Development Of Cerebral Aneurysms Research Articles

A prospective observational study on hemodynamic risk in cerebral aneurysm growth

Introduction: Hemodynamic factors are thought to play a major role in the development, growth, and rupture of cerebral aneurysms, but the hemodynamics related to enlargement remain unclear. We prospectively enrolled patients with unruptured cerebral aneurysms and performed Computational Fluid Dynamics (CFD) analysis using 3D CT images to investigate differences in hemodynamic environments between aneurysms that grew and those that did not grow over a 3-year period. Methods: This prospective observational study was approved by the National Hospital Organization Central Ethics Review Board. Hemodynamic distributions were examined using ANSYS-CFX software. Patient-specific arterial geometries and inflow velocities were obtained from 3D-CTA and carotid ultrasound Doppler examinations. The distributions of hemodynamic metrics of 17 enlarged and 70 unenlarged aneurysms was compared. In addition, the distributions of hemodynamic metrics of the neck, body, and dome of the aneurysm was also examined in 9 enlarged and 41 non-enlarged cases. A multivariate logistic analysis was performed to investigate the influence of the six hemodynamic metrics, i.e., the time-averaged wall shear stress (TAWSS), time-averaged WSS gradient (TAWSSG), oscillatory shear index (OSI), gradient oscillatory number (GON), transverse WSS (transWSS), and normalized transWSS (NtransWSS) after adjustment forknown risk factors for aneurysm growth, i.e., age, sex, hypertension, smoking history, and aneurysm location, size, and history of subarachnoid hemorrhage. Results: Regarding the distributions of hemodynamic metrics throughout the aneurysm, NtransWSS was significantly higher in the cases with growth than in the cases without growth (odds ratio 2.09, 95% CI 1.02-4.29). the distributions of hemodynamic metrics at each cerebral aneurysm growth site showed that NtransWSS at the dome was significantly higher in the growth cases than in the non-enlargement cases (odds ratio 4.14, 95% CI 1.02-16.80). Conclusion: The data suggest that multidirectional disturbance of wall shear stress is involved in cerebral aneurysm growth, and the disturbance at the dome of the aneurysm may be particularly strongly related. This study was supported by a Grant-in-Aid from the Japanese National Hospital Organization Multi-Center Clinical Research, AMED under grant no. JP15gm0810006h0301 and a JSPS KAKENHI Grant, no. 15K10323. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Abstract WMP116: A P2X4 Inhibitor Dramatically Suppresses the Progression of Cervical Internal Carotid Artery Stenosis - An Attempt to Develop a Therapeutic Agent for Carotid Artery Stenosis Focusing on the Role of Hemodynamic Factors-

Introduction: Medical treatment of internal carotid artery stenosis consists of treatment of underlying conditions such as hypertension, dyslipidemia, and diabetes mellitus, as well as antiplatelet therapy. Hemodynamic studies suggest that endothelial cells sense disturbances and stagnation of blood flow caused by vessel geometry, which trigger the progression of stenosis. Similarly, cerebral aneurysms are known to progress due to hemodynamic effects. We have shown in animal studies that inhibition of P2X4 purinoceptor, an endothelial blood flow sensing-related protein, significantly inhibits the development of cerebral aneurysms. In the present study, we examined whether P2X4 disruption can suppress the progression of internal carotid artery stenosis using an animal model of carotid artery stenosis. Methods: Carotid stenosis coils were implanted in the left carotid artery of 7-week-old P2X4(-/-) and (+/+) mice fed a high-cholesterol diet. Four weeks after placement, the carotid arteries were removed and the occlusion rates of the carotid arteries were compared. The expression of known stenosis-related inflammatory factors was also examined by Western blotting. Results: The carotid occlusion rate was significantly lower in the P2X4 gene-deficient mice, with 5 of 16 occlusions, compared with 9 of 13 occlusions in the control group (p=0.0394, Student's t-test). The expression levels of MCP-1, COX-2, TNFα, and IL-1β were significantly increased in the carotid arteries of P2X4(+/+) mice with the coil compared to the non-operated group (p=0.0073, 0.0012, 0.0016, 0.0031, respectively, Wilcoxon's signed rank test). The carotid arteries of P2X4(-/-) mice with coils showed significantly lower expression of all of the above compared to those of P2X4(+/+) mice (p=0.0233, 0.0020, 0.0098, 0.0046, respectively). Conclusions: These results suggest that inhibition of endothelial blood flow sensing by P2X4 disruption may have reduced the progression of carotid artery stenosis by suppressing the expression of a group of inflammatory factors associated with carotid artery stenosis. This may lead the way to new drug therapies for carotid artery stenosis.

Unilateral rete mirabile in multiple intracranial arteries with ipsilateral agenesis of the internal carotid artery: a case report

BackgroundRete mirabile of the cerebral artery is a rare anomaly, with most previous cases occurring in the middle cerebral artery or internal carotid artery. Here, we present the first report of unilateral rete mirabile in multiple intracranial arteries with ipsilateral internal carotid artery agenesis.Case presentationA 64-year-old Japanese woman was brought to the emergency department of our hospital in a deep coma. Computed tomography of the head showed severe intraventricular hemorrhage with subarachnoid hemorrhage. Computed tomography angiography showed not only congenital left internal carotid artery agenesis, but also rete mirabile of the left posterior communicating artery, the left posterior cerebral artery, and the left anterior cerebral artery. This unilateral vessel anomaly complex may have contributed to the formation of a peripheral aneurysm arising from a perforating branch of the pericallosal artery, which ruptured. The patient underwent urgent bilateral external ventricular drainage, but deteriorated and was declared brain dead.ConclusionsWe report the first case of unilateral rete mirabile in multiple intracranial arteries. Because the cerebral arteries in patients with rete mirabile may be vulnerable, close attention should be paid to the development of cerebral aneurysms.

Computational Fluid Dynamics Analysis Features in Aneurysm Development in Rats.

The investigation of how to control the development and growth of cerebral aneurysms is important for the prevention of subarachnoid hemorrhage. Although there have been several types of research studies on computational fluid dynamics (CFD) analysis of brain aneurysm development and growth, there has been no unified interpretation of the CFD analysis results. The purpose of this study is to clarify the characteristics of CFD analysis results related to the development of cerebral aneurysms using an animal model. Nineteen rat models of cerebral aneurysms were created, and the CFD analysis results between the cerebral aneurysm group [n = 10; the aneurysm was observed on magnetic resonance angiography (MRA) within 10 weeks after aneurysm induction surgery] and the nonaneurysm group (n = 9) were compared. All aneurysms were confirmed on the proximal segment of the left cerebral artery (P1), and the cross-sectional area and curvature of the left P1 were evaluated together. In the cerebral aneurysm group, there was a decrease in wall shear stress (WSS) that is consistent with the location of the aneurysm compared to the nonaneurysm group. The cross-sectional area of the left P1 gradually increased in the aneurysm group but not in the nonaneurysm group. The mean curvature in the entire left P1 was higher in the aneurysm group than in the nonaneurysm group. This study revealed that the development of cerebral aneurysms is due to changes in vascular morphology, namely, an increase in vessel diameter and a high curvature, and a decreased WSS consistent with the site of aneurysm development using this animal model.

Dynamic monitoring of morphological and hemodynamic evolution of small cerebral aneurysms

Highlights. Small cerebral aneurysms (<3 mm), which make up the majority of aneurysms, rupture more frequently, although medium (>3 mm) and giant (>15 mm) aneurysms and have a higher risk of rupture. This article proves for the first time that the rupture risk criteria developed for giant cerebral aneurysms do not work for small aneurysms. The development of small aneurysms in patients was analyzed and measured morphological features of aneurysms were compared with their calculated hydrodynamic characteristics.Aim. To study the dynamics of development of small cerebral aneurysms, to assess the applicability of existing methods for calculating the risk of rupture, to formulate new clarifying hypotheses for calculating the risk of rupture of small cerebral aneurysms.Methods. Patient data were provided by the Federal Center for Neurosurgery, Novosibirsk. CT angiography was performed using a Philips Ingenuite CT scanner (Philips Medical Systems, USA, 128 slices). Aneurysm size dynamics was assessed by measuring three main sizes with an accuracy of 0.1 mm using the IntelliSpace Portal Philips software environment. Numerical calculations were carried out using ANSYS CFX 2020R2.Results. Hemodynamic characteristics change according to the changes of the aneurysm dome. In the case when morphological characteristics of the aneurysm have not changed, a change in the geometry of the patient's circle of Willis (coW) is observed: the curvature of the arteries, the angles of bifurcations (the structure of coW remained unchanged). The PHASES score (absolute risks of rupture for aneurysms) was found to be unusable for the considered aneurysms.Conclusion. This work formulates and morphologically and hydrodynamically confirms for the first time in the volunteers that the change in risk estimates for such aneurysms is fundamentally affected, even insignificantly, by the change in the circle of Willis: a change in the curvature of individual segments of the cerebral arteries, as well as the angles of their bifurcations. The results obtained are aimed at modifying the existing risk criteria for rupture of cerebral aneurysms.

Abstract 122: The P2x4 Inhibitor, Paroxetine Dramatically Prevents Not Only Growth Of Unruptured Cerebral Aneurysms But Also Recanalization After Aneurysm Coil Embolization; A Retrospective Clinical Study, Drug For Aneurysm Study

Introduction: We have suggested that inhibition of P2X4 purinoceptor, which is involved in the endothelial flow sensing mechanism, prevents cerebral aneurysm development and growth in an animal model. Therefore, we retrospectively investigated whether a P2X4 inhibitor, paroxetine used as an antidepressant, has an inhibitory effect on the growth of unruptured cerebral aneurysms and the rate of recanalization after coil embolization. Methods: Among the cases registered in the J-ASPECT Study, the Japanese stroke inpatient reimbursement database, from 2010 to 2019, we searched for cases who were taking paroxetine and with registered unruptured cerebral aneurysm or had undergone cerebral aneurysm coil embolization. We then invited medical centers with these cases to participate in the study and enrolled cases that met the selection criteria by referring to the imaging data and patient background of the cases. The inhibitory effect in the paroxetine-treated group was compared with that of the control group in a multivariate analysis after adjustment for age, gender, and known risk factors. Results: There were 708 cases at 226 facilities nationwide that were potentially matched in the criteria. Seventy-four facilities participated, of which 74 cases at 45 facilities met the selection criteria. A total of 700 control cases were enrolled from 14 core participating centers. The rate of growth incidence of aneurysms was 0.0318 for paroxetine-treated cases (n=36) and 0.0960 for control cases (397). The significant factors (regression coefficients) were paroxetine (-2.26), specific sites of occurrence (-1.28), shape irregularity (1.63), age (0.11), female (1.54), hypertension (-0.55), statin (0.87), and family history of stroke (0.71). The significant factors (odds ratios) in recanalization after 1 year of coil embolization were paroxetine (0.21), complete embolization (0.26), ruptured aneurysm (3.95), and size (1.14). Conclusions: This retrospective study suggests that P2X4 inhibitors including paroxetine may be clinically applicable as agents to inhibit the growth of unruptured cerebral aneurysms and recanalization after 1 year of aneurysm coil embolization. The use of reimbursement information may be useful when collecting very rare cases.

Characteristics and Evolution of Cerebral Aneurysms Among Adults Living With HIV: A Retrospective, Longitudinal Case Series

Objective To describe the characteristics and evolution of cerebral aneurysms in a large cohort of adults living with human immunodeficiency virus (ALWH). Background HIV-associated vasculopathy, which can predispose to cerebral aneurysm development, may result from an inflammatory process whereby HIV viral proteins lead to increased chemoattractant and adhesion particles in the vessel wall. Additionally, adventitial layer inflammation has been shown to be strongly associated with HIV infection and vascular changes that may lead to cerebral aneurysm formation. A recent population-based matched cohort study demonstrated a higher rate of subarachnoid hemorrhage in ALWH. It is important to expand the current understanding of risk factors for aneurysm development and the longitudinal course of patients with HIV-associated vasculopathy to help reduce this source of potential morbidity. Design/Methods The Clinical Data Warehouse was queried for all adult patients evaluated at Boston Medical Center between January 1, 2000, and October 22, 2021 with a history of HIV and at least one cerebral aneurysm. Charts were reviewed for variables including timing of HIV and aneurysm diagnoses, antiretroviral (ART) duration, additional aneurysm risk factors, development of new aneurysms/growth of existing aneurysms, interventions, and clinical outcomes. Results A total of 50 patients (52% female) were identified, including 82 cerebral aneurysms. Forty-six percent of patients with a nadir CD4 count less than 200 cells/mm3 (N = 13) developed new aneurysms or were found to have aneurysm growth over time compared with 29% of patients with a CD4 nadir above 200 cells/mm3 (N = 21). New aneurysms were found or existing aneurysms grew in 67% of those not on ART at time of aneurysm diagnosis (N = 6), 38% of those with inconsistent ART use (N = 8), and 21% of those with consistent ART (N = 19). Conclusions Among ALWH, lower CD4 nadir and inconsistent ART use may contribute to aneurysm formation or growth. Further studies are needed to more thoroughly characterize this trend.

Somatic Variants in SVIL in Cerebral Aneurysms.

While somatic mutations have been well-studied in cancer, their roles in other complex traits are much less understood. Our goal is to identify somatic variants that may contribute to the formation of saccular cerebral aneurysms. We performed whole-exome sequencing on aneurysm tissues and paired peripheral blood. RNA sequencing and the CRISPR/Cas9 system were then used to perform functional validation of our results. Somatic variants involved in supervillin (SVIL) or its regulation were found in 17% of aneurysm tissues. In the presence of a mutation in the SVIL gene, the expression level of SVIL was downregulated in the aneurysm tissue compared with normal control vessels. Downstream signaling pathways that were induced by knockdown of SVIL via the CRISPR/Cas9 system in vascular smooth muscle cells (vSMCs) were determined by evaluating changes in gene expression and protein kinase phosphorylation. We found that SVIL regulated the phenotypic modulation of vSMCs to the synthetic phenotype via Krüppel-like factor 4 and platelet-derived growth factor and affected cell migration of vSMCs via the RhoA/ROCK pathway. We propose that somatic variants form a novel mechanism for the development of cerebral aneurysms. Specifically, somatic variants in SVIL result in the phenotypic modulation of vSMCs, which increases the susceptibility to aneurysm formation. This finding suggests a new avenue for the therapeutic intervention and prevention of cerebral aneurysms.

Alcohol Abuse Associated With Increased Risk of Angiographic Vasospasm and Delayed Cerebral Ischemia in Patients With Aneurysmal Subarachnoid Hemorrhage Requiring Mechanical Ventilation.

ObjectiveAlthough alcohol abuse has been indicated to cause cerebral aneurysm development and rupture, there is limited data on the impact of alcohol abuse on outcomes after an aneurysmal subarachnoid hemorrhage (aSAH). This study aims to investigate whether alcohol abuse increases the risk of angiographic vasospasm and delayed cerebral ischemia (DCI) in critically ill patients with aSAH.MethodsWe conducted a secondary analysis based on a retrospective study in a French university hospital intensive care unit (ICU). Patients with aSAH requiring mechanical ventilation hospitalized between 2010 and 2015 were included. Patients were segregated according to alcohol abuse (yes or no). Multivariable logistic regression analysis was used to identify the independent risk factors associated with angiographic vasospasm and DCI.ResultsThe patient proportion of alcohol abuse was dramatically greater in males than that in females (p < 0.001). The Simplified Acute Physiology Score II (SAPSII) score on admission did not show a statistical difference. Neither did the World Federation of Neurosurgical Societies (WFNS) and Fisher scores. Patients with alcohol abuse were more likely to develop angiographic vasospasm (OR 3.65, 95% CI 1.17–11.39; p = 0.0260) and DCI (OR 3.53, 95% CI 1.13–10.97; p = 0.0294) as evidenced by multivariable logistic regression analysis.ConclusionsIn this study, patients with alcohol abuse are at higher odds of angiographic vasospasm and DCI, which are related to poor prognosis following aSAH. These findings are important for the prevention and clinical management of aSAH.

The role of miR-26a, miR-29a and miR-448-3p in the development of cerebral aneurysm.

Cerebral aneurysms cause the weakening and abnormal expansion of the arterial wall. MicroRNAs (miRNAs) are small noncoding RNAs of approximately 22 nucleotides in length that regulate gene expression. This study aimed to elucidate the role of miRNAs in the development of cerebral aneurysms. This study compared the expression levels of miR-26a, miR-29a and miR-448-3p in 50 samples each of cerebral aneurysm tissues and normal superficial temporal artery tissues. The miRNA expression levels were also compared in terms of aneurysm location and rupture status, i.e., presence or absence of rupture. Expression levels of miR-26a, miR-29a and miR-448-3p were increased in aneurysm tissues compared with normal vascular tissues. No significant difference was found in the miRNA expression levels with respect to aneurysm location or rupture status. This study showed that miR-26a, miR-29a and miR-448-3p overexpression could play an important role in intracranial aneurysm development independent of aneurysm location and rupture status. miR-26a, miR-29a and miR-448-3p could act as potential therapeutic targets in patients with intracranial aneurysms; however, further studies are needed on this issue.

Comparative analysis of aneurysm subtypes associated genes based on protein\u2013protein interaction network

The arterial aneurysm refers to localized dilation of blood vessel wall and is common in general population. The majority of aneurysm cases remains asymptomatic until a sudden rupture which is usually fatal and of extremely high mortality (~ 50–60%). Therefore, early diagnosis, prevention and management of aneurysm are in urgent need. Unfortunately, current understanding of disease driver genes of various aneurysm subtypes is still limited, and without appropriate biomarkers and drug targets no specialized drug has been developed for aneurysm treatment. In this research, aneurysm subtypes were analyzed based on protein–protein interaction network to better understand aneurysm pathogenesis. By measuring network-based proximity of aneurysm subtypes, we identified a relevant closest relationship between aortic aneurysm and aortic dissection. An improved random walk method was performed to prioritize candidate driver genes of each aneurysm subtype. Thereafter, transcriptomes of 6 human aneurysm subtypes were collected and differential expression genes were identified to further filter potential driver genes. Functional enrichment of above driver genes indicated a general role of ubiquitination and programmed cell death in aneurysm pathogenesis. Especially, we further observed participation of BCL-2-mediated apoptosis pathway and caspase-1 related pyroptosis in the development of cerebral aneurysm and aneurysmal subarachnoid hemorrhage in corresponding transcriptomes.

Diabetes is not protective against the formation of unruptured cerebral aneurysm

ObjectivesDiabetes appears to decrease the risk of subarachnoid hemorrhage. However, it is not clear whether diabetes decreases the risk of aneurysm formation. The aim of our study to evaluate the risk of unruptured cerebral aneurysm in patients with diabetes mellitus. MethodsWe used data from participants who underwent brain magnetic resonance angiography (MRA) and laboratory tests at the Healthcare System Gangnam Center of Seoul National University Hospital between January 2010 and December 2013. From the 17,368 participants who underwent brain MRA, we analyzed 16,337 subjects whose diabetes status could be identified. ResultsThe number of participants with diabetes was 2299 (14.1%). The proportion of participants with cerebral aneurysms was 2.3% in the diabetic group and 2.7% in the non-diabetic group, which was not significantly different (P = 0.225). There were no significant differences in the size, location, and multiplicity of aneurysms between the diabetes and control groups. In multivariate logistic regression, older age showed significant risk effects on cerebral aneurysms, but female sex, hypertension, diabetes, obesity, and smoking did not show significant risk effects. ConclusionIn this study, diabetes did not affect the risk of cerebral aneurysm formation. In addition, neither smoking, nor hypertension was a significant risk factor for unruptured cerebral aneurysms. The lack of association between cerebral aneurysm and the traditional risk factors for subarachnoid hemorrhage requires further study. Risk factors for cerebral aneurysm development and those for cerebral aneurysm rupture may be different.

Relationship between cerebral aneurysms and variations in cerebral basal arterial network: a morphometric cross-sectional study in Computed Tomography Angiograms from a neurointerventional unit

ObjectiveSegments of cerebral basal arterial network (CBAN) dampen the peak pressure in blood flowing through these arteries, thus minimising the chances of development of cerebral aneurysms. The objective of this...

MicroRNA-124-5p delays the progression of cerebral aneurysm by regulating FoxO1.

Cerebral aneurysm (CA) is a common brain disease, and the development of cerebral aneurysm is driven by inflammation and hemodynamic stress. MicroRNA (miR)-124-5p is reported to be associated with inflammatory response in brain disease such as cerebral ischemia-reperfusion injury. However, the function and molecular mechanism of miR-124-5p in CA are not clear, thus, the effects of miR-124-5p on inflammatory response in CA were explored. Firstly, the expression of miR-124-5p in the peripheral blood of patients with CA and the control group was detected by reverse transcription-quantitative PCR. Then, the human umbilical vein endothelial cells (HUVECs) were used as an in vitro model system and stimulated with interleukin (IL)-1β to simulate the inflammatory environment of CA, and the expression of miR-124-5p was detected. Next, the effect of miR-124-5p on the migration and invasion of HUVECs was detected using Transwell assays. Meanwhile, the function of miR-124-5p on various inflammatory factors was determined by western blotting and enzyme-linked immunosorbent assay (ELISA). Next, the TargetScan website was used to predict FoxO1 as a target gene of miR-124-5p, and this target association was validated by double luciferase reporter assay and western blotting. Finally, the interaction of miR-124-5p with FoxO1 in CA was measured by Transwell western blotting and ELISA assays. The results showed that the expression level of miR-124-5p in the peripheral blood of patients with CA was lower compared with that of control group, and the miR-124-5p in HUVECs stimulated by IL-1β was less compared with that in normal HUVECs. Besides, miR-124-5p could inhibit the migration and invasion abilities of HUVECs and the release of inflammatory factors. Additionally, the overexpression of miR-124-5p was able to inhibit the expression of FoxO1. miR-124-5p-inhibitor promoted the migration and invasion of HUVECs, as well as inflammatory response, which was weakened following the introduction of FoxO1 small interfering RNA. Overall, the present study demonstrated that miR-124-5p could prevent the occurrence and development of cerebral aneurysm by downregulating the expression of FoxO1.

Wall shear stress gradient is independently associated with middle cerebral artery aneurysm development: a case-control CFD patient-specific study based on 77 patients

BackgroundPreviously published computational fluid dynamics (CFD) studies regarding intracranial aneurysm (IA) formation present conflicting results. Our study analysed the involvement of the combination of high wall shear stress (WSS) and a positive WSS gradient (WSSG) in IA formation.MethodsWe designed a case-control study with a selection of 38 patients with an unruptured middle cerebral artery (MCA) aneurysm and 39 non-aneurysmal controls to determine the involvement of WSS, oscillatory shear index (OSI), the WSSG and its absolute value (absWSSG) in aneurysm formation based on patient-specific CFD simulations using velocity profiles obtained from transcranial colour-coded sonography.ResultsAmong the analysed parameters, only the WSSG had significantly higher values compared to the controls (11.05 vs − 14.76 [Pa/mm], P = 0.020). The WSS, absWSSG and OSI values were not significantly different between the analysed groups. Logistic regression analysis identified WSS and WSSG as significant co-predictors for MCA aneurysm formation, but only the WSSG turned out to be a significant independent prognosticator (OR: 1.009; 95% CI: 1.001–1.017; P = 0.025). Significantly more patients (23/38) in the case group had haemodynamic regions of high WSS combined with a positive WSSG near the bifurcation apex, while in the control group, high WSS was usually accompanied by a negative WSSG (14/39). From the analysis of the ROC curve for WSSG, the area under the curve (AUC) was 0.654, with the optimal cut-off value −0.37 Pa/mm. The largest AUC was recognised for combined WSS and WSSG (AUC = 0.671). Our data confirmed that aneurysms tend to form near the bifurcation apices in regions of high WSS values accompanied by positive WSSG.ConclusionsThe development of IAs is determined by an independent effect of haemodynamic factors. High WSS impacts MCA aneurysm formation, while a positive WSSG mainly promotes this process.

Morphologic Variations in the Circle of Willis as a Risk Factor for Aneurysm Rupture in the Anterior and Posterior Communicating Arteries

Intracranial aneurysms are acquired abnormal vascular dilations. The most dangerous complication of a cerebral aneurysm is its rupture, with a high rate of mortality. This study aimed to determine whether there is an association between anatomic variations in the circle of Willis and ruptured aneurysms in the anterior and posterior communicating arteries. A cross-sectional study of adult patients with a diagnosis of intracranial aneurysm was carried out between March 2015 and March 2019. The patients were divided into groups of ruptured or unruptured aneurysm in the anterior and posterior communicating arteries. A total of 132 patients with anterior and posterior communicating artery aneurysms were included. The presence of anatomic variation in the circle of Willis presented a statistically significant association with ruptured aneurysms (odds ratio [OR], 2.28; 95% confidence interval [CI], 1.11-4.65; P= 0.024). There was a statistically significant difference between the presence of nonspherical aneurysm and rupture (OR, 6.9; 95% CI, 3.12-15.48; P < 0.0001). Multivariate logistic regression observed smoking (OR, 2.4; 95% CI, 1.01-5.9; P= 0.4), anterior complex variations (OR, 2.68; 95% CI, 1.01-7.18; P < 0.04), and nonspherical morphology (OR, 4.7; 95% CI, 1.93-11.45; P= 0.001) presented a statistically significant association with the rupture. Our results suggest that the studied variations of the circle of Willis and nonspherical morphology, in addition to playing a role in the development of cerebral aneurysms, may contribute to their rupture.

Low Carotid Flow Pulsatility Index Correlates With the Presence of Unruptured Intracranial Aneurysms.

BackgroundWe assessed cases of incidental unruptured intracranial aneurysm (UIA) discovered on screening magnetic resonance angiography to identify hemodynamic and atherosclerotic risk factors.Methods and ResultsThe data of 1376 healthy older subjects (age range, 31–91 years) without cerebro‐ or cardiovascular diseases who underwent brain magnetic resonance angiography as part of a medical checkup program at a health screening center were examined retrospectively. We looked for an increase in classical risk factors for UIAs (age, sex, hypertension, and smoking) and laboratory data related to lifestyle diseases among subjects with UIAs. Brachial‐ankle pulse wave velocity, central systolic blood pressure, radial augmentation index, and carotid flow pulsatility index were also compared between those with and without UIAs. We found UIAs in 79 (5.7%) of the subjects. Mean age was 67.1±9.0 years, and 55 (70%) were women. Of the 79 aneurysms, 75 (95%) were in the anterior circulation, with a mean diameter of 3.1 mm (range, 2.0–8.0 mm). Subjects with UIAs were significantly older and had more severe hypertension. The carotid flow pulsatility index was significantly lower in subjects with UIAs and negatively and independently correlated with UIAs. Tertile analysis stratified by carotid flow pulsatility index revealed that subjects with lower indices had higher levels of low‐density lipoprotein cholesterol.ConclusionsThe presence of UIAs correlated with lower carotid flow pulsatility index and elevated low‐density lipoprotein cholesterol in the data from a population of healthy older volunteers. A reduced carotid flow pulsatility index may affect low‐density lipoprotein cholesterol elevation by some molecular pathways and influence the development of cerebral aneurysms. This may guide aneurysm screening indications for institutions where magnetic resonance angiography is not routine.

Association between longitudinal blood pressure and prognosis after treatment of cerebral aneurysm: A nationwide population-based cohort study.

High blood pressure is a major risk factor for the development and rupture of cerebral aneurysm. Endovascular coil embolization and surgical clipping are established procedures to treat cerebral aneurysm. However, longitudinal data of blood pressure after the treatment of cerebral aneurysm and its impact on long-term prognosis are not well known. This retrospective cohort study included 1275 patients who underwent endovascular coil embolization (n = 558) or surgical clipping (n = 717) of cerebral aneurysm in 2002-2015 using the nationwide health screening database of Korea. Systolic and diastolic blood pressure of patients were repeatedly obtained from the nationwide health screening program. We performed a multivariate time-dependent Cox regression analysis of the primary composite outcome of stroke, myocardial infarction, and all-cause death. During the mean follow-up period of 6.13 ± 3.41 years, 89 patients suffered the primary outcome. Among the total 3546 times of blood pressure measurement, uncontrolled high blood pressure (systolic ≥140 mmHg or diastolic ≥90 mmHg) was 22.9%. There was a significantly increased risk of primary outcome with high systolic (adjusted HR [95% CI] per 10 mmHg, 1.16 [1.01-1.35]) and diastolic (adjusted HR [95% CI] per 10 mmHg, 1.32 [1.06-1.64]) blood pressure. High blood pressure is prevalent even in patients who received treatment for cerebral aneurysm, which is significantly associated with poor outcome. Strict control of high blood pressure may further improve the prognosis of patients with cerebral aneurysm.

Study of the Hemodynamics Effects of an Isolated Systolic Hypertension (ISH) Condition on Cerebral Aneurysms Models, Using FSI Simulations

Hemodynamics is recognized as a relevant factor in the development and rupture of cerebral aneurysms, so further studies related to different physiological conditions in human represent an advance in understanding the pathology and rupture risk. In this paper, Fluid-structure interaction simulations (FSI) were carried out in six models of cerebral aneurysms, in order to study the hemodynamics effects of an isolated systolic hypertension (ISH) condition and compare it to a normal or normotensive pressure condition and a higher hypertension condition. Interestingly, the ISH condition showed, in general, the greatest hemodynamics changes, evidenced in the Time-Averaged Wall Shear Stress (TAWSS), Oscillatory Shear Index (OSI), and Relative Residence Time (RRT) parameters, with respect to a normal condition. These results could imply that a not high-pressure condition (ISH), characterized with a different shape and an abrupt change in its diastolic and systolic range may present more adverse hemodynamic changes compared to a higher-pressure condition (such as a hypertensive condition) and therefore have a greater incidence on the arterial wall remodeling and rupture risk.

Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats.

Our current research aims to examine whether protocatechuic acid (PCA) can be used as a therapeutic agent for the development of cerebral aneurysm (CA) and to elucidate the mechanisms behind this. We assessed the effects of PCA at 50 and 100 mg/kg on the activation of signaling pathways for tissue necrosis factor (TNF)-α/nuclear factor (NF)-κB/nuclear factor erythroid 2 (Nrf-2) on progression and development in an elastase-induced CA model, accompanied by a high-salt diet to induce hypertension. The expression of inflammatory cytokines, chemokines, tumor necrosis factor-α, interleukins (IL)-8, IL-17, IL-6, IL-1β, and matrix metalloproteinase (MMP)-2 and MMP-9 was analyzed by ELISA, western blot, and reverse transcriptase quantative polymerase chain reaction. The expression levels of antioxidant enzymes and translocation of Nrf-2 were also determined. The group treated with PCA demonstrated a significant (P < 0.05) decrease in the aneurysmal size in rats compared to the CA-induced group. We found that PCA treatment suppressed the invasion of macrophage and activation of TNF-α/NF-κB/Nrf-2 signaling pathways. There was a significant decrease (P < 0.05) in pro-inflammatory cytokine and chemokine levels in a dose-dependent manner. We found that PCA treatment exerts protective effects by suppressing the development and progression of CA through the inhibition of inflammatory responses in macrophages via TNF-α/NF-κB/Nrf-2 signaling pathways, thus demonstrating that PCA can act as a treatment for CA.