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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: Isolated anterior cerebral artery occlusions (ACAo) in patients with acute ischemic stroke present significant challenges due to their rarity. The efficacy and safety of endovascular therapy (EVT) in comparison with best medical therapy (BMT) for ACAo remains unclear. This study aimed to assess the outcomes of these treatments., Methods: This multinational, multicenter study analyzed data from the MAD-MT registry. Data were collected retrospectively from 37 sites across North America, Asia, and Europe. Inverse probability of treatment weighting (IPTW) was applied to balance confounding variables. The primary outcome was functional independence (modified Rankin Scale (mRS) scores of 0-2) at 90 days. Secondary outcomes included excellent outcomes (mRS 0-1), mortality at 90 days, and NIH Stroke Scale (NIHSS) score on day 1 post treatment., Results: Of the 108 patients, 36 received BMT and 72 underwent EVT. The median age was 75 years, and 56% were male. At 90 days, 40% of patients achieved mRS 0-2, with no significant difference between EVT and BMT (38% vs 45%, p=0.46). Procedural success (mTICI 2b-3) was 91% in the EVT group, with a sICH rate of 2.9%. IPTW-adjusted analysis showed no significant difference between EVT and BMT for functional independence (OR 1.17, 95% CI 0.23 to 6.02, p=0.85), mortality (25% vs 21%, p=0.71) or day 1 NIHSS scores (Beta 2.2, 95% CI -0.51 to 4.8, p=0.11)., Conclusions: EVT showed high procedural success but did not significantly improve functional outcomes or mortality compared with BMT in patients with ACAo. Further randomized trials are needed to clarify EVT's role in ACAo., Competing Interests: Competing interests: RWR 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. AG reports consultancy for Rapid Medical and Phenox, not directly related to the present work. FC 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. NH received support from NINDS NS131756, NINR NR020231, and NINDS NS113844 during the conduct of the study. All unrelated to the present work. DSL is consultant as Imaging Core Lab to Cerenovus, Genentech, Medtronic, Stryker, Rapid Medical. LLLY 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. CJG reports a proctoring agreement with Medtronic and research funding by Penumbra. GM reports conflicts of interest with Microvention Europe, Stryker Neurovascular, Balt, Sim and Cure (consulting), Medtronic, Johnson & Johnson, Penumbra, Bracco, and Phenox (paid lectures), all not directly related to the present work. ASP 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). PJ is a consultant for Medtronic, Microvention and Cerus. BP reports consultancy Microvention, Stryker, Q’apel, and Nuvascular, all not directly related to the present work. JES has served as a consultant for AstraZeneca, and has received funding from the National Institutes of Health (R61NS135583), Viz.ai, Philips, and Medtronic. TNN reports Associate Editor of Stroke; advisory for Aruna Bio, Brainomix., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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: Large vessel occlusion acute ischemic stroke prognosis improved following the 2015 endovascular therapy (EVT) trials. Blood-based biomarkers may improve outcome prediction. We aimed to assess plasma brain-derived tau (BD-Tau) performance in predicting post-EVT large vessel occlusion acute ischemic stroke outcomes., Methods: We included 2 temporally independent prospective cohorts of anterior circulation in patients with large vessel occlusion acute ischemic stroke who successfully recanalized post-EVT. We measured plasma BD-Tau, GFAP (glial-fibrillary-acidic-protein), NfL (neurofilament-light-chain), and total-Tau upon admission, immediately, 24 hours, and 72 hours post-EVT. Twenty-four-hour neuroimaging and 90-day functional outcomes were independently assessed using the Alberta Stroke Program Early Computed Tomography Score (good outcome: >7 or unchanged) and the modified Rankin Scale (favorable outcome <3 or unchanged), respectively. Based on the first cohort (derivation), we built a multivariable logistic regression model to predict a 90-day functional outcome. Model results were evaluated using the second cohort (evaluation)., Results: In the derivation cohort (n=78, mean age=72.9 years, 50% women), 62% of patients had a good 24-hour neuroimaging outcome, and 45% had a favorable 90-day functional outcome. GFAP admission-to-EVT rate-of-change was the best predictor for early neuroimaging outcome but not for 90-day functional outcome. At admission, BD-Tau levels presented the highest discriminative performance for 90-day functional outcomes (area under the curve, 0.76 [95% CI, 0.65-0.87]; P <0.001). The model incorporating age, admission BD-Tau, and 24-hour Alberta Stroke Program Early Computed Tomography Score achieved excellent discrimination of 90-day functional outcome (area under the curve, 0.89 [95% CI, 0.82-0.97]; P <0.001). The score's predictive performance was maintained in the evaluation cohort (n=66; area under the curve, 0.82 [95% CI, 0.71-0.92]; P <0.001)., Conclusions: Admission plasma BD-Tau accurately predicted 90-day functional outcomes in patients with large vessel occlusion acute ischemic stroke after successful EVT. The proposed model may predict functional outcomes using objective measures, minimizing human-related biases and serving as a simplified prognostic tool for AIS., Competing Interests: Dr Maia reports compensation from Alnylam Pharmaceuticals and Bristol-Myers Squibb Company for consultant services. Dr Blennow reports compensation from Eli LIlly, EISAI INC, and F. Hoffmann-La Roche for consultant services. Dr Karikari reports grants from Vetenskapsrådet; a patent issued for Use of a ps396 assay to diagnose tauopathies https://patents.google.com/patent/WO2020193500A1/en; and grants from National Institutes of Health. Dr Zetterberg has served at scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Annexon, Apellis, Artery Therapeutics, AZTherapies, CogRx, Denali, Eisai, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, and given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, Biogen, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB, which is a part of the GU Ventures Incubator Program (outside submitted work). N.L. Knuth reports a patent on the use of BD-Tau.

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.)