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.

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.

Sex Differences in Outcomes of Late-Window Endovascular Stroke Therapy.

BACKGROUND: The association between sex and outcome after endovascular thrombectomy of acute ischemic stroke is unclear. The aim of this study was to compare the clinical and safety outcomes between men and women treated with endovascular thrombectomy in the late 6-to-24-hour window period. METHODS: This multicenter, retrospective observational cohort study included consecutive patients who underwent endovascular thrombectomy of anterior circulation stroke in the late window from 66 clinical sites in 10 countries from January 2014 to May 2022. The primary outcome was the 90-day ordinal modified Rankin Scale score. Secondary outcomes included 90-day functional independence (FI), return of Rankin (RoR) to prestroke baseline, FI or RoR, symptomatic intracranial hemorrhage, and mortality. Multivariable and inverse probability of treatment weighting methods were used. We explored the interaction of sex with baseline characteristics on the outcomes ordinal modified Rankin Scale and FI or RoR. RESULTS: Of 1932 patients, 1055 were women and 877 were men. Women were older (77 versus 69 years), had higher rates of atrial fibrillation, hypertension, and greater prestroke disability, but there was no difference in baseline National Institutes of Health Stroke Scale score. Inverse probability of treatment weighting analysis showed no difference between women and men in ordinal modified Rankin Scale (odds ratio, 0.98 [95% CI, 0.79-1.21]), FI or RoR (odds ratio, 0.98 [95% CI, 0.78-1.22]), severe disability or mortality (odds ratio, 0.99 [95% CI, 0.80-1.23]). The multivariable analysis of the above end points was concordant. There were no interactions between baseline characteristics and sex on the outcomes of ordinal modified Rankin Scale and FI or RoR. CONCLUSIONS: In late presenting patients with anterior circulation stroke treated with endovascular thrombectomy in the 6 to 24-hour window, there was no difference in clinical or safety outcomes between men and women.

Endovascular Versus Medical Therapy in Posterior Cerebral Artery Stroke: Role of Baseline NIHSS Score and Occlusion Site.

BACKGROUND: Acute ischemic stroke with isolated posterior cerebral artery occlusion (iPCAO) lacks management evidence from randomized trials. We aimed to evaluate whether the association between endovascular treatment (EVT) and outcomes in iPCAO acute ischemic stroke is modified by initial stroke severity (baseline National Institutes of Health Stroke Scale [NIHSS]) and arterial occlusion site. METHODS: Based on the multicenter, retrospective, case-control study of consecutive iPCAO acute ischemic stroke patients (PLATO study [Posterior Cerebral Artery Occlusion Stroke]), we assessed the heterogeneity of EVT outcomes compared with medical management (MM) for iPCAO, according to baseline NIHSS score (≤6 versus >6) and occlusion site (P1 versus P2), using multivariable regression modeling with interaction terms. The primary outcome was the favorable shift of 3-month modified Rankin Scale (mRS). Secondary outcomes included excellent outcome (mRS score 0-1), functional independence (mRS score 0-2), symptomatic intracranial hemorrhage, and mortality. RESULTS: From 1344 patients assessed for eligibility, 1059 were included (median age, 74 years; 43.7% women; 41.3% had intravenous thrombolysis): 364 receiving EVT and 695 receiving MM. Baseline stroke severity did not modify the association of EVT with 3-month mRS distribution (Pinteraction=0.312) but did with functional independence (Pinteraction=0.010), with a similar trend on excellent outcome (Pinteraction=0.069). EVT was associated with more favorable outcomes than MM in patients with baseline NIHSS score >6 (mRS score 0-1, 30.6% versus 17.7%; adjusted odds ratio [aOR], 2.01 [95% CI, 1.22-3.31]; mRS score 0 to 2, 46.1% versus 31.9%; aOR, 1.64 [95% CI, 1.08-2.51]) but not in those with NIHSS score ≤6 (mRS score 0-1, 43.8% versus 46.3%; aOR, 0.90 [95% CI, 0.49-1.64]; mRS score 0-2, 65.3% versus 74.3%; aOR, 0.55 [95% CI, 0.30-1.0]). EVT was associated with more symptomatic intracranial hemorrhage regardless of baseline NIHSS score (Pinteraction=0.467), while the mortality increase was more pronounced in patients with NIHSS score ≤6 (Pinteraction=0.044; NIHSS score ≤6: aOR, 7.95 [95% CI, 3.11-20.28]; NIHSS score >6: aOR, 1.98 [95% CI, 1.08-3.65]). Arterial occlusion site did not modify the association of EVT with outcomes compared with MM. CONCLUSIONS: Baseline clinical stroke severity, rather than the occlusion site, may be an important modifier of the association between EVT and outcomes in iPCAO. Only severely affected patients with iPCAO (NIHSS score >6) had more favorable disability outcomes with EVT than MM, despite increased mortality and symptomatic intracranial hemorrhage.

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.

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.

Anticoagulants versus Antiplatelet Treatment in the Medical Management of Carotid Floating Thrombus.

BACKGROUND: Carotid free-floating thrombus (CFT) is a rare cause of stroke describing an intraluminal thrombus that is loosely associated with the arterial wall and manifesting as a filling defect fully surrounded by flow on vascular imaging. Unfortunately, there is no clear consensus among experts on the ideal treatment for this pathology. METHODS: Retrospective analysis of acute ischemic stroke (AIS) and transient ischemic attack (TIA) patients diagnosed with CFT on computed tomography angiogram (CTA) between January 2015-March 2023. We aimed to compare two treatment regimens: anticoagulation (ACT) and antiplatelet (APT) in the treatment of CFT. APT regimens included the use of dual or single antiplatelets (DAPT or SAPT; aspirin, clopidogrel and ticagrelor) and ACT regimens included the use of direct oral anticoagulants, warfarin, heparin or low molecular weight heparin +/- ASA. Patients that underwent mechanical thrombectomy were excluded. RESULTS: During study time there were 8252 acute ischemic stroke hospitalizations, of which 135 (1.63 %) patients were diagnosed with CFT. Sixty-six patients were included in our analysis. Patients assigned to APT were older (60.41years ± 12.82;p < 0.01). Other demographic variables were similar between ACT and APT groups. Complete CFT resolution on repeat vascular imaging was numerically higher at 30 days (58.8 vs 31.6 %, respectively; p = 0.1) and at latest follow-up (70.8 vs 50 %; p = 0.1) on ACT vs APT, respectively without reaching statistical significance. Similarly, there was numerically higher rates of any ICH with ACT compared to APT but it did not achieve statistical significance (27.6 % vs 13.5 %; p = 0.5). There were similar rates of PH1/2 hemorrhagic transformation, independence at discharge and similar hospital length of stay between ACT and APT groups. Patients assigned to APT were more likely to be discharged on their assigned treatment compared to those assigned to ACT (86.5 vs 55.2 %; p < 0.001). The rate of 30-day recurrent stroke was comparable among ACT and APT at 30 days (3.4 vs 0 %; p = 0.1, respectively). Subgroup analysis comparing exclusive ACT vs Dual APT lead to similar results. CONCLUSION: Our study showed comparable efficacy and safety outcomes in CFT patients who were exclusively managed medically with ACT vs APT. Larger prospective studies are needed.

Endovascular Versus Medical Management of Posterior Cerebral Artery Occlusion Stroke: The PLATO Study.

BACKGROUND: The optimal management of patients with isolated posterior cerebral artery occlusion is uncertain. We compared clinical outcomes for endovascular therapy (EVT) versus medical management (MM) in patients with isolated posterior cerebral artery occlusion. METHODS: This multinational case-control study conducted at 27 sites in Europe and North America included consecutive patients with isolated posterior cerebral artery occlusion presenting within 24 hours of time last well from January 2015 to August 2022. Patients treated with EVT or MM were compared with multivariable logistic regression and inverse probability of treatment weighting. The coprimary outcomes were the 90-day modified Rankin Scale ordinal shift and ≥2-point decrease in the National Institutes of Health Stroke Scale. RESULTS: Of 1023 patients, 589 (57.6%) were male with median (interquartile range) age of 74 (64-82) years. The median (interquartile range) National Institutes of Health Stroke Scale was 6 (3-10). The occlusion segments were P1 (41.2%), P2 (49.2%), and P3 (7.1%). Overall, intravenous thrombolysis was administered in 43% and EVT in 37%. There was no difference between the EVT and MM groups in the 90-day modified Rankin Scale shift (aOR, 1.13 [95% CI, 0.85-1.50]; P=0.41). There were higher odds of a decrease in the National Institutes of Health Stroke Scale by ≥2 points with EVT (aOR, 1.84 [95% CI, 1.35-2.52]; P=0.0001). Compared with MM, EVT was associated with a higher likelihood of excellent outcome (aOR, 1.50 [95% CI, 1.07-2.09]; P=0.018), complete vision recovery, and similar rates of functional independence (modified Rankin Scale score, 0-2), despite a higher rate of SICH and mortality (symptomatic intracranial hemorrhage, 6.2% versus 1.7%; P=0.0001; mortality, 10.1% versus 5.0%; P=0.002). CONCLUSIONS: In patients with isolated posterior cerebral artery occlusion, EVT was associated with similar odds of disability by ordinal modified Rankin Scale, higher odds of early National Institutes of Health stroke scale improvement, and complete vision recovery compared with MM. There was a higher likelihood of excellent outcome in the EVT group despite a higher rate of symptomatic intracranial hemorrhage and mortality. Continued enrollment into ongoing distal vessel occlusion randomized trials is warranted.

No Racial Disparity in Outcome Measures After Endovascular Treatment for Stroke in the Elderly.

BACKGROUND AND PURPOSE: Despite the lower rates of good outcomes and higher mortality in elderly patients, age does not modify the treatment effect of mechanical thrombectomy for large vessel occlusion strokes. We aimed to study whether racial background influences the outcome after mechanical thrombectomy in the elderly population. METHODS: We reviewed a prospectively maintained database of patients with acute ischemic stroke treated with mechanical thrombectomy from October 2010 through June 2020 to identify all consecutive patients with age ≥80 years and anterior circulation large vessel occlusion strokes. The patients were categorized according to their race as Black and White. Univariable and multivariable analyses were performed to define the predictors of 90-day modified Rankin Scale and mortality in the overall population and in each race separately. RESULTS: Among 2241 mechanical thrombectomy, a total of 344 patients (median [interquartile range]; age 85 [82-88] years, baseline National Institutes of Health Stroke Scale score of 19 [15-23], Alberta Stroke Program Early CT Score 9 [7-9], 69.5% females) were eligible for the analysis. White patients (n=251; 73%) had significantly lower median body mass index (25.37 versus 26.89, P=0.04) and less frequent hypertension (78.9% versus 90.3%, P=0.01) but more atrial fibrillation (64.5% versus 44.1%, P=0.001) compared with African Americans (n=93; 27%). Other clinical, imaging, and procedural characteristics were comparable between groups. The rates of symptomatic intracerebral hemorrhage, 90-day modified Rankin Scale score of 0 to 2, and mortality were comparable among both groups. On multivariable analysis, race was neither a predictor of 90-day modified Rankin Scale score of 0 to 2 (White race: odds ratio, 0.899 [95% CI, 0.409-1.974], P=0.79) nor 90-day mortality (White race: odds ratio, 1.368; [95% CI, 0.715-2.618], P=0.34). CONCLUSIONS: In elderly patients undergoing mechanical thrombectomy for acute ischemic stroke, there was no racial difference in terms of outcome.

Direct to Angiosuite Versus Conventional Imaging in Suspected Large Vessel Occlusion: A Systemic Review and Meta-Analysis.

BACKGROUND: There is growing evidence to suggest that the direct transfer to angiography suite (DTAS) approach for patients with suspected large vessel occlusion stroke potentially requiring mechanical thrombectomy shortens treatment times and improves outcomes compared with the direct transfer to conventional imaging (DTCI) model. Therefore, we conducted this meta-analysis to compare both approaches to build more concrete evidence to support this innovative treatment concept. METHODS: All potentially relevant studies published in 4 electronic databases/search engines (PubMed, Web of Science, Cochrane Library, and Scopus) from inception to November 2021 were reviewed. Eligible studies were included if they enrolled ≥10 patients in both groups, were published in English, and reported baseline and procedural characteristics and outcomes. Relevant data were then extracted and analyzed. RESULTS: Among 4514 searched studies, 7 qualified for the analysis with 1971 patients (DTAS=675, DTCI=1296). Times from door to puncture (mean difference, -30.76 minutes [95% CI, -43.70 to -17.82]; P<0.001) as well as door-to-reperfusion (mean difference=-33.24 minutes [95% CI, -51.82 to -14.66]; P<0.001) were significantly shorter and the rates of functional independence (modified Rankin Scale score, 0-2: risk ratio [RR], 1.25 [95% CI, 1.02-1.53]; P=0.03) at 90 days were higher in the DTAS versus the DTCI approach. There was no difference across the DTAS and DTCI groups in terms of the rates of successful reperfusion (modified Thrombolysis in Cerebral Infarction score 2B-3: RR, 1.03 [95% CI, 0.95-1.12]; P=0.42), near-complete/full reperfusion (modified Thrombolysis in Cerebral Infarction 2C-3: RR, 0.89 [95% CI, 0.74-1.08]; P=0.23), symptomatic intracranial hemorrhage (RR, 0.81 [95% CI, 0.56-1.17]; P=0.26), or fair outcomes (modified Rankin Scale score, 0-3: RR, 1.14 [95% CI, 0.88-1.47]; P=0.32) or mortality (RR, 0.98 [95% CI, 0.67-1.44]; P=0.93) at 90 days. Subgroup analysis showed no significant difference in 90-day functional independence across approaches in transfer patients (RR, 1.20 [95% CI, 0.96-1.51]; P=0.11). CONCLUSIONS: Our meta-analysis showed that the DTAS approach seems to be associated with improved time metrics and functional outcomes with comparable safety to the DTCI approach. Ongoing multicenter randomized clinical trials will hopefully provide more definite data about this promising approach.

Perfusion Imaging and Clinical Outcome in Acute Minor Stroke With Large Vessel Occlusion.

BACKGROUND: Whether bridging therapy (intravenous thrombolysis [IVT] followed by mechanical thrombectomy) is superior to IVT alone in minor stroke with large vessel occlusion is unknown. Perfusion imaging may identify subsets of large vessel occlusion-related minor stroke patients with distinct response to bridging therapy. METHODS: We conducted a multicenter international observational study of consecutive IVT-treated patients with minor stroke (National Institutes of Health Stroke Scale score ≤5) who had an anterior circulation large vessel occlusion and perfusion imaging performed before IVT, with a subset undergoing immediate thrombectomy. Propensity score with inverse probability of treatment weighting was used to account for baseline between-groups differences. The primary outcome was 3-month modified Rankin Scale score 0 to 1. We searched for an interaction between treatment group and mismatch volume (critical hypoperfusion-core volume). RESULTS: Overall, 569 patients were included (172 and 397 in the bridging therapy and IVT groups, respectively). After propensity-score weighting, the distribution of baseline variables was similar across the 2 groups. In the entire population, bridging was associated with lower odds of achieving modified Rankin Scale score 0 to 1: odds ratio, 0.73 [95% CI, 0.55-0.96]; P=0.03. However, mismatch volume modified the effect of bridging on clinical outcome (Pinteraction=0.04 for continuous mismatch volume); bridging was associated with worse outcome in patients with, but not in those without, mismatch volume <40 mL (odds ratio, [95% CI] for modified Rankin Scale score 0-1: 0.48 [0.33-0.71] versus 1.14 [0.76-1.71], respectively). Bridging was associated with higher incidence of symptomatic intracranial hemorrhage in the entire population, but this effect was present in the small mismatch subset only (Pinteraction=0.002). CONCLUSIONS: In our population of large vessel occlusion-related minor stroke patients, bridging therapy was associated with lower rates of good outcome as compared with IVT alone. However, mismatch volume was a strong modifier of the effect of bridging therapy over IVT alone, notably with worse outcome with bridging therapy in patients with mismatch volume ≤40 mL. Randomized trials should consider adding perfusion imaging for patient selection.

Stenting and Angioplasty in Neurothrombectomy: Matched Analysis of Rescue Intracranial Stenting Versus Failed Thrombectomy.

BACKGROUND: Successful reperfusion is one of the strongest predictors of functional outcomes after mechanical thrombectomy (MT). Despite continuous advancements in MT technology and techniques, reperfusion failure still occurs in ≈15% to 30% of patients with large vessel occlusion strokes undergoing MT. We aim to evaluate the safety and efficacy of rescue intracranial stenting for large vessel occlusion stroke after failed MT. METHODS: The SAINT (Stenting and Angioplasty in Neurothrombectomy) Study is a retrospective analysis of prospectively collected data from 14 comprehensive stroke centers through January 2015 to December 2020. Patients were included if they had anterior circulation large vessel occlusion stroke due to intracranial internal carotid artery and middle cerebral artery-M1/M2 segments and failed MT. The cohort was divided into 2 groups: rescue intracranial stenting and failed recanalization (modified Thrombolysis in Cerebral Ischemia score 0-1). Propensity score matching was used to balance the 2 groups. The primary outcome was the shift in the degree of disability as measured by the modified Rankin Scale at 90 days. Secondary outcomes included functional independence (90-day modified Rankin Scale score 0-2). Safety measures included symptomatic intracranial hemorrhage and 90-day mortality. RESULTS: A total of 499 patients were included in the analysis. Compared with the failed reperfusion group, rescue intracranial stenting had a favorable shift in the overall modified Rankin Scale score distribution (acOR, 2.31 [95% CI, 1.61-3.32]; P<0.001), higher rates of functional independence (35.1% versus 7%; adjusted odds ratio [aOR], 6.33 [95% CI, 3.14-12.76]; P<0.001), and lower mortality (28% versus 46.5%; aOR, 0.55 [95% CI, 0.31-0.96]; P=0.04) at 90 days. Rates of symptomatic intracerebral hemorrhage were comparable across both groups (7.1% versus 10.2%; aOR, 0.99 [95% CI, 0.42-2.34]; P=0.98). The matched cohort analysis demonstrated similar results. Specifically, rescue intracranial stenting (n=107) had a favorable shift in the overall modified Rankin Scale score distribution (acOR, 3.74 [95% CI, 2.16-6.57]; P<0.001), higher rates of functional independence (34.6% versus 6.5%; aOR, 10.91 [95% CI, 4.11-28.92]; P<0.001), and lower mortality (29.9% versus 43%; aOR, 0.49 [95% CI, 0.25-0.94]; P=0.03) at 90 days with similar rates of symptomatic intracerebral hemorrhage (7.5% versus 11.2%; aOR, 0.87 [95% CI, 0.31-2.42]; P=0.79) compared with patients who failed to reperfuse (n=107). There was no heterogeneity of treatment effect across the prespecified subgroups for improvement in functional outcomes. CONCLUSIONS: Acute intracranial stenting appears to be a safe and effective rescue strategy in patients with large vessel occlusion stroke who failed MT. Randomized multicenter trials are warranted.

Reperfusion Without Functional Independence in Late Presentation of Stroke With Large Vessel Occlusion.

BACKGROUND: Reperfusion without functional independence (RFI) is an undesired outcome following thrombectomy in acute ischemic stroke. The primary objective was to evaluate, in patients presenting with proximal anterior circulation occlusion stroke in the extended time window, whether selection with computed tomography (CT) perfusion or magnetic resonance imaging is associated with RFI, mortality, or symptomatic intracranial hemorrhage (sICH) compared with noncontrast CT selected patients. METHODS: The CLEAR study (CT for Late Endovascular Reperfusion) was a multicenter, retrospective cohort study of stroke patients undergoing thrombectomy in the extended time window. Inclusion criteria for this analysis were baseline National Institutes of Health Stroke Scale score ≥6, internal carotid artery, M1 or M2 segment occlusion, prestroke modified Rankin Scale score of 0 to 2, time-last-seen-well to treatment 6 to 24 hours, and successful reperfusion (modified Thrombolysis in Cerebral Infarction 2c-3). RESULTS: Of 2304 patients in the CLEAR study, 715 patients met inclusion criteria. Of these, 364 patients (50.9%) showed RFI (ie, mRS score of 3-6 at 90 days despite successful reperfusion), 37 patients (5.2%) suffered sICH, and 127 patients (17.8%) died within 90 days. Neither imaging selection modality for thrombectomy candidacy (noncontrast CT versus CT perfusion versus magnetic resonance imaging) was associated with RFI, sICH, or mortality. Older age, higher baseline National Institutes of Health Stroke Scale, higher prestroke disability, transfer to a comprehensive stroke center, and a longer interval to puncture were associated with RFI. The presence of M2 occlusion and higher baseline Alberta Stroke Program Early CT Score were inversely associated with RFI. Hypertension was associated with sICH. CONCLUSIONS: RFI is a frequent phenomenon in the extended time window. Neither magnetic resonance imaging nor CT perfusion selection for mechanical thrombectomy was associated with RFI, sICH, and mortality compared to noncontrast CT selection alone. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04096248.

Histological composition of retrieved emboli in acute ischemic stroke is independent of pre-thrombectomy alteplase use.

BACKGROUND AND PURPOSE: Given recent evidence suggesting the clot composition may be associated with revascularization outcomes and stroke etiology, clot composition research has been a topic of growing interest. It is currently unclear what effect, if any, pre-thrombectomy thrombolysis has on clot composition. Understanding this association is important as it is a potential confounding variable in clot composition research. We retrospectively evaluated the composition of retrieved clots from ischemic stroke patients who did and did not receive pre-treatment tPA to study the effect of tPA on clot composition. MATERIALS AND METHODS: Consecutive patients enrolled in the Stroke Thromboembolism Registry of Imaging and Pathology (STRIP) were included in this study. All patients underwent mechanical thrombectomy and retrieved clots were sent to a central core lab for processing. Histological analysis was performed using Martius Scarlett Blue (MSB) staining and area of the clot was also measured on the gross photos. Student's t test was used for continuous variables and chi-squared test for categorical variables. RESULTS: A total of 1430 patients were included in this study. Mean age was 68.4±13.5 years. Overall rate of TICI 2c/3 was 67%. A total of 517 patients received tPA (36%) and 913 patients did not (64%). Mean RBC density for the tPA group was 42.97±22.62% compared to 42.80±23.18% for the non-tPA group (P=0.89). Mean WBC density for the tPA group was 3.74±2.60% compared to 3.42±2.21% for the non-tPA group (P=0.012). Mean fibrin density for the tPA group was 26.52±15.81% compared to 26.53±15.34% for the non-tPA group (P=0.98). Mean platelet density for the tPA group was 26.22±18.60% compared to 26.55±19.47% for the non-tPA group (P=0.75). tPA group also had significantly smaller clot area compared to non-tPA group. CONCLUSIONS: Our study 1430 retrieved emboli and ischemic stroke patients shows no interaction between tPA administration and clot composition. These findings suggest that tPA does not result in any histological changes in clot composition.

Lack of Reperfusion Rather Than Number of Passes Defines Futility in Stroke Thrombectomy: A Matched Case-Control Study.

Background and Purpose: There is a robust relationship between the duration of ischemia and functional outcomes after mechanical thrombectomy. Higher number of mechanical thrombectomy passes strongly correlate with lower chances of favorable outcomes. Indeed, previous studies have suggested that after multiple passes the procedure may be futile. However, using uncontrolled thresholds to define thrombectomy futility might be misleading. We aim to compare the outcome of successful reperfusion after 4 to 5 passes and ≥6 passes with those of failed reperfusion. Methods: A prospectively acquired mechanical thrombectomy database from January 2012 to October 2019 was reviewed. Patients were included if they had intracranial internal carotid artery or middle cerebral artery-M1/M2 occlusions and either achieved successful reperfusion after ≥4 passes or failed reperfusion. Reperfused patients (mTICI2b-3) were divided into 2 subgroups; (1) 4 to 5 passes and (2) ≥6 passes. Each subgroup was compared with a matched group of mechanical thrombectomy failure (mTICI0-2a). The primary outcome was the shift in the degree of disability at 90-day as measured by the modified Rankin Scale. Results: A total of 273 patients were included. As compared with matched failed reperfusion patients (n=62), those reperfused after 4 to 5 passes (n=62) had a favorable shift in the overall modified Rankin Scale score distribution (adjusted odds ratio, 3.992 [95% CI, 1.807­8.512], P=0.001] and higher rates of functional independence (31% versus 8.9%, P=0.004, adjusted odds ratio; 9.860 [95% CI, 2.323­41.845], P=0.002) at 90 days. Similarly, when compared with a matched group of failed reperfusion (n=42), patients reperfused after ≥6 passes (n=42) demonstrated a favorable shift in the overall modified Rankin Scale score distribution (adjusted odds ratio, 2.640 [95% CI, 1.073­6.686], P=0.037) and had higher rates of functional independence (36.8% vs 11.1%, P=0.004, adjusted odds ratio, 5.392 [95% CI, 1.185­24.530], P=0.029) at 90 day. Rates of parenchymal hematoma type-2 and 90-day mortality were comparable in the reperfused and nonreperfused groups. Conclusions: Achieving reperfusion despite multiple passes leads to improved outcomes compared with failed procedures. Arbitrary uncontrolled thresholds for a maximum number of passes to predict futile recanalization may lead to inappropriate early termination of procedures.

Epidemiological Surveillance of the Impact of the COVID-19 Pandemic on Stroke Care Using Artificial Intelligence.

BACKGROUND AND PURPOSE: The degree to which the coronavirus disease 2019 (COVID-19) pandemic has affected systems of care, in particular, those for time-sensitive conditions such as stroke, remains poorly quantified. We sought to evaluate the impact of COVID-19 in the overall screening for acute stroke utilizing a commercial clinical artificial intelligence platform. METHODS: Data were derived from the Viz Platform, an artificial intelligence application designed to optimize the workflow of patients with acute stroke. Neuroimaging data on suspected patients with stroke across 97 hospitals in 20 US states were collected in real time and retrospectively analyzed with the number of patients undergoing imaging screening serving as a surrogate for the amount of stroke care. The main outcome measures were the number of computed tomography (CT) angiography, CT perfusion, large vessel occlusions (defined according to the automated software detection), and severe strokes on CT perfusion (defined as those with hypoperfusion volumes >70 mL) normalized as number of patients per day per hospital. Data from the prepandemic (November 4, 2019 to February 29, 2020) and pandemic (March 1 to May 10, 2020) periods were compared at national and state levels. Correlations were made between the inter-period changes in imaging screening, stroke hospitalizations, and thrombectomy procedures using state-specific sampling. RESULTS: A total of 23 223 patients were included. The incidence of large vessel occlusion on CT angiography and severe strokes on CT perfusion were 11.2% (n=2602) and 14.7% (n=1229/8328), respectively. There were significant declines in the overall number of CT angiographies (-22.8%; 1.39-1.07 patients/day per hospital, P<0.001) and CT perfusion (-26.1%; 0.50-0.37 patients/day per hospital, P<0.001) as well as in the incidence of large vessel occlusion (-17.1%; 0.15-0.13 patients/day per hospital, P<0.001) and severe strokes on CT perfusion (-16.7%; 0.12-0.10 patients/day per hospital, P<0.005). The sampled cohort showed similar declines in the rates of large vessel occlusions versus thrombectomy (18.8% versus 19.5%, P=0.9) and comprehensive stroke center hospitalizations (18.8% versus 11.0%, P=0.4). CONCLUSIONS: A significant decline in stroke imaging screening has occurred during the COVID-19 pandemic. This analysis underscores the broader application of artificial intelligence neuroimaging platforms for the real-time monitoring of stroke systems of care.

Repeated Mechanical Endovascular Thrombectomy for Recurrent Large Vessel Occlusion: A Multicenter Experience.

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) is now the standard of care for large vessel occlusion (LVO) stroke. However, little is known about the frequency and outcomes of repeat MT (rMT) for patients with recurrent LVO. METHODS: This is a retrospective multicenter cohort of patients who underwent rMT at 6 tertiary institutions in the United States between March 2016 and March 2020. Procedural, imaging, and outcome data were evaluated. Outcome at discharge was evaluated using the modified Rankin Scale. RESULTS: Of 3059 patients treated with MT during the study period, 56 (1.8%) underwent at least 1 rMT. Fifty-four (96%) patients were analyzed; median age was 64 years. The median time interval between index MT and rMT was 2 days; 35 of 54 patients (65%) experienced recurrent LVO during the index hospitalization. The mechanism of stroke was cardioembolism in 30 patients (56%), intracranial atherosclerosis in 4 patients (7%), extracranial atherosclerosis in 2 patients (4%), and other causes in 18 patients (33%). A final TICI recanalization score of 2b or 3 was achieved in all 54 patients during index MT (100%) and in 51 of 54 patients (94%) during rMT. Thirty-two of 54 patients (59%) experienced recurrent LVO of a previously treated artery, mostly the pretreated left MCA (23 patients, 73%). Fifty of the 54 patients (93%) had a documented discharge modified Rankin Scale after rMT: 15 (30%) had minimal or no disability (modified Rankin Scale score ≤2), 25 (50%) had moderate to severe disability (modified Rankin Scale score 3-5), and 10 (20%) died. CONCLUSIONS: Almost 2% of patients treated with MT experience recurrent LVO, usually of a previously treated artery during the same hospitalization. Repeat MT seems to be safe and effective for attaining vessel recanalization, and good outcome can be expected in 30% of patients.

Influence of the COVID-19 Pandemic on Treatment Times for Acute Ischemic Stroke: The Society of Vascular and Interventional Neurology Multicenter Collaboration.

BACKGROUND AND PURPOSE: The pandemic caused by the novel coronavirus disease 2019 (COVID-19) has led to an unprecedented paradigm shift in medical care. We sought to evaluate whether the COVID-19 pandemic may have contributed to delays in acute stroke management at comprehensive stroke centers. METHODS: Pooled clinical data of consecutive adult stroke patients from 14 US comprehensive stroke centers (January 1, 2019, to July 31, 2020) were queried. The rate of thrombolysis for nontransferred patients within the Target: Stroke goal of 60 minutes was compared between patients admitted from March 1, 2019, and July 31, 2019 (pre-COVID-19), and March 1, 2020, to July 31, 2020 (COVID-19). The time from arrival to imaging and treatment with thrombolysis or thrombectomy, as continuous variables, were also assessed. RESULTS: Of the 2955 patients who met inclusion criteria, 1491 were admitted during the pre-COVID-19 period and 1464 were admitted during COVID-19, 15% of whom underwent intravenous thrombolysis. Patients treated during COVID-19 were at lower odds of receiving thrombolysis within 60 minutes of arrival (odds ratio, 0.61 [95% CI, 0.38-0.98]; P=0.04), with a median delay in door-to-needle time of 4 minutes (P=0.03). The lower odds of achieving treatment in the Target: Stroke goal persisted after adjustment for all variables associated with earlier treatment (adjusted odds ratio, 0.55 [95% CI, 0.35-0.85]; P<0.01). The delay in thrombolysis appeared driven by the longer delay from imaging to bolus (median, 29 [interquartile range, 18-41] versus 22 [interquartile range, 13-37] minutes; P=0.02). There was no significant delay in door-to-groin puncture for patients who underwent thrombectomy (median, 83 [interquartile range, 63-133] versus 90 [interquartile range, 73-129] minutes; P=0.30). Delays in thrombolysis were observed in the months of June and July. CONCLUSIONS: Evaluation for acute ischemic stroke during the COVID-19 period was associated with a small but significant delay in intravenous thrombolysis but no significant delay in thrombectomy time metrics. Taking steps to reduce delays from imaging to bolus time has the potential to attenuate this collateral effect of the pandemic.

Risk Factors for Distal Clot Migration during Mechanical Thrombectomy of Anterior Circulation Large Vessel Occlusion.

INTRODUCTION: Distal clot migration (DCM) is a known complication of mechanical thrombectomy (MT), but neither risk factors for DCM nor ways of how it might affect clinical outcomes have been extensively studied to date. METHODS: To identify risk factors for and outcomes in the setting of DCM, the records of all patients with acute ischemic stroke due to anterior circulation large vessel occlusion (LVO) treated with MT at a single center between May 2016 and June 2018 were retrospectively reviewed. Uni- and multivariable analyses were performed to evaluate predictors of DCM and good functional outcome (90-day modified Rankin Scale; mRS 0-2). RESULTS: A total of 65 patients were included, DCM was identified in 22 patients (33.8%). Patients with DCM had significantly higher pre-procedural intravenous tissue plasminogen activator (IV-tPA) administration (81.8 vs. 53.5%, p = 0.03), stentrievers thrombectomy (95.5 vs. 62.8%, p = 0.006), and longer median puncture to recanalization time (44 [34-97] vs. 30 [20-56] min, p = 0.028) as compared to group with non-DCM. Also, they had lower rates of Thrombolysis in Cerebral Infarction (TICI) 2b/3 recanalization (p = 0.002), higher median National Institutes of Health Stroke Scale (NIHSS) scores at discharge (p = 0.01), and lower rates of 90-day mRS (0-2; 18.2 vs. 48.8%; p = 0.016). On subgroup analysis, patients with middle cerebral artery occlusions who underwent MT with stentrievers <40 mm in length had a higher risk of DCM (p = 0.026). On multivariable analysis, IV-tPA administration (OR; 5.019, 95% CI [1.319-19.102], p = 0.018) and stentrievers thrombectomy (OR; 10.031, 95% CI [1.090-92.344]; p = 0.04) remained significant predictors of DCM. Baseline NIHSS score (OR; 0.872, 95% CI [0.788-0.965], p = 0.008) and DCM (OR; 0.250, 95% CI [0.075-0.866], p = 0.03) were independent predictors of 90-day mRS 0-2. CONCLUSION: In patients undergoing MT for anterior circulation LVO, DCM is associated with lower rates of TICI 2b/3 recanalization and worse functional outcomes at 90 days. IV-tPA administration and MT with short stentrievers are independent predictors of DCM development.

Distal Medium Vessel Occlusion Strokes: Understanding the Present and Paving the Way for a Better Future.

Distal medium vessel occlusions (DMVOs) are thought to cause as many as 25% to 40% of all acute ischemic strokes and may result in substantial disability amongst survivors. Although intravenous thrombolysis (IVT) is more effective for distal than proximal vessel occlusions, the overall efficacy of IVT remains limited in DMVO with less than 50% of patients achieving reperfusion and about 1/3 to 1/4 of the patients failing to achieve functional independence. Data regarding mechanical thrombectomy (MT) among these patients remains limited. The smaller, thinner, and more tortuous vessels involved in DMVO are presumably associated with higher procedural risks whereas a lower benefit might be expected given the smaller amount of tissue territory at risk. Recent advances in technology have shown promising results in endovascular treatment of DMVOs with room for future improvement. In this review, we discuss some of the key technical and clinical considerations in DMVO treatment including the anatomical and clinical terminology, diagnostic modalities, the role of IVT and MT, existing technology, and technical challenges as well as the contemporary evidence and future treatment directions.