The aim of this study was to quantify the effect of the new Low-profile Visualized Intraluminal Support (LVIS®D) device and the difference of fluid diverting effect compared with the Pipeline device and the Enterprise stent using computational fluid dynamics (CFD). In this research, we simulated three aneurysms constructed from 3D digital subtraction angiography (DSA). The Enterprise, LVIS and the Pipeline device were virtually conformed to fit into the vessel lumen and placed across the aneurysm orifice. Computational fluid dynamics analysis was performed to compare the hemodynamic differences such as WSS, Velocity and Pressure among these stents. Control referred to the unstented model, the percentage of hemodynamic changes were all compared to Control. A single LVIS stent caused more wall shear stress reduction than double Enterprise stents (39.96 vs. 30.51 %) and velocity (23.13 vs. 18.64 %). Significant reduction in wall shear stress (63.88 %) and velocity (46.05 %) was observed in the double-LVIS stents. A single Pipeline showed less reduction in WSS (51.08 %) and velocity (37.87 %) compared with double-LVIS stent. The double-Pipeline stents resulted in the most reduction in WSS (72.37 %) and velocity (54.26 %). Moreover, the pressure increased with minuscule extent after stenting, compared with the unstented model. This is the first study analyzing flow modifications associated with LVIS stents. We found that the LVIS stent has certain hemodynamic effects on cerebral aneurysms: a single LVIS stent caused more flow reductions than the double-Enterprise stent but less than a Pipeline device. Nevertheless, the double-LVIS stent resulted in a better flow diverting effect than a Pipeline device.

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 aneurismal 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 aneurismal recurrence after endovascular treatment. The difference in flow pattern could be caused by the incomplete occlusion of the aneurysms.

BACKGROUND AND PURPOSE: Although flow diverters have been reported with favorable clinical and angiographic outcomes in various literatures, randomized trials determining their true effectiveness and safety are still in lack. The Parent Artery Reconstruction for Large or Giant Cerebral Aneurysms Using the Tubridge Flow Diverter (PARAT) trial was designed to evaluate the safety and efficacy of the Tubridge flow diverter in the treatment of large or giant aneurysms in comparison with Enterprise stent-assisted coiling. MATERIALS AND METHODS: This prospective, multicenter, randomized trial was conducted at 12 hospitals throughout China. Enrolled adults with unruptured large/giant intracranial aneurysms were randomly assigned (1:1) to receive either Enterprise stent-assisted coiling or Tubridge flow diverter implantation. The primary end point was complete occlusion at 6-month follow-up, while secondary end points included technical success, mortality, target vessel–related stroke, aneurysm bleeding, in-stent stenosis, parent artery occlusion, and the frequency of all adverse events. RESULTS: Among 185 enrolled subjects, 41 withdrew before procedure initiation. Overall, 82 subjects underwent Tubridge implantation, and 62 subjects were primarily treated with stent-assisted coiling. The results of 6-month follow-up imaging included complete occlusion rates of 75.34% versus 24.53% for the Tubridge and stent-assisted coiling groups, respectively, with a calculated common odds ratio of 9.4 (95% confidence interval, 4.14–21.38; P < .001). There was a higher, nonsignificant frequency of complications for Tubridge subjects. Multivariate analysis showed a decreased stroke rate at the primary investigational site, with a marginal P value (P = .051). CONCLUSIONS: This trial showed an obviously higher rate of large and giant aneurysm obliteration with the Tubridge FD over Enterprise stent-assisted coiling. However, this higher obliteration rate came at the cost of a nonsignificantly higher rate of complications. Investigational site comparisons suggested that a learning curve for flow-diverter implantation should be recognized and factored into trial designs.

Background: Biological markers that can be used to predict the risk of intracranial aneurysms ( IA s) are not available. Methods and Results: To clarify whether circulating micro RNA s could be used as biomarkers for IA , we carried out microarray assays in a screening cohort of 40 IA patients (20 unruptured and 20 ruptured) and 20 healthy volunteers. We identified 20 micro RNA s that were unanimously changed in both ruptured and unruptured patients. We confirmed 60% of these changed micro RNA s by a separate microarray test with an independent validation cohort (n=143 including 93 IA patients). To identify potential biomarkers, we combined the 2 cohorts and performed quantitative real‐time polymerase chain reactions for selected target micro RNA s. Logistic regression analysis demonstrated that miR‐16 and miR‐25 were independent factors for IA occurrence ( P <0.001). After controlling for age, sex, smoking, and history of hypertension, the contributions of miR‐16 and miR‐25 were still highly significant ( P <0.001). The adjusted odds ratio values for miR‐16 and miR‐25 were 1.52 (95% CI 1.31 to 1.77) and 1.53 (1.30 to 1.79). Combining both miR‐16 and miR‐25 in a single model did not improve the performance of risk association. Conclusions: Our data suggest that circulating mi RNA s may be novel biological markers that are useful in assessing the likelihood of IA occurrence.

Background: Brain arteriovenous malformations (BAVM) represent a congenital anomaly of the cerebral vessels with a prevalence of 10–18/100 000. BAVM is the leading aetiology of intracranial haemorrhage in children. Our objective was to identify gene variants potentially contributing to disease and to better define the molecular aetiology underlying non-syndromic sporadic BAVM. Methods: We performed whole-exome trio sequencing of 100 unrelated families with a clinically uniform BAVM phenotype. Pathogenic variants were then studied in vivo using a transgenic zebrafish model. Results: We identified four pathogenic heterozygous variants in four patients, including one in the established BAVM-related gene, ENG, and three damaging variants in novel candidate genes: PITPNM3, SARS and LEMD3, which we then functionally validated in zebrafish. In addition, eight likely pathogenic heterozygous variants (TIMP3, SCUBE2, MAP4K4, CDH2, IL17RD, PREX2, ZFYVE16 and EGFR) were identified in eight patients, and 16 patients carried one or more variants of uncertain significance. Potential oligogenic inheritance (MAP4K4 with ENG, RASA1 with TIMP3 and SCUBE2 with ENG) was identified in three patients. Regulation of sma- and mad-related proteins (SMADs) (involved in bone morphogenic protein (BMP)/transforming growth factor beta (TGF-β) signalling) and vascular endothelial growth factor (VEGF)/vascular endotheliual growth factor recepter 2 (VEGFR2) binding and activity (affecting the VEGF signalling pathway) were the most significantly affected biological process involved in the pathogenesis of BAVM. Conclusions: Our study highlights the specific role of BMP/TGF-β and VEGF/VEGFR signalling in the aetiology of BAVM and the efficiency of intensive parallel sequencing in the challenging context of genetically heterogeneous paradigm.