Development and validation of a model for predicting the risk of brain arteriovenous malformation rupture based on three-dimensional morphological features

ObjectiveBrain arteriovenous malformation (bAVM) is an important reason for intracranial hemorrhage. This study aimed at developing and validating a model for predicting bAVMs rupture by using three-dimensional (3D) morphological features extracted from Computed Tomography (CT) angiography.Materials and methodsThe prediction model was developed in a cohort consisting of 412 patients with bAVM between January 2010 and December 2020. All cases were partitioned into training and testing sets in the ratio of 7:3. Features were extracted from the 3D model built on CT angiography. Logistic regression was used to develop the model, with features selected using L1 Regularization, presented with a nomogram, and assessed with calibration curve, receiver operating characteristic (ROC) curve and decision curve analyze (DCA).ResultsSignificant variations in associated aneurysm, deep located, number of draining veins, type of venous drainage, deep drainage, drainage vein entrance diameter (Dv), type of feeding arteries, middle cerebral artery feeding, volume, Feret diameter, surface area, roundness, elongation, mean density (HU), and median density (HU) were found by univariate analysis (p < 0.05). The prediction model consisted of associated aneurysm, deep located, number of draining veins, deep drainage, Dv, volume, Feret diameter, surface area, mean density, and median density. The model showed good discrimination, with a C-index of 0.873 (95% CI, 0.791–0.931) in the training set and 0.754 (95% CI, 0.710–0.795) in the testing set.ConclusionsThis study presented 3D morphological features could be conveniently used to predict hemorrhage from unruptured bAVMs

Association between methionine sulfoxide and risk of moyamoya disease

ObjectiveMethionine sulfoxide (MetO) has been identified as a risk factor for vascular diseases and was considered as an important indicator of oxidative stress. However, the effects of MetO and its association with moyamoya disease (MMD) remained unclear. Therefore, we performed this study to evaluate the association between serum MetO levels and the risk of MMD and its subtypes.MethodsWe eventually included consecutive 353 MMD patients and 88 healthy controls (HCs) with complete data from September 2020 to December 2021 in our analyzes. Serum levels of MetO were quantified using liquid chromatography-mass spectrometry (LC–MS) analysis. We evaluated the role of MetO in MMD using logistic regression models and confirmed by receiver-operating characteristic (ROC) curves and area under curve (AUC) values.ResultsWe found that the levels of MetO were significantly higher in MMD and its subtypes than in HCs (p < 0.001 for all). After adjusting for traditional risk factors, serum MetO levels were significantly associated with the risk of MMD and its subtypes (p < 0.001 for all). We further divided the MetO levels into low and high groups, and the high MetO level was significantly associated with the risk of MMD and its subtypes (p < 0.05 for all). When MetO levels were assessed as quartiles, we found that the third (Q3) and fourth (Q4) MetO quartiles had a significantly increased risk of MMD compared with the lowest quartile (Q3, OR: 2.323, 95%CI: 1.088–4.959, p = 0.029; Q4, OR: 5.559, 95%CI: 2.088–14.805, p = 0.001).ConclusionIn this study, we found that a high level of serum MetO was associated with an increased risk of MMD and its subtypes. Our study raised a novel perspective on the pathogenesis of MMD and suggested potential therapeutic targets

Single-cell atlas reveals different immune environments between stable and vulnerable atherosclerotic plaques

IntroductionRegardless of the degree of stenosis, vulnerable plaque is an important cause of ischemic stroke and thrombotic complications. The changes of the immune microenvironment within plaques seem to be an important factor affecting the characteristics of the plaque. However, the differences of immune microenvironment between stable and vulnerable plaques were remained unknown.MethodsIn this study, RNA-sequencing was performed on superficial temporal arteries from 5 traumatic patients and plaques from 3 atherosclerotic patients to preliminary identify the key immune response processes in plaques. Mass cytometry (CyTOF) technology was used to explore differences in immune composition between 9 vulnerable plaques and 12 stable plaques. Finally, immunofluorescence technique was used to validate our findings in the previous analysis.ResultsOur results showed that more CD86+CD68+ M1 pro-inflammatory macrophages were found in vulnerable plaques, while CD4+T memory cells were mainly found in stable plaques. In addition, a CD11c+ subset of CD4+T cells with higher IFN-r secretion was found within the vulnerable plaque. In two subsets of B cells, CD19+CD20-B cells in vulnerable plaques secreted more TNF-a and IL-6, while CD19-CD20+B cells expressed more PD-1 molecules.ConclusionIn conclusion, our study suggested that M1-like macrophages are the major cell subset affecting plaque stability, while functional B cells may also contribute to plaque stability

Hypo-high density lipoproteinemia is a predictor for recurrent stroke during the long-term follow-up after revascularization in adult moyamoya disease

ObjectivePrevious studies have reported that hypo-high-density lipoproteinemia (HHDL) was an independent risk factor for the cerebrovascular event. However, the risk of HHDL for stroke recurrence in moyamoya disease (MMD) during long-term follow-up after revascularization remains poorly understood. We aim to investigate the association between HHDL and stroke recurrence in adult patients with MMD.MethodsA total of 138 adult patients with MMD were prospectively recruited from 1 July to 31 December 2019. After excluding 15 patients who did not meet the inclusion criteria, all the 123 patients were enrolled. Participants were grouped according to the stroke recurrence and HHDL presentation, respectively. Clinical data and laboratory examinations were compared by the statistical analysis. The Kaplan–Meier survival analysis was conducted to compare the stroke-free survival rates between participants with HHDL and those without. Univariate and multivariate logistic regression analyses were performed to identify independent factors of the neurological status. Univariate and multivariate Cox regression analyses were conducted to identify the predictors for the recurrent stroke.ResultsParticipants with recurrent stroke group showed a lower level of high-density lipoprotein (HDL) (p = 0.030). More participants in the recurrent stroke group had HHDL (p = 0.045). What is more, there was statistical significance in the Kaplan–Meier curve of stroke incidence between the normal HDL group and the HHDL group (log-rank test, p = 0.034). Univariate logistic analysis results showed that HHDL (OR 0.916, 95% CI 0.237–3.543; p = 0.899) and HDL (OR 0.729, 95% CI 0.094–5.648; p = 0.763) were not predictive factors for the neurological status. In the multivariate Cox regression analysis, diabetes (HR 4.195, 95% CI 1.041–16.899; p = 0.044), HDL (HR 0.061, 95% CI 0.006–0.626; p = 0.019), and HHDL (HR 3.341, 95% CI 1.110–10.051; p = 0.032) were independent risk factors for the recurrent stroke.ConclusionsHypo-high-density lipoproteinemia might be a predictor or the potential therapeutic target for recurrent stroke during the long-term follow-up after revascularization in adult patients with MMD

Moyamoya disease associated with ankylosing spondylitis in a 9-year-old child: a case report

Abstract Background Ankylosing spondylitis was reported to associate with an increased risk of cerebrovascular diseases. In this article, we aimed to report the first case of ankylosing spondylitis associated with moyamoya disease treated with encephalo-duroarterio-synangiosis. Case presentation A 9-year-old boy with ankylosing spondylitis appeared a symptom of repeated transient ischemic attacks which performed as left hemiparesis. Magnetic resonance angiography showed a typical finding of left anterior cerebral artery, bilateral middle cerebral arteries and the supraclinoid portion of the right internal carotid artery stenosis with an abnormal vascular network at the base of the brain, diagnosed with moyamoya disease. He received a medication treatment but did not underwent revascularization surgery. After three months, ankylosing spondylitis symptoms got some relief, whereas transient ischemic attacks was more frequency. Due to the bad cerebral blood flow on acetazolamide computed tomography perfusion and poor clinical manifestation, he underwent a right encephalo-duroarterio-synangiosis. Postoperatively, the symptoms of transient ischemic attacks disappeared. Conclusions We reported the first case of ankylosing spondylitis associated with moyamoya disease. Moyamoya disease could appear in patients with ankylosing spondylitis. Revascularization surgery probably is an effective treatment for preventing preoperative ischemic events recurrence

Prognostic Significance of Homocysteine Level on Neurological Outcome in Brain Arteriovenous Malformations

Objective. We aimed to investigate the serum homocysteine (Hcy) level in patients with brain arteriovenous malformation (bAVM) and their impact on neurological outcome during hospitalization. Method. We retrospectively reviewed patients diagnosed with bAVMs in Beijing Tiantan Hospital from January 2019 to August 2020. Patients were divided into two groups according to the mRS (modified Rankin Scale) score at discharge. Clinical and laboratory characteristics were compared. Logistic regression analyses were performed to identify the potential risk factors for short-term neurological outcome. Results. A total of 175 bAVM patients were enrolled in the study, including 139 patients with favorable outcome (mRS≤2) and 36 patients with unfavorable outcome (mRS>2). Hyperhomocysteinemia was identified in 32.6% of cases (n=57). Serum Hcy level was related to seizure manifestation (P=0.034) and short-term neurological outcome (P=0.027). Logistic regression analysis showed that serum glucose (OR 1.897, 95% CI 1.115-3.229; P=0.018) and Hcy level (OR 0.838, 95% CI 0.720-0.976; P=0.023) were significantly associated with short-term disability. Conclusion. Our results indicated that the lower serum Hcy level is strongly associated with in-hospital unfavorable outcome. Further prospective studies of Hcy natural history and managements in bAVMs are required, which would be valuable for evaluating the disease-modifying efficacy of oral nutritional supplements in bAVM patients

Homocysteine Level and Risk of Hemorrhage in Brain Arteriovenous Malformations

Objective. We aimed to investigate the risk factors associated with hemorrhage and clarify the relation of homocysteine (Hcy) with brain arteriovenous malformations (bAVMs). Method. We retrospectively reviewed bAVM patients from Beijing Tiantan Hospital between January 2019 and December 2019. Clinical and laboratory variables were analyzed in enrolled patients with bAVMs. Potential predictors associated with hemorrhage were evaluated by logistic regression analysis. Results. A total of 143 bAVM patients were identified in the study, including 69 unruptured and 74 ruptured cases. Patients with hemorrhage were less likely to have hyperhomocysteinemia (P=0.023). Logistic regression analysis showed that increased maximum diameter of bAVM lesions (odds ratio (OR) 0.634, 95% confidence intervals (CI) 0.479-0.839; P=0.001) and serum Hcy level (OR 0.956, 95% CI 0.920-0.993; P=0.021) were associated with lower risk of hemorrhage in bAVMs. Conclusion. The present study provided evidence regarding the association between serum Hcy and hemorrhage in patients with bAVMs. Higher Hcy level was correlated with a lower risk of rupture. Detection of factors for subsequent hemorrhage is necessary to develop therapeutic strategies for bAVMs preferably

Serum Kynurenic Acid and Kynurenine Are Negatively Associated with the Risk of Adult Moyamoya Disease

Background and aim. Kynurenine (KYN) and kynurenic acid (KYNA) are key intermediate metabolites associated with inflammation and immune responses in the kynurenine pathway. It remains unknown whether KYN or KYNA is associated with the risk of adult moyamoya disease (MMD). The aim of this study was to prospectively investigate the association between serum KYN or KYNA and the risk of adult MMD. Methods. The study was conducted from July 2020 to December 2021. We measured serum KYN and KYNA levels for 360 adult MMD patients (259 cases of ischemic MMD, 101 cases of hemorrhagic MMD) and 89 age-sex-matched healthy controls. Clinical and laboratory characteristics were collected from the medical record. Results. After multivariate adjustment, decreased serum KYNA (OR, 0.085; 95% CI, 0.035–0.206; p = 0.000) or KYN (OR, 0.430; 95% CI, 0.225–0.820; p = 0.010) levels were associated with increased risk of MMD when upper and lower tertiles were compared. In addition, a higher trend of hemorrhagic MMD was found in MMD patients in KYNA tertile 1 compared with those in tertile 2 to 3 (OR, 0.584; 95% CI, 0.345–0.987; p = 0.044). Addition of serum KYNA (net reclassification improvement: 73.24%, p = 0.000; integrated discrimination improvement: 9.60%, p = 0.000) or KYN (integrated discrimination improvement: 1.70%, p = 0.037) to conventional risk factors significantly improved the risk prediction of MMD. In the exploratory analysis, we observed an interaction between KYN and age (≥40 versus <40 years) or homocysteine levels (≥13.0 versus <13.0 μmol/L) on the risk of MMD. Conclusions. Decreased serum KYNA or KYN levels were associated with an increased risk of adult MMD, suggesting that serum KYNA or KYN may be a valuable predictive biomarker for adult MMD

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

Abstract Background 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. Methods 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. Results 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). Conclusion 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