.10; 95% CI: 1.05, 1.16; P < .001) and the clinical information-only (MAE, 1.00; 95% CI: 0.94, 1.05; P = .04) models. The fused model achieved an area under the receiver operating characteristic curve (AUC) of 0.91 (95% CI: 0.89, 0.92) for predicting unfavorable outcomes, outperforming the clinical information-only model (AUC, 0.88; 95% CI: 0.87, 0.90; P < .001) and the imaging-only model (AUC, 0.85; 95% CI: 0.84, 0.87; P < .001). Conclusion A fused DL-based NCCT and clinical model outperformed an imaging-only model and a clinical-information-only model in predicting 90-day mRS scores. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Lee in this issue.

Background: Medium vessel occlusion (MeVO) strokes, particularly affecting the M2 segment of the middle cerebral artery, represent a critical proportion of acute ischemic strokes, posing significant challenges in management and outcome prediction. The efficacy of mechanical thrombectomy (MT) in MeVO stroke may warrant reliable predictors of functional outcomes. This study aimed to investigate the prognostic value of follow-up infarct volume (FIV) for predicting 90-day functional outcomes in MeVO stroke patients undergoing MT., Methods: This multicenter, retrospective cohort study analyzed data from the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry, covering patients with acute ischemic stroke due to M2 segment occlusion treated with MT. We examined the relationship between 90-day functional outcomes, measured by the modified Rankin Scale (mRS), and follow-up infarct volume (FIV), assessed through CT or MRI within 12-36 h post-MT., Results: Among 130 participants, specific FIV thresholds were identified with high specificity and sensitivity for predicting outcomes. A FIV ⩽5 ml was highly specific for predicting favorable and excellent outcomes. The optimal cut-off for both prognostications was identified at ⩽15 ml by the Youden Index, with significant reductions in the likelihood of favorable outcomes observed above a 40 ml threshold. Receiver Operator Curve (ROC) analyses confirmed FIV as a superior predictor of functional outcomes compared to traditional recanalization scores, such as final modified thrombolysis in cerebral infarction score (mTICI). Multivariable analysis further highlighted the inverse relationship between FIV and positive functional outcomes., Conclusions: FIV within 36 h post-MT serves as a potent predictor of 90-day functional outcomes in patients with M2 segment MeVO strokes. Establishing FIV thresholds may aid in the prognostication of stroke outcomes, suggesting a role for FIV in guiding post intervention treatment decisions and informing clinical practice. Future research should focus on validating these findings across diverse patient populations and exploring the integration of FIV measurements with other clinical and imaging markers to enhance outcome prediction accuracy., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Regenhardt serves on a DSMB for a trial sponsored by Rapid Medical, serves as site PI for studies sponsored by Penumbra and Microvention, and receives stroke research grant funding from the National Institutes of Health, Society of Vascular and Interventional Neurology, and Heitman Stroke Foundation.Dr. Guenego reports consultancy for Rapid Medical and Phenox, not directly related to the present work.Dr. Clarençon reports conflicts of interest with Medtronic, Balt Extrusion (consultant), ClinSearch (core lab), Penumbra, Stryker (payment for reading) and Artedrone (Board); all not directly related to the present work.Dr. Henninger received support from W81XWH-19-PRARP-RPA form the CDMRP/DoD, NS131756 and U24NS113844 from the NINDS, and NR020231 from the NINR and received compensation from Myrobalan, Inc. and General Dynamics during the conduct of this study unrelated to this work.Dr. Liebeskind is consultant as Imaging Core Lab to Cerenovus, Genentech, Medtronic, Stryker, Rapid Medical.Dr. Yeo reports Advisory work for AstraZeneca, Substantial support from NMRC Singapore and is a medical advisor for See-mode, Cortiro and Sunbird Bio, with equity in Ceroflo. All unrelated to the present work.Dr. Griessenauer reports a proctoring agreement with Medtronic and research funding by Penumbra.Dr. Marnat reports conflicts of interest with Microvention Europe, Stryker Neurovascular, Balt (consulting), Medtronic, Johnson & Johnson and Phenox (paid lectures), all not directly related to the present work.Dr. Puri is a consultant for Medtronic Neurovascular, Stryker NeurovascularBalt, Q’Apel Medical, Cerenovus, Microvention, Imperative Care, Agile, Merit, CereVasc and Arsenal Medical, he received research grants from NIH, Microvention, Cerenovus, Medtronic Neurovascular and Stryker Neurovascular, and holds stocks in InNeuroCo, Agile, Perfuze, Galaxy and NTI.Dr. Tjoumakaris is a consultant for Medtronic and Microvention (funds paid to institution, not personally).Dr. Jabbour is a consultant for Medtronic, Microvention and Cerus.

Background: While mechanical thrombectomy is considered standard of care for large vessel occlusions, scientific evidence to support treatment for distal and medium vessel occlusions remains scarce., Purpose: To evaluate feasibility, safety, and outcomes in patients with low National Institute of Health Stroke Scale scores undergoing mechanical thrombectomy for treatment of distal medium vessel occlusions., Materials and Methods: Retrospective data review and analysis of prospectively maintained databases at 41 academic centers in North America, Asia, and Europe between January 2017 and January 2022. Characteristics and outcomes were compared between groups with low stroke scale score (≤ 6) versus and higher stroke scale scores (> 6). Propensity score matching using the optimal pair matching method and 1:1 ratio was performed., Results: Data were collected on a total of 1068 patients. After propensity score matching, there were a total of 676 patients included in the final analysis, with 338 patients in each group. High successful reperfusion rates were seen in both groups, 90.2% in ≤ 6 and 88.7% in the > 6 stroke scale groups. The frequency of excellent and good functional outcome was seen more common in low versus higher stroke scale score patients (64.5% and 81.1% versus 39.3% and 58.6%, respectively). The 90-day mortality rate observed in the ≤ 6 stroke scale group was 5.3% versus 13.3% in the > 6 stroke scale group., Conclusion: Mechanical thrombectomy in distal and medium vessel occlusions, specifically in patients with low stroke scale scores is feasible, though it may not necessarily improve outcomes over IVT., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Intracranial atherosclerosis is a leading cause of stroke with a high recurrence rate despite treatment. Numerous factors are proposed to influence stroke recurrence due to intracranial atherosclerosis including lesion eccentricity, plaque characteristics, and computational fluid dynamic metrics, such as wall shear stress. An overlooked variable that intrinsically relates to intracranial atherosclerosis is the location of the arterial segment where the lesion occurs. Variations in cerebral blood flow, arterial anatomy, and flow dynamics are likely drivers of initial lesion development and thus likely to influence stroke recurrence. To date, treatment trials of intracranial atherosclerosis have not considered arterial segment lesion location as an independent variable, failing to account for variations in flow dynamics between each artery. There are limited available data on differences between arterial segments, confined to only post hoc analyses. In this review, we summarize available data on such differences between arterial segments. With the limited arterial segment data available, multiple differences in recurrence of stroke in territory of lesion were identified across trials., Competing Interests: Conflict(s) of Interest/Disclosure(s) Liebeskind: Consultant as Imaging Core Lab to Cerenovus, Genentech, Medtronic, Rapid Medical, Stryker.

Background and Purpose: The management of acute ischemic stroke (AIS) due to distal medium vessel occlusion (DMVO) remains uncertain, particularly in comparing the effectiveness of intravenous thrombolysis (IVT) plus mechanical thrombectomy (MT) versus IVT alone. This study aimed to evaluate the safety and efficacy in DMVO patients treated with either MT-IVT or IVT alone., Methods: This multinational study analyzed data from 37 centers across North America, Asia, and Europe. Patients with AIS due to DMVO were included, with data collected from September 2017 to July 2023. The primary outcome was functional independence, with secondary outcomes including mortality and safety measures such as types of intracerebral hemorrhage., Results: The study involved 1,057 patients before matching, and 640 patients post-matching. Functional outcomes at 90 days showed no significant difference between groups in achieving good functional recovery (modified Rankin Scale 0-1 and 0-2), with adjusted odds ratios (OR) of 1.21 (95% confidence interval [CI] 0.81 to 1.79; P=0.35) and 1.00 (95% CI 0.66 to 1.51; P>0.99), respectively. Mortality rates at 90 days were similar between the two groups (OR 0.75, 95% CI 0.44 to 1.29; P=0.30). The incidence of symptomatic intracerebral hemorrhage was comparable, but any type of intracranial hemorrhage was significantly higher in the MT-IVT group (OR 0.43, 95% CI 0.29 to 0.63; P<0.001)., Conclusion: The results of this study indicate that while MT-IVT and IVT alone show similar functional and mortality outcomes in DMVO patients, MT-IVT presents a higher risk of hemorrhagic complications, thus MT-IVT may not routinely offer additional benefits over IVT alone for all DMVO stroke patients. Further prospective randomized trials are needed to identify patient subgroups most likely to benefit from MT-IVT treatment in DMVO.

Background: The effect of endovascular therapy (EVT) on the outcome of stroke patients with a medium distal vessel occlusion (MDVO) is unclear. We report the results of MDVO patients treated with the 3 mm Trevo stent retriever (SR) and/or the AXS Catalyst 5 distal access catheter., Methods: Data was derived from a prospective, multicenter global registry (ASSIST registry) which enrolled patients treated with operator preferred EVT technique at 71 sites from January 2019 to January 2022. Three techniques were assessed: SR classic, direct aspiration, and a combined approach. Additional inclusion criteria were (a) EVT performed with the 3 mm Trevo SR and/or AXS Catalyst 5 distal access catheter on the first pass and (b) an occlusion of the M2 segment or M3 segment of the middle cerebral artery or the A1, A2 or A3 segment of the anterior cerebral artery. The primary outcome was achieving an expanded Thrombolysis in Cerebral Infarction (eTICI) score of 2c or 3 on the first pass, with the primary technique as adjudicated by core lab. The primary clinical outcome measure was a 90-day modified Rankin Scale (mRS) score of 0-2., Results: A total of 155 patients (10.4% of the ASSIST population) were included. Most patients had an M2 occlusion (93.5%). First pass eTICI reperfusion was achieved in 43.1% of the patients. No modifying effect of the frontline technique was found. The rate of mRS 0-2 (overall 65.0%) did not significantly differ between groups., Conclusion: The data suggests that the Trevo 3 mm SR and/or the AXS Catalyst 5 may be an option to treat medium distal vessel occlusion, but more data is needed to demonstrate safety and efficacy in this patient cohort. Further improvements are needed regarding materials and techniques to improve reperfusion results in this patient cohort in the future., (© 2024. The Author(s).)

Nearly one fifth of patients with venous thromboembolism (VTE) have cancer. When both of these conditions occur, especially in cases of cerebral vein thrombosis (CVT), patient management is often challenging. The aim of this study was to compare the characteristics and event courses in patients affected by CVT with and without cancer. Consecutive patients with CVT from the ACTION-CVT cohort study were included if cancer status was reported. Risk factors as well as the clinical and radiological characteristics of patients were compared. Univariable and multivariable analyses were performed to assess variables associated with cancer. Kaplan-Meier method and log-rank test, logistic regression analysis, and propensity score matching were used to investigate any association between cancer-related CVT and study outcomes (primary outcome at 3-months: recurrent VTE or major hemorrhage; recurrent VTE; major hemorrhage; recanalization status; all-cause-death). Overall, 1,023 patients with CVT were included, of which 6.5% had cancer. Older age (adjusted odds ratio [aOR] 1.28 per decade increase; 95% confidence interval [CI] 1.08-1.52) and absence of headache (aOR 0.47; 95% CI 0.27-0.84) were independently associated with cancer. Patients with cancer had a higher risk of recurrent VTE or major hemorrhage (aOR 3.87; 95% CI 2.09-7.16), all-cause-death (aOR 7.56 95% CI 3.24-17.64), and major hemorrhage (aOR 3.70 95% CI 1.76-7.80). Recanalization rates, partial or complete, was not significantly different. CVT patients with cancer were more likely to be older, have no referred headache, and have worse outcomes compared to CVT patients without cancer., (© 2024. The Author(s).)

Background The combination of intravenous thrombolysis (IVT) with mechanical thrombectomy (MT) may have clinical benefits for patients with medium vessel occlusion. Purpose To examine whether MT combined with IVT is associated with different outcomes than MT alone in patients with acute ischemic stroke (AIS) and medium vessel occlusion. Materials and Methods This retrospective study included consecutive adult patients with AIS and medium vessel occlusion treated with MT or MT with IVT at 37 academic centers in North America, Asia, and Europe. Data were collected from September 2017 to July 2021. Propensity score matching was performed to reduce confounding. Univariable and multivariable logistic regression analyses were performed to test the association between the addition of IVT treatment and different functional and safety outcomes. Results After propensity score matching, 670 patients (median age, 75 years [IQR, 64-82 years]; 356 female) were included in the analysis; 335 underwent MT alone and 335 underwent MT with IVT. Median onset to puncture (350 vs 210 minutes, P < .001) and onset to recanalization (397 vs 273 minutes, P < .001) times were higher in the MT group than the MT with IVT group, respectively. In the univariable regression analysis, the addition of IVT was associated with higher odds of a modified Rankin Scale (mRS) score 0-2 (odds ratio [OR], 1.44; 95% CI: 1.06, 1.96; P = .019); however, this association was not observed in the multivariable analysis (OR, 1.37; 95% CI: 0.99, 1.89; P = .054). In the multivariable analysis, the addition of IVT also showed no evidence of an association with the odds of first-pass effect (OR, 1.27; 95% CI: 0.9, 1.79; P = .17), Thrombolysis in Cerebral Infarction grades 2b-3 (OR, 1.64; 95% CI: 0.99, 2.73; P = .055), mRS scores 0-1 (OR, 1.27; 95% CI: 0.91, 1.76; P = .16), mortality (OR, 0.78; 95% CI: 0.49, 1.24; P = .29), or intracranial hemorrhage (OR, 1.25; 95% CI: 0.88, 1.76; P = .21). Conclusion Adjunctive IVT may not provide benefit to MT in patients with AIS caused by distal and medium vessel occlusion. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Wojak in this issue.

Objective: We aimed to evaluate the association between rescue therapy (RT) and functional outcomes compared to medical management (MM) in patients presenting after failed mechanical thrombectomy (MT)., Methods: This cross-sectional study utilized prospectively collected and maintained data from the Society of Vascular and Interventional Neurology Registry, spanning from 2011 to 2021. The cohort comprised patients with large vessel occlusions (LVOs) with failed MT. The primary outcome was the shift in the degree of disability, as gauged by the modified Rankin Scale (mRS) at 90 days. Additional outcomes included functional independence (90-day mRS score of 0-2), symptomatic intracranial hemorrhage (sICH), and 90-day mortality., Results: Of a total of 7,018 patients, 958 presented failed MT and were included in the analysis. The RT group comprised 407 (42.4%) patients, and the MM group consisted of 551 (57.5%) patients. After adjusting for confounders, the RT group showed a favorable shift in the overall 90-day mRS distribution (adjusted common odds ratio = 1.79, 95% confidence interval [CI] = 1.32-2.45, p < 0.001) and higher rates of functional independence (RT: 28.8% vs MM: 15.7%, adjusted odds ratio [aOR] = 1.93, 95% CI = 1.21-3.07, p = 0.005) compared to the MM group. RT also showed lower rates of sICH (RT: 3.8% vs MM: 9.1%, aOR = 0.52, 95% CI = 0.28-0.97, p = 0.039) and 90-day mortality (RT: 33.4% vs MM: 45.5%, aOR = 0.61, 95% CI = 0.42-0.89, p = 0.009)., Interpretation: Our findings advocate for the utilization of RT as a potential treatment strategy for cases of LVO resistant to first-line MT techniques. Prospective studies are warranted to validate these observations and optimize the endovascular approach for failed MT patients. ANN NEUROL 2024;96:343-355., (© 2024 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Objective: We aimed to assess the impact of time to endovascular thrombectomy (EVT) on clinical outcomes in the DAWN trial, while also exploring the potential effect modification of mode of stroke onset on this relationship., Methods: The association between every 1-h treatment delay with 90-day functional independence (modified Rankin Scale [mRS] score 0-2), symptomatic intracranial hemorrhage, and 90-day mortality was explored in the overall population and in three modes of onset subgroups (wake-up vs. witnessed vs. unwitnessed)., Results: Out of the 205 patients, 98 (47.8%) and 107 (52.2%) presented in the 6 to 12 hours and 12 to 24 hours time window, respectively. Considering all three modes of onset together, there was no statistically significant association between time last seen well to randomization with either functional independence or mortality at 90 days in either the endovascular thrombectomy (mRS 0-2 1-hour delay OR 1.07; 95% CI 0.93-1.24; mRS 6 OR 0.84; 95% CI 0.65-1.03) or medical management (mRS 0-2 1-hour delay OR 0.98; 95% CI 0.80-1.14; mRS 6 1-hour delay OR 0.94; 95% CI 0.79-1.09) groups. Moreover, there was no significant interaction between treatment effect and time (p = 0.439 and p = 0.421 for mRS 0-2 and 6, respectively). However, within the thrombectomy group, the models that tested the association between time last seen well to successful reperfusion (modified Treatment in Cerebral Infarction ≥2b) and 90-day functional independence showed a significant interaction with mode of presentation (p = 0.013). This appeared to be driven by a nominally positive slope for both witnessed and unwitnessed strokes versus a significantly (p = 0.018) negative slope in wake-up patients. There was no association between treatment times and symptomatic intracranial hemorrhage., Interpretation: Mode of onset modifies the effect of time to reperfusion on thrombectomy outcomes, and should be considered when exploring different treatment paradigms in the extended window. ANN NEUROL 2024;96:356-364., (© 2024 American Neurological Association.)

Artificial intelligence (AI) is currently being used as a routine tool for day-to-day activity. Medicine is not an exception to the growing usage of AI in various scientific fields. Vascular and interventional neurology deal with diseases that require early diagnosis and appropriate intervention, which are crucial to saving patients' lives. In these settings, AI can be an extra pair of hands for physicians or in conditions where there is a shortage of clinical experts. In this article, the authors have reviewed the common metrics used in interpreting the performance of models and common algorithms used in this field., Competing Interests: Disclosure A. Mowla: Speakers Bureau/Consultant to Cerenovus, Stryker, Wallaby Medical, RapidAI, BALT USA, LLC. D.S. Liebeskind: Consultant as imaging core lab to Cerenovus, Genentech, Medtronic, Stryker, Rapid Medical. Others have no disclosure., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Acute ischemic stroke (AIS) caused by distal medium vessel occlusions (DMVOs) represents a significant proportion of overall stroke cases. While intravenous thrombolysis (IVT) has been a primary treatment, advancements in endovascular procedures have led to increased use of mechanical thrombectomy (MT) in DMVO stroke patients. However, symptomatic intracerebral hemorrhage (sICH) remains a critical complication of AIS, particularly after undergoing intervention. This study aims to identify factors associated with sICH in DMVO stroke patients undergoing MT., Methods: This retrospective analysis utilized data from the Multicenter Analysis of Distal Medium Vessel Occlusions: Effect of Mechanical Thrombectomy (MAD-MT) registry, involving 37 centers across North America, Asia, and Europe. Middle cerebral artery (MCA) DMVO stroke patients were included. The primary outcome measured was sICH, as defined per the Heidelberg Bleeding Classification. Univariable and multivariable logistic regression were used to identify factors independently associated with sICH., Results: Among 1708 DMVO stroke patients, 148 (8.7%) developed sICH. Factors associated with sICH in DMVO patients treated with MT included older age (adjusted odds ratio (aOR) 1.01, 95% confidence interval (95% CI) 1.00 to 1.03, P=0.048), distal occlusion site (M3, M4) compared with medium occlusions (M2) (aOR 1.71, 95% CI 1.07 to 2.74, P=0.026), prior use of antiplatelet drugs (aOR 2.06, 95% CI 1.41 to 2.99, P<0.001), lower Alberta Stroke Program Early CT Scores (ASPECTS) (aOR 0.75, 95% CI 0.66 to 0.84, P<0.001), higher preoperative blood glucose level (aOR 1.00, 95% CI 1.00 to 1.01, P=0.012), number of passes (aOR 1.27, 95% CI 1.15 to 1.39, P<0.001), and successful recanalization (Thrombolysis In Cerebral Infarction (TICI) 2b-3) (aOR 0.43, 95% CI 0.28 to 0.66, P<0.001)., Conclusion: This study provides novel insight into factors associated with sICH in patients undergoing MT for DMVO, emphasizing the importance of age, distal occlusion site, prior use of antiplatelet drugs, lower ASPECTS, higher preoperative blood glucose level, and procedural factors such as the number of passes and successful recanalization. Pending confirmation, consideration of these factors may improve personalized treatment strategies., Competing Interests: Competing interests: Dr Regenhardt serves on a DSMB for a trial sponsored by Rapid Medical, serves as site PI for studies sponsored by Penumbra and Microvention, and receives stroke research grant funding from the National Institutes of Health, Society of Vascular and Interventional Neurology, and Heitman Stroke Foundation. Dr Guenego reports consultancy for Rapid Medical and Phenox, not directly related to the present work. Dr Clarençon reports conflicts of interest with Medtronic, Balt Extrusion (consultant), ClinSearch (core lab), Penumbra, Stryker (payment for reading) and Artedrone (Board); all not directly related to the present work. Dr Henninger received support from W81XWH-19-PRARP-RPA from the CDMRP/DoD, NS131756 and U24NS113844 from the NINDS, and NR020231 from the NINR and received compensation from Myrobalan, Inc and General Dynamics during the conduct of this study unrelated to this work. Dr Liebeskind is consultant as Imaging Core Lab to Cerenovus, Genentech, Medtronic, Stryker, Rapid Medical. Dr Yeo reports Advisory work for AstraZeneca, substantial support from NMRC Singapore and is a medical advisor for See-mode, Cortiro and Sunbird Bio, with equity in Ceroflo; all unrelated to the present work. Dr Griessenauer reports a proctoring agreement with Medtronic and research funding by Penumbra. Dr Marnat reports conflicts of interest with Microvention Europe, Stryker Neurovascular, Balt (consulting), Medtronic, Johnson & Johnson and Phenox (paid lectures), all not directly related to the present work. Dr Puri is a consultant for Medtronic Neurovascular, Stryker Neurovascular, Balt, Q’Apel Medical, Cerenovus, Microvention, Imperative Care, Agile, Merit, CereVasc and Arsenal Medical, he received research grants from NIH, Microvention, Cerenovus, Medtronic Neurovascular and Stryker Neurovascular, and holds stocks in InNeuroCo, Agile, Perfuze, Galaxy and NTI. Dr Tjoumakaris is a consultant for Medtronic and Microvention (funds paid to institution, not personally). Dr Jabbour is a consultant for Medtronic, Microvention and Cerus. HS and VY are guarantors of the study., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The efficacy of endovascular treatment (EVT) in acute ischaemic stroke due to distal medium vessel occlusion (DMVO) remains uncertain. Our study aimed to evaluate the safety and efficacy of EVT compared with the best medical management (BMM) in DMVO., Methods: In this prospectively collected, retrospectively reviewed, multicentre cohort study, we analysed data from the Multicentre Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy registry. Patients with acute ischaemic stroke due to DMVO in the M2, M3 and M4 segments who underwent EVT or received BMM were included. Primary outcome measures comprised 10 co-primary endpoints, including functional independence (mRS 0-2), excellent outcome (mRS 0-1), mortality (mRS 6) and haemorrhagic complications. Propensity score matching was employed to balance the cohorts., Results: Among 2125 patients included in the primary analysis, 1713 received EVT and 412 received BMM. After propensity score matching, each group comprised 391 patients. At 90 days, no significant difference was observed in achieving mRS 0-2 between EVT and BMM (adjusted OR 1.00, 95% CI 0.67 to 1.50, p>0.99). However, EVT was associated with higher rates of symptomatic intracerebral haemorrhage (8.4% vs 3.0%, adjusted OR 3.56, 95% CI 1.69 to 7.48, p<0.001) and any intracranial haemorrhage (37% vs 19%, adjusted OR 2.61, 95% CI 1.81 to 3.78, p<0.001). Mortality rates were similar between groups (13% in both, adjusted OR 1.48, 95% CI 0.87 to 2.51, p=0.15)., Conclusion: Our findings suggest that while EVT does not significantly improve functional outcomes compared with BMM in DMVO, it is associated with higher risks of haemorrhagic complications. These results support a cautious approach to the use of EVT in DMVO and highlight the need for further prospective randomised trials to refine treatment strategies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The extent of ischemic injury in acute stroke is assessed in clinical practice using the Acute Stroke Prognosis Early CT Score (ASPECTS) rating system. However, current ASPECTS semi-quantitative topographic scales assess only the middle cerebral artery (MCA) (original ASPECTS) and posterior cerebral (PC-ASPECTS) territories. For treatment decision-making in patients with anterior cerebral artery (ACA) occlusions and internal carotid artery (ICA) occlusions with large ischemic cores, measures of all hemispheric regions are desirable., Methods: In this cohort study, anatomic rating systems were developed for the anterior cerebral (AC-ASPECTS, 3 points) and anterior choroidal artery (ACh-ASPECTS, 1 point) territories. In addition, a total supratentorial hemisphere (H-ASPECTS, 16 points) score was calculated as the sum of the MCA ASPECTS (10 regions), supratentorial PC-ASPECTS (2 regions), AC-ASPECTS (3 regions), and ACh-ASPECTS (1 region). Three raters applied these scales to initial and 24 h CT and MR images in consecutive patients with ischemic stroke (IS) due to ICA, M1-MCA, and ACA occlusions., Results: Imaging ratings were obtained for 96 scans in 50 consecutive patients with age 74.8 (±14.0), 60% female, NIHSS 15.5 (9.25-20), and occlusion locations ICA 34%; M1-MCA 58%; and ACA 8%. Treatments included endovascular thrombectomy +/- thrombolysis in 72%, thrombolysis alone in 8%, and hemicraniectomy in 4%. Among experienced clinicians, inter-rater reliability for AC-, ACh-, and H-ASPECTS scores was substantial (kappa values 0.61-0.80). AC-ASPECTS abnormality was present in 14% of patients, and ACh-ASPECTS abnormality in 2%. Among patients with ACA and ICA occlusions, H-ASPECTS scores compared with original ASPECTS scores were more strongly associated with disability level at discharge, ambulatory status at discharge, discharge destination, and combined inpatient mortality and hospice discharge., Conclusion: AC-ASPECTS, ACh-ASPECTS, and H-ASPECTS expand the scope of acute IS imaging scores and increase correlation with functional outcomes. This additional information may enhance prognostication and decision-making, including endovascular thrombectomy and hemicraniectomy., Competing Interests: DL Consultant as Imaging Core Lab to Cerenovus, Genentech, Medtronic, Stryker, Rapid Medical. JS has received, for service on clinical trial steering committees and DSMBs advising on rigorous study design and conduct, hourly payments from Medtronic, Abbott, NeuroVasc, Phillips Medical, Bayer, Biogen, Roche, BrainsGate, BrainQ, CSL Behring, Stream Medical, and Occlutech, and stock options from Rapid Medical, NeuroMerit, Neuronics, and QuantalX. LetsGetProof. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Rodriguez, Taleb, Lee, Liebeskind and Saver.)

Background: Validating the National Institutes of Health NIH Stroke Scale (NIHSS) as a tool to assess deficit severity and prognosis in patients with acute intracerebral hemorrhage would harmonize the assessment of intracerebral hemorrhage (ICH) and acute ischemic stroke (AIS) patients, enable clinical use of a readily implementable and non-imaging dependent prognostic tool, and improve monitoring of ICH care quality in administrative datasets., Methods: Among randomized trial ICH patients, the relation between NIHSS scores early after Emergency Department arrival and 3-month outcomes of dependency or death (modified Rankin Scale, mRS 3-6) and case fatality was examined. NIHSS predictive performance was compared to a current standard prognostic scale, the intracerebral hemorrhage score (ICH score)., Results: Among the 384 patients, the mean age was 65 (±13), with 66% being male. The median NIHSS score was 16 (interquartile range (IQR) 9-25), the mean initial hematoma volume was 29 mL (±38), and the ICH score median was 1 (IQR 0-2). At 3 months, the mRS had a median of 4 (IQR 2-6), with dependency or death occurring in 70% and case fatality in 26%. The NIHSS and ICH scores were strongly correlated ( r  = 0.73), and each was strongly correlated with the 90-day mRS (NIHSS, r  = 0.61; ICH score, r  = 0.62). The NIHSS performed comparably to the ICH score in predicting both dependency or death ( c  = 0.80 vs. 0.80, p  = 0.83) and case fatality ( c  = 0.78 vs. 0.80, p  = 0.29). At threshold values, the NIHSS predicted dependency or death with 74.1% accuracy (NIHSS 17.5) and case fatality with 75.0% accuracy (NIHSS 18.5)., Conclusion: The NIHSS forecasts 3-month functional and case fatality outcomes with accuracy comparable to the ICH Score. Widely documented in routine clinical care and administrative data, the NIHSS can serve as a valuable measure for clinical prognostication, therapy development, and case-mix risk adjustment in ICH patients. Clinical trial registration Clinicaltrials.gov, NCT00059332., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kazaryan, Shkirkova, Saver, Liebeskind, Starkman, Bulic, Poblete, Kim-Tenser, Guo, Conwit, Villablanca, Hamilton and Sanossian.)

Background and Purpose: The value of intravenous thrombolysis (IVT) in eligible tandem lesion patients undergoing endovascular treatment (EVT) is unknown. We investigated treatment effect heterogeneity of EVT + IVT versus EVT-only in tandem lesion patients. Additional analyses were performed for patients undergoing emergent internal carotid artery (ICA) stenting., Methods: SWIFT DIRECT randomized IVT-eligible patients to either EVT + IVT or EVT-only. Primary outcome was 90-day functional independence (modified Rankin Scale score 0-2) after the index event. Secondary endpoints were reperfusion success, 24 h intracranial hemorrhage rate, and 90-day all-cause mortality. Interaction models were fitted for all predefined outcomes., Results: Among 408 included patients, 63 (15.4%) had a tandem lesion and 33 (52.4%) received IVT. In patients with tandem lesions, 20 had undergone emergent ICA stenting (EVT + IVT: 9/33, 27.3%; EVT: 11/30, 36.7%). Tandem lesion did not show treatment effect modification of IVT on rates of functional independence (tandem lesion EVT + IVT vs. EVT: 63.6% vs. 46.7%, non-tandem lesion EVT + IVT vs. EVT: 65.6% vs. 58.2%; p for interaction = 0.77). IVT also did not increase the risk of intracranial hemorrhage  among tandem lesion patients (tandem lesion EVT + IVT vs. EVT: 34.4% vs. 46.7%, non-tandem lesion EVT + IVT vs. EVT: 33.5% vs. 26.3%; p for interaction = 0.15). No heterogeneity was noted for other endpoints (p for interaction > 0.05)., Conclusions: No treatment effect heterogeneity of EVT + IVT versus EVT-only was observed among tandem lesion patients. Administering IVT in patients with anticipated emergent ICA stenting seems safe, and the latter should not be a factor to consider when deciding to administer IVT before EVT., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: A coordinated network of circulating inflammatory molecules centered on the pleotropic pro-atherogenic cytokine interleukin-18 (IL-18) is linked to cerebral small vessel disease. We sought to validate the association of this inflammatory biomarker network with incident stroke risk, cognitive impairment, and imaging metrics in a sample of the Framingham Offspring Cohort., Methods: Using available baseline measurements of serum levels of IL-18, GDF (growth and differentiation factor)-15, soluble form of receptor for advanced glycation end products, myeloperoxidase, and MCP-1 (monocyte chemoattractant protein-1) from Exam 7 of the Framingham Offspring Cohort (1998-2001), we constructed a population-normalized, equally weighted log-transformed mean Z -score value representing the average level of each serum analyte to create an inflammatory composite score (ICS5). Multivariable regression models were used to determine the association of ICS5 with incident stroke, brain magnetic resonance imaging features, and cognitive testing performance., Results: We found a significant association between ICS5 score and increased risk for incident all-cause stroke (hazard ratio, 1.48 [95% CI, 1.05-2.08]; P =0.024) and ischemic stroke (hazard ratio, 1.51 [95% CI, 1.03-2.21]; P =0.033) in the Exam 7 cohort of 2201 subjects (mean age 62±9 years; 54% female) aged 45+ years with an all-cause incident stroke rate of 6.1% (135/2201) and ischemic stroke rate of 4.9% (108/2201). ICS5 and its component serum markers are all associated with the Framingham Stroke Risk Profile score (β±SE, 0.19±0.02; P <0.0001). In addition, we found a significant inverse association of ICS5 with a global cognitive score, derived from a principal components analysis of the neuropsychological battery used in the Framingham cohort (-0.08±0.03; P =0.019). No association of ICS5 with magnetic resonance imaging metrics of cerebral small vessel disease was observed., Conclusions: Circulating serum levels of inflammatory biomarkers centered on IL-18 are associated with an increased risk of stroke and cognitive impairment in the Framingham Offspring Cohort. Linking specific inflammatory pathways to cerebral small vessel disease may enhance individualized quantitative risk assessment for future stroke and vascular cognitive impairment., Competing Interests: Disclosures C. Teran is a former University of California Log Angeles Health employee supported by National Institutes of Health funding. Dr Liebeskind is scientific advisor and on the Board of Directors of Sage Cerebrovascular Diagnostics, Inc. Dr McGrath receives grant support from the Health Research Board. Dr DeCarli is a consultant to Eisai and Novo Nordisk. Dr Himali receives grant support from NIH, the Alzheimer’s Drug Discovery Foundation, and the Alzheimer’s Association. Dr Seshadri is a consultant for Biogen and Eisai. Dr Hinman is a listed inventor on the following patents held by the Regents of the University of California that include blood measurement of the molecules included in this study: Japan Patent No. 7211626; Korea Patent No. 10-2538752; US Application 62/461,161; Canada Application 3,054,083; EPO Application 18755090.0. Dr Hinman is also the founder of Sage Cerebrovascular Diagnostics, Inc. which has an exclusive license from the Regents to commercialize diagnostic tests using these markers. The other authors report no conflicts.

Intracranial atherosclerotic disease (ICAD) is a leading cause of ischemic stroke worldwide. However, research on the pathophysiology of ICAD is scarce due to the relative inaccessibility of histology samples and the lack of comprehensive experimental models. As a result, much of the current understanding of ICAD relies on research on extracranial atherosclerosis. This approach is problematic as intracranial and extracranial arteries are anatomically, structurally, physiologically, and metabolically distinct, indicating that intracranial and extracranial atherosclerosis likely develop through different biologic pathways. The current standard of care for ICAD treatment relies predominantly on therapeutics developed to treat extracranial atherosclerosis and is insufficient given the alarmingly high risk of stroke. To provide a definitive treatment for the disease, a deeper understanding of the pathophysiology underlying ICAD is specifically required. True mechanistic understanding of disease pathogenesis is only possible using robust experimental models. In this review, we aim to identify the advantages and limitations of the existing in vivo and in vitro models of ICAD and basic atherosclerotic processes, which may be used to inform better models of ICAD in the future and drive new therapeutic strategies to reduce stroke risk., Competing Interests: Disclosures Dr Liebeskind is a consultant as Imaging Core Lab to Cerenovus, Genentech, Medtronic, Rapid Medical, and Stryker. The other authors report no conflicts.

Background: Mechanical thrombectomy (MT) has revolutionized the treatment of acute ischemic stroke (AIS) due to large vessel occlusion (LVO), but its efficacy and safety in medium vessel occlusion (MeVO) remain less explored. This multicenter, retrospective study aims to investigate the incidence and clinical outcomes of vessel perforations (confirmed by extravasation during an angiographic series) during MT for AIS caused by MeVO., Methods: Data were collected from 37 academic centers across North America, Asia, and Europe between September 2017 and July 2021. A total of 1373 AIS patients with MeVO underwent MT. Baseline characteristics, procedural details, and clinical outcomes were analyzed., Results: The incidence of vessel perforation was 4.8% (66/1373). Notably, our analysis indicates variations in perforation rates across different arterial segments: 8.9% in M3 segments, 4.3% in M2 segments, and 8.3% in A2 segments ( p  = 0.612). Patients with perforation had significantly worse outcomes, with lower rates of favorable angiographic outcomes (TICI 2c-3: 23% vs 58.9%, p  < 0.001; TICI 2b-3: 56.5% vs 88.3%, p  < 0.001). Functional outcomes were also worse in the perforation group (mRS 0-1 at 3 months: 22.7% vs 36.6%, p  = 0.031; mRS 0-2 at 3 months: 28.8% vs 53.9%, p  < 0.001). Mortality was higher in the perforation group (30.3% vs 16.8%, p  = 0.008)., Conclusion: This study reveals that while the occurrence of vessel perforation in MT for AIS due to MeVO is relatively rare, it is associated with poor functional outcomes and higher mortality. The findings highlight the need for increased caution and specialized training in performing MT for MeVO. Further prospective research is required for risk mitigation strategies., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Regenhardt serves on a DSMB for a trial sponsored by Rapid Medical, serves as site PI for studies sponsored by Penumbra and Microvention, and receives stroke research grant funding from the National Institutes of Health, Society of Vascular and Interventional Neurology, and Heitman Stroke Foundation. Dr. Guenego reports consultancy for Rapid Medical and Phenox, not directly related to the present work. Prof. Clarençon reports conflicts of interest with Medtronic, Balt Extrusion (consultant), ClinSearch (core lab), Penumbra, Stryker (payment for reading), and Artedrone (Board); all not directly related to the present work. Dr. Henninger received support from NINDS NS131756, during the conduct of the study. Dr. Liebeskind is consultant as Imaging Core Lab to Cerenovus, Genentech, Medtronic, Stryker, Rapid Medical. Dr. Nguyen reports advisory board with Idorsia. Dr. Yeo reports Advisory work for AstraZeneca, Substantial support from NMRC Singapore and is a medical advisor for See-mode, Cortiro, and Sunbird Bio, with equity in Ceroflo. All unrelated to the present work. Dr. Griessenauer reports a proctoring agreement with Medtronic and research funding by Penumbra. Dr. Marnat reports conflicts of interest with Microvention Europe, Stryker Neurovascular, Balt (consulting), Medtronic, Johnson & Johnson, and Phenox (paid lectures), all not directly related to the present work. Pr Sibon reports conflict of interest with Medtronic, Sanofi, Bayer, Boehringer-Ingelheim, Novartis, Novo-Nordisk, BMS-Pfizer (board and paid lectures), all not directly related to the present work. Dr. Yedavalli is a consultant for RAPID (Ischemaview, Menlo Park, CA). Dr. Vagal is a consultant for Viz AI. She is also PI of Imaging core lab for ENDOLOW study funded by Cerenovus (monies go to the institution). Dr. Gopinathan reports conflicts of interest with Microvention, Stryker Neurovascular, Medtronic, BD, Penumbra (paid lectures, workshops, and proctoring), all not directly related to the present work. Dr. Bernstock has an equity position in Treovir Inc., an oHSV clinical stage company and UpFront Diagnostics. JDB is also on the Centile Bioscience and NeuroX1 boards of scientific advisors.

The effect of arterial tortuosity on intracranial atherosclerosis (ICAS) is not well understood. This study aimed to evaluate the effect of global intracranial arterial tortuosity on intracranial atherosclerotic burden in patients with ischemic stroke. We included patients with acute ischemic stroke who underwent magnetic resonance angiography (MRA) and classified them into three groups according to the ICAS burden. Global tortuosity index (GTI) was defined as the standardized mean curvature of the entire intracranial arteries, measured by in-house vessel analysis software. Of the 516 patients included, 274 patients had no ICAS, 140 patients had a low ICAS burden, and 102 patients had a high ICAS burden. GTI increased with higher ICAS burden. After adjustment for age, sex, vascular risk factors, and standardized mean arterial area, GTI was independently associated with ICAS burden (adjusted odds ratio [adjusted OR] 1.33; 95% confidence interval [CI] 1.09-1.62). The degree of association increased when the arterial tortuosity was analyzed limited to the basal arteries (adjusted OR 1.48; 95% CI 1.22-1.81). We demonstrated that GTI is associated with ICAS burden in patients with ischemic stroke, suggesting a role for global arterial tortuosity in ICAS., (© 2024. The Author(s).)

Background: The use of thrombectomy in patients with acute stroke and a large infarct of unrestricted size has not been well studied., Methods: We assigned, in a 1:1 ratio, patients with proximal cerebral vessel occlusion in the anterior circulation and a large infarct (as defined by an Alberta Stroke Program Early Computed Tomographic Score of ≤5; values range from 0 to 10) detected on magnetic resonance imaging or computed tomography within 6.5 hours after symptom onset to undergo endovascular thrombectomy and receive medical care (thrombectomy group) or to receive medical care alone (control group). The primary outcome was the score on the modified Rankin scale at 90 days (scores range from 0 to 6, with higher scores indicating greater disability). The primary safety outcome was death from any cause at 90 days, and an ancillary safety outcome was symptomatic intracerebral hemorrhage., Results: A total of 333 patients were assigned to either the thrombectomy group (166 patients) or the control group (167 patients); 9 were excluded from the analysis because of consent withdrawal or legal reasons. The trial was stopped early because results of similar trials favored thrombectomy. Approximately 35% of the patients received thrombolysis therapy. The median modified Rankin scale score at 90 days was 4 in the thrombectomy group and 6 in the control group (generalized odds ratio, 1.63; 95% confidence interval [CI], 1.29 to 2.06; P<0.001). Death from any cause at 90 days occurred in 36.1% of the patients in the thrombectomy group and in 55.5% of those in the control group (adjusted relative risk, 0.65; 95% CI, 0.50 to 0.84), and the percentage of patients with symptomatic intracerebral hemorrhage was 9.6% and 5.7%, respectively (adjusted relative risk, 1.73; 95% CI, 0.78 to 4.68). Eleven procedure-related complications occurred in the thrombectomy group., Conclusions: In patients with acute stroke and a large infarct of unrestricted size, thrombectomy plus medical care resulted in better functional outcomes and lower mortality than medical care alone but led to a higher incidence of symptomatic intracerebral hemorrhage. (Funded by Montpellier University Hospital; LASTE ClinicalTrials.gov number, NCT03811769.)., (Copyright © 2024 Massachusetts Medical Society.)

Background and Purpose: The DWI-FLAIR mismatch is used to determine thrombolytic eligibility in patients with acute ischemic stroke when the time since stroke onset is unknown. Commercial software packages have been developed for automated DWI-FLAIR classification. We aimed to use e-Stroke software for automated classification of the DWI-FLAIR mismatch in a cohort of patients with acute ischemic stroke and in a comparative analysis with 2 expert neuroradiologists., Materials and Methods: In this retrospective study, patients with acute ischemic stroke who had MR imaging and known time since stroke onset were included. The DWI-FLAIR mismatch was evaluated by 2 neuroradiologists blinded to the time since stroke onset and automatically by the e-Stroke software. After 4 weeks, the neuroradiologists re-evaluated the MR images, this time equipped with automated predicted e-Stroke results as a computer-assisted tool. Diagnostic performances of e-Stroke software and the neuroradiologists were evaluated for prediction of DWI-FLAIR mismatch status., Results: A total of 157 patients met the inclusion criteria. A total of 82 patients (52%) had a time since stroke onset of ≤4.5 hours. By means of consensus reads, 81 patients (51.5%) had a DWI-FLAIR mismatch. The diagnostic accuracy (area under the curve/sensitivity/specificity) of e-Stroke software for the determination of the DWI-FLAIR mismatch was 0.72/90.0/53.9. The diagnostic accuracy (area under the curve/sensitivity/specificity) for neuroradiologists 1 and 2 was 0.76/69.1/84.2 and 0.82/91.4/73.7, respectively; both significantly ( P  < .05) improved to 0.83/79.0/86.8 and 0.89/92.6/85.5, respectively, following the use of e-Stroke predictions as a computer-assisted tool. The interrater agreement (κ) for determination of DWI-FLAIR status was improved from 0.49 to 0.57 following the use of the computer-assisted tool., Conclusions: This automated quantitative approach for DWI-FLAIR mismatch provides results comparable with those of human experts and can improve the diagnostic accuracies of expert neuroradiologists in the determination of DWI-FLAIR status., (© 2024 by American Journal of Neuroradiology.)

Purpose: Optimal imaging modalities to select patients for endovascular thrombectomy (EVT) in the late window of acute ischemic stroke due to large vessel occlusions (AIS-LVO) are not known. We conducted a systematic review comparing outcomes of patients selected by non-contrast computed tomography (NCCT)/CT angiography (CTA) vs. those selected by CT perfusion (CTP) or magnetic resonance imaging (MRI) for EVT in these patients., Methods: We searched PUBMED, EMBASE, and the Cochrane Library from January 1, 2000, to July 15, 2023, to identify studies comparing outcomes of patients selected for EVT by NCCT/CTA vs. CTP or MRI in the late time window for AIS-LVO. Primary outcome was independence (mRS 0-2) at 90 days or discharge. Secondary outcomes were symptomatic intracranial hemorrhage (sICH) and mortality. We pooled data across studies based on an inverse variance method., Results: Six cohort studies with 4208 patients were included. Pooled results showed no significant difference in the rate of independence at 90 days or discharge (RR 0.96, 95% CI 0.88-1.03) and sICH (RR 1.26, 0.85-1.86) between patients selected by NCCT/CTA vs. CTP or MRI for EVT in the late window of AIS-LVO. However, patients selected by NCCT/CTA vs. CTP or MRI for EVT were associated with a higher risk of mortality (RR 1.21, 1.06-1.39)., Conclusion: For AIS-LVO in the late window, patients selected by NCCT/CTA compared with those selected by CTP or MRI for EVT might have a comparable rate of functional independence and sICH. Baseline NCCT/CTA may triage AIS-LVO in the late window., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Intracranial aneurysms (IAs) remain a challenging neurological diagnosis associated with significant morbidity and mortality. There is a plethora of microsurgical and endovascular techniques for the treatment of both ruptured and unruptured aneurysms. There is no definitive consensus as to the best treatment option for this cerebrovascular pathology. The Aneurysm, Arteriovenous Malformation, and Chronic Subdural Hematoma Roundtable Discussion With Industry and Stroke Experts discussed best practices and the most promising approaches to improve the management of brain aneurysms., Methods: A group of experts from academia, industry, and federal regulators convened to discuss updated clinical trials, scientific research on preclinical system models, management options, screening and monitoring, and promising novel device technologies, aiming to improve the outcomes of patients with IA., Results: Aneurysm, Arteriovenous Malformation, and Chronic Subdural Hematoma Roundtable Discussion With Industry and Stroke Experts suggested the incorporation of artificial intelligence to capture sequential aneurysm growth, identify predictors of rupture, and predict the risk of rupture to guide treatment options. The consensus strongly recommended nationwide systemic data collection of unruptured IA radiographic images for the analysis and development of machine learning algorithms for rupture risk. The consensus supported centers of excellence for preclinical multicenter trials in areas such as genetics, cellular composition, and radiogenomics. Optical coherence tomography and magnetic resonance imaging contrast-enhanced 3T vessel wall imaging are promising technologies; however, more data are needed to define their role in IA management. Ruptured aneurysms are best managed at large volume centers, which should include comprehensive patient management with expertise in microsurgery, endovascular surgery, neurology, and neurocritical care., Conclusions: Clinical and preclinical studies and scientific research on IA should engage high-volume centers and be conducted in multicenter collaborative efforts. The future of IA diagnosis and monitoring could be enhanced by the incorporation of artificial intelligence and national radiographic and biologic registries. A collaborative effort between academic centers, government regulators, and the device industry is paramount for the adequate management of IA and the advancement of the field., Competing Interests: Disclosures Dr Tjoumakaris reports compensation from Medtronic for consultant services, MicroVention, Inc, for consultant services, and MicroVention, Inc, for consultant services. Dr Hanel reports compensation from Cerenovous for consultant services; stock holdings in eLum and BlinkTBI; compensation from Medtronic for consultant services; stock holdings in Endostream; compensation from Stryker for consultant services; stock holdings in Scientia, Cerebrotech, and RisT; compensation from MicroVention, Inc, for consultant services; compensation from Balt USA, LLC, for consultant services; stock holdings in Corindus, Inc, InNeuroCo, NTI, and Three Rivers Medical, Inc; and compensation from phenox, Inc, Q’Apel, and Rapid Medical Ltd for consultant services. Dr Mocco reports compensation from CVAid for consultant services; stock options in Tulavi; compensation from Penumbra, Inc, for other services; stock holdings in Q’Apel, Spinaker, Endostream, Sim&Cure, and Cerebrotech; compensation from Perflow for consultant services; stock options in Songbird, NRT, and Borvo; grants from PCORI; stock options in E8; employment by Mount Sinai Health System; stock holdings in Imperative Care, Inc; compensation from CVAid and RIST for consultant services; stock holdings in Viseon, Inc, Radical, Vastrax, and Neurolutions; compensation from Synchron for consultant services; stock options in Spinaker; compensation from MicroVention, Inc, for other services; stock holdings in Blinktbi, Echovate, NTI Managers, and Vizai; and compensation from Stryker for other services. Dr Ali-Aziz Sultan reports compensation from MicroVention, Inc, for other services. Dr Froehler reports compensation from OCULUS, Inc, Cerenovus, and Siemens for consultant services; grants from Genentech, Inc; grants from Siemens; and compensation from Balt USA, LLC, for consultant services. Dr Lieber reports stock holdings in Prometheus Therapapeutics, Inc. Dr Coon reports compensation from Medtronic, Inc, Imperative Care, Inc, MicroVention, Inc, Rapid Medical Ltd, Stryker Corporation, and Johnson and Johnson for consultant services. Dr Tateshima reports compensation from Rapid Medical Ltd, Medtronic, phenox, Inc, Cerenovus, MicroVention, Inc, and Stryker for consultant services. Dr Altschul reports securities holdings in Von Vascular, Inc, and compensation from Johnson and Johnson International, Stryker Corporation, Medtronic USA, Inc, and MicroVention, Inc, for consultant services. Dr Narayanan reports compensation from MicroVention, Inc, Johnson & Johnson Health Care Systems, Inc, and Imperative Care, Inc, for consultant services. Dr Taussky reports compensation from Medtronic for consultant services; compensation from phenox, Inc, for data and safety monitoring services; and compensation from Johnson & Johnson Health Care Systems, Inc, for consultant services. Dr Hoh reports stock options in Progressive Neuro; compensation from AstraZeneca for other services; stock options in Galaxy Therapeutics; grants from the National Institutes of Health; compensation from Janssen Pharmaceuticals for other services; employment by the College of Medicine, University of Florida; grants from the Brain Aneurysm Foundation; and stock options in Proprio Vision. Dr Gounis reports compensation from Wallaby Medical, Imperative Care, Inc, and Mivi Neurosciences for consultant services; stock holdings in GalaxyTherapeutics; compensation from Medtronic Neurovascular for consultant services; stock holdings in InNeuroCo, LLC; compensation from Q’Apel Medical, phenox, Inc, Cerenovus, Route 92 Medical, Inc, Alembic, LLC, and Stryker Corporation for consultant services; and stock holdings in Imperative Care, Inc, and Synchron. Dr Liebeskind reports compensation from Stryker, Medtronic, Rapid Medical Ltd, Cerenovus, and Genentech for consultant services. Dr Volovici reports employment by Erasmus Medisch Centrum and compensation from JAMA for consultant services. Dr Toth reports compensation from Medtronic USA, Inc, for other services and compensation from EBSCO and Penumbra, Inc, for consultant services. Dr Arthur reports compensation from Balt USA, LLC, Penumbra, Inc, MicroVention, Inc, Johnson and Johnson International, Siemens Medical Solutions USA, Inc, Stryker Corporation, Perfuze, Scientia, and Medtronic USA, Inc, for consultant services. Dr Wakhloo reports compensation from Stryker Corporation for consultant services, an ownership stake in Deinde Medical, compensation from Acotec for consultant services, an ownership stake in Prometheus Therapeutics, grants from Philips, an ownership stake in Neurofine, and compensation from Cerenovus Johnson & Johnson for consultant services. The other authors report no conflicts.

Background and Purpose: Predicting long-term clinical outcome in acute ischemic stroke is beneficial for prognosis, clinical trial design, resource management, and patient expectations. This study used a deep learning-based predictive model (DLPD) to predict 90-day mRS outcomes and compared its predictions with those made by physicians., Materials and Methods: A previously developed DLPD that incorporated DWI and clinical data from the acute period was used to predict 90-day mRS outcomes in 80 consecutive patients with acute ischemic stroke from a single-center registry. We assessed the predictions of the model alongside those of 5 physicians (2 stroke neurologists and 3 neuroradiologists provided with the same imaging and clinical information). The primary analysis was the agreement between the ordinal mRS predictions of the model or physician and the ground truth using the Gwet Agreement Coefficient. We also evaluated the ability to identify unfavorable outcomes (mRS >2) using the area under the curve, sensitivity, and specificity. Noninferiority analyses were undertaken using limits of 0.1 for the Gwet Agreement Coefficient and 0.05 for the area under the curve analysis. The accuracy of prediction was also assessed using the mean absolute error for prediction, percentage of predictions ±1 categories away from the ground truth (±1 accuracy [ACC]), and percentage of exact predictions (ACC)., Results: To predict the specific mRS score, the DLPD yielded a Gwet Agreement Coefficient score of 0.79 (95% CI, 0.71-0.86), surpassing the physicians' score of 0.76 (95% CI, 0.67-0.84), and was noninferior to the readers ( P  < .001). For identifying unfavorable outcome, the model achieved an area under the curve of 0.81 (95% CI, 0.72-0.89), again noninferior to the readers' area under the curve of 0.79 (95% CI, 0.69-0.87) ( P  < .005). The mean absolute error, ±1ACC, and ACC were 0.89, 81%, and 36% for the DLPD., Conclusions: A deep learning method using acute clinical and imaging data for long-term functional outcome prediction in patients with acute ischemic stroke, the DLPD, was noninferior to that of clinical readers., (© 2024 by American Journal of Neuroradiology.)

Purpose: Our purpose was to assess the efficacy and safety of the pRESET LITE stent retriever (Phenox, Bochum, Germany), designed for medium vessel occlusion (MeVO) in acute ischemic stroke (AIS) patients with a primary MeVO., Methods: We performed a retrospective analysis of the MAD MT Consortium, an integration of prospectively maintained databases at 37 academic institutions in Europe, North America, and Asia, of AIS patients who underwent mechanical thrombectomy with the pRESET LITE stent retriever for a primary MeVO. We subcategorized occlusions into proximal MeVOs (segments A1, M2, and P1) vs. distal MeVOs/DMVO (segments A2, M3-M4, and P2). We reviewed patient and procedural characteristics, as well as angiographic and clinical outcomes., Results: Between September 2016 and December 2021, 227 patients were included (50% female, median age 78 [65-84] years), of whom 161 (71%) suffered proximal MeVO and 66 (29%) distal MeVO. Using a combined approach in 96% of cases, successful reperfusion of the target vessel (mTICI 2b/2c/3) was attained in 85% of proximal MeVO and 97% of DMVO, with a median of 2 passes (IQR: 1-3) overall. Periprocedural complications rate was 7%. Control CT at day 1 post-MT revealed a hemorrhagic transformation in 63 (39%) patients with proximal MeVO and 24 (36%) patients with DMVO, with ECASS-PH type hemorrhagic transformations occurring in 3 (1%) patients. After 3 months, 58% of all MeVO and 63% of DMVO patients demonstrated a favorable outcome (mRS 0-2)., Conclusion: Mechanical thrombectomy using the pRESET LITE in a combined approach with an aspiration catheter appears effective for primary medium vessel occlusions across several centers and physicians., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Small, randomized trials of patients with cervical artery dissection showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with cervical artery dissection treated with antiplatelets versus anticoagulation., Methods: This is a multicenter observational retrospective international study (16 countries, 63 sites) that included patients with cervical artery dissection without major trauma. The exposure was antithrombotic treatment type (anticoagulation versus antiplatelets), and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with inverse probability of treatment weighting to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an as-treated crossover approach and only included outcomes occurring with the above treatments., Results: The study included 3636 patients (402 [11.1%] received exclusively anticoagulation and 2453 [67.5%] received exclusively antiplatelets). By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with inverse probability of treatment weighting, compared with antiplatelet therapy, anticoagulation was associated with a nonsignificantly lower risk of subsequent ischemic stroke by day 30 (adjusted hazard ratio [HR], 0.71 [95% CI, 0.45-1.12]; P =0.145) and by day 180 (adjusted HR, 0.80 [95% CI, 0.28-2.24]; P =0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR, 1.39 [95% CI, 0.35-5.45]; P =0.637) but was by day 180 (adjusted HR, 5.56 [95% CI, 1.53-20.13]; P =0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR, 0.40 [95% CI, 0.18-0.88]; P interaction =0.009)., Conclusions: Our study does not rule out the benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings., Competing Interests: Disclosures Disclosures provided by Dr Nguyen in compliance with American Heart Association annual Journal Editor Disclosure Questionnaire are available at https://www.ahajournals.org/editor-coi-disclosures. Dr Arnold reports compensation from Boehringer Ingelheim, AstraZeneca, Bayer, Bristol-Myers Squibb, Covidien, Daiichi Sankyo, Novartis, Sanofi, Pfizer, Medtronic, Novo Nordisk, and Amgen for consultant services. Dr Lester reports a provisional patent for Methods and compositions for disrupting tau aggregates. Dr Touze reports compensation from Elsevier for other services and employment by Caen. J.E. Kaufman reports grants from Goldschmidt Jacobson-Stiftung. Dr Traenka reports travel support from Bayer Healthcare. Dr Aguiar de Sousa reports compensation from Daiichi Sankyo, Bayer, AstraZeneca, Johnson & Johnson, and Fundação Bial for other services; compensation from the University of British Columbia for data and safety monitoring services; compensation from Organon & Co for consultant services. Dr Rosa reports grants from Merck Sharp & Dohme Corporation. Dr Field reports compensation from HLS Therapeutics, AstraZeneca Canada, and Roche for consultant services; service as a board member for Destine Health; and compensation from the Canadian Medical Protective Association for expert witness services; and grants from Bayer. Dr Leker reports compensation from Medtronic, Ischemaview, Bayer, Abbott Diabetes Care, Biogen, Janssen Biotech, and Boehringer Ingelheim for other services. Dr Nolte reports compensation from Daiichi Sankyo Europe GmbH, Boehringer Ingelheim, Pfizer, Bristol-Myers Squibb, and Alexion Pharmaceuticals for consultant services; and compensation from AstraZeneca, Abbott Canada, Deutsches Zentrum für Neurodegenerative Erkrankungen, Novartis, Portola Pharmaceuticals, Deutsches Zentrum für Herz-Kreislaufforschung, and Novartis for other services. Dr Poppe reports grants from Foundation Brain Canada, Heart and Stroke Foundation of Canada, and Stryker; and compensation from Roche for other services. Dr Liebeskind reports compensation from Medtronic, Genentech, Cerenovus, Stryker, and Rapid Medical Ltd, for consultant services. B. Mac Grory reports grants from the National Institutes of Health; employment by Duke University Medical Center; compensation from Bayer for other services; grants from the American Heart Association, Duke Bass Connections, and the Duke Office of Physician Scientist Development. Dr Al Kasab reports compensation from Stryker for other services and employment by Medical University of South Carolina. Dr Kicielinski reports compensation from Stryker, Penumbra Inc, Medtronic, and MicroVention Inc, for other services; travel support from MicroVention Inc; and employment by Medical University of South Carolina and Elsevier. Dr de Havenon reports stock options in TitinKM and Certus; grants from the National Institutes of Health; and compensation from Novo Nordisk for consultant services. Dr Siegler reports grants from Philips and employment by the University of Chicago. Dr Willey reports compensation from Edwards Lifesciences Corporation and Abbott Fund for end point review committee services; compensation from Uptodate for other services; and compensation from the Abbott Laboratories for consultant services. Dr Sharma reports a provisional patent for a stroke etiology classifier algorithm and grants from the National Institutes of Health Clinical Center. Dr Martins reports compensation from Pfizer, Medtronic, Servier Affaires Medicales, Daiichi Sankyo, Bayer, Novo Nordisk, Novartis, Penumbra Inc, and Boehringer Ingelheim for other services. Dr Simpkins reports grants from the National Institutes of Health. Dr Stretz reports grants from Massachusetts General Hospital. Dr Furie reports compensation from Janssen Biotech for consultant services. The other authors report no conflicts

Introduction: Stroke interventions that increase collateral flow have the potential to salvage penumbral tissue and increase the number of patients eligible for reperfusion therapy. We compared the efficacy of two different collateral therapeutics during transient middle cerebral artery occlusion (tMCAO) in normotensive and hypertensive rats., Methods: The change in collateral and core perfusion was measured using dual laser Doppler in response to either a pressor agent (phenylephrine, 10 mg/kg iv or vehicle) or a collateral vasodilator (TM5441, 5 mg/kg iv or vehicle) given 30 min into tMCAO in male Wistar and spontaneously hypertensive rats (SHRs)., Results: Pressor therapy increased collateral flow in the Wistar rats but was ineffective in the SHRs. The increase in collateral flow in the Wistar rats was associated with impaired cerebral blood flow autoregulation (CBFAR) that was intact in the SHRs. TM5441 caused a decrease in collateral perfusion in the Wistar rats and a modest increase in the SHRs. The pressor therapy reduced early infarction in both groups but increased edema in the SHRs, whereas TM5441 did not have any beneficial effects in either group., Conclusions: Thus, the pressor therapy was superior to a collateral vasodilator in increasing collateral flow and improving outcomes in the Wistar rats, likely due to pial collaterals that were pressure passive; the lack of CBF response in the SHRs to pressor therapy was likely due to intact CBFAR that limited perfusion. While TM5441 modestly increased CBF in the SHRs but not in the Wistar rats, it did not have a beneficial effect on stroke outcomes. These results suggest that collateral therapies may need to be selected for certain comorbidities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cipolla, Hunt, Liebeskind and Tremble.)

Background: Robotic-assisted neurointervention was recently introduced, with implications that it could be used to treat neurovascular diseases., Objective: To evaluate the effectiveness and safety of the robotic-assisted platform CorPath GRX for treating cerebral aneurysms., Methods: This prospective, international, multicenter study enrolled patients with brain aneurysms that required endovascular coiling and/or stent-assisted coiling. The primary effectiveness endpoint was defined as successful completion of the robotic-assisted endovascular procedure without any unplanned conversion to manual treatment with guidewire or microcatheter navigation, embolization coil(s) or intracranial stent(s) deployment, or an inability to navigate vessel anatomy. The primary safety endpoint included intraprocedural and periprocedural events., Results: The study enrolled 117 patients (74.4% female) with mean age of 56.6 years from 10 international sites,. Headache was the most common presenting symptom in 40/117 (34.2%) subjects. Internal carotid artery was the most common location (34/122, 27.9%), and the mean aneurysm height and neck width were 5.7±2.6 mm and 3.5±1.4 mm, respectively. The overall procedure time was 117.3±47.3 min with 59.4±32.6 min robotic procedure time. Primary effectiveness was achieved in 110/117 (94%) subjects with seven subjects requiring conversion to manual for procedure completion. Only four primary safety events were recorded with two intraprocedural aneurysm ruptures and two strokes. A Raymond-Roy Classification Scale score of 1 was achieved in 71/110 (64.5%) subjects, and all subjects were discharged with a modified Rankin Scale score of ≤2., Conclusions: This first-of-its-kind robotic-assisted neurovascular trial demonstrates the effectiveness and safety of the CorPath GRX System for endovascular embolization of cerebral aneurysm procedures., Trial Registration Number: NCT04236856., Competing Interests: Competing interests: VMP is an unpaid consultant for Siemens Healthinners Endovascular Robotics. The following authors have one or more competing interests: HR, NS, FC, DH, MP, JG, MK-O, RDT, RB. These competing interests include board membership, consultancy, employment, expert testimony grants, contract research, lectures/other education events, speakers’ bureau, and receipt of equipment or supplies, royalties, stock/stock options/other forms of ownership., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There are little available data regarding the influence of intravenous thrombolysis (IVT) on the efficacy of different first line endovascular treatment (EVT) techniques., Methods: We used the dataset of the SWIFT-DIRECT trial which randomized 408 patients to IVT + EVT or EVT alone at 48 international sites. The protocol required the use of a stent retriever (SR), but concomitant use of a balloon guide catheter (BGC) and/or distal aspiration (DA) catheter was left to the discretion of the operators. Four first line techniques were applied in the study population: SR, SR + BGC, SR + DA, SR + DA + BGC. To assess whether the effect of allocation to IVT + EVT versus EVT alone was modified by the first line technique, interaction models were fitted for predefined outcomes. The primary outcome was first pass mTICI 2c‑3 reperfusion (FPR)., Results: This study included 385 patients of whom 172 were treated with SR + DA, 121 with SR + DA + BGC, 57 with SR + BGC and 35 with SR. There was no evidence that the effect of IVT + EVT versus EVT alone would be modified by the choice of first line technique; however, allocation to IVT + EVT increased the odds of FPR by a factor of 1.68 (95% confidence interval, CI 1.11-2.54)., Conclusion: This post hoc analysis does not suggest treatment effect heterogeneity of IVT + EVT vs EVT alone in different stent retriever techniques but provides evidence for increased FPR if bridging IVT is administered before stent retriever thrombectomy., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Introduction: First pass effect (FPE), achievement of complete recanalization (mTICI 2c/3) with a single pass, is a significant predictor of favorable outcomes for endovascular treatment (EVT) in large vessel occlusion stroke (LVO). However, data concerning the impact on functional outcomes and predictors of FPE in medium vessel occlusions (MeVO) are scarce., Patients and Methods: We conducted an international retrospective study on MeVO cases. Multivariable logistic modeling was used to establish independent predictors of FPE. Clinical and safety outcomes were compared between the two study groups (FPE vs non-FPE) using logistic regression models. Good outcome was defined as modified Rankin Scale 0-2 at 3 months., Results: Eight hundred thirty-six patients with a final mTICI ⩾ 2b were included in this analysis. FPE was observed in 302 patients (36.1%). In multivariable analysis, hypertension (aOR 1.55, 95% CI 1.10-2.20) and lower baseline NIHSS score (aOR 0.95, 95% CI 0.93-0.97) were independently associated with an FPE. Good outcomes were more common in the FPE versus non-FPE group (72.8% vs 52.8%), and FPE was independently associated with favorable outcome (aOR 2.20, 95% CI 1.59-3.05). 90-day mortality and intracranial hemorrhage (ICH) were significantly lower in the FPE group, 0.43 (95% CI, 0.25-0.72) and 0.55 (95% CI, 0.39-0.77), respectively., Conclusion: Over 2/3 of patients with MeVOs and FPE in our cohort had a favorable outcome at 90 days. FPE is independently associated with favorable outcomes, it may reduce the risk of any intracranial hemorrhage, and 3-month mortality., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Regenhardt serves on a DSMB for a trial sponsored by Rapid Medical, serves as site PI for studies sponsored by Penumbra and Microvention, and receives stroke research grant funding from the National Institutes of Health, Society of Vascular and Interventional Neurology, and Heitman Stroke Foundation. Dr. Guenego reports consultancy for Rapid Medical and Phenox, not directly related to the present work. Prof. Clarençon reports conflicts of interest with Medtronic, Balt Extrusion (consultant), ClinSearch (core lab), Penumbra, Stryker (payment for reading) and Artedrone (Board); all not directly related to the present work. Dr. Henninger received support from NINDS NS131756, during the conduct of the study. Dr. Liebeskind is consultant as Imaging Core Lab to Cerenovus, Genentech, Medtronic, Stryker, Rapid Medical. Dr. Yeo reports Advisory work for AstraZeneca, Substantial support from NMRC Singapore and is a medical advisor for See-mode, Cortiro and Sunbird Bio, with equity in Ceroflo. All unrelated to the present work. Dr. Griessenauer reports a proctoring agreement with Medtronic and research funding by Penumbra. Dr. Marnat reports conflicts of interest with Microvention Europe, Stryker Neurovascular, Balt (consulting), Medtronic, Johnson & Johnson and Phenox (paid lectures), all not directly related to the present work. Dr. Nguyen reports advisory board with Idorsia and Brainomix. All other others do not report any conflict of interests related to this work.

Background: Thrombolytic agents, including tenecteplase, are generally used within 4.5 hours after the onset of stroke symptoms. Information on whether tenecteplase confers benefit beyond 4.5 hours is limited., Methods: We conducted a multicenter, double-blind, randomized, placebo-controlled trial involving patients with ischemic stroke to compare tenecteplase (0.25 mg per kilogram of body weight, up to 25 mg) with placebo administered 4.5 to 24 hours after the time that the patient was last known to be well. Patients had to have evidence of occlusion of the middle cerebral artery or internal carotid artery and salvageable tissue as determined on perfusion imaging. The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability and a score of 6 indicating death) at day 90. Safety outcomes included death and symptomatic intracranial hemorrhage., Results: The trial enrolled 458 patients, 77.3% of whom subsequently underwent thrombectomy; 228 patients were assigned to receive tenecteplase, and 230 to receive placebo. The median time between the time the patient was last known to be well and randomization was approximately 12 hours in the tenecteplase group and approximately 13 hours in the placebo group. The median score on the modified Rankin scale at 90 days was 3 in each group. The adjusted common odds ratio for the distribution of scores on the modified Rankin scale at 90 days for tenecteplase as compared with placebo was 1.13 (95% confidence interval, 0.82 to 1.57; P = 0.45). In the safety population, mortality at 90 days was 19.7% in the tenecteplase group and 18.2% in the placebo group, and the incidence of symptomatic intracranial hemorrhage was 3.2% and 2.3%, respectively., Conclusions: Tenecteplase therapy that was initiated 4.5 to 24 hours after stroke onset in patients with occlusions of the middle cerebral artery or internal carotid artery, most of whom had undergone endovascular thrombectomy, did not result in better clinical outcomes than those with placebo. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups. (Funded by Genentech; TIMELESS ClinicalTrials.gov number, NCT03785678.)., (Copyright © 2024 Massachusetts Medical Society.)

Importance: Stent retriever-based thrombectomy is highly beneficial in large vessel occlusion (LVO) strokes. Many stent retriever designs are currently available, but comparison of these technologies in well-conducted studies is lacking., Objective: To determine whether thrombectomy for LVO stroke with the pRESET stent retriever is noninferior to treatment with the Solitaire stent retriever., Design, Setting, and Participants: This study was a multicenter, prospective, randomized, controlled, open-label, adaptive, noninferiority trial with blinded primary end point evaluation. Between October 2019 and February 2022, multicenter participation occurred across 19 research hospitals and/or universities in the US and 5 in Germany. Patients with LVO stroke were enrolled and included up to 8 hours after symptom onset., Interventions: Patients underwent 1:1 randomization to thrombectomy with the pRESET or Solitaire stent retriever., Main Outcomes and Measures: The primary outcome was the difference in the rate of 90-day functional independence across the 2 devices, using a -12.5% noninferiority margin for the lower bound of the 1-sided 95% CI of the difference between pRESET and Solitaire retrievers., Results: Of 340 randomized patients, 170 (50.0%) were female, and the median (IQR) age was 73.0 (64.0-82.0) years. The study procedure was completed in 322 of the 340 randomized patients. The primary end point of 90-day functional independence was achieved by 95 patients (54.9%; 95% CI, 48.7-61.1) in the pRESET group and in 96 (57.5%; 95% CI, 51.2-63.8) in the Solitaire group (absolute difference, -2.57%; 95% CI, -11.42 to 6.28). As the lower bound of the 95% CI was greater than -12.5%, the pRESET retriever was deemed noninferior to the Solitaire retriever. The noninferiority of pRESET over Solitaire was also observed in the secondary clinical end point (90-day shift in modified Rankin Scale score) and in both angiographic end points (Expanded Treatment in Cerebral Infarction [eTICI] score of 2b50 or greater within 3 passes: 146 of 173 [84.4%] vs 149 of 167 [89.2%]; absolute difference, -4.83%; 95% CI, -10.84 to 1.19; eTICI of 2c or greater following the first pass: 76 of 173 [43.7%] vs 74 of 167 [44.3%]; absolute difference, -0.63%; 95% CI, -9.48 to 8.21). Symptomatic intracranial hemorrhage occurred in 0 patients in the pRESET group and 2 (1.2%) in the Solitaire group. Mortality occurred in 25 (14.5%) in the pRESET group and in 24 (14.4%) in the Solitaire group at 90 days. Findings of the per-protocol and as-treated analyses were in concordance with findings of the intention-to-treat analysis., Conclusions and Relevance: In this study, among patients with LVO stroke, thrombectomy with the pRESET stent retriever was noninferior to thrombectomy with the Solitaire stent retriever. Findings suggest that pRESET offers a safe and effective option for flow restoration and disability reduction in patients with LVO stroke.