Rupture Of Intracranial Aneurysms Research Articles

Emerging Treatments for Subarachnoid Hemorrhage.

The current landscape of therapeutic strategies for subarachnoid hemorrhage (SAH), a significant adverse neurological event commonly resulting from the rupture of intracranial aneurysms, is rapidly evolving. Through an in-depth exploration of the natural history of SAH, historical treatment approaches, and emerging management modalities, the present work aims to provide a broad overview of the shifting paradigms in SAH care. By synthesizing the historical management protocols with contemporary therapeutic advancements, patient-specific treatment plans can be individualized and optimized to deliver outstanding care for the best possible SAH-related outcomes.

Expression of Concern: Apc gene suppresses intracranial aneurysm formation and rupture through inhibiting the NF-κB signaling pathway mediated inflammatory response.

Expression of Concern: Apc gene suppresses intracranial aneurysm formation and rupture through inhibiting the NF-κB signaling pathway mediated inflammatory response.

An In vivo Pilot Study to Estimate the Swelling of the Aneurysm Wall Rabbit Model Generated with Pulsed Fluid Against the Aneurysm Wall.

This study addresses the critical issue of evaluating the risk of rupture of unruptured intracranial aneurysms (UIAs) through the assessment of the mechanical properties of the aneurysm wall. To achieve this, an original approach based on the development of an in vivo deformation device prototype (DDP) of the vascular wall is proposed. The DDP operates by pulsing a physiological fluid onto the vascular wall and measuring the resulting deformation using spectral photon counting computed tomography (SPCCT) imaging. In this preliminary study conducted on a rabbit animal model, an aneurysm was induced on the carotid artery, followed by deformation of the aneurysm sac wall using the DDP. The change in luminal volume of the aneurysm sac induced by the deformation of the vascular wall was then quantified. The initial experimental results demonstrated an increase in the luminal volume of the aneurysm sac in relation to the increased flow rate of the fluid pulsed by the DDP onto the arterial wall. Measurement of the pressure generated by the DDP in relation to the different flow rate values imposed by the pulsation system revealed experimental values of the same order of magnitude as dynamic blood pressure. Furthermore, theoretical pressure values on the deformed area, calculated using Euler's theorem, appeared to be correlated with experimental pressure measurements. This equivalence between theory and experiment is a key element in the use of the DDP for estimating the mechanical properties of the vascular wall, particularly for the use of finite element models to characterise the stress state of the deformed vascular wall. This preliminary work thus presents a novel, innovative, and promising approach for the evaluation and management of the risk of rupture of unruptured intracranial aneurysms.

Artificial intelligence applied to development of predictive stability model for intracranial aneurysms

BackgroundWe aimed to develop multiple machine learning models to predict the risk of early intracranial aneurysms (IAs) rupture, evaluate and compare the performance of predictive models.MethodsInformation related to patients diagnosed with IA by CT angiography and clinicians in Central hospital of Dalian University of Technology from January 2010 to June 2022 was collected, including clinical characteristics, blood indicators and IA morphological parameters. IA with rupture or maximum growth ≥ 0.5 mm within 1 month of first diagnosis was considered unstable. The relevant factors affecting IA stability were screened and predictive models were developed based on the above three levels, including random forest (RF), support vector machine (SVM), and artificial neural network (ANN). Sensitivity, specificity, accuracy and area under curve (AUC) value were used to evaluate the predictive models.ResultsA total of 989 IA patients were included in the study, including 561 stable patients and 428 unstable patients. For RF models, the training set showed that sensitivity, specificity, accuracy and the AUC values were 72.8–83.7%, 76.9–86.9%, 75.1–84.1% and 0.748 (0.719–0.778)–0.839 (0.814–0.864), respectively; after test set validation, the results were 71.9–78.8%, 75.0–84.0%, 73.6–81.1% and 0.734 (0.688–0.781)–0.809 (0.768–0.850), respectively. For SVM models, the training set were 66.0–80.2%, 76.5–85.5%, 71.7–82.3%, 0.712 (0.682–0.743)–0.913 (0.884–0.924), respectively; the test set were 44.2–78.3%, 63.4–84.4%, 57.9–80.9%, 0.699 (0.651–0.747)–0.806 (0.765–0.848), respectively. For ANN models, the training set were 66.8–83.0%, 75.3–82.3%, 71.6–82.1%, 0.783 (0.757–0.808)–0.897 (0.879–0.914); the test set were 63.1–76.3%, 65.5–84.0%, 64.4–80.6%, 0.680 (0.593–0.694)–0.860 (0.821–0.899). The results of variable importance showed that age, white blood cell count (WBC) and uric acid (UA) played an important role in predicting the stability of IA.ConclusionsThe predictive stability models of IA based on three artificial intelligence methods shows good clinical application. Age, WBC and UA played an important role in predicting the IA stability, and were potentially important predictors.

The value of systemic immune inflammation index, white blood cell to platelet ratio, and homocysteine in predicting the instability of small saccular intracranial aneurysms

Inflammation has a destructive effect on the homeostasis of the vascular wall, which is involved in the formation, growth, and rupture of human intracranial aneurysms (IAs) disease progression. However, inflammation-related markers have not been well studied in the risk stratification of unruptured IAs. The purpose of this study was to investigate the predictive value of serum inflammatory markers in the unstable progression of small saccular intracranial aneurysms (SIAs). This study retrospectively included 275 patients with small SIAs (aneurysm diameter less than or equal to 7 mm), to compare the level difference of serum inflammatory complex marker systemic immune-inflammatory index (SII), white blood cell to platelet ratio (WPR), and homocysteine (Hcy) in patients with stable (asymptomatic unruptured) and unstable (symptomatic unruptured, ruptured) small SIAs. 187 patients (68%) had aneurysm-related compression symptoms and rupture outcomes. In the multivariate logistic regression after adjusting for baseline differences, SII, WPR, and Hcy were independent risk factors for the instability of small SIAs, the prediction model combined with other risk factors (previous stroke history, aneurysm irregularity) showed good predictive ability for the instability of small SIAs, with an area under the curve of 0.905. In addition, correlation analysis showed that SII, WPR, and Hcy also had significant differences in patients with symptomatic unruptured and ruptured small SIAs, and higher inflammation levels often promoted the disease progression of small SIAs. Higher levels of SII, WPR and Hcy can be used as independent predictors of instability of small SIAs. As an economical and convenient biomarker, it is crucial for clinical treatment strategies of stable small SIAs.

Location specific rupture risk of intracranial aneurysms: case of ophthalmic aneurysms

BackgroundAneurysm location is a key element in predicting the rupture risk of an intracranial aneurysm. A common impression suggests that pure ophthalmic aneurysms are under-represented in ruptured intracranial aneurysms (RIAs)....

Predictive value of radiomics for intracranial aneurysm rupture: a systematic review and meta-analysis.

To systematically review the literature on radiomics for predicting intracranial aneurysm rupture and conduct a meta-analysis to obtain evidence confirming the value of radiomics in this prediction. A systematic literature search was conducted in PubMed, Web of Science, Embase, and The Cochrane Library databases up to March 2024. The QUADAS-2 tool was used to assess study quality. Stata 15.0 and Review Manager 5.4.1 were used for statistical analysis. Outcomes included combined sensitivity (Sen), specificity (Spe), positive likelihood ratio (+LR), negative likelihood ratio (-LR), diagnostic odds ratio (DOR), and their 95% confidence intervals (CI), as well as pre-test and post-test probabilities. The SROC curve was plotted, and the area under the curve (AUC) was calculated. Publication bias and small-study effects were assessed using the Deeks' funnel plot. The 9 included studies reported 4,284 patients, with 1,411 patients with intracranial aneurysm rupture (prevalence 32.9%). The overall performance of radiomics for predicting intracranial aneurysm rupture showed a combined Sen of 0.78 (95% CI: 0.74-0.82), Spe of 0.74 (95% CI: 0.70-0.78), +LR of 3.0 (95% CI: 2.7-3.4), -LR of 0.29 (95% CI: 0.25-0.35), DOR of 10 (95% CI: 9-12), and AUC of 0.83 (95% CI: 0.79-0.86). Significant heterogeneity was observed in both Sen (I2 = 90.93, 95% CI: 89.00-92.87%) and Spe (I2 = 94.28, 95% CI: 93.21-95.34%). Radiomics can improve the diagnostic efficacy of intracranial aneurysm rupture. More large-sample, prospective, multicenter clinical studies are needed to further evaluate its predictive value. https://www.crd.york.ac.uk/PROSPERO/.

Female hormonal and reproductive factors and the risk of subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH), primarily caused by rupture of intracranial aneurysm, has a high incidence rate in women. We aimed to evaluate the association between female hormonal and reproductive factors and SAH. A prospective cohort of 226,469 participants from the UK Biobank was followed for a median period of 14.75 years. Cox proportional hazards models and restricted cubic splines were used to explore the associations between 13 major factors and SAH, including menarche age, menopausal status, age at menopause, reproductive lifespan, pregnancy history, age at first and last live births, number of live births, adverse fertility outcomes, history of oral contraception or hormone-replacement therapy (HRT) use, and surgical history of hysterectomy or bilateral oophorectomy. SAH occurred in 769 of participants during the follow-up period. Both women with a younger age at menarche (< 12 years) and post-menopausal women had a higher SAH risk (hazard ratio (HR), 1.28; 95% confidence interval (CI), 1.06-1.54) and (HR, 1.48; 95% CI, 1.10-1.99), respectively. A higher risk of SAH was identified in those with an earlier age at menopause (< 40 years: HR, 2.09; 95% CI, 1.43-3.06; 40-44 years: HR, 1.68; 95% CI, 1.23-2.29). A shorter reproductive lifespan (< 30 years) was associated with increased SAH risk (HR, 1.64; 95% CI, 1.28-2.11), while a longer reproductive lifespan (> 42 years) showed a protective effect (HR, 0.65; 95% CI, 0.55-0.77). Younger age at first live birth (< 24 years) was associated with SAH (HR, 1.39; 95% CI, 1.13-1.72). Hysterectomy (HR, 2.55; 95% CI, 2.12-3.05) or bilateral oophorectomy (HR, 1.51; 95% CI, 1.14-2.01) also predisposed women to SAH. Age at last live birth, number of live births, pregnancy history, adverse fertility outcomes, and HRT or oral contraceptive use were not associated with SAH. Female hormonal and reproductive factors are important for evaluating SAH risk in women. In particular, earlier menopause is associated with an increased risk of SAH. The data utilized in this study were sourced from a third party and are not publicly accessible. The UK Biobank data that support the findings of this research are available from the UK Biobank (www.ukbiobank.ac.uk), subject to review and approval by the UK Biobank.

Vitamin D deficiency and intracranial aneurysms: Systematic Review

BackgroundLow vitamin D levels have been associated with an increased risk in patients with cerebrovascular diseases. However, solid evidence linking intracranial aneurysm (IA) to hypovitaminosis D is still lacking. This review aims to evaluate if there is a relationship between vitamin D deficiency and the incidence and rupture of IA. MethodsA systematic search of papers was performed in the following databases: MEDLINE, EMBASE, LILACS, and Web of Science. The selected papers covered data on vitamin D levels and the occurrence or rupture of IA and/or other complications of this condition. The risk of bias analysis was performed with tools developed by the National Heart, Lung, and Blood Institute. Tables were developed to synthesize the qualitative analysis of the data. ResultsSix studies from five different countries were included covering a total of 14,184 participants. A relationship between low vitamin D levels and IA incidence was detected in all studies. In terms of rupture and complications, there was a tendency of association with hypovitaminosis. DiscussionAmong the limitations of the papers, the following are noteworthy: sample size and selection, recording flaws inherent to retrospective designs, failure to consider confounding variables, and heterogeneity of data produced among the researches, making a quantitative analysis of the evidence unfeasible. From the results obtained, we can identify a higher incidence of hypovitaminosis D in patients with IA. Yet, further studies need to be conducted in investigating the relationships between low vitamin D levels and rupture or other complications (CRD42022363369).

Infectious endocarditis complicated with intracranial infected aneurysm rupture and sinus of valsalva aneurysm rupture

BackgroundInfectious endocarditis (IE) is an infectious disease caused by direct invasion of the heart valve, endocardium, or adjacent large artery endocardium by pathogenic microorganisms. Despite its relatively low incidence, it has a poor prognosis and a high mortality. Intracranial infectious aneurysms (IIA) and ruptured sinus of Valsalva aneurysm (RSVA) are rare complications of IE.Case presentationWe report a young male patient with symptoms of respiratory tract infection, heart murmurs and other symptoms and signs. The patient also had kidney function impairment and poor response to symptomatic therapy. Blood culture was negative, but echocardiography was positive, which met the diagnostic criteria for infective endocarditis. Moreover, an echocardiography showed a ruptured sinus of Valsalva aneurysm with a ventricular septal defect. Finally, secondary rupture of an IIA with multiple organ damage led to a poor clinical outcome.ConclusionTherefore, in the clinical setting, for young patients with unexplained fever, chest pain, or palpitations, we need to be highly vigilant, considering the possibility of infective endocarditis and promptly performing blood culture, echocardiography, cerebrovascular imaging and so on, in order to facilitate early proper diagnosis and treatment.

Multiple omics reveal link between the microbiota-gut-brain axis and intracranial aneurysm rupture

Multiple omics reveal link between the microbiota-gut-brain axis and intracranial aneurysm rupture

Intracranial Aneurysms and Cerebral Small Vessel Disease: Is There an Association between Large- and Small-Artery Diseases?

Background/Objectives: Intracranial aneurysms (IAs) may be connected to interactions between large and small intracranial vessels. We aimed to investigate the association between IAs and cerebral small-vessel disease (CSVD) and assess CSVD impact on IA patient management. Methods: This retrospective study analyzed clinical data and MRI features of CSVD in 192 subarachnoid hemorrhage (SAH) patients: 136 with incidental IA, 147 with severe CSVD without SAH/IA, and 50 controls without SAH, IA, or severe CSVD. MRI assessments followed the Standards for Reporting Vascular Changes on Neuroimaging (STRIVE), with a total burden of small-vessel disease (TBSVD) score calculated. Statistical analyses included forward selection and binary logistic regression. Results: TBSVD differed significantly across groups (p < 0.001), except between SAH and IA groups (p = 0.8). Controls had the lowest TBSVD (1.00; 1.22 ± 0.996), followed by SAH (2.00; 2.08 ± 1.013) and IA groups (2.00; 2.04 ± 1.141), with the highest in the CSVD group (1.00; 1.22 ± 0.996). White-matter hyperintensity (WMH) patterns varied with IA rupture status (p = 0.044); type A was prevalent in SAH patients and type D in the IA group. Incorporating MRI CSVD features and TBSVD into risk assessments did not enhance IA prediction or outcome models. Conclusions: IA patients exhibit a higher CSVD burden than controls, suggesting a link between small and large intracranial vessels. WMH patterns distinguish between ruptured and unruptured IA patients, offering potential markers for IA rupture risk assessment and signaling a paradigm shift in understanding IAs and CSVD.

Sex Differences in Intracranial Aneurysms: A Matched Cohort Study.

Background: Aneurysmal subarachnoid hemorrhage (SAH) predominantly affects women, accounting for 65% of cases. Women have a 1.3 times higher relative risk than men, with the incidence rising particularly in women aged 55-85 years. Women also have a higher prevalence of unruptured intracranial aneurysms (IAs), especially after the age of 50 years, and are at greater risk of aneurysm growth and rupture. This study aimed to isolate the influence of sex on rupture rate, bleeding severity, functional outcomes, and complications by using a matched cohort, while also examining the impact of sex on aneurysm localization and multiplicity. Methods: We utilized a retrospectively collected database of 300 patients with 511 IAs. Inclusion criteria included the availability of clinical data and 3D angiography for semi-automatic reconstruction of IA morphology. Female patients and their IA were matched with male patients according to clinical parameters and 21 morphological characteristics using an interactive visual exploration tool for multidimensional matching. Results: Contrary to previously published results, our study found no significant sex differences in rupture rates or vasospasm rates between male and female patients. The severity of SAH, functional outcomes, and complications such as hydrocephalus were also similar in women and men. However, women exhibited a higher prevalence of multiple aneurysms and distinct localization patterns. Conclusions: This study underscores the complex role of sex in IA development and rupture. Although sex-specific biological factors influence aneurysm characteristics, they do not necessarily translate into differences in clinical outcomes. Further research is needed to explore these factors and their impact on aneurysm development and management.

Impact of blood viscosity on hemodynamics of large intracranial aneurysms

BackgroundHemodynamic factors play an important role in the formation and rupture of intracranial aneurysms. Blood viscosity has been recognized as a potential factor influencing the hemodynamics of aneurysms. Computational fluid dynamics (CFD) is one of the main methods to study aneurysm hemodynamics. However, current CFD studies often set the viscosity to a standard value, neglecting the effect of individualized viscosity on hemodynamics. We investigate the impact of blood viscosity on hemodynamics in large intracranial aneurysm (IA) and assess the potential implications for aneurysm growth and rupture risk. MethodsCFD simulations of 8 unruptured large internal carotid artery aneurysms were conducted using pulsatile inlet conditions. For each aneurysm, CFD simulations were performed at 5 different viscosity levels (0.004, 0.006, 0.008, 0.010, and 0.012 Pa·s). Differences in hemodynamic parameters across viscosity levels were compared using paired t-tests, and the correlation between viscosity and hemodynamic parameters was analyzed. ResultsIncreasing blood viscosity leads to significant decrease in blood flow velocity within aneurysms. Time-averaged wall shear stress (WSS) showed significant positive correlation with viscosity, particularly at the aneurysm neck. Oscillatory shear index (OSI) showed general decreasing trend with increased viscosity, while it displayed an irregular pattern in a few cases. ConclusionsVariations in viscosity markedly influence velocity, WSS, and OSI in aneurysms, suggesting a role in modulating aneurysm growth and rupture risk. Incorporating patient-specific viscosity values in CFD simulations is vital for accurate and reliable outcomes.

Integrated metagenomic and metabolomic analysis reveals distinctive stage-specific gut-microbiome-derived metabolites in intracranial aneurysms

ObjectiveOur study aimed to explore the influence of gut microbiota and their metabolites on intracranial aneurysms (IA) progression and pinpoint-related metabolic biomarkers derived from the gut microbiome.DesignWe recruited 358 patients...

Phosphorylated NPY1R regulates phenotypic transition of vascular smooth muscle cells, inflammatory response and macrophage infiltration to promote intracranial aneurysm progression

BackgroundRupture of intracranial aneurysm (IA) could give rise to spontaneous subarachnoid hemorrhage, leading to a high disability rate and even death. NPY1R expression was upregulated in aneurysm tissues of IA patients. However, the role and underlying mechanism of NPY1R remains unknown. MethodsThe IA model of mice was established using inducing systemic hypertension and injecting elastase. The expression of genes and proteins was detected by RT-qPCR and western blot. The number of T cells, macrophages, and neutrophils in IA mice was detected using flow cytometry and IF assay. The levels of inflammatory factors were measured using ELISA. Patho-morphology and inflammatory cells in aneurysm tissues were evaluated by HE staining. The interaction between TK and NPY1R was validated using Co-IP. ResultsNPY1R expression was greatly elevated in aneurysm tissues in IA patients and mice, which were positively related to macrophage infiltration. Besides, exogenous overexpression of NPY1R resulted in the promotion of contractile phenotype to the synthetic phenotype of vascular smooth muscle cells (VSMCs), inflammatory response and M1 macrophage polarization. In terms of the underlying mechanism, NPY1R protein could be modified by TK-mediated phosphorylation and TKI could decrease IA formation and suppresse contractile phenotype to synthetic phenotype of VSMCs, inflammatory response and M1 macrophage polarization in IA mice. Furthermore, ablating mouse macrophages abolished NPY1R overexpression-mediated promotion of IA formation and rupture in mice. ConclusionPhosphorylated NPY1R contributed to IA progression through promoting contractile phenotype to synthetic phenotype of VSMCs, inflammatory response and M1 macrophage polarization in IA.

Does it stable? Intracranial aneurysm wall enhancement might be the warning signals: a meta-analysis of observational studies.

Magnetic resonance vessel wall imaging (MR-VWI) is an emerging imaging technology used to assess the progressive risk of unruptured intracranial aneurysms (UIAs). Unlike the standard evaluation model, MR-VWI is still debatable. This study aims to further define the potential relationship between aneurysm wall enhancement (AWE) and aneurysm stability. Using "intracranial aneurysm", "magnetic resonance", and "enhancement" as keywords, relevant studies were systematically searched in PubMed, Embase, and Cochrane, and the qualified studies were enrolled for further analysis. There were 13 case-control studies, 4 cohort studies, and 2,678 cases of intracranial aneurysms included in the meta-analysis. It was shown that AWE was correlated with intracranial aneurysm rupture (OR = 35.90, 95% CI: 15.58 to 82.75, p < 0.001), growth (OR = 6.69, 95% CI: 2.69 to 16.63, p < 0.001), and presence of symptoms (OR = 14.46, 95% CI: 9.07 to 23.05, p < 0.001). This finding had a high diagnostic value, but the correlation was probably not independent of aneurysm size. The pooled relative risks of the follow-up studies revealed that the risk of UIA progression was approximately 3.33 times higher with AWE than without AWE (RR = 3.33, 95% CI: 2.33 to 4.78, p < 0.001). In addition, the pooled results demonstrated that quantitative indices of VWI enhancement were equally linked with aneurysm stability (OR = 19.61, 95% CI: 10.63 to 36.17, p < 0.001). AWE is an effective imaging method to assess the stability of UIAs, and it can be a marker for the prophylactic treatment of small unruptured intracranial aneurysms in the future, which remains to be validated by prospective studies with large samples.

Molecular Mechanisms Underlying Intracranial Aneurysm Rupture

Intracranial aneurysms, a major cause of subarachnoid hemorrhage(SAH), pose a significant social burden due to their poor patient outcomes. Recent studies, including those using animal models, have shed light on a new disease concept: intracranial aneurysms as a chronic inflammatory disease. This process is triggered by abnormal hemodynamic forces and mediated by immune cells like macrophages and neutrophils. The initiation of intracranial aneurysms is a two-step process. First, high wall shear stress and mechanical stretch work together to promote macrophage infiltration into the arterial walls. This infiltration is facilitated by endothelial cells and fibroblasts, which are activated to produce chemoattractants. Once the lesions enlarge, low wall shear stress and turbulent flow take over, maintaining macrophage infiltration. As the disease progresses towards rupture, infiltration creates hypoxic conditions that exacerbate the situation. These conditions, in turn, induce the formation of neovessels at the weakest point of the aneurysm and promote specific inflammatory microenvironments rich in neutrophils. The excessive tissue destruction caused by neutrophil-mediated inflammation ultimately leads to lesion rupture. Therefore, intracranial aneurysm rupture requires not only structural changes but also qualitative alterations within the chronic inflammatory environment. This suggests that factors mediating chronic inflammation could be potential targets for predicting or preventing aneurysm rupture.

Synthesizing Feature-Aligned and Category-aware Electronic Medical Records for Intracranial Aneurysm Rupture Prediction.

Rupture prediction is crucial for precise treatment and follow-up management of patients with intracranial aneurysms (IAs). Considerable machine learning (ML) methods have been proposed to improve rupture prediction by leveraging electronic medical records (EMRs), however, data scarcity and category imbalance strongly influence performance. Thus, we propose a novel data synthesis method i.e., Transformer-based conditional GAN (TransCGAN), to synthesize highly authentic and category-aware EMRs to address above challenges. Specifically, we first align feature-wise context relationship and distribution between synthetic and original data to enhance synthetic data quality. To achieve this, we first integrate the Transformer structure into GAN to match the contextual relationship by processing the long-range dependencies among clinical factors and introduce a statistical loss to maintain distributional consistency by constraining the mean and variance of the synthesis features. Additionally, a conditional module is designed to assign the category of the synthesis data, thereby addressing the challenge of category imbalance. Subsequently, the synthetic data are merged with the original data to form a large-scale and category-balanced training dataset for IAs rupture prediction. Experimental results show that using TransCGAN's synthetic data enhances classifier performance, achieving AUC of 0.89 and outperforming state-of-the-art resampling methods by 5 %-33 % in F1 score.

PRCP is a promising drug target for intracranial aneurysm rupture supported via multi-omics analysis

BackgroundCerebral aneurysms are life-threatening cerebrovascular disorders. Currently, there are no effective treatments for preventing disease progression. Mendelian randomisation (MR) is widely used to repurify licensed drugs and identify new therapeutic...