Tenecteplase for Stroke at 4.5 to 24 Hours with Perfusion-Imaging Selection.

BACKGROUND: Thrombolytic agents, including tenecteplase, are generally used within 4.5 hours after the onset of stroke symptoms. Information on whether tenecteplase confers benefit beyond 4.5 hours is limited. METHODS: We conducted a multicenter, double-blind, randomized, placebo-controlled trial involving patients with ischemic stroke to compare tenecteplase (0.25 mg per kilogram of body weight, up to 25 mg) with placebo administered 4.5 to 24 hours after the time that the patient was last known to be well. Patients had to have evidence of occlusion of the middle cerebral artery or internal carotid artery and salvageable tissue as determined on perfusion imaging. The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability and a score of 6 indicating death) at day 90. Safety outcomes included death and symptomatic intracranial hemorrhage. RESULTS: The trial enrolled 458 patients, 77.3% of whom subsequently underwent thrombectomy; 228 patients were assigned to receive tenecteplase, and 230 to receive placebo. The median time between the time the patient was last known to be well and randomization was approximately 12 hours in the tenecteplase group and approximately 13 hours in the placebo group. The median score on the modified Rankin scale at 90 days was 3 in each group. The adjusted common odds ratio for the distribution of scores on the modified Rankin scale at 90 days for tenecteplase as compared with placebo was 1.13 (95% confidence interval, 0.82 to 1.57; P = 0.45). In the safety population, mortality at 90 days was 19.7% in the tenecteplase group and 18.2% in the placebo group, and the incidence of symptomatic intracranial hemorrhage was 3.2% and 2.3%, respectively. CONCLUSIONS: Tenecteplase therapy that was initiated 4.5 to 24 hours after stroke onset in patients with occlusions of the middle cerebral artery or internal carotid artery, most of whom had undergone endovascular thrombectomy, did not result in better clinical outcomes than those with placebo. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups. (Funded by Genentech; TIMELESS ClinicalTrials.gov number, NCT03785678.).

Blood Pressure after Successful Endovascular Therapy: A Systematic Review and Meta-Analysis of Randomized Control Trials.

OBJECTIVE: There are limited data evaluating the optimum blood pressure (BP) goal post mechanical thrombectomy (MT) and its effect on outcomes of patients with large vessel occlusions (LVO). The objective of this study was to compare the efficacy and safety of intensive versus conventional BP control after reperfusion with MT via a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: We searched PubMed and Embase to obtain articles related to BP control post MT through September 2023. The primary outcome was functional independence (modified Rankin Scale [mRS] 0-2) at 3 months, while secondary outcomes included excellent outcome (mRS 0-1), symptomatic intracranial hemorrhage (sICH), and mortality. RESULTS: Four RCTs with 1,566 patients (762 randomized into intensive BP control vs. 806 randomized into conventional BP control) were included. Analysis showed that there was a lower likelihood of functional independence (mRS 0-2: odds ratio [OR]: 0.68, 95% confidence interval [CI] 0.51-0.91, p = 0.009) in the more intensive treatment group compared with the conventional treatment group. There was no statistically significant difference in achieving excellent outcome (mRS0-1: OR: 0.82, 95% CI: 0.63-1.07; p = 0.15), risk of sICH or mortality. INTERPRETATION: This systematic review and meta- analysis Indicates that in patients who achieved successful MT for acute ischemic stroke with LVO, intensive BP control was associated with a lower likelihood of functional independence at 3 months without significant difference in likelihood of achieving excellent outcome, sICH risk, or mortality. ANN NEUROL 2024;95:858-865.

Expansion of Telestroke Coverage in Community Hospitals: Unifying Stroke Care and Reducing Transfer Rate.

OBJECTIVE: Telestroke (TS) service has been shown to improve stroke diagnosis timing and accuracy, facilitate treatment decisions, and decrease interfacility transfers. Expanding TS service to inpatient units at the community hospital provides an opportunity to follow up on stroke patients and optimize medical management. This study examines the outcome of expanding TS coverage from acute emergency room triage to incorporate inpatient consultation. METHODS: We studied the effect of expanding TS to inpatient consultation service at 19 regional hospitals affiliated with Promedica Stroke Network. We analyzed data pre- and post-TS expansion. We reviewed changes in TS utilization, admission rate, thrombolytic therapy, patient transfer rate, and diagnosis accuracy. RESULTS: Between January 2018 and June 2022, a total of 9,756 patients were evaluated in our stroke network (4,705 in pre- and 5,051 in the post-TS expansion). In the post-TS expansion period, stroke patients' admission at the spoke hospital increased from 18/month to 40/month, and for TIA from 11/month to 16/month. TS cart use increased from 12% to 35.2%. Patient transfers to hub hospital decreased by 31%. TS service expansion did not affect intravenous thrombolytic therapy rate or door-to-needle time. There was no difference in length of stay or readmission rate, and the patients at the spoke hospitals had a higher rate of home discharge 57.38% compared with 52.58% at hub hospital. INTERPRETATION: Telestroke service expansion to inpatient units helped decrease transfers and retain patients in their communities, increased stroke and TIA diagnosis accuracy, and did not compromise patients' hospitalization or outcome. ANN NEUROL 2024;95:576-582.

Cervical Dissection in Patients With Tandem Lesions Is Associated With Distal Embolism and Lower Recanalization Success.

BACKGROUND: Tandem lesions consist of cervical internal carotid artery (ICA) stenosis or occlusion, most commonly of atherosclerosis or dissection etiology, plus a large vessel occlusion. In this study, we compare outcomes in patients with atherosclerosis versus dissection of the cervical ICA. METHODS: This multicenter retrospective cohort study includes data from tandem lesion patients who underwent endovascular treatment from 2015 to 2020. Atherosclerosis was defined as ICA stenosis/occlusion associated with a calcified lesion and dissection by the presence of a tapered or flame-shaped lesion and intramural hematoma. Primary outcome: 90-day functional independence (modified Rankin Scale score, 0-2); secondary outcomes: 90-day favorable shift in the modified Rankin Scale score, modified Thrombolysis in Cerebral Infarction score 2b-3, modified Thrombolysis in Cerebral Infarction score 2c-3, symptomatic intracranial hemorrhage, parenchymal hematoma type 2, petechial hemorrhage, distal embolization, early neurological improvement, and mortality. Analysis was performed with matching by inverse probability of treatment weighting. RESULTS: We included 526 patients (68 [59-76] years; 31% females); 11.2% presented dissection and 88.8%, atherosclerosis. Patients with dissection were younger, had lower rates of hypertension, hyperlipidemia, diabetes, and smoking history. They also exhibited higher rates of ICA occlusion, multiple stents (>1), and lower rates of carotid self-expanding stents. After matching and adjusting for covariates, there were no differences in 90-day functional independence. The rate of successful recanalization was significantly lower in the dissection group (adjusted odds ratio, 0.38 [95% CI, 0.16-0.91]; P=0.031), which also had significantly higher rates of distal emboli (adjusted odds ratio, 2.53 [95% CI, 1.15-5.55]; P=0.021). There were no differences in other outcomes. Acute ICA stenting seemed to increase the effect of atherosclerosis in successful recanalization. CONCLUSIONS: This study reveals that among patients with acute stroke with tandem lesions, cervical ICA dissection is associated with higher rates of distal embolism and lower rates of successful recanalization than atherosclerotic lesions. Using techniques to minimize the risk of distal embolism may mitigate this contrast. Further prospective randomized trials are warranted to fully understand these associations.

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.

A comprehensive comparison of machine learning models for ICH prognostication: Retrospective review of 1501 intra-cerebral hemorrhage patients from the Qatar stroke database.

Multiple prognostic scores have been developed to predict morbidity and mortality in patients with spontaneous intracerebral hemorrhage(sICH). Since the advent of machine learning(ML), different ML models have also been developed for sICH prognostication. There is however a need to verify the validity of these ML models in diverse patient populations. We aim to create machine learning models for prognostication purposes in the Qatari population. By incorporating inpatient variables into model development, we aim to leverage more information. 1501 consecutive patients with acute sICH admitted to Hamad General Hospital(HGH) between 2013 and 2023 were included. We trained, evaluated, and compared several ML models to predict 90-day mortality and functional outcomes. For our dataset, we randomly selected 80% patients for model training and 20% for validation and used k-fold cross validation to train our models. The ML workflow included imbalanced class correction and dimensionality reduction in order to evaluate the effect of each. Evaluation metrics such as sensitivity, specificity, F-1 score were calculated for each prognostic model. Mean age was 50.8(SD 13.1) years and 1257(83.7%) were male. Median ICH volume was 7.5 ml(IQR 12.6). 222(14.8%) died while 897(59.7%) achieved good functional outcome at 90 days. For 90-day mortality, random forest(RF) achieved highest AUC(0.906) whereas for 90-day functional outcomes, logistic regression(LR) achieved highest AUC(0.888). Ensembling provided similar results to the best performing models, namely RF and LR, obtaining an AUC of 0.904 for mortality and 0.883 for functional outcomes. Random Forest achieved the highest AUC for 90-day mortality, and LR achieved the highest AUC for 90-day functional outcomes. Comparing ML models, there is minimal difference between their performance. By creating an ensemble of our best performing individual models we maintained maximum accuracy and decreased variance of functional outcome and mortality prediction when compared with individual models.

Predictors of early intracerebral hemorrhage in patients with cerebral sinus venous thrombosis: Systematic review and meta-analysis.

OBJECTIVES: Patients with cerebral venous thrombosis (CVT) may present with early intracerebral hemorrhage (EICH). The objective of this study was to identify predictors for EICH in CVT patients via a systematic review and meta-analysis of observational studies. Additionally, we aimed to evaluate the clinical outcomes associated with the presence of EICH in these patients. METHODS: Literature search on PubMed, EMBASE and Cochrane Library databases from inception up to 1 February 2024 was conducted. Five studies with predictors of EICH were included in qualitative synthesis and meta-analysis. RESULTS: Pooled analysis demonstrated a statistically significant association between female gender and EICH (odd ratios (OR) = 1.51, 95 % confidence interval (CI) = 1.23-1.85, p < 0.01). The ICH patients had higher likelihood of seizures (OR = 3.07, 95 % CI = 1.69-5.58, p < 0.01), focal neurological deficits (OR = 4.07, 95 % CI = 2.57-6.44, p < 0.01), and decreased level of consciousness (OR = 3.89, 95 % CI = 2.53-5.87, p < 0.01). Superior Sagittal Sinus thrombosis was associated with higher likelihood of EICH (OR: 1.49, 95 % CI 1.05-2.13, P = 0.03). No statistically significant association was demonstrated between presence of EICH and pregnancy, presence of hematological diseases or thrombophilia, or other site of venous thrombosis (deep venous system, or multiple sinuses involvement). Furthermore, patients who exhibited early EICH were notably less likely to attain a favorable functional outcome (mRS 0-2) (OR: 0.28; 95 % CI 0.16-0.49; p < 0.001). CONCLUSION: This meta-analysis demonstrates that among CVT patients, female patients with new onset seizures, focal neurological deficits and decreased level of consciousness are more likely to present with EICH.

Systolic blood pressure reduction strategies in acute ischemic stroke patients following endovascular thrombectomy: a systematic review and meta-analysis.

BACKGROUND AND AIMS: There is no clear consensus on ideal systolic blood pressure (SBP) target post-endovascular thrombectomy (EVT) in patients with acute ischemic stroke. This study intends to investigate the relationship between reducing SBP and clinical outcomes and to determine the therapeutic efficacy of moderate and intensive SBP reduction post EVT. METHODS: A comprehensive search was conducted across five electronic databases to identify studies relevant to our analysis. Data from these studies were then analyzed using pooled relative risk (RR) along with their corresponding 95 % confidence intervals (CI) for our categorical outcomes. functional independence at 90 days post-EVT was defined as a modified Rankin score (mRS) 0-2. RESULTS: Our meta-analysis included eight studies with 2922 patients: 1376 patients were treated with intensive SBP reduction, 306 with moderate SBP reduction, and 1243 with standard SBP reduction. There was no difference in the risk of functional independence at 90 days post-EVT with both intensive-SBP reduction (target 120-140 mmHg, relative risk (RR) =1.05, 95 % CI 0.82, 1.34, p = 0.72) and moderate-SBP reduction (>160 mm Hg) (RR= 0.95, 95 % CI 0.69, 1.31, p = 0.76) compared with standard SBP reduction (>180 mm Hg). The risk of symptomatic intracranial hemorrhage (sICH) did not significantly differ between standard-SBP reduction and intensive-SBP reduction (RR = 0.93, 95 % CI 0.66, 1.31, p = 0.36) or moderate-SBP reduction (0.72 (95 % CI [0.28, 1.87], p = 0.50) groups, respectively. Intensive-SBP reduction significantly decreased the risk of hemicraniectomy. CONCLUSIONS: We did not identify any difference in functional independence at 90 days in acute ischemic stroke patients with either intensive-SBP reduction or moderate-SBP reduction compared with standard SBP reduction post-EVT.

Comparing Functional Outcomes and Safety Profiles of First-Line Aspiration Thrombectomy Versus Stentriever for Acute Basilar Artery Occlusion: Propensity Analysis of the PC-SEARCH Thrombectomy Registry.

BACKGROUND: Aspiration catheters (ASPs) and stentriever thrombectomy devices have comparable safety and efficacy in anterior circulation ischemic strokes. However, there is lack of high-quality comparative data in acute basilar artery occlusions. Our objective is to compare the outcomes and safety of ASPs and stentriever devices in acute basilar artery occlusions. METHODS: This is an analysis of the retrospectively established PC-SEARCH Thrombectomy (Posterior-Circulation Ischemic Stroke Evaluation: Analyzing Radiographic and Intraprocedural Predictors for Mechanical Thrombectomy) registry. Patients were dichotomized based on their first-line thrombectomy device (ASP and stentriever) and associated with their 90-day functional outcomes, intraprocedural metrics, and safety measures. Propensity analysis based on unequal baseline characteristics was performed. Consecutive patients with acute basilar artery occlusions who received mechanical thrombectomy were included from January 2015 to December 2021. Patients received either first-line contact aspiration or stentriever mechanical thrombectomy. Primary clinical and safety outcomes were 90-day functional independence measured by a modified Rankin Scale score of 0 to 3 and symptomatic intracranial hemorrhage, respectively. Secondary outcomes included puncture-recanalization times, first-pass recanalization rates, crossovers to other thrombectomy device, and neurological/hospital complications. RESULTS: Five hundred eighteen patients were included in the registry, and a total of 383 patients were included (mean [SD] age, 65.5 [15] years; 228 [59%] men) in this analysis. Of these, 219 patients were first-line ASP while 164 patients received first-line stentriever devices. Median premorbid modified Rankin Scale was zero and median presenting National Institutes of Health Stroke Scale was 17 (interquartile range, 8-26). The proportion of favorable functional outcome was similar between the 2 techniques before (47.3% versus 42.5%; odds ratio, 1.22 [95% CI, 0.78-1.89]; P=0.38) and after propensity matching (odds ratio, 1.46 [95% CI, 0.85-2.49]; P=0.17). In our propensity-matched cohorts, puncture-recanalization times (18 versus 52 minutes; P<0.01) favored first-line ASP; however, first-pass recanalization rates (43.5% versus 44.5%; P=0.90) were similar between groups. First-line ASP was associated with higher rates of crossover (22% versus 6%; P<0.01), whereas stentriever was associated with higher rates of symptomatic intracranial hemorrhage (9.8% versus 3.4%; P=0.04). CONCLUSIONS: First-line ASP and stentriever methods demonstrated similar functional outcome and recanalization rates. Stentriever methods were associated with higher rates of symptomatic intracranial hemorrhage, whereas ASPs were associated with higher rates of crossover to alternative technique in patients with acute basilar occlusions.

Safety Outcomes of Mechanical Thrombectomy Versus Combined Thrombectomy and Intravenous Thrombolysis in Tandem Lesions.

BACKGROUND: We aimed to describe the safety and efficacy of mechanical thrombectomy (MT) with or without intravenous thrombolysis (IVT) for patients with tandem lesions and whether using intraprocedural antiplatelet therapy influences MT's safety with IVT treatment. METHODS: This is a subanalysis of a pooled, multicenter cohort of patients with acute anterior circulation tandem lesions treated with MT from 16 stroke centers between January 2015 and December 2020. Primary outcomes included symptomatic intracranial hemorrhage (sICH) and parenchymal hematoma type 2. Additional outcomes included hemorrhagic transformation, successful reperfusion (modified Thrombolysis in Cerebral Infarction score 2b-3), complete reperfusion (modified Thrombolysis in Cerebral Infarction score 3), favorable functional outcome (90-day modified Rankin Scale score 0-2), excellent functional outcome (90-day modified Rankin Scale score 0-1), in-hospital mortality, and 90-day mortality. RESULTS: Of 691 patients, 512 were included (218 underwent IVT+MT and 294 MT alone). There was no difference in the risk of sICH (adjusted odds ratio [aOR], 1.22 [95% CI, 0.60-2.51]; P=0.583), parenchymal hematoma type 2 (aOR, 0.99 [95% CI, 0.47-2.08]; P=0.985), and hemorrhagic transformation (aOR, 0.95 [95% CI, 0.62-1.46]; P=0.817) between the IVT+MT and MT alone groups after adjusting for confounders. Administration of IVT was associated with an increased risk of sICH in patients who received intravenous antiplatelet therapy (aOR, 3.04 [95% CI, 0.99-9.37]; P=0.05). The IVT+MT group had higher odds of a 90-day modified Rankin Scale score 0 to 2 (aOR, 1.72 [95% CI, 1.01-2.91]; P=0.04). The odds of successful reperfusion, complete reperfusion, 90-day modified Rankin Scale score 0 to 1, in-hospital mortality, or 90-day mortality did not differ between the IVT+MT versus MT alone groups. CONCLUSIONS: Our study showed that the combination of IVT with MT for tandem lesions did not increase the overall risk of sICH, parenchymal hematoma type 2, or overall hemorrhagic transformation independently of the cervical revascularization technique used. However, intraprocedural intravenous antiplatelet therapy during acute stent implantation might be associated with an increased risk of sICH in patients who received IVT before MT. Importantly, IVT+MT treatment was associated with a higher rate of favorable functional outcomes at 90 days.

Low dose intravenous cangrelor versus glycoprotein IIb/IIIa inhibitors in endovascular treatment of tandem lesions.

OBJECTIVES: Intravenous (IV) periprocedural antiplatelet therapy (APT) for patients undergoing acute carotid stenting during mechanical thrombectomy (MT) is not fully investigated. We aimed to compare the safety profile of IV low dose cangrelor versus IV glycoprotein IIb/IIIa (GP-IIb/IIIa) inhibitors in patients with acute tandem lesions (TLs). MATERIALS AND METHODS: We retrospectively identified all cases of periprocedural administration of IV cangrelor or GP-IIb/IIIa inhibitors during acute TLs intervention from a multicenter collaboration. Patients were divided in two groups according to the IV APT regimen at the time of MT procedure: 1) cangrelor and 2) GP-IIb/IIIa inhibitors (tirofiban and eptifibatide). Safety outcomes included rates of symptomatic intracranial hemorrhage (sICH), parenchymal hematoma type 1 and 2 (PH1-PH2), and hemorrhagic infarction type 1 and 2 (HI1-HI2). RESULTS: Sixty-three patients received IV APT during MT, 30 were in the cangrelor group, and 33 were in the GP-IIb/IIIa inhibitors group. There were no significant differences in the rates of sICH (3.3% vs. 12.1%, aOR=0.21, 95%CI 0.02-2.18, p=0.229), HI1-HI2 (21.4% vs 42.4%, aOR=0.21, 95%CI 0.02-2.18, p=0.229), and PH1-PH2 (17.9% vs. 12.1%, aOR=1.63, 95%CI 0.29-9.83, p=0.577) between both treatment groups. However, there was a trend toward reduced hemorrhage rates with cangrelor. Cangrelor was associated with increased odds of complete reperfusion (aOR=5.86; 95%CI 1.57-26.62;p=0.013). CONCLUSIONS: In this retrospective non-randomized cohort study, our findings suggest that low dose cangrelor has similar safety and increased rate of complete reperfusion compared to IV GP-IIb/IIIa inhibitors. Further prospective studies are warranted to confirm this association.

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.

Association of Recent Use of Non-Vitamin K Antagonist Oral Anticoagulants With Intracranial Hemorrhage Among Patients With Acute Ischemic Stroke Treated With Alteplase.

Importance: Current guidelines recommend against use of intravenous alteplase in patients with acute ischemic stroke who are taking non-vitamin K antagonist oral anticoagulants (NOACs). Objective: To evaluate the safety and functional outcomes of intravenous alteplase among patients who were taking NOACs prior to stroke and compare outcomes with patients who were not taking long-term anticoagulants. Design, Setting, and Participants: A retrospective cohort study of 163 038 patients with acute ischemic stroke either taking NOACs or not taking anticoagulants prior to stroke and treated with intravenous alteplase within 4.5 hours of symptom onset at 1752 US hospitals participating in the Get With The Guidelines-Stroke program between April 2015 and March 2020, with complementary data from the Addressing Real-world Anticoagulant Management Issues in Stroke registry. Exposures: Prestroke treatment with NOACs within 7 days prior to alteplase treatment. Main Outcomes and Measures: The primary outcome was symptomatic intracranial hemorrhage occurring within 36 hours after intravenous alteplase administration. There were 4 secondary safety outcomes, including inpatient mortality, and 7 secondary functional outcomes assessed at hospital discharge, including the proportion of patients discharged home. Results: Of 163 038 patients treated with intravenous alteplase (median age, 70 [IQR, 59 to 81] years; 49.1% women), 2207 (1.4%) were taking NOACs and 160 831 (98.6%) were not taking anticoagulants prior to their stroke. Patients taking NOACs were older (median age, 75 [IQR, 64 to 82] years vs 70 [IQR, 58 to 81] years for those not taking anticoagulants), had a higher prevalence of cardiovascular comorbidities, and experienced more severe strokes (median National Institutes of Health Stroke Scale score, 10 [IQR, 5 to 17] vs 7 [IQR, 4 to 14]) (all standardized differences >10). The unadjusted rate of symptomatic intracranial hemorrhage was 3.7% (95% CI, 2.9% to 4.5%) for patients taking NOACs vs 3.2% (95% CI, 3.1% to 3.3%) for patients not taking anticoagulants. After adjusting for baseline clinical factors, the risk of symptomatic intracranial hemorrhage was not significantly different between groups (adjusted odds ratio [OR], 0.88 [95% CI, 0.70 to 1.10]; adjusted risk difference [RD], -0.51% [95% CI, -1.36% to 0.34%]). There were no significant differences in the secondary safety outcomes, including inpatient mortality (6.3% for patients taking NOACs vs 4.9% for patients not taking anticoagulants; adjusted OR, 0.84 [95% CI, 0.69 to 1.01]; adjusted RD, -1.20% [95% CI, -2.39% to -0%]). Of the secondary functional outcomes, 4 of 7 showed significant differences in favor of the NOAC group after adjustment, including the proportion of patients discharged home (45.9% vs 53.6% for patients not taking anticoagulants; adjusted OR, 1.17 [95% CI, 1.06 to 1.29]; adjusted RD, 3.84% [95% CI, 1.46% to 6.22%]). Conclusions and Relevance: Among patients with acute ischemic stroke treated with intravenous alteplase, use of NOACs within the preceding 7 days, compared with no use of anticoagulants, was not associated with a significantly increased risk of intracranial hemorrhage.

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.

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.

Emergent Management of Tandem Lesions in Acute Ischemic Stroke.

Background and Purpose- Although intracranial thrombectomy represents the standard treatment approach for anterior circulation tandem occlusions, whether the extracranial lesion requires acute stenting remains unclear. Our aim was to investigate differences in clinical and procedural outcomes related to stenting extracranial lesions in a registry of patients undergoing thrombectomy for acute stroke. Methods- Data were analyzed from the STRATIS registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke)-a prospective, nonrandomized study of patients undergoing neurothrombectomy with the Solitaire device. A total of 984 patients treated at 55 sites were analyzed. Univariate and multivariable logistic regression was used to assess relationship between outcome and procedural technique. Results- Of 147 (14.9%) patients with tandem lesions treated, stenting of the extracranial lesion during thrombectomy was performed in 80 patients and withheld in 67 patients. There were no differences between groups with respect to age, ASPECTS (Alberta Stroke Program Early CT Score), or intravenous-tPA (tissue-type plasminogen activator) use. However, the patients in the stenting group had lower baseline National Institutes of Health Stroke Scale (16 versus 17.9; P=0.07), shorter onset to arterial puncture time (133.6 versus 163.4 minutes; P=0.04), and lower rates of atrial fibrillation (6.3% versus 25.4%) as compared to the nonstenting group. Good outcomes (modified Rankin Scale, 0-2 at 90 days) were higher in the stenting group (68.5% versus 42.2%; P=0.003) with no difference in mortality or symptomatic hemorrhage. After adjustment for covariates, stenting continued to be associated with superior outcomes. Conclusions- Acute stenting of an extracranial carotid stenosis during neurothrombectomy can be achieved with equal safety compared with no stenting. Carotid stenting in the acute phase may lead to better outcomes; this should ideally be confirmed by randomized trials.

Intraarterial Thrombolysis as Rescue Therapy for Large Vessel Occlusions.

Background and Purpose- Mechanical thrombectomy (MT) devices have led to improved reperfusion and clinical outcomes in acute ischemic stroke patients with emergent large vessel occlusions; however, less than one-third of patients achieve complete reperfusion. Use of intraarterial thrombolysis in the context of MT may provide an opportunity to enhance these results. Here, we evaluate the use of intraarterial rtPA (recombinant tissue-type plasminogen activator) as rescue therapy (RT) after failed MT in the North American Solitaire Stent-Retriever Acute Stroke registry. Methods- The North American Solitaire Stent-Retriever Acute Stroke registry recruited sites within North America to submit data on acute ischemic stroke patients treated with the Solitaire device. After restricting the population of 354 patients to use of RT and anterior emergent large vessel occlusions, we compared patients who were treated with and without intraarterial rtPA after failed MT. Results- A total of 37 and 44 patients was in the intraarterial rtPA RT and the no intraarterial rtPA RT groups, respectively. Revascularization success (modified Thrombolysis in Cerebral Infarction ≥2b) was achieved in more intraarterial rtPA RT patients (61.2% versus 46.6%; P=0.13) with faster times to recanalization (100±85 versus 164±235 minutes; P=0.36) but was not statistically significant. The rate of symptomatic intracranial hemorrhage (13.9% versus 6.8%; P=0.29) and mortality (42.9% versus 44.7%; P=0.87) were similar between the groups. Good functional outcome (modified Rankin Scale score of ≤2) was numerically higher in intraarterial rtPA patients (22.9% versus 18.4%; P=0.64). Further restriction of the RT population to M1 occlusions only and time of onset to groin puncture ≤8 hours, resulted in significantly higher successful revascularization rates in the intraarterial rtPA RT cohort (77.8% versus 38.9%; P=0.02). Conclusions- Intraarterial rtPA as RT demonstrated a similar safety and clinical outcome profile, with higher reperfusion rates achieved in patients with M1 occlusions. Prospective studies are needed to delineate the role of intraarterial thrombolysis in MT.

Recent Trends in Electively Treated Unruptured Intracranial Aneurysms.

BACKGROUND AND PURPOSE: To determine recent treatment and outcome trends in patients undergoing elective surgical clipping (SC) or endovascular therapy (EVT) for unruptured intracranial aneurysms (UIAs) in the United States. METHODS: Data were extracted and analyzed from the National Inpatient Sample, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality for all patients admitted for elective EVT or SC of UIAs between 2011 and 2014. Treatment trends, in-hospital mortality, complication rates, length of stay (LOS) and total hospital costs were evaluated and analyzed. RESULTS: A total of 31,070 patients with UIAs were included in our analysis, of which 14,411 and 16,659 underwent elective SC and EVT, respectively. There was no significant difference in in-hospital mortality rates between the 2 groups. EVT was associated with lower in-hospital complication rates, decreased median LOS (.8 days versus 3.3 days, P ≤ .0001), and an increased likelihood of discharge to home (92.9% versus 72.9%, P = .0001). Median total hospital charges were similar in both treatment cohorts. Independent predictors of mortality in the elective population were age over 40 years (P ≤ .0001), weekend treatment (P ≤ .0001), and high co-morbidity status (P ≤ .0001). CONCLUSIONS: In-hospital mortality rates were similar in elective EVT and SC UIA patients; however, EVT was associated with lower in-hospital complication rates and shorter LOS.

Emergent carotid endarterectomy versus stenting in acute stroke patients with tandem occlusion.

OBJECTIVE: Acute stroke due to tandem cervical internal carotid artery (ICA) and intracranial large-vessel occlusion (ILVO) has a high rate of morbidity and mortality. The most appropriate treatment strategy for the extracranial culprit lesion remains unclear. In this study, we report our institutional outcomes with two approaches: emergent carotid endarterectomy (CEA) and carotid artery stenting (CAS). METHODS: Patients with tandem ICA-ILVO were identified in a prospective mechanical thrombectomy (MT) database between July 2012 and April 2016. Patients had a concomitant complete ICA origin occlusion and occlusion of the intracranial ICA or M1 or M2 middle cerebral artery segment. Baseline characteristics, procedural data, and treatment times were reviewed. End points included good recanalization of both ICA and ILVO, symptomatic intracerebral hemorrhage (defined by clinical decline of >4 points on the National Institutes of Health Stroke Scale), and functional outcome at 90 days. RESULTS: Forty-five patients had tandem ICA-ILVO occlusion; 27 patients underwent emergent CAS and 12 patients underwent emergent CEA after MT. Successful Thrombolysis in Cerebral Infarction grade 2B/3 recanalization was achieved in 92% of the CEA and 96% of the CAS patients (P = .53). Three CAS patients (11%) and none of the CEA patients had symptomatic intracerebral hemorrhage (P = .54). At 90 days, 75% (9/12) of the CEA patients were functionally independent compared with 70% (19/27) in the CAS group (P = 1.0). No deaths were noted in the CEA group compared with five (18.5%) in the CAS arm (P = .30). CONCLUSIONS: Our study indicates that early recanalization with MT followed by emergent CEA is safe and feasible, which suggests that both CAS and CEA should be considered in the emergent treatment of patients with tandem occlusion.