Rupture Of Intracranial Aneurysms Research Articles

The relationship between staying up late and risk of intracranial aneurysm rupture: A single-center study

ObjectiveTo evaluate the impact of staying up late (SUL) on the risk of intracranial aneurysm (IA) rupture. MethodsThis case-control study included 452 patients diagnosed with IA. They were divided into ruptured and unruptured groups. Staying up late was categorized in three levels (11–12 o’clock, 12-1 o’clock, after 1 o’clock) according to the time of falling asleep. To explore the relationship between staying up late and risk of IA rupture, univariate and multivariate logistic regression analyses were performed. ResultsMultivariate analysis found a significant difference in the percentage of patients falling asleep at 12-1 o’clock (OR, 2.25; 95% CI, 1.10–4.59) or after 1 o’clock (OR, 4.68; 95% CI, 1.74–12.55) between the ruptured and unruptured groups. The following risk factors differed significantly between the two groups: hypertension (OR, 2.05; 95% CI, 1.33–3.17), current smoking (OR, 1.72; 95% CI, 1.09–2.71), irregular IA (OR, 1.85; 95% CI, 1.15–3.00), IA size ≥8mm (OR, 1.92; 95% CI, 1.22–3.02), MCA location (OR, 2.45; 95% CI, 1.19–5.02), and aspect ratio (OR, 1.33; 95% CI, 1.02–1.73). ConclusionPatients who fell asleep later than 12 midnight on average showed higher risk of IA rupture. The reasons for this are not very clear. A review of the literature suggests that this association may be related to a series of physiological, pathophysiological, endocrine and metabolic changes.

Correlation between seasonal and meteorological factors with the monthly frequency of intracranial aneurysms rupture in northeast Mexico

Intracranial aneurysms are considered acquired lesions, occur with an incidence of 3–5% in general population. Subarachnoid hemorrhage (SAH) due to ruptured aneurysms represents 85 of all spontaneous subarachnoid hemorrhages and this represents 15% of all cerebral vascular events. Risk factors for aneurysmal rupture are age, gender, size and location of the aneurysm, hypertension, smoking, and alcoholism. Whether seasonal or meteorological factors influence the likelihood of aneurysm rupture is controversial. An observational, retrospective, cross-sectional and non-comparative study of male and female patients over 18 years old who were admitted to our unit in northeast Mexico with the diagnosis of spontaneous SAH due to aneurysmal rupture from January 2014 to March 2020. Climate information was obtained from data of the climate history of the different airport stations in the northeast of the country and the information was correlated to determine if meteorological variables interfere in the incidence of SAH due to aneurysm rupture. Our study showed a significant seasonal fluctuation on the occurrence of aneurysmal SAH. A statistically significant relationship between temperature, humidity and aneurismal SAH. The atmospheric pressure did not show a statistically significant relationship with SAH incidence due to aneurysm rupture.

Shedding the Light on the Natural History of Intracranial Aneurysms: An Updated Overview.

The exact molecular pathways underlying the multifactorial natural history of intracranial aneurysms (IAs) are still largely unknown, to the point that their understanding represents an imperative challenge in neurovascular research. Wall shear stress (WSS) promotes the genesis of IAs through an endothelial dysfunction causing an inflammatory cascade, vessel remodeling, phenotypic switching of the smooth muscle cells, and myointimal hyperplasia. Aneurysm growth is supported by endothelial oxidative stress and inflammatory mediators, whereas low and high WSS determine the rupture in sidewall and endwall IAs, respectively. Angioarchitecture, age older than 60 years, female gender, hypertension, cigarette smoking, alcohol abuse, and hypercholesterolemia also contribute to growth and rupture. The improvements of aneurysm wall imaging techniques and the implementation of target therapies targeted against inflammatory cascade may contribute to significantly modify the natural history of IAs. This narrative review strives to summarize the recent advances in the comprehension of the mechanisms underlying the genesis, growth, and rupture of IAs.

MicroRNA-513b-5p targets COL1A1 and COL1A2 associated with the formation and rupture of intracranial aneurysm

Collagen-type I alpha 1 chain (COL1A1) and COL1A2 are abnormally expressed in intracranial aneurysm (IA), but their mechanism of action remains unclear. This study was performed to investigate the mechanism of COL1A1 and COL1A2 affecting the occurrence and rupture of IA. Quantitative real-time polymerase chain reaction was used to measure the expression of hsa-miR-513b-5p, COL1A1, COL1A2, TNF-α, IL-6, MMP2, MMP3, MMP9 and TIMP4 in patients with ruptured IA (RA) (n = 100), patients with un-ruptured IA (UA) (n = 100), and controls (n = 100). Then, human vascular smooth muscle cells (HASMCs) were cultured, and dual luciferase reporter assay was performed to analyse the targeting relationship between miR-513b-5p and COL1A1 or COL1A2. The effects of the miR-513b-5p mimic and inhibitor on the proliferation, apoptosis, and death of HASMC and the RIP1-RIP3-MLKL and matrix metalloproteinase pathways were also explored. The effect of silencing and over-expression of COL1A1 and COL1A2 on the role of miR-513b-5p were also evaluated. Finally, the effects of TNF-α on miR-513b-5p targeting COL1A1 and COL1A2 were tested. Compared with those in the control group, the serum mRNA levels of miR-513b-5p, IL-6 and TIMP4 were significantly decreased in the RA and UA groups, but COL1A1, COL1A2, TNF-α, IL-1β, MMP2, MMP3 and MMP9 were significantly increased (p < 0.05). Compared with those in the UA group, the expression of COL1A1, COL1A2, TNF-α, IL-1β and MMP9 was significantly up-regulated in the RA group (p < 0.05). Results from the luciferase reporter assay showed that COL1A1 and COL1A were the direct targets of miR-513b-5p. Further studies demonstrated that miR-513b-5p targeted COL1A1/2 to regulate the RIP1-RIP3-MLKL and MMP pathways, thereby enhancing cell death and apoptosis. Over-expression of COL1A1 or COL1A2, rather than silencing COL1A1/2, could improve the inhibitory effect of miR-513b-5p on cell activity by regulating the RIP1-RIP3-MLKL and MMP pathways. Furthermore, over-expression of miR-513b-5p and/or silencing COL1A1/2 inhibited the TNF-α-induced cell proliferation and enhanced the TNF-α-induced cell death and apoptosis. The mechanism may be related to the inhibition of collagen I and TIMP4 expression and promotion of the expression of RIP1, p-RIP1, p-RIP3, p-MLKL, MMP2 and MMP9. MiR-513b-5p targeted the inhibition of COL1A1/2 expression and affected HASMC viability and extracellular mechanism remodelling by regulating the RIP1-RIP3-MLKL and MMP pathways. This process might be involved in the formation and rupture of IA.

The Potential Role of hsa_circ_0005505 in the Rupture of Human Intracranial Aneurysm.

Objective: Recently, abundant number of studies have revealed many functions of circular RNAs in multiple diseases, however, the role of circular RNA in the rupture of human intracranial aneurysm is still unknown. This study aims to explore the potential functions of circular RNA in the rupture of human intracranial aneurysms. Methods: The differentially expressed circular RNAs between un-ruptured intracranial aneurysms (n = 5) and ruptured intracranial aneurysms (n = 5) were analyzed with the Arraystar human circRNAs microarray. Quantitative real-time PCR (qPCR) was used to verify the results of the circRNA microarray. The role of circular RNA in intracranial aneurysm rupture was assessed in vitro. MTT assay, CCK-8 assay, Caspase3/7 assay, assay of cell apoptosis and Celigo wound healing was conducted to evaluate the relationship between circular RNA and the rupture of human intracranial aneurysms. Results: A total of 13,175 circRNA genes were detected. Among them 63 circRNAs upregulated and 54 circRNAs downregulated significantly in ruptured intracranial aneurysms compared with un-ruptured intracranial aneurysms (p < 0.05 Fold Change > 1.5). Five upregulated circRNAs were selected for further study (hsa_circ_0001947, hsa_circ_0043001, hsa_circ_0064557, hsa_circ_0058514, hsa_circ_0005505). The results of qPCR showed only hsa_circ_0005505 significantly upregulated (p < 0.05). The expression of hsa_circ_0005505 was higher in ruptured intracranial aneurysm tissues. And our in vitro data showed that hsa_circRNA_005505 promotes the proliferation, migration and suppresses the apoptosis of vascular smooth muscle cell. Conclusion: This study revealed an important role of hsa_circ_0005505 in the proliferation, migration and apoptosis of vascular smooth muscle cell, and indicated that hsa_circ_0005505 may associate with the pathological process of intracranial aneurysms.

Long‐term survival outcomes and prognostic factors related to ruptured intracranial aneurysms: A comparison of surgical and endovascular options in a propensity score–matched, nationwide population‐based cohort study

To determine the long-term survival outcomes of and prognostic factors for survival in patients with a ruptured intracranial aneurysm (RIA) who underwent endovascular coil embolization or surgical clipping. We selected patients who had received a diagnosis of RIA between January 1, 2011 and December 31, 2017. Propensity score matching was performed, and Cox proportional hazards model curves were plotted to analyze all-cause mortality in patients undergoing different treatments. The matching process yielded a final cohort of 8102 patients (4051 and 4051 in endovascular coil embolization and surgical clipping groups, respectively) who were eligible for inclusion. In multivariate Cox regression analyses, the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for endovascular coil embolization compared with surgical clipping were 0.87 (95% CI, 0.79-0.97). The aHRs for the ages of 65 to 74, 75 to 84, and ≥85years compared with the ages of 20 to 64years were 1.82 (95% CI, 1.60-2.07), 3.35 (95% CI, 2.93-3.84), and 6.99 (95% CI, 5.51-8.86), respectively. Surgical clipping; old age; male sex; treatment during 2011 to 2013; presence of diabetes, congestive heart failure, hypertension, chronic kidney disease, or end-stage renal disease; history of stroke or transient ischemic attack; Charlson Comorbidity Index ≥2; attendance of nonacademic hospitals; and low income were significant independent prognostic factors for poor survival. Compared with surgical clipping, endovascular coil embolization led to more favorable survival outcomes in patients with RIAs.

Protective effects of BP-1-102 against intracranial aneurysms-induced impairments in mice

The development of non-invasive pharmacological therapies to prevent the progression and rupture of intracranial aneurysms (IAs) is an important field of research. This study attempts to reveal the role of BP-1-102, an oral bioavailable signal transducer and activator of transcription 3 (STAT3) inhibitor, in IA. We first constructed an IA mouse model by injecting elastase into the cerebrospinal fluid with simultaneous induction of hypertension by deoxycorticosterone acetate (DOCA) implantation. The results showed that the proportion of IA rupture in mice after BP-1-102 administration was significantly reduced, and the survival time was significantly extended. Further research showed that compared with the vehicle group, the proportion of macrophages infiltrated at the aneurysm and the expression of pro-inflammatory cytokines in the BP-1-102 administration group were significantly reduced. The contractile phenotype vascular smooth muscle cell (VSMC) specific markers, SM22α and αSMA, were significantly upregulated in the BP-1-102 group. Furthermore, we found that BP-1-102 inhibited the expression of critical proteins in the nuclear factor kappa-B and Janus kinase 2/STAT3 signalling pathways. Our study shows that BP-1-102 significantly decreases the rupture of IA, reduces the inflammatory responses and modulates the phenotype of VSMCs, suggesting that BP-1-102 could be utilised as a potential intervention drug for IA.

Risk Factors of Anterior Circulation Intracranial Aneurysm Rupture: Extracranial Carotid Artery Tortuosity and Aneurysm Morphologic Parameters.

Background: This study was conducted to explore the risk factors of anterior circulation intracranial aneurysm rupture based on extracranial carotid artery (ECA) tortuosity.Methods: This retrospective study, conducted from January 1, 2017, to March 1, 2021, collected and reviewed the clinical and imaging data of 308 patients with anterior circulation intracranial aneurysm [133 (43.2%) patients in the ruptured aneurysm group; 175 (56.8%) patients in the unruptured aneurysm group]. Computed tomography angiography (CTA) of the head and neck was used to determine the ECA tortuosity (normal, simple tortuosity, kink, coil) and the morphologic parameters of the aneurysms. The relationship of aneurysm rupture to ECA tortuosity and the morphologic parameters were analyzed.Results: After univariate analysis, kink, angle of flow inflow (FA), aspect ratio (AR), aneurysm length (L), the distance from the tortuosity to the aneurysm (distance), and size ratio (SR) were significantly correlated with anterior circulation intracranial aneurysm rupture (p < 0.05). Spearman correlation analysis showed that ECA tortuosity was correlated with FA and SR (p < 0.05). Multiple logistic analyses showed that FA [odds ratio (OR), 1.013; 95% CI, 1.002–1.025], SR (OR, 1.521; 95% CI, 1.054–2.195), and kink (OR, 1.823; 95% CI, 1.074–3.096) were independently associated with aneurysm rupture.Conclusion: Study results suggest that FA, SR, and ECA kink were independent risk factors associated with anterior circulation intracranial aneurysm rupture.

Systemic immune response against the oral pathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans is associated with the formation and rupture of intracranial aneurysms.

Periodontal infections are associated with the formation and rupture of intracranial aneurysms (IAs). This study investigated the role of two key periodontal pathogens, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. Immunoglobulin A (IgA) and IgG antibodies against P.gingivalis and A.actinomycetemcomitans were measured with enzyme immune assay from the serum of 227 IA patients, of whom 64 also underwent clinical oral examination. As a control group, 1096 participants in a cross-sectional health survey, Health 2000, underwent serological studies and oral examination. Logistic regression was used for multivariate analysis. Immunohistochemistry was performed to demonstrate bacteria-derived epitopes in the IA wall. Widespread gingivitis and severe periodontitis were more common in IA patients than in controls (2× and 1.5×, respectively). IgA antibodies against P.gingivalis and A.actinomycetemcomitans were 1.5× and 3-3.4× higher, respectively, in both unruptured and ruptured IA patients compared to controls (p≤0.003). IgG antibodies against P.gingivalis were 1.8× lower in unruptured IA patients (p<0.001). In multivariate analysis, high IgA, but low IgG, antibody levels against P.gingivalis (odds ratio [OR]=1.4, 95% confidence interval [Cl] = 1.1-1.8 and OR=1.5, 95% Cl = 1.1-1.9; OR=0.6, 95% Cl = 0.4-0.7 and OR=0.5, 95% Cl = 0.4-0.7) and against A.actinomycetemcomitans (OR=2.3, 95% Cl = 1.7-3.1 and OR=2.1, 95% Cl = 1.5-2.9; OR=0.6, 95% Cl = 0.4-0.8 and OR=0.6, 95% Cl = 0.5-0.9) were associated with the risk of IA formation and rupture. Immunohistochemistry showed P.gingivalis epitopes in the IA wall. Exposure to the periodontal pathogens P.gingivalis and A.actinomycetemcomitans and dysfunctional acquired immune response against them may increase the risk of IA formation and IA rupture.

A Modification to a Murine Model for Intracranial Aneurysm Formation and Rupture.

Between 3.6% and 6.0% of the population has an intracranial aneurysm. The mechanisms underlying intracranial aneurysm formation and rupture are not fully known. Several rodent models have been developed to better understand intracranial aneurysm pathophysiology. Hypertension, hemodynamic changes, and vessel injury are all necessary for aneurysm induction; however, multiple invasive procedures may disrupt an animal’s physiology. Therefore, we hypothesized that our method for inducing hypertension could be modified to create a simpler model. We previously developed a highly reproducible murine model of intracranial aneurysm formation and rupture that involves hemodynamic changes through ligation of the left common carotid artery, vessel wall degradation using elastase and a lysyl oxidase inhibitor, and hypertension through a high-salt diet, continuous angiotensin II infusion, and right renal artery ligation. In order to create a simpler model, we sought to eliminate renal artery ligation. We assessed aneurysm formation, aneurysm rupture, and blood pressure in two separate cohorts of C57BL/6 mice: one cohort underwent our model as above, while another cohort did not receive right renal artery ligation. Our results demonstrate that intracranial aneurysm formation and rupture rates did not differ between each group. Further, the blood pressures between cohorts did not differ at various timepoints in the model. Both cohorts, however, did have a significant increase in blood pressure from baseline, suggesting that renal artery ligation is not needed for inducing hypertension. These findings demonstrate that our murine model can be modified to eliminate right renal artery ligation. Thus, we propose this modification to our murine model for studying intracranial aneurysm pathophysiology.

A Dissipation Function-Based Method for Calculating the Energy Loss of Intracranial Aneurysms.

At present, the energy loss (EL) mechanism of intracranial aneurysm (IA) rupture is explored based on the global EL calculated by Bernoulli equation, but the details of EL are still unclear. This study aimed to explore the temporal and spatial characteristics of EL of IAs and reveal its mechanism. A novel method for calculating the EL of IAs based on dissipation function (DF) was proposed. DF was derived from the differential form of the energy equation and reflected the irreversible conversion from mechanical energy to internal energy caused by the friction between the fluid micelles. Eight sidewall IAs located at the posterior communicating segment of the internal carotid artery were collected; the three-dimensional (3D) geometric models of IAs were established employing image segmentation and 3D reconstruction. Computational fluid dynamics was applied to obtain hemodynamic parameters of IAs. The temporal and spatial characteristics of EL of IAs were achieved utilizing our proposed method. The simulation results indicated that EL occurred mainly in the boundary layer and the region adjacent to high-velocity inflow jet, EL increased rapidly during cardiac systole and reached its maximum at end-systolic phase and then decreased gradually during diastole until the end of cardiac cycle. The proposed method achieved some improvements over the traditional Bernoulli equation–based method by acquiring the temporal and spatial characteristics of EL, and it could provide insights into the EL of IAs and contribute to further rupture mechanism investigation.

Impact of the COVID-19 pandemic on patients with rupture of intracranial aneurysm at the Dos de Mayo National Hospital in Lima Peru

Objective: To evaluate the impact on the outcome of patients with a ruptured aneurysm, who are admitted to the Dos de Mayo National Hospital in the context of the COVID-19 pandemic. Methods: 42 operated for ruptured aneurysms were included in the context of the COVID-19 pandemic between March 1 and December 31, 2020 (group A), and a control group of 44 patients operated on between March 1 and December 31, 2019 (group B). Upon admission, the poor neurological status defined by the WFNS&gt; 3, the Fisher IV high-grade tomographic status with intracerebral hematoma or acute hydrocephalus, which required external ventricular drainage (EVD), and the presence of vasospasm were evaluated. The Modified Rankin Scale was evaluated at discharge. Statistical analysis was performed to compare both groups. Results: The rates of poor neurological presentation and complications during the presurgical evolution (intracerebral hemorrhage and acute hydrocephalus that required EVD) were higher in group A (p = 0.002 and p &lt;0.05, respectively). The delay in the admission of the patient to the emergency room to receive treatment was 7.5 days in group A and 4.95 days for group B. All these factors contributed to a lower possibility of recovery in group A, which was correlated with higher Values on the Modified Rankin Scale at discharge for this group (p = 0.04). Conclusion: We did not find national reports on ruptured aneurysms treated in the context of the pandemic, this being one of the first studies that demonstrate the impact of the COVID-19 pandemic in patients with ruptured intracranial aneurysm. The population should be educated on how to act in case of specific symptoms such as sudden intense headache, neurological deficit, or acute chest pain, which should receive timely care, immediate referral, and priority of treatment in referral hospitals in order to reduce morbidity and mortality of complex neurological pathologies. Keywords: Intracranial Aneurysm, Aneurysm, Ruptured, Cerebral Hemorrhage, Pandemics, COVID-19. (Source: MeSH NLM)

Reliability and Agreement of 2D and 3D Measurements on MRAs for Growth Assessment of Unruptured Intracranial Aneurysms

Reliable and reproducible measurement of unruptured intracranial aneurysm growth is important for unruptured intracranial aneurysm rupture risk assessment. This study aimed to compare the reliability and reproducibility of 2D and 3D growth measurements of unruptured intracranial aneurysms. 2D height, width, and neck and 3D volume measurements of unruptured intracranial aneurysms on baseline and follow-up TOF-MRAs were performed by two observers. The reliability of individual 2D and 3D measurements and of change (growth) between paired scans was assessed (intraclass correlation coefficient) and stratified for aneurysm location. The smallest detectable change on 2D and 3D was determined. Proportions of growing aneurysms were compared, and Bland-Altman plots were created. Seventy-two patients with 84 unruptured intracranial aneurysms were included. The interobserver reliability was good-to-excellent for individual measurements (intraclass correlation coefficient > 0.70), poor for 2D change (intraclass correlation coefficient < 0.5), and good for 3D change (intraclass correlation coefficient = 0.76). For both 2D and 3D, the reliability was location-dependent and worse for irregularly shaped aneurysms. The smallest detectable changes for 2D height, width, and neck and 3D volume measurements were 1.5 , 2.0, and 1.9 mm and 0.06 mL, respectively. The proportion of growing unruptured intracranial aneurysms decreased from 10% to 2%, depending on the definition of growth (1 mm or the smallest detectable changes for 2D and 3D). The interobserver reliability of the size measurements of individual 2D and 3D unruptured intracranial aneurysms was good-to-excellent but lower for 2D and 3D growth measurements. For growth assessment, 3D measurements are more reliable than 2D measurements. The smallest detectable change for 2D measurements was larger than 1 mm, the current clinical definition of unruptured intracranial aneurysm growth.

Altered MicroRNA Expression in Intracranial Aneurysmal Tissues: Possible Role in TGF-β Signaling Pathway.

The molecular mechanisms behind the rupture of intracranial aneurysms remain obscure. MiRNAs are key regulators of a wide array of biological processes altering protein synthesis by binding to target mRNAs. However, variations in miRNA levels in ruptured aneurysmal wall have not been completely examined. We hypothesized that altered miRNA signature in aneurysmal tissues could potentially provide insight into aneurysm pathophysiology. Using a high-throughput miRNA microarray screening approach, we compared the miRNA expression pattern in aneurysm tissues obtained during surgery from patients with aneurysmal subarachnoid hemorrhage (aSAH) with control tissues (GEO accession number GSE161870). We found that the expression of 70 miRNAs was altered. Expressions of the top 10 miRNA were validated, by qRT-PCR and results were correlated with clinical characteristics of aSAH patients. The level of 10 miRNAs (miR-24-3p, miR-26b-5p, miR-27b-3p, miR-125b-5p, miR-143-3p, miR-145-5p, miR-193a-3p, miR-199a-5p, miR-365a-3p/365b-3p, and miR-497-5p) was significantly decreased in patients compared to controls. Expression of miR-125b-5p, miR-143-3p and miR-199a-5p was significantly decreased in patients with poor prognosis and vasospasm. The target genes of few miRNAs were enriched in Transforming growth factor-beta (TGF-β) and Mitogen-activated protein kinases (MAPK) pathways. We found significant negative correlation between the miRNA and mRNA expression (TGF-β1, TGF-β2, SMAD family member 2 (SMAD2), SMAD family member 4 (SMAD4), MAPK1 and MAPK3) in aneurysm tissues. We suggest that miR-26b, miR-199a, miR-497and miR-365, could target multiple genes in TGF-β and MAPK signaling cascades to influence inflammatory processes, extracellular matrix and vascular smooth muscle cell degradation and apoptosis, and ultimately cause vessel wall degradation and rupture.

Third Nerve Palsy Due to Intracranial Aneurysms and Recovery after Endovascular Coiling.

The modality of treatment of third nerve palsy (TNP) associated with intracranial aneurysms remains controversial. While treatment varies with the location of the aneurysm, microsurgical clipping of PComm aneurysms has generally been the traditional choice, with endovascular coiling emerging as a reasonable alternative. Patients with TNP due to an intracranial aneurysm who subsequently underwent treatment at a mid-sized Canadian neurosurgical center over a 15-year period (2003-2018) were examined. A total of 616 intracranial aneurysms in 538 patients were treated; the majority underwent endovascular coiling with only 24 patients treated with surgical clipping. Only 37 patients (6.9%) presented with either a partial or complete TNP and underwent endovascular embolization; of these, 17 presented with a SAH secondary to intracranial aneurysm rupture. Aneurysms associated with TNP included PComm (64.9%), terminal ICA (29.7%), proximal MCA (2.7%), and basilar tip (2.7%) aneurysms. In general, smaller aneurysms and earlier treatment were provided for patients for ruptured aneurysms with a shorter mean interval to TNP recovery. In the endovascularly treated cohort initially presenting with TNP, seven presented with a complete TNP and the remaining were partial TNPs. TNP resolved completely in 20 patients (55.1%) and partially in 10 patients (27.0%). Neither time to coiling nor SAH at presentation were significantly associated with the recovery status of TNP. Endovascular coil embolization is a viable treatment modality for patients presenting with an associated cranial nerve palsy.

Roles of Phytoestrogen in the Pathophysiology of Intracranial Aneurysm

The incidences of intracranial aneurysm and aneurysmal subarachnoid hemorrhage are high in postmenopausal women. Although population-based studies suggest that hormone replacement therapy is beneficial for postmenopausal women with intracranial aneurysms, estrogen replacement may no longer be recommended for the prevention of chronic diseases given its association with adverse outcomes, such as cancer and ischemic stroke. The isoflavone daidzein and its intestinal metabolite equol are bioactive phytoestrogens and potent agonists of estrogen receptors. Given their estrogenic properties, we investigated whether the isoflavones daidzein and equol are protective against the formation and rupture of intracranial aneurysms in a mouse model of the postmenopausal state. We induced intracranial aneurysms in ovariectomized adult female mice using a combination of induced systemic hypertension and a single injection of elastase into the cerebrospinal fluid. We fed the mice with an isoflavone-free diet with/without daidzein supplementation, or in a combination of intraperitoneal equol, or oral vancomycin treatment. We also used estrogen receptor beta knockout mice. Both dietary daidzein and supplementation with its metabolite, equol, were protective against aneurysm formation in ovariectomized mice. The protective effects of daidzein and equol required estrogen receptor-β. The disruption of the intestinal microbial conversion of daidzein to equol abolished daidzein’s protective effect against aneurysm formation. Mice treated with equol had lower inflammatory cytokines in the cerebral arteries, suggesting that phytoestrogens modulate inflammatory processes important to intracranial aneurysm pathogenesis. Our study establishes that both dietary daidzein and its metabolite, equol, protect against aneurysm formation in ovariectomized female mice through the activation of estrogen receptor-β and subsequent suppression of inflammation. Dietary daidzein’s protective effect required the intestinal conversion to equol. Our results indicate the potential therapeutic value of dietary daidzein and its metabolite, equol, for the prevention of the formation of intracranial aneurysms and related subarachnoid hemorrhage.

Preventive screening for intracranial aneurysms.

BackgroundSubarachnoid hemorrhage from rupture of an intracranial aneurysm (aneurysmal subarachnoid hemorrhage) is a devastating subset of stroke. Since brain damage from the initial hemorrhage is a major cause for the poor outcome after aneurysmal subarachnoid hemorrhage, prevention of aneurysmal subarachnoid hemorrhage has the highest potential to prevent poor outcome from aneurysmal subarachnoid hemorrhage.AimIn this review, we describe the groups at high risk of aneurysmal subarachnoid hemorrhage who may benefit from preventive screening for unruptured intracranial aneurysms followed by preventive treatment of unruptured intracranial aneurysms found. Furthermore, we describe the advantages and disadvantages of screening and advise how to perform counseling on screening.Summary of reviewModeling studies show that persons with two or more affected first-degree relatives with aneurysmal subarachnoid hemorrhage and patients with autosomal dominant polycystic kidney disease (ADPKD) are candidates for screening for unruptured intracranial aneurysms. One modeling study also suggests that persons with only one affected first-degree relative with aneurysmal subarachnoid hemorrhage are also likely candidates for screening. Another group who may benefit from screening are persons ≥35 years who smoke(d) and are hypertensive, given their high lifetime risk of aneurysmal subarachnoid hemorrhage of up to 7%, but the prevalence of unruptured intracranial aneurysms in such persons and the efficiency and cost-effectiveness of screening in this group are not yet known. The ultimate goal of screening is to increase the number of quality years of life of the screening candidates, and therefore the benefits but also many downsides of screening –such as risk of incidental findings, very small unruptured intracranial aneurysms that require regular follow-up, preventive treatment with inherent risk of complications and anxiety – should be discussed with the candidate so that an informed decision can be made before intracranial vessels are imaged.ConclusionsSeveral groups of persons who may benefit from screening have been identified, but since these constitute only a minority of all aneurysmal subarachnoid hemorrhage patients, additional high-risk groups still need to be identified. Further research is also needed to identify persons at low or high risk of aneurysmal development and rupture within the groups identified thus far to improve the efficiency of screening. Moreover, if new medical treatment strategies that can reduce the risk of rupture of unruptured intracranial aneurysm become available, the groups of persons who may benefit from screening could increase considerably.

The relationship between the level of vitamin D and ruptured intracranial aneurysms

The purpose of our research is to explore whether vitamin D levels were associated with the rupture of intracranial aneurysms. In this retrospective study, 105 patients diagnosed with ruptured intracranial aneurysms (RIAs) and 185 patients diagnosed with unruptured intracranial aneurysms (UIAs) at The First Affiliated Hospital of Zhengzhou University were recruited from September 2019 to September 2020. Patients’ demographic and clinical information, including vitamin D levels, were recorded and compared. Univariate analysis showed that patients with UIAs had higher vitamin D levels than RIAs (p = 0.019). In addition, there were significant differences in aneurysm location (p < 0.001), aspirin use (p = 0.001), and comorbid diabetes mellitus (p = 0.037) between patients with UIAs and RIAs. Binary logistic regression analysis showed that the level of vitamin D was independently associated with RIAs [odds ratio (OR) 0.960; 95% confidence intervals (CI), 0.926–0.996, p = 0.028].

Correlation between high hair cortisol level and intracranial aneurysm rupture.

Measurement of cortisol in hair is a reliable method for determining long-term cortisol exposure reflecting chronic stress. Research using hair cortisol concentration has been limited to mainly cardiometabolic diseases. The association between hair cortisol concentration and aneurysmal rupture has not yet been studied. We aimed to investigate the relationship between the degree of chronic stress as measured by hair cortisol concentration and aneurysmal rupture.Sixty-eight patients diagnosed with intracranial aneurysms were included in this study (ruptured group, 30; unruptured group, 38). Hair cortisol was measured in 3-cm hair segments, reflecting roughly 3 months of hair growth. For a risk factor analysis, patient-specific factors and aneurysm-specific factors as well as hair cortisol concentration were investigated.Hair cortisol concentrations were significantly higher in the ruptured group than in the unruptured group (55.8 ± 22.0 ng/dL vs. 19.1 ± 6.4 ng/dL; P < .001). High hair cortisol concentration was found to be an independent risk factor for aneurysmal rupture (odds ratio [OR]: 2.245, 95% confidence interval [CI]: 1.825–2.753; P = .013). Additionally, a history of cerebrovascular disease was significantly associated with an increased risk of aneurysmal rupture (OR: 1.577, 95% CI: 1.099–2.262; P = .040).Based on our results, we suggest that chronic stress as measured by hair cortisol concentration could be an independent risk factor for intracranial aneurysmal rupture.

Clinical and Morphological Characteristics of Ruptured Small (

Context:Small intracranial aneurysms (IAs) are considered to have a low risk of rupture; however, in clinical practice, we often encounter patients with subarachnoid hemorrhage (SAH) due to rupture of small IAs.Aims:This study aims to clarify the clinical and morphological characteristics of ruptured small IA, focusing on posterior communicating artery (PCoA) aneurysms as a prone site.Settings and Design:We retrospectively reviewed 102 consecutive patients with SAH due to ruptured PCoA aneurysm who underwent microsurgical or endovascular aneurysm repair between April 2013 and March 2018.Subjects and Methods:All PCoA aneurysms were diagnosed using three-dimensional rotation angiography or three-dimensional computed tomography angiography. Information regarding the following clinical characteristics was collected: age, sex, past medical history, current smoking, antithrombotic therapy, multiplicity, hydrocephalus, intracerebral hemorrhage, intraventricular hemorrhage, and World Federation of Neurosurgical Societies (WFNS) Grade on admission.Statistical Analysis Used:We analyzed factors of ruptured small IA, focusing on PCoA aneurysms using univariate and multivariate regression analyses.Results:Univariate and multivariate analyses revealed that low aspect ratio (AR) (odds ratio [OR] = 0.33, P = 0.01) and nonfetal type of PCoA (OR = 0.31, P = 0.02) might be independent characteristics of ruptured small PCoA aneurysms. However, age, sex, past medical history, WFNS grade, and treatment outcome were not different between the small and nonsmall PCoA aneurysms. The aneurysm size was not associated to the selection of treatment, proportion of complications, and treatment outcome.Conclusions:In cases of ruptured PCoA aneurysms, low AR and nonfetal type of PCoA might be associated with rupture of small aneurysms.