Kallmes, David F.

Background: There is an unmet need to better understand the likelihood of a good functional outcome in older and frailer populations undergoing endovascular therapy (EVT) following large-vessel occlusion (LVO) ischemic stroke. One approach is to improve the understanding of pre-morbid brain health (“brain frailty”) as a predictor of functional outcome. This study explored the relationship between the spatial pattern of brain atrophy and functional outcome to determine whether this is a predictor of outcomes following EVT. Methods: Patients with LVO from four hospitals in Europe and the USA were included. Three cohorts were used as a derivation cohort, and the fourth served for validation. Presenting CT imaging was processed using Brainomix in-house software to automatically localize and quantify atrophy (frailty-index). Masks from the derivation cohort were used to localize regions of atrophy significantly associated with poorer functional outcome (modified Ranking Scale 3-6) using a voxel-based, multivariate method (Sparse Canonical-Correlation-Analysis) (see Figure 1). For both derivation and validation cohorts, the degrees of overlap between each patient’s atrophy mask and the regions associated at a group level with poor outcome were calculated. This was used as an independent predictor of functional outcome in multivariate analysis adjusting for overall brain frailty-index, recanalization status, and ASPECT score Results: The derivation cohort consisted of 658 patients (mean age 69.6±15.0, median ASPECTS 9 [7-10]), while the validation cohort consisted of 447 patients (mean age 64.7 ±15.5, median ASPECTS 8 [5-10] ). Atrophy localized to the lateral ventricles and sylvian fissure was significantly associated with poorer outcomes (Figure 1). In both derivation and validation cohort, the presence of this spatial pattern of brain frailty (quantified using the degree of overlap) was an independent predictor of poor functional outcome (Table 1). Conclusion: A better understanding of pre-stroke brain health, such as the distribution of atrophy, may provide additional information to inform the prediction of outcome following LVO. This could improve patient selection for treatment following ischemic stroke through better prognostication and a more personalized approach to decision making.

Background: Symptomatic intracranial hemorrhage (sICH) is the most dreaded complication after reperfusion therapy for acute ischemic stroke. We performed a meta-analysis of randomized controlled trials to estimate and compare risks of sICH after mechanical thrombectomy (MT) depending on the location of the large vessel occlusion, concomitant use of intravenous thrombolysis, timing of treatment, and core size. Methods: Randomized controlled trials were included following a comprehensive search strategy on different databases from inception to March 1, 2024. Random-effect models in a meta-analysis were employed to get the pooled risk ratios (RRs) and their corresponding 95% confidence intervals (95% CI) for sICH with MT, compared to other reperfusion treatment regimens, including best medical treatment and intravenous thrombolysis (IVT). Results: MT in the anterior circulation was associated with a significantly higher risk of sICH as compared with no-MT (RR: 1.46; 95%CI: 1.03-2.07; P = 0.037). Risk of sICH was comparable between the MT and MT+IVT groups (RR: 0.77; 95%CI: 0.57-1.03; P = 0.079). There was no difference in sICH risk with MT as compared with no-MT within 6 hours of last known well (RR: 1.14; 95%CI: 0.78-1.66; P = 0.485) and beyond that time (RR: 1.29; 95%CI: 0.80-2.08; P = 0.252); the risk of sICH was also comparable between MT conducted within 6 hours of last known well and MT conducted beyond that time (P = 0.512). The sICH risk for MT in the posterior circulation (RR: 7.48; 95%CI: 2.27-24.61) was significantly higher than for MT in the anterior circulation (RR: 1.18; 95%CI: 0.90-1.56) (P = 0.003). MT was also associated with a significantly higher sICH risk than no-MT among patients with large-core strokes (RR: 1.71; 95%CI: 1.09-2.66, P = 0.018). Conclusion: When evaluating cumulative evidence from randomized controlled trials, the risk of sICH is increased after MT compared with patients not treated with MT. Yet, the difference is largely driven by the greater risk of sICH in patients treated with MT for posterior circulation occlusions and, to a lesser degree, large core strokes. Concomitant use of intravenous thrombolysis and the use of MT in the extended therapeutic window do not raise the risk of sICH.

Background: Angiographic shape of occlusion, like the clot meniscus sign and the claw-sign, have been reported to potentially impact recanalization rate and clinical outcome in patient undergoing mechanical thrombectomy for acute ischemic strokes. Method: Following PRISMA guidelines, a systematic literature search was conducted across PubMed, Scopus, and Web of Science databases. Patients were grouped into clot meniscus/claw sign positive and negative groups based on the definitions obtained from each study. Primary outcomes included technical success, with a meta-analysis performed using a random-effects model to calculate proportions and odds ratios (OR) with 95% confidence intervals (Cl). Results: We included seven studies recruiting 1572 patients. The results indicated that the positive and negative groups had comparable first-pass effect (OR: 1.95; 95%CI: 0.76 – 5.01; P = 0.167) and final recanalization (OR: 1.36; 95%CI: 0.81 – 2.27; P = 0.248) rates. However, the rate of having a favorable functional outcome was significantly higher in the positive than negative sign groups (OR: 1.91; 95%CI: 1.25 – 2.92; P < 0.003). Within the sign-positive population, the use of contact aspiration was associated with a significantly higher rate of recanalization compared to using a stent retriever (OR: 0.18; 95%CI: 0.07 – 0.49; P < 0.001). This result did not translate into a clinical impact, as both stent retriever and contact aspiration showed comparable rates of functional independence at three months (OR: 0.22; 95%CI: 0.02 – 2.33; P = 0.210). Conclusion: The presence of the clot meniscus/claw sign is not associated with recanalization outcomes after thrombectomy. However, it might be a good sign to predict which thrombectomy technique might be associated with better recanalization, although current evidence might need further confirmation.

Background Left ventricular assist devices (LVADs) are used as definitive therapy or as a bridge to heart transplant in patients with advanced heart failure. Thromboembolic complications such as acute ischemic stroke (AIS) are common among patients with LVAD support. This study aims to evaluate the current evidence on the efficacy and safety of mechanical thrombectomy (MT) in patients with AIS due to large vessel occlusions (LVO) and LVAD-support. Methods A comprehensive systematic review was conducted in PubMed, Embase, and Scopus to find observational studies with reports of ≥5 MTs in adult patients with LVAD support (PROSPERO registration code CRD42024597541). Rates of successful and complete reperfusion, favorable functional outcomes at 90 days (modified Rankin Scale (mRS) 0–2 or equal to pre-stroke mRS), mortality at 90 days, any intracerebral hemorrhage (ICH) and symptomatic ICH (sICH) were pooled using generalized linear mixed models. Results Eight studies were included with data from 51 patients and 62 MTs. The rate of successful reperfusion was 87.4% (95% CI 62.5% to 96.6%) and complete reperfusion rate was 57.3% (95% CI 35.1% to 76.9%). Rate of favorable functional recovery was 62.5% (95% CI 42.2% to 79.2%). Rate of sICH was 6.4% (95% CI 0.9% to 34.0%). Mortality rate was 16.7% (95% CI 7.1% to 34.7%). Between 25–40% of patients who were waiting for a heart transplant before their stroke received a heart transplant after MT. Conclusions MT for the emergent treatment of AIS in the setting of LVAD is relatively safe and efficacious for achieving successful reperfusion and good functional recovery.

Background The impact of certain comorbidities on mechanical thrombectomy (MT) outcomes remains largely unexplored. Diabetes mellitus (DM) and admission hyperglycemia have been associated with poor clinical outcomes for patients treated with MT. In this study, we sought to investigate the effects of DM and admission hyperglycemia on MT outcomes. Methods Following PRISMA guidelines, a systematic literature search was conducted in Medline, Embase, Scopus, and Web of Science databases. Data regarding successful recanalization (modified Thrombolysis in Cerebral Infarction [mTICI] ≥2b), functional independence (modified Rankin Scale [mRS] 0–2), excellent outcomes (mRS 0–1), symptomatic intracranial hemorrhage (sICH), and mortality were extracted from the included studies. The pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated using random effects model. Results Twenty-one studies comprising 9708 patients were included. A total of 2311 patients (24%) had a history of DM, and 2026 patients (21%) had admission hyperglycemia. Admission hyperglycemia was associated with significantly lower odds of mTICI ≥2b (OR = 0.7, 95% CI = 0.55–0.89), mRS 0–2 (OR = 0.47, 95% CI = 0.41–0.53), and mRS 0–1 (OR = 0.43, 95% CI = 0.34–0.55) as compared to normoglycemic state. Patients with hyperglycemia had significantly higher rates of sICH (OR = 2.05, 95% CI = 1.66–2.54) and mortality (OR = 1.99, 95% CI = 1.58–2.52) than normoglycemic patients. Diabetes mellitus was associated with significantly high rates of mortality (OR = 1.74, 95% CI = 1.31–2.3) and lower rates of mRS 0–2 (OR = 0.60, 95% CI = 0.48–0.76) in sensitivity analyses. Conclusion Our results indicate that admission blood glucose levels and DM can negatively affect MT outcomes. Further research should focus on optimizing MT outcomes for these patients.

Introduction Mechanical thrombectomy for ischemic stroke has traditionally been performed via transfemoral access (TFA). However, newer literature on the subject suggests that trans‐radial access (TRA) may be equally efficacious. Materials and Methods Using relevant keywords, online databases (including Pubmed, Google Scholar, Embase, and Cochrane) were queried from inception until May 2024. Abstracts and full texts were screened according to Preferred Reporting Items for Systematic Reviews and Meta‐analysis (PRISMA) guidelines to shortlist studies that met the inclusion criteria. Risk of bias assessment was performed according to the New Castle Ottawa Scale and Cochrane risk of bias tool 2.0. All dichotomous outcomes were reported as odds ratio (OR) with 95% confidence interval (CI). RevMan software was used to perform the statistical analysis. Results Thirteen observational studies and one randomized clinical trial were included in this meta‐analysis. The total sample size was 4973, of which 4074 patients (81.2%) were included in the TFA group and 899 (18.8%) were included in the TRA group. No significant differences were observed between the two groups in terms of successful recanalization (OR=0.92; 95% CI 0.66‐1.27; p =0.60), first‐pass recanalization (OR=0.84; 95% CI 0.69‐1.01, p =0.06), access to reperfusion time (mean difference ‐2.99 minutes; 95% CI ‐8.33 to 2.44, p =0.27) and favorable functional outcome. Mortality and rates of intracranial hemorrhage were comparable between the two groups as well, but access site complications were significantly lower in the TRA group (OR=0.57; 95% CI 0.37‐0.88; p =0.01). Conclusion Trans‐radial access for thrombectomy in large vessel acute ischemic strokes is comparable to trans‐femoral access in terms of efficacy and has a lower incidence of access site complications. Randomized clinical trial data on head‐to‐head comparison of two techniques is limited, underscoring the importance of conducting pragmatic clinical trials.

Background: Symptomatic intracranial hemorrhage (sICH) is the most dreaded complication after reperfusion therapy for acute ischemic stroke. We performed a meta-analysis of randomized controlled trials to estimate and compare risks of sICH after mechanical thrombectomy (MT) depending on the location of the large vessel occlusion, concomitant use of intravenous thrombolysis, timing of treatment, and core size. Methods: Randomized controlled trials were included, following a comprehensive search of different databases from inception to 1 March 2024. Random-effect models in a meta-analysis were employed to obtain the pooled risk ratios (RRs) and their corresponding 95% confidence intervals (95% CI) for sICH with MT, and were then compared to other reperfusion treatment regimens, including best medical treatment and intravenous thrombolysis (IVT). Results: MT in the anterior circulation was associated with a significantly higher risk of sICH as compared with no-MT (RR: 1.46; 95%CI: 1.03–2.07; p = 0.037). The risk of sICH was comparable between the MT and MT+IVT groups (RR: 0.77; 95%CI: 0.57–1.03; p = 0.079). There was no difference in sICH risk with MT as compared with no-MT within 6 h of last known well (RR: 1.14; 95%CI: 0.78–1.66; p = 0.485) and beyond that time (RR: 1.29; 95%CI: 0.80–2.08; p = 0.252); the risk of sICH was also comparable between MT conducted within 6 h of last known well and MT conducted beyond that time (p = 0.512). The sICH risk for MT in the posterior circulation (RR: 7.48; 95%CI: 2.27–24.61) was significantly higher than for MT in the anterior circulation (RR: 1.18; 95%CI: 0.90–1.56) (p = 0.003). MT was also associated with a significantly higher sICH risk than no-MT among patients with large core strokes (RR: 1.71; 95%CI: 1.09–2.66, p = 0.018). Conclusions: When evaluating cumulative evidence from randomized controlled trials, the risk of sICH is increased after MT compared with patients not treated with MT. Yet, the difference is largely driven by the greater risk of sICH in patients treated with MT for posterior circulation occlusions and, to a lesser degree, large core strokes. Concomitant use of intravenous thrombolysis and the use of MT in the extended therapeutic window do not raise the risk of sICH.

ABSTRACT As the number of cerebral aneurysms treated with flow diverters continues to increase, it is important to understand what factors influence not only thrombus formation within the aneurysm cavity but also fibrin accumulation across the device and its associated disruption and blockage of the inflow stream. Both processes contribute to the eventual occlusion of the aneurysm or its continued patency and incomplete occlusion which may require future re‐treatment. To investigate fibrin accumulation on flow diverters placed across the neck of cerebral aneurysms, a previously developed computational model that couples flow and fibrin dynamics is used in combination with experimental in vitro models of cerebral aneurysms treated with flow diverters. Fibrin accumulation was previously investigated in four glass models of cerebral aneurysms with varying parent artery geometries placed in a flow loop at different flow rates. Corresponding computational models were constructed and compared with the experimental findings. The computational model based on fibrin production stimulated from flow shear stress and subsequent adhesion to device wires was able to reproduce and explain the fibrin accumulation patterns observed in the experimental aneurysms treated with flow diverters. Specifically, these models indicated that increasing vessel curvature, flow rate, and thrombin concentration induced faster fibrin accumulation and associated aneurysm inflow disruption and blockage. The models described and tested in this paper are valuable to understand the detailed mechanisms leading to aneurysm occlusion and healing or incomplete occlusions after treatment with flow diverting devices.

Background Identifying eloquent regions associated with poor outcomes based on CT perfusion (CTP) may help inform personalized decisions on selection for endovascular therapy (EVT) in patients with large vessel occlusion (LVO) ischemic stroke. This study aimed to characterize the relationship between CTP-defined hypoperfusion and National Institutes of Health Stroke Scale (NIHSS) subitem deficits. Methods Patients with anterior circulation LVO, baseline CTP, itemized NIHSS at presentation and 24 hours were included. CTP was analyzed using e-CTP (Brainomix, UK). Time to maximal contrast (Tmax) prolongation was defined as >6 s, and penumbra as the difference between Tmax and ischemic core (relative cerebral blood flow<30%). Voxel-lesion-symptom mapping was performed using sparse canonical correlation analysis. For each NIHSS subitem, and total NIHSS, the associations were plotted between Tmax voxels with baseline NIHSS, and penumbra voxels with delta NIHSS (24 hours minus baseline). Results This study included 171 patients. Total NIHSS was predicted by hypoperfusion in left frontal cortex and subcortical white matter tracts. Voxels associated with neurological recovery were symmetrical and subcortical. Limb deficits were associated with respective motor cortex regions and descending motor tracts, with negative correlation within the contralateral hemispheres. A similar but smaller cluster of voxels within the penumbra was associated with NIHSS improvement. Language impairment correlated with left frontal cortex and superior temporal gyrus voxels. With the exception of dysarthria, significant associations were observed and more diffusely distributed in all other NIHSS subitems. Conclusions These results demonstrate the feasibility of hypoperfusion-to-symptom mapping in LVO. Symptom-based mapping from presenting imaging could refine treatment decisions targeting specific neurological deficits.