Risk factors for the progression of unruptured intracranial aneurysms in patients followed by CT/MR angiography.

BACKGROUND: The progression of an unruptured intracranial aneurysm (UIA) is associated with a higher rupture risk. The aim of this study was to identify the risk factors for the progression of UIAs among Chinese adults and compare them with the ELAPSS (Earlier subarachnoid hemorrhage, IA Location, Age, Population, IA Size and Shape) score. METHODS: Four hundred thirty-eight consecutive patients with 491 UIAs were followed and reviewed retrospectively from August 2011 to November 2019. Follow-up images of the UIAs were used to determine changes in IA size and shape. Patients and IAs were divided into non-progression and progression groups. In addition to the clinical characteristics of the patients, the features of the IAs (e.g., size and shape) were evaluated by computed tomography angiography (CTA) or magnetic resonance angiography (MRA). Independent risk factors for UIA progression were studied using multiple Cox proportional hazards regression analysis. In addition, the diagnostic value of the ELAPSS score for the prediction of UIA progression was calculated. RESULTS: Seventy-two IAs in 68 patients progressed during a mean follow-up time of 24.2±19.68 months. IAs located at the bifurcation [odds ratio (OR) 2.600], with an irregular shape (OR 2.981) or having a high aspect ratio (AR, OR 2.430) were correlated with progression. Based on these three factors, the threshold value of our predictive score was 0.5, and the area under the curve (AUC), sensitivity and specificity were 0.756, 93.1% and 40.6%, respectively, while the AUC, sensitivity and specificity of the ELAPSS score were 0.711, 55.6%, and 75.2%, respectively. CONCLUSIONS: IAs located at the bifurcation, with an irregular shape and with an elevated AR are risk factors for UIA progression in the Chinese population. Our predictive score is of great value in predicting the risk of UIA progression.

Risk of Rupture of Small Intracranial Aneurysms (≤5 mm) Among the Chinese Population.

OBJECTIVE: We sought to develop a model to predict the risk of small intracranial aneurysm (SIA; ≤5 mm) rupture among Chinese adults and to compare the score predicted by our model with the PHASES (population, hypertension, age, size, earlier subarachnoid hemorrhage, aneurysm site) score. METHODS: From August 2011 to June 2015, 366 patients with 394 SIAs were retrospectively evaluated and followed up for ≥5 years. The clinical characteristics of the patients were reviewed from their medical records, and the SIA features were evaluated from the imaging studies. The independent risk factors for SIA rupture were studied using multiple Cox proportional hazards regression analysis. The diagnostic value of the PHASES score for the prediction of SIA rupture was also calculated. RESULTS: Six SIAs in 6 different patients had ruptured during a mean follow-up of 6.4 years. An irregular shape (odds ratio [OR], 31.464), a high aspect ratio (OR, 40.573), and a high size ratio (OR, 20.541) increased the risk of rupture. The predictive score incorporated these three factors. The threshold was 1.5, and the area under the curve, sensitivity, and specificity were 0.986, 100%, and 94.6%, respectively. For the PHASES score, the area under the curve, sensitivity, and specificity were 0.702, 83.3%, and 62.1%, respectively. CONCLUSIONS: An irregular shape, a high aspect ratio, and a high size ratio were associated with SIA rupture in the Chinese population. Our predictive score is of great value in predicting the risk of SIA rupture.

Wall enhancement ratio determined by vessel wall MRI associated with symptomatic intracranial aneurysms.

PURPOSE: To study the association of the enhancement ratio (ER) of aneurysmal wall enhancement (AWE) with symptomatic intracranial aneurysms (IAs), we hypothesized that the ER of AWE would be stronger in symptomatic IAs than in asymptomatic IAs, as assessed by high-resolution magnetic resonance imaging (HRMRI). MATERIALS AND METHODS: Between February 2016 and February 2018, 80 consecutive patients with 89 unruptured IAs were reviewed. Patients and IAs were divided into symptomatic and asymptomatic groups. In addition to the clinical characteristics, the IA features (e.g., size, shape) were evaluated via computed tomography angiography, while the ER and enhanced patterns were evaluated by HRMRI. Multiple logistic regression analysis was performed to determine the independent risk factors for symptomatic IAs. Receiver operating characteristic curve analysis was used for the final model to obtain the optimal thresholds. RESULTS: Multiple logistic regression analysis indicated that only the ER was associated with symptomatic IAs. The threshold value of the ER was 60.5%. CONCLUSIONS: A higher ER was more frequently identified in symptomatic IAs. More attention should be paid to this factor in the management of IAs.

Relationships between aneurysmal wall enhancement and conventional risk factors in patients with intracranial aneurysm: A high-resolution MRI study.

BACKGROUND AND PURPOSE: Aneurysmal wall enhancement (AWE) is thought to reflect wall inflammation and is a novel imaging biomarker for intracranial aneurysm (IA) risk evaluation. However, the relationship between AWE and other conventional risk factors (e.g., size) remains unclear. The aim of this study was to investigate the relationship between AWE and other risk factors. MATERIAL AND METHODS: Seventy-six consecutive patients from February 2016 to April 2017 with 88 unruptured IAs were reviewed. Patients and IAs were divided into with AWE and without AWE groups according to high-resolution magnetic resonance imaging (HRMRI) images. In addition to the patients' clinical characteristics, the features of the IAs (e.g., size and aspect ratio (AR)) were evaluated via computed tomography angiography. Multiple logistic regression analysis was used to identify the association between AWE and other risk factors. A receiver operating characteristic curve analysis was performed for the final model to obtain optimal thresholds. RESULTS: IAs with an irregular shape (OR 12.544) and a high AR (OR 32.891) were associated with AWE. The threshold value of the AR was 1.05. CONCLUSIONS: AWE on contrast-enhanced HRMRI was correlated with IAs with an irregular shape and a high AR. AWE may be a marker of instability and even risk of rupture.

Predictive Value of Combined LIPS and ANG-2 Level in Critically Ill Patients with ARDS Risk Factors.

To investigate the predictive value of the acute physiology and chronic health evaluation 2 (APACHE2) score and lung injury prediction score (LIPS) for acute respiratory distress syndrome (ARDS) when combined with biomarkers for this condition in patients with ARDS risk factors. In total, 158 Han Chinese patients with ARDS risk factors were recruited from the Respiratory and Emergency Intensive Care Units. The LIPS, APACHE2 score, primary diagnosis at admission, and ARDS risk factors were determined within 6 h of admission, and PaO2/FiO2 was determined on the day of admission. Blood was collected within 24 h of admission for the measurement of angiopoietin-2 (ANG-2), sE-selectin, interleukin-6 (IL-6), and interleukin-8 (IL-8) levels. ARDS was monitored for the next 7 days. Univariate and multivariate analyses and receiver operating characteristic (ROC) analyses were employed to construct a model for ARDS prediction. Forty-eight patients developed ARDS within 7 days of admission. Plasma ANG-2 level, sE-selectin level, LIPS, and APACHE2 score in ARDS patients were significantly higher than those in non-ARDS patients. ANG-2 level, LIPS, and APACHE2 score were correlated with ARDS (P < 0.001, P < 0.006, and P < 0.042, resp.). When the APACHE2 score was used in combination with the LIPS and ANG-2 level to predict ARDS, the area under the ROC curve (AUC) was not significantly increased. Compared to LIPS or ANG-2 alone, LIPS in combination with ANG-2 had significantly increased positive predictive value (PPV) and AUC for the prediction of ARDS. In conclusion, plasma ANG-2 level, LIPS, and APACHE2 score are correlated with ARDS. Combined LIPS and ANG-2 level displays favorable sensitivity, specificity, and AUC for the prediction of ARDS.

Computed Tomography Angiography Evaluation of Risk Factors for Unstable Intracranial Aneurysms.

OBJECTIVE: To evaluate risk factors for instability in intracranial aneurysms (IAs) using computed tomography angiography (CTA). METHODS: A total of 614 consecutive patients diagnosed with 661 IAs between August 2011 and February 2016 were reviewed. Patients and IAs were divided into stable and unstable groups. Along with clinical characteristics, IA characteristics were evaluated by CTA. Multiple logistic regression analysis was used to identify the independent risk factors associated with unstable IAs. Receiver operating characteristic (ROC) curve analysis was performed on the final model, and optimal thresholds were obtained. RESULTS: Patient age (odds ratio [OR], 0.946), cerebral atherosclerosis (CA; OR, 0.525), and IAs located at the middle cerebral artery (OR, 0.473) or internal carotid artery (OR, 0.512) were negatively correlated with instability, whereas IAs with irregular shape (OR, 2.157), deep depth (OR, 1.557), or large flow angle (FA; OR, 1.015) were more likely to be unstable. ROC analysis revealed threshold values of age, depth, and FA of 59.5 years, 4.25 mm, and 87.8°, respectively. CONCLUSIONS: The stability of IAs is significantly affected by several factors, including patient age and the presence of CA. IA shape and location also have an impact on the stability of IAs. Growth into an irregular shape, with a deep depth, and a large FA are risk factors for a change in IAs from stable to unstable.

Wall enhancement ratio and partial wall enhancement on MRI associated with the rupture of intracranial aneurysms.

OBJECTIVES: To evaluate the risk factors for rupture of intracranial aneurysms (IAs) using high resolution MRI (HRMRI). METHODS: 91 consecutive patients with 106 IAs were reviewed from February 2016 to April 2017. Patients and IAs were divided into ruptured and unruptured groups. In addition to the clinical characteristics of the patients, the features of IAs (eg, shape) were evaluated by CT angiography, whereas wall thickness, enhanced patterns, and enhancement ratio (ER) were evaluated by MRI. Multiple logistic regression analysis was used to identify independent risk factors associated with the rupture of IAs. Receiver operating characteristic curve analysis was performed on the final model, and the optimal thresholds were obtained. RESULTS: ER (OR 6.638) and partial wall enhancement (PWE) (OR 6.710) were not markers of aneurysms more prone to rupture, but simply were more commonly found in the ruptured aneurysm cohort. The threshold value for ER was 61.5%. CONCLUSIONS: ER (≥61.5%) and IAs with PWE are better predictors of rupture. Increased attentions should be paid to these factors during assessment of IA rupture.

Risk Factors for the Rupture of Intracranial Aneurysms Using Computed Tomography Angiography.

OBJECTIVE: To study the clinical and morphologic characteristics associated with risk factors for the rupture of intracranial aneurysms (IAs). METHODS: A total of 1115 consecutive patients with 1282 IAs were reviewed from August 2011 to February 2016. The patients and IAs were divided into ruptured and unruptured groups. Based on the clinical and morphologic findings, the risk factors for IA rupture were assessed using statistical methods. RESULTS: Age, hypertension, diabetes mellitus, and cerebral atherosclerosis were associated with ruptured IAs. IAs located in the anterior cerebral artery, the anterior communicating artery, the posterior communicating artery, and the internal carotid artery were associated with ruptured IAs. Ruptures were also associated with arterial bifurcations, irregular aneurysm shapes, and all continuous data, except neck width. Binary logistic regression showed that IAs located at bifurcations (odds ratio [OR], 1.804), with irregular shapes (OR, 4.677), with high aspect ratios (ARs) (OR, 5.037) or with small mean diameters (MDs) (OR, 0.495) are more prone to rupture. Receiver operating characteristic analysis showed that the threshold values of the AR and MD were 1 and 3.70 mm, respectively. CONCLUSIONS: Morphologic characteristics, such as being located at bifurcations, being irregularly shaped, having a high AR (>1), and having a small MD (<3.70 mm), were better predictors of rupture.

Regulatory factor X1 depresses ApoE-dependent Aß uptake by miRNA-124 in microglial response to oxidative stress.

Decreased proteolytic clearance of soluble amyloid ß (Aß) in microglia affects Aß accumulation on Alzheimer's disease progression. However, the potential molecular mechanism by which microglial Aß uptake is regulated remains unclear. In this study, we identified a microRNA, miR-124, that was down-regulated in aging with a function in regulating apolipoprotein E (ApoE)-dependent Aß uptake by targeting regulatory factor X1 (RFX1) transcripts on BV2 microglia cell. Decreased expression of miRNA-124 in BV2 cells exposed to mild hydrogen peroxide increased RFX1 protein level and decreased the expression of ApoE, a gene which has been suggested to enhance cellular Aß uptake in microglia. We also identified a miR-124 binding site in the 3'-UTR of RFX1 mRNA and a RFX1 binding site in the first intron of ApoE gene. Furthermore, interfering this signaling pathway by knocking down RFX1 significantly improved Aß uptake in BV2 cells. These data demonstrate the mechanism through which decreased miR-124 expression under oxidative stress slowed Aß uptake and suggest that RFX1 might be a target for improving Aß clearance during aging.

Expression and cellular distribution of vascular endothelial growth factor-C system in cortical tubers of the tuberous sclerosis complex.

Cortical tubers are malformations of cortical development in patients with tuberous sclerosis complex (TSC), and highly associated with pediatric intractable epilepsy. Recent evidence has shown that signaling mediated through vascular endothelial growth factor-C (VEGF-C) and its receptors, VEGFR-2 and VEGFR-3, has direct effects on both neurons and glial cells. To understand the potential role of VEGF-C system in the pathogenesis of cortical tubers, we investigated the expression patterns of VEGF-C signaling in cortical tubers compared with age-matched normal control cortex (CTX). We found that VEGF-C, VEGFR-2 and VEGFR-3 were clearly upregulated in tubers at both the mRNA and protein levels, compared with CTX. The in situ hybridization and immunostaining results demonstrated that VEGF-C, VEGFR-2 and VEGFR-3 were highly expressed in dysplastic neurons (DNs), giant cells (GCs) and reactive astrocytes within tubers. Most DNs/GCs expressing VEGF-C and its receptors co-labeled with neuronal rather than astrocytic markers, suggesting a neuronal lineage. In addition, protein levels of Akt-1, p-Bad and ERK1/2, the important downstream factors of the VEGF-C pathway, were significantly increased in cortical tubers, indicating involvement of VEGF-C-dependent prosurvival signaling in cortical tubers. Taken together, our results suggest a putative role for the VEGF-C signaling pathway in the pathogenesis of cortical tubers.