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.

Background and ObjectivesThe management of anterior circulation tandem lesion stroke remains controversial, given its under-representation in randomized thrombectomy trials and uncertainty regarding optimal extracranial carotid intervention. We aimed to determine whether emergent carotid stenting (eCAS) during endovascular thrombectomy (EVT) for anterior circulation tandem lesions improves 90-day functional outcomes compared with a no-stenting strategy.MethodsWe conducted an international multicenter longitudinal retrospective cohort study (CERES-TANDEM, NCT06965036) of consecutive adults treated at 49 comprehensive stroke centers in Europe, North America, and Singapore for anterior circulation acute ischemic stroke due to tandem lesions from January 1, 2018, to December 31, 2024. Exclusion criteria were primary hemorrhagic stroke, absence of intracranial occlusion, presentation >24 hours from symptom onset, and age younger than 18 years. We compared 90-day modified Rankin Scale (mRS) scores between participants receiving eCAS and those receiving no stenting during EVT. The primary estimand was mRS shift, analyzed by stabilized inverse probability of treatment weighting (IPTW)-weighted ordinal regression. Additional estimands were direct-effect estimand adjusting for successful recanalization (defined as Thrombolysis in Cerebral Infarction grade 2b or higher) and symptomatic intracranial hemorrhage (sICH) (estimand 2) and stratum estimand restricting to never-crossers (estimand 3).ResultsOf 4,053 patients (mean age 70 years, 65.5% female), 2,522 underwent eCAS and 1,531 received no stenting. After IPTW, eCAS was associated with an improved 90-day functional outcome (common odds ratio (OR) 1.31; 95% CI 1.17-1.47;p < 0.001) and higher odds of mRS score 0-1 (OR 1.27; 95% CI 1.08-1.50; p = 0.005) and mRS score 0-2 (OR 1.30; 95% CI 1.13-1.51; p < 0.001), without a significant increase in sICH (OR 1.21; 95% CI 0.93-1.56; p = 0.15). Findings were consistent in direct-effect (common OR 1.17; 95% CI 1.04-1.31; p = 0.008) and stratum (common OR 1.37; 95% CI 1.21-1.55; p < 0.001) estimands. There was no interaction for intracranial occlusion site, IV thrombolysis, sedation technique, EVT approach, or access site. Sensitivity analysis including recanalization in IPTW-weighted estimand 1 framework confirmed the association of eCAS with improved 90-day functional outcomes (common OR 1.14, 95% CI1.02-1.27, p = 0.008).DiscussionIn this large real-world cohort, eCAS during EVT for anterior circulation tandem lesions was associated with superior 90-day functional recovery without increased hemorrhagic risk. These findings support consideration of eCAS in clinical practice and warrant confirmation in randomized trials.Trial Registration InformationRegistered in clinicaltrials.gov, NCT06965036.Classification of EvidenceThis study provides Class II evidence that in patients with stroke due to anterior circulation tandem lesions, eCAS during EVT improves 90-day functional outcomes compared with EVT alone.

BackgroundEndovascular therapy (EVT) stands as an established and effective intervention for acute ischemic stroke in patients harboring tandem lesions (TLs). However, the optimal anesthetic strategy for EVT in TL patients remains unclear. This study aims to evaluate the impact of distinct anesthetic techniques on outcomes in acute ischemic stroke patients presenting with TLs.MethodsPatient-level data, encompassing cases from 16 diverse centers, were aggregated for individuals with anterior circulation TLs treated between January 2015 and December 2020. A stratification based on anesthetic technique was conducted to distinguish between general anesthesia (GA) and procedural sedation (PS). Multivariable logistic regression models were built to discern the association between anesthetic approach and outcomes, including the favorable functional outcome defined as 90-day modified Rankin Score (mRS) of 0–2, ordinal shift in mRS, symptomatic intracranial hemorrhage (sICH), any hemorrhage, successful recanalization (modified Thrombolysis In Cerebral Infarction (mTICI) score ≥2b), excellent recanalization (mTICI 3), first pass effect (FPE), early neurological improvement (ENI), door-to-groin and recanalization times, intrahospital mortality, and 90-day mortality.ResultsAmong 691 patients from 16 centers, 595 patients (GA 38.7%, PS 61.3%) were included in the final analysis. There were no significant differences noted in the door-to-groin time (80 (46–117.5) mins vs 54 (21–100), P=0.607) and groin to recanalization time (59 (39.5–85.5) mins vs 54 (38–81), P=0.836) among the groups. The odds of a favorable functional outcome (36.6% vs 52.6%; adjusted OR (aOR) 0.56, 95% CI 0.38 to 0.84, P=0.005) and a favorable shift in the 90-day mRS (aOR 0.71, 95% CI 0.51 to 0.99, P=0.041) were lower in the GA group. No differences were noted for sICH (3.9% vs 4.7%, P=0.38), successful recanalization (89.1% vs 86.5%, P=0.13), excellent recanalization (48.5% vs 50.3%, P=0.462), FPE (53.6% vs 63.4%, P=0.05), ENI (38.9% vs 38.8%, P=0.138), and 90-day mortality (20.3% vs 16.3%, P=0.525). An interaction was noted for favorable functional outcome between the type of anesthesia and the baseline Alberta Stroke Program Early CT Score (ASPECTS) (P=0.033), degree of internal carotid artery (ICA) stenosis (P<0.001), and ICA stenting (P<0.001), and intraparenchymal hematoma between the type of anesthesia and intravenous thrombolysis (P=0.019). In a subgroup analysis, PS showed better functional outcomes in patients with age ≤70 years, National Institutes of Health Stroke Scale (NIHSS) score <15, and acute ICA stenting.ConclusionsOur findings suggest that the preference for PS not only aligns with comparable procedural safety but is also associated with superior functional outcomes. These results prompt a re-evaluation of current anesthesia practices in EVT, urging clinicians to consider patient-specific characteristics when determining the optimal anesthetic strategy for this patient population.

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.

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.

BACKGROUND:Rapid and complete recanalization is a primary goal in the endovascular treatment of large vessel occlusion stroke. The effectiveness and safety of super large bore aspiration catheters (0.088″ inner diameter) for the treatment of large vessel occlusion stroke have not been demonstrated in a randomized trial. METHODS:SUMMIT MAX (A Prospective, Randomized, Controlled, Interventional Clinical Trial to Evaluate the Safety and Effectiveness of the Route 92 Medical MonoPoint Reperfusion System for Aspiration Embolectomy in Acute Ischemic Stroke Patients) was a prospective, randomized, controlled, open-label clinical trial of patients with internal carotid artery and middle cerebral artery M1 occlusions, comparing the super large bore HiPoint Reperfusion system (Route 92 Medical) to the Vecta Aspiration system (Stryker Neurovascular). We hypothesized that the effectiveness and safety of the HiPoint reperfusion system were noninferior (12.5% noninferiority margin) to the Vecta Aspiration system. The primary effectiveness end point was successful reperfusion, defined as modified Treatment in Cerebral Infarction≥2b as adjudicated by an independent core lab, using only the assigned study device, with any use of a nonstudy device before or after the use of study device defined as failure. The primary safety end point was symptomatic intracranial hemorrhage within 24 hours (-8/+24) post-procedure. RESULTS:There were 250 patients enrolled of whom 166 met the criteria for the modified intent-to-treat population: 89 in HiPoint and 77 in Vecta. The median age was 69 years; 54.2% were female. Successful reperfusion with any adjunctive therapy counted as a failure was 77.5% (69/89) in the HiPoint group versus 50.6% (39/77) in the Vecta group (P<0.0001 for noninferiority). Symptomatic intracranial hemorrhage within 24 hours (-8/+24 hours) post-procedure was similar between groups (3.6% versus 2.7%, respectively). At 90 days, good clinical outcome (mRS score of ≤2) was achieved in 50.6% in the HiPoint group and 53.3% in the Vecta group (absolute difference, -2.8% [95% CI, -18.2% to 12.7%]; P=0.75). CONCLUSIONS:In this randomized trial of patients with anterior large vessel occlusion, the super large bore HiPoint system was noninferior to the Vecta system in achieving successful reperfusion, with a similar safety profile. This study supports the super large bore HiPoint system for mechanical thrombectomy. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT05018650.

BACKGROUND:Several social and biological factors are shown to differentially affect stroke outcomes between men and women. We evaluated whether clinical outcomes and endovascular thrombectomy (EVT) treatment effects differed between the sexes in patients presenting with large ischemic stroke. METHODS:The SELECT2 trial (A Randomized Controlled Trial to Optimize Patient's Selection for Endovascular Treatment in Acute Ischemic Stroke) was a randomized controlled trial assessing the efficacy and safety of EVT in patients with large strokes across the United States, Canada, Europe, Australia, and New Zealand between October 2019 and September 2022. In this subanalysis, baseline characteristics and clinical and imaging outcomes were compared between women and men, each further divided into cohorts receiving medical treatment without and with EVT. Functional outcomes at 90-day and 1-year follow-ups were assessed using regression models, adjusting for potential confounders. Sex-related effect modification was examined. RESULTS:Women accounted for 145 (41%) of 352 patients enrolled in the SELECT2 trial. Seventy-one (49%) of 145 women and 109 (53%) of 207 men underwent EVT. Endovascular intervention was associated with better functional outcomes (women: adjusted generalized odds ratio, 1.73 [1.22-2.45]; men: adjusted generalized odds ratio, 1.66 [1.24-2.23]; P-int: 0.94), functional independence (women: EVT, 20% versus medical management, 4%; adjusted risk ratio [aRR], 5.04 [1.59-16.02]; men: EVT, 20% versus medical management, 9%; aRR, 1.99 [0.99-4.02]; P-int: 0.20), and independent ambulation (women: EVT, 39% versus medical management, 16%; aRR, 2.44 [1.40-4.24]; men: EVT, 38% versus medical management, 20%; aRR, 1.98 [1.29-3.03]; P-int: 0.67) in both men and women at 90-day follow-up, without significant heterogeneity. Similar results were observed at 1-year follow-up. In women, as age increased (aRR, 0.97 [95% CI, 0.95-0.99]; P=0.004 per year) and core volume estimates increased (aRR, 0.99 [95% CI, 0.98-1.00]; P=0.015 per mL increase), the rate of independent ambulation after EVT decreased. A similar association of age and core volume was seen in men. CONCLUSIONS:EVT treatment benefit was maintained in both women and men, with higher rates of functional independence and independent ambulation as compared with medical management. Age and estimated core infarct volume were independently associated with independent ambulation in both male and female patients. EVT should be equally considered for patients of both sexes meeting large core eligibility criteria. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT03876457.

Background The incidence of intracerebral hemorrhage (ICH) and its effect on the outcomes after endovascular thrombectomy (EVT) for patients with large core infarcts have not been well-characterized. Methods SELECT2 trial follow-up imaging was evaluated using the Heidelberg Bleeding Classification (HBC) to define hemorrhage grade. The association of ICH with clinical outcomes and treatment effect was examined. Results Of 351 included patients, 194 (55%) and 189 (54%) demonstrated intracranial and intracerebral hemorrhage, respectively, with a higher incidence in EVT (134 (75%) and 130 (73%)) versus medical management (MM) (60 (35%) and 59 (34%), both P<0.001). Hemorrhagic infarction type 1 (HBC=1a) and type 2 (HBC=1b) accounted for 93% of all hemorrhages. Parenchymal hematoma (PH) type 1 (HBC=1c) and type 2 (HBC=2) were observed in 1 (0.6%) EVT-treated and 4 (2.2%) MM patients. Symptomatic ICH (sICH) (SITS-MOST definition) was seen in 0.6% EVT patients and 1.2% MM patients. No trend for ICH with core volumes (P=0.10) or Alberta Stroke Program Early CT Score (ASPECTS) (P=0.74) was observed. Among EVT patients, the presence of any ICH did not worsen clinical outcome (modified Rankin Scale (mRS) at 90 days: 4 (3-6) vs 4 (3-6); adjusted generalized OR 1.00, 95% CI 0.68 to 1.47, P>0.99) or modify EVT treatment effect (P-interaction=0.77). Conclusions ICH was present in 75% of the EVT population, but PH or sICH were infrequent. The presence of any ICH did not worsen functional outcomes or modify EVT treatment effect at 90-day follow-up. The high rate of hemorrhages overall still represents an opportunity for adjunctive therapies in EVT patients with a large ischemic core.

Introduction Pulsatile tinnitus (PT) affects similar to 10% of the population and can be debilitating. Venous etiologies of PT are increasingly recognized. Identifying the symptomatic vessel, particularly with multiple venous anomalies, remains challenging.Methods In this case series, we utilized venous balloon occlusion testing (vBOT) as a real-time diagnostic tool to identify symptomatic vessels in non-sinus stenosis venous PT. vBOT involved using a transform balloon (7 mm x 7 mm) under fluoroscopic guidance to occlude the venous anomaly, with immediate assessment of symptom resolution.Results We report four cases involving high-riding jugular bulbs, jugular bulb diverticula, and enlarged emissary veins. vBOT successfully identified the culprit vessels, guiding targeted endovascular coil embolization. These procedures led to significant symptom resolution in all cases, though the varied patient responses underscored the importance of a tailored, iterative approach, particularly in those with bilateral symptoms or multiple venous variants.Conclusion This series illustrates the utility of vBOT in accurately identifying symptomatic vessels in non-sinus stenosis venous PT, enabling effective, targeted interventions. While vBOT is a valuable diagnostic tool, its limitations, including potential false negatives due to PT variability or ambient noise, must be considered. Incorporating vBOT into the diagnostic framework for PT can enhance precision in vessel selection and improve patient outcomes, particularly in cases with uncommon venous etiologies.

BACKGROUND AND OBJECTIVES:The management of anterior circulation tandem lesion stroke remains controversial, given its under-representation in randomized thrombectomy trials and uncertainty regarding optimal extracranial carotid intervention. We aimed to determine whether emergent carotid stenting (eCAS) during endovascular thrombectomy (EVT) for anterior circulation tandem lesions improves 90-day functional outcomes compared with a no-stenting strategy. METHODS:We conducted an international multicenter longitudinal retrospective cohort study (CERES-TANDEM, NCT06965036) of consecutive adults treated at 49 comprehensive stroke centers in Europe, North America, and Singapore for anterior circulation acute ischemic stroke due to tandem lesions from January 1, 2018, to December 31, 2024. Exclusion criteria were primary hemorrhagic stroke, absence of intracranial occlusion, presentation >24 hours from symptom onset, and age younger than 18 years. We compared 90-day modified Rankin Scale (mRS) scores between participants receiving eCAS and those receiving no stenting during EVT. The primary estimand was mRS shift, analyzed by stabilized inverse probability of treatment weighting (IPTW)-weighted ordinal regression. Additional estimands were direct-effect estimand adjusting for successful recanalization (defined as Thrombolysis in Cerebral Infarction grade 2b or higher) and symptomatic intracranial hemorrhage (sICH) (estimand 2) and stratum estimand restricting to never-crossers (estimand 3). RESULTS:Of 4,053 patients (mean age 70 years, 65.5% female), 2,522 underwent eCAS and 1,531 received no stenting. After IPTW, eCAS was associated with an improved 90-day functional outcome (common odds ratio (OR) 1.31; 95% CI 1.17-1.47;p < 0.001) and higher odds of mRS score 0-1 (OR 1.27; 95% CI 1.08-1.50; p = 0.005) and mRS score 0-2 (OR 1.30; 95% CI 1.13-1.51; p < 0.001), without a significant increase in sICH (OR 1.21; 95% CI 0.93-1.56; p = 0.15). Findings were consistent in direct-effect (common OR 1.17; 95% CI 1.04-1.31; p = 0.008) and stratum (common OR 1.37; 95% CI 1.21-1.55; p < 0.001) estimands. There was no interaction for intracranial occlusion site, IV thrombolysis, sedation technique, EVT approach, or access site. Sensitivity analysis including recanalization in IPTW-weighted estimand 1 framework confirmed the association of eCAS with improved 90-day functional outcomes (common OR 1.14, 95% CI1.02-1.27, p = 0.008). DISCUSSION:In this large real-world cohort, eCAS during EVT for anterior circulation tandem lesions was associated with superior 90-day functional recovery without increased hemorrhagic risk. These findings support consideration of eCAS in clinical practice and warrant confirmation in randomized trials. TRIAL REGISTRATION INFORMATION:Registered in clinicaltrials.gov, NCT06965036. CLASSIFICATION OF EVIDENCE:This study provides Class II evidence that in patients with stroke due to anterior circulation tandem lesions, eCAS during EVT improves 90-day functional outcomes compared with EVT alone.

Ischemic stroke remains a leading cause of disability worldwide. Preliminary studies have suggested that noninvasive, frequency-tuned, low-intensity electromagnetic network targeting field (ENTF) stimulation may have recovery benefit for patients with stroke. To evaluate the safety and effectiveness of ENTF therapy in reducing global disability among patients in the subacute ischemic stroke phase with moderate to severe disability and upper-extremity impairment. This multicenter, double-blind, sham-controlled, randomized clinical trial was conducted at 15 US-based acute care and inpatient rehabilitation facilities from December 2021 to November 2023. Participants were enrolled 4 to 21 days after a stroke and had a baseline modified Rankin Scale (mRS) score of 3 or 4 (moderate or moderately severe global disability) and Fugl-Meyer Assessment for Upper Extremity score of 10 to 45 (higher scores indicating better arm function). Target sample size was 150 participants. Participants were randomly allocated to receive either active or sham ENTF stimulation. Modified intention-to-treat approach was used in primary efficacy and safety analyses. Participants allocated to the active or sham ENTF stimulation were treated with a proprietary brain-computer interface–based stimulation device paired with an evidence-based, functional, repetitive, home-based physical and occupational exercise regimen for 45 one-hour sessions, 5 times per week within the first 90 days after a stroke. The primary end point was change in global disability, assessed with the mRS (score range: 0 [indicating normal or no symptoms] to 6 [indicating death]), from baseline to day 90. Secondary end points were change from baseline to day 90 in upper-limb impairment, arm motor function, gait speed, hand function, and physical and functional limitations as well as day-90 health-related quality of life, each of which was assessed with a specific metric. The trial was stopped early after enrollment of 100 participants (50 in active group, 50 in sham group) when a promising zone threshold was not attained at planned interim analysis of the first 78 evaluable participants. Participants had a mean age of 59.0 (12.5) years and included 66 males (67.3%). The median (IQR) time from stroke to first ENTF treatment was 14 (12-19) days. Study groups were similar in age, sex, and baseline mRS scores, but imbalances were noted with participants in the active, compared with the sham, group having more right-hemisphere strokes (31 of 49 [63.3%] vs 22 of 49 [44.9%]), more severe upper-extremity impairment (Shoulder Abduction Finger Extension score <5; 31 of 49 [63.3%] vs 24 of 49 [49.0%]), and fewer small-vessel infarcts (14 of 49 [28.6%] vs 21 of 49 [42.9%]). For the primary outcome, the mean (SD) disability reduction on mRS at day 90 was not statistically significantly higher in the active group than in the sham group (−1.96 [0.12] vs −1.72 [0.12]), including mRS score of 0 to 1 attained in 12 participants (26.0%) vs 5 participants (10.0%) (odds ratio, 2.99; 95% CI, 0.96-9.30; P = .05). Point estimates for secondary outcomes favored the active group, although the differences were not statistically significant, in the prespecified analysis. No ENTF device–related serious adverse events were noted. This trial found that ENTF therapy is safe. Although the difference between groups was not statistically significant, ENTF therapy may reduce global disability in patients with severe baseline disability after ischemic stroke. These results warrant confirmation in a higher powered pivotal trial of ENTF therapy. ClinicalTrials.gov Identifier NCT05044507

BACKGROUND AND OBJECTIVES: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. METHODS: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. RESULTS: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). DISCUSSION: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. TRIAL REGISTRATION INFORMATION:ClinicalTrials.gov ID: NCT03876457. CLASSIFICATION OF EVIDENCE: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.

Introduction: Endovascular thrombectomy (EVT) reduces disability in patients with large ischemic core stroke. Increasing core volume is prognostic but does not modify treatment effect. CT hypodensity can vary within an area of core. We assessed the relationship between the severity of CT core hypodensity and clinical outcome in the SELECT2 trial. Methods: Non-contrast CT ischemic core was drawn manually by two blinded investigators with consensus review by a third investigator. An absolute Hounsfield unit (HU) threshold for severe hypodensity was set at the lower 99% confidence interval [CI] for normal contralateral thalamic grey matter. Outcomes assessed included ordinal mRS, functional independence (mRS 0-2), independent ambulation (mRS 0-3), and mortality at 90 days. The association between the volume of severe hypodensity and outcome was adjusted for age, baseline NIHSS, and total baseline core volume, via logistic and proportional odds models with treatment*hypodensity interaction. Results: Of 317 assessable patients, the median hypodensity of ischemic core was 31HU (IQR 28-33). Median density of normal thalamus was 38HU. The severe hypodensity threshold (lower 99% CI) was 26HU with median volume affected 14mL (IQR 5.6-29.2) or median 19% (IQR 9-35%) of the total hypodensity volume. The volume of core ≤26HU (per 1 mL increase) was associated with a 90-day mRS shift towards worse outcomes in EVT patients (n=161, adjusted common odds ratio, acOR 1.03, 95%CI 1.01-1.05) but not medical management ([MM], n=156, acOR 1.00, 95%CI 0.98-1.02, p-interaction 0.005); lower functional independence in EVT (aOR 0.96 95%CI 0.93-0.99) but not MM (aOR 1.02, 95%CI 0.99-1.06, p-interaction 0.004); lower independent ambulation in EVT (aOR 0.97, 95%CI 0.94-0.99) but not MM (aOR 1.01, 95%CI 0.98-1.04, p-interaction 0.002) and higher mortality in EVT (aOR 1.03, 95%CI 1.01-1.05) but not MM (aOR 1.00, 95%CI 0.98-1.02, p-interaction 0.02). Conclusion: In patients with large ischemic core, areas of significant CT hypodensity are associated with worse clinical outcomes after EVT but not MM. This is independent of total core volume and modifies the treatment effect of EVT. This may improve prognostic decision-making and drive developments in automated image processing.

Venous thromboembolism (VTE) is a common but preventable complication observed in critically ill patients. Deep vein thrombosis (DVT) is the most common type of VTE, with clinical significance based on location and symptoms. There is an increased incidence of DVT and pulmonary embolism (PE) in ischemic stroke patients using unfractionated heparin (UFH) for VTE prophylaxis compared with those using enoxaparin. However, UFH is still used in some patients due to its perceived safety, despite conflicting literature suggesting that enoxaparin may have a protective effect. The current study aimed to determine the incidence of VTEs in patients with acute ischemic strokes on UFH versus enoxaparin for VTE prophylaxis, subclassifying the VTEs depending on their location and symptoms. It also aimed to examine the safety profile of both drugs. A total of 909 patients admitted to the Neuro-ICU with the diagnosis of acute ischemic stroke were identified, and 634 patients were enrolled in the study—170 in the enoxaparin group and 464 in the UFH group—after applying the exclusion criteria. Nineteen patients in the UFH group (4.1%) and 3 patients in the enoxaparin group (1.8%) had a VTE. The incidence of DVT in the UFH group was 12 (2.6%), all of which were symptomatic, compared with 3 (1.8%) in the enoxaparin group, wherein one case was symptomatic. Nine patients (1.9%) in the UFH group developed a PE during the study period, and all of them were symptomatic. No patients in the enoxaparin group developed PE. No statistically significant difference was found between both groups. However, 18 patients in the UFH group (3.9%) experienced intracranial hemorrhage compared with none in the enoxaparin group, and this difference was statistically significant. Enoxaparin was found to be as effective as and potentially safer than UFH when used for VTE prophylaxis in stroke patients.

OBJECTIVE The optimal technique for treating tandem lesions (TLs) with endovascular therapy is debatable. The authors evaluated the functional, safety, and procedural outcomes of different approaches in a multicenter study. METHODS Anterior circulation TL patients treated from January 2015 to December 2020 were divided on the basis of antegrade versus retrograde approach and included. The evaluated outcomes were favorable modified Rankin Scale (mRS) score (mRS score 0-2) at 3 months, ordinal shift in mRS score, successful recanalization, excellent recanalization, first-pass effect (FPE), time from groin puncture to successful recanalization, symptomatic intracranial hemorrhage (sICH), and 90-day mortality. RESULTS Among 691 patients treated at 16 centers, 286 patients (174 antegrade and 112 retrograde approach patients) with acute stenting were included in the final analysis. There were no significant differences in mRS score 0-2 at 90 days (52.2% vs 50.0%, adjusted odds ratio [aOR] 0.83, 95% CI 0.42-1.56, p = 0.54), favorable shift in 90-day mRS score (aOR 1.03, 95% CI 0.66-1.29, p = 0.11), sICH (4.0% vs 4.5%, aOR 0.64, 95% CI 0.24-1.51, p = 0.45), successful recanalization (89.4% vs 93%, aOR 0.49, 95% CI 0.19-1.28, p = 0.19), excellent recanalization (51.4% vs 58.9%, aOR 0.59, 95% CI 0.40-1.07, p = 0.09), FPE (58.3% vs 69.7%, aOR 0.62, 95% CI 0.44-1.15, p = 0.21), and mortality at 90 days (16.6% vs 14.0%, aOR 0.94, 95% CI 0.35-2.44, p = 0.81) between the groups. The median (interquartile range) groin puncture to recanalization time was significantly longer in the antegrade group (59 [43-90] minutes vs 49 [35-73] minutes, p = 0.036). CONCLUSIONS The retrograde approach was associated with faster recanalization times with a similar functional and safety profile when compared with the antegrade approach in patients with acute ischemic stroke with TL. https://thejns.org/doi/abs/10.3171/2023.10.JNS231702

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 2025;97:698-708.