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To explore the relationship between morphological and hemodynamic parameters, baseline characteristics, and long-term outcomes in patients with moyamoya disease (MMD) using a computational fluid dynamics model. We retrospectively reviewed 129 patients at Beijing Tiantan hospital between July 2020 and December 2021. Perioperative clinical variables and Suzuki stage were recorded. Logistic regression analysis was employed to identify the risk factors for unfavorable long-term outcomes. The association between morphological, CT perfusion parameters, hemodynamic parameters and the Suzuki stage, clinical variables of MMD was also analyzed. Patients with high relative Wall Shear Stress (rWSS) were older and had more cases with higher Suzuki stage and worse follow-up mRS scores (p < 0.05). High rWSS at the terminal ICA and diabetes mellitus were identified as independent predictors of unfavorable long-term outcomes [OR = 3.039(1.191-7.754), p = 0.020; OR = 3.164(1.141-8.723), p = 0.027, respectively]. ROC analysis demonstrated that predictive models incorporating rWSS improved AUC values, with the highest AUC in Model 2 (AUC = 0.889). High rWSS was significantly associated with future TIA and stroke events (p = 0.032). We speculated that high rWSS and diabetes mellitus were independent risk factors for unfavorable long-term outcomes in patients with MMD. rWSS and morphological parameters are crucial for predicting MMD progression and understanding its pathogenesis., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Moyamoya disease (MMD) is closely associated with the Ring Finger Protein 213 ( RNF213 ), a susceptibility gene for MMD. However, its biological function remains unclear. We aimed to elucidate the role of RNF213 in the damage incurred by human endothelial cells under oxygen-glucose deprivation (OGD). We analyzed autophagy in peripheral blood mononuclear cells (PBMCs) derived from patients carrying either RNF213 wildtype (WT) or variant (p.R4810K). Subsequently, human umbilical vein endothelial cells (HUVECs) were transfected with RNF213 WT (HUVEC WT ) or p.R4810K (HUVEC R4810K ) and exposed to OGD for 2 h. Immunoblotting was used to analyze autophagy marker proteins, and endothelial function was analyzed by tube formation assay. Autophagic vesicles were observed using transmission electron microscopy. Post-OGD exposure, we administered rapamycin and cilostazol as potential autophagy inducers. The RNF213 variant group during post-OGD exposure (vs. pre-OGD) showed autophagy inhibition, increased protein expression of SQSTM1/p62 ( p <  0.0001) and LC3-II ( p =  0.0039), and impaired endothelial function ( p =  0.0252). HUVEC R4810K during post-OGD exposure (versus pre-OGD) showed a remarkable increase in autophagic vesicles. Administration of rapamycin and cilostazol notably restored the function of HUVEC R4810K and autophagy. Our findings support the pivotal role of autophagy impaired by the RNF213 variant in MMD-induced endothelial cell dysfunction., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Assessing the glymphatic system activity using diffusion tensor imaging analysis along with the perivascular space (DTI-ALPS) may be helpful to understand the pathophysiology of moyamoya disease (MMD). 63 adult patients with MMD and 20 healthy controls (HCs) were included for T1-weighted images, T2-FLAIR, pseudocontinuous arterial spin labeling, and DTI. 60 patients had digital subtraction angiography more than 6 months after combined revascularization. The Suzuki stage, postoperative Matsushima grade, periventricular anastomoses (PA), enlarged perivascular spaces (EPVS), deep and subcortical white matter hyperintensities (DSWMH), DTI-ALPS, cerebral blood flow (CBF), and cognitive scales of MMD patients were assessed. MMD patients were divided into early and advanced stage based on the Suzuki stage. We detected lower DTI-ALPS in patients with advanced stage relative to HCs (p = 0.046) and patients with early stage (p = 0.004), hemorrhagic MMD compared with ischemic MMD (p = 0.048), and PA Grade 2 compared with Grade 0 (p = 0.010). DTI-ALPS was correlated with the EPVS in basal ganglia (r = -0.686, p < 0.001), Suzuki stage (r = -0.465, p < 0.001), DSWMH (r = -0.423, p = 0.001), and global CBF (r = 0.300, p = 0.017) and cognitive scores (r = 0.343, p = 0.018). The DTI-ALPS of patients with good postoperative collateral formation was higher compared to those with poor postoperative collateral formation (p = 0.038). In conclusion, the glymphatic system was impaired in advanced MMD patients and may affected cognitive function and postoperative neoangiogenesis., (© 2024 The Author(s). Journal of Neuroscience Research published by Wiley Periodicals LLC.)

Introduction: In Moyamoya angiopathy (MMA), mechanisms underlying cognitive impairment remain debated. We aimed to assess the association of cognitive impairment with the degree and the topography of cerebral hypoperfusion in MMA., Methods: A retrospective analysis of neuropsychological and perfusion MRI data from adults with MMA was performed. Ischemic and haemorrhagic lesion masks were created to account for cerebral lesions in the analysis of cerebral perfusion. Whole brain volume of hypoperfused parenchyma was outlined on perfusion maps using different Tmax thresholds from 4 to 12 s. Regional analysis produced mean Tmax values at different regions of interest. Analyses compared perfusion ratios in patients with and without cognitive impairment, with multivariable logistic regression analysis to identify predictive factors., Results: Cognitive impairment was found in 20/48 (41.7%) patients. Attention/processing speed and memory were equally impaired (24%) followed by executive domain (23%). After adjustment, especially for lesion volume, hypoperfused parenchyma volume outlined by Tmax > 4 s or Tmax > 5 s thresholds was an independent factor of cognitive impairment (OR for Tmax > 4 s = 1.06 [CI 95% 1.008-1.123]) as well as attention/processing speed (OR for Tmax > 4 s = 1.07 [CI 95% 1.003-1.133]) and executive domains (OR for Tmax > 5 s = 1.08 [CI 95% 1.004-1.158]). Regarding cognitive functions, patients with processing speed and flexibility impairment had higher frontal Tmax compared to other ROIs and to patients with normal test scores., Discussion: Cerebral hypoperfusion emerged as an independent factor of cognitive impairment in MMA particularly in attention/processing speed and executive domains, with a strong contribution of frontal areas., Conclusion: Considering this association, revascularization surgery could improve cognitive impairment., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The pathogenesis and development of Moyamoya disease are still unclear. This study aimed to investigate the effect of desmoglein-2 (DSG2) on Moyamoya disease and determine the inhibitory effect of DSG2 in vascular remodeling in Moyamoya disease.RNA sequencing, immunohistochemistry (IHC), and western blotting were used to detect the expression of DSG2 in the superficial temporal artery (STA) tissues of Moyamoya disease. The association between DSG2 and endothelial cells' biological activities was investigated by cell counting kit-8 (CCK-8), migration assay, tube formation assay, flow cytometry with Annexin V-FITC/PI staining, and TUNEL apoptotic cell detection kit. Pathways affected by overexpression or knockdown of DSG2 were identified in endothelial cells.The expression of DSG2 in the STA tissues of Moyamoya disease was lower than that in normal controls. Overexpression of DSG2 inhibits the proliferation and migration but promotes apoptosis in endothelial cells, and low DSG2 levels result in impaired angiogenesis. In addition, there was an interaction between DSG2 and MMP-9, and DSG2 acted through the PI3K signaling in endothelial cells.Our results indicate that DSG2 affects PI3K signaling in vascular endothelial cells, and MMP-9 is involved in DSG2-mediated vascular changes in Moyamoya disease., (© 2024. The Author(s).)

Unilateral moyamoya disease (MMD) represents a distinct subtype characterised by occlusive changes in the circle of Willis and abnormal vascular network formation. However, the aetiology and pathogenesis of unilateral MMD remain unclear. In this study, genetic screening of a family with unilateral MMD using whole-genome sequencing helped identify the c.1205 C > A variant of FOXM1, which encodes the transcription factor FOXM1 and plays a crucial role in angiogenesis and cell proliferation, as a susceptibility gene mutation. We demonstrated that this mutation significantly attenuated the proangiogenic effects of FOXM1 in human brain endothelial cells, leading to reduced proliferation, migration, and tube formation. Furthermore, FOXM1 c.1205 C > A results in increased apoptosis of human brain endothelial cells, mediated by the downregulation of the transcription of the apoptosis-inhibiting protein BCL2. These results suggest a potential role for the FOXM1 c.1205 C > A mutation in the pathogenesis of unilateral MMD and may contribute to the understanding and treatment of this condition., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Moyamoya disease (MMD) is a rare disorder causing ischemic and hemorrhagic juvenile stroke. It is associated with the founder susceptibility variant p.R4810K in the RNF213 gene in East Asia. Our aim was to enhance understanding of MMD in so far poorly characterized Southeast Asians and exploring differences with Caucasian Europeans., Methods: By retrospective analysis of medical records and systematic database search on PubMed for all published cases, we identified Southeast Asian patients with MMD. We extracted and pooled proportions using fixed-effects models. Our own cohort was tested for the East Asian RNF213 founder variant p.R4810K. One of our Southeast Asian patients underwent post-mortem histopathological examination., Results: The study cohort comprised 32 Southeast Asians. Mean age at onset in the entire cohort was 32.5 ± 20.3 years (n = 24), 43.4 ± 8.7 years in patients admitted to our center (n = 11), and 23.4 ± 22.4 years in patients from the international literature (n = 13). Female-to-male ratio was 1.6:1. MMD predominantly affected bilateral anterior intracranial vessels. Cerebral ischemia outnumbered transient ischemic attacks (TIAs) and intracranial hemorrhage. TIAs, arterial hypertension and obesity were significantly less frequent in Southeast Asian patients compared to Caucasian Europeans. p.R4810K was absent in all examined Southeast Asians despite of typical histopathological signs of MMD in one autopsy case., Conclusion: Clinical and histopathological manifestations of MMD in Southeast Asians are similar to those in Caucasian Europeans. The genotype of MMD in Southeast Asians differs from that of most East Asian patients., (© 2024. The Author(s).)

Systemic vasculopathy has occasionally been reported in cases of moyamoya disease (MMD). Since the pathological relationship between moyamoya vasculopathy (MMV) and moyamoya-related systemic vasculopathy (MMRSV) remains unclear, it was examined herein by a review of histopathologic studies in consideration of clinicopathological and genetic viewpoints. Although luminal stenosis was a common finding in MMV and MMRSV, histopathologic findings of vascular remodeling markedly differed. MMV showed intimal hyperplasia, marked medial atrophy, and redundant tortuosity of the internal elastic lamina, with outer diameter narrowing called negative remodeling. MMRSV showed hyperplasia, mainly in the intima and sometimes in the media, with disrupted stratification of the internal elastic lamina. Systemic vasculopathy has also been observed in patients with non-MMD carrying the RNF213 (ring finger protein 213) mutation, leading to the concept of RNF213 vasculopathy. RNF213 vasculopathy in patients with non-MMD was histopathologically similar to MMRSV. Cases of MMRSV have sometimes been diagnosed with fibromuscular dysplasia. Fibromuscular dysplasia is similar to MMD not only in the histopathologic findings of MMRSV but also from clinicopathological and genetic viewpoints. The significant histopathologic difference between MMV and MMRSV may be attributed to a difference in the original vascular wall structure and its resistance to pathological stress between the intracranial and systemic arteries. To understand the pathogeneses of MMD and MMRSV, a broader perspective that includes RNF213 vasculopathy and fibromuscular dysplasia as well as an examination of the 2- or multiple-hit theory consisting of genetic factors, vascular structural conditions, and vascular environmental factors, such as blood immune cells and hemodynamics, are needed., Competing Interests: Disclosures Dr Fujimura reports compensation from Daiichi Sankyo Company LTD for other services; grants from Kaneka, Japan; Idorsia, Japan; and CellSeed. The other author reports no conflicts.

Moyamoya disease (MMD) is a cerebrovascular disease which is characterized by the chronic progression of steno-occlusive changes at the terminal portion of internal carotid arteries and the development of "moyamoya vessels." Dysregulation of the extracellular matrix is regarded as a key pathophysiology underlying unique vascular remodeling. Here, we measured the concentration of elastin crosslinkers desmosine and isodesmosine in the plasma of MMD patients. We aimed to reveal its diagnostic values of desmosines in the progression of steno-occlusive lesions. The concentrations of plasma desmosines were determined by liquid chromatography-tandem mass spectrometry. The temporal profiles of steno-occlusive lesions on magnetic resonance angiography were retrospectively evaluated, and the correlation between the progression of steno-occlusive changes in intracranial arteries and plasma desmosines concentrations was further analyzed. Plasma desmosines were significantly higher in MMD patients with disease progression compared to MMD patients without disease progression. Also, the incidence of disease progression was higher in MMD patients with plasma desmosines levels over limit of quantitation (LOQ) than those with plasma desmosines levels below LOQ. In conclusion, plasma desmosines could be potential biomarkers to predict the progression of steno-occlusive changes in MMD patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Brainstem injury occurs secondary to radiation to the posterior fossa in up to 2% of pediatric patients. It may occur after months to years after treatment. It has been associated with age less than 5 years and with comorbid conditions such as cerebrovascular disease, diabetes mellitus, and hypertension. Radiation necrosis is often symptomatic and can be fatal. A pathogenic variant in RNF213 was found in a patient who suffered fatal radiation necrosis. This mutation has been associated with moyamoya disease and may predispose to radiation necrosis., (© 2023 Wiley Periodicals LLC.)

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., Competing Interests: Disclosures None.

Moyamoya disease is an uncommon cerebrovascular disorder characterized by steno-occlusive changes in the circle of Willis and abnormal vascular network development. Ring finger protein 213 (RNF213) has been identified as an important susceptibility gene for Asian patients, but researchers have not completely elucidated whether RNF213 mutations affect the pathogenesis of moyamoya disease. Using donor superficial temporal artery samples, whole-genome sequencing was performed to identify RNF213 mutation types in patients with moyamoya disease, and histopathology was performed to compare morphological differences between patients with moyamoya disease and intracranial aneurysm. The vascular phenotype of RNF213-deficient mice and zebrafish was explored in vivo, and RNF213 knockdown in human brain microvascular endothelial cells was employed to analyse cell proliferation, migration and tube formation abilities in vitro. After bioinformatics analysis of both cell and bulk RNA-seq data, potential signalling pathways were measured in RNF213-knockdown or RNF213-knockout endothelial cells. We found that patients with moyamoya disease carried pathogenic mutations of RNF213 that were positively associated with moyamoya disease histopathology. RNF213 deletion exacerbated pathological angiogenesis in the cortex and retina. Reduced RNF213 expression led to increased endothelial cell proliferation, migration and tube formation. Endothelial knockdown of RNF213 activated the Hippo pathway effector Yes-associated protein (YAP)/tafazzin (TAZ) and promoted the overexpression of the downstream effector VEGFR2. Additionally, inhibition of YAP/TAZ resulted in altered cellular VEGFR2 distribution due to defects in trafficking from the Golgi apparatus to the plasma membrane and reversed RNF213 knockdown-induced angiogenesis. All these key molecules were validated in ECs isolated from RNF213-deficient animals. Our findings may suggest that loss-of-function of RNF213 mediates the pathogenesis of moyamoya disease via the Hippo pathway., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Moyamoya disease (MMD), also known as abnormal cerebral vascular network disease, is characterized by progressive occlusion or stenosis of the internal carotid and cerebral arteries, as well as the formation of an abnormal cerebral vascular network. It can occur anywhere in the world but is most common in China, Japan, and the Republic of Korea. In recent years, there have been increasing reports on the coexistence of thyroid diseases and MMD, but the mechanism of their coexistence is still unclear. For this article, we used keywords such as "moyamoya disease", "thyroid", "Grave disease", "thyrotoxicosis", and "thyroid autoimmune antibodies" to search for 52 articles that met the requirements in medical databases such as PubMed and Web of Science. This article also reviews the research on the role of thyroid hormone, the mechanism of immune antibodies, the possible correlation between thyroid diseases and MMD disease genes, and the treatment methods, and discusses the possible relationship between MMD and thyroid diseases to provide a reference for the pathogenesis and treatment of MMD with thyroid diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Liu, Tan, Liu and Yang.)

With the increasing use of 3-tesla MRI scanners and the development of applicable sequences, it has become possible to achieve high-resolution, good contrast imaging, which has enabled the imaging of the walls of small-diameter intracranial arteries. In recent years, the usefulness of vessel wall imaging has been reported for numerous intracranial arterial diseases, such as for the detection of vulnerable plaque in atherosclerosis, diagnosis of cerebral arterial dissection, prediction of the rupture of cerebral aneurysms, and status of moyamoya disease and cerebral vasculitis. In this review, we introduce the histological characteristics of the intracranial artery, discuss intracranial vessel wall imaging methods, and review the findings of vessel wall imaging for various major intracranial arterial diseases.

Objectives: Data regarding MR vessel-wall imaging (VWI) in patients with Moyamoya disease (MMD) is sparse, particularly in non-asian cohorts. We contribute data regarding the frequency of vessel wall contrast-enhancement (VW-CE) and its potential clinical significance in a European patient group., Materials and Methods: Patients with a diagnosis of MMD who were examined by VWI were included in the study. VW-CE of stenoocclusive lesions of the terminal internal carotid artery and/or its proximal branches was rated qualitatively. Changes of VW-CE on available follow-up were recorded. VW-CE was correlated with diffusion-restricted lesions and magnetic resonance angiography (MRA) findings., Results: Eleven patients (eight female, three male) were included. Twenty-eight stenoocclusive lesions were analyzed, of which 16 showed VW-CE (57.1%). VW-CE was mostly concentric (n=15), rather than eccentric (n=1). In all three patients in whom follow-up VWI was available, changes of VW-CE were documented. Diffusion-restricted lesions were more frequently related to stenoocclusive lesions with VW-CE (n=9) than without VW-CE (n=2), bordering statistical significance. The affected arteries were assessed as stenotic and as occluded in 14 cases each and VW-CE was seen significantly more often in stenotic (n=12) than in occluded arteries (n=4). No correlation was found between the presence of VW-CE and moyamoya stages determined by MRA., Conclusions: Our data suggest that concentric VW-CE is a relatively frequent finding in European MMD patients. VW-CE may change over time and occur in certain stages, possibly representing "active stenosing". Larger studies are needed to validate these findings and determine the clinical relevance of VW-CE in MMD., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Moyamoya arteriopathy (MMA) is a rare cerebrovascular disorder that causes recurrent ischemic and hemorrhagic strokes, leading young patients to severe neurological deficits. The pathogenesis of MMA is still unknown. The disease onset in a wide number of pediatric cases raises the question of the role of genetic factors in the disease's pathogenesis. In these patients, MMA's clinical course, or progression, is largely unclear. By performing a comprehensive molecular and cellular profile in the plasma and CSF, respectively, of MMA pediatric patients, our study is aimed at assessing the levels of circulating endothelial progenitor cells (cEPC) and the release of selected proteins at an early disease stage to clarify MMA pathogenesis and progression. We employed cytofluorimetric methods and immunoassays in pediatric MMA patients and matched control subjects by age and sex. We detected increased levels of cEPC in peripheral blood and an upregulation of angiogenic markers in CSF (i.e., angiopoietin-2 and VEGF-A). This finding is probably associated with deregulated angiogenesis, as stated by the moderate severity of collateral vessel network development (Suzuki III-IV). The absence of significant modulation of neurofilament light in CSF led us to rule out the presence of substantial neuronal injury in MMA children. Despite the limited cohort of pediatric patients, we found some peculiar cellular and molecular characteristics in their blood and CSF samples. Our findings may be confirmed by wider and perspective studies to identify predictive or prognostic circulating biomarkers and potential therapeutic targets for personalized care of MMA pediatric patients.

Moyamoya disease (MMD) is a chronic steno-occlusion cerebrovascular disease accompanied by the formation of the abnormal vascular network at the base of the brain. The etiology of MMD is not fully clarified. Lack of pathological specimens hinders the research progress. Induced pluripotent stem cells (iPSC) derived from patients with outstanding differentiation potential and infinite proliferation ability could conquer the problem of insufficient samples. The technology of iPSC holds the promise of clarifying the underlying molecular mechanism in the development of MMD. In this review, we summarized the latest progress and difficulties in the research of mechanism and detailed the application of iPSC in MMD, aiming to provide an outlook of iPSC in molecular mechanism and novel therapies of MMD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Moyamoya is a cerebrovascular condition that predisposes affected patients to stroke and is characterized as the progressive stenosis of the internal carotid artery (ICA) and compensatory development of collaterals at the base of the brain. Patients with moyamoya syndrome also present with comorbidities such as various autoimmune diseases and coagulopathies. We developed a surgical method using micro-coils to induce ICA-specific stenosis in mice, which induces moyamoya-like vasculopathies. An advantage of this surgical model of hypoperfusion is that it can be combined with other comorbid models to investigate pathologies associated with moyamoya syndrome., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Moyamoya disease (MMD) is a chronic cerebrovascular disease with unknown etiology. The pathogenesis of vascular changes remains unclear. Ischemic and hemorrhagic adult MMD patients and healthy volunteers were enrolled to collect serum for data-independent acquisition (DIA)-based proteomic analysis and ELISA validation. DIA serum proteomic revealed that apolipoprotein C-I (APOC1), apolipoprotein D (APOD), and apolipoprotein A-IV (APOA4) were decreased. The reductases glutathione S-transferase omega-1 (GSTO1) and peptidyl-prolyl cis-trans isomerase A (PPIA) were upregulated, and ADAMTS-like protein 4 (ADAMTSL4) was downregulated in both ischemic and hemorrhagic MMD. Afamin (AFM) and transforming growth factor-beta-induced protein ig-h3 (TGFBI) increased in ischemic patients but decreased in hemorrhagic patients. Serum ELISA results confirmed that APOA4, APOC1, and APOD were decreased compared to controls. Then, we retrospectively analyzed biochemical indexes of 200 MMD patients. A total of 54 enrolled MMD patients showed decreased total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-c). APOA4, APOC1, and APOD were vital factors in the HDL decrease in MMD patients. Lipoprotein dysfunction in MMD patients is involved in MMD. Intimal thickening by enhanced adhesion, middle layer vascular smooth muscle cell migration, and decreased lipid antioxidant function represented by HDL are potential pathogeneses of vascular changes in MMD., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study aimed to identify the high-resolution magnetic resonance imaging (HRMRI) features of moyamoya disease (MMD) patients with anterior intracerebral hemorrhage (ICH) and attempted to reveal potential mechanisms of anterior ICH. Eligible adult MMD patients were consecutively included, and the morphological features of lenticulostriate arteries (LSAs), vessel wall structure of terminal internal carotid artery (ICA) and periventricular anastomosis were evaluated by HRMRI. 78 MMD patients containing 21 patients with anterior ICH, 31 ischemic patients and 26 asymptomatic patients were included. The mean value of total length of LSAs in anterior ICH group (90.79 ± 37.00 mm) was distinctively lower (p < 0.001) compared with either ischemic group (138.04 ± 46.01 mm) or asymptomatic group (170.50 ± 39.18 mm). Lumen area of terminal ICA was significantly larger (p < 0.001) in hemorrhagic group (4.33 ± 2.02 mm 2 ) compared with ischemic group (2.29 ± 1.17 mm 2 ) or asymptomatic group (3.00 ± 1.34 mm 2 ). Multivariate analysis revealed the total length of LSAs (OR 0.689, 95%CI, 0.565-0.840; p < 0.001) and lumen area of terminal ICA (OR 2.085, 95%, 1.214-3.582; p = 0.008) were significantly associated with anterior ICH. Coexistence of reduced LSAs and relatively preserved lumen area of terminal ICA with an AUC of 0.901 (95%CI, 0.812-0.990) could be a potential predictor of anterior ICH in MMD patients.

Objective: To investigate the characteristics of the proximal internal carotid artery (ICA) and their relationships with ipsilateral intracranial stroke in sufferers of moyamoya disease (MMD) with champagne bottle neck sign (CBNS)., Patients and Methods: Forty-four patients with MMD（mean age 43.98 ± 10.54 years, 21 males）confirmed by digital subtraction angiography were enrolled and carotid magnetic resonance vessel wall imaging was introduced in this study. CBNS was defined as the ratio of the diameters of proximal ICA to the common carotid artery (CCA) (DpICA/CCA) < 0.5. The wall thickness and enhancement of the proximal ICA was measured on postcontrast T1-VISTA images. The correlations between these characteristics of the proximal ICA and ipsilateral intracranial stroke were analysed., Results: Among the 44 patients with MMD, twelve patients (27.3 %) had bilateral CBNS and fourteen patients (31.8 %) without CBNS. Compared with normal extracranial arteries, in arteries with CBNS, the proximal ICA had a smaller diameter (3.03 ± 1.05 mm vs 3.95 ± 1.10 mm, p < 0.001), the maximum wall thickness of the proximal ICA was thicker (1.34 ± 0.31 mm vs 1.06 ± 0.26 mm, p < 0.001), and arterial wall contrast enhancement was more frequently observed (66.7 % vs 2 %, p = 0.001). Logistic regression analysis revealed that the wall enhancement of the proximal ICA with CBNS (OR = 15.16, 95 % CI, 2.32-99.02; P = 0.005) was independently associated with intracranial multiple lesions. The AUC of the wall enhancement of the proximal ICA with CBNS was 0.79(P = 0.003)., Conclusions: Vessel wall enhancement of the proximal ICA with CBNS is independently associated with intracranial stroke in the ipsilateral hemispheres of patients with MMD, particularly those with multiple lesions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Moyamoya disease is a medical condition that shows the typical characteristics like continuous and chronic thickening of the walls and the contraction of the internal carotid artery; as a result, the internal diameter of the artery gets narrowed. There are six phases of the disease ranging from I to VI (moyamoya vessels completely disappear, followed by the complete blockage of the arteries). Surgery is a commonly recommended treatment for the moyamoya disease. Our research study identifies the effect of autologous bone marrow stem cell therapy (ABMSCT) on the levels of inflammatory factors and Conexin43 (Cx43) protein in patients suffering from moyamoya. In our study, we have selected 52 moyamoya patients admitted to our hospital from 30 July 2019 to 10 February 2020. The control group (CG) was treated with superficial temporal artery to a middle cerebral artery (STA-MCA) bypass + encephalo-duro-myosinangiosis (EDMS). The experimental group (Exp. Grp) was treated with ABMSC. The cerebral vascular tissue of the patients was treated with hematoxylin-eosin (HE) staining. Immunohistochemical staining was used to identify the levels of Cx43 protein. The concentrations of vascular endothelial growth factor (VEGF), inflammatory factor interleukin-6 (IL6), interleukin-1 β (IL1 β ), tumor necrosis factor (TNF α ), and anti-inflammatory factor interleukin-1 β (IL1 β ) were determined by enzyme-linked immunosorbent assay (ELISA). We have found that after treatment of the expression of Cx43 protein, the proportions of grade IV (7.7%), grade III (311.5%), and grade II (3.8%) patients in the Exp. Grp were lower than those in the CG. The proportion of grade I patients in the Exp. Grp (77%) was higher than that in the CG (38.5%). After treatment, the inflammatory factors IL6 (0.97 ± 0.82 pg/mL), IL1 β (8.33 ± 1.21 pg/mL), and TNF α (1.73 ± 0.71 pg/mL) in the Exp. Grp were lower than those in the CG. The anti-inflammatory factor IL1 β (15.09 ± 4.72 pg/mL) increased in the Exp. Grp compared with the CG (11.25 ± 3.48 pg/mL) post treatment. Intracranial infection, hydrocephalus, hemiplegia, and transient neurological dysfunction in the Exp. Grp were lower than those in the CG, with statistical differences ( P < 0.05). Our study suggests that the treatment of autologous bone marrow stem cells (ABMSC) was beneficial to balance the inflammatory response of disorders, reduce the damage of vascular tissue in the brain, and regulate tissue repair by co-acting with various inflammatory factors as compared to traditional surgery. We conclude that the involvement of Cx43 in the occurrence and development of moyamoya. We also have found that the risk factors of intracranial infection after ABMSCT were less as compared to those after conventional surgery., Competing Interests: The authors declare that they have no conflicts of interest with respect to this article., (Copyright © 2022 Liming Zhao et al.)

Objective: Patients with moyamoya vasculopathy often experience cognitive impairments. In this prospective single-center study, the authors investigated the profile of neurocognitive impairment and its relation with the severity of ischemic brain lesions and hemodynamic compromise., Methods: Patients treated in a Dutch tertiary referral center were prospectively included. All patients underwent standardized neuropsychological evaluation, MRI, digital subtraction angiography, and [15O]H2O-PET (to measure cerebrovascular reactivity [CVR]). The authors determined z-scores for 7 cognitive domains and the proportion of patients with cognitive impairment (z-score < -1.5 SD in at least one domain). The authors explored associations between patient characteristics, imaging and CVR findings, and cognitive scores per domain by using multivariable linear regression and Bayesian regression analysis., Results: A total of 40 patients (22 children; 75% females) were included. The median age for children was 9 years (range 1-16 years); for adults it was 39 years (range 19-53 years). Thirty patients (75%) had an infarction, and 31 patients (78%) had impaired CVR (steal phenomenon). Six of 7 cognitive domains scored below the population norm. Twenty-nine patients (73%) had cognitive impairment. Adults performed better than children in the cognitive domain visuospatial functioning (p = 0.033, Bayes factor = 4.0), and children performed better in processing speed (p = 0.041, Bayes factor = 3.5). The authors did not find an association between infarction, white matter disease, or CVR and cognitive domains., Conclusions: In this Western cohort, cognitive functioning in patients with moyamoya vasculopathy was below the population norm, and 73% had cognitive impairment in at least one domain. The cognitive profile differed between adults and children. The authors could not find an association with imaging findings.

Background: At present, the etiology and pathogenesis of Moyamoya disease (MMD) are not completely clear. Patients are usually diagnosed after cerebrovascular events. Therefore, it is of great clinical significance to explore the predictive factors of MMD., Objective: This study aimed to investigate the serum level of CoQ10B, the amount of endothelial progenitor cells (EPCs), and mitochondrial function of EPCs in MMD patients., Methods: Forty-one MMD patients and 20 healthy controls were recruited in this study. Patients with MMD were divided into two groups: Ischemic type (n=23) and hemorrhagic type (n=18). Blood samples were collected from the antecubital vein and analyzed by CoQ10B ELISA and flow cytometry. Measures of mitochondrial function of EPCs include oxygen consumption rate (OCR), mitochondrial membrane potential, Ca2+ concentration, adenosine triphosphatases activity and ROS level., Results: The serum CoQ10B level in MMD patients was significantly lower than that in healthy controls (p<0.001). The relative number of EPCs in MMD patients was significantly higher than that in healthy controls (p<0.001). Moreover, the OCR, mitochondrial membrane potential and ATPase activity were decreased and the Ca2+ and reactive oxygen species levels were increased in MMD patients (p<0.001)., Conclusions: Our results showed obviously decreased serum CoQ10B level and increased EPCs number in patients with MMD compared with healthy patients, and the mitochondria function of EPCs in MMD patients was abnormal.

Ring Finger Protein 213 (RNF213), also known as Mysterin, is the major susceptibility factor for Moyamoya Arteriopathy (MA), a progressive cerebrovascular disorder that often leads to brain stroke in adults and children. Although several rare RNF213 polymorphisms have been reported, no major susceptibility variant has been identified to date in Caucasian patients, thus frustrating the attempts to identify putative therapeutic targets for MA treatment. For these reasons, the investigation of novel biochemical functions, substrates and unknown partners of RNF213 will help to unravel the pathogenic mechanisms of MA and will facilitate variant interpretations in a diagnostic context in the future. The aim of the present review is to discuss novel perspectives regarding emerging RNF213 roles in light of recent literature updates and dissect their relevance for understanding MA and for the design of future research studies. Since its identification, RNF213 involvement in angiogenesis and vasculogenesis has strengthened, together with its role in inflammatory signals and proliferation pathways. Most recent studies have been increasingly focused on its relevance in antimicrobial activity and lipid metabolism, highlighting new intriguing perspectives. The last area could suggest the main role of RNF213 in the proteasome pathway, thus reinforcing the hypotheses already previously formulated that depict the protein as an important regulator of the stability of client proteins involved in angiogenesis. We believe that the novel evidence reviewed here may contribute to untangling the complex and still obscure pathogenesis of MA that is reflected in the lack of therapies able to slow down or halt disease progression and severity.

Moyamoya disease (MMD) is a rare, progressive cerebrovascular disorder, with an unknown aetiology and pathogenesis. It is characterized by steno-occlusive changes at the terminal portion of the internal carotid artery (ICA), which is accompanied by variable development of the basal collaterals called moyamoya vessels. In this study, we investigate the potential for structural T1 magnetic resonance imaging (MRI) to help characterize MMD clinically, with the help of regionally distributed relative signal intensities (RRSIs) and volumes (RRVs). These RRSIs and RRVs provide the ability to characterize aspects of regional brain development and represent an extension to existing automated biomarker extraction technologies. This study included 269 MRI examinations from MMD patients and 993 MRI examinations from neurotypical controls, with regional biomarkers compared between groups with the area under the receiver operating characteristic curve (AUC). Results demonstrate abnormal presentation of RRSIs and RRVs in the insula (15- to 20-year old cohort, left AUC: 0.74, right AUC: 0.71) and the lateral orbitofrontal region (5- to 10-year old cohort, left AUC: 0.67; 15-20 year cohort, left AUC: 0.62, right AUC: 0.65). Results indicate that RRSIs and RRVs may help in characterizing brain development, assist in the assessment of the presentation of the brains of children with MMD and help overcome standardization challenges in multiprotocol clinical MRI. Further investigation of the potential for RRSIs and RRVs in clinical imaging is warranted and supported through the release of open-source software., (© 2021 International Society for Developmental Neuroscience.)

Background: Variants in the ring finger protein 213 ( RNF213 ) gene are known to be associated with increased predisposition to cerebrovascular diseases development. Genomic studies have identified RNF213 as a major risk factor of Moyamoya disease in East Asian descendants. However, little is known about the RNF213 (ring finger protein 213) biological functions or its associated pathogenic mechanisms underlying Moyamoya disease., Methods: To investigate RNF213 loss-of-function effect in endothelial cell, stable RNF213-deficient human cerebral endothelial cells were generated using the CRISPR-Cas9 genome editing technology., Results: In vitro assays, using RNF213 knockout brain endothelial cells, showed clear morphological changes and increased blood-brain barrier permeability. Downregulation and delocalization of essential interendothelial junction proteins involved in the blood-brain barrier maintenance, such as PECAM-1 (platelet endothelial cell adhesion molecule-1), was also observed. Brain endothelial RNF213-deficient cells also showed an abnormal potential to transmigration of leukocytes and secreted high amounts of proinflammatory cytokines., Conclusions: Taken together, these results indicate that RNF213 could be a key regulator of cerebral endothelium integrity, whose disruption could be an early pathological mechanism leading to Moyamoya disease. This study also further reinforces the importance of blood-brain barrier integrity in the development of Moyamoya disease and other RNF213-associated diseases.

Single-nucleotide polymorphisms (SNPs) in RNF213 , which encodes a 591-kD protein with AAA+ ATPase and RING E3 domains, are associated with a rare, autosomal dominant cerebrovascular disorder, moyamoya disease (MMD). MMD-associated SNPs primarily localize to the C-terminal region of RNF213 , and some affect conserved residues in the RING domain. Although the autosomal dominant inheritance of MMD could most easily explained by RNF213 gain-of-function, the type of ubiquitylation catalyzed by RNF213 and the effects of MMD-associated SNPs on its E3 ligase activity have remained unclear. We found that RNF213 uses the E2-conjugating enzymes UBE2D2 and UBE2L3 to catalyze distinct ubiquitylation events. RNF213-UBED2 catalyzes K6 and, to a lesser extent, K48-dependent poly-ubiquitylation in vitro, whereas RNF213-UBE2L3 catalyzes K6-, K11-, and K48-dependent poly-ubiquitylation events. MMD-associated SNPs encode proteins with decreased E3 activity, and the most frequent MMD allele, RNF213 R4810K , is a dominant-negative mutant that decreases ubiquitylation globally. By contrast, MMD-associated RNF213 SNPs do not affect ATPase activity. Our results suggest that decreased RNF213 E3 ligase activity is central to MMD pathogenesis., (© 2022 Bhardwaj et al.)

Moyamoya disease (MMD) is characterized by narrowing of the distal internal carotid artery and the circle of Willis (CoW) and leads to recurring ischemic and hemorrhagic stroke. A retrospective review of data from 50 pediatric MMD patients revealed that among the 24 who had a unilateral stroke and were surgically treated, 11 (45.8%) had a subsequent, contralateral stroke. There is no reliable way to predict these events. After a pilot study in Acta -/- mice that have features of MMD, we hypothesized that local hemodynamics are predictive of contralateral strokes and sought to develop a patient-specific analysis framework to noninvasively assess this stroke risk. A pediatric MMD patient with an occlusion in the right middle cerebral artery and a right-sided stroke, who was surgically treated and then had a contralateral stroke, was selected for analysis. By using an unsteady Navier-Stokes solver within an isogeometric analysis framework, blood flow was simulated in the CoW model reconstructed from the patient's postoperative imaging data, and the results were compared with those from an age- and sex-matched control subject. A wall shear rate (WSR) > 60,000 s -1 (about 12 × higher than the coagulation threshold of 5000 s -1 and 9 × higher than control) was measured in the terminal left supraclinoid artery; its location coincided with that of the subsequent postsurgical left-sided stroke. A parametric study of disease progression revealed a strong correlation between the degree of vascular morphology altered by MMD and local hemodynamic environment. The results suggest that an occlusion in the CoW could lead to excessive contralateral WSRs, resulting in thromboembolic ischemic events, and that WSR could be a predictor of future stroke., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Moyamoya disease (MMD) is an uncommon cerebrovascular disease which leads to progressive stenosis and occlusion of the bilateral internal carotid artery and main intracerebral arteries. Concerns are always on how the hemisphere with infarction affects cognitive function, while little attention is paid to the role that the non-infarcted hemisphere plays. Therefore, we aimed to detect cortical indexes, especially cortical complexity in the left or right hemisphere separately in patients with MMD after stroke., Methods: 28 patients with MMD (14 males, 14 females) and 14 healthy controls were included in this study. All participants underwent cognitive tests and magnetic resonance imaging (MRI) scan. The preprocessing of three-dimensional T1 weighted images were performed by standard surface-based morphometry. Surface-based morphometry statistical analysis was carried out with a threshold of False Discovery Rate (FDR) P < 0.05 and fractal dimension (FD) was used to provide a quantitative description of cerebral cortical complexity., Results: Widespread cognitive dysfunctions were found in MMD patient with stroke. Extensive FD reduction in the left hemisphere with right-sided infarction, mainly in the superior temporal, inferior frontal, and insula, while the post central gyrus, superior parietal, and inferior parietal gyrus also showed a wide range of significant differences (FDR corrected P < 0.05). Meanwhile, FD changes in the right hemisphere with left-sided infarction are restricted to the precuneus and cingulate isthmus (FDR corrected P < 0.05)., Conclusions: Extensive cognitive impairment was reconfirmed in Moyamoya disease with stroke, while wild and asymmetrical decrease of cortical complexity is observed on both sides. These differences could be relative to unbalanced cognitive dysfunction, and may be the result of a long-term chronic ischemia and compensatory of the contralateral hemisphere to the infarction., (© 2021. The Author(s).)

Objective: The authors' objective was to investigate the influence of the RNF213 p.R4810K variant on the clinical presentation and outcomes of Japanese pediatric patients with moyamoya disease., Methods: A total of 129 Japanese patients with pediatric-onset moyamoya disease (onset age ≤ 15 years) who visited the authors' department from 2012 to 2020 participated in this study. After RNF213 p.R4810K genotyping of each patient was performed, the relationship between genotype and clinical presentation or outcomes, including onset age, initial presentation, surgical outcomes, and subsequent cerebrovascular events, was evaluated. Patients without the p.R4810K variant were tested for RNF213 variants other than p.R4810K. The authors especially focused on the results of patients who presented with moyamoya disease at younger than 1 year of age (infantile onset)., Results: Compared with the patients with heterozygous variants, patients without the p.R4810K variant were younger at onset (7.1 ± 3.7 vs 4.4 ± 0.9 years), and all 4 patients with infantile onset lacked the p.R4810K variant. A greater proportion of patients without the p.R4810K variant presented with infarction than patients with the heterozygous variant (24.0% vs 7.6%) and a decreased proportion presented with transient ischemic attack (36.0% vs 71.7%). No significant correlation was observed between p.R4810K genotype and clinical outcomes, including surgical outcomes and subsequent cerebrovascular events; however, a decreased proportion of patients without the p.R4810K variant had good surgical outcomes compared with that of patients with the heterozygous variant (76.5% vs 92.2%). Among the 25 patients without the p.R4810K variant, 8 rare variants other than p.R4810K were identified. Three of 4 patients with infantile onset had RNF213 variants other than p.R4810K, which had a more severe functional effect on this gene than p.R4810K., Conclusions: Absence of the RNF213 p.R4810K variant may be a novel biomarker for identification of a severe form of pediatric moyamoya disease.

Background: Cerebral arteriovenous malformation (AVM) can rarely occur in conjunction with moyamoya disease (MMD). There is still no consensus on how to treat AVM when accompanied by MMD. In this study, we assessed the clinical features and suggested appropriate management when AVM was combined with MMD., Methods: From August 1994 to December 2020, 7 out of 4004 patients with MMD were found to have AVM. The Karnofsky Performance Scale (KPS) was used to evaluate the clinical outcomes of AVM and MMD. KPS greater than 80 was classified as a good outcome. In addition, the radiologic outcomes of the patients were evaluated., Results: The incidence of AVM with MMD was 1.7 per 1000 persons. Five patients underwent bypass surgery for MMD, and 5 patients underwent Gamma Knife surgery (GKS) for concurrent AVM. Postoperative perfusion magnetic resonance imaging and brain single photon emission computerized tomography showed improved cerebral hemodynamics in 4 out of 7 territories. Postoperative cerebral angiography showed good revascularization in 4 out of 8 territories. After GKS, 4 patients showed complete obliteration, and 1 patient showed a significantly decreased AVM size. Six patients showed favorable clinical outcomes (KPS 80-100), and 1 patient with delayed GKS for AVM had a poor outcome (KPS 20) due to AVM rupture., Conclusions: In this study, AVM tended to occur where the angiographic stage of MMD was higher. When AVM is combined with MMD, MMD bypass surgery is recommended based on symptoms and cerebral perfusion status. For AVM, less invasive but effective treatments, such as GKS, should be implemented as soon as possible., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A mutation in RNF213 (c.14576G>A), a gene associated with moyamoya disease (>80%), plays a role in terminal internal carotid artery (ICA) stenosis (>15%) (ICS). Studies on RNF213 and cerebral aneurysms (AN), which did not focus on the site of origin or morphology, could not elucidate the relationship between the two. However, a report suggested a relationship between RNF213 and AN in French-Canadians. Here, we investigated the relationship between ICA saccular aneurysm (ICA-AN) and RNF213 . We analyzed RNF213 expression in subjects with ICA-AN and atherosclerotic ICS. Cases with a family history of moyamoya disease were excluded. AN smaller than 4 mm were confirmed as AN only by surgical or angiographic findings. RNF213 was detected in 12.2% of patients with ICA-AN and 13.6% of patients with ICS; patients with ICA-AN and ICS had a similar risk of RNF213 mutation expression (odds ratio, 0.884; 95% confidence interval, 0.199-3.91; p = 0.871). The relationship between ICA-AN and RNF213 (c.14576G>A) was not correlated with the location of the ICA and bifurcation, presence of rupture, or multiplicity. When the etiology and location of AN were more restricted, the incidence of RNF213 mutations in ICA-AN was higher than that reported in previous studies. Our results suggest that strict maternal vessel selection and pathological selection of AN morphology may reveal an association between genetic mutations and ICA-AN development. The results of this study may form a basis for further research on systemic vascular diseases, in which the RNF213 (c.14576G>A) mutation has been implicated.

Morphological changes in the child skull due to mechanical and metabolic stimulation and synostosis of the suture are well known. On the other hand, few studies have focused on clinical conditions relevant for adult skull deformity. We retrospectively reviewed computed tomography (CT) findings obtained from 365 cases that were treated for head injuries, moyamoya disease, cervical internal carotid artery stenosis, and mental diseases, and investigated the morphological changes in the skull associated with these diseases. The findings from head injuries were used not only for control subjects, but also for the analysis of generational changes in skull shape based on birth year. Head shape had a brachiocephalic tendency with occipital flattening in people born from the 1950s onwards. Cases of moyamoya disease, cervical internal carotid artery stenosis, and mental diseases showed significantly thicker frontal and occipital bone than those of control subjects. The skull thickening was especially noticeable in the frontal bone in moyamoya disease. Plagiocephaly was significantly frequent in moyamoya disease. These uncommon skull shapes are useful CT findings in screening subjects for early evidence of mental diseases and intracranial ischemic diseases with arterial stenosis., (© 2021. The Author(s).)

Objective: We evaluated what few studies emphasized the postoperative collateral formation and cerebral hemodynamics of hemorrhagic moyamoya disease (MMD)., Methods: Hemorrhagic MMD patients treated surgically were retrospectively collected and dichotomized into combined bypass (CB) and indirect bypass (IB) groups. CB used superficial temporal artery-to-middle cerebral artery anastomosis combined with encephaloduroarteriomyosynangiosis (STA-MCA+EDAMS), and IB used encephaloduroarteriomyosynangiosis (EDAMS) for revascularization. Postoperative complications and clinical prognosis, as well as pre- and post-operative Modified Rankin Scale (mRS), collateral circulation status, and cerebral hemodynamics were observed and compared between the CB and IB groups., Results: A total of 37 patients with hemorrhagic MMD were identified. Of the 68 cerebral hemispheres, 47(69.1%) were combined revascularization, and the rest were indirect. During an average follow-up of 16.5 ± 8.7 months, the recurrent stroke events were significantly lower, as well as having a postoperative mRS scores≤ 2. A satisfactory postoperative collateral formation, and an improved dilation or extension of the anterior choroidal/posterior communication artery (AchA/PcoA) were significantly higher in the CB group than in the IB group (all P < .05). Compared with preoperative cerebral hemodynamics, relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), mean transit time (MTT), and relative time to peak (rTTP) in the CB group; rCBF, rCBV, and MTT in the IB group were significantly improved (all P < .001). The CB group's postoperative rCBF was significantly improved compared with the IB group (P < .001)., Conclusions: STA-MCA bypass combined with EDAMS can obtain better postoperative collateral formation, cerebral hemodynamics, and clinical prognosis than EDAMS alone., (Copyright © 2021. Published by Elsevier B.V.)

Moyamoya-like vasculopathy, the "puff of smoke"-like small vessels in the brain, is initially identified in patients with Moyamoya disease (MMD), a rare cerebrovascular disease, and later found in patients with various types of neurological conditions, including Down syndrome, Stroke, and vascular dementia. It is thus of interest to understand how this vasculopathy is developed. Here, we provided evidence for cortical astrocytic neogenin (NEO1) deficiency to be a risk factor for its development. NEO1, a member of deleted in colorectal cancer (DCC) family netrin receptors, was reduced in brain samples of patients with MMD. Astrocytic Neo1-loss resulted in an increase of small blood vessels (BVs) selectively in the cortex. These BVs were dysfunctional, with leaky blood-brain barrier (BBB), thin arteries, and accelerated hyperplasia in veins and capillaries, resembled to the features of moyamoya-like vasculopathy. Additionally, we found that both MMD patient and Neo1 mutant mice exhibited altered gene expression in their cortex in proteins critical for not only angiogenesis [e.g., an increase in vascular endothelial growth factor (VEGFa)], but also axon guidance (e.g., netrin family proteins) and inflammation. In aggregates, these results suggest a critical role of astrocytic NEO1-loss in the development of Moyamoya-like vasculopathy, providing a mouse model for investigating mechanisms of Moyamoya-like vasculopathy., (Published by Elsevier Inc.)

The aim of this study was to develop and validate a nomogram model to predict the risk of decreased activities of daily living (ADLs) in patients with moyamoya disease (MMD) following revascularization. The nomogram model was constructed based on data from 292 patients with MMD that were treated at Qilu Hospital of Shandong University from January 2018 to June 2019. The prediction model was assessed using a dataset of 119 patients with MMD collected from July 2019 to June 2020. Patients were evaluated with a general information questionnaire and the Mini Mental Status Examination, Hospital Anxiety and Depression Scale, Social Support Rating Scale, and ADL Scale. Multivariable logistic regression analysis was applied to build a prediction model incorporating the features selected in the least absolute shrinkage and selection operator regression model. Discrimination, calibration, and clinical usefulness of the prediction model were assessed using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis. Predictors contained in the nomogram included gender, age, monthly income, hypertension, and cognitive function and depression scores. The areas under the ROC curves of the training and testing datasets were 0.938 and 0.853, respectively. The prediction model displayed good calibration, and the decision curve analysis showed that it had a wide range of clinical applications. This novel predictive could be conveniently used to predict the risk of the decreased living activity ability in patients with MMD., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021 Yani Zhao et al.)

Moyamoya disease (MMD) is a cerebrovascular disease that presents with vascular stenosis and a hazy network of collateral formations in angiography. However, the detailed pathogenic pathway remains unknown. Studies have indicated that in addition to variations in the of genetic factor RNF213 , unusual circulating angiogenetic factors observed in patients with MMD may play a critical role in producing "Moyamoya vessels". Circulating angiogenetic factors, such as growth factors, vascular progenitor cells, cytokines, inflammatory factors, and other circulating proteins, could promote intimal hyperplasia in vessels and excessive collateral formation with defect structures through endothelial hyperplasia, smooth muscle migration, and atypical neovascularization. This study summarizes the hypothesized pathophysiology of how these circulating factors affect MMD and the interactive modulation between them.

Purpose: The purpose of this study was to identify factors influencing health behavior compliance in adult patients with moyamoya., Methods: A descriptive correlation study was conducted to investigate the factors influencing health behavior compliance. Participants were 142 adult patients diagnosed with moyamoya disease who were hospitalized or visited an outpatient clinic in the Gyeonggi province. Data were collected from December 16, 2019 to April 14, 2020 using self-report questionnaires and analyzed using the IBM SPSS 26.0 Win software., Results: The hierarchical multiple regression analysis demonstrated that self-efficacy (β = .60, p < .001), social support (β = .13, p = .032), and age (β = .21, p = .005) affected the health behavior of adults with moyamoya disease. These 3 variables explained 62.0% of the variance of health behavior compliance, and the most influential factor was self-efficacy., Conclusion: Based on the results of this study, it concludes that nursing interventions should be focused on self-efficacy and social support to improve health behavior compliance with adult patients diagnosed with moyamoya disease. For that, various strategies to enhance self-efficacy and social support should be developed and actively applied in the clinical setting for adult moyamoya patients., Competing Interests: Ju-Eun Song has been the Associate Editor of JKAN but has no role in the review process. Except for that, no potential conflict of interest relevant to this article was reported., (© 2021 Korean Society of Nursing Science.)

Moyamoya disease (MMD) is a chronic, steno-occlusive cerebrovascular disorder of unknown etiology. Surgical treatment is the only known effective method to restore blood flow to affected areas of the brain. However, there are lack of generally accepted noninvasive tools for therapeutic outcome monitoring. As dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) is the standard MR perfusion imaging technique in the clinical setting, we investigated a dataset of nineteen pediatric MMD patients with one preoperational and multiple periodic DSC MRI examinations for four to thirty-eight months after indirect revascularization. A rigid gamma variate model was used to derive two nondeconvolution-based perfusion parameters: time to peak (TTP) and full width at half maximum (FWHM) for monitoring transitional bolus delay and dispersion changes respectively. TTP and FWHM values were normalized to the cerebellum. Here, we report that 74% (14/19) of patients improve in both TTP and FWHM measurements, and whereof 57% (8/14) improve more noticeably on FWHM. TTP is in good agreement with Tmax in estimating bolus delay. Our study data also suggest bolus dispersion estimated by FWHM is an additional, informative indicator in pediatric MMD monitoring.