Intracranial Aneurysms In Patients Research Articles

Clinical characteristics and treatment strategies for pituitary adenoma associated with intracranial aneurysm

BackgroundThis study aimed to investigate clinical features and treatment strategies for intracranial aneurysm (IA) associated with pituitary adenoma (PA).MethodsWe enrolled patients with lesions in the sellar region and age-matched general population who were confirmed with IA from two hospitals. Four types of treatment strategies were performed, which included Type I (both IA and PA were treated with surgery), Type II (IA was treated with surgery and PA was performed by non-surgical treatment), Type III (PA was performed with surgery and observation was available for IA) and Type IV (both IA and PA were performed with non-surgical treatment).ResultsThe incidence of IA was 2.2% in the general population, 6.1% in patients with PA, 4.3% in patients with Rathke cleft cyst, 2.8% in patients with meningioma and none were found with IA in patients with craniopharyngioma. Age over 50 years (OR, 2.69; 95% CI, 1.20–6.04; P = 0.016), female (OR, 3.83, P = 0.003), and invasive tumor (OR, 3.26, P = 0.003) were associated with a higher incidence of IA in patients with PA. During the mean follow-up of 49.2 months, no patients experienced stroke, and recurrence of aneurysms and aneurysms treated with observation were stable. Of four patients with recurrence of PA, three patients were treated for type I and one patient for type III.ConclusionsPreoperative evaluation for aneurysm screening is necessary due to the high incidence of IA in PA patients. Our current treatment strategies may provide a benefit for these patients.

Circ_0008571 modulates the phenotype of vascular smooth muscle cells by targeting miR-145-5p in intracranial aneurysms

BackgroundThe dysfunction of human vascular smooth cells (hVSMCs) is significantly connected to the development of intracranial aneurysms (IAs). By suppressing the activity of microRNAs (miRNAs), circular RNAs (circRNAs) participate in IA pathogenesis. Nevertheless, the role of hsa_circ_0008571 in IAs remains unclear. MethodscircRNA sequencing was used to identify circRNAs from human IA tissues. To determine the function of circ_0008571, Transwell, wound healing, and cell proliferation assays were conducted. To identify the target of circ_0008571, the analyses of CircInteractome and TargetScan, as well as the luciferase assay were carried out. Furthermore, circ_0008571 knockdown and over-expression were performed to investigate its functions in IA development and the underlying molecular mechanisms. ResultsBoth hsa_circ_0008571 and Integrin beta 8 (ITGB8) were downregulated, while miR-145-5p transcription was elevated in the aneurysm wall of IAs patients compared to superficial temporal artery tissues. In vitro, cell migration and growth were dramatically suppressed after hsa_circ_0008571 overexpression. Mechanistically, has_circ_0008571 could suppress miR-145-5p activity by direct sponging. Moreover, we found that ITGB8 expression and the activation of the TGF-β-mediated signaling pathway were significantly enhanced. ConclusionThe hsa_circ_0008571-miR-145-5p-ITGB8 axis plays an essential role in IA progression.

Intracranial arterial calcification in patients with unruptured and ruptured intracranial aneurysms.

Arterial calcification is thought to protect against rupture of intracranial aneurysms, but studies in a representative population of intracranial aneurysm patients have not yet been performed. The aim was to compare the prevalence of aneurysm wall calcification and intracranial carotid artery calcification (ICAC) between patients with an unruptured intracranial aneurysm (UIA) and a ruptured intracranial aneurysm (RIA). We matched 150 consecutive UIA patients to 150 RIA patients on age and sex. Aneurysm wall calcification and ICAC were quantified on non-contrast enhanced computed tomography images with the modified Agatston score. We compared the prevalence of aneurysm wall calcification, ICAC, and severe ICAC (defined as a modified Agatston score in the fourth quartile) between UIA and RIA patients using univariate and multivariate conditional logistic regression models adjusted for aneurysm characteristics and cardiovascular risk factors. Aneurysm wall calcification was more prevalent in UIA compared to RIA patients (OR 5.2, 95% CI: 2.0-13.8), which persisted after adjustment (OR 5.9, 95% CI: 1.7-20.2). ICAC prevalence did not differ between the two groups (crude OR 0.9, 95% CI: 0.5-1.8). Severe ICAC was more prevalent in UIA patients (OR 2.0, 95% CI: 1.1-3.6), but not after adjustment (OR 1.0, 95% CI: 0.5-2.3). Aneurysm wall calcification but not ICAC was more prevalent in UIAs than in RIAs, which corresponds to the hypothesis that calcification may protect against aneurysmal rupture. Aneurysm wall calcification should be further assessed as a predictor of aneurysm stability in prospective cohort studies. Calcification of the intracranial aneurysm wall was more prevalent in unruptured than ruptured intracranial aneurysms after adjustment for cardiovascular risk factors. Calcification may therefore protect the aneurysm against rupture, and aneurysm wall calcification is a candidate predictor of aneurysm stability. Aneurysm wall calcification was more prevalent in patients with unruptured than ruptured aneurysms, while internal carotid artery calcification was similar. Aneurysm wall calcification but not internal carotid artery calcification is a candidate predictor of aneurysm stability. Cohort studies are needed to assess the predictive value of aneurysm wall calcification for aneurysm stability.

Intracranial aneurysms in patients with acute ischemic stroke prevalence and influence on mechanical thrombectomy over 14 years in a tertiary-care center

IntroductionThe prevalence of intracranial aneurysms (IA) in patients with acute ischemic stroke (AIS) requiring mechanical thrombectomy (MT) is unclear. ObjectiveTo describe the prevalence of IA in patients with AIS and their influence on MT. Materials & methodsThis is a retrospective cohort study on all patients admitted with a diagnosis of AIS from January 2008 to March 2022 at a tertiary academic center. The records were reviewed for demographic, clinical, imaging, and outcomes data. Only patients who had CTA at admission were included in this analysis. ResultsAmong 2265 patients admitted with AIS, this diagnosis was confirmed in 2113 patients (93.3 %). We included 1111 patients (52.6 %) who had head CTA and 321 (28.9 %) who underwent MT. The observed prevalence of aneurysms on CTA was 4.5 % (50/1111 patients), and 8 (16 %) had multiple aneurysms. MT was performed in 7 patients harboring IAs: 6 ipsilateral (5 proximal and 1 distal to the occlusion)and 1 contralateral aneurysm.. The patient with a contralateral aneurysm had a TICI 2B score In patients with ipsilateral aneurysms, TICI 2B or 3 was achieved in 3 cases (50 %), which is significantly lower than historical control of MT (91.6 %) without IA (p = 0.01). No aneurysms ruptured during MT. The aneurysm noted distal to the occlusion was mycotic. ConclusionIn this analysis, the observed prevalence of IA in patients with AIS was 4.5%. Ipsilateral aneurysms (proximal or distal to the occlusion site) deserve particular attention, given the potential risk of rupture during MT. Aneurysms located distal to the occlusion were mycotic and the rate of recanization in patients with ipsilateral aneurysms was low compared to historical controls. Further studies are needed to improve the outcomes in patients with IA requiring MT.

Natural history and growth rate of intracranial aneurysms in Loeys-Dietz syndrome: implications for treatment.

Loeys-Dietz syndrome (LDS) is a heritable aortopathy associated with craniofacial abnormalities and dilatation and dissection of the aorta and its branches, as well as increased risk for intracranial aneurysms (ICAs). Given the rarity of the disease, the authors aimed to better define the natural history and role for the treatment for ICAs in these patients. The medical records of 83 patients with LDS were retrospectively reviewed to obtain clinical and genetic history and vascular imaging of the aorta, aortic branches, and intracranial vessels. Serial radiology reports and cervical and intracranial vascular images were reviewed to determine presence, location, and size of ICAs. In total, 55 patients (66.3%) had at least two screening intracranial vascular examinations, and 19 (22.9%) had at least 1 ICA detected. Aneurysms were typically small (mean ± SD 3.2 ± 1.8 mm). ICAs were most often located in the cavernous carotid, followed by the ophthalmic and anterior cerebral artery vessels. The rate of ICA growth was 0.43 ± 0.53 mm/year, similar to that of the general population. Three patients underwent intervention for an ICA, with 1 procedure complicated by stroke and resulting in transient hemiparesis. Several illustrative cases detail the authors' experience with ICA growth, de novo aneurysm formation, and ICA intervention in this rare patient population. ICAs in patients with LDS are common, are frequently small, and have a growth rate similar to that of unruptured ICAs in the general population. More aggressive or earlier intervention for asymptomatic ICAs identified in LDS patients compared with the general population is likely unwarranted based on the authors' experience at their institution.

Anchura del bulbo de la arteria carótida interna: un nuevo parámetro potencial para la predicción de enfermedades vasculares cerebrales

ObjectiveTo investigate the relationship between the width of the internal carotid artery (ICA) bulb and cerebral vascular diseases including stroke and intracranial aneurysms. Material and methodsIn total 300 patients who had supra-aortic computed tomography angiography (CTA) were enrolled in this study from 2015 to 2021. The study groups consisted of 100 ischemic stroke patients, 100 patients with intracranial aneurysms, and 100 control subjects. The intracranial aneurysm patient group was divided into two subgroups according to the presence of subarachnoid hemorrhage (SAH). The largest diameters of the ICA C1 (cervical) and C2 (petrous) segments in all individuals were measured bilaterally on CTA images. The ICA diameter ratios of the cases were measured using the formula (C1-C2)/C1. The relationship between the age and ICA vessel analysis was evaluated as well. ResultsThe mean ICA bulb width values in the ischemic stroke patient group and the intracranial aneurysm patient group were significantly higher than the control group (P<.001). The ICA C1 and C2 segment diameter values and ICA diameter ratio were smaller in the intracranial aneurysm patients with SAH than those who had not (P= 0.7). There was a statistically significant but weak relationship between the age and ICA diameter ratios in all study groups (R-squared value of 0.26, P= 0.03). ConclusionICA bulb width is a parameter that can be easily evaluated with neuroimaging modalities and is a successful method that may be used for predicting the risk of ischemic stroke or the presence of an intracranial aneurysm.

The Impact of Preprocedural Platelet Function Testing on Periprocedural Complication Rates Associated With Pipeline Flow Diversion: An International Multicenter Study.

Dual antiplatelet therapy (DAPT) is necessary to minimize the risk of periprocedural thromboembolic complications associated with aneurysm embolization using pipeline embolization device (PED). We aimed to assess the impact of platelet function testing (PFT) on reducing periprocedural thromboembolic complications associated with PED flow diversion in patients receiving aspirin and clopidogrel. Patients with unruptured intracranial aneurysms requiring PED flow diversion were identified from 13 centers for retrospective evaluation. Clinical variables including the results of PFT before treatment, periprocedural DAPT regimen, and intracranial complications occurring within 72 h of embolization were identified. Complication rates were compared between PFT and non-PFT groups. Differences between groups were tested for statistical significance using the Wilcoxon rank sum, Fisher exact, or χ 2 tests. A P -value <.05 was statistically significant. 580 patients underwent PED embolization with 262 patients dichotomized to the PFT group and 318 patients to the non-PFT group. 13.7% of PFT group patients were clopidogrel nonresponders requiring changes in their pre-embolization DAPT regimen. Five percentage of PFT group [2.8%, 8.5%] patients experienced thromboembolic complications vs 1.6% of patients in the non-PFT group [0.6%, 3.8%] ( P = .019). Two (15.4%) PFT group patients with thromboembolic complications experienced permanent neurological disability vs 4 (80%) non-PFT group patients. 3.7% of PFT group patients [1.5%, 8.2%] and 3.5% [1.8%, 6.3%] of non-PFT group patients experienced hemorrhagic intracranial complications ( P > .9). Preprocedural PFT before PED treatment of intracranial aneurysms in patients premedicated with an aspirin and clopidogrel DAPT regimen may not be necessary to significantly reduce the risk of procedure-related intracranial complications.

Internal carotid artery bulb width: a novel potential parameter for the prediction of cerebral vascular diseases

ObjectiveTo investigate the relationship between the width of the internal carotid artery (ICA) bulb and cerebral vascular diseases including stroke and intracranial aneurysms. Material and methodsIn total 300 patients who had supra-aortic computed tomography angiography (CTA) were enrolled in this study from 2015 to 2021. The study groups consisted of 100 ischemic stroke patients, 100 patients with intracranial aneurysms, and 100 control subjects. The intracranial aneurysm patient group was divided into two subgroups according to the presence of subarachnoid hemorrhage (SAH). The largest diameters of the ICA C1 (cervical) and C2 (petrous) segments in all individuals were measured bilaterally on CTA images. The ICA diameter ratios of the cases were measured using the formula C1-C2C1. The relationship between the age and ICA vessel analysis was evaluated as well. ResultsThe mean ICA bulb width values in the ischemic stroke patient group and the intracranial aneurysm patient group were significantly higher than the control group (p < 0.001). The ICA C1 and C2 segment diameter values and ICA diameter ratio were smaller in the intracranial aneurysm patients with SAH than those who had not (p = 0.7). There was a statistically significant but weak relationship between the age and ICA diameter ratios in all study groups (R-squared value of 0.26, p = 0.03). ConclusionICA bulb width is a parameter that can be easily evaluated with neuroimaging modalities and is a successful method that may be used for predicting the risk of ischemic stroke or the presence of an intracranial aneurysm.

Influence of Perioperative Three-Dimensional Computed Tomography (CT) Angiography and Surgical Clipping for Unruptured Cerebral Aneurysms on Renal Function in Patients with Chronic Kidney Disease

BackgroundSurgical clipping is a valuable treatment option for unruptured intracranial aneurysms in patients with chronic kidney disease (CKD). However, the comprehensive impact of clipping and perioperative three-dimensional computed tomography angiography (3D-CTA) on renal function remains unclear. This study aimed to evaluate the effects of perioperative 3D-CTA and surgical clipping on renal function in patients with CKD. MethodsWe retrospectively analyzed 529 patients who underwent surgical clipping and perioperative 3D-CTA. An estimated glomerular filtration rate (eGFR) < 60 was defined as CKD. Patients were stratified according to their renal function (group 1: eGFR ≥ 60, group 2: 45 ≤ eGFR < 60, group 3: 30 ≤ eGFR < 45, group 4: eGFR < 30 ml/min/1.73 m2), and eGFR was assessed preoperatively and 1 week and several months postoperatively. ResultsOf the 529 patients, 442 did not have CKD and 87 had CKD. Hypertension, hyperlipidemia and hyperuricemia were significantly more common in those with CKD. After the surgery and perioperative series of 3D-CTA, renal function deterioration was not observed in any group, whether in the acute or chronic postoperative period. Notably, eGFR significantly increased in groups 2 (66.7 ± 10.1, p<0.01) and 3 (48.9 ± 9.2, p=0.02) 1 week postoperatively, despite the CKD. ConclusionsSurgical clipping of unruptured intracranial aneurysms and perioperative 3D-CTA with normal-dose contrast media did not impair renal function in patients with CKD. These results could be valuable in determining treatment strategies for those with CKD and intracranial aneurysms.

Exploring the potential of VGLL3 methylation as a prognostic indicator for intracranial aneurysm with gender-specific considerations.

DNA methylation is widely recognized to play a role in intracranial aneurysm (IA) pathogenesis. We investigated the levels of methylation of vestigial-like 3 (VGLL3) in IA and explored its potential as a prognostic indicator. A total of 48 patients with IA and 48 healthy controls were included in the present study. Methylation levels of CpG sites were assessed using bisulfite pyrosequencing, and levels of VGLL3, TEAD, and YAP in the blood were measured by real-time quantitative polymerase chain reaction testing. VGLL3 methylation was significantly higher in controls than in IA patients (P=0.001), and this phenomenon was more pronounced in females (P<0.001). Compared with the control group, the expression levels of VGLL3 and TEAD in the blood of IA patients were significantly increased, while YAP was significantly decreased. VGLL3 methylation was positively correlated with HDL (P=0.003) and female Lpa concentration (r = 0.426, P=0.03), and was also negatively correlated with age (P=0.003), APOE (P=0.005), and VGLL3 mRNA expression (P<0.001). Methylation and mRNA expression of VGLL3 may serve as indicators of IA risk in females (AUC = 0.810 and 0.809). VGLL3 methylation may participate in the pathogenesis of IA by regulating the expression of the VGLL3/TEAD/YAP pathway, and its gene methylation and expression levels have IA risk prediction value.

A nomogram for predicting the risk of cerebral vasospasm after neurosurgical clipping in patients with aneurysmal subarachnoid hemorrhage.

Cerebral vasospasm (CVS) is a common complication that occurs after neurosurgical clipping of intracranial aneurysms in patients with aSAH. This complication can lead to clinical deterioration and a poor prognosis. The aim of this study is to explore the risk factors for CVS in aSAH patients who have undergone neurosurgical clipping, develop a nomogram for CVS, and evaluate its performance. Patients with aSAH who underwent neurosurgical clipping in the Department of Neurosurgery from January 2018 to January 2023 were selected as the subjects of this research. The clinical data of these patients were retrospectively analyzed. Logistic multivariate regression analysis was employed to identify the independent risk factors of CVS. A clinical prediction model in the form of a nomogram for CVS was developed using the R programming language and subsequently evaluated for its performance and quality. A total of 156 patients with aSAH were included in the analysis, comprising 109 patients in the training set and 47 patients in the validation set. In the training cohort, 27 patients (24.77%) developed CVS after neurosurgical clipping, while in the validation cohort, 15 patients (31.91%) experienced CVS. Multivariate regression analysis revealed that age, Hcy, WBC, glucose/potassium ratio, aneurysm location, and modified Fisher grade were independent risk factors for CVS. The nomogram exhibited excellent discriminative performance in both the training set (AUC = 0.885) and the validation set (AUC = 0.906). CVS was a prevalent complication following neurosurgical clipping in patients with aSAH, with a highly intricate pathogenesis and pathophysiological course. Early prediction of CVS represented a significant challenge in clinical practice. In this study, age, Hcy, WBC, glucose/potassium ratio, aneurysm location, and modified Fisher grade emerged as independent risk factors for CVS. The resulting nomogram demonstrated substantial predictive value.

The preliminary study suggests an association between NF-ĸB pathway activation and increased plasma 20S proteasome activity in intracranial aneurysm patients

The significant role of increased activation of 20S proteasomes in the development of abdominal aortic aneurysms has been well-established in a mouse model. The available literature lacks similar studies concerning brain aneurysms. The aim of the study was to verify the hypothesis that patients with unruptured intracranial aneurysms (UIA) have increased 20S proteasome ChT-L activity compared to the control group of individuals without vascular lesions in the brain. In the next step, the relationship between the activity of 20S proteasomes ChT-L and precursor proteins from the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) family, namely NF-κB1 (p105), NF-κB2 (p100), NF-κB p65, and the inflammatory chemokine MCP-1, was examined. Patients with UIA had significantly higher 20S ChT-L proteasome activity compared to the control group. Patients with multiple aneurysms had significantly higher 20S proteasome ChT-L activity compared to those with single aneurysms. In patients with UIA, the activity of the 20S proteasome ChT-L negatively correlated with the concentration of NF-κB1 (p105) and NF-κB p65 precursor proteins and positively correlated with the concentration of the cerebrospinal fluid chemokine MCP-1. Our results may suggest that increased 20S proteasome ChT-L activity in UIA patients modulates inflammation in the cerebral arterial vessel via the MCP-1 chemokine as a result of activation of the canonical NF-κB pathway.

Factors associated with early-onset intracranial aneurysms in patients with autosomal dominant polycystic kidney disease.

Recently, the importance of attribute-based medicine has been emphasized. The effects of early-onset intracranial aneurysms on patients can be significant and long-lasting. Herein, we compared the factors associated with intracranial aneurysms in patients with autosomal dominant polycystic kidney disease (ADPKD) according to age categories (≥ 50years, < 50years). We included 519 ADPKD patients, with a median age of 44years, estimated glomerular filtration rate of 54.5mL/min/1.73 m2, and total follow-up duration of 3104 patient-years. Logistic regression analyses were performed to determine factors associated with intracranial aneurysms. Regarding the presence ofintracranial aneurysm, significant interactions were identified between the age category (age ≥ 50years), female sex (P = 0.0027 for the interaction) and hypertension (P = 0.0074 for the interaction). Female sex and hypertension were associated with intracranial aneurysm risk factors only in patients aged ≥ 50years. The presence of intracranial aneurysm was significantly associated with chronic kidney disease (CKD) stages 4-5 (odds ratio [OR] = 3.87, P = 0.0007) and family history of intracranial aneurysm or subarachnoid hemorrhage (OR = 2.30, P = 0.0217) in patients aged < 50years. For patients aged ≥ 50years, in addition to the abovementioned factors [OR = 2.38, P = 0.0355 for CKD stages 4-5; OR = 3.49, P = 0.0094 for family history of intracranial aneurysm or subarachnoid hemorrhage], female sex (OR = 4.51, P = 0.0005), and hypertension (OR = 5.89, P = 0.0012) were also associated with intracranial aneurysm. Kidney dysfunction and family history of intracranial aneurysm or subarachnoid hemorrhage are risk factors for early-onset intracranial aneurysm. Patients aged < 50years with a family history of intracranial aneurysm or subarachnoid hemorrhage or with CKD stages 4-5 may be at an increased risk of early-onset intracranial aneurysm.

Abstract TP5: Impact of Race on Outcomes in the Endovascular and Microsurgical Treatment in Patients With Intracranial Aneurysms: Analysis of the Stroke Thrombectomy and Aneurysm Registry

Introduction: Impact of race on outcomes in the treatment of intracranial aneurysm (IA) remains unclear. We aimed to investigate the relationship between race classified into White, Black, Hispanic, and other ("other" includes Native American or Alaska Native, Asian or Pacific Islander, and other race) and treatment outcomes in patients with ruptured and unruptured IAs. Methods: Stroke Thrombectomy and Aneurysm Registry (STAR) was a retrospective observational study. Data from 9 centers in the United States, Europe, and Asia for IA patients who undertook endovascular treatment (EVT) or microsurgical treatment (MST) between January 2016 and December 2020 were included for analysis. The primary outcome was 90-day mRS 0-2. Secondary outcomes included periprocedural cerebral infarction and intracranial hemorrhage, perioperative symptomatic cerebral vasospasm in ruptured IA and mortality, and all causes of mortality within 90 days. Results: 2,836 IA patients treated with EVT or MST were included. Among these 2,836 patients, 1,053 patients were White, 350 were Black, 264 were Hispanic, and 1,169 were other. The primary outcome in Hispanic patients was significantly lower than White patients (adjusted odds ratio [aOR] 0.36, 95% CI, 0.23-0.56, P &lt; .001). The periprocedural cerebral infarction, perioperative mortality, and all causes of mortality in Hispanic patients were significantly higher than White patients (aOR 2.53, 95% CI, 1.40-4.58, P = .002, aOR 1.84, 95% CI, 1.00-3.38, P = .049, aOR 1.83, 95% CI, 1.06-3.17, P = .03, respectively). However, these outcomes were not significantly different in Black and other patients compared to White patients. Conclusions: This study demonstrates Hispanic IA patients are more likely to have a poor outcome at 90 days following EVT or MST than White patients.

Metabolic alterations of peripheral blood immune cells and heterogeneity of neutrophil in intracranial aneurysms patients.

Intracranial aneurysms (IAs) represent a severe cerebrovascular disease that can potentially lead to subarachnoid haemorrhage. Previous studies have demonstrated the involvement of peripheral immune cells in the formation and progression of IAs. Nevertheless, the impact of metabolic alterations in peripheral immune cells and changes in neutrophil heterogeneity on the occurrence and progression of IAs remains uncertain. Single-cell Cytometry by Time-of-Flight (CyTOF) technology was employed to profile the single-cell atlas of peripheral blood mononuclear cells (PBMCs) and polymorphonuclear cells (PMNs) in 72 patients with IAs. In a matched cohort, metabolic shifts in PBMC subsets of IA patients were investigated by contrasting the expression levels of key metabolic enzymes with their respective counterparts in the healthy control group. Simultaneously, compositional differences in peripheral blood PMNs subsets between the two groups were analysed to explore the impact of altered heterogeneity in neutrophils on the initiation and progression of IAs. Furthermore, integrating immune features based on CyTOF analysis and clinical characteristics, we constructed an aneurysm occurrence model and an aneurysm growth model using the random forest method in conjunction with LASSO regression. Different subsets exhibited distinct metabolic characteristics. Overall, PBMCs from patients elevated CD98 expression and increased proliferation. Conversely, CD36 was up-regulated in T cells, B cells and monocytes from the controls but down-regulated in NK and NKT cells. The comparison also revealed differences in the metabolism and function of specific subsets between the two groups. In terms of PMNs, the neutrophil landscape within patients group revealed a pronounced shift towards heightened complexity. Various neutrophil subsets from the IA group generally exhibited lower expression levels of anti-inflammatory functional molecules (IL-4 and IL-10). By integrating clinical and immune features, the constructed aneurysm occurrence model could precisely identify patients with IAs with high prediction accuracy (AUC=0.987). Furthermore, the aneurysm growth model also exhibited superiority over ELAPSS scores in predicting aneurysm growth (lower prediction errors and out-of-bag errors). These findings enhanced our understanding of peripheral immune cell participation in aneurysm formation and growth from the perspectives of immune metabolism and neutrophil heterogeneity. Moreover, the predictive model based on CyTOF features holds the potential to aid in diagnosing and monitoring the progression of human IAs.

Stability of infundibular dilatations: a single center follow-up study and systematic review of the literature

PurposeAlthough infundibular dilatations (IDs) have been thought to be benign anatomical variants, case reports suggest that they can grow and rupture. The aim of this study was to determine whether IDs have a tendency to grow or rupture.MethodsThe study population was collected from the Tampere University Hospital (TAUH) Aneurysm Database. The presence of IDs was screened from the medical records and imaging studies of 356 intracranial aneurysm patients left to follow-up from 2005 to 2020. The imaging studies were reviewed to confirm the IDs, and their clinical course. Finally, we performed a systematic review of published cases of ID leading to aneurysmatic rupture from PubMed.ResultsWe found 97 typical IDs in 83 patients and 9 preaneurysmal lesions resembling ID in 9 patients. Out of the typical cone-shaped IDs, none grew or ruptured in a total follow-up of 409 patient-years. One preaneurysmal lesion ruptured during a follow-up: this lesion had components of both infundibular dilatation and aneurysm at the beginning of follow-up. In the systematic literature search, we found 20 cases of aneurysmatic SAHs originating from an ID. Of those, only 7 had imaging available prerupture. All 7 IDs were typically cone-shaped, but a branching vessel originating from the apex of ID was only seen in 4/7.ConclusionTypical infundibular dilatations seem to be benign anatomical variants that are stable and, thus, do not need prophylactic treatment or imaging follow-up. Likely, the SAHs reported from IDs were actually caused by misdiagnosed preaneurysmal lesions.

Increased serum levels of high-mobility group box 1 protein and the location characteristics in the patients of intracranial aneurysms

ObjectiveInflammation-related factors play a crucial role in intracranial aneurysms (IA) initiation, progression, and rupture. High mobility group box 1 (HMGB-1) serves as an alarm to drive the pathogenesis of the inflammatory disease. This study aimed to evaluate the role of HMGB-1 in IA and explore the correlation with other inflammatory-related factors. MethodsA total of twenty-eight adult male Japanese white rabbits were included in with elastase-induced aneurysms, n = 18) and the control group (normal rabbits, n = 10). To assess the expression of HMGB-1, both reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) was performed on serum samples obtained from human subjects (10 patients with IA and 10 healthy donors) as well as from rabbits (aneurysm group and control group). Immunohistochemistry and immunofluorescence were employed to evaluate the expression levels of elastic fibers, HMGB-1, tumor necrosis factor-alpha (TNF-α), and triggering receptor expressed on myeloid cells-1 (TREM-1). ResultsThe expression of HMGB-1 was found to be significantly higher in the IA group compared to the control group, both at the mRNA and protein levels (P < 0.0001). Similar findings were observed in the rabbit aneurysm model group compared to the control group (P < 0.0001). HMGB-1 expression was observed to be more abundant in the inner wall of the aneurysm compared to the external wall, whereas in the control group, it was rarely scattered. Additionally, the localization patterns of TNF-α and TREM-1 exhibited similar characteristics to HMGB-1. ConclusionOur findings demonstrate that HMGB-1 is highly expressed in both IA patients and rabbit aneurysm models. Furthermore, the similar localization patterns of HMGB-1, TNF-α, and TREM-1 suggest their potential involvement in the inflammatory processes associated with IA. These results highlight the potential of HMGB-1 as a novel therapeutic target for IA.

Current understanding of macrophages in intracranial aneurysm: relevant etiological manifestations, signaling modulation and therapeutic strategies.

Macrophages activation and inflammatory response play crucial roles in intracranial aneurysm (IA) formation and progression. The outcome of ruptured IA is considerably poor, and the mechanisms that trigger IA progression and rupture remain to be clarified, thereby developing effective therapy to prevent subarachnoid hemorrhage (SAH) become difficult. Recently, climbing evidences have been expanding our understanding of the macrophages relevant IA pathogenesis, such as immune cells population, inflammatory activation, intra-/inter-cellular signaling transductions and drug administration responses. Crosstalk between macrophages disorder, inflammation and cellular signaling transduction aggravates the devastating consequences of IA. Illustrating the pros and cons mechanisms of macrophages in IA progression are expected to achieve more efficient treatment interventions. In this review, we summarized the current advanced knowledge of macrophages activation, infiltration, polarization and inflammatory responses in IA occurrence and development, as well as the most relevant NF-κB, signal transducer and activator of transcription 1 (STAT1) and Toll-Like Receptor 4 (TLR4) regulatory signaling modulation. The understanding of macrophages regulatory mechanisms is important for IA patients' clinical outcomes. Gaining insight into the macrophages regulation potentially contributes to more precise IA interventions and will also greatly facilitate the development of novel medical therapy.

WNTA5-mediated miR-374a-5p regulates vascular smooth muscle cell phenotype transformation and M1 macrophage polarization impacting intracranial aneurysm progression

miR-374a-5p expression and localization in intracranial aneurysm (IA) tissues were detected, and its correlation with vascular smooth muscle cells (VSMCs) and macrophage markers was analyzed. Using platelet-derived growth factor-BB (PDGF-BB) induced VSMC model, elastase-induced IA rat model. Subsequently, miR-374a-5p was knocked down or overexpressed. We investigated the effects of miR-374a-5p on phenotypic conversion, and in vivo experiments were also carried out to verify the findings. The targeted relationship between miR-374a-5p and WNTA5 was analyzed. The effect of WNT5A inhibition on VSMC phenotypic transformation and THP-1-derived macrophage polarization was explored. Clinical studies have shown that miR-374a-5p was upregulated in IA patients. miR-374a-5p was negatively correlated with SM22α, α-SMA, CD206, and positively correlated with CD86. In vitro experiments showed that knocking down miR-374a-5p reversed the promotion of SM22α and α-SMA expression by PDGF-BB, while overexpression of miR-374a-5p had the opposite effect. In addition, knocking down miR-374a-5p also reversed the decrease in Calponin, TIMP3, TIMP4, and IL-10 levels caused by PDGF-BB, and further reduced the levels of MMP1, MMP3, MMP9, IL-1β, IL-6, and TNF-α. These findings were further validated in vivo. In IA rats, there were notable increases in both systolic and diastolic blood pressure, along with an elevated M1/M2 ratio and the occurrence of vascular lesions. However, these symptoms were improved after knocking down miR-374a-5p. Furthermore, miR-374a-5p could target the WNT signals (WNT2B, WNT3, and WNT5A). miR-374a-5p regulated the VSMC phenotypic conversion and M1 macrophage polarization by targeting WNT5A, thereby impacting the progression of IA.

Plasma levels of CD36 and glutathione as biomarkers for ruptured intracranial aneurysm.

Evidence has proved that intracranial aneurysm (IA) formation and rupture might be closely related to inflammatory response and oxidative stress. Our objective was to evaluate the potential of CD36 and glutathione (GSH) as biomarkers for IA. In this study, the enzyme-linked immunosorbent assay was used to measure the plasma levels of CD36 and GSH in 30 IA patients and 30 healthy controls. Then, correlation analysis, receiver operating characteristic (ROC) curve, and logistic regression analysis were performed. The results showed that the plasma level of CD36 in IA patients was significantly higher than that in the control group (P < 0.0001), and plasma GSH was significantly lower compared with that in the control group (P < 0.0001). ROC analysis showed that CD36 and GSH had high sensitivity (90.0 and 96.6%) and specificity (96.6 and 86.6%) for IA diagnosis. The combined sensitivity and specificity achieved were 100 and 100%, respectively. The plasma levels of CD36 and GSH did not show a significant correlation with age, the Glasgow Coma Scale, Hunter-Hess score, aneurysm size, aneurysm height, aneurysm neck, and aspect ratio. The AUC of the logistic regression model based on CD36 and GSH was 0.505. Our results suggested that the combination of plasma CD36 and GSH could serve as potential biomarkers for IA rupture.