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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 [ABSTRACT FROM AUTHOR]

Background Proper identification of infarct extent is crucial for thrombectomy and prognostication. We sought to study the frequency and topographic aspects of those cases in which CT perfusion (CTP) misses a core lesion that is present on initial non-contrast CT (NCCT). Methods A review was carried out of a prospectively collected database of endovascular patients with anterior circulation large vessel occlusion strokes from January 2014 to November 2018. Patients with an e-ASPECTS <10 and adequate CTP maps were included. Total missed ischemic core (TMC) was defined as a CTP core lesion (relative cerebral blood flow <30%) <1 mL with a visualized hypodensity on NCCT. Results In total, 629 patients were analyzed of which 161 (25.6%) had a TMC. On univariate analysis, TMC was associated with isolated deep middle cerebral artery (MCA) strokes (77.6% vs 56.6%, p<0.001), lower National Institutes of Health Stroke Scale (NIHSS) score (9 (15-20) vs 17 (13-21), p=0.007) and longer times to treatment (452 (288-652) min vs 355 (236-655) min, p=0.03). After adjusting for identifiable confounders, isolated deep MCA stroke was an independent predictor of TMC (OR 2.49 (95% CI 1.63 to 3.8), p<0.001). There were no differences between patients presenting with a TMC and those not with good outcomes (modified Rankin Scale 0-2) (50.8% vs 47.6%, p=0.53) or 90-day mortality (23% vs 17.6%, p=0.17). However, TMC was associated with lower rates of any parenchymal hematomas (5.2% vs 14.6%, p=0.02; aOR 0.11 (95% CI 0.01 to 0.91), p=0.04) and smaller final infarct volumes (20.5 (11.3-42.9) mL vs 47.5 (20.3-85) mL, p<0.001). Conclusions CTP may completely fail to detect ischemic core in as many as 25% of cases, especially in isolated deep MCA strokes. Technical refinements of the post-processing algorithms are therefore warranted. TMC infarcts may have a lower risk of reperfusion hemorrhage, potentially due to greater preservation of the neurovascular unit structure in face of delayed recovery of cerebral blood flow. [ABSTRACT FROM AUTHOR]

Background: The effect of time from stroke onset to thrombectomy in the extended time window remains poorly characterized. Aim: We aimed to analyze the relationship between time to treatment and clinical outcomes in the early versus extended time windows. Methods: Proximal anterior circulation occlusion patients from a multicentric prospective registry were categorized into early (≤6 h) or extended (>6–24 h) treatment window. Patients with baseline National Institutes of Health Stroke Scale (NIHSS) ≥ 10 and intracranial internal carotid artery or middle cerebral artery-M1-segment occlusion and pre-morbid modified Rankin scale (mRS) 0–1 ("DAWN-like" cohort) served as the population for the primary analysis. The relationship between time to treatment and 90-day mRS, analyzed in ordinal (mRS shift) and dichotomized (good outcome, mRS 0–2) fashion, was compared within and across the extended and early windows. Results: A total of 1603 out of 2008 patients qualified. Despite longer time to treatment (9[7–13.9] vs. 3.4[2.5–4.3] h, p < 0.001), extended-window patients (n = 257) had similar rates of symptomatic intracranial hemorrhage (sICH; 0.8% vs. 1.7%, p = 0.293) and 90-day-mortality (10.5% vs. 9.6%, p = 0.714) with only slightly lower rates of 90-day good outcomes (50.4% vs. 57.6%, p = 0.047) versus early-window patients (n = 709). Time to treatment was associated with 90-day disability in both ordinal (adjusted odd ratio (aOR), ≥ 1-point mRS shift: 0.75; 95%CI [0.66–0.86], p < 0.001) and dichotomized (aOR, mRS 0–2: 0.73; 95%CI [0.62–0.86], p < 0.001) analyses in the early- but not in the extended-window (aOR, mRS shift: 0.96; 95%CI [0.90–1.02], p = 0.15; aOR, mRS0–2: 0.97; 95%CI [0.90–1.04], p = 0.41). Early-window patients had significantly lower 90-day functional disability (aOR, mRS shift: 1.533; 95%CI [1.138–2.065], p = 0.005) and a trend towards higher rates of good outcomes (aOR, mRS 0–2: 1.391; 95%CI [0.972–1.990], p = 0.071). Conclusions: The impact of time to thrombectomy on outcomes appears to be time dependent with a steep influence in the early followed by a less significant plateau in the extended window. However, every effort should be made to shorten treatment times regardless of ischemia duration. [ABSTRACT FROM AUTHOR]

Background Age and infarct volume are among the most powerful predictors of outcome after large vessel occlusion acute strokes (LVOS). Objective To study the impact of age- adjusted final infarct volume (FIV) on functional outcomes. Methods Review of a prospectively collected thrombectomy database at a tertiary care center between September 2010 and February 2018. Consecutive patients with anterior circulation LVOS who achieved full reperfusion (modified Thrombolysis in Cerebral Infarction 3) were categorized into four age groups: (G1) <60 years, (G2) 60-69, (G3) 70-79, (G4) ≥80 years. The Youden Index was used to identify the optimal FIV cut- off point for good outcome (modified Rankin Scale score 0--2) discrimination in each group and the overall population. The predictive ability of these specific thresholds was evaluated using binary logistic regressions and compared with the non- age- adjusted cut- off point. Results 516 patients were analyzed (G1: n=171, G2: n=130, G3: n=103, G4: n=112). Patients with poor outcome had a larger FIV in each group (p<0.01 for all). The target FIV cut- off point decreased with increased age: G1: 45.7 mL (sensitivity 56%, specificity 80%); G2: 30.4 mL (sensitivity 63%, specificity 75%); G3: 20.2 mL (sensitivity 76%, specificity 65%); G4: 16.9 mL (sensitivity 68%, specificity 70%). The non- age- adjusted cut- off point was 19.2 mL (sensitivity 70%, specificity 59%). In multivariate analysis, adjusting for confounders including age and FIV, achieving a FIV less than the age- adjusted threshold was an independent predictor of good outcome (aOR=2.72, 95% CI 1.41 to 5.24, p<0.001). In contrast, a similar model including the non- age- adjusted target cut- off point failed to reveal an association with good outcome (aOR=1.72, 95% CI 0.93 to 3.19, p<0.085). Furthermore, the latter model had a weaker outcome predictive ability as assessed by the Akaike information criterion (409 vs 403). Conclusions Age- adjusted infarct volume represents a strong outcome discriminator beyond age and infarct volume in isolation and might help to refine patient selection and improve outcome prognostication in stroke thrombectomy. [ABSTRACT FROM AUTHOR]

Background Patients with large vessel occlusion stroke (LVOS) and a low Alberta Stroke Program Early CT Score (ASPECTS) are often not offered endovascular therapy (ET) as they are thought to have a poor prognosis. Objective To compare the outcomes of patients with low and high ASPECTS undergoing ET based on baseline infarct volumes. Methods Review of a prospectively collected endovascular database at a tertiary care center between September 2010 and March 2020. All patients with anterior circulation LVOS and interpretable baseline CT perfusion (CTP) were included. Subjects were divided into groups with low ASPECTS (0-5) and high ASPECTS (6- 10) and subsequently into limited and large CTP- core volumes (cerebral blood flow 30% >70 cc). The primary outcome measure was the difference in rates of 90- day good outcome as defined by a modified Rankin Scale (mRS) score of 0 to 2 across groups. Results 1248 patients fit the inclusion criteria. 125 patients had low ASPECTS, of whom 16 (12.8%) had a large core (LC), whereas 1123 patients presented with high ASPECTS, including 29 (2.6%) patients with a LC. In the category with a low ASPECTS, there was a trend towards lower rates of functional independence (90- day modified Rankin Scale (mRS) score 0- 2) in the LC group (18.8% vs 38.9%, p=0.12), which became significant after adjusting for potential confounders in multivariable analysis (aOR=0.12, 95% CI 0.016 to 0.912, p=0.04). Likewise, LC was associated with significantly lower rates of functional independence (31% vs 51.9%, p=0.03; aOR=0.293, 95% CI 0.095 to 0.909, p=0.04) among patients with high ASPECTS. Conclusions Outcomes may vary significantly in the same ASPECTS category depending on infarct volume. Patients with ASPECTS -5 but baseline infarct volumes -70 cc may achieve independence in nearly 40% of the cases and thus should not be excluded from treatment. [ABSTRACT FROM AUTHOR]

Background There is a paucity of data regarding mechanical thrombectomy (MT) in distal arterial occlusions (DAO). We aim to evaluate the safety and efficacy of MT in patients with DAO and compare their outcomes with proximal arterial occlusion (PAO) strokes. Methods The Trevo Registry was a prospective openlabel MT registry including 2008 patients from 76 sites across 12 countries. Patients were categorized into: PAO: intracranial ICA, and MCA--M1; and DAO: MCA--M2, MCA--M3, ACA, and PCA. Baseline and outcome variables were compared across the PAO vs DAO patients with pre-morbid mRS 0--2. Results Among 407 DAOs including 350 (86.0%) M2, 25 (6.1%) M3, 10 (2.5%) ACA, and 22 (5.4%) PCA occlusions, there were 376 DAO with pre-morbid mRS 0--2 which were compared with 1268 PAO patients. The median baseline NIHSS score was lower in DAO (13 [8--18] vs 16 [12--20], P<0.001). There were no differences in terms of age, sex, IV-tPA use, co-morbidities, or time to treatment across DAO vs PAO. The rates of post-procedure reperfusion, symptomatic intracranial hemorrhage (sICH), and 90-mortality were comparable between both groups. DAO showed significantly higher rates of 90-day mRS 0--2 (68.3% vs 56.5%, P<0.001). After adjustment for potential confounders, the level of arterial occlusion was not associated with the chances of excellent outcome (DAO for 90-day mRS 0--1: OR; 1.18, 95% CI [0.90 to 1.54], P=0.225), successful reperfusion or SICH. However, DAO patients were more likely to be functionally independent (mRS 0--2: OR; 1.45, 95% CI [1,09 to 1.92], P=0.01) or dead (OR; 1.54, 95% CI [1.06 to 2.27], P=0.02) at 90 days. Conclusion Endovascular therapy in DAO appears to result in a comparable safety and technical success profile as in PAO. The potential benefits of DAO thrombectomy should be investigated in future randomized trials. [ABSTRACT FROM AUTHOR]

Background The first-pass effect (FPE) has emerged as a key metric for efficacy in mechanical thrombectomy (MT). The hyperdense vessel sign (HDVS) on non-contrast head CT (NCCT) indicates a higher clot content of red blood cells. Objective To assess whether the HDVS could serve as an imaging biomarker for guiding first-line device selection in MT. Methods A prospective MT database was reviewed for consecutive patients with anterior circulation large vessel occlusion stroke who underwent thrombectomy with stent retriever (SR) or contact aspiration (CA) as first-line therapy between January 2012 and November 2018. Pretreatment NCCT scans were evaluated for the presence of HDVS. The primary outcome was FPE (modified Thrombolysis in Cerebral Infarction score 2c/3). The primary analysis was the interaction between HDVS and thrombectomy modality on FPE. Secondary analyses aimed to evaluate the predictors of FPE. Results A total of 779 patients qualified for the analysis. HDVS and FPE were reported in 473 (60.7%) and 286 (36.7%) patients, respectively. The presence of HDVS significantly modified the effect of thrombectomy modality on FPE (p=0.01), with patients with HDVS having a significantly higher rate of FPE with a SR (41.3% vs 22.2%, p=0.001; adjusted OR 2.11 (95% CI 1.20 to 3.70), p=0.009) and non-HDVS patients having a numerically better response to CA (41.4% vs 33.9%, p=0.28; adjusted OR 0.58 (95% CI 0.311 to 1.084), p=0.088). Age (OR 1.01 (95% CI 1.00 to 1.02), p=0.04) and balloon guide catheter (OR 2.08 (95% CI 1.24 to 3.47), p=0.005) were independent predictors of FPE in the overall population. Conclusion Our data suggest that patients with HDVS may have a better response to SRs than CA for the FPE. Larger confirmatory prospective studies are warranted. [ABSTRACT FROM AUTHOR]

background First pass reperfusion (FPR) has been established as a key performance metric in mechanical thrombectomy (MT). The impact of FPR may be more relevant in fast progressors. We aim to study the impact of baseline Alberta Stroke Program Early CT Score (ASPECTS) on non- contrast CT and hypoperfusion intensity ratio (HIR) on CT perfusion on clinical outcomes after FPR. Methods A prospective MT database was reviewed for patients with isolated occlusion of the intracranial internal carotid artery and/or middle cerebral artery M1 segment who underwent MT with complete reperfusion (modified Thrombolyis in Cerebral Infarction score 2c--3) from January 2012 to May 2019. The overall population was divided into ASPECTS >7 versus ≤7 and the subgroup of patients with baseline CT perfusion was divided into HIR <0.3 versus ≥0.3. Univariable and multivariable analyses were performed to establish the predictors of 90- day functional independence (modified Rankin Scale (mRS) ≤2) in each subgroup. results A total of 436 patients were included in the analyses. FPR was achieved in 254 (58.3%) patients. ASPECTS modified the effect of FPR on clinical outcomes, with FPR predicting good outcomes in patients with ASPECTS ≤7 (46% vs 29%, adjusted OR 3.748; 95% CI 1.590 to 8.838, p=0.003) while no significant effect was detected in those with ASPECTS >7 (62.3% vs 53.1%, adjusted OR 1.372; 95% CI 0.798 to 2.358, p=0.25). Similarly, FPR predicted good outcomes in patients with HIR ≥0.3 (54.8% vs 41.9%, adjusted OR 2.204; 95% CI 1.148 to 4.233, p=0.01) but not in those with HIR <0.3 (62.9% vs 52.8%, adjusted OR 1.524; 95% CI 0.592 to 3.920, p=0.38). Conclusions The impact of FPR on functional outcomes is highly dependent on baseline imaging characteristics, with a more prominent influence in patients presenting with lower ASPECTS and/or higher HIR. [ABSTRACT FROM AUTHOR]

Background Given the relative strength of prior mechanical thrombectomy (MT) data in face of the perceived poor natural history of emergent large vessel occlusion strokes, randomization to medical therapy during the recent clinical MT trials raised ethical challenges at individual and institutional levels despite overall clinical equipoise. Methods In a thrombectomy stroke registry, we compared treatment rates preceding and following the SWIFT-PRIME and DAWN trials. Based on effect sizes of treatment in both trials, we estimated missed opportunities due to randomization to medical therapy and estimated the societal benefit resulting from additional patients who benefited as a result of these studies. Results The average monthly thrombectomy rate in the SWIFT-PRIME time window increased from 14.1±4 patients-per-month (ppm) to 23.8±6 ppm (p<0.001). Twelve subjects were enrolled in SWIFT-PRIME and we estimated a missed opportunity of benefiting 2.3 of six subjects randomized to medical therapy. This was offset by providing treatment to an additional 9.7 ppm, resulting in an additional functional benefit to 3.7 ppm. Similarly, the thrombectomy rate in the DAWN window increased from 8.6±4 ppm pre-DAWN to 11.9±3.6 ppm post-DAWN (p<0.01). 38 subjects were enrolled in the DAWN trial with a missed opportunity to benefit eight of 16 subjects randomized to medical therapy. This was offset by the ability to offer MT to an additional 3.3 ppm, bringing definite benefit to an additional 1.65 ppm. Conclusion Completion of recent trials resulted in observable increases in rates of thrombectomy, translating to functional benefits that rapidly offset any missed opportunities due to randomization to medical therapy arms. [ABSTRACT FROM AUTHOR]

Background Age, neurologic deficits, core volume (CV), and clinical core or radiographic mismatch are considered in selection for endovascular therapy (ET) in anterior circulation emergent large vessel occlusion (aELVO). semiquantitative CV estimation by alberta stroke Programme early cT score (cT ASPECTS) and quantitative CV estimation by CT perfusion (CTP) are both used in selection paradigms. Objective To compare the prognostic value of CTP CV with CT ASPECTS in AELVO. Methods Patients in an institutional endovascular registry who had AELVO, pre-ET national institutes of health stroke scale (NIHSS) score, non-contrast CT head and CTP imaging, and prospectively collected 3-month modified rankin scale (mRS) score were included. Age-and NIHSS-adjusted models, including either CT ASPECTS or CTP volumes (relative cerebral blood flow <30% of normal tissue, total hypoperfusion, and radiographic mismatch), were compared using receiver operator characteristic analyses. results We included 508 patients with AELVO (60.8% M1 middle cerebral artery, 34% internal carotid artery, mean age 64.1±15.3 years, median baseline NIHSS score 16 (12-20), median baseline cT ASPECTS 8 (7-9), mean cV 16.7±24.8 ml). age, pre-ET NIHSS, CT ASPECTS, cV, hypoperfusion, and perfusion imaging mismatch volumes were predictors of good outcome (mRS score 0-2). There were no differences in prognostic accuracies between reference (age, baseline NIHSS, CT ASPECTS; area under the curve (AUC)=0.76) and additional models incorporating combinations of age, NIHSS, and CTP metrics including cV, total hypoperfusion or mismatch volume (AUCS 0.72-0.75). Predicted outcomes from cT asPecTs or cTP cV-based models had excellent agreement (R²=0.84, p<0.001). Conclusions incorporating cTP measures of core or penumbral volume, instead of CT ASPECTS, did not improve prognostication of 3-month outcomes, suggesting prognostic equivalence of CT ASPECTS and CTP CV. [ABSTRACT FROM AUTHOR]

Background Longer stent retrievers have recently become available and have theoretical advantages over their shorter counterparts. We aim to evaluate whether stent retriever length impacts reperfusion rates in stroke thrombectomy. Methods This was a retrospective analysis of a prospectively collected thrombectomy database in which equal diameter (4 mm) stent retrievers were used as the first-line strategy for intracranial internal carotid or middle cerebral artery M1 or M2 occlusions along with a balloon guide catheter from June 2011 to March 2017. The population was dichotomized into long (Trevo 4x30 mm/Solitaire 4x40 mm) or short (Trevo 4x20 mm/ Solitaire 4x20 mm) retrievers. The primary outcome was first-pass modified Thrombolysis in Cerebral Infarction (mTICI) 2b/3 reperfusion. Results Of 1126 thrombectomies performed within the study period, 420 were included. Age, gender, National Institutes of Health Stroke Scale, ASPECTS, IV tissue plasminogen activator use, stroke etiology, occlusion site, time from last-known-normal to puncture, distribution of Trevo and Solitaire, and the use of newer generation local thromboaspiration devices were comparable between the long and short retrievers. The short retriever group had more frequent hypertension, dyslipidemia, and atrial fibrillation. First-pass mTICI 2b/3 reperfusion was more common in the long retriever group (62% vs 50%; P=0.01). Parenchymal hematomas type 2, subarachnoid hemorrhage, 90-day modified Rankin Scale score 0-2, and mortality were comparable. Multivariable analysis indicated that long retriever (OR 2.2; 95% CI 1.3 to 3.6; P=0.001), radiopaque device (OR 2.1; 95% CI 1.2 to 3.4; P=0.003), and adjuvant local aspiration (OR 2.4; 95% CI 1.3 to 4.3; P=0.003) were independently associated with first-pass reperfusion. Conclusions The use of longer stent retrievers is an independent predictor of first-pass mTICI 2b/3 reperfusion. First-pass reperfusion was also associated with the use of radiopaque devices and adjuvant local aspiration. [ABSTRACT FROM AUTHOR]

Introduction it remains unclear whether patients presenting with large vessel occlusion strokes and mild symptoms benefit from thrombectomy. Objective To compare outcomes of endovascular therapy versus medical management in patients with large vessel occlusion strokes and national institute of health stroke scale (NIHss) score ≤5. Methods This was a retrospective analysis combining two large prospectively collected datasets including patients with (1) admission NIHss score ≤5, (2) premorbid modified rankin scale (mrs) score 0-2, and (3) middle cerebral-M1/M2, intracranial carotid, anterior cerebral or basilar artery occlusions. Groups receiving (1) endovascular treatment and (2) medical management were compared. The primary and secondary outcome measures were NIHss shift (discharge NIHss minus admission NIHss) and the rates of mrs 0-2 at discharge and 3-6 months, respectively. Univariate, multivariate, and matched analyses were performed. Results Eighty-eight patients received medical management and 30 thrombectomy. Multivariable analysis indicated thrombectomy was the only predictor of favorable NIHss shift (β -3.7, 95% CI -6.0 to -1.5, p=0.02), as well as independence at discharge (β -21.995% CI -41.4to -20.8, p<0.01) and 3-6-month follow-up (β -21.1, 95% CI -39.1 to -19.7, p<0.01). A matched analysis (based on age, baseline NIHss and intravenous tissue plasminogen activator use) produced 26 pairs. Endovascular therapy was statistically associated with lower NIHss at discharge (p=0.04), favorable NIHss shift (p=0.03), and increased independence rates at discharge (p=0.03) and 3-6-month follow-up (p=0.04). Conclusion In patients presenting with minimal stroke symptoms (NIHss score ≤5) and large vessel occlusion strokes, mechanical thrombectomy appears to be associated with a favorable shift of NIHss at discharge, as well as higher rates of independence at discharge and long-term follow-up. Confirmatory prospective studies are warranted. [ABSTRACT FROM AUTHOR]

Background and purpose Technological advances have helped to improve the efficiency of treating patients with large vessel occlusion in acute ischemic stroke. Unfortunately, the sequence of events prior to reperfusion may lead to significant treatment delays. This study sought to determine if high-volume (HV) centers were efficient at delivery of endovascular treatment approaches. Methods A retrospective review was performed of nine centers to assess a series of time points from obtaining a CT scan to the end of the endovascular procedure. Demographic, radiographic and angiographic variables were assessed by multivariate analysis to determine if HV centers were more efficient at delivery of care. Results A total of 442 consecutive patients of mean age 66±14 years and median NIH Stroke Scale score of 18 were studied. HV centers were more likely to treat patients after intravenous administration of tissue plasminogen activator and those transferred from outside hospitals. After adjusting for appropriate variables, HV centers had significantly lower times from CT acquisition to groin puncture (OR 0.991, 95% CI 0.989 to 0.997, p=0.001) and total procedure times (OR 0.991, 95% CI 0.986 to 0.996, p=0.001). Additionally, patients treated at HV centers were more likely to have a good clinical outcome (OR 1.86, 95% CI 1.11 to 3.10, p<0.018) and successful reperfusion (OR 1.82, 95% CI 1.16 to 2.86, p<0.008). Conclusions Significant delays occur in treating patients with endovascular therapy in acute ischemic stroke, offering opportunities for improvements in systems of care. Ongoing prospective clinical trials can help to assess if HV centers are achieving better clinical outcomes and higher reperfusion rates. [ABSTRACT FROM AUTHOR]