Kallmes, David F.

Background Sealing of the aneurysm neck with a Woven EndoBridge (WEB) device is recommended for disrupting the blood flow inside the aneurysm. This study investigates the relationship between WEB neck apposition and aneurysm occlusion rates. Methods Aneurysms treated with a WEB from March 2017 to May 2022 at a single center were included. WEB neck apposition (poor/good) and WEB protrusion (yes/no) were evaluated on post-detachment high resolution cone beam CT images. Angiographic occlusion was assessed with the Bicêtre Occlusion Scale score (BOSS). Univariate and multivariable analysis tested the association between neck apposition and occlusion rates. Results The study included 159 aneurysms in 141 patients (mean age 55.8±11.2 years; 64.2% women). Good neck apposition and protrusion were noted in 123 (77.4%) and 30 (18.9%) cases, respectively. Inter-rater agreements were good for neck apposition (κ=0.75) and protrusion (κ=0.78). Complete and adequate occlusion was achieved in 104 (65%) and 130 (82%) cases, respectively (median follow-up 18 months). Good neck apposition was a strong independent predictor for both adequate (adjusted OR (aOR)=5.9, 95% CI 2.4 to 14.9; P<0.001) and complete occlusion (aOR=7.1, 95% CI 3.0 to 18.1; P<0.001). Protrusion was more frequent in the adequate occlusion group versus the aneurysm recurrence group without reaching statistical significance (P=0.06), but was associated with more thromboembolic complications (9/30 (30%) vs 12/129 (9%); P<0.01). WEB shape modification was significantly greater in poor apposition cases (P=0.03). Conclusions Achieving good neck apposition of the WEB strongly predicts aneurysm occlusion during follow-up. WEB protrusion should be minimized due to the increase in thromboembolic risk with limited impact on aneurysm occlusion.

Background: Stroke guideline statements are important references for clinicians due to the rapidly evolving nature of treatments. Guideline statements should be informed by up-to-date systematic reviews (SRs) and meta-analyses (MAs) because they provide the highest level of evidence. To investigate the utilization of SRs/MAs in stroke management guidelines, we conducted a literature review of guidelines and extracted relevant information regarding SRs/MAs. Methods: A literature review was conducted in PubMed with supplementation using the Trip medical database with the term “stroke” as the target population, followed by using the filter “guidelines”. We extracted the number of included SRs/MAs, the years of publication, the country of origin, and other characteristics of interest. Descriptive statistics were generated using the R software version 4.2.1. Results: We included 27 guideline statements. The median number of overall SRs or MAs within the guidelines was 4.0 (interquartile range [IQR] = 2–9). For MAs only, the median number included in the guidelines was 3.0 (IQR = 2.0–5.5). Canadian guidelines had the oldest citations, with a median gap of 12.0 (IQR = 5.2–18.0) years for the oldest citation, followed by European (median = 12; IQR = 9.5–13.5) and US (median = 10.0; IQR = 5.2–16) guidelines. Conclusions: Stroke guideline writing groups and issuing bodies should devote greater effort to the inclusion of up-to-date SRs/MAs in their guideline statements so that clinicians can reference recent data with the highest level of evidence.

Background The flow diversion treatment of aneurysms located distal to the Circle of Willis has recently increased in frequency. We conducted a systematic review and meta-analysis of the clinical and radiological outcomes of flow diverter (FD) embolization in treating M1 aneurysms. Methods PubMed, Web of Science, Ovid Medline, Ovid Embase, and Scopus were searched up to May 2024 using the Nested Knowledge platform. We included studies assessing the long-term clinical and radiological outcomes for M1 aneurysms. Results of FDs classified as Pipeline Embolization Devices (PED) versus other types of FDs. Angiographic occlusion rates, ischemic and hemorrhagic complications, and favorable clinic outcomes were included. All data were analyzed using R software version 4.2.2. Results Thirteen studies with 112 total patients (58 patients for PED and 54 patients for other FD devices) were included in our meta-analysis. The overall adequate (complete + near-complete) occlusion rates were 85.1%. The complete occlusion rate was higher with PED than with other FD devices (72.9% PED and 41.6% for non-PED FDs, respectively, p -value <.01). The ischemic complications were 9.9% and 9.0% for the PED and non-PED groups, respectively ( p -value = .89). The overall modified Rankin Scale 0–2 was 100% for the non-PED and 97.1% for the PED group ( p -value = .51). In-stent stenosis rate was 7.5% for PED devices compared to 2.6% in the non-PED group ( p -value = .35). Conclusions This relatively small meta-analysis showed high rates of adequate and complete occlusion in FD treatment of M1 segment aneurysms, with favorable safety profiles. PEDs were associated with higher rates of complete aneurysm occlusion compared to other types of FDs.

OBJECTIVE Fibrin deposition represents a key step in aneurysm occlusion, promoting endothelization of implants and connective tissue organization as part of the aneurysm-healing mechanism. In this study, the authors introduce a novel in vitro testing platform for flow diverters based on human fibrinogen. METHODS A flow diverter was deployed in 4 different glass models. The glass models had the same internal parent artery (4 mm) and aneurysm (8 mm) diameters with varying parent artery angulations (paraophthalmic, sidewall, bifurcation, and slightly curved models). The neck size and area were 4 mm and 25 mm 2 , respectively. Human fibrinogen (330 mg/dl) was circulated within the glass models at varying flow rates (0, 3, 4, and 5 ml/sec) with or without heparin, calcium chloride, and thrombin for as long as 6 hours or until complete fibrin coverage of the flow diverter’s neck was achieved. Aneurysm neck coverage was defined as macroscopic fibrin deposition occluding the flow diverters’ pores. Flow characteristics after flow diverter deployment were assessed with computational fluid dynamics analysis. The effects of flow rates, heparin, calcium chloride, and thrombin on fibrin deposition rates were tested using 1-way ANOVA and the Tukey test. RESULTS A total of 84 replicates were performed. Human fibrin did not accumulate on the flow diverter stents under static conditions. The fibrin deposition rate on the aneurysm neck was significantly greater with the 5 ml/sec flow rate as compared to 3 ml/sec for all models. The paraophthalmic model had the highest inflow velocity of 48.7 cm/sec. The bifurcation model had the highest maximum shear stress (SS) and maximum normalized shear stress values at the device cells at 843.3 dyne/cm 2 and 35.1 SS/SS inflow , respectively. The fibrin deposition rates of the paraophthalmic and bifurcation models were significantly higher than those of sidewall and slightly curved models for all additive or flow rate comparisons (p = 0.001 for all comparisons). The incorporation of thrombin significantly increased the fibrin deposition rates across all models (p = 0.001 for all models). CONCLUSIONS Rates of fibrin deposition varied widely across different configurations and additive conditions in this novel in vitro model system. Fibrin accumulation started at the aneurysm inflow zone where flow velocity and shear stress were the highest. The primary factors influencing fibrin deposition included flow velocities, shear stress, and the addition of thrombin at a physiological concentration. Further research is needed to test the clinical utility of fibrinogen-based models for patient-specific aneurysms.

Background Intracranial dissecting aneurysms present a challenging subset linked to considerable morbidity and mortality, necessitating effective therapeutic strategies to prevent complications. Traditional treatments face technical limitations, while emerging endovascular modalities like stent-assisted coiling, multiple stenting, and flow-diverting devices (FDDs) offer promise in reducing periprocedural risks and enhancing patient outcomes. The aim of this study is to compare the safety and efficacy outcomes of endovascular treatment for intracranial dissecting aneurysms using FDDs versus stents (with or without coiling). Methods A systematic review and meta-analysis were conducted following established guidelines. The search included PubMed, Scopus, Web of Science, and Embase databases up to July 30, 2023. Eligible studies reporting outcomes of interest in both FDD and stent-treated groups were included, and the data was extracted and analyzed using STATA software. Results Six studies were analyzed, involving 131 patients in the FDD group and 199 patients in the stent group. The pooled rates for favorable functional outcomes (86.8% vs. 86%), mortality (3.9% vs. 6%), adequate occlusion (79.7% vs. 86.3%), aneurysm recurrence (1.3% vs. 13.3%), in-stent stenosis/thrombosis (7% vs. 6.9%), ischemic events/infarctions (6.7% vs. 7.8%), retreatment (7% vs. 8.6%), and technical success (100% vs. 98.7%) were comparable in individuals treated with FDDs and stents (p > 0.05 in all cases). Additionally, complete occlusion rates were not significantly different between FDD (62.7%) and stent-treated patients (75.2%) (p = 0.06). However, after excluding one study in a leave-one-out analysis of the random effects meta-analysis, a significant difference in the pooled rates of this outcome was observed between the FDD (59.2%) and stent (75.2%) groups (p = 0.034). Conclusion FDDs present a promising approach for the treatment of intracranial dissecting aneurysms, yielding outcomes that are roughly comparable to stent-based methods. However, the absence of randomized trials and data limitations highlight the need for further research to enhance treatment strategies.

The New Zealand rabbit elastase-induced arterial aneurysm of the right common carotid artery remains a widely used model for assessing the effectiveness and safety of new neuroendovascular devices.1 This model offers a simple and reliable platform for pre-clinical in vivo investigations, crucial for comprehending the biological processes underlying aneurysm healing after endovascular treatment.2 Notably, the induced aneurysm exhibits morphological, hemodynamic, and histological characteristics similar to human intracranial aneurysms. The creation of the aneurysm is performed using open and endovascular techniques. Each step of the procedure requires a meticulous and controlled gesture to ensure reproducibility of the aneurysm and minimize animal misuse. In video 1 we present a step-by-step procedural guide for aneurysm creation and follow-up. We hope this resource will help in promoting this model and provide useful guidance for researchers in the field. Video 1 Surgical procedure of creating elastase-induced aneurysms in rabbits.

OBJECTIVE Fibrin deposition is integral to thrombus formation and wound healing. The role of fibrin deposition and subsequent metabolism following flow diversion for aneurysm treatment remains poorly characterized. This study aimed to evaluate the role of fibrin in early thrombus organization after flow diverter treatment. METHODS Thirty-five elastase-induced aneurysms were induced in New Zealand white rabbits and subjected to endoluminal flow diversion treatment. The device-bearing arteries were harvested at 1, 3, and 6 months postimplantation and processed for histopathological examination, including a modified picro-Mallory stain (Carstairs method) to visualize fibrin and platelets, immunohistochemical targeting of smooth muscle actin (SMA), and H&E staining for conventional morphological evaluation. Quantitative analysis of tissue components was carried out using the Orbit Image Analysis software. The samples were also assessed qualitatively to investigate the morphology and location of fibrin and other thrombus components within the intra-aneurysmal thrombi. Statistical analyses were conducted using R software version 4.3.1. RESULTS Fibrin constituted 27.9% of the thrombus tissue within the aneurysm sac for aneurysms harvested at 1 month, and this rate was significantly lower in the 3-month group (10.2%, p = 0.018). The proportion of blood cells within the sac was also notably higher in the 1-month group compared with other time points. The primary tissue filling the dome at 1 month (14/15, 93%) was an unorganized thrombus primarily composed of fibrin, platelets, and red blood cells. Conversely, aneurysms harvested at 1 month had the lowest collagen level (25.6%). However, collagen became the dominant tissue component within the aneurysm sac, accounting for 71.8% of tissue in the 3-month group (p = 0.007). There were no differences observed among the examined components between the 3-month and 6-month groups. On qualitative analysis, collagen-producing SMA-positive myofibroblasts were located near or in between fibrin molecules. Healed aneurysms exhibited myofibroblasts, collagen, and a well-organized fibrin network on the aneurysm neck. In contrast, unhealed aneurysms displayed a poorly organized fibrin network with scattered myofibroblasts at the neck area. CONCLUSIONS These findings indicate that fibrin plays a foundational role in the gradual occlusion of aneurysms after flow diverter treatment. Endovascular approaches that enhance fibrin accumulation could potentially improve aneurysm occlusion rates. Further research is needed to establish the precise role of fibrin in aneurysm occlusion.

Background Wide neck bifurcation aneurysms (WNBAs) are a subtype of aneurysms that are especially complex to treat. We aim to conduct a systematic review and meta-analysis to synthesize the available literature on the safety and efficacy of employing endovascular clip system (eCLIPs) in the treatment of WNBAs. Methods We report this study in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 guidelines. PubMed, Embase, Web of Science, and Scopus were queried for this review. Screening and extraction were performed by at least two authors to ensure accuracy and completeness, and a senior author arbitrated any discrepancies. All data were analyzed using R software version 4.3.0. and random-effects model. Results Four studies were finally included, of which three were prospective and one was retrospective. Successful adjunctive coiling occurred in 91.38% (95% CI = 70.71–97.9) of cases and overall technical success was achieved in 88.61% (95 CI = 75.54–95.15) of cases. The pooled complete occlusion (Raymond-Roy Class I) was 50.65% (95% CI = 39.63–61.60) and adequate occlusion (Raymond-Roy Class I/II) was 84.42% (95% CI = 74.53–90.93). Thrombo-embolic complication had a pooled rate of 1.22% (95% CI = 0.17–8.15), retreatment rate was 6.10% (95% CI = 2.56–13.83), and mortality reported in 3.66% (95% CI = 1.18–10.74) of patients. Conclusion The use of eCLIPs may be a safe and efficacious treatment for WNBAs. Future randomized controlled trials are needed for further validation of the findings.