Matouk, Charles

Introduction: Real-world data showed that less than half of the acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) presenting with low Alberta Stroke Program Early Computed Tomography Score (ASPECTS) (2-5) achieved favorable outcomes at 90 days after mechanical thrombectomy (MT). In this study, we aim to investigate the relationship between the number of MT passes at which successful recanalization is obtained and outcomes in LVO-related AIS patients with low ASPECTS. Methods: This retrospective cohort study was performed on the data from 31 thrombectomy-capable centers between 2013 to 2022. Successful recanalization was defined as modified Thrombolysis in Cerebral Ischemia Score≥ 2b. The primary outcome was a 90-day modified Rankin Scale (mRS) of 0-3. Secondary outcomes were symptomatic intracranial hemorrhage and intracranial hemorrhage within 24 hours and mortality at 90 days. Outcomes were compared among patients with unsuccessful recanalization, and successful recanalization at first, second, third, and more than four passes. Results: A total of 297 patients with a median age of 70 [IQR 59-78] years were included and 140 (47.1%) were female. In 239 (80.4%) patients, successful recanalization was achieved: 88 patients (29.6 %) with 1 pass, 59 patients (19.9 %) with 2 passes, 35 patients(11.8%) with 3 passes, and 57 patients (19.2%) with more than 4 passes. Compared to unsuccessful recanalization, successful recanalization at first pass (adjusted OR 5.25, 95% CI 1.78 - 17.1), second passes (adjusted OR 5.20, 95% CI 1.68 - 17.6), and passes 4 (adjusted OR 4.90, 95% CI 1.68 - 17.6) was related to 90-day mRS 0-3. Recanalization status and MT attempt number were not related to secondary outcomes except for 90-day mortality. Compared to unsuccessful recanalization, successful recanalization at second and third passes were inversely related to 90-day mortality (adjusted OR 0.37, 95% CI 0.14 - 0.93; adjusted OR 0.33, 95% CI 0.11 - 0.95, respectively). Conclusion: The present results indicated that successful recanalization was related to 90-day good outcome regardless of the number of MT passes but the odds of achieving favorable outcome declines with each pass.

Introduction: The combination of intravenous or intra-arterial thrombolysis with mechanical thrombectomy (MT) for acute ischemic stroke (AIS) has been thoroughly investigated. However, no study has explored the outcomes of combining both intravenous and intra-arterial thrombolysis with MT. Methods: Data from Stroke Thrombectomy and Aneurysm Registry (STAR) from 2013 to 2023 was utilized. We compared AIS patients with LVO who underwent MT with combined intra-venous and intra-arterial thrombolysis (IV+IA) and with intra-venous thrombolysis alone (IV). We performed propensity score (PS) matching between the two groups using age, sex, premorbid mRS, admission NIHSS, occluded vessel, ASPECTS score, time from symptoms onset to arterial puncture, and frontline technique. Primary outcomes were any intracranial hemorrhage (ICH) and symptomatic ICH (sICH). Secondary outcomes included successful recanalization (mTICI ≥2C), early neurological improvement (defined as 4 or more points improvement in NIHSS score in 24 hours), 90-day modified Rankin Scale (mRS) 0-2, mRS 0-1, and mortality. Results: A total of 2495 LVO-related AIS patients were included, consisting of the IA+IV group (n = 266) and the IV group (n = 2228). Propensity matching yielded 192 well-matched patients in each group. No significant differences were observed between the groups in either ICH or sICH (odds ratio [OR]: 0.96, 95% confidence interval [CI]: 0.61-1.52, p = 0.60; OR: 0.92, 95% CI: 0.42-2.03, p > 0.90, respectively). The IA+IV group had a significantly lower proportion of successful recanalization (OR: 0.41, 95% CI: 0.27-0.62, p < 0.001), and early neurological improvement (OR: 0.55, 95% CI: 0.30-1.00). However, 90-day mRS 0-2, mRS 0-1, and mortality rates showed no significant differences between the two groups. Conclusion: The findings of this study suggest that the combined use of IA and IV thrombolysis in AIS patients undergoing MT is safe. Although the IA+IV group demonstrated lower rates of recanalization and early neurological improvement, long-term functional outcomes and mortality rates were comparable to the IV-thrombolysis group, indicating a potential delayed benefit of additional IA thrombolysis therapy.

Introduction: While balloon guide catheters (BGCs) enhance safety and efficacy of mechanical thrombectomy in large vessel occlusions, their impact on distal medium vessel occlusion (DMVO) remains underexplored. This study aimed to compare the outcomes of BGC vs non-BGC in DMVO thrombectomy. Methods: This retrospective study focused on DMVO cases defined as occlusions in M2-M4 middle cerebral artery, anterior cerebral artery, and posterior cerebral artery. Baseline characteristics and technical and clinical outcomes were compared between the two groups, with subgroup analysis in first-line thrombectomy techniques, including ADAPT, stent retriever, and Solumbra. First pass effect (FPE) was defined as a modified Thrombolysis in Cerebral Infarction (mTICI) score ≥ 2C after the first pass. Results: A total of 1,508 patients were included, of whom 231 (15.3%) were in the BGC group and 1,277 (84.7%) were in the Non-BGC group. The BGC group was associated with a lower mTICI score ≥ 2C (overall: 43.2% vs. 52.7%, p = 0.01; ADAPT: 42.2% vs. 57.1%, p = 0.01; Solumbra: 32.4% vs. 51.4%, p = 0.005), longer puncture to intracranial access time (overall: 15 vs. 8 min, p < 0.001; ADAPT: 17 vs. 8 min, p < 0.001; Solumbra: 12 vs. 8 min, p = 0.02), and longer puncture to recanalization time (overall: 97 vs. 35 min, p < 0.001; ADAPT: 100 vs. 28 min, p < 0.001; Solumbra: 78 vs. 46 min, p < 0.001; Stent retriever: 95 vs. 45 min, p < 0.001 ). The BGC group also had a lower FPE rate (17.4% vs. 30.7%, p = 0.03) in the Solumbra subgroup. In terms of clinical outcomes, the BGC group had a lower rate of distal embolization (overall: 8.8% vs. 14.9%, p = 0.02), but there were no significant differences in other clinical outcomes between the two groups in first-line thrombectomy techniques. Conclusions: Our findings showed that the use of BGC in DMVO had a lower mTICI score, reduced FPE rates, decreased distal embolization, and longer procedure times. Figure 1: Figure 2:

Introduction: The efficacy of mechanical thrombectomy (MT) for tandem vertebrobasilar occlusion (tVBO) is not well established in patients with basilar artery occlusion (BAO). Objective: To investigate the treatment outcomes of MT in tVBO. Method: This international, multicenter, retrospective cohort included patients with MT for tVBO and isolated BAO from 2013 to 2023. The primary outcome was the 90-day modified Rankin Scale (mRS) score 0-2. Secondary outcomes included complete recanalization (modified Thrombolysis in Cerebral Ischemia [mTICI] ≥ 2C) and 90-day mortality rate. These outcomes were compared between tVBO and isolated BAO groups. Adjustment factors were age, sex, admission National Institutes of Health Stroke Scale (NIHSS), pre-morbid mRS, onset to groin duration, and intravenous tissue plasminogen activator. Results: Among 10,229 patients, 689 had BAO. Of those, 61 (9.7%) had a tVBO. Median age was 61 [IQR 53-74] years and 29 (47.5%) patients were female. Compared to isolated BAO, tVBO group had lower age (61 [53-74] versus 68 [58-79], P<0.001) and lower admission NIHSS (15 [7 - 22] versus 17 [9-26], P≤0.05). There was no significant difference in the rate of complete recanalization between the two groups (adjusted odds ratio [aOR]: 0.83; 95% CI: 0.39-1.79; P=0.60) However, the tVBO group had significantly lower odds of a favorable outcome compared to the isolated BAO group (aOR: 0.35; 95% CI: 0.13-0.83; P=0.023) and higher odds of 90-day mortality (aOR: 3.51; 95% CI: 1.59-7.85; P=0.002). Binary regression analysis revealed that age (OR 0.98; 95% CI 0.96 - 1.00; P=0.019), admission NIHSS (OR 0.90; 95% CI 0.87-0.93; P<0.001), premorbid mRS (OR 0.71; 95% CI 0.53-0.93; P=0.016), successful recanalization (OR 2.94; 95% CI 1.71-5.15; P<0.001), and tVBO (OR 0.33; 95% CI 0.11-0.86; P=0.031) were significant predictors of 90-day favorable outcome. Conclusion: tVBO was associated with poor outcomes. Further efforts should be aimed at improving outcomes for this subpopulation.

Objective: To determine whether first pass effect (FPE) after mechanical thrombectomy (MT) for anterior circulation large vessel occlusion acute ischemic stroke (LVO-AIS) is modified by procedural time (PT). Methods: The Stroke Thrombectomy and Aneurysm Registry (STAR), a multi-center international dataset, was retrospectively analyzed for anterior circulation LVO-AIS treated by MT who achieved excellent reperfusion (TICI 2c/3). The primary outcome was good functional outcome as defined by a 90-day modified Rankin Scale (mRS) 0-2. The primary study exposure was first pass success (FPS, 1 pass vs ≥2 passes) and the secondary exposure was PT. Logistic regression models were fit-adjusted and marginal effects used to assess the interaction of PT (≤30 vs >30 minutes) and FPS, adjusting for potential confounders including time from last known well to start of MT. Results: A total of 1,310 patients had excellent reperfusion. These patients were divided into two cohorts based on PT: ≤30 minutes (777 patients, 59.3%) and > 30 minutes (533 patients, 40.7%). Good functional outcome was observed in 658 patients (50.2%). The interaction term between FPS and PT was significant (p=0.018). Individuals with FPS in ≤30 minutes had 11.5% higher adjusted predicted probability of good outcome compared with those who required ≥2 passes (58.2% vs. 46.7%, p=0.001). However, there was no significant difference in the adjusted predicted probability of good outcome based on FPS in individuals with PT >30 minutes (p=0.763). This relationship appeared identical in models with PT treated as a continuous variable. Conclusion: In a large, real-world, multi-national dataset, we find that FPE is importantly modified by PT. The added clinical benefit of FPE is lost in longer procedures (>30 minutes). These data argue for a new metric for MT procedures, namely, FPE 30 , that better represents the ideal of fast, complete reperfusion with a single pass of a thrombectomy device.

Background As the number of thrombectomy passes increases during endovascular therapy (EVT) for acute stroke, neurointerventionalists must weigh the risks of potential complications against the risk of failing to recanalize the affected vessel. Thus, we investigated the effectiveness and safety of EVT for patients with acute stroke in which ≥5 EVT passes were performed. Methods This retrospective cohort study from January 2013 to December 2022 included 31 thrombectomy‐capable centers. Patients in whom ≥5 EVT passes were made were included in the analysis. The patients with successful recanalization defined as modified Thrombolysis in Cerebral Infarction ≥2b at 5, 6, 7, or more passes were compared with unsuccessful recanalization. We also compared procedure time, separated by 30 minutes. Primary outcome was a favorable 90‐day outcome (modified Rankin scale score of 0–2). Secondary outcomes were intracranial hemorrhage and death. Results A total of 407 patients met the inclusion criteria, of which 175 were women (43.1%); the mean age was 67.3 years. In 265 (65.1%) patients, successful recanalization was achieved: 134 patients with 5 passes, 67 patients with 6 passes, and 64 with ≥7 passes. Intravenous recombinant tissue plasminogen activator administration was more common in the unsuccessful recanalization group (successful recanalization with 5, 6, and ≥7 EVT passes and unsuccessful recanalization: 35.3%, 30.3%, 18.8%, and 45.4%, respectively). Successful recanalization with 5, 6, and ≥7 EVT passes was associated with favorable outcome compared with unsuccessful recanalization group (adjusted odds ratio successful recanalization with 5, 6, and ≥7 EVT passes to unsuccessful recanalization [95% CIs]: 8.29 [2.13–32.3]; 14.0 [3.27–60.3]; and 5.26 [1.12–24.8], respectively). However, symptomatic intracranial hemorrhage was not significantly different between the groups. Regarding procedure time, favorable outcome was not significantly different in each group, while symptomatic intracranial hemorrhage occurred more frequently in the 60 to 89 minutes group compared with the <30 minutes group (adjusted odds ratio, 60–89 minutes group to <30 minutes group [95% CI]: 5.86 [1.09–31.6]). Conclusion These findings suggest that a benefit in outcome persists for recanalization, without significant increase in complications. In addition, there was no significant difference in favorable outcomes among procedure time.

Abstract Background Flow diversion is a common endovascular treatment for cerebral aneurysms, but studies comparing different types of flow diverters are scarce. Objective To perform a propensity score matched cohort study comparing the Pipeline Embolization Device (PED) and Flow Redirection Intraluminal Device (FRED) for posterior circulation aneurysms. Methods Consecutive aneurysms of the posterior circulation treated at 25 neurovascular centers with either PED or FRED were collected. Propensity score matching was used to control for age, duration of follow-up imaging, adjunctive coiling, and aneurysm location, size, and morphology; previously ruptured aneurysms were excluded. The two devices were compared for the following outcomes: procedural complications, aneurysm occlusion, and functional outcome. Results A total of 375 aneurysms of the posterior circulation were treated in 369 patients. The PED was used in 285 (77.2%) and FRED in 84 (22.8%) procedures. Aneurysms treated with the PED were more commonly fusiform and larger than those treated with FRED. To account for these important differences, propensity score matching was performed resulting in 33 PED and FRED unruptured aneurysm pairs. No differences were found in occlusion status and neurologic thromboembolic or hemorrhagic complications between the two devices. The proportion of patients with favorable functional outcome was higher with FRED (100% vs 87.9%, p=0.04). Conclusion Comparative analysis of PED and FRED for the treatment of unruptured posterior circulation aneurysms did not identify significant differences in aneurysm occlusion or neurologic complications. Variations in functional outcomes warrant additional investigations.

ObjectiveObservational studies point to an inverse correlation between low‐density lipoprotein (LDL) cholesterol levels and risk of intracerebral hemorrhage (ICH), but it remains unclear whether this association is causal. We tested the hypothesis that genetically elevated LDL is associated with reduced risk of ICH.MethodsWe constructed one polygenic risk score (PRS) per lipid trait (total cholesterol, LDL, high‐density lipoprotein [HDL], and triglycerides) using independent genomewide significant single nucleotide polymorphisms (SNPs) for each trait. We used data from 316,428 individuals enrolled in the UK Biobank to estimate the effect of each PRS on its corresponding trait, and data from 1,286 ICH cases and 1,261 matched controls to estimate the effect of each PRS on ICH risk. We used these estimates to conduct Mendelian Randomization (MR) analyses.ResultsWe identified 410, 339, 393, and 317 lipid‐related SNPs for total cholesterol, LDL, HDL, and triglycerides, respectively. All four PRSs were strongly associated with their corresponding trait (all p < 1.00 × 10‐100). While one SD increase in the PRSs for total cholesterol (odds ratio [OR] = 0.92; 95% confidence interval [CI] = 0.85–0.99; p = 0.03) and LDL cholesterol (OR = 0.88; 95% CI = 0.81–0.95; p = 0.002) were inversely associated with ICH risk, no significant associations were found for HDL and triglycerides (both p > 0.05). MR analyses indicated that 1mmol/L (38.67mg/dL) increase of genetically instrumented total and LDL cholesterol were associated with 23% (OR = 0.77; 95% CI = 0.65–0.98; p = 0.03) and 41% lower risks of ICH (OR = 0.59; 95% CI = 0.42–0.82; p = 0.002), respectively.InterpretationGenetically elevated LDL levels were associated with lower risk of ICH, providing support for a potential causal role of LDL cholesterol in ICH. ANN NEUROL 2020 ANN NEUROL 2020;88:56–66

Abstract BACKGROUND Both stent-assisted coiling (SAC) and flow diversion with the Pipeline Embolization device (PED; Medtronic Inc) have been shown to be safe and clinically effective for treatment of small (<10 mm) unruptured aneurysms. However, the economic impact of these different techniques has not been established. OBJECTIVE To analyze the cost-effectiveness between stent-assisted coiling and flow diversion using PED, including procedural costs, long-term outcomes, and aneurysm recurrence. METHODS A decision-analytical study was performed with Markov modeling methods to simulate patients undergoing SAC or PED for treatment for unruptured aneurysms of sizes 5 and 7 mm. Input probabilities were derived from prior literature, and 1-way, 2-way, and probabilistic sensitivity analyses (PSA) were performed. RESULTS In base case calculation and PSA, PED was the dominant strategy for both the size groups, with and without consideration of indirect costs. One-way sensitivity analyses show that the conclusion remained robust when varying the retreatment rate of SAC from 0% to 50%, and only changes when the retreatment rate of PED > 49%. PED remained the more cost-effective strategy when the morbidity and mortality of PED increased by <55% and when those of SAC decreased by <37%. SAC only became cost-effective when the total cost of PED is >$73000 more expensive than the total cost of SAC. CONCLUSION With increasing use of PED for treatment of small unruptured anterior circulation aneurysms, our study indicates that PED is cost-effective relative to stent coiling irrespective of aneurysm size. This is due to lower aneurysm recurrence rate, as well as better health outcomes.