Kallmes, David F

Background Collateral blood flow markers have been associated with outcomes after thrombectomy in patients presenting with acute ischemic stroke due to large vessel occlusion (AIS-LVO). Hypoperfusion intensity ratio (HIR), a metric reflecting tissue level collaterals, is one such marker with the potential to delineate patients who do and do not do well after thrombectomy. We determined if HIR correlated with successful reperfusion after thrombectomy. Methods Using Nested Knowledge, we screened literature for studies comparing patients with favorable versus unfavorable HIR, distinguished by a cutoff of 0.4, who underwent thrombectomy triage. The primary outcome was reperfusion success, as measured by thrombolysis in cerebral infarction ≥2b and secondary outcomes included rate of symptomatic intracranial hemorrhage, mortality at 90 days, and modified Rankin scale scores 0–2 at 90 days. A random effects model was used to compute pooled prevalence rates and their corresponding 95% confidence intervals (CI). Results Three studies with 973 patients, 496 with favorable HIR, and 477 with unfavorable HIR were included in this meta-analysis. The odds of reperfusion success were not significantly different between patients who had favorable versus unfavorable HIR (OR 0.96, 95% CI: 0.31–3.04) across two of the studies. Analysis of the remaining outcome variables was precluded by significant heterogeneity in data element reporting. Conclusions This meta-analysis was considerably limited by heterogeneity. Future meta-analyses on this topic, and other topics in the field of neurointervention would benefit from improved harmonization of study design and data element reporting.

Background Flow diverter treatment may inevitably require jailing of the branch vessels. While the patency of covered branch arteries and associated safety risks have been a topic of substantial interest, the question of whether the characteristics of branch vessels affect flow diversion's efficacy remains unanswered. In this study, we aimed to assess the impact of branch arteries on the efficacy of endoluminal flow diverters, specifically focusing on posterior communicating artery (Pcomm) aneurysms. Methods Following PRISMA guidelines, we systematically searched the MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane databases with predefined keywords. Studies providing data for flow diversion outcomes in Pcomm aneurysms were included. Outcomes of interest included complete and adequate aneurysm obliteration, ischemic and hemorrhagic complications, and Pcomm occlusion in the follow-up period. A random or fixed effects model was used to calculate the odds ratios (ORs) and pooled event rates with their corresponding confidence intervals (CI). Results The overall complete and adequate aneurysm occlusion rates were 72.25% (95% CI: 64.46–78.88%) and 88.37% (95% CI: 84.33–92.6), respectively. Fetal-type Pcomm aneurysms had significantly lower complete aneurysm occlusion rates than the nonfetal-type Pcomm aneurysms (OR: 0.12, 95% CI: 0.05–0.29). Overall ischemic and hemorrhagic complication rates were 2.62% (95% CI = 0.71–5.32) and 0.71% (95% CI: 0–2.24), respectively. There were no significant associations between Pcomm morphology and complications (OR: 3.61, 95% CI = 0.42–31.06 for ischemic complications and OR: 2.31, 95% CI = 0.36–14.6 for hemorrhage). Overall Pcomm occlusion rate was 32.04% (95% CI = 19.96–47.13), and the Pcomm patency was significantly lower in nonfetal-type Pcomm aneurysms (OR: 0.10, 95% CI = 0.02–0.44). Conclusion Our meta-analysis suggests that flow diversion is a safe treatment option for Pcomm aneurysms, regardless of fetal-type Pcomm morphology. However, on the other hand, our findings indicate that Pcomm anatomy or the presence of jailed large branches can affect the efficacy of flow diverter treatment.

Background Intra-procedural characterization of stroke thromboemboli might guide mechanical thrombectomy (MT) device choice to improve recanalization rates. Electrochemical impedance spectroscopy (EIS) has been used to characterize various biological tissues in real time but has not been used in thrombus. Objective To perform a feasibility study of EIS analysis of thrombi retrieved by MT to evaluate: (1) the ability of EIS and machine learning to predict red blood cell (RBC) percentage content of thrombi and (2) to classify the thrombi as “RBC-rich” or “RBC-poor” based on a range of cutoff values of RBC. Methods ClotbasePilot was a multicentric, international, prospective feasibility study. Retrieved thrombi underwent histological analysis to identify proportions of RBC and other components. EIS results were analyzed with machine learning. Linear regression was used to evaluate the correlation between the histology and EIS. Sensitivity and specificity of the model to classify the thrombus as RBC-rich or RBC-poor were also evaluated. Results Among 514 MT,179 thrombi were included for EIS and histological analysis. The mean composition in RBC of the thrombi was 36% ± 24. Good correlation between the impedance-based prediction and histology was achieved (slope of 0.9, R 2 = 0.53, Pearson coefficient = 0.72). Depending on the chosen cutoff, ranging from 20 to 60% of RBC, the calculated sensitivity for classification of thrombi ranged from 77 to 85% and the specificity from 72 to 88%. Conclusion Combination of EIS and machine learning can reliably predict the RBC composition of retrieved ex vivo AIS thrombi and then classify them into groups according to their RBC composition with good sensitivity and specificity.

Background Dual antiplatelet therapy (DAPT) is frequently used in treating cerebral aneurysms with flow diverters (FDs), whereas single antiplatelet therapy (SAPT) is used mostly with coated FDs and in ruptured aneurysms. We conducted a systematic review and meta-analysis to explore the safety profile of SAPT in FDs. Methods PubMed, Web of Science, OVID Embase, OVID Medline, and Scopus were searched to 1st November 2022. Outcomes of interest included ischemic and hemorrhagic complications, conversion to DAPTs, and in-stent stenosis rates under long-term SAPT. SAPT is divided into aspirin (ASA) vs. non-ASA group (ticagrelor or prasugrel). Subgroup analysis was performed for ruptured vs. non-ruptured aneurysms and coated vs. non-coated FDs. All data were analyzed using R software version 4.2.2. Results Twelve studies with 240 total patients (43 patients in the ASA group and 197 patients in the non-ASA group) were included in our meta-analysis. The pooled ischemic occlusion rate was 9.8% (95% CI = 4.87−18.95: p-value = 0.09) for SAPTs. The ASA group had significantly higher ischemic complication rates compared to the non-ASA group (20.8% vs. 6.3%, respectively, p-value = 0.02). The pooled hemorrhagic complication rate was 3.5% (95% CI = 1.38−8.81: p-value > 0.99). The hemorrhagic rates of ASA group were 9.3%% (95% CI = 3.54−22.30) over the non-ASA group 2.1% (95% CI = 0.58−7.54) ( p-value > 0.99). The overall in-stent stenosis rate was 2.3% (95% CI = 1.06−5.14: p-value > 0.99). The ischemic complication rates were comparable between coated vs non-coated FDs (10.7% vs. 5.5% p-value = 0.39). In stent stenosis rate were 1.9% (95% CI = 0.72−4.96) in coated FDs over 4.4% (95% CI = 1.11−16.11) ( p-value = 0.32). The ruptured and non-ruptured groups also showed comparable results in terms of ischemic (17.6% vs. 7.1% respectively, p-value = 0.24) and hemorrhagic complications (9.8% vs. 1.1%, respectively, p-value = 0.08). Conclusions Flow diverter treatment under ASA monotherapy resulted in relatively high ischemic complication rates. However, SAPT with prasugrel or ticagrelor monotherapy is promising for coated FDs and ruptured aneurysm treatments. Given the overall small sample size and also the likely presence of known and unknown biases regarding choice of antiplatelet therapy between groups, larger cohort studies are needed to evaluate SAPT treatment outcomes.

Aim: Stent-retriever (SR) thrombectomy has demonstrated superior outcomes in patients with acute ischemic stroke compared with medical management alone, but differences among SRs remain unexplored. We conducted a Systematic Review/Meta-Analysis to compare outcomes between three SRs: EmboTrap ® , Solitaire™, and Trevo ® . Methods: We conducted a PRISMA-compliant Systematic Review among English-language studies published after 2014 in PubMed/MEDLINE that reported SRs in ≥25 patients. Functional and safety outcomes included 90-day modified Rankin scale (mRS 0-2), mortality, symptomatic intracranial hemorrhage (sICH), and embolization to new territory (ENT). Recanalization outcomes included modified thrombolysis in cerebral infarction (mTICI) and first-pass recanalization (FPR). We used a random effects Meta-Analysis to compare outcomes; subgroup and outlier-influencer analysis were performed to explore heterogeneity. Results: Fifty-one articles comprising 9,804 patients were included. EmboTrap had statistically significantly higher rates of mRS 0-2 (57.4%) compared with Trevo (50.0%, p = 0.013) and Solitaire (45.3%, p < 0.001). Compared with Solitaire (20.4%), EmboTrap (11.2%, p < 0.001) and Trevo (14.5%, p = 0.018) had statistically significantly lower mortality. Compared with Solitaire (7.7%), EmboTrap (3.9%, p = 0.028) and Trevo (4.6%, p = 0.049) had statistically significantly lower rates of sICH. There were no significant differences in ENT rates across all three devices (6.0% for EmboTrap, 5.3% for Trevo, and 7.7% for Solitaire, p = 0.518). EmboTrap had numerically higher rates of recanalization; however, no statistically significant differences were found. Conclusion: The results of our Systematic Review/Meta-Analysis suggest that EmboTrap may be associated with significantly improved functional outcomes compared with Solitaire and Trevo. EmboTrap and Trevo may be associated with significantly lower rates of sICH and mortality compared with Solitaire. No significant differences in recanalization and ENT rates were found. These conclusions are tempered by limitations of the analysis including variations in thrombectomy techniques in the field, highlighting the need for multi-arm RCT studies comparing different SR devices to confirm our findings.

Background Funding may impact the quality and findings of systematic reviews (SRs). We aimed to compare the methodological quality of funded and non-funded SRs that investigated the outcomes in ischemic stroke patients undergoing mechanical thrombectomy. Methods We conducted a comprehensive search strategy in different databases, including Ovid Cochrane Central Register of Controlled Trials, Ovid Embase, Ovid Medline (including epub ahead of print, in-process & other non-indexed citations), PubMed, Scopus and Web of Science Core Collection to retrieve all relevant SRs. Random sequence generation matched each funded SR with a non-funded one. A Measurement Tool to Assess Systematic Reviews (AMSTAR)-2 tool was used to assess the bias and quality of the included SRs. We also used uni- and multivariate analysis to perform our analysis, and results were expressed in odds ratio (OR) and 95% confidence interval (CI). Results We retrieved 150 articles, which were randomized and matched into 100 SRs, including 50 funded and 50 non-funded studies. By multivariate analysis, we found that including randomized clinical trials (RCTs) (OR: 5.7; 95% CI: 1.8–17.8; p = 0.003) and reporting conflict of interests (OR: 5.2; 95 CI: 1.1–24; p = 0.036) were the only significant differences between funded and non-funded SRs. No significant differences were found regarding the overall confidence for low-quality (OR: 0.54; 95% CI: 0.09–3.2; p = 0.49) and moderate/high-quality SRs (OR: 0.17; 95% CI: 0.02–1.87; p = 0.14). Conclusion Funded studies tend to include RCTs more often and report conflict of interests with no significant impact on overall confidence.

Background Collateral status may facilitate clot removal and affect rates of successful reperfusion following endovascular therapy (EVT) for acute ischemic stroke (AIS). Methods Following the PRISMA guidelines, a systematic literature review of the English language literature was conducted using PubMed, Scopus, Web of Science, and Embase. Papers which focused on collateral status and patients treated with EVT for AIS were included in our analysis. Outcomes of interest included collateral score grading, rates of successful reperfusion defined as thrombolysis in cerebral infarction (TICI) score 2b-3 and onset to revascularization time. We calculated pooled odds ratio (OR) or mean difference (MD) and their corresponding 95% confidence intervals (CI) based on collateral status. Results 16 studies, with 6073 patients, were included in our analysis. Among the included studies, there were six different collateral grading scales, which were dichotomized into “good to moderate” and “poor” collaterals. Odds of successful reperfusion were significantly higher among patients with good to moderate collateral circulation compared to those with poor collaterals (OR = 1.61; 95% CI = 1.24 to 2.09; P -value < 0.001); however, there was heterogeneity among included studies (I2 = 5 4%; P -value = 0.008). Onset to revascularization time was comparable between patients with good to moderate collateral circulation compared to those with poor collaterals (MD = 3.91 min; 95% CI = −8.71 to 16.53; P -value = 0.544); however, there was heterogeneity among included studies (I2= 60%; P -value = 0.014). Conclusions The presence of good collaterals may increase the odds of achieving successful reperfusion following EVT for AIS. Improved collateral flow was associated with improved angiographic outcomes, although future work is needed to determine if a causal relationship exists.

Introduction Mechanical thrombectomy (MT) is the standard of care in eligible patients presenting with acute ischemic stroke (AIS). The question of whether intravenous thrombolysis (IVT) improves outcomes in conjunction with MT remains unanswered. We performed a systematic review and meta-analysis of published randomized controlled trials (RCT) to explore outcomes of MT with and without IVT. Methods Following the PRISMA guidelines, a systematic literature review of the English language literature was conducted using PubMed, Embase, Web of science, and Scopus. Outcomes of interest included 90-day modified Rankin Scale (mRS) 0–2, thrombolysis in cerebral infarction (TICI) score 2b-3, symptomatic intracranial hemorrhage (sICH), distal embolization, and mortality. We calculated pooled risk ratios (RRs) and their corresponding 95% confidence intervals (CI). Results Six RCTs with 2334 patients compared outcomes of patients treated with MT alone and MT with IVT. Both treatments resulted in comparable rates of mRS 0–2 (RR = 0.96, 95% CI = 0.88–1.04; p -value = 0.282), sICH (RR = 0.80, 95% CI = 0.55–1.17; p -value = 0.253), mortality at 90-days (RR = 1.06, 95% CI = 0.88–1.28; p -value = 0.529), and distal embolization (RR = 1.10, 95% CI = 0.79–1.52; p -value = 0.572). MT alone was associated with a lower rate of TICI 2b-3 compared to MT with IVT (RR = 0.96, 95% CI = 0.93–0.99; p -value = 0.006). Conclusions In this meta-analysis of six RCTs, MT alone was comparable to MT plus IVT for mRS 0–2, sICH, mortality, and distal embolization; however, MT alone resulted in lower rates of TICI 2b-3. Further trials are needed to determine which patient populations benefit from MT plus IVT and to increase the power of future meta-analyses.

Background There is limited evidence on the optimal endovascular strategy for treatment of distal medium-vessel occlusions (DMVO). The low-profile Tigertriever 13 stent-triever shows early promise as an adaptable device that can navigate the distal vasculature without increasing complication risk in DMVO. Methods Using Nested Knowledge, we screened literature for RCTs and cohort studies on the endovascular treatment of DMVO. The primary outcome was reperfusion success, as measured by thrombolysis in cerebral infarction (TICI) ≥ 2b and secondary outcomes included rate of symptomatic intracranial hemorrhage (sICH), mortality at 90 days, and modified Rankin scale (mRS) scores 0–2 at 90 days. A random-effects model was used to compute pooled prevalence rates and their corresponding 95% confidence intervals (CI). Results Eleven studies with 1402 patients, 167 patients treated by Tigertriever 13 and 1235 patients treated by other devices, were included in the meta-analysis. The rate of reperfusion success was similar in patients treated by Tigertriever 13 (83.2% [95% CI: 71.5–96.7%]) versus other devices (81.6% [95% CI: 75.3–88.4%], p > 0.05). The rate of sICH was also similar in patients treated by Tigertriever 13 (7.2% [95% CI: 4.1–12.5%]) versus other devices (6.9% [95% CI: 5.5–8.8%]). There was significant heterogeneity in the reporting of mortality and mRS. Conclusions Tigertriever 13 had similar rates of reperfusion success and sICH as other devices used for the treatment of DMVO. Heterogeneity in data element reporting prevented further analyses. Further studies evaluating Tigertriever 13 and other potential devices in DMVO should attempt to harmonize data element reporting.