Background: Cognitive impairment in adult moyamoya disease (MMD) is thought to be the result of ischemic stroke; however, the presence and extent of cognitive decline in asymptomatic patients is unclear. Methods: After classification using T2-weighted fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI), a total of 19 MMD patients with a history of cerebral infarction, 21 asymptomatic MMD patients, and 20 healthy controls matched for age, sex, and years of education were prospectively included in this study. A detailed neuropsychological evaluation of two moyamoya subgroups and normal controls was conducted. Results: Asymptomatic patients showed varying degrees of decline in intelligence (Raven’s Standard Progressive Matrices, P = 0.001), spatial imagination (mental rotation, P = 0.014), working memory (verbal working memory-backward digit span, P = 0.011), and computational ability (simple subtraction, P = 0.014; complex subtraction, P < 0.001) compared with normal controls. MMD patients with cerebral infarction had more severe impairment in complex arithmetic (P = 0.027) and word short-term memory (P = 0.01) than those without symptoms. Conclusion: In asymptomatic MMD patients, a variety of cognitive impairment precedes the onset of clinical symptoms such as cerebral infarction, which may be a long-term complication of conservative treatment.

BACKGROUND: Moyamoya disease (MMD) is a rare progressive vascular disease that leads to intracranial internal carotid artery stenosis and eventual occlusion. However, its pathogenesis remains unclear. The purpose of this study is to explore the role of abnormally expressed proteins in the pathogenesis of MMD. METHODS: Data-independent acquisition mass spectrometry identifies the differentially expressed proteins in MMD serum by detecting the serum from 60 patients with MMD and 20 health controls. The differentially expressed proteins were validated using enzyme linked immunosorbent assays. Immunofluorescence for superficial temporal artery and middle cerebral artery specimens was used to explore the morphological changes of vascular wall in MMD. In vitro experiments were used to explore the changes and mechanisms of differentially expressed proteins on endothelial cells. RESULTS: Proteomic analysis showed that a total of 14 726 peptides and 1555 proteins were quantified by mass spectrometry data. FLNA (filamin A) and ZYX (zyxin) proteins were significantly higher in MMD serum compared with those in health controls (Log ₂ FC >2.9 and >2.8, respectively). Immunofluorescence revealed an intimal hyperplasia in superficial temporal artery and middle cerebral artery specimens of MMD. FLNA and ZYX proteins increased the proportion of endothelial cells in S phase and promoted their proliferation, angiogenesis, and cytoskeleton enlargement. Mechanistic studies revealed that AKT (serine/threonine kinase)/GSK-3β (glycogen synthase kinase 3β)/β-catenin signaling pathway plays a major role in these FLNA- and ZYX-induced changes in endothelial cells. CONCLUSIONS: This study provides proteomic data on a large sample size of MMD. The differential expression of FLNA and ZYX in patient with MMD and following in vitro experiments suggest that these upregulated proteins are related to the pathology of cerebrovascular intimal hyperplasia in MMD and are involved in MMD pathogenesis, with diagnostic and therapeutic ramifications.

Background: Ischemic Moyamoya disease is one of the important causes of stroke, which leads to severe impairment in cognitive functions. This cognitive impairment occurs prior to stroke. However, the cognitive functions that are impaired and the mechanisms of these impairments have not been determined.Methods: We analyzed 12 patients with Moyamoya disease and 12 controls. All participants underwent cognitive tests and magnetic resonance imaging (MRI) scans. The diffusion tensor imaging (DTI) data was processed using Tract-Based Spatial Statistics (TBSS). Significantly different white matter areas were correlated with different cognitive functions.Results: There were significant differences in intelligence and subtraction between the patients and controls (p < 0.05). The parameters of DTI such as fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) have different changes in anterior thalamic radiation, inferior fronto-occipital fasciculus (IFO), superior longitudinal fasciculus (SLF), uncinate fasciculus (UF), inferior longitudinal fasciculus, forceps minor, and other regions between the two groups.Conclusion: Left UF and IFO may be the key brain regions affecting arithmetic function, while bilateral IFO has an effect on intelligence. RD and AD may be better indicators for early prediction of chronic white matter damage than FA, while MD tends to have a comprehensive indirect change. There is cognitive impairment in ischemic MMD, which is closely related to white matter impairment.Trial registration: Clinical Trial Registration, Unique identifier:ChiCTR1900023610. Registered 4 June 2019 – Prospective study registered.

Background: Moyamoya disease (MMD) stands as a prominent cause of stroke among children and adolescents in East Asian populations. Although a growing body of evidence suggests that dysregulated inflammation and autoimmune responses might contribute to the development of MMD, a comprehensive and detailed understanding of the alterations in circulating immune cells associated with MMD remains elusive.Methods: In this study, we employed a combination of single‐cell RNA sequencing (scRNA‐seq), mass cytometry and RNA‐sequencing techniques to compare immune cell profiles in peripheral blood samples obtained from patients with MMD and age‐matched healthy controls.Results: Our investigation unveiled immune dysfunction in MMD patients, primarily characterized by perturbations in T‐cell (TC) subpopulations, including a reduction in effector TCs and an increase in regulatory TCs (Tregs). Additionally, we observed diminished natural killer cells and dendritic cells alongside heightened B cells and monocytes in MMD patients. Notably, within the MMD group, there was an augmented proportion of fragile Tregs, whereas the stable Treg fraction decreased. MMD was also linked to heightened immune activation, as evidenced by elevated expression levels of HLA‐DR and p‐STAT3.Conclusions: Our findings offer a comprehensive view of the circulating immune cell landscape in MMD patients. Immune dysregulation in patients with MMD was characterized by alterations in T‐cell populations, including a decrease in effector T‐cells and an increase in regulatory T‐cells (Tregs), suggest a potential role for disrupted circulating immunity in the aetiology of MMD.

Background: Intracranial aneurysm (IA) is common and occasionally results in life‐threatening hemorrhagic strokes. However, the cell architecture and inflammation in the IA dome remain less understood. Methods and Results: Single‐cell RNA sequencing was performed on ruptured and unruptured human IA domes for delineating the cell atlas, gene expression perturbations, and inflammation features. Two external bulk mRNA sequencing–based data sets and serological results of 126 patients were collected for validation. As a result, a total of 21 332 qualified cells were captured. Vascular cells, including endothelial cells, smooth muscle cells, fibroblasts, and pericytes, were assigned in extremely sparse numbers (4.84%), and were confirmed by immunofluorescence staining. Pericytes, characterized by ABCC9 and HIGD1B , were identified in the IA dome for the first time. Abundant immune cells were identified, with the proportion of monocytes/macrophages and neutrophils being remarkably higher in ruptured IA. The lymphocyte compartment was also thoroughly categorized. By leveraging external data sets and machine learning algorithms, macrophages were robustly associated with IA rupture, irrespective of their polarization status. The single nucleotide polymorphism rs2280543, which is identified in East Asian populations, was associated with macrophage metabolic reprogramming through regulating TALDO1 expression. Conclusions: This study provides insights into the cellular architecture and inflammatory features in the IA dome and may enlighten novel therapeutics for unruptured IA.

Background and Purpose: This study sought to identify the efficacy and intraoperative operational details of single-stage combined embolization and microsurgery strategy for Spetzler-Martin (SM) grade III/IV/V arteriovenous malformations (AVMs). Methods: The authors retrospectively reviewed consecutive SM grade III/IV/V AVMs who underwent hybrid procedures and surgical resection alone procedures from January 2016 to February 2018. Outcomes [modified Rankin Scale (mRS)] were compared between hybrid group and surgical resection alone group in ruptured or unruptured subgroup. Factors associated with long-term disability were assessed using multivariable logistic regression analyses. Results: A total of 100 AVM patients (47 corrected using hybrid procedures whereas 53 by surgical resection alone) were evaluated. After a mean follow-up of 2.3 ± 0.6 years, we found no difference in long-term prognosis and incidences of disability rates between these two strategies. However, the hybrid strategy offers significant advantage in accelerating the resection process [ruptured (P = 0.000); unruptured (P = 0.002)]. In the analysis of risk factors, excessive embolization (Grade C, 60–100%) was significantly associated with long-term disability in the hybrid cohorts (P = 0.041; odds ratio, 24.000; 95% CI, 1.140–505.194), and involvement of deep perforating arteries was the significant predictor of long-term disability in the surgical resection alone cohort (P = 0.025; odds ratio, 15.389; 95% CI, 1.412–167.66). In the subgroup analysis of the hybrid cohort, moderate embolization (Grade B, 30–60%) was recommended because of the low risk ratio of major intraoperative bleeding (P = 0.033). Conclusions: Single-stage combined embolization and resection is an efficient strategy for the treatment of SM grade III/IV/V AVMs. Although the long-term outcomes were similar to surgical resection alone, the hybrid strategy had obvious advantages of shorter resection. In the hybrid technique, moderate embolization was recommended, and excessive embolization might be detrimental to the subsequent microsurgical resection. Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT04136860.