Trial of Endovascular Therapy for Acute Ischemic Stroke with Large Infarct.

BACKGROUND: The role of endovascular therapy for acute stroke with a large infarction has not been extensively studied in differing populations. METHODS: We conducted a multicenter, prospective, open-label, randomized trial in China involving patients with acute large-vessel occlusion in the anterior circulation and an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower values indicating larger infarction) or an infarct-core volume of 70 to 100 ml. Patients were randomly assigned in a 1:1 ratio within 24 hours from the time they were last known to be well to undergo endovascular therapy and receive medical management or to receive medical management alone. The primary outcome was the score on the modified Rankin scale at 90 days (scores range from 0 to 6, with higher scores indicating greater disability), and the primary objective was to determine whether a shift in the distribution of the scores on the modified Rankin scale at 90 days had occurred between the two groups. Secondary outcomes included scores of 0 to 2 and 0 to 3 on the modified Rankin scale. The primary safety outcome was symptomatic intracranial hemorrhage within 48 hours after randomization. RESULTS: A total of 456 patients were enrolled; 231 were assigned to the endovascular-therapy group and 225 to the medical-management group. Approximately 28% of the patients in both groups received intravenous thrombolysis. The trial was stopped early owing to the efficacy of endovascular therapy after the second interim analysis. At 90 days, a shift in the distribution of scores on the modified Rankin scale toward better outcomes was observed in favor of endovascular therapy over medical management alone (generalized odds ratio, 1.37; 95% confidence interval, 1.11 to 1.69; P = 0.004). Symptomatic intracranial hemorrhage occurred in 14 of 230 patients (6.1%) in the endovascular-therapy group and in 6 of 225 patients (2.7%) in the medical-management group; any intracranial hemorrhage occurred in 113 (49.1%) and 39 (17.3%), respectively. Results for the secondary outcomes generally supported those of the primary analysis. CONCLUSIONS: In a trial conducted in China, patients with large cerebral infarctions had better outcomes with endovascular therapy administered within 24 hours than with medical management alone but had more intracranial hemorrhages. (Funded by Covidien Healthcare International Trading [Shanghai] and others; ANGEL-ASPECT ClinicalTrials.gov number, NCT04551664.).

G6PD maintains the VSMC synthetic phenotype and accelerates vascular neointimal hyperplasia by inhibiting the VDAC1-Bax-mediated mitochondrial apoptosis pathway.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) plays an important role in vascular smooth muscle cell (VSMC) phenotypic switching, which is an early pathogenic event in various vascular remodeling diseases (VRDs). However, the underlying mechanism is not fully understood. METHODS: An IP‒LC‒MS/MS assay was conducted to identify new binding partners of G6PD involved in the regulation of VSMC phenotypic switching under platelet-derived growth factor-BB (PDGF-BB) stimulation. Co-IP, GST pull-down, and immunofluorescence colocalization were employed to clarify the interaction between G6PD and voltage-dependent anion-selective channel protein 1 (VDAC1). The molecular mechanisms involved were elucidated by examining the interaction between VDAC1 and apoptosis-related biomarkers, as well as the oligomerization state of VDAC1. RESULTS: The G6PD level was significantly elevated and positively correlated with the synthetic characteristics of VSMCs induced by PDGF-BB. We identified VDAC1 as a novel G6PD-interacting molecule essential for apoptosis. Specifically, the G6PD-NTD region was found to predominantly contribute to this interaction. G6PD promotes VSMC survival and accelerates vascular neointimal hyperplasia by inhibiting VSMC apoptosis. Mechanistically, G6PD interacts with VDAC1 upon stimulation with PDGF-BB. By competing with Bax for VDAC1 binding, G6PD reduces VDAC1 oligomerization and counteracts VDAC1-Bax-mediated apoptosis, thereby accelerating neointimal hyperplasia. CONCLUSION: Our study showed that the G6PD-VDAC1-Bax axis is a vital switch in VSMC apoptosis and is essential for VSMC phenotypic switching and neointimal hyperplasia, providing mechanistic insight into early VRDs.

Integrated analysis of tRNA-derived small RNAs in proliferative human aortic smooth muscle cells.

BACKGROUND: Abnormal proliferation of vascular smooth muscle cells (VSMCs) contributes to vascular remodeling diseases. Recently, it has been discovered that tRNA-derived small RNAs (tsRNAs), a new type of noncoding RNAs, are related to the proliferation and migration of VSMCs. tsRNAs regulate target gene expression through miRNA-like functions. This study aims to explore the potential of tsRNAs in human aortic smooth muscle cell (HASMC) proliferation. METHODS: High-throughput sequencing was performed to analyze the tsRNA expression profile of proliferative and quiescent HASMCs. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to validate the sequence results and subcellular distribution of AS-tDR-001370, AS-tDR-000067, AS-tDR-009512, and AS-tDR-000076. Based on the microRNA-like functions of tsRNAs, we predicted target promoters and mRNAs and constructed tsRNA-promoter and tsRNA-mRNA interaction networks. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to reveal the function of target genes. EdU incorporation assay, Western blot, and dual-luciferase reporter gene assay were utilized to detect the effects of tsRNAs on HASMC proliferation. RESULTS: Compared with quiescent HASMCs, there were 1838 differentially expressed tsRNAs in proliferative HASMCs, including 887 with increased expression (fold change > 2, p < 0.05) and 951 with decreased expression (fold change < ½, p < 0.05). AS-tDR-001370, AS-tDR-000067, AS-tDR-009512, and AS-tDR-000076 were increased in proliferative HASMCs and were mainly located in the nucleus. Bioinformatics analysis suggested that the four tsRNAs involved a variety of GO terms and pathways related to VSMC proliferation. AS-tDR-000067 promoted HASMC proliferation by suppressing p53 transcription in a promoter-targeted manner. AS-tDR-000076 accelerated HASMC proliferation by attenuating mitofusin 2 (MFN2) levels in a 3'-untranslated region (UTR)-targeted manner. CONCLUSIONS: During HASMC proliferation, the expression levels of many tsRNAs are altered. AS-tDR-000067 and AS-tDR-000076 act as new factors promoting VSMC proliferation.

Hemodynamic impacts of flow diverter devices on the ophthalmic artery.

BACKGROUND: Flow diverter devices are increasingly used for endovascular treatment of internal carotid artery aneurysms. Treatment of ophthalmic segment aneurysms with flow diverter devices also includes coverage of the ophthalmic artery but may result in complications. It is unclear, however, whether these devices mechanically block blood flow in the ophthalmic artery. Also unclear is the relationship between deployment of a flow diverter device and post-treatment occlusion. We studied hemodynamic changes in the ophthalmic artery after deployment of a flow diverter device to determine the relationship between those changes and post-stent occlusion of the artery. METHODS: We analyzed hemodynamic modifications in the ophthalmic artery in 21 patients (19 women, 2 men; mean age 53.43 ± 7.32 years) treated by a single pipeline embolization device. Patient-specific geometries were determined from three-dimensional digital subtraction angiography and the stenting process was simulated. Computational fluid dynamics technology was used to analyze the change in ophthalmic artery hemodynamics. We compared pre-treatment and post-treatment flow velocity of the ophthalmic artery. RESULTS: Among the 21 patients with aneurysms located in the ophthalmic segment, no ophthalmic artery occlusion was found during immediate or follow-up angiography. Post-stent flow velocity in the ophthalmic artery decreased from 0.35 ± 0.19 to 0.33 ± 0.20 m/s, with the difference not being statistically significant (P = 0.106). CONCLUSION: Our results showed no significant change in ophthalmic artery blood flow after pipeline embolization device deployment. Hence, post-stent occlusion of the ophthalmic artery could not be explained by reduced blood flow. Delayed thrombosis and neointimal formation maybe the keys to ophthalmic artery occlusion and need further investigation.

China Intracranial Aneurysm Project (CIAP): protocol for a registry study on a multidimensional prediction model for rupture risk of unruptured intracranial aneurysms.

BACKGROUND: Ruptured aneurysms, the commonest cause of nontraumatic subarachnoid hemorrhage, can be catastrophic; the mortality and morbidity of affected patients being very high. Some risk factors, such as smoking, hypertension and female sex have been identified, whereas others, such as hemodynamics, imaging, and genomics, remain unclear. Currently, no accurate model that includes all factors for predicting such rupture is available. We plan to use data from a large cohort of Chinese individuals to set up a multidimensional model for predicting risk of rupture of unruptured intracranial aneurysms (UIAs). METHODS: The China Intracranial Aneurysm Project-2 (CIAP-2) will comprise screening of a cohort of 500 patients with UIA (From CIAP-1) and focus on hemodynamic factors, high resolution magnetic resonance imaging (HRMRI) findings, genetic factors, and biomarkers. Possible risk factors for rupture of UIA, including genetic factors, biomarkers, HRMRI, and hemodynamic factors, will be analyzed. The first project of the China Intracranial Aneurysm Project (CIAP-1; chaired by the Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China) will prospectively collect a cohort of 5000 patients with UIA from 20 centers in China, and collect baseline information for each patient. Multidimensional data will be acquired in follow-up assessments. Statistically significant clinical features in the UIA cohort will also be analyzed and integrated into the model for predicting risk of UIA rupture. After the model has been set up, the resultant evidence-based prediction will provide a preliminary theoretical basis for treating aneurysms at high risk of rupture. DISCUSSION: This study will explore the risk of rupture of aneurysms and develop a scientific multidimensional model for predicting rupture of unruptured intracranial aneurysms. Clinical Trials registration A Study on a Multidimensional Prediction Model for Rupture Risk of Unruptured Intracranial Aneurysms (CIAP-2), NCT03133624. Registered: 16 April 2017. https://clinicaltrials.gov/ct2/show/NCT03133624.

The Effect of Placing Flow-Diverting Stents in Intracranial Collateral Arteries of Miniature Pig.

BACKGROUND Flow-diverting stent (FDS) has been suggested as an effective intracranial aneurysm treatment. However, the effects of FDS on collateral branches of an aneurysm parent artery still remain unknown. Thus, the present study aimed to comprehensively evaluate the effects of placing a FDS in the intracranial collateral artery, using a miniature pig animal model. MATERIAL AND METHODS Ten healthy miniature pigs were included in the study: one pig was reserved as a control and the remaining nine pigs were placed in three experimental groups: FDS (i.e., Pipeline), LVIS, and Solitaier-AB stent groups. Pigs in the experimental groups were examined by cerebral angiography immediately after stent placement, followed by hemodynamic analyses. In addition, magnetic resonance imaging (MRI) of the brain of pigs in the experimental groups was performed to inspect the brain for obstruction and blood flow. Stents were examined for the growth of neointimas. RESULTS The results showed that neointimas, consisting of smooth muscle cells, collagenous fibers, and macrophages, were 0.67 mm thick on average and partially covered the stent wires. The thickness of neointimas in the FDS group was significantly higher than in the two conventional intracranial stent groups. There was no obvious obstruction identified in collateral arteries where the FDS was placed. CONCLUSIONS These results indicated that neointimas in collateral arteries of a miniature pig would be slightly thickened after one month of FDS placement; and FDS was shown to be safe for collateral arteries.

Endovascular Treatment of 147 Cases of Cavernous Carotid Aneurysms: A Single-Center Experience.

BACKGROUND: Cavernous carotid aneurysms (CCAs) are characterized by pain and neuro-ophthalmologic deficits. The optimal treatment remains unclear, especially for asymptomatic CCAs. This study investigated the efficacy of endovascular treatment for CCAs in our center. METHODS: Data obtained from patients who underwent endovascular treatment for CCAs from July 2011 to July 2014 were reviewed. A retrospective analysis was conducted regarding the general condition, clinical presentation, aneurysm characteristics, therapeutic strategy, and prognosis of CCA patients. RESULTS: One hundred forty-seven patients who exhibited 155 CCAs were included, which comprised 46 asymptomatic and 101 symptomatic CCA cases. Forty-eight cases presented with headache, 5 cases presented with subarachnoid hemorrhage, 20 cases presented with diplopia, 38 cases presented with cranial nerve palsy, and 27 cases presented with ischemic stroke. The mean aneurysm sizes were 15.3 ± 12.2 and 8.1 ± 7.1 mm in the symptomatic and asymptomatic groups, respectively. Different treatments were administered: coil occlusion (n = 15), stent/balloon-assisted coil occlusion (n = 123), and parent artery occlusion (PAO) (n = 17). The PAO-treated group exhibited the highest aneurysm occlusion rate. Follow-up data were available for 131 cases, which included 86 symptomatic and 45 asymptomatic cases. There were no deaths. Among the symptomatic patients, 40.7% improved, 58.1% remained stable, and 1.2% worsened; 12 patients exhibited regrowth and 6 patients had repeated endovascular treatment. The asymptomatic patients remained stable, including 5 patients who exhibited regrowth and 2 patients who had repeated endovascular treatment. CONCLUSION: Endovascular treatment is safe and effective for CCAs and should be considered in patients with minimal complications, as well as in asymptomatic patients with stable symptoms.

Evaluation of the EMBOPIPE flow diverter device: in vivo and in vitro experiments.

BACKGROUND: Although flow diverter device (FDD) has brought revolutionized advances in endovascular treatment of intracranial aneurysms, it also presents considerable drawbacks as well, as the innovation for novel device has never stopped. This preclinical research aims to evaluate the safety and efficacy of a newly developed FDD, the EMBOPIPE, through in vivo and in vitro experiments. METHODS: Aneurysms were induced in 20 New Zealand white rabbits which were randomized to three follow-up groups according to the time elapsed after EMBOPIPE implantation (28, 90, and 180 days). Additional EMBOPIPEs were implanted in the abdominal aorta to cover the renal artery in nine rabbits. Angiography was performed immediately after device placement in all groups. Aneurysm occlusion, patency of renal arteries, and pathological outcomes were assessed. For the in vitro experiments, we measured the thrombogenic potential of EMBOPIPEs (n = 5) compared with bare stents (n = 5) using the Chandler loop model. Evaluation indicators were the platelet counts, macroscopic observations and scanning electron microscopy. RESULTS: EMBOPIPEs were successfully deployed in 19 of 20 rabbit aneurysms (95.0%). The rates of complete or near-complete aneurysm occlusion were 73.3%, 83.3%, and 100% in the 28-, 90-, and 180-day groups, respectively. All renal arteries covered by EMBOPIPEs remained patent, and the mean difference in renal artery diameter before and after the device placement in the three groups was 0.07 mm, 0.10 mm, and 0.10 mm, respectively (p = 0.77). Renal pathology was normal in all cases. The pathological findings of the aneurysms were as follows: thickened and adequate neointimal coverage at the aneurysm neck, minimal inflammatory response, near-complete smooth muscle cell layer, and endothelialization along the device. In vitro experiments showed that the platelet counts were significantly higher in EMBOPIPE blood samples than in bare stent samples and that platelet adhesion to the device was lower in the EMBOPIPE stent struts compared with bare stent struts through macroscopic observations and scanning electron microscopy. CONCLUSIONS: The EMBOPIPE can achieve high rates of aneurysm occlusion while maintaining excellent branch artery patency. It exhibited wonderful pathological results. This novel device with phosphorylcholine surface modification could reduce platelet thrombus attached to the stent struts.

Effects of calcium channel blockers on perioperative ischemic events in hypertensive patients with intracranial aneurysms undergoing neurointervention.

BACKGROUND: Although calcium channel blockers (CCBs) are useful in stroke prevention, their specific role in preventing stroke in hypertensive patients with intracranial aneurysms undergoing endovascular stent placement remains unclear. METHODS: We retrospectively examined 458 hypertensive patients with intracranial aneurysms who underwent stent treatment, drawn from a larger multicenter cohort comprising 1326 patients across eight centers. Patients were dichotomized into two groups according to use of a CCB. Propensity score matching (PSM) was performed to balance group differences in patient and aneurysm characteristics. We conducted a comparison of patient and aneurysm characteristics, ischemic complications, and clinical outcomes between the two groups. RESULTS: The CCB and non-CCB groups comprised 279 and 179 patients, respectively. PSM resulted in 165 matched pairs. After PSM, the incidence of ischemic events within 1 month of the procedure (4.2% vs 10.9%; P=0.022) and proportion of patients with modified Rankin Scale score >2 at last follow-up (1.5% vs 7.8%; P=0.013) were significantly lower in the CCB group. Among patients treated with combination therapy, inclusion of a CCB was associated with a lower incidence of ischemic events (1.5% vs 13.3%; P=0.345), but the difference was not statistically significant after correction. CONCLUSIONS: CCB use in hypertensive patients undergoing endovascular stenting for treatment of intracranial aneurysms is associated with a lower incidence of ischemic events and a lower incidence of unfavorable neurological outcomes, especially when used in combination therapy.

Comparison of Gelatin/Polylysine- and Silk Fibroin/SDF-1α-Coated Mesenchymal Stem Cell-Seeded Intracranial Stents.

Endothelialization of the aneurysmal neck is essential for aneurysm healing after endovascular treatment. Mesenchymal stem cell (MSC)-seeded stents can promote aneurysm repair. The biological effects of coated and uncoated nitinol intracranial stents seeded with MSCs on vascular cells and macrophage proliferation and inflammation are investigated. Two stent coatings that exert pro-aggregation effects on MSCs via different mechanisms are examined: gelatin/polylysine (G/PLL), which enhances cell adhesion, and silk fibroin/SDF-1α (SF/SDF-1α), which enhances chemotaxis. The aim is to explore the feasibility of MSC-seeded coated stents in the treatment of intracranial aneurysms. The G/PLL coating provides the highest cytocompatibility and blood compatibility substrate for MSCs and vascular cells and promotes cell adhesion and proliferation. Moreover, it enhances MSC secretion and regulation of vascular cell and macrophage proliferation and chemotaxis. Although the SF/SDF-1α coating promotes MSC secretion and vascular cell chemotaxis, it induces a greater degree of macrophage proliferation, chemotaxis, and secretion of pro-inflammatory factors. MSC-seeded stents coated with G/PLL may benefit stent surface endothelialization and reduce the inflammatory response after endovascular treatment of intracranial aneurysm. These effects may improve aneurysm healing and increase the cure rate.

Roles of light transmission aggregometry and CYP2C19 genotype in predicting ischaemic complications during interventional therapy for intracranial aneurysms.

BACKGROUND AND PURPOSE: Light transmission aggregometry (LTA) and CYP2C19 genotype analysis are commonly used to evaluate the antiplatelet effects of clopidogrel during the interventional treatment of intracranial aneurysms. The aim of this study was to determine which test can predict ischaemic events during these treatments. METHODS: Patient demographic information, imaging data, laboratory data and ischaemic complications were recorded. LTA and CYP2C19 genotype results were compared, and multiple linear regression was performed to examine factors related to platelet reactivity. Multivariate regression analysis was performed to determine whether LTA and CYP2C19 could predict ischaemic complications and to identify other clinical risk factors. Receiver operating characteristic curve analysis was conducted to calculate the cut-off value for predicting ischaemic complications. A subgroup analysis was also performed for different CYP2C19 genotype metabolisers, as well as for patients with flow diverters and traditional stents. RESULTS: A total of 379 patients were included, of which 22 developed ischaemic events. Maximum platelet aggregation induced by ADP (ADP-MPA) could predict ischaemic events (p<0.001; area under the curve, 0.752 (95% CI 0.663 to 0.842)), and its cut-off value was 41.5%. ADP-MPA (p=0.001) and hypertension duration >10 years (p=0.022) were independent risk factors for ischaemic events, while the CYP2C19 genotype was not associated with ischaemic events. In the subgroup analysis, ADP-MPA could predict ischaemic events in fast metabolisers (p=0.004) and intermediate metabolisers (p=0.003). The cut-off value for ischaemic events was lower in patients with flow diverters (ADP-MPA=36.4%) than in patients with traditional stents (ADP-MPA=42.9%). CONCLUSIONS: ADP-MPA can predict ischaemic complications during endovascular treatment of intracranial aneurysms. Patients with flow diverters require stronger antiplatelet medication than patients with traditional stents.

Use of Tirofiban to Prevent Ischemic Events in Patients with CYP2C19 Loss-of-Function Alleles during Flow Diversion of Intracranial Aneurysm: A Multicenter Cohort Study.

To analyze the effect of tirofiban on ischemic events in CYP2C19 loss-of-function (LOF) allele carriers during pipeline embolization device (PED) implantation. Demographic information, imaging data, ischemic complications, CYP2C19 genotyping, and platelet function test results were collected from patients with PED-treated intracranial aneurysms at three centers. Multivariate logistic regression was used to analyze risk factors for ischemic events. Patients were grouped according to LOF alleles and antiplatelet drugs, the baseline information of LOF allele carriers and non-carriers were compared, and the efficacy of tirofiban was analyzed by comparing the incidence of ischemic events in each group. In total, 278 patients were included in the study, 24 of whom had an ischemic event. 157 (56.5%) patients carried the LOF allele and were more likely to develop resistance to clopidogrel (P < 0.001) and hypertension (P = 0.010). Multivariate logistic regression analysis revealed that the independent risk factors for ischemic events were age of > 55 years (OR = 3.308, P = 0.028), LOF alleles (OR = 3.960, P = 0.036), and clopidogrel nonresponsiveness (OR = 3.301, P = 0.014). For LOF allele carriers, prophylactic use of tirofiban after PED implantation helped to reduce ischemic events (4.3% vs. 16.4%, P = 0.039). This study supports CYP2C19 genotyping before flow diversion because LOF alleles increase the risk of ischemic events. Prophylactic use of tirofiban may help reduce ischemic events in LOF allele carriers.

Hsa_circ_0001402 alleviates vascular neointimal hyperplasia through a miR-183-5p-dependent regulation of vascular smooth muscle cell proliferation, migration, and autophagy.

INTRODUCTION: Vascular neointimal hyperplasia, a pathological process observed in cardiovascular diseases such as atherosclerosis and pulmonary hypertension, involves the abundant presence of vascular smooth muscle cells (VSMCs). The proliferation, migration, and autophagy of VSMCs are associated with the development of neointimal lesions. Circular RNAs (circRNAs) play critical roles in regulating VSMC proliferation and migration, thereby participating in neointimal hyperplasia. However, the regulatory roles of circRNAs in VSMC autophagy remain unclear. OBJECTIVES: We aimed to identify circRNAs that are involved in VSMC autophagy-mediated neointimal hyperplasia, as well as elucidate the underlying mechanisms. METHODS: Dual-luciferase reporter gene assay was performed to validate two competing endogenous RNA axes, hsa_circ_0001402/miR-183-5p/FKBP prolyl isomerase like (FKBPL) and hsa_circ_0001402/miR-183-5p/beclin 1 (BECN1). Cell proliferation and migration analyses were employed to investigate the effects of hsa_circ_0001402, miR-183-5p, or FKBPL on VSMC proliferation and migration. Cell autophagy analysis was conducted to reveal the role of hsa_circ_0001402 or miR-183-5p on VSMC autophagy. The role of hsa_circ_0001402 or miR-183-5p on neointimal hyperplasia was evaluated using a mouse model of common carotid artery ligation. RESULTS: Hsa_circ_0001402 acted as a sponge for miR-183-5p, leading to the suppression of miR-183-5p expression. Through direct interaction with the coding sequence (CDS) of FKBPL, miR-183-5p promoted VSMC proliferation and migration by decreasing FKBPL levels. Besides, miR-183-5p reduced BECN1 levels by targeting the 3'-untranslated region (UTR) of BECN1, thus inhibiting VSMC autophagy. By acting as a miR-183-5p sponge, overexpression of hsa_circ_0001402 increased FKBPL levels to inhibit VSMC proliferation and migration, while simultaneously elevating BECN1 levels to activate VSMC autophagy, thereby alleviating neointimal hyperplasia. CONCLUSION: Hsa_circ_0001402, acting as a miR-183-5p sponge, increases FKBPL levels to inhibit VSMC proliferation and migration, while enhancing BECN1 levels to activate VSMC autophagy, thus alleviating neointimal hyperplasia. The hsa_circ_0001402/miR-183-5p/FKBPL axis and hsa_circ_0001402/miR-183-5p/BECN1 axis may offer potential therapeutic targets for neointimal hyperplasia.

Effects of Enterprise 2 stent-assisted coil embolization for wide-necked intracranial aneurysms.

BACKGROUND: This study analyzed the safety and efficacy of Enterprise 2 stent-assisted coil embolization for wide-necked intracranial aneurysms by examining stent-vessel apposition, operative complications, embolization outcomes, and clinical outcomes. METHODS: We retrospectively reviewed the medical records of patients with wide-necked intracranial aneurysms who underwent Enterprise 2 stent-assisted coiling in our hospital from November 2018 to October 2019. Intraoperative VasoCT was performed immediately after stent release in a continuous cohort of patients to observe stent-vessel apposition. Patient demographic, clinical, and imaging data were recorded and analyzed. RESULTS: A total of 106 wide-necked aneurysms in 106 patients were treated. Stent release was successful in all patients. Twenty-one patients were enrolled consecutively for VasoCT scanning, and incomplete stent apposition was observed in 5 (23.8%). Perioperative complications occurred in 10 patients (9.4%): cerebral infarction in 6, intraoperative coil prolapse in 1, puncture site pseudoaneurysm in 1, deep vein thrombosis at multiple sites in 1, and transient brainstem mass effect in 1. Among the 95 aneurysms with angiographic follow-up, embolization was satisfactory (Raymond-Roy classifications I and II) in 89 (93.7%). Hyperlipidemia was an independent risk factor for incomplete aneurysm occlusion. At the last clinical follow-up, seven patients had a poor clinical outcome (modified Rankin Scale score ≥ 3). Independent risk factors for poor outcomes were preoperative subarachnoid hemorrhage at presentation and cerebral infarction. CONCLUSION: Enterprise 2 stent-assisted coiling for treatment of wide-necked intracranial aneurysms showed good safety and efficacy; however, incomplete stent apposition can still occur in vessels with a large curvature. Preoperative subarachnoid hemorrhage at presentation and cerebral infarction are the main reasons for poor clinical outcomes after stent-assisted coil embolization.

Reconstructive Endovascular Treatment of Basilar Trunk and Vertebrobasilar Junction Aneurysms: A Review of 77 Consecutive Cases.

Background: Basilar trunk and vertebrobasilar junction (BTVBJ) aneurysms have a poor prognosis and are challenging to treat. Objective: This study aimed to evaluate the efficacy of reconstructive endovascular treatment for BTVBJ aneurysms and explore a treatment selection paradigm. Methods: Clinical and angiographic data from 77 patients with 80 BTVBJ aneurysms who underwent endovascular treatment with flow diverters (FDs) or conventional stent-assisted coiling between January 2016 and December 2020 were retrospectively analyzed. Aneurysm characteristics and treatment outcomes were compared between treatment groups. Results: Among the 77 study patients, 34 (44.2%) were treated with FDs and 43 (55.8%) with conventional stent-assisted coiling. Overall, 72.7% of patients achieved favorable clinical outcome at follow-up. The rate of procedure-related complications was 23.4%. The aneurysm occlusion rate at last follow-up did not differ between the FD and conventional stent groups (79.2% vs. 77.1%, p = 0.854). Although the occlusion rate immediately after the procedure was lower in the FD group (29.4%), incidence of progressive occlusion was significantly higher (62.5 vs. 5.7%; p < 0.001). The proportion of patients with large and giant aneurysms (≥10 mm) was significantly higher in the FD group (70.6 vs. 34.8%; p = 0.002). In patients with large or giant aneurysms, favorable clinical outcome at last follow-up was achieved in 75% of patients in the FD group but only 43.8% of patients in the conventional stent group (p = 0.046). Moreover, the complication rate was lower in the FD group, but the difference was not significant (20.8 vs. 37.5%; p = 0.247). The same analyses were performed for patients with small aneurysms (<10 mm) but no significant differences between the two groups were observed. Conclusion: Endovascular treatment of small BTVBJ aneurysms using either FDs or conventional stents was feasible and effective. In patients with large or giant aneurysms, treatment using FDs achieved higher rates of occlusion and favorable clinical outcome at last follow-up than conventional stent-assisted coiling.

Outcomes of reconstructive endovascular treatment of vertebrobasilar dissecting aneurysms with intramural hematoma.

Background: Vertebrobasilar dissecting aneurysms (VBDAs) with an intramural hematoma (IMH) usually cause symptoms because of mass effect and grow in size over time. Clinical outcomes are generally poor. Objective: This study aimed to examine outcomes of reconstructive endovascular treatment (EVT) in patients with VBDAs with IMH. Safety and effectiveness were compared between flow diverters (FDs) and conventional stents. Methods: We retrospectively analyzed the clinical and radiological data of 36 VBDAs with IMH in 36 patients who underwent EVT with either FDs or conventional stents from January 2012 to December 2020 at our institution. Results: Among the 36 study patients, 20 were treated with FDs and 16 with conventional stents. Incidence of procedure-related complications did not significantly differ between the two stents. IMH growth occurred after EVT in a significantly higher proportion of conventional stent group aneurysms (zero vs. 31.3% [5/16]; p = 0.012). Among the five aneurysms with IMHs that grew, all recurred. Change in IMH size after EVT was significantly lower in the FD group (-2.7 vs. +8.1%, p = 0.036). However, after the recurrent aneurysms were removed from the conventional stent group, change in IMH size did not significantly differ between the two groups (-2.7 vs. +1.0%, p = 0.332). The proportion of patients who experienced an improvement in mRS score after EVT was significantly higher in the FD group (60 vs. 25%, p = 0.036). Conclusion: IMHs in VBDAs stop growing after successful reconstructive EVT. Although both FD and conventional stent treatment are effective, FD treatment may be superior based on clinical outcomes and effect on IMH size.

High shear stress and flow velocity in partially occluded aneurysms prone to recanalization.

BACKGROUND AND PURPOSE: Hemodynamic factors are thought to play an important role in the initiation, growth, and rupture of cerebral aneurysms. However, the hemodynamic features in the residual neck of the partially embolized aneurysms and their influences on recanalization are rarely reported. In this study, we characterized the hemodynamics of partially occluded aneurysms, which were proven to undergo recanalization during follow-up using computational fluid dynamic analysis. METHODS: From May 2007 to June 2009, we identified 11 partial aneurysms during follow-up, including 5 recanalized cases and 6 stable cases with 3-dimensional digital subtraction angiography. We retrospectively characterized the hemodynamic features around the residual aneurysmal pouch using the available postprocedural digital subtraction angiography image data. The occluded part of the aneurysm was regarded as completely separated from the circulation. RESULTS: The overall blood flow patterns before embolization were almost the same in the recanalized and stable groups. After occlusion, the flow pattern changes, wall shear stress (WSS), and velocity at the remnant neck demonstrated different changes between the 2 groups. Specifically, in the recanalized group, high WSS regions were found near the neck in all 5 cases, with 4 of them being even higher than those before occlusion. Interestingly, in all cases, the high WSS area of the remnant neck coincided with the location where the aneurysm recanalization occurred. In the stable group, 5 out of 6 cases demonstrated lower WSS and velocity at the remnant neck after occlusion. CONCLUSIONS: High WSS and blood flow velocity were consistently observed near the remnant neck of partially embolized aneurysms prone to future recanalization, suggesting that hemodynamic factors may have an important role in aneurysmal recurrence after endovascular treatment. The difference in flow pattern could be caused by the incomplete occlusion of the aneurysms.

Hemodynamic analysis of intracranial aneurysms with daughter blebs.

BACKGROUND AND PURPOSE: Intracranial aneurysms with daughter blebs appear to have a higher risk of rupture. Whether hemodynamic factors are involved in this phenomenon is not clear. METHODS: 54 patient-specific aneurysms harboring 69 daughter blebs were divided into ruptured and unruptured groups based on their clinical history. Realistic models were retrospectively constructed and analyzed by a computational fluid dynamic method. RESULTS: There were no differences in the aspect ratio and morphology type of the aneurysms, the size of blebs or other common risk factors between the two groups. The wall shear stress (WSS) was significantly lower while the oscillatory shear index (OSI) was higher in the daughter blebs than in the primary aneurysms. Bleb-bearing aneurysms with a rupture history displayed significantly lower WSS in the daughter bleb. Of the daughter blebs, 73.9% were localized to the impingement region of the inflow jet. CONCLUSION: These observations indicate that low WSS and high OSI in the daughter blebs might be involved in increasing the risk of rupture. The localized striking force caused by inflow jets may contribute to the development of daughter blebs. However, a precise role of hemodynamics in predicting the future rupture of daughter blebs needs further study.

Pipeline Embolization Device With Adjunctive Coils for the Treatment of Unruptured Large or Giant Vertebrobasilar Aneurysms: A Single-Center Experience.

Objective: To evaluate effectiveness and safety of Pipeline embolization device (PED) for large or giant verterbrobasilar aneurysms (LGVBAs), and to compare the therapeutic effects of PED with and without adjunctive coils. Methods: We retrospectively analyzed 21 cases of unruptured LGVBAs who were treated in our hospital with PED. These cases were divided into "PED group" and "PED with adjunctive coils group." We compared the aneurysm characteristics and treatment outcomes between the two groups. Results: The overall neurological complication rate was 28.6% (6/21) and the mortality rate was 4.8% (1/21). There were 12 patients in the PED group and nine in the PED with adjunctive coils group. There were no significant differences in age, smoking, hypertension, aneurysm size, aneurysm location, or operation time between the two groups. The complete aneurysm embolization rate and favorable outcome rate (modified Rankin Scale = 0,1) of the PED with adjunctive coils group was 78% (7/9) and 100% (9/9), respectively, which were both better compared with the PED group with 63.6% (7/11) and 83% (10/12), respectively. However, these differences were not statistically significant. Conclusion: The effectiveness and safety of PED for LGVBAs is acceptable. Treatment results did not differ between the PED and PED with adjunctive coils groups; therefore, whether coils should be used may depend the operator. Our results suggest that correct use of the coils does not increase complications. We suggest that PED with adjunctive coils should be used for some selected LGVBAs.

Endovascular Treatment of Tiny Aneurysms With Low-Profile Visualized Intraluminal Support Devices Using a "Compressed" Stent Technique.

Objective: To investigate the safety and efficacy of low-profile visualized intraluminal support (LVIS) stent-assisted coiling of intracranial tiny aneurysms using a "compressed" stent technique. Methods: We retrospectively analyzed patients with tiny aneurysms treated in our hospital with LVIS devices using a compressed stent technique. We analyzed patients' imaging outcomes, clinical outcomes, and complications. Results: Forty-two tiny aneurysms in 42 patients were included in this study cohort; 8 patients presented with subarachnoid hemorrhage at admission. The immediate postoperative complete embolization rate was 76.2% (32/42). After an average of 8.5 months of imaging follow-up, the complete embolization rate was 90.5% (38/42), and no aneurysm recanalization occurred. After an average of 24.4 months of clinical follow-up, 95.2% (40/42) of the patients achieved favorable clinical outcomes (modified Rankin scale = 0/1). Operation-related complications occurred in two patients (4.8%); one intraoperative acute thrombosis, and one significant unilateral decreased vision during the postoperative follow-up. Conclusion: LVIS stent-assisted coiling of intracranial tiny aneurysms using a compressed stent technique is safe and effective. Combined stent compression technology is beneficial to maximize the complete embolization of aneurysms and reduce aneurysm recanalization. This study expands the clinical applicability of LVIS stents.