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BACKGROUND AND OBJECTIVES: There is growing evidence for endovascular thrombectomy (EVT) in patients with large ischemic core infarct and large vessel occlusion (LVO). The objective of this study was to compare the efficacy and safety of EVT vs medical management (MM) using a systematic review and meta-analysis of observational studies and randomized controlled trials (RCTs). METHODS: We searched the PubMed, Embase, Cochrane Library, and Web of Science databases to obtain articles related to mechanical thrombectomy for large ischemic core from inception until February 10, 2023. The primary outcome was independent ambulation (modified Rankin Scale [mRS] 0-3). Effect sizes were computed as risk ratio (RR) with random-effect or fixed-effect models. The quality of articles was evaluated through the Cochrane risk assessment tool and the Newcastle-Ottawa Scale. This study was registered in PROSPERO (CRD42023396232). RESULTS: A total of 5,395 articles were obtained through the search and articles that did not meet the inclusion criteria were excluded by review of the title, abstract, and full text. Finally, 3 RCTs and 10 cohort studies met the inclusion criteria. The RCT analysis showed that EVT improved the 90-day functional outcomes of patients with large ischemic core with high-quality evidence, including independent ambulation (mRS 0-3: RR 1.78, 95% CI 1.28-2.48, p < 0.001) and functional independence (mRS 0-2: RR 2.59, 95% CI 1.89-3.57, p < 0.001), but without significantly increasing the risk of symptomatic intracranial hemorrhage (sICH: RR 1.83, 95% CI 0.95-3.55, p = 0.07) or early mortality (RR 0.95, 95% CI 0.78-1.16, p = 0.61). Analysis of the cohort studies showed that EVT improved functional outcomes of patients without an increase in the incidence in sICH. DISCUSSION: This systematic review and meta-analysis indicates that in patients with LVO stroke with a large ischemic core, EVT was associated with improved functional outcomes over MM without increasing sICH risk. The results of ongoing RCTs may provide further insight in this patient population.

Background and purposeThe Stroke Treatment Academic Industry Roundtable (STAIR) sponsored an imaging session and workshop during the Stroke Treatment Academic Industry Roundtable XI via webinar on October 1 to 2, 2020, to develop consensus recommendations, particularly regarding optimal imaging at primary stroke centers.MethodsThis forum brought together stroke neurologists, neuroradiologists, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke, industry representatives, and members of the US Food and Drug Administration to discuss imaging priorities in the light of developments in reperfusion therapies, particularly in an extended time window, and reinvigorated interest in brain cytoprotection trials.ResultsThe imaging session summarized and compared the imaging components of recent acute stroke trials and debated the optimal imaging strategy at primary stroke centers. The imaging workshop developed consensus recommendations for optimizing the acquisition, analysis, and interpretation of computed tomography and magnetic resonance acute stroke imaging, and also recommendations on imaging strategies for primary stroke centers.ConclusionsRecent positive acute stroke clinical trials have extended the treatment window for reperfusion therapies using imaging selection. Achieving rapid and high-quality stroke imaging is therefore critical at both primary and comprehensive stroke centers. Recommendations for enhancing stroke imaging research are provided.

Background Different studies have demonstrated the benefit of endovascular treatment (EVT) up to 24 hours after acute ischemic stroke (AIS) onset. Recent cohort observational studies suggest that patients with large vessel occlusion AIS may benefit from EVT beyond 24 hours from the last known well (LKW) when adequately selected. We aimed to examine the safety and efficacy of EVT beyond 24 hours from LKW using a meta-analysis of all the literature available. Methods A systematic search from inception to April 2023 was conducted for studies including AIS patients with EVT beyond 24 hours from LKW in Medline, Embase, Scopus, and Web of Science. Outcomes of interest included favorable functional outcome (90-day modified Rankin scale (mRS) 0-2), successful reperfusion (modified Thrombolysis in Cerebral Infarction (mTICI) 2b-3), symptomatic intracerebral hemorrhage (sICH), and 90- day mortality. Data were pooled using a random-effects model. Results Twelve studies with 894 patients were included. The rate of favorable functional outcome was 40% (95% CI 31% to 49%; I²=76%). The rate of successful reperfusion was 83% (95% CI 80% to 85%; I²=0%). The sICH rate was 7% (95% CI 5% to 9%; I²=0%) and the 90-day mortality rate was 28% (95% CI 24% to 33%; I²=0%). There was no significant difference in favorable outcomes (OR=0.69; 95% CI 0.41 to 1.14) and 90-day mortality (OR=1.35; 95% CI 0.90 to 2.00) among patients who underwent EVT <24 hours versus >24 hours. Conclusions EVT beyond 24 hours from LKW may achieve favorable clinical outcomes and high reperfusion rates, with acceptable intracranial hemorrhage rates in selected patients. Considering the current certainty of the evidence and heterogenous individual study results, larger prospective trials are warranted. [ABSTRACT FROM AUTHOR]

Key Points: Question: Does the benefit from endovascular thrombectomy for patients with large ischemic strokes caused by large vessel occlusion vary by the extent of presenting ischemic injury? Findings: In an exploratory analysis of a randomized clinical trial that included 336 participants, while functional outcomes worsened as baseline ischemic core volumes increased, endovascular thrombectomy was associated with better clinical outcomes across a wide spectrum of ischemic changes and penumbra profiles on various imaging modalities compared with medical management. Meaning: Endovascular thrombectomy, compared with medical management, improved clinical outcomes across a wide spectrum of ischemic core volumes and penumbral profiles; however, large ischemic core volume is an important prognostic factor to consider when individualizing treatment decisions. Importance: Whether endovascular thrombectomy (EVT) efficacy for patients with acute ischemic stroke and large cores varies depending on the extent of ischemic injury is uncertain. Objective: To describe the relationship between imaging estimates of irreversibly injured brain (core) and at-risk regions (mismatch) and clinical outcomes and EVT treatment effect. Design, Setting, and Participants: An exploratory analysis of the SELECT2 trial, which randomized 352 adults (18-85 years) with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) and large ischemic core to EVT vs medical management (MM), across 31 global centers between October 2019 and September 2022. Intervention: EVT vs MM. Main Outcomes and Measures: Primary outcome was functional outcome—90-day mRS score (0, no symptoms, to 6, death) assessed by adjusted generalized OR (aGenOR; values >1 represent more favorable outcomes). Benefit of EVT vs MM was assessed across levels of ischemic injury defined by noncontrast CT using ASPECTS score and by the volume of brain with severely reduced blood flow on CT perfusion or restricted diffusion on MRI. Results: Among 352 patients randomized, 336 were analyzed (median age, 67 years; 139 [41.4%] female); of these, 168 (50%) were randomized to EVT, and 2 additional crossover MM patients received EVT. In an ordinal analysis of mRS at 90 days, EVT improved functional outcomes compared with MM within ASPECTS categories of 3 (aGenOR, 1.71 [95% CI, 1.04-2.81]), 4 (aGenOR, 2.01 [95% CI, 1.19-3.40]), and 5 (aGenOR, 1.85 [95% CI, 1.22-2.79]). Across strata for CT perfusion/MRI ischemic core volumes, aGenOR for EVT vs MM was 1.63 (95% CI, 1.23-2.16) for volumes ≥70 mL, 1.41 (95% CI, 0.99-2.02) for ≥100 mL, and 1.47 (95% CI, 0.84-2.56) for ≥150 mL. In the EVT group, outcomes worsened as ASPECTS decreased (aGenOR, 0.91 [95% CI, 0.82-1.00] per 1-point decrease) and as CT perfusion/MRI ischemic core volume increased (aGenOR, 0.92 [95% CI, 0.89-0.95] per 10-mL increase). No heterogeneity of EVT treatment effect was observed with or without mismatch, although few patients without mismatch were enrolled. Conclusion and Relevance: In this exploratory analysis of a randomized clinical trial of patients with extensive ischemic stroke, EVT improved clinical outcomes across a wide spectrum of infarct volumes, although enrollment of patients with minimal penumbra volume was low. In EVT-treated patients, clinical outcomes worsened as presenting ischemic injury estimates increased. Trial Registration: ClinicalTrials.gov Identifier: NCT03876457 This exploratory analysis of the SELECT2 trial assesses the relationship between imaging estimates of irreversibly injured brain (core) and at-risk regions (mismatch) and the association of mismatch with clinical outcomes and endovascular treatment effect in adult patients with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery and large ischemic core in 31 global centers between October 2019 and September 2022. [ABSTRACT FROM AUTHOR]

Background and purposeIntra-arterial therapy (IAT) promotes recanalization of large artery occlusions in acute ischemic stroke. Despite high recanalization rates, poor clinical outcomes are common. We attempted to optimize a score that combines clinical and imaging variables to more accurately predict poor outcome after IAT in anterior circulation occlusions.MethodsPatients with acute ischemic stroke undergoing IAT at University of Texas (UT) Houston for large artery occlusions (middle cerebral artery or internal carotid artery) were reviewed. Independent predictors of poor outcome (modified Rankin Scale, 4-6) were studied. External validation was performed on IAT-treated patients at Emory University.ResultsA total of 163 patients were identified at UT Houston. Independent predictors of poor outcome (P≤0.2) were identified as score variables using sensitivity analysis and logistic regression. Houston Intra-Arterial Therapy 2 (HIAT2) score ranges 0 to 10: age (≤59=0, 60-79=2, ≥80 years=4), glucose (

Introduction: Endovascular treatment (EVT) is a widely proven method to treat patients diagnosed with intracranial large vessel occlusion (LVO). Through this method of treatment, it has been hypothesized that a lower number of thrombectomy passes is an indicator of higher rates of modified Thrombolysis in Cerebral Infarction 2B-3 (mTICI) reperfusion and favorable outcomes at 90-days defined as modified Rankin Scale 0-2 (mRS). Methods: Through the utilization of a prospectively collected endovascular database between 2012-2020, variables such as demographics, co-morbid conditions, intracerebral hemorrhage, mass effect, mortality rate, and good/poor outcomes regarding mTICI score and mRS assessment at 90-days were examined. The outcomes between patients receiving EVT who were treated with < 3 thrombectomy passes or ≥3 passes were compared. Results: Out of 454 patients treated with mechanical thrombectomy of qualifying intracranial internal carotid artery (ICA) or middle cerebral artery occlusion, site of occlusion (ICA, ICA-T M1, and M2/M3), a total of 372 (81.9%) were treated with < 3 passes (average age 70.34 ± 13.75 years, 46.0% women), and 82 (18.1%) were treated with ≥3 passes (average age 70.30 ± 13.72 years, 48.8% women). Significantly higher rates of mass effect (p = 0.043), mRS score 3–6 (p = 0.029), mortality (p = 0.025), and poor reperfusion (p < 0.0001) were noted in patients treated with ≥3 passes. Conclusion: A higher number of thrombectomy passes, characterized as ≥3 in this study, was associated with significantly worsened patient outcome regarding mRS and mortality. Further research is required to determine whether the number of thrombectomy passes is an accurate predictor of treatment outcome. [ABSTRACT FROM AUTHOR]

Objective: Reperfusion therapy is highly beneficial for ischemic stroke. Reduction in both infarct growth and edema are plausible mediators of clinical benefit with reperfusion. We aimed to quantify these mediators and their interrelationship. Methods: In a pooled, patient‐level analysis of the EXTEND‐IA trials and SELECT study, we used a mediation analysis framework to quantify infarct growth and cerebral edema (midline shift) mediation effect on successful reperfusion (modified Treatment in Cerebral Ischemia ≥ 2b) association with functional outcome (modified Rankin Scale distribution). Furthermore, we evaluated an additional pathway to the original hypothesis, where infarct growth mediated successful reperfusion effect on midline shift. Results: A total 542 of 665 (81.5%) eligible patients achieved successful reperfusion. Baseline clinical and imaging characteristics were largely similar between those achieving successful versus unsuccessful reperfusion. Median infarct growth was 12.3ml (interquartile range [IQR] = 1.8–48.4), and median midline shift was 0mm (IQR = 0–2.2). Of 249 (37%) demonstrating a midline shift of ≥1mm, median shift was 2.75mm (IQR = 1.89–4.21). Successful reperfusion was associated with reductions in both predefined mediators, infarct growth (β = −1.19, 95% confidence interval [CI] = −1.51 to −0.88, p < 0.001) and midline shift (adjusted odds ratio = 0.36, 95% CI = 0.23–0.57, p < 0.001). Successful reperfusion association with improved functional outcome (adjusted common odds ratio [acOR] = 2.68, 95% CI = 1.86–3.88, p < 0.001) became insignificant (acOR = 1.39, 95% CI = 0.95–2.04, p = 0.094) when infarct growth and midline shift were added to the regression model. Infarct growth and midline shift explained 45% and 34% of successful reperfusion effect, respectively. Analysis considering an alternative hypothesis demonstrated consistent results. Interpretation: In this mediation analysis from a pooled, patient‐level cohort, a significant proportion (~80%) of successful reperfusion effect on functional outcome was mediated through reduction in infarct growth and cerebral edema. Further studies are required to confirm our findings, detect additional mediators to explain successful reperfusion residual effect, and identify novel therapeutic targets to further enhance reperfusion benefits. ANN NEUROL 2023;93:793–804 [ABSTRACT FROM AUTHOR]