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Background: Pipeline embolization device (PED) deployment combined with coil therapy for large complex intracranial aneurysms is effective and considered superior to PED deployment alone. However, the optimal strategy for use of coils remains unclear. We used patient-specific aneurysm models and finite element analysis to determine the ideal packing density of coils after PED placement., Methods: Finite element analysis was used to provide a higher-fidelity model for accurate post-treatment computational fluid dynamics analysis to simulate the real therapeutic process of PED and all coils. We then calculated and analyzed the reduction ratio of velocity to identify the hemodynamic change during PED deployment and each coil embolization., Results: Sixteen consecutive patients underwent PED plus coil procedures to treat internal carotid artery intracranial aneurysms. After PED deployment, the intra-aneurysmal flow velocity significantly decreased (15.3 vs 10.0 cm/s; p<0.001). When the first coil was inserted, the flow velocity in the aneurysm further decreased and the reduction was significant (10.0 vs 5.3 cm/s; p<0.001). Analysis of covariance showed that the effect of the reduction ratio of velocity of the second coil was significantly lower than that of the first coil (p<0.001)-that is, when the packing density increased to 7.06%, the addition of coils produced no further hemodynamic effect., Conclusion: Adjunct coiling could improve the post-PED hemodynamic environment in treated intracranial aneurysms. However, dense packing is not necessary because the intra-aneurysmal hemodynamics tend to stabilize as the packing density reaches an average of 7.06% or after insertion of the second coil., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The Low-profile Visualized Intraluminal Support device (LVIS) has been successfully used to treat cerebral aneurysm, and the push-pull technique has been used clinically to compact the stent across aneurysm orifice. Our aim was to exhibit the hemodynamic effect of the compacted LVIS stent., Methods: Two patient-specific aneurysm models were constructed from three-dimensional angiographic images. The uniform LVIS stent, compacted LVIS and Pipeline Embolization Device (PED) with or without coil embolization were virtually deployed into aneurysm models to perform hemodynamic analysis. Intra-aneurysmal flow parameters were calculated to assess hemodynamic differences among different models., Results: The compacted LVIS had the highest metal coverage across the aneurysm orifice (case 1, 46.37%; case 2, 67.01%). However, the PED achieved the highest pore density (case 1, 19.56 pores/mm 2 ; case 2, 18.07 pores/mm 2 ). The compacted LVIS produced a much higher intra-aneurysmal flow reduction than the uniform LVIS. The PED showed a higher intra-aneurysmal flow reduction than the compacted LVIS in case 1, but the results were comparable in case 2. After stent placement, the intra-aneurysmal flow was further reduced as subsequent coil embolization. The compacted LVIS stent with coils produced a similar reduction in intra-aneurysmal flow to that of the PED., Conclusions: The combined characteristics of stent metal coverage and pore density should be considered when assessing the flow diversion effects of stents. More intra-aneurysmal flow reductions could be introduced by compacted LVIS stent than the uniform one. Compared with PED, compacted LVIS stent may exhibit a flow-diverting effect comparable to that of the PED.

Background: Genetic risk factors play an important role in the pathogenesis of familial intracranial aneurysms (FIAs); however, the molecular mechanisms remain largely unknown., Objective: To investigate potential FIA-causing genetic variants by rare variant interrogation and a family-based genomics approach in a large family with an extensive multigenerational pedigree with FIAs., Method: Exome sequencing (ES) was performed in a dominant likely family with intracranial aneurysms (IAs). Variants were analyzed by an in-house developed pipeline and prioritized using various filtering strategies, including population frequency, variant type, and predicted variant pathogenicity. Sanger sequencing was also performed to evaluate the segregation of the variants with the phenotype., Results: Based on the ES data obtained from five individuals from a family with 7/21 living members affected with IAs, a total of 14 variants were prioritized as candidate variants. Familial segregation analysis revealed that NFX1 c.2519T>C (p.Leu840Pro) segregated in accordance with Mendelian expectations with the phenotype within the family-that is, present in all IA-affected cases and absent from all unaffected members of the second generation. This missense variant is absent from public databases (1000genome, ExAC, gnomAD, ESP5400), and has damaging predictions by bioinformatics tools (Gerp ++ score = 5.88, CADD score = 16.43, MutationTaster score = 1, LRT score = 0). In addition, 840Leu in NFX1 is robustly conserved in mammals and maps in a region before the RING-type zinc finger domain., Conclusion: NFX1 c.2519T>C (p.Leu840Pro) may contribute to the pathogenetics of a subset of FIAs., Competing Interests: Competing interests: No, there are no competing interests for any author., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: Stability stratification of intracranial aneurysms (IAs) is crucial for individualized clinical management, especially for small IAs. We aim to develop and validate a nomogram based on clinical and morphological risk factors for individualized instability stratification of small IAs. Methods: Six hundred fifty-eight patients with unstable (n = 293) and stable (n = 416) IAs <7 mm were randomly divided into derivation and validation cohorts. Twelve clinical risk factors and 18 aneurysm morphological risk factors were extracted. Combined with important risk factors, a clinical-morphological predictive nomogram was developed. The nomogram performance was evaluated in the derivation and the validation cohorts in terms of discrimination, calibration, and clinical usefulness. Results: Five independent instability-related risk factors were included in the nomogram: location, irregularity, side/bifurcation type, flow angle, and height-to-width ratio. In the derivation cohort, the area under the curve (95% CI) of the nomogram was 0.803 (95% CI, 0.764–0.842), and good agreement between predicted instability risk and actual instability status could be detected in the calibration plot. The nomogram also exhibited good discriminations and calibration in the validation cohort: the area under the curve (95% CI) was 0.744 (95% CI, 0.677–0.812). Small IAs with scores <90 were considered to have low risk of instability, and those with scores of 90 or greater were considered to have high risk of instability. Conclusions: The nomogram based on clinical and morphological risk factors can be used as a convenient tool to facilitate individualized decision-making in the management of small IAs. [ABSTRACT FROM AUTHOR]