Transcription factor CEBPB mediates intracranial aneurysm rupture by inflammatory and immune response.

INTRODUCTION: Genetic factors play a major part in mediating intracranial aneurysm (IA) rupture. However, research on the role of transcription factors (TFs) in IA rupture is rare. AIMS: Bioinformatics analysis was performed to explore the TFs and related functional pathways involved in IA rupture. RESULTS: A total of 63 differentially expressed transcription factors (DETFs) were obtained. Significantly enriched biological processes of these DETFs were related to regulation of myeloid leukocyte differentiation. The top 10 DETFs were screened based on the MCC algorithm from the protein-protein interaction network. After screening and validation, it was finally determined that CEBPB may be the hub gene for aneurysm rupture. The GSEA results of CEBPB were mainly associated with the inflammatory response, which was also verified by the experimental model of cellular inflammation in vitro. CONCLUSION: The inflammatory and immune response may be closely associated with aneurysm rupture. CEBPB may be the hub gene for aneurysm rupture and may have diagnostic value. Therefore, CEBPB may serve as the diagnostic signature for RIAs and a potential target for intervention.

How to perform intra-aneurysmal coil embolization after Pipeline deployment: a study from a hemodynamic viewpoint.

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.

Prediction and analysis of periprocedural complications associated with endovascular treatment for unruptured intracranial aneurysms using machine learning.

Background: The management of unruptured intracranial aneurysm (UIA) remains controversial. Recently, machine learning has been widely applied in the field of medicine. This study developed predictive models using machine learning to investigate periprocedural complications associated with endovascular procedures for UIA. Methods: We enrolled patients with solitary UIA who underwent endovascular procedures. Periprocedural complications were defined as neurological adverse events resulting from endovascular procedures. We incorporated three machine learning algorithms into our prediction models: artificial neural networks (ANN), random forest (RF), and logistic regression (LR). The Shapley Additive Explanations (SHAP) approach and feature importance analysis were used to identify and prioritize significant features associated with periprocedural complications. Results: In total, 443 patients were included. Forty-eight (10.83%) procedure-related complications occurred. In the testing set, the ANN model produced the largest value (0.761) for area under the curve (AUC). The RF model also achieved an acceptable AUC value of 0.735, while the AUC value of the LR model was 0.668. SHAP and feature importance analysis identified distal aneurysm, aneurysm size and treatment modality as most significant features for the prediction of periprocedural complications following endovascular treatment for UIA. Conclusion: Periprocedural complications after endovascular treatment for UIA are not negligible. Prediction of periprocedural complications via machine learning is feasible and effective. Machine learning can serve as a promising tool in the decision-making process for UIA treatment.

Risk factors for repeated recurrence of cerebral aneurysms treated with endovascular embolization.

Purpose: To explore the risk factors of recurrence after second endovascular embolization of recurrent aneurysms and the characteristics of recurrent refractory aneurysms to help clinical decision-making. Materials and methods: Forty-nine patients with recurrent aneurysms who underwent repeated embolization were retrospectively enrolled and divided into the recurrent and non-recurrent group. The risk factors of recurrence, complications and follow-up results of repeated embolization, and characteristics of recurrent refractory aneurysms were analyzed. Results: Among the 49 patients with the second embolization, 5 were lost to follow-up, 9 recurred, and 35 did not. Univariate analysis showed that aneurysm size (P = 0.022), aneurysm classification (P = 0.014), and Raymond-Roy grade after the second embolization (P = 0.001) were statistically different between the two groups. Multivariate analysis demonstrated the Raymond-Roy grade as an independent risk factor for the recurrence of aneurysms after the second embolization (P = 0.042). The complication rate after the second embolization was 4%. There were five recurrent refractory aneurysms with an average aneurysm size of 23.17 ± 10.45 mm, including three giant aneurysms and two large aneurysms. To achieve complete or near-complete embolization of the recurrent refractory aneurysms, multiple treatment approaches were needed with multiple stents or flow diverting devices. Conclusion: Aneurysm occlusion status after the second embolization is an independent risk factor for the recurrence of intracranial aneurysms. Compared with near-complete occlusion, complete occlusion can significantly reduce the risk of recurrence after second embolization. In order to achieve complete or near-complete occlusion, recurrent refractory aneurysms need multiple treatments with the use of multiple stents or flow diverting devices.

Association Between Aneurysmal Hemodynamics and Rupture Risk of Unruptured Intracranial Aneurysms.

Background: Assessing rupture risk in patients with unruptured intracranial aneurysms (UIAs) remains challenging. Hemodynamics plays an important role in the natural history of intracranial aneurysms. This study aimed to compare aneurysmal hemodynamic features between patients with different rupture risk as determined by PHASES score. Methods: We retrospectively examined 238 patients who harbored a solitary saccular UIA. Patients were stratified by rupture risk into low-, intermediate-, and high-risk groups according to PHASES score. Flow simulations were performed to compare differences in hemodynamics among the groups. Results: Aneurysmal time-averaged wall shear stress (WSSa) and normalized WSS (WSSn) decreased progressively as PHASES score increased. WSSa and WSSn significantly differed among the low-, intermediate-, and high-risk groups (p < 0.001). WSSa was significantly lower in the high-risk group than the low-risk group (p < 0.001) and the intermediate-risk group (p = 0.004). WSSn was also significantly lower in the high-risk group than the low-risk group (p < 0.001) and the intermediate-risk group (p = 0.001). Conclusions: Low WSS was significantly associated with higher risk of intracranial aneurysm rupture as determined by PHASES score, indicating that hemodynamics may play an important role in aneurysmal rupture. In the future, a multidimensional rupture risk prediction model that includes hemodynamic parameters should be investigated.

Risk factors for periprocedural ischemic stroke following endovascular treatment of intracranial aneurysms.

BACKGROUND: The aim of this study was to comprehensively evaluate the risk factors of periprocedural ischemic stroke associated with endovascular treatment of intracranial aneurysms using a real-world database. METHODS: From August 2016 to March 2017, 167 patients were enrolled. Univariate analysis and multivariate logistic regression analysis were used to examine the risk factors for periprocedural ischemic stroke. RESULTS: Among the 167 cases, periprocedural ischemic stroke occurred in 20 cases (11.98%). After univariate analysis, the ischemic group had a higher proportion of large (≥ 10 mm) aneurysms than the control group (45.0% vs. 23.1%, p = 0.036). The incidence of periprocedural ischemic stroke was higher in cases treated by flow diverter (21.6%) or stent-assisted coiling (11.8%) than in cases treated by coiling only (2.7%), and the differences were statistically significant (p = 0.043). After multivariate logistic regression analysis, treatment modality was the independent risk factor for periprocedural ischemic stroke. Compared with the coiling-only procedure, flow diverter therapy was associated with a significantly higher rate of periprocedural ischemic stroke (OR 9.931; 95% CI 1.174-84.038; p = 0.035). CONCLUSIONS: Aneurysm size and treatment modality were associated with periprocedural ischemic stroke. Larger aneurysms were associated with increased risk of periprocedural ischemic stroke. Flow diverter therapy was associated with significantly more periprocedural ischemic stroke than the coiling procedure alone.

Significant flow velocity reduction at the intracranial aneurysm neck after endovascular treatment leads to favourable angiographic outcome: a prospective study.

BACKGROUND: With widely usage of flow diverter in intracranial aneurysm treatment, some previously used predictors may not be effective in evaluating the recurrence risk. We aimed to comprehensively re-evaluate the predictors of intracranial aneurysm outcome with various endovascular treatment methods and devices. METHODS: This is a prospective registered study. We analysed 6-month and 18-month follow-up angiographic data from the prospective study. Data on patient demographics, aneurysm morphology and type of treatment were recorded. Patient-specific haemodynamic simulations were performed. An unfavourable angiographic outcome was defined as recurrence of aneurysm in cases with coiling or stent-assisted coiling, patency of aneurysm in cases with flow diverters or retreatment during follow-up. RESULTS: In total, 165 patients (177 intracranial aneurysms) with at least one angiographic follow-up data were analysed. For the short-term (6-month) results, after univariate analysis, the demographic, morphological and treatment-related factors did not achieve significantly statistical differences. The reduction ratio (RR) of velocity at aneurysm neck after embolisation was significantly lower in the unfavourable angiographic group than the favourable angiographic outcome group (p=0.002). After the Cox regression analysis, the RR of velocity at aneurysm neck was the only independent factor associated with favourable angiographic outcome (OR 0.028; p=0.001) and had an acceptable area under the curve (0.714) with a clear cut-off value (46.14%). Similarly, for the analysis of midterm (18-month) results, the RR of velocity at the aneurysm neck was the only independent significant factor for the unfavourable angiographic outcome (OR 0.050; p=0.017). The area under the curve was 0.754 and the cut-off value was 48.20%. CONCLUSIONS: The haemodynamics showed an independent effect on angiographic follow-up results and may provide helpful suggestions for clinical practice in the future.

Dynamic contrast-enhanced MRI analysis for prognosis of intracranial dissecting aneurysm with intramural haematoma after endovascular treatment: an observational registry study.

BACKGROUND AND PURPOSE: Intracranial dissecting aneurysm (IDA) with intramural haematoma (IMH) is an intractable cerebrovascular disease. The outcome of IDA with IMH after endovascular treatment varies across different individuals: some IMHs stop growing after endovascular treatment, while others continue to grow, even after embolisation of the parent artery. Currently, the mechanism for the continuous growth of IMH after endovascular treatment is still unclear. Continuous haemorrhage of the vasa vasorum in the IMH is considered to be associated with continuous enlargement of the IMH; however, this theory has not been proved by in vivo imaging. METHODS AND ANALYSIS: This study will establish a prospective cohort of 80 patients who had an IDA with IMH and received endovascular treatment. Demographic characteristics, IDA morphological characteristics and treatment characteristics will be collected prospectively. All patients will undergo dynamic contrast-enhanced MRI (DCE-MRI) before and 6 months after the endovascular treatment. According to the follow-up results of the MRI, the IDAs will be divided into two groups: a haematoma stabilisation group and a haematoma enlargement group. Then, quantitative analysis of the vasa vasorum in the IMH will be performed, and differences between the two groups will be compared with determine the association between DCE-MRI related parameters and the outcomes of IMH changes. ETHICS AND DISSEMINATION: The research was approved by the ethics committee of Beijing Tian Tan Hospital (KY 2019-024-03) and written informed consents would be obtained from all patients included in this study. The results of this study will be disseminated in professional printed media. TRIAL REGISTRATION NUMBER: NCT03940859. Registered: 7 May, 2019. https://clinicaltrials.gov/ct2/show/NCT03940859.

Exome sequencing of 112 trios identifies recessive genetic variants in brain arteriovenous malformations.

BACKGROUND: Brain arteriovenous malformation (BAVM) is a main cause of cerebral hemorrhage and hemorrhagic stroke in adolescents. Morphologically, a BAVM is an abnormal connection between cerebrovascular arteries and veins. The genetic etiology of BAVMs has not been fully elucidated. In this study, we aim to investigate potential recessive genetic variants in BAVMs by interrogation of rare compound heterozygous variants. METHODS: We performed whole exome sequencing (WES) on 112 BAVM trios and analyzed the data for rare and deleterious compound heterozygous mutations associated with the disease. RESULTS: We identified 16 genes with compound heterozygous variants that were recurrent in more than one trio. Two genes (LRP2, MUC5B) were recurrently mutated in three trios. LRP2 has been previously associated with BAVM pathogenesis. Fourteen genes (MYLK, HSPG2, PEAK1, PIEZO1, PRUNE2, DNAH14, DNAH5, FCGBP, HERC2, HMCN1, MYH1, NHSL1, PLEC, RP1L1) were recurrently mutated in two trios, and five of these genes (MYLK, HSPG2, PEAK1, PIEZO1, PRUNE2) have been reported to play a role in angiogenesis or vascular diseases. Additionally, abnormal expression of the MYLK protein is related to spinal arteriovenous malformations. CONCLUSION: Our study indicates that rare recessive compound heterozygous variants may underlie cases of BAVM. These findings improve our understanding of BAVM pathology and indicate genes for functional validation.

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.

Risk Factors of Angiographic Recurrence After Endovascular Coil Embolization of Intracranial Saccular Aneurysms: A Retrospective Study Using a Multicenter Database.

Background: Endovascular therapy of intracranial aneurysms has a high recurrence rate. This study aimed to evaluate the risk factors of recurrence after endovascular coil embolization of intracranial aneurysms. Methods: From January 2014 to May 2015, 504 patients with 558 intracranial aneurysms who were treated by endovascular therapy were recruited from four high-volume centers. We used multivariate Cox proportional hazard regression to evaluate the risk factors associated with the angiographic recurrence of intracranial saccular aneurysms after endovascular coil embolization. Results: Angiographic follow-up was available for 504 patients (558 aneurysms), with a mean duration of 11.42 months. Of the 558 aneurysms, 57 (10.2%) aneurysms showed recurrence. Aneurysm size (p = 0.028), therapy (non-stent assisted coiling or stent-assisted coiling) (p = 0.008), the Raymond scale (p = 0.040), aneurysm rupture status (p < 0.001), and packing density (p < 0.001) showed significant associations with angiographic follow-up outcome. A low packing density was independently associated with aneurysmal recurrence after multivariate Cox proportional hazard regression analysis (p < 0.001). Conclusion: Endovascular treatment is effective for these lesions. Multiple factors could attribute to the aneurysmal recurrence after endovascular coil embolization. The low packing density is the independent risk factor for aneurysmal recurrence. These findings should be verified by larger multicenter and multi-population studies.

Endovascular treatment of bilateral intracranial vertebral artery aneurysms: an algorithm based on a 10-year neurointerventional experience.

BACKGROUND: The management of bilateral intracranial vertebral artery dissecting aneurysms (IVADAs) is controversial, and requires the development of endovascular treatment modalities and principles. We aim to investigate the endovascular treatment strategy and outcomes of bilateral IVADAs. METHODS: We identified all bilateral IVADAs at a high-volume neurointerventional centre over a 10-year period (from January 2009 to December 2018). Radiographic and clinical data were recorded, and a treatment algorithm was derived. RESULTS: Twenty-seven patients with bilateral IVADAs (54 IVADAs in total, 51 unruptured, 3 ruptured) were diagnosed. Four patients (14.8%) received single-stage endovascular treatment, 12 patients (44.4%) with staged endovascular treatment and 11 patients (40.8%) with unilateral endovascular treatment of bilateral IVADAs. Thirty-six IVADAs (85.7%) have complete obliteration at the follow-up angiography. Two of three ruptured IVADAs with stent-assisted coiling recanalised, and had further recoiling. Three patients (11.1%) have intraprocedural or postprocedural complications (two in single-stage and one in staged). Twenty-five patients (92.6%) had a favourable clinical outcome, and two patients (7.4%, all in single-stage) showed an unfavourable clinical outcome at follow-up. For the patients with unilateral reconstructive endovascular treatment, the contralateral untreated IVADAs were stable and had no growth or ruptured during follow-up period. None of all IVADAs had rebleeding during the clinical follow-up. CONCLUSIONS: Endovascular treatment can be performed in bilateral IVADAs with high technical success, high complete obliteration rates and acceptable morbidity/mortality. Contralateral IVADAs had low rates of aneurysm growth and haemorrhage when treated in a staged/delayed fashion.

Hemodynamic differences by increasing low profile visualized intraluminal support (LVIS) stent local compaction across intracranial aneurysm orifice.

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/mm2; case 2, 18.07 pores/mm2). 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.

Discrimination of intracranial aneurysm rupture status: patient-specific inflow boundary may not be a must-have condition in hemodynamic simulations.

BACKGROUND: Computational fluid dynamics (CFD) are important in evaluating the hemodynamics of intracranial aneurysm rupture, and the setting of inflow boundary conditions is critical. We evaluated intracranial aneurysm hemodynamics based on generalized versus patient-specific inflow boundary conditions to examine the effect of different hemodynamic results on the discrimination of intracranial aneurysm rupture status. METHODS: We enrolled 148 patients with 156 intracranial aneurysms. For each included aneurysm, we performed CFD simulation once based on patient-specific and once based on generalized inflow boundary conditions. First, we compared the hemodynamics of intracranial aneurysms based on different inflow boundary conditions. Then, we divided the included aneurysms into a ruptured and unruptured group and compared the hemodynamics between the two groups under patient-specific and generalized inflow boundary conditions. RESULTS: For the hemodynamic parameters using specific inflow boundary conditions, more complex flow (p = 0.002), larger minimum WSS (p = 0.024), lower maximum low WSS area (LSA) (p = 0.038), and oscillatory shear index (p = 0.002) were found. Furthermore, we compared the hemodynamics between ruptured and unruptured groups based on different inflow boundary conditions. We found that the significant hemodynamic parameters associated with rupture status were the same, including the proportion of aneurysms with flow complex and unstable flow and the minimum and maximum of LSA (p = 0.011, p = 0.003, p = 0.001 and p = 0.004, respectively). CONCLUSION: Patient-specific and generalized inflow boundary conditions of aneurysmal hemodynamics resulted in significant differences. However, the significant parameters associated with rupture status were the same in both conditions, indicating that patient-specific inflow boundary conditions may not be necessary for predicting rupture risk.

Stability Assessment of Intracranial Aneurysms Using Machine Learning Based on Clinical and Morphological Features.

Machine learning (ML) as a novel approach could help clinicians address the challenge of accurate stability assessment of unruptured intracranial aneurysms (IAs). We developed multiple ML models for IA stability assessment and compare their performances. We enrolled 1897 consecutive patients with unstable (n = 528) and stable (n = 1539) IAs. Thirteen patient-specific clinical features and eighteen aneurysm morphological features were extracted to generate support vector machine (SVM), random forest (RF), and feed-forward artificial neural network (ANN) models. The discriminatory performances of the models were compared with statistical logistic regression (LR) model and the PHASES score in IA stability assessment. Based on the receiver operating characteristic (ROC) curve and area under the curve (AUC) values for each model in the test set, the AUC values for RF, SVM, and ANN were 0.850 (95% CI 0.806-0.893), 0.858 (95 %CI 0.816-0.900), and 0.867 (95% CI 0.828-0.906), demonstrating good discriminatory ability. All ML models exhibited superior performance compared with the statistical LR and the PHASES score (the AUC values were 0.830 and 0.589, respectively; RF versus PHASES, P < 0.001; RF versus LR, P = 0.038). Important features contributing to the stability discrimination included three clinical features (location, sidewall/bifurcation type, and presence of symptoms) and three morphological features (undulation index, height-width ratio, and irregularity). These findings demonstrate the potential of ML to augment the clinical decision-making process for IA stability assessment, which may enable more optimal management for patients with IAs in the future.

Statin treatment for unruptured intracranial aneurysms study: a study protocol for a double-blind, placebo-controlled trial.

BACKGROUND AND PURPOSE: A large proportion of patients with unruptured intracranial aneurysm (IA) are not suitable for surgical clipping and endovascular treatment. For these patients, anti-inflammatory medications are worth exploring due to inflammation of aneurysmal wall being a major factor in higher risk of rupture. Statin has been proven to reduce inflammation of atherosclerosis and maybe a suitable candidate. This study aimed to evaluate whether atorvastatin will reduce inflammatory of the aneurysm wall measured by the signal index of aneurysm wall enhancement. METHODS AND ANALYSIS: The Statin Treatment for UnruptureD Intracranial anEurysms Study is a single-centre, phase 2, randomised, controlled, double-blind clinical trial. 60 patients with unruptured IAs with aneurysm wall enhancement will be enrolled in Beijing Tiantan Hospital. The patients will be randomised to receive atorvastatin 20 mg or placebo orally per day for 12 months. The primary outcome will be the change in aneurysm wall enhancement measured by the signal index during the 12 months treatment with atorvastatin. The secondary study outcomes will be the change in aneurysm wall enhancement measured by the signal index at 3 months, the changes in aneurysmal morphology and inflammation-related factors (C reactive protein, tumour necrosis factor-α, interleukin-1ß and interleukin-6) at 3 and 12 months. This study is the first to explore the role of atorvastatin in reducing inflammation in unruptured IA, which could lay the groundwork for future phase III trial. ETHICS AND DISSEMINATION: Beijing Tiantan Hospital's Ethics committee approved the research and written informed consents would be obtained from all participant or representative included in this study. TRIAL REGISTRATION NUMBER: NCT04149483.

Factors affecting recurrence and management of recurrent cerebral aneurysms after initial coiling.

OBJECTIVE: To investigate factors affecting recurrence and effects and safety of endovascular retreatment for aneurysms recurrent after embolization. METHODS: Among 815 aneurysms treated with embolization, recurrence was in 114 aneurysms (14.0%). Forty-three recurrent aneurysms were managed with re-embolization. Procedural complications, angiographic, and clinical results of retreatment were analyzed. RESULTS: Patients with recurrent aneurysms were significantly (P < 0.01) younger than without recurrence (51.09 ± 10.46 vs. 53.88 ± 9.61 years). Recurrent aneurysms (n = 114) were significantly (P = 0.00) greater (11.12 ± 8.35 vs. 5.81 ± 3.44 mm) with a significantly (P = 0.00) greater neck (4.34 ± 2.26 vs. 2.90 ± 1.44 mm) than without recurrence. The rupture status of aneurysms significantly (P = 0.00) affected recurrence at follow-up. Significantly (P = 0.00) more aneurysms without recurrence were treated with advanced embolization techniques (81.0% vs. 62.3%) and got complete occlusion at the first embolization than those with recurrence (93.7% vs. 36.8%). In treating 43 recurrent aneurysms, stent-assisted recoiling was used in 48.8% in the first retreatment and 50% in the second and third retreatment procedures. Angiographic follow-up in 38 (88.4%) cases showed complete or near complete occlusion in 30 aneurysms, with the rest eight aneurysms experiencing a second recurrence (21.1%). Of the eight aneurysms with the second recurrence, five underwent the second endovascular retreatment, with complete aneurysm occlusion achieved in three cases (60%), near-complete occlusion in one (20%), and incomplete occlusion in one case at immediate angiography and six-month follow-up. Procedure-related complications occurred in three patients. CONCLUSIONS: Endovascular retreatment of recurrent previously coiled aneurysms is safe and effective even though advanced embolization techniques are frequently involved especially for large and giant aneurysms.

Nomogram for Stability Stratification of Small Intracranial Aneurysm Based on Clinical and Morphological Risk Factors.

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.

Variation of Mass Effect After Using a Flow Diverter With Adjunctive Coil Embolization for Symptomatic Unruptured Large and Giant Intracranial Aneurysms.

Background: Mass effect associated with large or giant aneurysms is an intractable problem for traditional endovascular treatments. Preventing recurrence of aneurysms requires dense coiling, which may aggravate the mass effect. However, the flow diverter (FD) is a new device that avoids the need for dense coiling. This study was performed to investigate whether use of FDs with adjunctive coil embolization can relieve the aneurysmal mass effect and to explore the factors that affect the variation of compressional symptoms. Methods: We retrospectively evaluated patients with compressional symptoms caused by unruptured aneurysms who underwent endovascular treatment with an FD with adjunctive coil embolization at our center from January 2015 to December 2017. Imaging follow-up included digital subtraction angiography (DSA) ranging from 11 to 14 months and magnetic resonance imaging (MRI) ranging from 24 to 30 months; the former was used to evaluate the intracavitary volume, and the latter was used to measure the variation of the mass effect. Follow-up physical examinations were performed to observe variations of symptoms. Results: In total, 22 patients with 22 aneurysms were treated by an FD combined with coil embolization. All 22 patients underwent the last clinical follow-up. Regarding compressional symptoms, 12 (54.54%) patients showed improvement, 6 (27.27%) were fully recovered, and 6 (27.27%) showed improvement but with incomplete cranial palsy. However, five (22.72%) patients showed no change, four (18.18%) showed worsening symptoms compared with their preoperative state, and one (4.55%) died of delayed rupture. Seventeen of the 22 patients underwent MRI. Of these 17 patients, the aneurysm shrank in 13 (76.47%) and no significant change occurred in 4 (23.53%). In the multivariate analysis, a short duration from symptom occurrence to treatment (p = 0.03) and younger patient age (p = 0.038) were statistically significant factors benefiting symptom improvement, and shrinkage of the aneurysm was associated with favorable clinical outcomes (p = 0.006). Conclusions: Use of the FD with adjunctive loose coil embolization might help to alleviate the compressional symptoms caused by intracranial aneurysms. Shrinkage of the aneurysm, a short duration of symptoms, and younger patient age might contribute to favorable outcomes of mass effect-related symptoms.

Corrigendum: Application of the Pipeline Embolization Device for Giant Vertebrobasilar Dissecting Aneurysms in Pediatric Patients.

[This corrects the article DOI: 10.3389/fneur.2019.00179.].