Rupture Of Intracranial Aneurysms Research Articles

Osteopontin in post-subarachnoid hemorrhage pathologies.

Rupture of intracranial aneurysms causes subarachnoid hemorrhage (SAH), of which the treatment remains the most difficult among cerebrovascular disorders even in this modern medical era. Following successful surgical ablation of ruptured intracranial aneurysms, other conditions may be encountered including delayed cerebral ischemia and chronic hydrocephalus, in addition to early brain injury. Osteopontin (OPN) is one of matricellular proteins that have cytokine-like effect on various cells and act as secretory extracellular matrix proteins between cells. The complexity of OPN functions is attributed to its several isoforms, cleavage sites and functional changes determined by its differing isoforms following various cleavages or other post-translational modifications. Notably, OPN functions beneficially or harmfully in accordance with the context of OPN upregulation. In the field of aneurysmal SAH, OPN has exerted neuroprotective effects against early brain injury and delayed cerebral ischemia by suppressing apoptosis of neurons, disruption of blood-brain barrier, and/or cerebrovascular constriction, while excessive and prolonged secretion of OPN can be harmful through the occurrence of chronic hydrocephalus requiring shunt surgery. This is a review article that is focused on OPN's potential roles in post-SAH pathologies.

TPA-NMDAR Signaling Blockade Reduces the Incidence of Intracerebral Aneurysms.

Intracranial aneurysms (IAs) are pathological dilatations affecting cerebral arteries, and their ruptures lead to devasting intracranial hemorrhages. Although the mechanisms underlying the IA formation and rupture are still unclear, some factors have been identified as critical in the control of the vascular remodeling pathways associated with aneurysms. In a preclinical model, we have previously proposed the implication of the vascular serine protease, the tissue-type plasminogen activator (tPA), as one of the key players in this pathology. Here, we provide insights into the mechanism by which tPA is implicated in the formation and rupture of aneurysms. This was addressed using a murine model of IAs combined with (i) hydrodynamic transfections of various tPA mutants based on the potential implications of the different tPA domains in this pathophysiology and (ii) a pharmacological approach using a monoclonal antibody targeting tPA-dependent NMDA receptor (NMDAR) signaling and in vivo magnetic resonance brain imaging (MRI). Our results show that the endovascular tPA-NMDAR axis is implicated in IA formation and possibly their rupture. Accordingly, the use of a monoclonal antibody designed to block tPA-dependent endothelial NMDAR signaling (Glunomab®) decreases the rate of intracranial aneurysm formation and their rupture. The present study gives new insights into the IA pathophysiology by demonstrating the implication of the tPA-dependent endothelial NMDAR signaling. In addition, the present data proposes that a monoclonal antibody injected intravenously to target this process, i.e., Glunomab® could be a useful therapeutic candidate for this devastating disease.

What Are the Predictors of Intracranial Aneurysm Rupture in Indonesian Population Based on Angiographic Findings? Insight from Intracranial Aneurysm Registry on Three Comprehensive Stroke Centres in Indonesia.

Objectives What are the Predictors of Intracranial Aneurysm (IA) Rupture based on angiographic findings among patients in Indonesia's Population Based on Angiographic Findings. Materials and Methods We conducted a cross-sectional study on subjects with IA not caused by congenital aetiologies or other vascular malformations with cerebral angiography performed from January 2017 to January 2021. Demographic data and aneurysm profile, which include aneurysm count, size, location, and rupture event, were collected. The correlation between risk factors and IA rupture events was determined using bivariate and multivariate analysis. Results From 100 angiography data (33 males and 67 females), the mean subject age is 51.94 ± 10.78. We observe a total of 121 IAs from all subjects. Most of the IAs are in the anterior circulation (104 aneurysms, 85.96%), have small size (77 aneurysms, 63.64%), and are found in ruptured conditions (90 aneurysms, 74.38%). Males have a greater aneurysm count (1.36 ± 0.74 vs. 1.13 ± 0.55, p = 0.036) and larger aneurysm size (p = 0.002). Aneurysm size is significantly correlated with its location (p = 0.008). Medium size (p = 0.019; OR 2.62, 95% CI 1.08-6.36) and location other than the internal carotid artery are associated with increased rupture event. Multivariate analysis revealed that gender (p = 0.031; aOR 5.37, 95% CI 1.17-24.70) is a significant risk factor of IA rupture event. Conclusion IA profiling will enable clinicians to determine the risk of rupture and treatment plans for the Indonesian population. Further studies with a larger sample size are required to confirm these findings.

Hsa_circ_0031608: A Potential Modulator of VSMC Phenotype in the Rupture of Intracranial Aneurysms.

Background and PurposePhenotypic modulation of vascular smooth muscle cells (VSMCs) plays an important role in the development of intracranial aneurysms (IAs). Growing evidence has demonstrated that circular RNAs (circRNAs) may serve as a potential modulator of VSMC phenotype in various vascular diseases. This study aimed to assess the potential function of circRNAs in the rupture of IAs and VSMC phenotypic modulation.MethodsUsing surgically dissected human ruptured (n = 8) and unruptured (n = 8) IA lesions, differentially expressed circRNAs were screened by transcriptomic sequencing and verified using qRT-PCR. Based on the screened circRNA, we predicted and screened the combined miRNA and downstream mRNAs to construct circRNA-miRNA-mRNA networks. Further in vitro experiments were performed to investigate the relationship between the validated circRNA and the phenotypic switching of VSMCs.ResultsWe found 1,373 differentially expressed genes in ruptured versus unruptured aneurysms. The top five dysregulated circRNAs were selected for qRT-PCR validation. We found hsa_circ_0031608 was both highly expressed in ruptured IAs and pro-inflammatory transformation of VSMCs. Then, a regulatory circRNA-miRNA-mRNA with one circRNA node, six miRNA nodes, and 84 mRNA nodes was constructed. GO analysis and KEGG pathway enrichment analysis were performed on mRNAs in the network. Then, a PPI network was built based on these mRNAs and five hub genes were identified (FOXO3, DICER1, CCND2, IGF1R, and TNRC6B) by the cytoHubba plugin in Cytoscape software. In vitro, overexpression of hsa_circ_0031608 influenced the expression of VSMC phenotypic markers validated by qPCR and Western blotting. Furthermore, hsa_circ_0031608 promoted the migration and proliferation capacity of VSMCs.Conclusionhsa_circ_0031608 regulated the phenotypic modulation of VSMCs and played an important role in the rupture of IAs. The specific mechanism should be further studied and confirmed.

Combination of Morphological and Hemodynamic Parameters for Assessing the Rupture Risk of Intracranial Aneurysms: A Retrospective Study on Mirror Middle Cerebral Artery Aneurysms.

Discordant findings were frequently reported by studies dedicated to exploring the association of morphological/hemodynamic factors with the rupture of intracranial aneurysms (IAs), probably owing to insufficient control of confounding factors. In this study, we aimed to minimize the influences of confounding factors by focusing IAs of interest on mirror aneurysms and, meanwhile, modeling IAs together with the cerebral arterial network to improve the physiological fidelity of hemodynamic simulation. Fifty-two mirror aneurysms located at the middle cerebral artery (MCA) in 26 patients were retrospectively investigated. Numerical tests performed on two randomly selected patients demonstrated that over truncation of cerebral arteries proximal to the MCA during image-based model reconstruction led to uncertain changes in computed values of intra-aneurysmal hemodynamic parameters, which justified the minimal truncation strategy adopted in our study. Five morphological parameters (i.e., volume (V), height (H), dome area (DA), nonsphericity index (NSI), and size ratio (SR)) and two hemodynamic parameters (i.e., peak wall shear stress (WSS) (peakWSS), and pressure loss coefficient (PLc)) were found to differ significantly between the ruptured and unruptured aneurysms and proved by receiver operating characteristic (ROC) analysis to have potential value for differentiating the rupture status of aneurysm with the areas under curve (AUCs) ranging from 0.681 to 0.763. Integrating V, SR, peakWSS, and PLc or some of them into regression models considerably improved the classification of aneurysms, elevating AUC up to 0.864, which indicates that morphological and hemodynamic parameters have complementary roles in assessing the risk of aneurysm rupture.

Validation of the predictive accuracy of \u201cclinical + morphology nomogram\u201d for the rebleeding risk of ruptured intracranial aneurysms after admission

BackgroundRebleeding can cause a catastrophic outcome after aneurysmal subarachnoid hemorrhage. A clinical + morphology nomogram was promoted in our previous study to assist in discriminating the rupture intracranial aneurysms (RIAs) with a high risk of rebleeding. The aim of this study was to validate the predictive accuracy of this nomogram model.MethodThe patients with RIAs in two medical centers from December 2020 to September 2021 were retrospectively reviewed, whose clinical and morphological parameters were collected. The Cox regression model was employed to identify the risk factors related to rebleeding after their admission. The predicting accuracy of clinical + morphological nomogram, ELAPSS score and PHASES score was compared based on the area under the curves (AUCs).ResultsOne hundred thirty-eight patients with RIAs were finally included in this study, 20 of whom suffering from rebleeding after admission. Hypertension (hazard ratio (HR), 2.54; a confidence interval of 95% (CI), 1.01–6.40; P = 0.047), bifurcation (HR, 3.88; 95% CI, 1.29–11.66; P = 0.016), and AR (HR, 2.68; 95% CI, 1.63–4.41; P < 0.001) were demonstrated through Cox regression analysis as the independent risk factors for rebleeding after admission. The clinical + morphological nomogram had the highest predicting accuracy (AUC, 0.939, P < 0.01), followed by the bifurcation (AUC, 0.735, P = 0.001), AR (AUC, 0.666, P = 0.018), and ELAPSS score (AUC, 0.682, P = 0.009). Hypertension (AUC, 0.693, P = 0.080) or PHASES score (AUC, 0.577, P = 0.244) could not be used to predict the risk of rebleeding after admission. The calibration curve for the probability of rebleeding showed a good agreement between the prediction through clinical + morphological nomogram and actual observation.ConclusionHypertension, bifurcation site, and AR were independent risk factors related to the rebleeding of RIAs after admission. The clinical + morphological nomogram could help doctors to identify the high-risk RIAs with a high predictive accuracy.

Genome-wide linkage analysis combined with genome sequencing in large families with intracranial aneurysms

Rupture of an intracranial aneurysm (IA) leads to aneurysmal subarachnoid haemorrhage (ASAH), a severe type of stroke. Some rare variants that cause IA in families have been identified, but still, the majority of genetic causes, as well as the biological mechanisms of IA development and rupture, remain unknown. We aimed to identify rare, damaging variants for IA in three large Dutch families with multiple affected members with IA (N = 9, 11, and 6). By combining linkage analysis and genome sequencing (GS), we identified six rare and damaging variants for which all cases within one of the families were heterozygous. These variants were p.Tyr87Cys in SYCP1, p.Phe1077Leu in FMNL2, p.Thr754Lys in TBC1D2, p.Arg321His in ZNF782, p.Arg979Trp in CCDC180, and p.Val125Met in NCBP1. None of the variants showed association with IA status in a large cohort of 937 patients from the general IA patient population and 1046 controls. Gene expression in IA and cerebral artery tissue further prioritized FMNL2 and TBC1D2 as potential important players in IA pathophysiology. Further studies are needed to characterize the functional consequences of the identified variants and their role in the biological mechanisms of IA.

137 A Review of Current Criteria for Risk of Aneurysmal Subarachnoid Haemorrhage

Abstract Introduction There is a need to evaluate the existing guidelines regarding the size criteria for the risk of rupture of intracranial aneurysms. The current understanding is that small intracranial aneurysms (less than 7 mm) are not at significant risk for rupture according to the ISUIA 1 &amp; 2 trials. However, there have been several published series of rupture and subarachnoid haemorrhage from aneurysms less than 5 mm in both, anterior and posterior cerebral circulation. Methods We conducted a systematic review of aneurysmal subarachnoid haemorrhage, specifically to identify their size and the anatomical location at the time of rupture, using the healthcare databases advanced search. Results Our search yielded 1438 results matching our inclusion criteria. Our results demonstrated that 50.4 – 76.8% of aneurysms were under 7 mm in diameter at the time of rupture. Subarachnoid haemorrhage from smaller aneurysms (&amp;lt;5 mm) was also shown to present with poor prognoses (Hunt and Hess grades 4–5). There were no significant differences observed between the anterior and posterior circulation. Conclusions The existing criterion to determine the risk of rupture of intracranial aneurysms need to be updated, accounting for multiple clinical factors including, but not limited to, the size. With advances in endovascular treatments in recent years, the associated intra-procedural risks are greatly reduced compared to traditional neurosurgical approaches, making the argument for intervention at earlier presentations.

Irregular Pulsation of Intracranial Aneurysm Detected by Four-Dimensional CT Angiography and Associated With Small Aneurysm Rupture: A Single-Center Prospective Analysis.

ObjectivesPredicting the risk of rupture of small intracranial aneurysms remains challenging. The irregular pulsation of aneurysms detected by four-dimensional CT angiography (4D-CTA) could be an imaging marker of aneurysm vulnerability. We aimed to investigate the association of irregular pulsation with small aneurysm rupture.Materials and MethodsThis was a prospective study on intracranial aneurysms detected by 4D-CTA from October 2017 to January 2020. A total of 242 consecutive patients with 316 aneurysms were enrolled. Irregular pulsation was defined as a temporary focal protuberance on more than 3 consecutive frames of the 20 phases in the RR interval. Small aneurysms were defined as those <7 mm. Univariate and multivariate analyses were performed to determine the independent predictors of small aneurysm rupture.ResultsA total of 169 patients with 217 small intracranial aneurysms were included. Fourteen (6.5%) of the aneurysms had ruptured, and 77 (35.5%) had irregular pulsation. There were no significant differences in age, sex, hypertension, smoking, diabetes, drinking, or hyperlipidemia between the ruptured and unruptured aneurysm groups. The univariate analysis showed that smaller vessel size (p = 0.008), larger size ratio (p = 0.003), larger aspect ratio (p = 0.006), larger flow angle (p = 0.001), large vessel angle (p = 0.004), middle cerebral artery aneurysms (p = 0.046), anterior cerebral artery/posterior communicating artery/posterior circulation aneurysm (p = 0.006), irregular aneurysm (p = 0.001), and t presence of irregular pulsation (p = 0.001) were associated with small aneurysm rupture. The multivariate analysis showed that the presence of irregular pulsation (p = 0.003), anterior cerebral artery/posterior communicating artery/posterior circulation aneurysms (p = 0.014), and larger flow angle (p = 0.006) was independently associated with aneurysm rupture. Multivariate analysis of predictors of the irregular pulsation of small aneurysms showed that the aneurysm rupture (p = 0.022), irregular aneurysm (p < 0.001), and large size ratio (p = 0.005) were independently associated with the presence of irregular pulsation.ConclusionsThe ruptured small aneurysms more often had irregular pulsation. The irregular pulsation was independently associated with aneurysm rupture and may help evaluate the risk of rupture of small intracranial aneurysms.

Morphology-aware multi-source fusion-based intracranial aneurysms rupture prediction.

We proposed a new approach to train deep learning model for aneurysm rupture prediction which only uses a limited amount of labeled data. Using segmented aneurysm mask as input, a backbone model was pretrained using a self-supervised method to learn deep embeddings of aneurysm morphology from 947 unlabeled cases of angiographic images. Subsequently, the backbone model was finetuned using 120 labeled cases with known rupture status. Clinical information was integrated with deep embeddings to further improve prediction performance. The proposed model was compared with radiomics and conventional morphology models in prediction performance. An assistive diagnosis system was also developed based on the model and was tested with five neurosurgeons. Our method achieved an area under the receiver operating characteristic curve (AUC) of 0.823, outperforming deep learning model trained from scratch (0.787). By integrating with clinical information, the proposed model's performance was further improved to AUC = 0.853, making the results significantly better than model based on radiomics (AUC = 0.805, p = 0.007) or model based on conventional morphology parameters (AUC = 0.766, p = 0.001). Our model also achieved the highest sensitivity, PPV, NPV, and accuracy among the others. Neurosurgeons' prediction performance was improved from AUC=0.877 to 0.945 (p = 0.037) with the assistive diagnosis system. Our proposed method could develop competitive deep learning model for rupture prediction using only a limited amount of data. The assistive diagnosis system could be useful for neurosurgeons to predict rupture. • A self-supervised learning method was proposed to mitigate the data-hungry issue of deep learning, enabling training deep neural network with a limited amount of data. • Using the proposed method, deep embeddings were extracted to represent intracranial aneurysm morphology. Prediction model based on deep embeddings was significantly better than conventional morphology model and radiomics model. • An assistive diagnosis system was developed using deep embeddings for case-based reasoning, which was shown to significantly improve neurosurgeons' performance to predict rupture.

Imaging Modalities for Intracranial Aneurysm: More Than Meets the Eye.

Intracranial aneurysms (IA) are often asymptomatic and have a prevalence of 3 to 5% in the adult population. The risk of IA rupture is low, however when it occurs half of the patients dies from subarachnoid hemorrhage (SAH). To avoid this fatal evolution, the main treatment is an invasive surgical procedure, which is considered to be at high risk of rupture. This risk score of IA rupture is evaluated mainly according to its size and location. Therefore, angiography and anatomic imaging of the intracranial aneurysm are crucial for its diagnosis. Moreover, it has become obvious in recent years that several other factors are implied in this complication, such as the blood flow complexity or inflammation. These recent findings lead to the development of new IA imaging tools such as vessel wall imaging, 4D-MRI, or molecular MRI to visualize inflammation at the site of IA in human and animal models. In this review, we will summarize IA imaging techniques used for the patients and those currently in development.

Development and External Validation of a Dynamic Nomogram With Potential for Risk Assessment of Ruptured Multiple Intracranial Aneurysms.

Background and PurposeAbout 20.1% of intracranial aneurysms (IAs) carriers are multiple intracranial aneurysms (MIAs) patients with higher rupture risk and worse prognosis. A prediction model may bring some potential benefits. This study attempted to develop and externally validate a dynamic nomogram to assess the rupture risk of each IA among patients with MIA.MethodWe retrospectively analyzed the data of 262 patients with 611 IAs admitted to the Hunan Provincial People's Hospital between November 2015 and November 2021. Multivariable logistic regression (MLR) was applied to select the risk factors and derive a nomogram model for the assessment of IA rupture risk in MIA patients. To externally validate the nomogram, data of 35 patients with 78 IAs were collected from another independent center between December 2009 and May 2021. The performance of the nomogram was assessed in terms of discrimination, calibration, and clinical utility.ResultSize, location, irregular shape, diabetes history, and neck width were independently associated with IA rupture. The nomogram showed a good discriminative ability for ruptured and unruptured IAs in the derivation cohort (AUC = 0.81; 95% CI, 0.774–0.847) and was successfully generalized in the external validation cohort (AUC = 0.744; 95% CI, 0.627–0.862). The nomogram was calibrated well, and the decision curve analysis showed that it would generate more net benefit in identifying IA rupture than the “treat all” or “treat none” strategies at the threshold probabilities ranging from 10 to 60% both in the derivation and external validation set. The web-based dynamic nomogram calculator was accessible on https://wfs666.shinyapps.io/onlinecalculator/.ConclusionExternal validation has shown that the model was the potential to assist clinical identification of dangerous aneurysms after longitudinal data evaluation. Size, neck width, and location are the primary risk factors for ruptured IAs.

Should we screen for intracranial aneurysms in children with autosomal dominant polycystic kidney disease?

This is an overview of the challenges associated with screening for asymptomatic intracranial aneurysms (ICA) in children with autosomal dominant polycystic kidney disease (ADPKD). ADPKD is the most common inherited kidney disease affecting 1 in 1,000 people. ICAs are an extra-kidney manifestation of ADPKD, and while the exact pathophysiology of how they develop is unknown, we know that they more commonly occur in the adult rather than paediatric population. ICAs can be found in up to 9–11.5% of adults with ADPKD, but ICA rupture remains a rare event in adults with an incidence of 0.04 per 100 patient years. ICA size is an important factor in determining the risk of aneurysm rupture and therefore affects the decision on intervention in asymptomatic adults. For some, unruptured aneurysms cause no clinical significance, but those that rupture can be associated with devastating morbidity and mortality. Therefore, if detected, the treatment for unruptured ICAs is usually endovascular coiling, alongside recognising the importance of preventative interventions such as hypertension management. There are, however, no current guidelines for either adult or paediatric patients with ADPKD supporting regular screening for asymptomatic ICAs, although there is a suggestion for individualised practice, for example, with those with a positive family history. The UK clinical guidelines for ADPKD in children make research recommendations due to a lack of published literature, which in itself indicates that ICA rupture is an extremely rare phenomenon in children.

Abstract TMP110: Impairment Of Efferocytosis Promotes The Rupture Of Intracranial Aneurysm

Background: Efferocytosis is an apoptotic cell clearing process that reduces the tissue-damaging effects of excessive apoptotic cells. Mer receptor tyrosine kinase (Mertk) is present on the surface of phagocyte cells, such as macrophages, and mediates efferocytosis of apoptotic cells. Cleavage of Mertk by metalloproteinases impairs efferocytosis. Several studies suggested that the severity of atherosclerosis, myocardial infarction, and aortic aneurysms were increased in Mertk KO mice due to the impairment of efferocytosis. Higher levels of apoptosis are found in ruptured aneurysms compared to in unruptured aneurysms, suggesting impaired efferocytosis in rupture-prone aneurysms. However, whether impaired efferocytosis plays a role in the pathophysiology of intracranial aneurysms is unclear. In this project, we investigated the effect of impaired efferocytosis in intracranial aneurysms. Hypothesis: We hypothesize that impairment of efferocytosis promotes the rupture of intracranial aneurysms. Methods: We induced intracranial aneurysms by combining systemic hypertension and a single injection of elastase into the cerebrospinal fluid in mice. Aneurysm rupture rate was used as the primary endpoint. We used Mertk knockout (KO) mice. Results: There was no statistical difference in the formation rate of aneurysms between litter-mate control wild-type mice (WT) and Mertk KO mice. Interestingly, the aneurysmal rupture rate was significantly higher in Mertk KO mice (Mertk vs. WT: 94.7% vs. 61.5%, P &lt; 0.05%). Conclusions: Our experiment suggested that impairment of efferocytosis promotes aneurysm rupture. Inhibiting cleavage of Mertk may be a strategy for preventing the rupture of intracranial aneurysms.

Abstract 112: Roles Of Platelets In Aneurysm Formation And Rupture

Platelets were once exclusively connected to thrombus; however, they play more diverse roles. Platelets have been found to be mediators of adhesion and transmigration of leukocytes at sites of inflammation. Inflammation is emerging as a key factor in the formation and subsequent rupture of intracranial aneurysms. In the presence of endothelial damage as well as increased shear stress, platelets are activated and, thus, become capable of modulating inflammation. Both conditions are present at the site of intracranial aneurysm. Evaluation of ruptured and unruptured aneurysms have demonstrated the presence of thrombus intramurally and intraluminally. Furthermore, multiple cohort studies on the use of aspirin, an inhibitor of platelet aggregation, have shown a significant reduction in the incidence of aneurysmal rupture. We hypothesize that platelets promote the formation and rupture of intracranial aneurysm. To evaluate this hypothesis, c-mpl receptor knockout mice were used. These mice are thrombocytopenic due to impaired megakaryocyte function, making them an ideal model to test our hypothesis. Intracranial aneurysm was induced in mice by a combination of systemic hypertension and a single injection of elastase into the cerebrospinal fluid. The rate of aneurysm formation and rupture were used as endpoints. To evaluate systemic thrombocytopenia in study mice, platelet count in plasma samples was assessed. Platelets in c-mpl knockout mice were 85% lower than in wild-type controls (mean ± SD: 226*10 3 ± 9*10 3 /μL vs 1438*10 3 ± 183*10 3 /μL, P&lt; 0.05). Formation rate of aneurysm was reduced in c-mpl knockout as opposed to wild-type counterparts (65% vs 87%, P&lt;0.05). More importantly, there was also a reduction in rupture rate of aneurysms in c-mpl knockout compared to wild-type (45% vs 72%, P&lt;0.05). Our findings show that systemic reduction of platelets results in a decreased rate of aneurysm formation and rupture. We plan to investigate more specific interactions at the site of intracranial aneurysm between platelets and leukocytes or endothelial factors. We aim to find the molecules mediating these interactions in hopes that a therapeutic target can be identified.

Abstract TP256: The Role Of Dietary Iron Restriction In The Pathophysiology Of Intracranial Aneurysm Rupture

Background: Iron is an essential element for maintaining vascular wall, however iron depositions in vascular wall cause tissue damage by oxidative stress via Fenton/Haber-Weiss reaction. We hypothesized that iron promotes intracranial aneurysmal formation and rupture through oxidative stress and vascular inflammation. Using a mouse model of intracranial aneurysm, we examined whether iron restriction reduces aneurysm formation and rupture. Methods: To induce aneurysm, we combined induced systemic hypertension (deoxycorticosterone acetate-salt hypertension) and a single injection of elastase (35mU) into the cerebrospinal fluid at the right basal cistern. The mice were divided into two groups and fed with iron restricted diet (IRD) (0.32mg/100g) or normal diet (ND) (600mg/100g) for 5 weeks. Results: IRD significantly reduced the aneurysmal rupture compared to ND (ND versus IRD: 76% versus 37%; P &lt; 0.05). Whereas, there was no significant difference in the overall incidence of aneurysms between the ND and IRD groups (ND versus IRD: 68% versus 69%; P =1.00). Conclusion: Our data demonstrate that iron restriction reduces intracranial aneurysm rupture.

Abstract WP10: Automated Methods Of Aneurysm Growth Detection Compared With Clinical Assessment And Follow-up

Introduction: In cases where the risk of intracranial aneurysms (IA) rupture is low or secondary to other patient health concerns, unruptured IA may be monitored through imaging. In this work, we applied different computational methods to detect IA growth and compared the results to clinical findings. Hypothesis: We hypothesize that automated methods of IA growth detection are comparable to clinical assessment. Methods: The study cohort consisted of 20 female patients with saccular IA diagnosed between 2005-2011 in UCLA Medical Center. 6 were located at the PcoA, 10 at the superior hypophyseal artery, and 4 at the ophthalmic artery. 8 IA were determined to be growing. Baseline IA size was 3.85±4.30 mm. For each case, initial and first follow-up CTA image studies (interval 2.50±2.75 yrs) were analyzed. Cohort follow-up continued for an average of 8.5±5.75 yrs. Automated methods to detect IA growth included maximum diameter (HMAX), surface area (SA), volume (V), and a novel 2-stage morphing approach which deforms the baseline IA surface mesh to that of the subsequent scan and yields a set of characteristics that describe the changes: dMPL, dSA, dV, and dICDD. Statistical methods used included the Mann-Whitney U test and Chi-Square Test with significance set at p &lt;0.01, and ROC AUC analysis. Results: The stable and growth groups did not significantly differ with respect to case details and medical history, including IA size, location, imaging interval, age, family history, stroke, hypertension, thyroid disease, cancer, and atherosclerosis. Clinically determined change in IA diameter (p=0.007, AUC=0.927), computed HMAX (p=0.0002, AUC=0.958), SA (p=0.001, AUC=0.917), V (p=0.001, AUC=0.927), and dSA (p=0.005, AUC=0.865) were significantly different between the groups. The duration of follow-up significantly differed between the groups (p&lt;0.01), largely due to treatment of growing IA. During follow-up only one IA changing from stable to growing, and 5 of 6 subsequently treated IA were from within the initial growth group. Conclusion: Several automated measures provided comparable performance to clinical size when assessing IA growth. HMAX in particular may be useful to assist clinical evaluation, as it was slightly more effective than recorded clinical size alone.

Aneurysm size and blood pressure severity in patients with intracranial aneurysms and sleep apnea.

Obstructive sleep apnea is a risk factor for hypertension. Hypertension is associated with aneurysm formation, growth, and rupture of intracranial aneurysm (IA). Retrospectively, symptoms of obstructive sleep apnea are more prevalent in patients with IAs. Studies investigating the prevalence and effect of objectively measured sleep apnea in these patients are sparse. We report on the baseline data of an ongoing prospective study. We cross-sectionally analyzed whether obstructive sleep apnea was associated with larger IAs and increased need for antihypertensive medications in a population of patients with unruptured IA. 130 adult (≥ 18 years) patients with unruptured IAs were recruited. Patients with ischemic stroke or intracranial hemorrhage within 3 months prior to screening were excluded. We assessed obstructive sleep apnea by full-night respiratory polygraphy. Aneurysm size and antihypertensive medication-as a surrogate parameter for the severity of hypertension-were compared between patients with and without obstructive sleep apnea (apnea-hypopnea index >5 events/h). Aneurysm growth and rupture rate were retrospectively analyzed. 101 patients completed the study protocol. Obstructive sleep apnea was diagnosed in 68.0% (17) of male and 34.2% (26) of female participants and associated with more severe hypertension (1.536 ± 0.2 vs 0.74 ± 0.1 drugs; P = .01) and larger aneurysms (6.9 ± 1.0 vs 3.8 ± 0.5 mm; P = .01). Patients with obstructive sleep apnea had more antihypertensive medication and larger IAs, probably due to accelerated aneurysm growth. Sleep apnea should be considered in patients with IAs. More research is needed to investigate the effects of sleep apnea on IAs and aneurysm outcome. Registry: ClinicalTrials.gov; Name: Incidence and Effects of Sleep Apnea on Intracerebral Aneurysms-IESA Study; URL: https://clinicaltrials.gov/ct2/show/NCT02880059; Identifier: NCT02880059. Zaremba S, Albus L, Hadjiathanasiou A, Vatter H, Wüllner U, Güresir E. Aneurysm size and blood pressure severity in patients with intracranial aneurysms and sleep apnea. J Clin Sleep Med. 2022;18(6):1539-1545.

Serum IL-1, Pyroptosis and Intracranial Aneurysm Wall Enhancement: Analysis Integrating Radiology, Serum Cytokines and Histology.

Background and PurposeAneurysm wall enhancement (AWE) is correlated with the rupture and growth risk of unruptured intracranial aneurysms (UIAs). Pyroptosis is a proinflammation mode of lytic cell death, mediated by pyroptosis-related proteins, i.e., gasdermin D and interleukin 1 β (IL-1β). Integrating serum cytokines and histology, this study aimed to investigate the correlation between AWE and pyroptosis in UIAs.MethodsUIA patients receiving microsurgical clipping were prospectively enrolled from January 2017 and June 2020. UIA samples were collected, as well as the corresponding blood samples. In this study, high-resolution magnetic resonance was employed to identify the AWE. The serum 46-cytokines examination and the histological analysis were conducted to determine pyroptosis, CD68 and MMP2. The IL-1 ra/beta ratio was determined by complying with the serum IL-1β and IL-1.ra. A comparison was drawn in the differences between UIAs with and without AWE. Lastly, the correlation between inflammation in UIA samples and serums was investigated.ResultsThis study included 34 UIA patients. The serum proinflammatory cytokines [IL-1β (P < 0.001) and TNF-α (P < 0.001)] were up-regulated, and serum anti-inflammatory cytokine (IL-1.ra, P = 0.042) were down-regulated in patients with AWE UIAs. The patients with AWE UIAs achieved a higher IL-1.ra/beta ratio (P < 0.001). The multivariate logistic analysis demonstrated IL-1β [odds ratio (OR), 1.15; 95% confidence interval (CI), 1.02–1.30; P = 0.028] and IL-1.ra (OR, 0.998; 95% CI, 0.997–1.000; P = 0.017) as the risk factors correlated with the AWE. IL-1.ra/beta ratio achieved the highest predictive accuracy [area under the curve (AUC), 0.96] for AWE, followed by IL-1.ra (AUC, 0.90), IL-1β (AUC, 0.88) and TNF-α (AUC, 0.85). As compared with the UIAs without AWE, the AWE UIAs were manifested as a severer wall remodeling, with higher relative levels of pyroptosis-related proteins, CD68 and MMP2. The serum IL-1β, IL-1.ra and IL-1.ra/beta ratio had a positive correlation with the relative levels of pyroptosis-related proteins, CD68 and MMP2 in UIA tissues.ConclusionThe serum IL-1β and IL-1.ra were correlated with the AWE. More pyroptosis-related proteins were identified in UIAs with AWE. The serum IL-1β and IL-1.ra were correlated with the pyroptosis-related proteins in aneurysm tissues.

Can Endovascular Treatment of Fusiform Intracranial Aneurysms Restore the Healthy Hemodynamic Environment?-A Virtual Pilot Study.

Numerous studies assess intracranial aneurysm rupture risk based on morphological and hemodynamic parameter analysis in addition to clinical information such as aneurysm localization, age, and sex. However, intracranial aneurysms mostly occur with a saccular shape located either lateral to the parent artery or at a bifurcation. In contrast, fusiform intracranial aneurysms (FIAs), i.e., aneurysms with a non-saccular, dilated form, occur in approximately 3–13% of all cases and therefore have not yet been as thoroughly studied. To improve the understanding of FIA hemodynamics, this pilot study contains morphological analyses and image-based blood flow simulations in three patient-specific cases. For a precise and realistic comparison to the pre-pathological state, each dilation was manually removed and the time-dependent blood flow simulations were repeated. Additionally, a validated fast virtual stenting approach was applied to evaluate the effect of virtual endovascular flow-diverter deployment focusing on relevant hemodynamic quantities. For two of the three patients, post-interventional information was available and included in the analysis. The results of this numerical pilot study indicate that complex flow structures, i.e., helical flow phenomena and the presence of high oscillating flow features, predominantly occur in FIAs with morphologically differing appearances. Due to the investigation of the individual healthy states, the original flow environment could be restored which serves as a reference for the virtual treatment target. It was shown that the realistic deployment led to a considerable stabilization of the individual hemodynamics in all cases. Furthermore, a quantification of the stent-induced therapy effect became feasible for the treating physician. The results of the morphological and hemodynamic analyses in this pilot study show that virtual stenting can be used in FIAs to quantify the effect of the planned endovascular treatment.