BACKGROUND:Cerebral edema is a life-threatening complication of ischemic stroke that disproportionally affects patients with large established infarction. We assessed whether endovascular thrombectomy (EVT) reduces or exacerbates edema development, and the association between edema with short-term and long-term outcomes in this high-risk population. METHODS:In this prespecified secondary analysis of the SELECT2 randomized clinical trial (Randomized Controlled Trial to Optimize Patient's Selection for Endovascular Treatment in Acute Ischemic Stroke), which tested the efficacy and safety of EVT versus medical management in adult patients with acute anterior circulation large vessel occlusion presenting with large ischemic core (defined as Alberta Stroke Program Early Computed Tomography Score of 3-5 or core volume ≥50 mL on computed tomography perfusion or diffusion magnetic resonance imaging), we assessed maximum midline shift (MLS) within 7 days of randomization between treatment groups using a probabilistic index model. RESULTS:After exclusion of 10 patients who underwent hemicraniectomy before follow-up imaging, 342 patients were analyzed. The median MLS on follow-up magnetic resonance imaging or computed tomography was 6.39 mm (interquartile range, 0-12.0) in the EVT and 4.18 mm (interquartile range, 0-9.66) in medical management patients (P=0.021). EVT was independently associated with greater MLS (adjusted odds ratio, 1.63 [95% CI, 1.25-2.12]; P=0.0027) after adjusting for age and core volume. There was no interaction between EVT and core volume at presentation on the association with MLS (P>0.79). MLS was associated with the development of early neurological worsening (adjusted odds ratio, 1.15 [95% CI, 1.07-1.23]; P<0.001), and a lower likelihood of long-term functional improvement assessed on modified Rankin Scale score at 90 days (adjusted odds ratio, 0.96 [95% CI, 0.93-0.98]; P=0.0029). On mediation analysis, cerebral edema reduced the effect of EVT on functional outcome by 10.6%. CONCLUSIONS:Despite overall clinical benefit, EVT in patients presenting with a large ischemic core was associated with increased cerebral edema, which, in turn, was associated with early neurological worsening and worse functional outcome at 90 days. Early recognition and individualized treatment to prevent secondary injury from cerebral edema in this population are warranted. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT03876457.

Introduction: Direct-to-angio(DTA) approach has been shown to reduce time to endovascular thrombectomy(EVT) and is associated with improved functional outcomes, but detailed evaluation of DTA approach in late and very late windows has not been explored yet. We aimed to assess the association of DTA vs repeat imaging(RI) approach with functional and safety outcomes across <6hr vs ≥ 6hr and <12hr vs ≥12hr time windows. Methods: In a secondary analysis of a retrospective cohort study, transferred patients who received EVT under DTA vs RI approach were stratified based on time from last known well(LKW) to procedure into <6hr vs ≥ 6hr and <12hr vs ≥12hr. The association of DTA vs RI approach with functional and safety outcomes were assessed using appropriate regression models, adjusted for age, occlusion location, stroke severity, serum glucose, time to procedure and successful reperfusion(mTICI 2b-3) status. Results: Of 1140 participants, 621(54%) received EVT <6 hours(DTA:202, RI:419) and 519(46%) received EVT ≥6 hours(DTA:125, RI:394) – of which 196(17%) received EVT ≥12 hours(DTA:47, RI:149). Age, sex, stroke severity and anesthesia type were similar, however, DTA patients had lower serum glucose and more frequent witnessed stroke onset. Better functional outcome with DTA sustained among <12hr(acOR:1.44, 95%CI:1.09-1.90, p=0.01) vs ≥12hr(acOR:2.60, 95%CI:1.32-5.13, p=0.006, p-int=0.19), with similer other functional outcomes. sICH was similar across <12hr(DTA:9.4% vs RI:9.9%, aOR:1.09, 95%CI:0.65-1.83, p=0.73) and ≥12hr(DTA:4.3% vs RI:11.6%, aOR:0.16, 95%CI:0.02-1.35, p=0.09, p-int=0.16). Both low (NIHSS<15) and high NIHSS (≥15) at presentation had improved outcomes with DTA among ≥12hr (<15: acOR:2.79, 95%CI: 0.90-8.66, p=0.075, ≥15: acOR:3.03, 95%CI: 1.29-7.09, p=0.011, p-int=0.83). Similar results were also observed across <6hr vs ≥6hr. Conclusions: Association of DTA with improved outcomes persevered ≥6 and ≥12hr of LKW, without an increase in symptomatic hemorrhage, including patients with both low and high stroke severity. These exploratory findings suggest that feasibility of DTA approach can be extended to EVT patients in late and very late time window without undue safety risks.

Introduction: Severe CT-hypodensity, representing blood-brain-barrier (BBB) injury, has been shown to modify endovascular therapy (EVT) treatment effect in patients presenting with large core stroke. Net water uptake (NWU), reflecting average hypodensity within the lesion, is another measure of BBB injury and has been shown to be prognostic of poor outcome, but whether it modifies EVT treatment effect is unclear. Methods: We performed a comparative analysis of severe CT-hypodensity and NWU in patients enrolled into SELECT2, a randomized trial of EVT and medical management (MM) in patients with large core stroke (ASPECTS 3-5 or CTP core ≥50ml). Visible CT-hypodensity was manually outlined on baseline imaging. Severe CT-hypodensity was defined as the volume of core voxels <26HU (Hounsfield units). NWU was calculated using the standard method of percentage relative hypodensity versus a contralateral mirror region-of-interest, after exclusion of CSF and artifacts. The primary outcome was mRS 0-3 at 90 days. The associations between severe CT-hypodensity, NWU and the primary outcome were evaluated in separate logistic regression models within EVT and MM arms, adjusted for age, NIHSS, and total CT-core volume. Model performance between severe hypodensity and NWU was compared using Bayesian Information Criterion (BIC). Results: In 318 patients (51% EVT, 49% MM), the median volume of severe hypodensity (EVT: 13.8mL [IQR: 5.1 - 27.0], MM: 15.9mL [IQR: 6.7 - 31.5]) and NWU (EVT: 9.2% [IQR: 6.3 - 13.3], MM: 9.8% [IQR: 7.4 - 13.4]) was balanced between the two treatment groups. The volume of severe hypodensity (per 1mL increase) was associated with a lower odds of mRS 0-3 with EVT (aOR=0.97, 95% CI:0.94-99) but not with MM (aOR=1.01, 95% CI:0.98-1.05, p-interaction<0.01). An increase in NWU (per % increase) was not significantly associated with a lower odds of mRS 0-3 with EVT (aOR=0.96, 95%CI: 0.89-1.024) or MM (aOR=0.96, 95% CI:0.87-1.05, p-interaction=0.86; Figure). Models including severe hypodensity provided a better fit for the primary outcome, compared to models including NWU (delta BIC of 5, favoring severe hypodensity). Conclusions: In patients with large core stroke, the volume of severe CT-hypodensity was associated with clinical outcome and modified EVT treatment effect. NWU did not modify EVT treatment effect. These findings suggest that severe CT-hypodensity may be the preferred imaging criterion when considering EVT treatment decisions.

BACKGROUND:Patients with extensive ischaemic change are often excluded from endovascular thrombectomy. We aimed to synthesise the evidence from recent trials in these patients by performing a systematic review and individual patient data meta-analysis to estimate treatment benefit, including within clinical and imaging subgroups. METHODS:In this systematic review and meta-analysis, we searched PubMed and Embase for randomised trials published between March 1, 2018, and March 1, 2025, that evaluated efficacy and safety of endovascular thrombectomy compared with medical management in patients with large-core ischaemic stroke (based on an Alberta Stroke Program Early CT Score [ASPECTS] of ≤5 or estimated ischaemic core ≥50 mL) presenting within 24 h of onset. Individual patient-level data from all eligible trials were obtained. A central imaging core laboratory readjudicated ASPECTS and reanalysed ischaemic core volume. A two-stage meta-analysis with random-effects model was used to evaluate the distribution of 90-day modified Rankin Scale (mRS) scores (the primary outcome) using adjusted pooled generalised odds ratios (aGenORs). Missing data were handled by multiple imputation. Safety outcomes were all-cause mortality within 90-day follow-up and neurological worsening within 24-48 h of randomisation, reported as adjusted pooled relative risk (aRR); and symptomatic intracerebral haemorrhage within 36 h of randomisation (reported as risk difference). Subgroup analyses based on clinical and imaging characteristics were done, including subgroups defined by ischaemic core volume, ASPECTS, and time window from onset to randomisation. The meta-analysis was registered with PROSPERO (CRD420251058584). FINDINGS:We included 1886 patients (944 assigned to endovascular thrombectomy and 942 assigned to medical management) from six trials. Baseline characteristics were similar between treatment groups. At day 90, the distribution of mRS scores was improved in patients in the endovascular thrombectomy group (median score 4 [IQR 3-6]; n=940) versus those in the medical management group (5 [4-6]; n=931; aGenOR 1·63 [95% CI 1·42-1·88], p<0·0001). The endovascular thrombectomy group also had reduced mortality (292 [31·1%]) compared with the medical management group (347 [37·3%]; aRR 0·82 [95% CI 0·70-0·97], p=0·022). No significant differences were observed in symptomatic intracranial haemorrhage (ten [1·1%] of 944 vs nine [1·0%] of 942 patients; pooled unadjusted risk difference -0·17 percentage points [95% CI -1·01 to 0·67], p=0·69) or neurological worsening (197 [22·0%] of 896 patients vs 161 [17·9%] of 899; aRR 1·19 [0·87-1·62], p=0·27). Improved functional outcomes with endovascular thrombectomy were consistent across clinical and imaging subgroups, except for those with an estimated ischaemic core volume of 150 mL or greater, in whom point estimates favoured endovascular thrombectomy, particularly in the early time window (0-6 h), but wide 95% CIs limited interpretation. INTERPRETATION:Endovascular thrombectomy was associated with improved functional outcomes and reduced mortality versus medical management in patients with large-core ischaemic stroke presenting within 24 h of onset. With the exception of very extensive ischaemic changes (core volume ≥150 mL) presenting beyond 6 h, where evidence remains limited, benefit was sustained across ASPECTS and ischaemic core strata for patients presenting up to 24 h after onset. FUNDING:None.

INTRODUCTION:Partially thrombosed intracranial aneurysms (PTIAs) are rare, complex, and have a distinct natural history compared with non-thrombosed aneurysms. PTIAs show increased rates of recurrence despite angiographic intraluminal occlusion following endovascular treatment (EVT). Our single-center experience, along with a systematic review, identifies presenting features, rates of angiographic occlusion, complications, recurrence, and retreatment. METHODS:A single-center retrospective review of consecutive patients with PTIA using imaging-based inclusion criteria was performed. Rates of angiographic occlusion, complications, recurrence, and retreatment were evaluated. In conjunction, a systematic review was conducted in accordance with PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) guidelines through PubMed, Scopus, and Google Scholar searches for studies on EVT of PTIA. After pooling patients undergoing EVT, presenting features and rates of occlusion and retreatment were assessed. RESULTS:Between 2018 and 2023, 22 PTIAs met imaging-based inclusion criteria. Eighteen underwent EVT: four coiling, two stent-assisted coiling, 11 flow diversion (FD), and one FD-assisted coiling. Mass effect was the most common symptom to herald diagnosis (8/18, 44.4%). Of 12 patients with adequate follow-up, 58% had near-complete or complete occlusion, 22% recurred, and 22% were retreated. For the systematic review, a total of 12 retrospective studies were included. In pooled analysis (n=259), including the present series, complete occlusion was achieved in 62%, 80%, 78%, and 100% for coiling±stent, Woven EndoBridge (WEB), FD, and parent vessel occlusion (PVO), respectively. Retreatment occurred in 51%, 54%, 15%, and 3% with coiling±stent, WEB, FD, and PVO, respectively. CONCLUSION:PTIAs have a complex pathogenesis, poor natural history, and often undergo retreatment. The results suggest FD to be an increasingly utilized treatment option. Coil±stent and the WEB device appear to have poorer outcomes and higher retreatment rates. If able to tolerate, PVO remains a viable option with high occlusion and low retreatment rates.

Prognosis after acute stroke varies widely and is usually guided by imaging and clinical markers. Factors such as frailty, cognition, comorbidities, mental health, social support, and financial status strongly influence recovery but are rarely considered. To address this gap, we developed the ELAN Score, a structured 10-point tool across six domains: cognition, pre-existing disability/frailty, comorbidities, mental health, social support and financial factors. Using a global survey, we aimed to evaluate associations between individual ELAN domains and clinicians’ prediction of recovery and coping potential after a stroke. In an international online survey, stroke neurologists, neurointerventionalists, and allied specialists were randomly assigned 30 of 324 case vignettes. Each vignette described a patient with large vessel occlusion, good ASPECTS who achieved TICI 3 reperfusion, and systematically varied the severity of ELAN-specific domains. Participants were blinded to the ELAN score; scores were calculated in the background using pre-specified domain weights. Respondents were asked to estimate: the probability of return to pre-stroke functional status, and the probability of coping with an unfavorable outcome. Associations between ELAN score, individual domains, and perceived outcomes were examined using mixed-effects Poisson regression adjusted for clinician demographics, specialty, and country, with participant ID as random effect. Forty-eight participants (33% stroke neurologists, 37% interventionists; 78% >10 years’ experience; 37% women) from 18 countries completed the survey. Higher ELAN scores were significantly associated with lower probability of both respondent-predicted functional recovery and coping potential (adjIRR 0.93, 95% CI 0.91–0.95 and 0.91, 95% CI 0.90–0.93, respectively, Figure 1). In multivariable models, cognitive impairment, pre-existing disability, multiple comorbidities, and limited financial resources were consistently perceived as predictors of poor recovery, while cognition, disability, and finances were key for coping potential (Tables 1–2). Mental health and social support were not perceived as independent predictors. Clinicians in this international vignette-based survey recognized cognition, disability, and financial status as key determinants of outcome. Future work should test ELAN prospectively in diverse healthcare systems and evaluate whether structured incorporation of these factors improves prognostic accuracy.

Background: Endovascular treatment (EVT) is effective for patients with large ischemic cores caused by a large vessel occlusion. The size and severity of hypodense tissue on non-contrast CT (NCCT) in the ischemic core predict poor outcomes despite successful EVT. Automated ASPECTS tools can estimate the size and severity of hypodensity on NCCT, but these estimates do not accurately represent the ischemic core. Deep learning (DL) based segmentation of hypodensity on NCCT may offer improved precision. We compared the associations between (1) ischemic core volume on CTP, (2) manually segmented, or (3) DL segmented hypodensity volumes on NCCT and outcomes after EVT or medical management (MM) in patients with a large ischemic core. Methods: We performed a post-hoc analysis of SELECT2 trial patients. The volume of total hypodense (all segmented voxels) and severely hypodense (segmented voxels with ≤26 HU) tissue was measured on baseline NCCT using an externally validated DL model or manual segmentations (Figure 1). The ischemic core volume was determined using CTP (rCBF<30%). We assessed agreement between DL and manually delineated volumes with the concordance correlation coefficients (CCC). Zou's Modified Poisson regression adjusted for age and baseline NIHSS was used to estimate the association of volume measures with 90-day independent ambulation (modified Rankin Scale ≤3), stratified by MM and EVT arms. Interaction p-values assessed whether volume measures modified EVT benefit. Results: 316 patients were included (154 MM, 162 EVT). Agreement between manual and DL segmented volumes was (CCC: 0.73[95%CI:0.67-0.78]) for total hypodense volume and (CCC: 0.90[95%CI:0.88-0.92]) for severely hypodense volume (Figure 2A-2B). Although manual and DL total hypodense volume on NCCT and ischemic core volume on CTP or MRI were associated with lower proportions of independent ambulation after EVT, we observed no association with EVT benefit (rows 1-3 Table 1). Severely hypodense volumes determined with either DL or manual segmentations were associated with a lower chance of independent ambulation after EVT and were significantly associated with reduced EVT benefit (rows 4-5 Table 1, Figure 2C-D). Conclusion: Severely hypodense volumes on NCCT are comparable between automated deep learning and manual segmentations. Our findings suggest that automated deep learning quantification of severe hypodensity on NCCT can help to identify patients less likely to benefit from EVT.

OBJECTIVE Venous sinus stent placement is an increasingly common endovascular technique for treating medically refractory symptoms related to idiopathic intracranial hypertension (IIH). Given that data suggest that a considerable number of patients experience symptom relapse or recurrence, understanding prognosticators of treatment failure is of particular interest. METHODS The authors performed a single-center retrospective review of the medical records of surgically naive patients with IIH who underwent unilateral transverse sinus stent (TSS) placement. Pre-stent clinical, anatomical, and manometric variables were evaluated against post-stent outcomes to determine significant predictors of unfavorable outcomes after treatment. RESULTS Forty-two surgically naive patients with IIH underwent unilateral TSS insertion between April 2011 and February 2024. At a mean follow-up of 41 months, 47.6% had ongoing symptoms, 38.1% received escalated medical therapy, 23.8% underwent stent restenosis, and 23.8% underwent procedural retreatment. Younger age at the time of initial stent insertion was associated with post-stent operative retreatment (OR 1.15, p = 0.04), while lower pre-stent BMI predicted resolution of papilledema (OR 0.84, p = 0.003). Higher pre-stent BMI and lower pre-stent pressure gradients were associated with several unfavorable outcomes. CONCLUSIONS Modifiable and unmodifiable risk factors may impact TSS durability for IIH. Larger multicenter studies are warranted to stratify risk for futile TSS outcomes and characterize the ideal IIH candidate for therapy.

Objectives Since 2015, clinical trials have broadened the indications for mechanical thrombectomy for acute ischemic stroke (AIS), including extended time windows and larger infarct cores. Evolving guidelines may create uncertainty in the standard of care. Malpractice litigation offers insight into how these standards are interpreted. This study aimed to identify malpractice allegation patterns. Design Retrospective descriptive medico-legal study of published US malpractice cases. Setting Search terms including “stroke,” “thrombectomy,” and “medical malpractice” were queried in Google Scholar Case Law, LexisNexis, Westlaw, CaseText, and Bloomberg Law through 2026. Participants 25 representative malpractice cases involving stroke thrombectomy for AIS were identified from 365 reviewed case files. Main outcome measures Plaintiff allegations, litigation rulings, defendant characteristics, vascular anatomy, and recurring medico-legal fact patterns. Results From 2009 to 2026, 25 of 365 case files involved thrombectomy malpractice. Four patterns formed plaintiffs’ arguments: adherence to hospital protocol (n=10; 40%), dismissive communication (n=3; 12%), delay or failure to obtain imaging (n=19; 76%) and delay or failure to obtain expert consultation (n=15; 60%). Allegations of failure to diagnose or treat occurred in nine cases (47%). No cases alleged thrombectomy procedural complications. Rulings favored defendants (n=5; 24%), plaintiffs (n=4; 19%), or no final ruling (n=12; 57%). Conclusions Failure to treat and delayed diagnosis were the most common allegations against physicians managing thrombectomy patients, consistent with intravenous stroke thrombolysis litigation. However, these findings are limited by small sample size and reliance on publicly available case law. As thrombectomy indications evolve, scrutiny surrounding imaging and treatment decisions may increase.

BACKGROUND:Wide-necked intracranial aneurysms present unique challenges for endovascular treatment. The Comaneci device is a novel temporary bridging device designed to assist coil embolization without parent vessel occlusion. METHODS:The SUccess in Comaneci-assist Coils Embolization Surveillance Study (SUCCESS) was a multicenter, prospective, postmarket surveillance study conducted at 17 US centers. Ninety consecutive patients with wide-necked intracranial aneurysms were treated with Comaneci-assisted coiling. The primary effectiveness endpoint was successful aneurysm occlusion (Raymond-Roy class I/II) at procedure end. Primary safety endpoints included periprocedural events within 24 hours and clinical outcomes at discharge and 30 days. RESULTS:Of 90 enrolled patients (mean age 63 years, 63% female), 32 (36%) presented with ruptured aneurysms. Most common locations were anterior communicating (33%), internal carotid (20%), and posterior communicating arteries (19%). Successful occlusion was achieved in 85.6% of cases at procedure end and 94.7% at 6 months. Good clinical outcome (modified Rankin Scale (mRS) 0-2) was maintained from baseline (73%) through 30 days (81%) and 6 months (83%). Thromboembolic events occurred in 5.5% of cases, all asymptomatic. Device-related complications were minimal, with coil entanglement in 0.3% of deployed coils and no instances of deployment/retrieval failure. All-cause mortality was 4.4%, confined to the ruptured aneurysm cohort. CONCLUSIONS:The SUCCESS study demonstrates high rates of successful aneurysm occlusion with Comaneci-assisted coiling, with occlusion rates persisting through 6 month follow-up. The safety profile was favorable, with low rates of thromboembolic events compared with other assist techniques. These results support the use of the Comaneci device for wide-necked aneurysm treatment in both ruptured and unruptured settings. TRIAL REGISTRATION NUMBER:NCT04518670.

Background and ObjectivesAlthough previous trials have established the efficacy and safety of endovascular thrombectomy (EVT) in large ischemic core strokes, most of them excluded patients with extracranial internal carotid artery (e-ICA) occlusion. We aimed to compare outcomes in patients with e-ICA occlusion and large ischemic core infarcts treated with EVT vs medical management (MM).MethodsThis was a secondary analysis of the SELECT2 trial, a randomized controlled trial conducted at 31 international sites. Adult patients with proximal intracranial anterior circulation large ischemic strokes, defined as Alberta Stroke Program Early CT Score (ASPECTS) 3-5 on noncontrast CT or ischemic core >= 50 mL on CT-perfusion/magnetic resonance-diffusion imaging, and concomitant e-ICA occlusion were selected. The primary outcomes were the distribution of modified Rankin Scale (mRS) score at 90-day follow-up and symptomatic intracranial hemorrhage (sICH).ResultsAmong 352 enrolled patients, 62 (17.6%) with e-ICA occlusions were included. Of those 62 patients, 37 received EVT (median [interquartile range (IQR)] age, 65 [58-71] years; 15 women [38.5%]) and 25 received MM (median [IQR] age, 66 [61-71] years; 7 women [28%]). ASPECTS (EVT: 5 [3-5] vs MM: 5 [4-5]) and ischemic core volume (EVT: 100 [69-134] mL vs MM: 103 [78-135] mL) were similar between groups. The successful reperfusion rate with EVT was 64.9%. Patients receiving EVT demonstrated significantly better functional outcomes (adjusted generalized odds ratio 2.51; 95% CI 1.43-4.39; p = 0.001) and a higher proportion of patients achieving 90-day independent ambulation (EVT: 37.8% vs MM: 8%; adjusted relative ratio [aRR] 4.58; 95% CI 1.18-17.79; p = 0.037) and functional independence (EVT: 21.6% vs MM: 8%; aRR 2.16; 95% CI 0.53-8.83; p = 0.285). Furthermore, no heterogeneity of EVT benefit was observed by the presence or absence of e-ICA occlusion (p-interaction = 0.248). There were no sICH or parenchymal hemorrhage type 2 events in either group, and mortality was similar in the 2 groups (aRR 0.75; 95% CI 0.39-1.45; p = 0.388).DiscussionAmong patients with e-ICA occlusions and large ischemic core stroke, EVT was associated with better functional outcomes without significant safety concerns when compared with MM. Our findings suggest that EVT in these patients is beneficial, while the optimal treatment of the extracranial carotid occlusion remains unclear.Trial Registration InformationName of the trial: SELECT2 trial. Registration number: ClinicalTrials.gov Identifier: NCT03876457. Date of registration submission: August 3, 2019. Date of first patient enrollment: November 10, 2019.Classification of EvidenceThis study provides Class II evidence that for patients with large core acute ischemic stroke and concomitant e-ICA occlusion, EVT is associated with better functional outcome at 90 days compared with MM alone.

BACKGROUND:We aimed to determine whether extensive severe computed tomography (CT) hypodensity, representing blood-brain barrier injury, would be associated with a reduced benefit of endovascular therapy (EVT) in patients presenting with large core stroke. METHODS:This study is an exploratory analysis of SELECT2 (Randomized Controlled Trial to Optimize Patient's Selection for Endovascular Treatment in Acute Ischemic Stroke), a randomized controlled trial of EVT versus medical management in patients with large ischemic core who presented to 31 comprehensive stroke centers across the United States, Canada, Europe, Australia, and New Zealand. Visible CT hypodensity was outlined, and a threshold of severe CT hypodensity was defined as the lower 99% CI of contralateral thalamic gray matter in Hounsfield units (HU). The association between the volume of severe CT hypodensity and modified Rankin Scale (mRS) score of 0 to 3 was evaluated using logistic regression models, with adjustment for age, National Institutes of Health Stroke Scale, total noncontrast CT core volume, and a volume-by-treatment interaction. The relationship between severe CT hypodensity volume and the probability of an mRS score of 0 to 3 was used to select clinically relevant volume cut points for further evaluation. The treatment effect of EVT versus medical management on independent ambulation and hemicraniectomy was assessed in 2 subgroups based on these volume cut points. RESULTS:In 322 patients, the median CT density was 31 HU (interquartile range, 28-34). The selected threshold of severe CT hypodensity was 26 HU. The volume of ischemic core ≤26 HU (per 1 mL increase) was associated with lower odds of mRS score of 0 to 3 after EVT (adjusted odds ratio [aOR], 0.96 [95% CI, 0.94-0.99]), but not medical management (aOR, 1.01 [95% CI, 0.98-1.03]; Pinteraction<0.01). In 101 patients with ≥26 mL of severe CT hypodensity, EVT, compared with medical management, was not associated with mRS score of 0 to 3 (aOR, 0.98 [95% CI, 0.33-2.88]) and was associated with hemicraniectomy (≥26 mL: aOR, 3.45 [95% CI, 1.09-10.86] versus <26 mL: aOR, 0.74 [95% CI, 0.31-1.75]; Pinteraction=0.03), whereas among 221 patients with <26 mL of severe hypodensity EVT was associated with mRS score of 0 to 3 (aOR, 7.20 [95% CI, 3.55-15.47]; Pinteraction<0.01). CONCLUSIONS:Severe hypodensity within large ischemic regions modifies the thrombectomy treatment effect and increases the likelihood of hemicraniectomy, independent of lesion volume. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT03876457.

Introduction: For patients transferred for EVT considerations, direct-to-angio approach is shown to reduce time to procedure and improve clinical outcomes. We aimed to assess if IV thrombolytics status prior to transfer modifies the association between direct-to-angio approach and improved clinical outcomes in transferred patients who received EVT. Methods: In a secondary analysis of a retrospective cohort of transferred EVT patients from 6 centers across US and Europe, patients were stratified based on IV thrombolytic status. Association of direct-to-angio approach vs repeated imaging approach with functional outcomes was assessed among patients with and without IV thrombolytics using appropriate regression models adjusted for age, stroke severity, time to procedure, occlusion location, serum glucose and successful reperfusion status. Heterogeneity of association was evaluated using multiplicative interaction. Results: Of 1135 patients with documented IV thrombolysis status, 612 (54%) received IVT – with younger age (IVT - 68 (57-78)y, no IVT - 70 (60-79)y, p=0.032) and higher CT ASPECTS (IVT: 8 (7-10) vs no IVT: 8 (7-9), p=0.038), but similar NIHSS (IVT: 17 (13-21) vs no IVT: 17 (12-21), p=0.91). Estimates of association favored direct-to-angio approach among both no IVT (acOR: 2.06, 95% CI: 1.38 to 3.08, p-value<0.001) and IVT (acOR: 1.33, 95% CI: 0.95 to 1.86, p-value: 0.099), without significant heterogeneity (p-interaction: 0.17). Similar findings were also observed for functional independence (IVT - aOR: 1.64, 95% CI: 1.08 to 2.49, p-value: 0.021; no IVT: aOR: 2.12, 95% CI: 1.25 to 3.58, p-value: 0.005; p-interaction: 0.57) and independent ambulation (IVT: aOR: 1.45, 95% CI: 0.93 to 2.26, p-value: 0.097; No IVT: aOR: 2.92, 95% CI: 1.68 to 5.06, p-value<0.001; p-interaction: 0.10) – Table 1. Interpretation: From a retrospective cohort of transferred patients who received EVT, use of IV thrombolytics at baseline did not modify the association between DTA vs RI approach and functional outcomes at 90-day follow-up, suggesting the feasibility of DTA approach regardless of baseline IVT status.

The association of anesthesia approach during endovascular thrombectomy (EVT) with clinical outcomes in large strokes is unexplored. We aimed to evaluate whether general anesthesia (GA), compared with non-GA, was associated with better functional outcomes in the SELECT2 trial. In a prespecified secondary analysis of the SELECT2 trial that enrolled patients with large strokes on noncontrast CT (Alberta Stroke Program Early CT Score [ASPECTS] 3-5), CT perfusion/MRI (core volume ≥50 mL), or both, functional outcomes were compared in EVT-treated patients who received GA or non-GA and whether this association was modified by stroke severity (NIH Stroke Scale score), ischemic injury estimates, and collateral status was evaluated. The primary outcome was 90-day functional status (ordinal modified Rankin Scale [mRS]). Secondary outcomes were functional independence (mRS scores 0-2), independent ambulation (mRS scores 0-3), complete dependence or death (mRS scores 5-6), and mortality. Of 178 EVT patients (median [interquartile range] age 66 [58-75] years, stroke severity 19 [15-23], CT-ASPECTS 4 [3-5], and core volume 101.5 [70-138] mL, 71 women [39.9%]), 104 (58%) received GA. Time from randomization to arterial puncture was longer with GA (40 [23-59] minutes) vs non-GA (27 [18-47] minutes), but procedural duration (GA: 57 [31.5-77] minutes vs non-GA: 49.5 [30-71] minutes) was similar. Successful reperfusion (modified treatment in cerebral infarction [mTICI] score 2b-3) rates were similar (GA 81 (78%) vs non-GA 62 (84%), adjusted relative risk [aRR] 0.91, 95% CI 0.79-1.06). In addition, mRS distribution did not differ between GA and non-GA groups (adjusted generalized odds ratio 1.21, 95% CI 0.86-1.70), as well as independent ambulation (GA: 41% vs non-GA: 34%, aRR 1.22, 95% CI 0.86-1.74) and functional independence (GA: 22% vs non-GA: 18%, aRR 1.32, 95% CI 0.75-2.35). Stroke severity, ASPECTS, ischemic core volume, or collaterals did not modify the association between anesthesia and functional outcome (all p-interaction >0.05). Patients experienced systolic blood pressure (SBP) variability ≥40 mm Hg and minimum intraprocedural SBP (<100 mm Hg) more frequently with GA, but this did not modify GA association with functional outcomes (p-interaction = 0.77 and 0.89, respectively). In patients with large core strokes randomized in SELECT2, EVT outcomes did not differ significantly based on anesthesia approach (GA or non-GA) without heterogeneity across stroke severity and size. While GA was associated with higher SBP variability and lower minimum SBP, this did not modify GA association with functional outcomes. While allocation to anesthesia approach was nonrandomized, our findings suggest that optimizing institutional protocols for preferred anesthesia technique, whether GA or non-GA, may enhance EVT procedural outcomes. ClinicalTrials.gov ID: NCT03876457. This study provides Class II evidence that in patients presenting within 24 hours with large vessel occlusion strokes undergoing EVT, the 90-day mRS score is comparable in those with or without GA.