Kadirvel, Ramanathan

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 In 2015, mechanical thrombectomy (MT) was deemed the standard of care for acute ischemic stroke (AIS) in the anterior circulation due to large vessel occlusion (LVO). To determine if outcomes in patients treated with MT have changed, we conducted a systematic review and meta-analysis of published randomized controlled trials (RCTs). Methods A systematic literature review of the English language literature was conducted using PubMed. We included RCTs that focused on patients with AIS treated with MT. The primary outcome of interest was good functional outcome defined as modified Rankin Scale (mRS) 0–2 at 90 days. Safety outcomes included rates of symptomatic intracranial hemorrhage (sICH) and mortality at 90 days. Using Joinpoint Regression Analysis Program, we calculated the average annual percent change (AAPC) for the outcomes of interest. Results We included 23 RCTs with 5784 patients. The years of mid-enrollment among the included RCTs ranged from 2012–2020. There was an AAPC of +3.82% between 2012 and 2020 (95% CI 0.4 to 7.3; P -value = 0.033) in rates of good functional outcome. There was an AAPC of +6.98% between 2012 and 2020 (95% CI 0.5 to 13.9; P -value = 0.039) in rates of sICH. There was an AAPC of −0.49% between 2012 and 2020 (95% CI −4.4 to 3.5; P -value = 0.77) in rates of mortality. Conclusion Between 2012 and 2020, rates of good functional outcome and sICH increased, while rates of mortality remained consistent in RCTs investigating MT for AIS. Multiple factors likely influenced our results, including increased use of MT and utilization of adjunctive therapies alongside MT.

Background Endovascular coil embolization (ECE) for intracranial aneurysms has been proven as an effective minimally invasive treatment. However, the aneurysm recanalization after coiling is a serious complication of this technique. Among all the proposed factors associated with recanalization, the impact of packing density (PD) is still controversial. Objective To clarify the role of PD in the aneurysm recanalization following ECE, via conducting a systematic review and meta-analysis. Methods A systematic literature search was conducted using PubMed, Scopus, Embase, and Web of Science databases, until November 28, 2022, by adhering to the Preferred Reporting Items for Systematic Review and Meta-Analyses statement guidelines. Considering the eligibility criteria, all the studies reporting the outcomes of interest were included. Data elements of interest were extracted and analyzed using R software version 4.2.1. Results The pooled analysis of the 17 eligible papers revealed a 29% higher PD of the nonrecanalized aneurysms (ROM = 1.29, 95% confidence interval [CI] = 1.18–1.40, p < 0.001), even after removing outlier studies to reduce heterogeneity. However, the pooled estimates from multivariable regression models within nine included studies showed no significant effect of PD on recanalization odds when incorporated into a multivariable model with other predictors (odds ratio [OR] = 0.93, 95% CI = 0.84–1.02, p = 0.126), even after removing outlier studies. Conclusion The current literature does not support PD as a significant predictor of aneurysm treatment outcomes, especially with adjusting for other variables. This finding necessitates further prospective multicenter studies with a larger sample size to overcome the current methodological shortcomings.

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.

Importance Patients with atrial fibrillation (AF) treated with mechanical thrombectomy (MT) for acute ischemic stroke (AIS) have been reported to experience worse outcomes compared with patients without AF. Objective To assess differences between patients with AF and their counterparts without AF treated with MT for AIS, focusing on safety outcomes, clinical outcomes, and baseline characteristics in both groups. Data Sources A systematic literature review of the English language literature from inception to July 14, 2022, was conducted using Web of Science, Embase, Scopus, and PubMed databases. Study Selection Studies that focused on patients with and without AF treated with MT for AIS were included. Multiple reviewers screened studies to identify studies included in analysis. Data Extraction and Synthesis Data were extracted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline to ensure accuracy. Data were pooled using a random-effects model. Main Outcomes and Measures The primary outcome of interest was rate of modified Rankin Scale (mRS) scores of 0 to 2 at 90 days. Secondary outcomes of interest included rates of successful reperfusion, defined as thrombolysis in cerebral infarction (TICI) scores of 2b to 3, 90-day mortality, symptomatic intracranial hemorrhage (SICH), and baseline patient characteristics. Results Of 1696 initially retrieved studies, 10 studies were included, with 6543 patients. Patients with AF were a mean of 10.17 (95% CI, 8.11-12.23) years older ( P &amp;lt; .001) and had higher rates of hypertension (OR, 1.89 [95% CI, 1.57-2.27]; P &amp;lt; .001) and diabetes (OR, 1.16 [95% CI, 1.02-1.31]; P = .02). Overall, there were comparable rates of mRS scores of 0 to 2 between patients with AF and patients without AF (odds ratio [OR], 0.72 [95% CI, 0.47-1.10]; P = .13), with significant heterogeneity among the included studies. After sensitivity analysis, the rate of mRS scores of 0 to 2 was significantly lower among patients with AF (OR, 0.65 [95% CI, 0.52-0.81]; P &amp;lt; .001). Successful reperfusion rates were similar between the groups (OR, 1.11 [95% CI, 0.78-1.58]; P = .57). The rate of SICH was similar between groups (OR, 1.05 [95% CI, 0.84-1.31]; P = .68). Mortality was significantly higher in the AF group (OR, 1.47 [95% CI, 1.12-1.92]; P = .005). Conclusions and Relevance In this systematic review and meta-analysis, patients with AF experienced worse 90-day outcomes, even in the setting of similar rates of successful reperfusion. This was likely associated with greater age and greater rates of comorbidities among patients with AF.

Background Delayed neurological improvement (DNI) is a phenomenon that involves patient improvement in the absence of early neurological change following treatment for acute ischemic stroke. The patient characteristics associated with this condition are largely unexplored. Methods Following the PRISMA guidelines, a systematic review of the English language literature was conducted using PubMed, Embase, Web of science, and Scopus. We calculated pooled odds ratios (ORs), mean differences (MDs), and their corresponding 95% confidence intervals (CIs) to test the association between patient characteristics and achievement of DNI. Results Seven studies, with 3266 patients, were included in our analysis. All studies reported a different definition of DNI, with five studies focusing on rates of good functional outcome at 90 days post-treatment in the absence of early neurological improvement. Use of intravenous thrombolytics was associated with increased rates of DNI (OR 1.96, 95% CI 1.28 to 3.00; p = 0.002). Atrial fibrillation was associated with decreased rates of DNI (OR 0.69, 95% CI 0.57 to 0.82; p < 0.001), as was hypertension (OR 0.66, 95% CI 0.53 to 0.83, p < 0.001), and diabetes mellitus (OR 0.71, 95% CI 0.56 to 0.90; p = 0.005). On average, patients who achieved DNI were 6.30 years younger than their non-DNI counterparts ( MD −6.30, 95% CI −9.19 to −3.41; p < 0.001). There were modest associations between male sex and DNI (OR 1.36, 95% CI 1.01 to 1.74, p = 0.042), and smoking and DNI (OR 1.28, 95% CI 1.03 to 1.59, p = 0.027). Conclusions DNI is a phenomenon that is not presently well understood. Lack of uniformity among definitions of DNI hinders efforts to explore DNI and the factors associated with its occurrence. Future studies should work to establish a consensus definition of DNI to determine its causes and significance more accurately.

OBJECTIVE Bioresorbable flow diverters (BRFDs) could significantly improve the performance of next-generation flow diverter technology. In the current work, magnesium and iron alloy BRFDs were prototyped and compared in terms of porosity/pore density, radial strength, flow diversion functionality, and resorption kinetics to offer insights into selecting the best available bioresorbable metal candidate for the BRFD application. METHODS BRFDs were constructed with braided wires made from alloys of magnesium (MgBRFD) or iron (FeBRFD). Pore density and crush resistance force were measured using established methods. BRFDs were deployed in silicone aneurysm models attached to flow loops to investigate flow diversion functionality and resorption kinetics in a simulated physiological environment. RESULTS The FeBRFD exhibited higher pore density (9.9 vs 4.3 pores/mm2) and crush resistance force (0.69 ± 0.05 vs 0.53 ± 0.05 N/cm, p = 0.0765, n = 3 per group) than the MgBRFD, although both crush resistances were within the range previously reported for FDA-approved flow diverters. The FeBRFD demonstrated greater flow diversion functionality than the MgBRFD, with significantly higher values of established flow diversion metrics (mean transit time 159.6 ± 11.9 vs 110.9 ± 1.6, p = 0.015; inverse washout slope 192.5 ± 9.0 vs 116.5 ± 1.5, p = 0.001; n = 3 per group; both metrics expressed as a percentage of the control condition). Last, the FeBRFD was able to maintain its braided structure for > 12 weeks, whereas the MgBRFD was almost completely resorbed after 5 weeks. CONCLUSIONS The results of this study demonstrated the ability to manufacture BRFDs with magnesium and iron alloys. The data suggest that the iron alloy is the superior material candidate for the BRFD application due to its higher mechanical strength and lower resorption rate relative to the magnesium alloy.

Background: New trials are planned regularly to provide the highest quality of evidence and invade new occlusion territories, which requires a pre-defined reporting strategy with consistent, common data elements for more straightforward collective evidence synthesis. We sought to review all active endovascular thrombectomy trials to investigate their patient selection criteria, intervention description, and reported outcomes. Methods: A literature search was systematically conducted on clinicaltrials.gov for active trials and all intervention, inclusion criteria, and outcomes reported were extracted. A qualitative synthesis of the frequency of study design types and data elements are graphically and narratively presented. Results: A total of 32 studies were tagged and included in the final qualitative analysis. The inclusion criteria were highly variable, including different cut-offs for the last well-known baseline National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, and modified Rankin scale (mRS). Half of the studies (16/32) mentioned “thrombectomy” without defining which technique or device was used, and the final thrombolysis in cerebral infarction scale was provided in 19 (59.4%) studies. Heterogeneity was also present among the studies reporting a first-pass effect, both in how studies defined the outcome and in used ranges for mRS. Mortality and intracerebral hemorrhage (ICH) were more homogenous in their presentation and follow-up. Conclusions: There is a great degree of heterogeneity in the active thrombectomy trials concerning inclusion criteria, interventions used, and how outcomes are being reported.

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 Early neurological deterioration (END) is a potential predictor for 90-day outcomes following mechanical thrombectomy for acute ischemic stroke (AIS). We performed a systematic review and meta-analysis to better understand whether END can be used as a surrogate for long-term outcomes. Methods Following the PRISMA guidelines, a systematic literature review of the English language literature was conducted using PubMed, MEDLINE, and Embase. END definition was cataloged for each included study. Outcomes of interest included 90-day modified Rankin Scale (mRS) 0–2, symptomatic intracranial hemorrhage (sICH), mortality, and thrombolysis in cerebral infarction (TICI) 2b-3. We calculated pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CI) for all definitions of END. Results We included seven studies with 2992 patients in our analysis. There was a significant, inverse association with END and mRS 0–2 rates (OR = 0.15; 95% CI = 0.08–0.29; P-value< 0.001). Moreover, END was a significant predictor of increased odds for reported sICH rates (OR = 16.37; 95% CI = 7.66–34.99; P-value< 0.001). Furthermore, there was a significant association between END and increase in mortality rates (OR = 6.79; 95% CI = 2.62–17.62; P-value< 0.001). There was no significant association between END and rates of TICI 2b-3 (OR = 0.53; 95% CI = 0.27–1.05; p = 0.069). Conclusions Broadly defined, END holds value as a potential predictor of rates of mRS 0–2 at 90 days and is associated with higher rates of mortality and sICH, but had no correlation with TICI 2b-3.