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Objective: Among patients with large vessel occlusion (LVO) and large ischemic cores, critical decisions often need to be made about decompressive hemicraniectomy (DHC) or early withdrawal of life-sustaining therapy (WLST). In this study, we aimed to evaluate utilization of DHC and early WLST and factors associated with them in patients with large strokes from the SELECT2 trial., Methods: We analyzed the entire SELECT2 trial population, which randomized 352 patients with stroke due to LVO and large ischemic cores to endovascular thrombectomy (EVT) or medical management. We used the as-treated principle to compare the use of DHC and early WLST within 7 days after randomization. We further assessed functional outcomes (modified Rankin Score) after these decisions., Results: Of 352 patients enrolled in this study, 55 received DHC and 81 transitioned to early WLST. Patients treated with EVT were as likely to undergo DHC (16% vs 15%, adjusted relative risk [aRR] = 1.19, 95% CI:0.75-1.88, p = 0.46) or WLST (22% vs 24%, aRR = 0.94, 95% CI: 0.66-1.34, p = 0.72) as those given medical management. DHC was used more frequently in younger patients and WLST more in older patients. EVT efficacy was maintained after adjusting for DHC (adjusted generalized odds ratio [aGenOR] = 1.68, 95% CI: 1.24-2.11, p < 0.001), with no interaction between DHC and treatment (p-interaction = 0.93). At 1 year, 21% of DHC-treated patients were ambulatory; the outcomes were universally poor after early WLST., Interpretation: In the SELECT2 trial of patients with large ischemic core, DHC was performed in ~1 of 6 patients and early WLST in ~1 of 5 patients, without differences based on treatment with EVT or medical management, nor successful reperfusion. DHC or WLST did not detract from thrombectomy treatment benefit. Additionally, ~20% of patients achieved independent ambulation despite receiving DHC by the 1-year follow-up. The similar distribution of these critical care decisions provides reassurance that the overall trial outcomes were not biased by open-label treatment allocation. ANN NEUROL 2024., (© 2024 American Neurological Association.)

Endovascular thrombectomy (EVT) was shown to be safe and efficacious in patients with large core stroke in multiple randomized controlled trials. However, the impact of reperfusion and other procedural metrics on EVT outcomes in this population has not been well-characterized., Methods: From the SELECT2 trial, we evaluated the association between reperfusion status, first-pass effect (near-complete or complete reperfusion [extended thrombolysis in cerebral infarction (eTICI) 2c-3] in 1 pass), procedure time and primary technique (aspiration vs stent-retriever) with functional outcomes in patients receiving EVT across ASPECTS (3 vs 4 vs 5) and core estimate strata (<70 vs ≥70ml, <100 vs ≥100ml, and <150 vs ≥150ml)., Results: Of 180 patients who received thrombectomy, 144 (80%) achieved successful reperfusion (eTICI 2b-3) and demonstrated better clinical outcomes (adjusted generalized odds ratios [aGenOR]: 1.48, 95% confidence interval [CI]: 1.01-2.15), compared with unsuccessful reperfusion. Results were consistent across ASPECTS and core estimate strata. Additionally, complete or near-complete reperfusion (eTICI 2c-3) was associated with better functional outcome (aGenOR: 1.99, 95% CI: 1.33-2.97) in patients achieving successful reperfusion. Functional outcome point estimates favored those with first-pass-effect (42 of 167 (25%), aGenOR: 1.46, 95% CI: 0.96-2.24). Longer procedure time was associated with worse modified Rankin scale (mRS) distribution (aGenOR: 0.92, 95% CI: 0.87-0.96, p-value = 0.001 for 10 minutes increment). Aspiration-first technique was used in 43 of 154 (25%) patients and was not associated with higher reperfusion (88% vs 78%, p = 0.18) or better functional outcome (aGenOR: 0.74, 95% CI: 0.50-1.10) as compared with stent-retriever first., Interpretation: Successful reperfusion resulted in improved clinical outcomes in large core patients across baseline ischemic core strata. Near complete or complete reperfusion was further associated with better outcomes, whereas prolonged procedures were associated with worse outcomes. Results were consistent regardless of the technique used. ANN NEUROL 2024., (© 2024 American Neurological Association.)

Endovascular thrombectomy (EVT) safety and efficacy in patients with large core infarcts receiving oral anticoagulants (OAC) are unknown. In the SELECT2 trial (NCT03876457), 29 of 180 (16%; vitamin K antagonists 15, direct OACs 14) EVT, and 18 of 172 (10%; vitamin K antagonists 3, direct OACs 15) medical management (MM) patients reported OAC use at baseline. EVT was not associated with better clinical outcomes in the OAC group (EVT 6 [4-6] vs MM 5 [4-6], adjusted generalized odds ratio 0.89 [0.53-1.50]), but demonstrated significantly better outcomes in patients without OAC (EVT 4 [3-6] vs MM 5 [4-6], adjusted generalized odds ratio 1.87 [1.45-2.40], p = 0.02). The OAC group had higher comorbidities, including atrial fibrillation (70% vs 17%), congestive heart failure (28% vs 10%), and hypertension (87% vs 72%), suggesting increased frailty. However, the results were consistent after adjustment for these comorbidities, and was similar regardless of the type of OACs used. Whereas any hemorrhage rates were higher in the OAC group receiving EVT (86% in OAC vs 70% in no OAC), no parenchymal hemorrhage or symptomatic intracranial hemorrhage were observed with OAC use in both the EVT and MM arms. Although we did not find evidence that the effect was due to excess hemorrhage or confounded by underlying cardiac disease or older age, OAC use alone should not exclude patients from receiving EVT. Baseline comorbidities and ischemic injury extent should be considered while making individualized treatment decisions. ANN NEUROL 2024;96:887-894., (© 2024 American Neurological Association.)

Background: Psilocybin is a psychedelic 5HT2A receptor agonist found in "magic mushrooms". Recent studies have indicated that 5HT2A agonists, such as dimethyltryptamine, given before middle cerebral artery occlusion (MCAo), improve staircase behavior, increased BDNF expression, and reduce brain infarction in stroke rats. The objective of this study is to determine the protective effect of psilocybin in cellular and animal models of stroke., Methods: Adult male and timed-pregnant Sprague-Dawley rats were used for this study. The neural protective effects of psilocybin were determined in primary rat cortical neurons and adult rats. Rats were subjected to a 60-min middle cerebral artery occlusion. Brain tissues were collected for histological and qRTPCR analysis., Results: Psilocybin reduced glutamate-mediated neuronal loss in rat primary cortical neuronal cultures. Psilocybin-mediated protection in culture was antagonized by the BDNF inhibitor ANA12. Pretreatment with psilocybin reduced brain infarction and neurological deficits in stroke rats. Early post-treatment with psilocybin improved locomotor behavior, upregulated the expression of MAP2 and synaptophysin, and down-regulated the expression of IBA1 in the stroke brain. ANA12 significantly attenuated psilocybin-mediated reduction in brain infarction and improvements in locomotor behavior., Conclusions: Psilocybin reduced brain infarction and improved locomotor behavior in stroke rats; the protective mechanisms involve regulating BDNF expression. Our data support a novel therapeutic approach of psilocybin in stroke., (© 2024. The Author(s).)

Background: Our study explores the efficacy and economic benefits of neurosurgical teleconsultations in managing intracerebral hemorrhage (ICH), focusing on reducing unnecessary patient transfers and associated costs., Methods: We conducted a cost-savings analysis at our institution of a previously published pilot study involving a cohort of patients with ICH who were potential candidates for airlift to our tertiary care center but instead received neurosurgical consultation via teleconsultation to avoid the transfer. Data on patient demographics, distances, and costs were collected and analyzed to assess the economic impact of teleconsultations., Results: The cohort comprised 14 patients; we noted significant cost savings from avoiding interhospital transfers, ranging from $84,346.52 to $120,495.03 per patient. Teleconsultations facilitated immediate, collaborative decision-making between healthcare providers at community hospitals and a tertiary care center, reducing the need for expensive air transportation and unnecessary hospital transfers., Conclusions: Neurosurgical teleconsultations offer a cost-effective alternative to traditional patient transfer methods for ICH management, providing substantial economic benefits while maintaining high physician and patient-family satisfaction levels. This study underscores the potential of our teleneurosurgery program to significantly reduce costs by reducing unnecessary financial burdens on patients' families and healthcare systems., (Copyright © 2024. Published by Elsevier Inc.)

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.

Importance: Patients with large ischemic core stroke have poor clinical outcomes and are frequently not considered for interfacility transfer for endovascular thrombectomy (EVT)., Objective: To assess EVT treatment effects in transferred vs directly presenting patients and to evaluate the association between transfer times and neuroimaging changes with EVT clinical outcomes., Design, Setting, and Participants: This prespecified secondary analysis of the SELECT2 trial, which evaluated EVT vs medical management (MM) in patients with large ischemic stroke, evaluated adults aged 18 to 85 years with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) as well as an Alberta Stroke Program Early CT Score (ASPECTS) of 3 to 5, core of 50 mL or greater on imaging, or both. Patients were enrolled between October 2019 and September 2022 from 31 EVT-capable centers in the US, Canada, Europe, Australia, and New Zealand. Data were analyzed from August 2023 to January 2024., Interventions: EVT vs MM., Main Outcomes and Measures: Functional outcome, defined as modified Rankin Scale (mRS) score at 90 days with blinded adjudication., Results: A total of 958 patients were screened and 606 patients were excluded. Of 352 enrolled patients, 145 (41.2%) were female, and the median (IQR) age was 66.5 (58-75) years. A total of 211 patients (59.9%) were transfers, while 141 (40.1%) presented directly. The median (IQR) transfer time was 178 (136-230) minutes. The median (IQR) ASPECTS decreased from the referring hospital (5 [4-7]) to an EVT-capable center (4 [3-5]). Thrombectomy treatment effect was observed in both directly presenting patients (adjusted generalized odds ratio [OR], 2.01; 95% CI, 1.42-2.86) and transferred patients (adjusted generalized OR, 1.50; 95% CI, 1.11-2.03) without heterogeneity (P for interaction = .14). Treatment effect point estimates favored EVT among 82 transferred patients with a referral hospital ASPECTS of 5 or less (44 received EVT; adjusted generalized OR, 1.52; 95% CI, 0.89-2.58). ASPECTS loss was associated with numerically worse EVT outcomes (adjusted generalized OR per 1-ASPECTS point loss, 0.89; 95% CI, 0.77-1.02). EVT treatment effect estimates were lower in patients with transfer times of 3 hours or more (adjusted generalized OR, 1.15; 95% CI, 0.73-1.80)., Conclusions and Relevance: Both directly presenting and transferred patients with large ischemic stroke in the SELECT2 trial benefited from EVT, including those with low ASPECTS at referring hospitals. However, the association of EVT with better functional outcomes was numerically better in patients presenting directly to EVT-capable centers. Prolonged transfer times and evolution of ischemic change were associated with worse EVT outcomes. These findings emphasize the need for rapid identification of patients suitable for transfer and expedited transport., Trial Registration: ClinicalTrials.gov Identifier: NCT03876457.