Kadirvel, Ram

Background Procedural success following mechanical thrombectomy for acute ischemic stroke is assessed using the thrombolysis in cerebral infarction scale. We conducted a systematic review and meta-analysis to determine whether outcomes differed between first pass thrombolysis in cerebral infarction 2b and multiple pass thrombolysis in cerebral infarction 2c-3. Methods We conducted a systematic review of the literature using PubMed, Embase, Scopus, and Web of Science. We included original studies in which outcomes were stratified based on first pass thrombolysis in cerebral infarction 2b and multiple pass thrombolysis in cerebral infarction 2c-3. The primary outcome of interest was the rate of modified Rankin Scale 0-2. Secondary outcomes of interest were rates of modified Rankin Scale 0-1, symptomatic intracranial hemorrhage, and mortality. We calculated odds ratios and corresponding 95% confidence intervals. Results Four studies with 1554 patients were included in the quantitative analysis. Rate of modified Rankin Scale 0–2 (odds ratio = 0.91, 95% confidence interval = 0.70–1.18; P -value = 0.49), modified Rankin Scale 0–1 (odds ratio = 1.21, 95% confidence interval = 0.86–1.71; P -value = 0.27), symptomatic intracranial hemorrhage (odds ratio = 1.36, 95% confidence interval = 0.47–3.98; P -value = 0.57), and mortality (odds ratio = 0.91, 95% confidence interval = 0.67–1.25; P -value = 0.56) did not differ between first pass thrombolysis in cerebral infarction 2b and multiple pass thrombolysis in cerebral infarction 2c-3. There was no heterogeneity among included studies for modified Rankin Scale 0–2, modified Rankin Scale 0–1, or mortality; however, there was moderate heterogeneity among studies for symptomatic intracranial hemorrhage ( I 2 = 53%, P -value = 0.12). Conclusions Clinical and safety outcomes did not differ between first pass thrombolysis in cerebral infarction 2b and multiple pass thrombolysis in cerebral infarction 2c-3. Future prospective studies and clinical trials should determine whether first pass thrombolysis in cerebral infarction 2b is a viable endpoint to thrombolysis in cerebral infarction 2c-3.

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 Risks and benefits of intravenous thrombolysis (IVT) in patients undergoing mechanical thrombectomy (MT) have been a topic of interest. However, IVT’s specific effects on stent retriever (SR) and aspiration thrombectomy (ASP) outcomes remain largely unexplored. In this meta-analysis, we aimed to investigate the effects of IVT on SR and ASP thrombectomy outcomes. Methods In accordance with PRISMA guidelines, a systematic literature review was conducted using Medline, Embase, Scopus, Web of Science, and Cochrane Center of Clinical Trials databases. Outcomes of interest included successful recanalization (modified Thrombolysis In Cerebral Infarction (mTICI) ≥2b), modified first pass efficacy (mFPE), functional independence (modified Rankin Scale (mRS) ≤2), symptomatic intracranial hemorrhage (sICH), and embolization to new territories (ENT). Results Four randomized controlled trials with 1176 patients were included. SR and ASP resulted in similar mTICI ≥2b, mFPE, and mRS 0–2 rates in patients with and without IVT administration. SR without IVT was associated with a significantly lower rate of mFPE compared with the SR+IVT (RR 0.85, 95% CI 0.74 to 0.97). Furthermore, ASP without IVT resulted in a lower rate of mRS 0–2 than the ASP+IVT with a strong trend towards significance (RR 0.78, 95% CI 0.60 to 1.01). Finally, bridging therapy did not increase sICH and ENT rates after ASP or SR thrombectomy. Conclusions Our findings suggest that SR and ASP thrombectomy have comparable safety and efficacy profiles, regardless of prior IVT administration. Additionally, our results indicate that the addition of IVT may improve certain efficacy outcomes based on the employed first-line MT technique.

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.

Background Federal research funding is highly sought after but may be challenging to attain. A clear understanding of funding for specific diseases, such as cerebrovascular disorders, might help researchers regarding which National Institutes of Health (NIH) institutes fund research into specific disorders and grant types. Objective To examine the current scope of NIH grant funding for cerebrovascular conditions. Methods The NIH-developed RePORTER was used to extract active NIH-funded studies related to cerebrovascular diseases through January 2023. Duplicate studies were removed, and projects were manually screened and labeled in subcategories as clinical and basic science and as research subcategories. Extracted data included total funding, grant types, institutions that received funding, and diseases studied. Python (version 3.9) and SciPy library were used for statistical analyses. Results We identified 1232 cerebrovascular projects across seven diseases with US$699 952 926 in total funding. The cerebrovascular diseases with the greatest number of grants were ischemic stroke (705, or 57.2% of all funded projects), carotid disease (193, or 15.7%), and hemorrhagic stroke (163, or 13.2%). R01 grants were the most common mechanism of funding (632 grants, or 51.3%). The National Institute of Neurological Disorders and Stroke (NINDS) funded the most projects (504 projects; US$325 536 405), followed by the National Heart, Lung, and Blood Institute (NHLBI) (376 projects; US$216 784 546). Conclusion Cerebrovascular disease receives roughly US$700 million in NIH funding. Ischemic stroke accounts for the majority of NIH-funded cerebrovascular projects, and R01 grants are the most common funding mechanism. Notably, NHLBI provides a large proportion of funding, in addition to NINDS.

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.

Background The Contour is a new generation intrasaccular flow disruption tool that aims to cover the aneurysm neck and is sized according to the neck diameter. While several case series have been published, no literature review has been performed on this promising device. Objective To assess the safety and effectiveness profile of the Contour Neurovascular System for wide-necked aneurysms. Methods We followed the recommendations of the PRISMA checklist Four databases were searched with a supplemental manual search. All data were analyzed using R software version 4.2.1. Results We finally included six studies with 131 treated aneurysms. The overall procedural time was 97.27 (95% CI = 70.07–124.47) minutes, ranging from 78.9 to 136.0 min. The pooled adequate occlusion rate was 84.21% (95% CI = 75.45–90.25), and the overall functional independence rate was 94.74% (87.97–97.79). The overall adverse event rate was 4.70 (95% CI = 3.24–6.76), varying among different events from 0.78 to 8.53%. Thromboembolic events were the most commonly encountered in 8.53% of the patients (95% CI = 4.78–14.74), followed by headache and minor stroke with incidence rates of 5.88 (95% CI = 2.83–11.83) and 4.35 (95% CI = 1.41–12.63), respectively. The overall procedural time in studies using the Contour system only was 86.17 (95% CI = 68.70–10.64) minutes, while it was 136 (95% CI = 90.96–181.04) in the Contour-assisted coiling procedures. However, both techniques were comparable regarding adequate occlusion rates and functional independence. Conclusion With the anticipation of future studies, the Contour Neurovascular System is a safe and effective treatment option for wide-necked intracranial aneurysms.

Background Previous studies comparing a direct aspiration first pass technique (ADAPT) and stent retrievers have inconsistent methodologies and data reporting, limiting the ability to accurately assimilate data from different studies that would inform treatment of acute ischemic stroke (AIS) treatment. Objective To conduct a systematic review to discuss and compare the findings of all relevant meta-analysis studies comparing the efficacy of the ADAPT and stent retriever techniques. Methods The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), where meta-analyses comparing the efficacy of the ADAPT technique and stent retrievers in the treatment of AIS were included. We extracted all relevant data from the included studies and assessed the quality of the included meta-analyses using the Assessment of Multiple Systematic Review (AMSTAR-2). Results Seven relevant studies met our inclusion criteria and were suitable for the qualitative synthesis. All included studies obtained data from randomized controlled trials (RCTs) and observational investigations (including levels II, III, and IV). At the same time, none of them used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) for quality assessment. In accordance with AMSTAR-2, two studies were rated ‘high’, while the other five were rated ‘moderate’. Conclusions Present evidence is insufficient to clarify the superiority of one modality over the other. Further RCTs on this comparison must be conducted prior to designing further meta-analyses or making conclusive interpretations. Procedure duration and cost should be taken into consideration for any future studies.