CLEAR Thrombectomy Score: An Index to Estimate the Probability of Good Functional Outcome With or Without Endovascular Treatment in the Late Window for Anterior Circulation Occlusion.

BACKGROUND: With the expanding eligibility for endovascular therapy (EVT) of patients presenting in the late window (6-24 hours after last known well), we aimed to derive a score to predict favorable outcomes associated with EVT versus best medical management. METHODS AND RESULTS: A multinational observational cohort of patients from the CLEAR (Computed Tomography for Late Endovascular Reperfusion) study with proximal intracranial occlusion (2014-2022) was queried (n=58 sites). Logistic regression analyses were used to derive a 9-point score for predicting good functional outcome (modified Rankin Scale score 0-2 or return to premorbid modified Rankin Scale score) at 90 days, with sensitivity analyses for prespecified subgroups conducted using bootstrapped random forest regressions. Secondary outcomes included 90-day functional independence (modified Rankin Scale score 0-2), poor outcome (modified Rankin Scale score 5-6), and 90-day survival. The score was externally validated with a single-center cohort (2014-2023). Of the 3231 included patients (n=2499 EVT), a 9-point score included age, early computed tomography ischemic changes, and stroke severity, with higher points indicating a higher probability of a good functional outcome. The areas under the curve for the primary outcome among EVT and best medical management subgroups were 0.72 (95% CI, 0.70-0.74) and 0.87 (95% CI, 0.84-0.90), respectively, with similar performance in the external validation cohort (area under the curve, 0.71 [95% CI, 0.66-0.76]). There was a significant interaction between the score and EVT for good functional outcome, functional independence, and poor outcome (all Pinteraction<0.001), with greater benefit favoring patients with lower and midrange scores. CONCLUSIONS: This score is a pragmatic tool that can estimate the probability of a good outcome with EVT in the late window. REGISTRATION: URL: https://www.Clinicaltrials.gov; Unique identifier: NCT04096248.

Endovascular Therapy in the Extended Time Window for Large Vessel Occlusion in Patients With Pre-Stroke Disability.

BACKGROUND AND PURPOSE: We compared the outcomes of endovascular therapy (EVT) in an extended time window in patients with large-vessel occlusion (LVO) between patients with and without pre-stroke disability. METHODS: In this prespecified analysis of the multinational CT for Late Endovascular Reperfusion study (66 participating sites, 10 countries between 2014 and 2022), we analyzed data from patients with acute ischemic stroke with a pre-stroke modified Rankin Scale (mRS) score of 0-4 and LVO who underwent EVT 6-24 hours from the time last seen well. The primary outcome was the composite of functional independence (FI; mRS score 0-2) or return to the pre-stroke mRS score (return of Rankin, RoR) at 90 days. Outcomes were compared between patients with pre-stroke disability (pre-stroke mRS score 2-4) and those without (mRS score 0-1). RESULTS: A total of 2,231 patients (median age, 72 years; median National Institutes of Health Stroke Scale score, 16) were included in the present analysis. Of these, 564 (25%) had pre-stroke disability. The primary outcome (FI or RoR) was observed in 30.7% of patients with pre-stroke disability (FI, 16.5%; RoR, 30.7%) compared to 44.1% of patients without (FI, 44.1%; RoR, 13.0%) (P<0.001). In multivariable logistic regression analysis with inverse probability of treatment weighting, pre-stroke disability was not associated with significantly lower odds of achieving FI or RoR (adjusted odds ratio 0.73, 95% confidence interval 0.43-1.25). Symptomatic intracranial hemorrhage occurred in 6.3% of both groups (P=0.995). CONCLUSION: A considerable proportion of patients with late-presenting LVO and pre-stroke disability regained pre-stroke mRS scores after EVT. EVT may be appropriate for patients with pre-stroke disability presenting in the extended time window.

Safety and clinical outcomes of endovascular therapy versus medical management in late presentation of large ischemic stroke.

INTRODUCTION: The benefit of endovascular therapy (EVT) among stroke patients with large ischemic core (ASPECTS 0-5) in the extended time window outside of trial settings remains unclear. We analyzed the effect of EVT among these stroke patients in real-world settings. PATIENTS AND METHODS: The CT for Late Endovascular Reperfusion (CLEAR) study recruited patients from 66 centers in 10 countries between 01/2014 and 05/2022. The extended time-window was defined as 6-24 h from last-seen-well to treatment. The primary outcome was shift of the 3-month modified Rankin scale (mRS) score. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and mortality. Outcomes were analyzed with ordinal and logistic regressions. RESULTS: Among 5098 screened patients, 2451 were included in the analysis (median age 73, 55% women). Of patients with ASPECTS 0-5 (n = 310), receiving EVT (n = 209/310) was associated with lower 3-month mRS when compared to medical management (median 4 IQR 3-6 vs 6 IQR 4-6; aOR 0.4, 95% CI 0.2-0.7). Patients undergoing EVT had higher sICH (11.2% vs 4.0%; aOR 4.1, 95% CI 1.2-18.8) and lower mortality (31.6% vs 58.4%, aOR 0.4; 95% CI 0.2-0.9) compared to medically managed patients. The relative benefit of EVT was comparable between patients with ASPECTS 0 and 5 and 6-10 in the extended time window (interaction aOR 0.9; 95% CI 0.5-1.7). CONCLUSION: In the extended time window, patients with ASPECTS 0-5 may have preserved relative treatment benefit of EVT compared to patients with ASPECTS 6-10. These findings are in line with recent trials showing benefit of EVT among real-world patients with large ischemic core in the extended time window. TRIAL REGISTRATION NUMBER: clinicaltrials.gov; Unique identifier: NCT04096248.

Noncontrast CT Selected Thrombectomy vs Medical Management for Late-Window Anterior Large Vessel Occlusion.

BACKGROUND AND OBJECTIVES: There is uncertainty whether patients with large vessel occlusion (LVO) presenting in the late 6-hour to 24-hour time window can be selected for endovascular therapy (EVT) by noncontrast CT (NCCT) and CT angiography (CTA) for LVO detection. We evaluated the clinical outcomes of patients selected for EVT by NCCT compared with those medically managed in the extended time window. METHODS: This multinational cohort study was conducted at 66 sites across 10 countries. Consecutive patients with proximal anterior LVO stroke selected for EVT by NCCT or medically managed and presenting within 6-24 hours of time last seen well (TSLW) from January 2014 to May 2022 were included. The primary end point was the 90-day ordinal shift in the modified Rankin Scale (mRS) score. Inverse probability treatment weighting (IPTW) and multivariable methods were used. RESULTS: Of 5,098 patients screened, 839 patients were included, with a median (interquartile range) age of 75 (64-83) years; 455 (54.2%) were women. There were 616 patients selected to undergo EVT by NCCT (73.4%) and 223 (26.6%) who were medically managed. In IPTW analyses, there was a more favorable 90-day ordinal mRS shift in patients selected by NCCT to EVT vs those who were medically managed (odds ratio [OR] 1.99, 95% CI 1.53-2.59; p < 0.001). There were higher rates of 90-day functional independence (mRS 0-2) in the EVT group (40.1% vs 18.4%, OR 3.31, 95% CI 2.11-5.20; p < 0.001). sICH was nonsignificantly higher in the EVT group (8.5% vs 1.4%, OR 3.77, 95% CI 0.72-19.7, p = 0.12). Mortality at 90 days was lower in the EVT vs MM group (23.9% vs 32.3%, OR 0.61, 95% CI 0.45-0.83, p = 0.002). DISCUSSION: In patients with proximal anterior LVO in the extended time window, there was a lower rate of disability and mortality in patients selected with NCCT and CTA to EVT compared with those who were medically managed. These findings support the use of NCCT as a simpler and more inclusive approach to patient selection in the extended window. TRIAL REGISTRATION INFORMATION: This study was registered at ClinicalTrials.gov under NCT04096248. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with proximal anterior circulation occlusion presenting with ischemic stroke from 6 to 24 hours, compared with medical management, those undergoing thrombectomy based on NCCT have reduced disability and mortality at 90 days.

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.

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.

Predicting Functional Outcome Using 24-Hour Post-Treatment Characteristics: Application of Machine Learning Algorithms in the STRATIS Registry.

FOR SOCIAL MEDIA: @AliciaCastongu2, @FazalZaidi9, @oozaidat, @Mouhammad_Jumaa OBJECTIVE: Machine learning (ML) algorithms have emerged as powerful predictive tools in the field stroke. Here, we examine the predictive accuracy of ML models for predicting functional outcomes using 24-hour post-treatment characteristics in the Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke (STRATIS) Registry. METHODS: ML models, adaptive boost, random forest (RF), classification and regression trees (CART), C5.0 decision tree (C5.0), support vector machine (SVM), least absolute shrinkage and selection operator (LASSO), and logistic regression (LR), and traditional LR models were used to predict 90-day functional outcome (modified Rankin Scale score 0-2). Twenty-four-hour National Institutes of Health Stroke Scale (NIHSS) was examined as a continuous or dichotomous variable in all models. Model accuracy was assessed using the area under characteristic curve (AUC). RESULTS: The 24-hour NIHSS score was a top-predictor of functional outcome in all models. ML models using the continuous 24-hour NIHSS scored showed moderate-to-good predictive performance (range mean AUC: 0.76-0.92); however, RF (AUC: 0.92 ± 0.028) outperformed all ML models, except LASSO (AUC: 0.89 ± 0.023, p = 0.0958). Importantly, RF demonstrated a significantly higher predictive value than LR (AUC: 0.87 ± 0.031, p = 0.048) and traditional LR (AUC: 85 ± 0.06, p = 0.035) when using the 24-hour continuous NIHSS score. Predictive accuracy was similar between the 24-hour NIHSS score dichotomous and continuous ML models. INTERPRETATION: In this substudy, we found similar predictive accuracy for functional outcome when using the 24-hour NIHSS score as a continuous or dichotomous variable in ML models. ML models had moderate-to-good predictive accuracy, with RF outperforming LR models. External validation of these ML models is warranted. ANN NEUROL 2023;93:40-49.

Endovascular vs Medical Management for Late Anterior Large Vessel Occlusion With Prestroke Disability: Analysis of CLEAR and RESCUE-Japan.

BACKGROUND AND OBJECTIVES: Current guidelines do not address recommendations for mechanical thrombectomy (MT) in the extended time window (>6 hours after time last seen well [TLSW]) for large vessel occlusion (LVO) patients with preexisting modified Rankin Scale (mRS) > 1. In this study, we evaluated the outcomes of MT vs medical management in patients with prestroke disability presenting in the 6- to 24-hour time window with acute LVO. METHODS: We analyzed a multinational cohort (61 sites, 6 countries from 2014 to 2020) of patients with prestroke (or baseline) mRS 2 to 4 and anterior circulation LVO treated 6-24 hours from TLSW. Patients treated in the extended time window with MT vs medical management were compared using multivariable logistic regression and inverse probability of treatment weighting (IPTW). The primary outcome was the return of Rankin (ROR, return to prestroke mRS by 90 days). RESULTS: Of 554 included patients (448 who underwent MT), the median age was 82 years (interquartile range [IQR] 72-87) and the National Institutes of Health Stroke Scale (NIHSS) was 18 (IQR 13-22). In both MV logistic regression and IPTW analysis, MT was associated with higher odds of ROR (adjusted OR [aOR] 3.96, 95% CI 1.78-8.79 and OR 3.10, 95% CI 1.20-7.98, respectively). Among other factors, premorbid mRS 4 was associated with higher odds of ROR (aOR, 3.68, 95% CI 1.97-6.87), while increasing NIHSS (aOR 0.90, 95% CI 0.86-0.94) and decreasing Alberta Stroke Program Early Computed Tomography Scale score (aOR per point 0.86, 95% CI 0.75-0.99) were associated with lower odds of ROR. Age, intravenous thrombolysis, and occlusion location were not associated with ROR. DISCUSSION: In patients with preexisting disability presenting in the 6- to 24-hour time window, MT is associated with a higher probability of returning to baseline function compared with medical management. CLASSIFICATION OF EVIDENCE: This investigation's results provide Class III evidence that in patients with preexisting disability presenting 6-24 hours from the TLSW and acute anterior LVO stroke, there may be a benefit of MT over medical management in returning to baseline function.

Mechanical Thrombectomy in the Late Presentation of Anterior Circulation Large Vessel Occlusion Stroke: A Guideline From the Society of Vascular and Interventional Neurology Guidelines and Practice Standards Committee.

Background and Purpose: Recent clinical trials investigating endovascular therapy (EVT) in the extended time window have opened new treatment paradigms for late-presenting patients with large vessel occlusion (LVO) stroke. The aim of this guideline is to provide up to date recommendations for the diagnosis, selection, and medical or endovascular treatment of patients with LVO presenting in the extended time window. Methods: The Society of Vascular & Interventional Neurology (SVIN) Guidelines and Practice Clinical Standards (GAPS) committee assembled a writing group and recruited interdisciplinary experts to review and evaluate the current literature. Recommendations were assigned by the writing group using the SVIN-GAPS Class of Recommendation/Level of Evidence algorithm and SVIN GAPS guideline format. The final guideline was approved by all members of the writing group, the GAPS committee, and the SVIN board of directors. Results: Literature review yielded three high quality randomized trials and several observational studies that have been extracted to derive the enclosed summary recommendations. In patients with LVO presenting in the 6-to-24-hour window, and with clinical imaging mismatch as defined by the DAWN and DEFUSE 3 studies, EVT is recommended. Non contrast CT can be used to evaluate infarct size as sole imaging modality for patient selection, particularly when access to CT perfusion or MRI is limited, or if their performance would incur substantial delay to treatment. In addition, several clinical questions were reviewed based on the available evidence and consensus grading. Conclusion: These guidelines provide practical recommendations based on recent evidence on the diagnosis, selection, and treatment of patients with LVO stroke presenting in the extended time window.

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.

Noncontrast Computed Tomography vs Computed Tomography Perfusion or Magnetic Resonance Imaging Selection in Late Presentation of Stroke With Large-Vessel Occlusion.

Importance: Advanced imaging for patient selection in mechanical thrombectomy is not widely available. Objective: To compare the clinical outcomes of patients selected for mechanical thrombectomy by noncontrast computed tomography (CT) vs those selected by computed tomography perfusion (CTP) or magnetic resonance imaging (MRI) in the extended time window. Design, Setting, and Participants: This multinational cohort study included consecutive patients with proximal anterior circulation occlusion stroke presenting within 6 to 24 hours of time last seen well from January 2014 to December 2020. This study was conducted at 15 sites across 5 countries in Europe and North America. The duration of follow-up was 90 days from stroke onset. Exposures: Computed tomography with Alberta Stroke Program Early CT Score, CTP, or MRI. Main Outcomes and Measures: The primary end point was the distribution of modified Rankin Scale (mRS) scores at 90 days (ordinal shift). Secondary outcomes included the rates of 90-day functional independence (mRS scores of 0-2), symptomatic intracranial hemorrhage, and 90-day mortality. Results: Of 2304 patients screened for eligibility, 1604 patients were included, with a median (IQR) age of 70 (59-80) years; 848 (52.9%) were women. A total of 534 patients were selected to undergo mechanical thrombectomy by CT, 752 by CTP, and 318 by MRI. After adjustment of confounders, there was no difference in 90-day ordinal mRS shift between patients selected by CT vs CTP (adjusted odds ratio [aOR], 0.95 [95% CI, 0.77-1.17]; P = .64) or CT vs MRI (aOR, 0.95 [95% CI, 0.8-1.13]; P = .55). The rates of 90-day functional independence (mRS scores 0-2 vs 3-6) were similar between patients selected by CT vs CTP (aOR, 0.90 [95% CI, 0.7-1.16]; P = .42) but lower in patients selected by MRI than CT (aOR, 0.79 [95% CI, 0.64-0.98]; P = .03). Successful reperfusion was more common in the CT and CTP groups compared with the MRI group (474 [88.9%] and 670 [89.5%] vs 250 [78.9%]; P < .001). No significant differences in symptomatic intracranial hemorrhage (CT, 42 [8.1%]; CTP, 43 [5.8%]; MRI, 15 [4.7%]; P = .11) or 90-day mortality (CT, 125 [23.4%]; CTP, 159 [21.1%]; MRI, 62 [19.5%]; P = .38) were observed. Conclusions and Relevance: In patients undergoing proximal anterior circulation mechanical thrombectomy in the extended time window, there were no significant differences in the clinical outcomes of patients selected with noncontrast CT compared with those selected with CTP or MRI. These findings have the potential to widen the indication for treating patients in the extended window using a simpler and more widespread noncontrast CT-only paradigm.

Middle Cerebral Artery M2 Thrombectomy in the STRATIS Registry.

Background and Purpose: The safety and benefit of mechanical thrombectomy in the treatment of acute ischemic stroke patients with M2 segment middle cerebral artery occlusions remain uncertain. Here, we compare clinical and angiographic outcomes in M2 versus M1 occlusions in the STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) Registry. Methods: The STRATIS Registry was a prospective, multicenter, nonrandomized, observational study of acute ischemic stroke large vessel occlusion patients treated with the Solitaire stent-retriever as the first-choice therapy within 8 hours from symptoms onset. Primary outcome was defined as functional disability at 3 months measured by dichotomized modified Rankin Scale. Secondary outcomes included reperfusion rates and rates of symptomatic intracranial hemorrhage. Results: A total of 984 patients were included, of which 538 (54.7%) had M1 and 170 (17.3%) had M2 occlusions. Baseline demographics were well balanced within the groups, with the exception of mean baseline National Institutes of Health Stroke Scale score which was significantly higher in the M1 population (17.3±5.5 versus 15.7±5.0, P≤0.001). No difference was seen in mean puncture to revascularization times between the cohorts (46.0±27.8 versus 45.1±29.5 minutes, P=0.75). Rates of successful reperfusion (modified Thrombolysis in Cerebral Infarction≥2b) were similar between the groups (91% versus 95%, P=0.09). M2 patients had significantly increased rates of symptomatic ICH at 24 hours (4% versus 1%, P=0.01). Rates of good functional outcome (modified Rankin Scale score of 0­2; 58% versus 59%, P=0.83) and mortality (15% versus 14%, P=0.75) were similar between the 2 groups. There was no difference in the association of outcome and onset to groin puncture or onset to successful reperfusion in M1 and M2 occlusions. Conclusions: In the STRATIS Registry, M2 occlusions achieved similar rates of successful reperfusion, good functional outcome, and mortality, although increased rates of symptomatic ICH were demonstrated when compared with M1 occlusions. The time dependence of benefit was also similar between the 2 groups. Further studies are needed to understand the benefit of mechanical thrombectomy for M2 occlusions. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02239640.

Duration of symptomatic stroke and successful reperfusion with endovascular thrombectomy for anterior circulation large vessel occlusive stroke.

BACKGROUND: It has been reported that longer time intervals from stroke onset to endovascular therapy are associated with lower rates of successful reperfusion in acute ischemic stroke patients with large vessel occlusion. However, procedural variables and potential mechanisms of this association have not been fully elucidated. METHODS: We performed a secondary analysis of individual patient data from the North American Solitaire Stent Retriever Acute Stroke (NASA) and Trevo Stent-Retriever Acute Stroke (TRACK) registries. We included patients with occlusion of the internal carotid artery or middle cerebral artery (M1 and M2 segments) who were treated by mechanical thrombectomy within 24 hours of last known normal. The primary outcome was reperfusion, defined as a Thrombolysis In Cerebral Infarction (TICI) score ≥2b. The secondary outcome was reperfusion on the first pass. The primary predictor was duration of symptomatic stroke, defined as time from last known normal to time of final pass. Adjusted logistic regression models were utilized to determine associations between variables and outcome. RESULTS: We included 506 patients, of which 401 (79.3%) achieved successful reperfusion (TICI 2b/3). The mean (SD) duration of symptomatic stroke was 6.8 (3.5) hours and in the adjusted logistic regression model the duration of symptomatic stroke was associated with reperfusion (OR 0.90, 95% CI 0.84 to 0.96) and reperfusion on the first pass (OR 0.89, 95% CI 0.83 to 0.95). In that model, the predicted probability of reperfusion was 88% (95% CI 0.83 to 0.92) at 1 hour, 81% (95% CI 0.78 to 0.84) at 6 hours, 70% (95% CI 0.63 to 0.77) at 12 hours, and 42% (95% CI 0.17 to 0.67) at 24 hours (ptrend=0.001). Reperfused patients were significantly younger, more likely to be male, and to have had a balloon guide catheter used during the procedure. CONCLUSION: In a real-world cohort of acute ischemic stroke patients with anterior circulation occlusion treated with endovascular therapy, longer duration of symptomatic stroke is associated with lower rates of successful reperfusion and reperfusion on the first pass.

Safety and efficacy of intra-arterial fibrinolytics as adjunct to mechanical thrombectomy: a systematic review and meta-analysis of observational data.

BACKGROUND: Achieving the best possible reperfusion is a key determinant of clinical outcome after mechanical thrombectomy (MT). However, data on the safety and efficacy of intra-arterial (IA) fibrinolytics as an adjunct to MT with the intention to improve reperfusion are sparse. METHODS: We performed a PROSPERO-registered (CRD42020149124) systematic review and meta-analysis accessing MEDLINE, PubMed, and Embase from January 1, 2000 to January 1, 2020. A random-effect estimate (Mantel-Haenszel) was computed and summary OR with 95% CI were used as a measure of added IA fibrinolytics versus control on the risk of symptomatic intracranial hemorrhage (sICH) and secondary endpoints (modified Rankin Scale ≤2, mortality at 90 days). RESULTS: The search identified six observational cohort studies and three observational datasets of MT randomized-controlled trial data reporting on IA fibrinolytics with MT as compared with MT alone, including 2797 patients (405 with additional IA fibrinolytics (100 urokinase (uPA), 305 tissue plasminogen activator (tPA)) and 2392 patients without IA fibrinolytics). Of 405 MT patients treated with additional IA fibrinolytics, 209 (51.6%) received prior intravenous tPA. We did not observe an increased risk of sICH after administration of IA fibrinolytics as adjunct to MT (OR 1.06, 95% CI 0.64 to 1.76), nor excess mortality (0.81, 95% CI 0.60 to 1.08). Although the mode of reporting was heterogeneous, some studies observed improved reperfusion after IA fibrinolytics. CONCLUSION: The quality of evidence regarding peri-interventional administration of IA fibrinolytics in MT is low and limited to observational data. In highly selected patients, no increase in sICH was observed, but there is large uncertainty.

Neurological Predictors of Clinical Outcomes in Hospitalized Patients With COVID-19.

Introduction: Multiple risk factors of mortality have been identified in patients with COVID-19. Here, we sought to determine the effect of a history of neurological disorder and development of neurological manifestations on mortality in hospitalized patients with COVID-19. Methods: From March 20 to May 20, 2020, hospitalized patients with laboratory confirmed or highly suspected COVID-19 were identified at four hospitals in Ohio. Previous history of neurological disease was classified by severity (major or minor). Neurological manifestations during disease course were also grouped into major and minor manifestations. Encephalopathy, ischemic or hemorrhagic stroke, and seizures were defined as major manifestations, whereas minor neurological manifestations included headache, anosmia, dysgeusia, dizziness or vertigo, and myalgias. Multivariate logistic regression models were used to determine significant predictors of mortality in patients with COVID-19 infection. Results: 574/626 hospitalized patients were eligible for inclusion. Mean age of the 574 patients included in the analysis was 62.8 (SD 17.6), with 298 (51.9%) women. Of the cohort, 240(41.8%) patients had a prior history of neurological disease (HND), of which 204 (35.5%) had a major history of neurological disease (HND). Mortality rates were higher in patients with a major HND (30.9 vs. 15.4%; p = 0.00002), although this was not a significant predictor of death. Major neurological manifestations were recorded in 203/574 (35.4%) patients during disease course. The mortality rate in patients who had major neurological manifestations was 37.4% compared to 11.9% (p = 2 × 10-12) in those who did not. In multivariate analysis, major neurological manifestation (OR 2.1, CI 1.3-3.4; p = 0.002) was a predictor of death. Conclusions: In this retrospective study, history of pre-existing neurological disease in hospitalized COVID-19 patients did not impact mortality; however, development of major neurological manifestations during disease course was found to be an independent predictor of death. Larger studies are needed to validate our findings.

Outcomes of treatment modalities for ruptured intracranial aneurysms based on age - A meta-analysis.

BACKGROUND: Data comparing the effect of age on outcomes of patients who underwent either endovascular coiling (EVC) or neurosurgical clipping (NSC) for ruptured intracranial aneurysms remains limited. OBJECTIVE: To better elucidate the preferred intervention for ruptured aneurysm management by presenting the results of our systematic review of the literature that evaluated the potential advantages of the two interventions between different age groups. METHODS: Systematic review of PubMed and Embase was performed (2002 - June 10, 2019) following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2013 guidelines. Median ages of EVC and NSC cohorts were 54 and 56, respectively. Ages below the median were used in our "younger" cohort; ages above the median were used in our "older" cohort. RESULTS: We reviewed 13 studies on 7,137 patients. In the younger cohort, there were 2840 (EVC: 1412, NSC: 1428) patients. In the older cohort, there were 4297 (EVC: 2552, NSC: 1745) patients. Overall, there was a significant difference in functionality between EVC (77.70%) and NSC (69.23%) (OR=1.69; 95% C.I.: 1.10-2.60, p = 0.0212). In our younger cohort, functionality was significantly different between EVC (77%) and NSC (69%) (OR=1.54; 95% C.I.: 1.29-1.84, p < 0.001). For the older cohort, there was no significant difference in functionality, complications, or efficacy. CONCLUSIONS: We have highlighted the importance of considering age prior to deciding which intervention is most appropriate for ruptured aneurysms, with higher morbidity and mortality with NSC versus EVC in the younger population.

Interventional Stroke Care in the Era of COVID-19.

The current coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 has led to immense strain on healthcare systems and workers. Patients with severe symptoms of COVID-19 may also present with acute neurological emergencies such as ischemic stroke. Ischemic stroke in these patients may result from COVID-19 related complications or decompensation of previously asymptomatic cerebrovascular disorders, or concurrent ischemic stroke from common stroke risk factors in a patient with COVID-19. Acute ischemic stroke patients with large vessel occlusions require emergent triage, intensive care, and mechanical thrombectomy. Management of patients with large vessel occlusions (LVO) requires special considerations in the current pandemic. Physicians must now account for prognosis of severe COVID-19, resource utilization, and risk of infection to healthcare workers when determining eligibility for mechanical thrombectomy (MT). Here, we describe important prognostic factors including age, laboratory, and imaging findings to consider for MT selection and provide suggestions for taking care of patients with LVO and possible or confirmed COVID-19. It is recommended to perform MT in patients within the established guidelines, and consider a conservative approach in cases where there is clinical equipoise to minimize futile reperfusion. Lastly, we describe an illustrative case of a patient with ischemic stroke and COVID-19.

First Pass Effect in Patients Treated With the Trevo Stent-Retriever: A TRACK Registry Study Analysis.

Background and Objective: The first pass effect (FPE; achieving complete recanalization with a single thrombectomy device pass) has been shown to be associated with higher rates of good clinical outcomes in patients with acute ischemic stroke. Here, we investigate clinical and radiographic factors associated with FPE in a large U.S. post-marketing registry (TRACK, Trevo Stent-Retriever Acute Stroke). Methods: We analyzed the TRACK database (multicenter registry of 634 patients from 23 centers from March 2013 through August 2015), which 609 patients were included in the final analysis. FPE was defined as a single pass/use of device, TICI 2c/3 recanalization, and no use of rescue therapy. Analysis of individual patient data from TRACK were performed to analyze clinical and radiographic characteristics associated with FPE as well-compared clinical outcomes defined as modified Rankin Scale (mRS) score at 30 and 90 days from hospital discharge to the non-FPE group. Results: The rate of FPE in TRACK was 23% (140/609). There was no association between patient demographics and FPE, including age (p = 0.36), sex (p = 0.50), race (p = 0.50), location of occlusion (p = 0.26), baseline NIHSS (p = 0.62), or past medical history. There was no difference in the use of a balloon-guide catheter or general anesthesia (49 and 57% with FPE vs. 47 and 64%, p = 0.63 and p = 0.14, respectively). Clinical outcomes were significantly associated with FPE; 63 vs. 44% in non-FPE patients achieved mRS 0-2 at 90 days (p = 0.0004). Conclusion: Our study showed that achieving complete recanalization with a single thrombectomy pass using the Trevo device was highly beneficial. The most common clinical factors that are used to determine eligibility for endovascular therapy, such as NIHSS severity, location of occlusion or patient age were not predictive of the ability to achieve FPE.

Long-term implementation of a prehospital severity scale for EMS triage of acute stroke: a real-world experience.

BACKGROUND: Data on the implementation of prehospital large vessel occlusion (LVO) scales to identify and triage patients with acute ischemic stroke (AIS) in the field are limited, with the majority of studies occurring outside the USA. OBJECTIVE: To report our long-term experience of a US countywide emergency medical services (EMS) acute stroke triage protocol using the Rapid Arterial oCclusion Evaluation (RACE) score. METHODS: Our prospective database was used to identify all consecutive patients triaged within Lucas County, Ohio by the EMS with (1) a RACE score ≥5, taken directly to an endovascular capable center (ECC) as RACE-alerts (RA) and (2) a RACE score <5, taken to the nearest hospital as stroke-alerts (SA). Baseline demographics, RACE score, time metrics, final diagnosis, treatments, and clinical and angiographic outcomes were captured. The sensitivity and specificity for patients with a RACE score ≥5 with LVO, eligible for mechanical thrombectomy (MT), were calculated. RESULTS: Between July 2015 and June 2018, 492 RA and 1147 SA were triaged within our five-hospital network. Of the RA, 37% had AIS secondary to LVOs. Of the 492 RA and 1147 SA, 125 (25.4%) and 38 (3.3%), respectively, underwent MT (OR=9.9; 95% CI 6.8 to 14.6; p<0.0001). Median times from onset-to-ECC arrival (74 vs 167 min, p=0.03) and dispatch-to-ECC arrival (31 vs 46 min, p=0.0002) were shorter in the RA-MT than in the SA-MT cohort. A RACE cut-off point ≥5 showed a sensitivity and specificity of 0.77 and 0.75 for detection of patients with LVO eligible for MT, respectively. CONCLUSIONS: We have demonstrated the long-term feasibility of a countywide EMS-based prehospital triage protocol using the RACE Scale within our hospital network.

Insights Into Intra-arterial Thrombolysis in the Modern Era of Mechanical Thrombectomy.

Background and Purpose: The role of intra-arterial (IA) thrombolysis in modern endovascular therapy is not well-understood. Here, we surveyed neurointerventionalists to understand their current clinical practices and opinions of IA thrombolysis in the new era of mechanical thrombectomy (MT). Method: A 24-question anonymous survey was distributed via email to the members of the Society of Vascular and Interventional Neurology. Results: One hundred and four responses were included in the analysis. Most respondents were interventional neurologists (76.9%) and had ≥5-years in neuro-interventional practice (80.8%). IA thrombolytics are presently used by 60.6%. Aspiration plus stent-retriever was the most common MT approach used with IA-thrombolysis (66.0%). IA-thrombolysis was used in mainly three approaches: (1) treatment of primary distal occlusions, (2) as rescue after proximal occlusion thrombectomy, and (3) or as adjunct therapy to primary MT approach. The most frequent IA-rtPA dose was 3-10 mg, with 1 mg/min infusion rate (56.6%). 84.9% do not have a standardized protocol for administering IA-rtPA. About half (50.9%) believed there should be no time limit for administering IA lytic if there is a favorable imaging profile, while 30.2% indicated ≤6 h. Most respondents (76.5%) would consider using IA-tenecteplase in a trial setting. Only 12.9% felt there was no role for IA thrombolysis in modern endovascular practice. Respondents with ≥10-years' experience were less supportive of the future of IA lytic (98.0 vs. 76.4%, p = 0.006). Conclusion: IA-thrombolysis is currently used in clinical practice; however, there is no clear consensus on best practices or criteria for administration. Further studies are needed to define the role of IA-thrombolysis in the context of MT.