Trial of Endovascular Treatment of Acute Basilar-Artery Occlusion.

BACKGROUND: Data from trials investigating the effects and risks of endovascular thrombectomy for the treatment of stroke due to basilar-artery occlusion are limited. METHODS: We conducted a multicenter, prospective, randomized, controlled trial of endovascular thrombectomy for basilar-artery occlusion at 36 centers in China. Patients were assigned, in a 2:1 ratio, within 12 hours after the estimated time of basilar-artery occlusion to receive endovascular thrombectomy or best medical care (control). The primary outcome was good functional status, defined as a score of 0 to 3 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]), at 90 days. Secondary outcomes included a modified Rankin scale score of 0 to 2, distribution across the modified Rankin scale score categories, and quality of life. Safety outcomes included symptomatic intracranial hemorrhage at 24 to 72 hours, 90-day mortality, and procedural complications. RESULTS: Of the 507 patients who underwent screening, 340 were in the intention-to-treat population, with 226 assigned to the thrombectomy group and 114 to the control group. Intravenous thrombolysis was used in 31% of the patients in the thrombectomy group and in 34% of those in the control group. Good functional status at 90 days occurred in 104 patients (46%) in the thrombectomy group and in 26 (23%) in the control group (adjusted rate ratio, 2.06; 95% confidence interval [CI], 1.46 to 2.91, P<0.001). Symptomatic intracranial hemorrhage occurred in 12 patients (5%) in the thrombectomy group and in none in the control group. Results for the secondary clinical and imaging outcomes were generally in the same direction as those for the primary outcome. Mortality at 90 days was 37% in the thrombectomy group and 55% in the control group (adjusted risk ratio, 0.66; 95% CI, 0.52 to 0.82). Procedural complications occurred in 14% of the patients in the thrombectomy group, including one death due to arterial perforation. CONCLUSIONS: In a trial involving Chinese patients with basilar-artery occlusion, approximately one third of whom received intravenous thrombolysis, endovascular thrombectomy within 12 hours after stroke onset led to better functional outcomes at 90 days than best medical care but was associated with procedural complications and intracerebral hemorrhage. (Funded by the Program for Innovative Research Team of the First Affiliated Hospital of USTC and others; ATTENTION ClinicalTrials.gov number, NCT04751708.).

Association of Mismatch Profiles and Clinical Outcome from Endovascular Therapy in Large Infarct: A Post-Hoc Analysis of the ANGEL-ASPECT Trial.

OBJECTIVES: We investigated whether patients with large infarct and the presence or absence of perfusion mismatch are associated with endovascular treatment benefit. METHODS: This is a post-hoc analysis of the Endovascular Therapy in Anterior Circulation Large Vessel Occlusion with a Large Infarct (ANGEL-ASPECT) randomized trial, which enrolled patients within 24 hours of onset with ASPECTS 3 to 5 or ASPECTS 0 to 2 with an infarct core 70 to 100 ml. Mismatch ratio was defined as time-to-maximum (Tmax) >6 s cerebral volume/ischemic core volume, and mismatch volume was defined as Tmax >6 s volume minus ischemic core volume. We divided patients into mismatch ratio ≥1.2 and mismatch volume ≥10 ml, and mismatch ratio ≥1.8 and mismatch volume ≥15 ml groups. The primary outcome was the 90-day modified Rankin Scale score ordinal distribution. Safety outcomes were symptomatic intracranial hemorrhage and 90-day mortality. RESULTS: There were 425 patients included. In both the mismatch ratio ≥1.2 and mismatch volume ≥10 ml (mismatch+, n = 395; mismatch-, n = 31) and mismatch ratio ≥1.8 and mismatch volume ≥15 ml groups (mismatch+, n = 346; mismatch-, n = 80), better 90-day modified Rankin Scale outcomes were found in the endovascular treatment group compared with the MM group (4 [2-5] vs 4 [3-5], common odds ratio [cOR], 1.9, 95% confidence interval [CI] 1.3-2.7, p = 0.001; 4 [2-5] vs 4 [3-5], cOR, 1.9, 95% CI 1.3-2.8, p = 0.001, respectively), but not in patients without mismatch ratio ≥1.2 and mismatch volume ≥10 ml (5 [3-6] vs 5 [4-6], cOR, 1.2, 95% CI 0.3-4.1, p = 0.83), and mismatch ratio ≥1.8 and mismatch volume ≥15 ml (4 [3-6] vs 5 [3-6], cOR, 1.2, 95% CI 0.6-2.7, p = 0.60). However, no interaction effect was found in both subgroups (p interaction >0.10). CONCLUSION: Endovascular treatment was more efficacious than MM in patients with mismatch profiles, but no treatment effect or interaction was noted in the no mismatch profile patients. However, the small sample size of patients with no mismatch may have underpowered our analysis. A pooled analysis of large core trials stratified by mismatch is warranted. ANN NEUROL 2024;96:729-738.

Mode of Onset Modifies the Effect of Time to Endovascular Reperfusion on Clinical Outcomes after Acute Ischemic Stroke: An Analysis of the DAWN Trial.

OBJECTIVE: We aimed to assess the impact of time to endovascular thrombectomy (EVT) on clinical outcomes in the DAWN trial, while also exploring the potential effect modification of mode of stroke onset on this relationship. METHODS: The association between every 1-h treatment delay with 90-day functional independence (modified Rankin Scale [mRS] score 0-2), symptomatic intracranial hemorrhage, and 90-day mortality was explored in the overall population and in three modes of onset subgroups (wake-up vs. witnessed vs. unwitnessed). RESULTS: Out of the 205 patients, 98 (47.8%) and 107 (52.2%) presented in the 6 to 12 hours and 12 to 24 hours time window, respectively. Considering all three modes of onset together, there was no statistically significant association between time last seen well to randomization with either functional independence or mortality at 90 days in either the endovascular thrombectomy (mRS 0-2 1-hour delay OR 1.07; 95% CI 0.93-1.24; mRS 6 OR 0.84; 95% CI 0.65-1.03) or medical management (mRS 0-2 1-hour delay OR 0.98; 95% CI 0.80-1.14; mRS 6 1-hour delay OR 0.94; 95% CI 0.79-1.09) groups. Moreover, there was no significant interaction between treatment effect and time (p = 0.439 and p = 0.421 for mRS 0-2 and 6, respectively). However, within the thrombectomy group, the models that tested the association between time last seen well to successful reperfusion (modified Treatment in Cerebral Infarction ≥2b) and 90-day functional independence showed a significant interaction with mode of presentation (p = 0.013). This appeared to be driven by a nominally positive slope for both witnessed and unwitnessed strokes versus a significantly (p = 0.018) negative slope in wake-up patients. There was no association between treatment times and symptomatic intracranial hemorrhage. INTERPRETATION: Mode of onset modifies the effect of time to reperfusion on thrombectomy outcomes, and should be considered when exploring different treatment paradigms in the extended window. ANN NEUROL 2024;96:356-364.

Rescue Therapy for Failed Mechanical Thrombectomy in Acute Ischemic Stroke: A Pooled Analysis of the Society of Vascular and Interventional Neurology Registry.

OBJECTIVE: We aimed to evaluate the association between rescue therapy (RT) and functional outcomes compared to medical management (MM) in patients presenting after failed mechanical thrombectomy (MT). METHODS: This cross-sectional study utilized prospectively collected and maintained data from the Society of Vascular and Interventional Neurology Registry, spanning from 2011 to 2021. The cohort comprised patients with large vessel occlusions (LVOs) with failed MT. The primary outcome was the shift in the degree of disability, as gauged by the modified Rankin Scale (mRS) at 90 days. Additional outcomes included functional independence (90-day mRS score of 0-2), symptomatic intracranial hemorrhage (sICH), and 90-day mortality. RESULTS: Of a total of 7,018 patients, 958 presented failed MT and were included in the analysis. The RT group comprised 407 (42.4%) patients, and the MM group consisted of 551 (57.5%) patients. After adjusting for confounders, the RT group showed a favorable shift in the overall 90-day mRS distribution (adjusted common odds ratio = 1.79, 95% confidence interval [CI] = 1.32-2.45, p < 0.001) and higher rates of functional independence (RT: 28.8% vs MM: 15.7%, adjusted odds ratio [aOR] = 1.93, 95% CI = 1.21-3.07, p = 0.005) compared to the MM group. RT also showed lower rates of sICH (RT: 3.8% vs MM: 9.1%, aOR = 0.52, 95% CI = 0.28-0.97, p = 0.039) and 90-day mortality (RT: 33.4% vs MM: 45.5%, aOR = 0.61, 95% CI = 0.42-0.89, p = 0.009). INTERPRETATION: Our findings advocate for the utilization of RT as a potential treatment strategy for cases of LVO resistant to first-line MT techniques. Prospective studies are warranted to validate these observations and optimize the endovascular approach for failed MT patients. ANN NEUROL 2024;96:343-355.

Influence of Infarct Morphology and Patterns on Cognitive Outcomes After Endovascular Thrombectomy.

BACKGROUND: To assess the association of qualitative and quantitative infarct characteristics and 3 cognitive outcome tests, namely the Montreal Cognitive Assessment (MOCA) for mild cognitive impairment, the Boston Naming Test for visual confrontation naming, and the Sunnybrook Neglect Assessment Procedure for neglect, in large vessel occlusion stroke. METHODS: Secondary observational cohort study using data from the randomized-controlled ESCAPE-NA1 trial (Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke), in which patients with large vessel occlusion undergoing endovascular treatment were randomized to receive either intravenous Nerinetide or placebo. MOCA, Sunnybrook Neglect Assessment Procedure, and 15-item Boston Naming Test were obtained at 90 days. Total infarct volume, gray matter, and white matter infarct volumes were manually measured on 24-hour follow-up imaging. Infarcts were also visually classified as either involving the gray matter only or both the gray and white matter and scattered versus territorial. Associations of infarct variables and cognitive outcomes were analyzed using multivariable ordinal or binary logistic regression models. RESULTS: Of 1105 patients enrolled in ESCAPE-NA1, 1026 patients with visible infarcts on 24-hour follow-up imaging were included. MOCA and Sunnybrook Neglect Assessment Procedure were available for 706 (68.8%) patients and the 15-item Boston Naming Test was available for 682 (66.5%) patients. Total infarct volume was associated with worse MOCA scores (adjusted common odds ratio per 10 mL increase, 1.05 [95% CI, 1.04-1.06]). After adjusting for baseline variables and total infarct volume, mixed gray and white matter involvement (versus gray matter-only adjusted common odds ratio, 1.92 [95% CI, 1.37-2.69]), white matter infarct volume (adjusted common odds ratio per 10 mL increase 1.36 [95% CI, 1.18-1.58]) and territorial (versus scattered) infarct pattern (adjusted common odds ratio, 1.65 [95% CI, 1.15-2.38]) were associated with worse MOCA scores. Results for Sunnybrook Neglect Assessment Procedure and 15-item Boston Naming Test were similar, except for the territorial infarct pattern, which did not reach statistical significance in multivariable analysis. CONCLUSIONS: Besides total infarct volume, infarcts that involve the white matter and that show a territorial distribution were associated with worse cognitive outcomes, even after adjusting for total infarct volume.

Emerging Adjuvant Thrombolytic Therapies for Acute Ischemic Stroke Reperfusion.

Thrombolytic therapies for acute ischemic stroke are widely available but only result in recanalization early enough, to be therapeutically useful, in 10% to 30% of cases. This large gap in treatment effectiveness could be filled by novel therapies that can increase the effectiveness of thrombus clearance without significantly increasing the risk of harm. This focused update will describe the current state of emerging adjuvant treatments for acute ischemic stroke reperfusion. We focus on new treatments that are designed to (1) target different components that make up a stroke thrombus, (2) enhance endogenous fibrinolytic systems, (3) reduce stagnant blood flow, and (4) improve recanalization of distal thrombi and postendovascular thrombectomy.

Intravenous Tirofiban Versus Alteplase Before Endovascular Treatment in Acute Ischemic Stroke: A Pooled Analysis of the DEVT and RESCUE BT Trials.

BACKGROUND: The present study aimed to evaluate the efficacy and safety of intravenous tirofiban versus alteplase before endovascular treatment (EVT) in acute ischemic stroke patients with intracranial large vessel occlusion. METHODS: This was a post hoc analysis using data from 2 multicenter, randomized trials: the DEVT trial (Direct Endovascular Treatment for Large Vessel Occlusion Stroke) from May 2018 to May 2020 and the RESCUE BT trial (Intravenous Tirofiban Before Endovascular Thrombectomy for Acute Ischemic Stroke) from October 2018 to October 2021. Patients with acute intracranial large vessel occlusion within 4.5 hours from last known well were dichotomized into 2 groups: tirofiban plus EVT versus alteplase bridging with EVT. The primary outcome was functional independence (modified Rankin Scale score of 0-2) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage and 3-month mortality. Multivariable logistic regression (adjusting for baseline systolic blood pressure, occlusion site, onset-to-puncture time, anesthesia, and first choice of EVT) and propensity score overlap weighting (balance in demographic covariates, stroke characteristics, and initial management between groups) were performed. RESULTS: One-hundred and eighteen alteplase-treated patients in the DEVT trial and 98 tirofiban-treated patients in the RESCUE BT trial were included (median age, 70 years; 115 [53.2%] men). The rate of functional independence was 60.2% in the tirofiban group compared with 46.6% in the alteplase group (adjusted odds ratio, 1.25 [95% CI, 0.60-2.63]). Compared with alteplase, tirofiban was not associated with increased risk of symptomatic intracranial hemorrhage (6.8% versus 9.2%; P=0.51) and mortality (17.8% versus 19.4%; P=0.76). The propensity score overlap weighting analyses showed consistent outcomes. CONCLUSIONS: Among patients with intracranial large vessel occlusion within 4.5 hours of onset, tirofiban plus EVT was comparable to alteplase bridging with EVT regarding the efficacy and safety outcomes. These findings should be interpreted as preliminary and require confirmation in a randomized trial. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifiers: ChiCTR-IOR-17013568 and ChiCTR-INR-17014167.

Projections of Endovascular Therapy-Eligible Patients With Stroke for the US Population.

BACKGROUND: As stroke endovascular thrombectomy (EVT) treatment indications expand, understanding population-based EVT eligibility becomes critical for resource planning. We aimed to project current and future population-based EVT eligibility in the United States. METHODS: We conducted a post hoc analysis of the physician-adjudicated GCNKSS (Greater Cincinnati Northern Kentucky Stroke Study; 2015 epoch), a population-based, cross sectional, observational study of stroke incidence, treatment, and outcomes across a 5-county region. All hospitalized patients ≥18 years of age with acute ischemic stroke were ascertained using the International Classification of Diseases, Ninth Revision codes 430-436 and Tenth Revision codes I60-I67 and G45-G46 and extrapolated to the US adult census 2020. We determined the rate of EVT eligibility within the GCNKSS population using time from last known well to presentation (0-5 versus 5-23 hours), presenting National Institutes of Health Stroke Scale, and prestroke modified Rankin Scale. Both conservative and liberal estimates of prevalence of large vessel occlusion and large core were then applied based on literature review (unavailable within the 2015 GCNKSS). This eligibility was then extrapolated to the 2020 US population. RESULTS: Of the 1 057 183 adults within GCNKSS in 2015, 2741 had an ischemic stroke and 2176 had data available for analysis. We calculated that 8659 to 17 219 patients (conservative to liberal) meet the current guideline-recommended EVT criteria (nonlarge core, no prestroke disability, and National Institutes of Health Stroke Scale score ≥6) in the United States. Estimates (conservative to liberal) for expanded EVT eligibility subpopulations include (1) 5316 to 10 635 by large core; (2) 10 635 to 21 270 by mild presenting deficits with low National Institutes of Health Stroke Scale score; (3) 13 572 to 27 089 by higher prestroke disability; and (4) 7039 to 14 180 by >1 criteria. These expanded eligibility subpopulations amount to 36 562 to 73 174 patients. CONCLUSIONS: An estimated 8659 to 17 219 adult patients in the United States met strict EVT eligibility criteria in 2020. A 4-fold increase in population-based EVT eligibility can be anticipated with incremental adoption of recent or future positive trials. US stroke systems need to be rapidly optimized to handle all EVT-eligible patients with stroke.

Endovascular Versus Medical Management in Distal Medium Vessel Occlusion Stroke: The DUSK Study.

BACKGROUND: Endovascular treatment (EVT) is part of the usual care for proximal vessel occlusion strokes. However, the safety and effectiveness of EVT for distal medium vessel occlusions remain unclear. We sought to compare the clinical outcomes of EVT to medical management (MM) for isolated distal medium vessel occlusions. METHODS: This is a retrospective analysis of prospectively collected data from seven comprehensive stroke centers. Patients were included if they had isolated distal medium vessel occlusion strokes due to middle cerebral artery M3/M4, anterior cerebral artery A2/A3, or posterior cerebral artery P1/P2 segments. Patients treated with EVT or MM were compared with multivariable logistic regression and inverse probability of treatment weighting. The primary outcome was the shift in the degree of disability as measured by the modified Rankin Scale (mRS) at 90 days. Secondary outcomes included 90-day good (mRS score, 0-2) and excellent (mRS score, 0-1) outcomes. Safety measures included symptomatic intracranial hemorrhage and 90-day mortality. RESULTS: A total of 321 patients were included in the analysis (EVT, 179; MM, 142; 40.8% treated with intravenous thrombolysis). In the inverse probability of treatment weighting model, there were no significant differences between EVT and MM in terms of the overall degree of disability (mRS ordinal shift; adjusted odds ratio [aOR], 1.25 [95% CI, 0.95-1.64]; P=0.110), rates of good (mRS score, 0-2; aOR, 1.32 [95% CI, 0.97-1.80]; P=0.075) and excellent (aOR, 1.32 [95% CI, 0.94-1.85]; P=0.098) outcomes, or mortality (aOR, 1.20 [95% CI, 0.78-1.85]; P=0.395) at 90 days. The multivariable regression model showed similar findings. Moreover, there was no difference between EVT and MM in rates of symptomatic intracranial hemorrhage in the multivariable regression model (aOR, 0.57 [95% CI, 0.21-1.58]; P=0.277), but the inverse probability of treatment weighting model showed a lower likelihood of symptomatic intracranial hemorrhage (aOR, 0.46 [95% CI, 0.24-0.85]; P=0.013) in the EVT group. CONCLUSIONS: This multicenter study failed to demonstrate any significant outcome differences among patients with isolated distal medium vessel occlusions treated with EVT versus MM. These findings reinforce clinical equipoise. Randomized clinical trials are ongoing and will provide more definite evidence.

Outcomes of Bridging Intravenous Thrombolysis Versus Endovascular Therapy Alone in Late-Window Acute Ischemic Stroke.

BACKGROUND: Studies comparing bridging intravenous thrombolysis (IVT) with direct endovascular therapy (EVT) in patients with acute ischemic stroke who present late are limited. We aimed to compare the clinical outcomes and safety of bridging IVT in patients with acute ischemic stroke due to anterior circulation large vessel occlusion who underwent EVT 6 to 24 hours after time last known well. METHODS: We enrolled patients with anterior circulation large vessel occlusion stroke and a National Institutes of Health Stroke Scale score of ≥6 from 20 centers across 10 countries in the multicenter retrospective CLEAR study (CT for Late Endovascular Reperfusion) between January 2014 and May 2022. We used inverse probability of treatment weighting modeling adjusted for clinical and imaging confounders to compare functional outcomes, reperfusion success, symptomatic intracranial hemorrhage, and mortality between EVT patients with and without prior IVT. RESULTS: Of 5098 patients screened for eligibility, we included 2749 patients, of whom 549 received bridging IVT before EVT. The timing of IVT was not recorded. Witnessed stroke onset and transfer rates were higher in the bridging IVT group (25% versus 12% and 77% versus 55%, respectively, P value for both <0.0001), and time intervals between stroke onset and treatment were shorter (time last known well-start of EVT median 560 minutes [interquartile range, 432-791] versus 724 minutes [interquartile range, 544-912]; P<0.0001). After adjustment for confounders, there was no difference in functional outcome at 3 months (adjusted common odds ratio for modified Rankin Scale shift, 1.03 [95% CI, 0.89-1.19]; P=0.72) or successful reperfusion (adjusted odds ratio, 1.19 [95% CI, 0.81-1.75]; P=0.39). There were no safety concerns associated with bridging IVT versus direct EVT (symptomatic intracranial hemorrhage: adjusted odds ratio, 0.75 [95% CI, 0.38-1.48]; P=0.40; mortality: adjusted odds ratio, 1.14 [95% CI, 0.89-1.46]; P=0.31). Results were unchanged when the analysis was limited to patients who received IVT >6 hours after last known well. CONCLUSIONS: In patients with an anterior circulation large vessel occlusion stroke who underwent EVT 6 to 24 hours from last known well, bridging IVT was not associated with a difference in outcomes compared with direct EVT. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04096248.

Value of intravenous thrombolysis in endovascular treatment for large-vessel anterior circulation stroke: individual participant data meta-analysis of six randomised trials.

BACKGROUND: Intravenous thrombolysis is recommended before endovascular treatment, but its value has been questioned in patients who are admitted directly to centres capable of endovascular treatment. Existing randomised controlled trials have indicated non-inferiority of endovascular treatment alone or have been statistically inconclusive. We formed the Improving Reperfusion Strategies in Acute Ischaemic Stroke collaboration to assess non-inferiority of endovascular treatment alone versus intravenous thrombolysis plus endovascular treatment. METHODS: We conducted a systematic review and individual participant data meta-analysis to establish non-inferiority of endovascular treatment alone versus intravenous thrombolysis plus endovascular treatment. We searched PubMed and MEDLINE with the terms "stroke", "endovascular treatment", "intravenous thrombolysis", and synonyms for articles published from database inception to March 9, 2023. We included randomised controlled trials on the topic of interest, without language restrictions. Authors of the identified trials agreed to take part, and individual participant data were provided by the principal investigators of the respective trials and collated centrally by the collaborators. Our primary outcome was the 90-day modified Rankin Scale (mRS) score. Non-inferiority of endovascular treatment alone was assessed using a lower boundary of 0·82 for the 95% CI around the adjusted common odds ratio (acOR) for shift towards improved outcome (analogous to 5% absolute difference in functional independence) with ordinal regression. We used mixed-effects models for all analyses. This study is registered with PROSPERO, CRD42023411986. FINDINGS: We identified 1081 studies, and six studies (n=2313; 1153 participants randomly assigned to receive endovascular treatment alone and 1160 randomly assigned to receive intravenous thrombolysis and endovascular treatment) were eligible for analysis. The risk of bias of the included studies was low to moderate. Variability between studies was small, and mainly related to the choice and dose of the thrombolytic drug and country of execution. The median mRS score at 90 days was 3 (IQR 1-5) for participants who received endovascular treatment alone and 2 (1-4) for participants who received intravenous thrombolysis plus endovascular treatment (acOR 0·89, 95% CI 0·76-1·04). Any intracranial haemorrhage (0·82, 0·68-0·99) occurred less frequently with endovascular treatment alone than with intravenous thrombolysis plus endovascular treatment. Symptomatic intracranial haemorrhage and mortality rates did not differ significantly. INTERPRETATION: We did not establish non-inferiority of endovascular treatment alone compared with intravenous thrombolysis plus endovascular treatment in patients presenting directly at endovascular treatment centres. Further research could focus on cost-effectiveness analysis and on individualised decisions when patient characteristics, medication shortages, or delays are expected to offset a potential benefit of administering intravenous thrombolysis before endovascular treatment. FUNDING: Stryker and Amsterdam University Medical Centers, University of Amsterdam.

Comparison of CT Perfusion Software Packages for Thrombectomy Eligibility.

INTRODUCTION: Computed tomography perfusion (CTP) has played an important role in patient selection for mechanical thrombectomy (MT) in acute ischemic stroke. We aimed to investigate the agreement between perfusion parametric maps of 3 software packages - RAPID (RapidAI-IschemaView), Viz CTP(Viz.ai), and e-CTP(Brainomix) - in estimating baseline ischemic core volumes of near completely/completely reperfused patients. METHODS: We retrospectively reviewed a prospectively maintained MT database to identify patients with anterior circulation large vessel occlusion strokes (LVOS) involving the internal carotid artery or middle cerebral artery M1-segment and interpretable CTP maps treated during September 2018 to November 2019. A subset of patients with near-complete/complete reperfusion (expanded thrombolysis in cerebral infarction [eTICI] 2c-3) was used to compare the pre-procedural prediction of final infarct volumes. RESULTS: In this analysis of 242 patients with LVOS, RAPID and Viz CTP relative cerebral blood flow (rCBF) < 30% values had substantial agreement (ρ = 0.767 [95% confidence interval [CI] = 0.71-0.81]) as well as for RAPID and e-CTP (ρ = 0.668 [95% CI = 0.61-0.71]). Excellent agreement was seen for time to maximum of the residue function (Tmax ) > 6 seconds between RAPID and Viz CTP (ρ = 0.811 [95% CI = 0.76-0.84]) and substantial for RAPID and e-CTP (ρ = 0.749 [95% CI = 0.69-0.79]). Final infarct volume (FIV) prediction (n = 136) was substantial in all 3 packages (RAPID ρ = 0.744; Viz CTP ρ = 0.711; and e-CTP ρ = 0.600). CONCLUSION: Perfusion parametric maps of the RAPID, Viz CTP, and e-CTP software have substantial agreement in predicting final infarct volume in near-completely/completely reperfused patients. ANN NEUROL 2023;94:848-855.

Real-World Outcomes of Endovascular Thrombectomy for Basilar Artery Occlusion: Results of the BArONIS Study.

OBJECTIVE: To evaluate clinical outcomes of endovascular thrombectomy (EVT) for acute basilar artery occlusion (BAO) using population-level data from the United States. METHODS: Weighted discharge data from the National Inpatient Sample were queried to identify adult patients with acute BAO during the period of 2015 to 2019 treated with EVT or medical management only. Complex samples statistical methods and propensity-score adjustment using inverse probability of treatment weighting (IPTW) were performed to assess clinical endpoints. RESULTS: Among 3,950 BAO patients identified, 1,425 (36.1%) were treated with EVT [mean age 66.7 years, median National Institute of Health Stroke Scale (NIHSS) score 22]. On unadjusted analysis, 155 (10.9%) EVT patients achieved favorable functional outcomes (discharge disposition to home without services), while 515 (36.1%) experienced in-hospital mortality, and 20 (1.4%) developed symptomatic intracranial hemorrhage (sICH). Following propensity-score adjustment by IPTW accounting for age, stroke severity, and comorbidity burden, EVT was independently associated with favorable functional outcome [adjusted odds ratio (aOR) 1.25, 95% confidence interval (CI) 1.07, 1.46; p = 0.004], but not with in-hospital mortality or sICH. In an IPTW-adjusted sub-group analysis of patients with NIHSS scores >20, EVT was associated with both favorable functional outcome (discharge disposition to home or to acute rehabilitation) (aOR 1.55, 95% CI 1.24, 1.94; p < 0.001) and decreased mortality (aOR 0.78, 95% CI 0.69, 0.89; p < 0.001), but not with sICH. INTERPRETATION: This retrospective population-based analysis using a large national registry provides real-world evidence of a potential benefit of EVT in acute BAO patients. ANN NEUROL 2023;94:55-60.

Higher Procedural Volumes Are Associated with Faster Treatment Times, Better Functional Outcomes, and Lower Mortality in Patients Undergoing Endovascular Treatment for Acute Ischemic Stroke.

OBJECTIVE: We aimed to characterize the association of hospital procedural volumes with outcomes among acute ischemic stroke (AIS) patients undergoing endovascular therapy (EVT). METHODS: This was a retrospective, observational cohort study using data prospectively collected from January 1, 2016 to December 31, 2019 in the Get with the Guidelines-Stroke registry. Participants were derived from a cohort of 60,727 AIS patients treated with EVT within 24 hours at 626 hospitals. The primary cohort excluded patients with pretreatment National Institutes of Health Stroke Scale (NIHSS) < 6, onset-to-treatment time > 6 hours, and interhospital transfers. There were 2 secondary cohorts: (1) the EVT metrics cohort excluded patients with missing data on time from door to arterial puncture and (2) the intravenous thrombolysis (IVT) metrics cohort only included patients receiving IVT ≤4.5 hours after onset. RESULTS: The primary cohort (mean ± standard deviation age = 70.7 ± 14.8 years; 51.2% female; median [interquartile range] baseline NIHSS = 18.0 [13-22]; IVT use, 70.2%) comprised 21,209 patients across 595 hospitals. The EVT metrics cohort and IVT metrics cohort comprised 47,262 and 16,889 patients across 408 and 601 hospitals, respectively. Higher procedural volumes were significantly associated with higher odds (expressed as adjusted odds ratio [95% confidence interval] for every 10-case increase in volume) of discharge to home (1.03 [1.02-1.04]), functional independence at discharge (1.02 [1.01-1.04]), and lower rates of in-hospital mortality (0.96 [0.95-0.98]). All secondary measures were also associated with procedural volumes. INTERPRETATION: Among AIS patients primarily presenting to EVT-capable hospitals (excluding those transferred from one facility to another and those suffering in-hospital strokes), EVT at hospitals with higher procedural volumes was associated with faster treatment times, better discharge outcomes, and lower rates of in-hospital mortality. ANN NEUROL 2023.

Mediation of Successful Reperfusion Effect through Infarct Growth and Cerebral Edema: A Pooled, Patient-Level Analysis of EXTEND-IA Trials and SELECT Prospective Cohort.

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 (ß = -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.

Sex differences in acute stroke metrics and outcome dependent on COVID status.

BACKGROUND AND PURPOSE: Biological sex is known to have an impact on quality metrics of acute stroke. We aimed to determine whether COVID positivity accentuates this effect and constitutes worse outcome. METHODS: The present analysis was based on the Global COVID-19 Stroke Registry, a retrospective, international, cohort study of consecutive ischemic stroke patients receiving intravenous thrombolysis and/or endovascular thrombectomy between 1 March 2020 and 30 June 2021. We investigated differences between the sexes in patient characteristics, acute stroke metrics as well as post-stroke outcome in COVID-positive and COVID-negative stroke patients undergoing acute revascularization procedures. RESULTS: A total of 15,128 patients from 106 centers were recorded in the Global COVID-19 Stroke Registry, 853 (5.6%) of whom were COVID-positive. Overall, COVID-positive individuals were treated significantly slower according to every acute stroke metric compared to COVID-negative patients. We were able to show that key quality indicators in acute stroke treatment were unfavorable for COVID-negative women compared to men (last-seen-well-to-door time + 11 min in women). Furthermore, COVID-negative women had worse 3-month outcomes (3-month modified Rankin Scale score [interquartile range] 3.0 [4.0] vs. 2.0 [3.0]; p < 0.01), even after adjusting for confounders. In COVID-positive individuals no such difference between the sexes, either in acute management metrics or in 3-month outcome, was seen. CONCLUSION: Known sex-related differences in acute stroke management exist and extend to times of crisis. Nevertheless, if patients were COVID-19-positive at stroke onset, women and men were treated the same, which could be attributed to structured treatment pathways.

Assessment of the safety and efficacy of the Zoom 45 and 55 reperfusion catheters for medium and distal mechanical thrombectomies: A multi-institutional study.

INTRODUCTION: The Zoom aspiration catheters harbor novel dimensions and construction to enhance trackability and deliverability. In addition, a beveled tip may improve thrombus interaction and aspiration force for a set inner diameter. This study evaluates their utility in medium and distal vessel occlusions. OBJECTIVE: To evaluate the safety and efficacy of Zoom 45 and 55 aspiration catheters in medium and distal vessel thrombectomy. METHODS: Patients treated for distal vessel occlusions via mechanical thrombectomy utilizing either the Zoom 45/55 catheter or a historical control catheter between 2021-2022 at two institutions were included in this study. Medium and distal occlusions were defined as any anterior or posterior cerebral artery branch as well as the M2-4 segment of the middle cerebral artery (MCA). Preprocedural, procedural, and postprocedural variables were obtained. RESULTS: Thirty-eight patients underwent thrombectomy with Zoom 45 or 55 catheters; four had multiple occluded vessels. Occlusion location included the M2 in 32 cases, M3-4 in 7 cases, A2 in 2 cases and P2 in 1 case. The mean number of passes per occlusion was 1.6 and overall successful reperfusion (TICI 2b or greater) was achieved in 84 % of cases. There were no symptomatic procedure-related complications such as perforation or post-procedural symptomatic ICH. Modified Rankin scores rates of 0-2, 3-5, and 6 at three months post-procedure were 35.7 %, 21.4 %, and 42.9 %, respectively. CONCLUSIONS: The Zoom beveled tip aspiration catheters are safe and effective for more challenging medium and distal vessel occlusions.

Risk factors and operative risk of large vessel occlusion and stroke during cardiac surgery.

OBJECTIVE: Perioperative Large Vessel Occlusions (LVOs) occurring during and following surgery are of immense clinical importance. As such, we aim to present risk factors and test if the Society of Thoracic Surgery (STS) mortality and stroke risk scores can be used to assess operative risk. METHODS: Using data containing 7 index cardiac operations at a single tertiary referral center from 2010 to 2022, logistic and multivariate regression analysis was performed to identify factors that correlate to higher operative LVO and stroke rate. Odds ratios and confidence intervals were also obtained to test if the STS-Predicted Risk of Mortality (PROM) and -Predicted Risk of Stroke (PROS) scores were positively correlated to operative LVO and stroke rate. RESULTS: Multivariate modeling showed primary risk factors for an operative LVO were diabetes (OR: 1.727 [95 % CI: 1.060-2.815]), intracranial or extracranial carotid stenosis (OR: 3.661 [95 % CI: 2.126-6.305]), and heart failure as defined by NYHA class (Class 4, OR: 3.951 [95 % CI: 2.092-7.461]; compared to Class 1). As the STS-PROM increased, the relative rate of LVO occurrence increased (very high risk, OR: 6.576 [95 % CI: 2.92-14.812], high risk, OR: 2.667 [1.125-6.322], medium risk, OR: 2.858 [1.594-5.125]; all compared to low risk). STS-PROS quartiles showed a similar relation with LVO risk (quartile 4, OR: 7.768 [95 % CI: 2.740-22.027], quartile 3, OR: 5.249 [1.800-15.306], quartile 2, OR:2.980 [0.960-9.248]; all compared to quartile 1). CONCLUSIONS: Patients with diabetes, carotid disease and heart failure are at high risk for operative LVO. Both STS-PROM and -PROS can be useful metrics for preoperative measuring of LVO risks.

Cost-benefit analysis of intraoperative neuromonitoring for cardiac surgery.

BACKGROUND: Intraoperative neuromonitoring (IONM) can detect large vessel occlusion (LVO) in real-time during surgery. The aim of this study was to conduct a cost-benefit analysis of utilizing IONM among patients undergoing cardiac surgery. METHODS: A decision-analysis tree with terminal Markov nodes was constructed to model functional outcome, as measured via the modified Rankin Scale (mRS), among 65-year-old patients undergoing cardiac surgery. Our cost-benefit analysis compares the use of IONM (electroencephalography and somatosensory evoked potential) against no IONM in preventing neurological complications from perioperative LVO during cardiac surgery. The study was performed over a lifetime horizon from a societal perspective in the United States. Base case and one-way probabilistic sensitivity analyses were performed. RESULTS: At a baseline LVO rate of 0.31%, the mean attributable lifetime expenditure for IONM-monitored cardiac surgeries relative to unmonitored cardiac surgeries was $1047.41 (95% CI, $742.12 - $1445.10). At a critical LVO rate of approximately 3.67%, the costs of both monitored and unmonitored cardiac surgeries were the same. Above this critical rate, implementing IONM became cost-saving. On one-way sensitivity analysis, variation in LVO rate from 0% - 10% caused lifetime costs attributable to receiving IONM to range from $1150.47 - $29404.61; variations in IONM cost, percentage of intervenable LVOs, IONM sensitivity, and mechanical thrombectomy cost exerted comparably minimal influence over lifetime costs. DISCUSSION: We find considerable cost savings favoring the use of IONM under certain parameters corresponding to high-risk patients. This study will provide financial perspective to policymakers, clinicians, and patients alike on the appropriate use of IONM during cardiac surgery.

Association Between Endovascular Therapy Time to Treatment and Outcomes in Patients With Basilar Artery Occlusion.

BACKGROUND: Basilar artery occlusion (BAO) is a devastating condition without definitive evidence to guide treatment. Whereas the association between faster treatment times with endovascular therapy (EVT) and better outcomes in anterior circulation is well established, whether this relationship exists for patients with BAO is not well delineated. METHODS: We used individual-level patient data from the Get With The Guidelines-Stroke nationwide US registry prospectively collected from January 2015 to December 2019. We identified individuals with BAO treated with EVT within 24 hours of symptom onset. The primary outcomes examined were in-hospital mortality, discharge home, ambulatory at discharge, independent at discharge (modified Rankin Scale score 0 to 2), substantial reperfusion (modified Thrombolysis in Cerebral Infarction score 2b or 3), and symptomatic intracranial hemorrhage. Using logistic regression models, we evaluated the association between time from symptom onset to treatment with EVT and outcomes. RESULTS: Among 3015 patients with BAO treated with EVT, the mean age was 65.9 years, 38.8% were women, and the median National Institutes of Health Stroke Scale score at presentation was 17 (interquartile range, 8-26). Median onset to EVT time was 406 minutes (interquartile range, 252-688). From 2015 to 2019, there was an overall increase in the median onset to EVT times (380-411 minutes; P=0.016) but no significant change in the proportion of patients treated within 6 hours of symptom onset (48.4%-44.0%; P=0.17). After risk adjustment for patient and hospital-level factors, there were significantly lower odds of in-hospital mortality (adjusted odds ratio [aOR], 0.55 [95% CI, 0.45-0.68]) and symptomatic intracranial hemorrhage (aOR, 0.52 [95% CI, 0.32-0.84]) and significantly higher odds of ambulation at discharge (aOR, 1.72 [95% CI, 1.37-2.16]), discharge home (aOR, 2.19 [95% CI, 1.73-2.77]), and independence at discharge (aOR, 2.21 [95% CI, 1.66-2.95]) when onset to EVT time was ≤6 hours compared with >6 hours. The fastest decay in good outcomes per hour occurred within 6 hours of symptom onset. CONCLUSIONS: Among patients receiving EVT for BAO, faster treatment from symptom onset was associated with improved outcomes. These findings support efforts to achieve rapid treatment with EVT for patients with BAO.