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Stroke Oct 2023Adult moyamoya disease and syndrome are rare disorders with significant morbidity and mortality. A writing group of experts was selected to conduct a literature search,... (Review)
Review
Adult moyamoya disease and syndrome are rare disorders with significant morbidity and mortality. A writing group of experts was selected to conduct a literature search, summarize the current knowledge on the topic, and provide a road map for future investigation. The document presents an update in the definitions of moyamoya disease and syndrome, modern methods for diagnosis, and updated information on pathophysiology, epidemiology, and both medical and surgical treatment. Despite recent advancements, there are still many unresolved questions about moyamoya disease and syndrome, including lack of unified diagnostic criteria, reliable biomarkers, better understanding of the underlying pathophysiology, and stronger evidence for treatment guidelines. To advance progress in this area, it is crucial to acknowledge the limitations and weaknesses of current studies and explore new approaches, which are outlined in this scientific statement for future research strategies.
Topics: United States; Humans; Adult; American Heart Association; Moyamoya Disease; Stroke
PubMed: 37609846
DOI: 10.1161/STR.0000000000000443 -
Brain : a Journal of Neurology Nov 2023Moyamoya disease is an uncommon cerebrovascular disorder characterized by steno-occlusive changes in the circle of Willis and abnormal vascular network development. Ring...
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.
Topics: Humans; Animals; Mice; Moyamoya Disease; Endothelial Cells; Hippo Signaling Pathway; Zebrafish; Neovascularization, Pathologic; Genetic Predisposition to Disease; Adenosine Triphosphatases; Ubiquitin-Protein Ligases
PubMed: 37399508
DOI: 10.1093/brain/awad225 -
Cerebrovascular Diseases Extra 2024There is a significant burden of stroke in Asia. Asia has the largest population in the world in 2023, estimated at 4.7 billion. Approximately 9.5-10.6 million strokes... (Review)
Review
BACKGROUND
There is a significant burden of stroke in Asia. Asia has the largest population in the world in 2023, estimated at 4.7 billion. Approximately 9.5-10.6 million strokes will be anticipated annually in the backdrop of a diverse group of well-developed and less developed countries with large disparities in stroke care resources. In addition, Asian countries are in varying phases of epidemiological transition.
SUMMARY
In this review, we examined recent epidemiological features of ischaemic stroke and intracerebral haemorrhage in Asia with recent developments in hyperacute stroke reperfusion therapy and technical improvements in intracerebral haemorrhage. The article also discussed the spectrum of cerebrovascular diseases in Asia, which include intracranial atherosclerosis, intracerebral haemorrhage, infective aetiologies of stroke, moyamoya disease, vascular dissection, radiation vasculopathy, and cerebral venous thrombosis.
KEY MESSAGES
The review of selected literature and recent updates calls for attention to the different requirements for resources within Asia and highlights the breadth of cerebrovascular diseases still requiring further research and more effective therapies.
Topics: Humans; Asia; Risk Factors; Cerebral Hemorrhage; Ischemic Stroke; Treatment Outcome; Stroke; Healthcare Disparities; Prevalence; Prognosis
PubMed: 38657577
DOI: 10.1159/000538928 -
Frontiers in Neurology 2023
PubMed: 37731851
DOI: 10.3389/fneur.2023.1270197 -
Scientific Reports Jul 2023Moyamoya disease (MMD) is a chronic and progressive cerebrovascular stenosis or occlusive disease that occurs near Willis blood vessels. The aim of this study was to...
Moyamoya disease (MMD) is a chronic and progressive cerebrovascular stenosis or occlusive disease that occurs near Willis blood vessels. The aim of this study was to investigate the mutation of DIAPH1 in Asian population, and to compare the angiographic features of MMD patients with and without the mutation of the DIAPH1 gene. Blood samples of 50 patients with MMD were collected, and DIAPH1 gene mutation was detected. The angiographic involvement of the posterior cerebral artery was compared between the mutant group and the non-mutant group. The independent risk factors of posterior cerebral artery involvement were determined by multivariate logistic regression analysis. DIAPH1 gene mutation was detected in 9 (18%) of 50 patients, including 7 synonymous mutations and 2 missense mutations. However, the incidence of posterior cerebral artery involvement in mutation positive group was very higher than that in mutation negative group (77.8% versus 12%; p = 0.001). There is an association between DIAPH1 mutation and PCA involvement (odds ratio 29.483, 95% confidence interval 3.920-221.736; p = 0.001). DIAPH1 gene mutation is not a major genetic risk gene for Asian patients with moyamoya disease but may play an important role in the involvement of posterior cerebral artery.
Topics: Humans; Moyamoya Disease; Posterior Cerebral Artery; Cerebral Angiography; Cerebrovascular Circulation; Formins
PubMed: 37400591
DOI: 10.1038/s41598-023-37665-1 -
Frontiers in Cellular and Infection... 2023Ring finger protein 213 (RNF213) is a large E3 ubiquitin ligase with a molecular weight of 591 kDa that is associated with moyamoya disease, a rare cerebrovascular... (Review)
Review
Ring finger protein 213 (RNF213) is a large E3 ubiquitin ligase with a molecular weight of 591 kDa that is associated with moyamoya disease, a rare cerebrovascular disease. It is located in the cytosol and perinuclear space. Missense mutations in this gene have been found to be more prevalent in patients with moyamoya disease compared with that in healthy individuals. Understanding the molecular function of RNF213 could provide insights into moyamoya disease. RNF213 contains a C3HC4-type RING finger domain with an E3 ubiquitin ligase domain and six AAA+ adenosine triphosphatase (ATPase) domains. It is the only known protein with both AAA+ ATPase and ubiquitin ligase activities. Recent studies have highlighted the role of RNF213 in fighting against microbial infections, including viruses, parasites, bacteria, and chlamydiae. This review aims to summarize the recent research progress on the mechanisms of RNF213 in pathogenic infections, which will aid researchers in understanding the antimicrobial role of RNF213.
Topics: Humans; Moyamoya Disease; Ubiquitin-Protein Ligases; Genes, Regulator; Transcription Factors; Anti-Infective Agents; Adenosine Triphosphatases
PubMed: 37655297
DOI: 10.3389/fcimb.2023.1205355 -
Frontiers in Cellular and Infection... 2023When it comes to the onset of moyamoya disease (MMD), environmental variables are crucial. Furthermore, there is confusion about the relationship between the gut...
BACKGROUND AND PURPOSE
When it comes to the onset of moyamoya disease (MMD), environmental variables are crucial. Furthermore, there is confusion about the relationship between the gut microbiome, an environmental variable, and MMD. Consequently, to identify the particular bacteria that cause MMD, we examined the gut microbiome of MMD individuals and healthy controls (HC).
METHODS
A prospective case-control investigation was performed from June 2021 to May 2022. The fecal samples of patients with MMD and HC were obtained. Typically, 16S rRNA sequencing was employed to examine their gut microbiota. The QIIME and R softwares were used to examine the data. The linear discriminant analysis effect size analysis was used to determine biomarkers. Multivariate analysis by linear models (MaAsLin)2 were used to find associations between microbiome data and clinical variables. Model performance was assessed using the receiver operating characteristic curve and the decision curve analysis.
RESULTS
This investigation involved a total of 60 MMD patients and 60 HC. The MMD group's Shannon and Chao 1 indices were substantially lower than those of the HC cohort. β-diversity was significantly different in the weighted UniFrac distances. At the phylum level, the relative abundance of / was significantly higher/lower in the MMD group than that in the HC group. By MaAsLin2 analysis, the relative abundance of the 2 genera, and , increased in the MMD group, while the relative abundance of the 2 genera, and decreased in the MMD group. A predictive model was constructed by using these 4 genera. The area under the receiver operating characteristic curve was 0.921. The decision curve analysis indicated that the model had usefulness in clinical practice.
CONCLUSIONS
The gut microbiota was altered in individuals with MMD, and was characterized by increased abundance of and and decreased abundance of and . These 4 genera could be used as biomarkers and predictors in clinical practice.
Topics: Humans; Adult; Gastrointestinal Microbiome; Moyamoya Disease; RNA, Ribosomal, 16S; Feces; Bacteria; Fusobacterium; Biomarkers; Bifidobacterium
PubMed: 37915847
DOI: 10.3389/fcimb.2023.1252681 -
World Journal of Clinical Cases Jan 2024Moyamoya disease (MMD), characterized by progressive internal carotid artery stenosis and collateral vessel formation, prompts cerebral perfusion complications and is...
Moyamoya disease (MMD), characterized by progressive internal carotid artery stenosis and collateral vessel formation, prompts cerebral perfusion complications and is stratified into idiopathic and Moyamoya syndrome subtypes. A multifaceted approach toward MMD management addresses cerebral infarctions through revascularization surgery and adjunctive medical therapy, while also navigating risks such as intracranial hemorrhage and cerebral infarction resulting from arterial stenosis and fragile collateral vessels. Addressing antithrombotic management reveals a potential role for treatments like antiplatelet agents and anticoagulants, despite the ambiguous contribution of thrombosis to MMD-related infarctions and the critical balance between preventing ischemic events and averting hemorrhagic complications. Transcranial doppler has proven useful in thromboembolic detection, despite persisting challenges concerning the efficacy and safety of antithrombotic treatments. Furthermore, antihypertensive interventions aim to manage blood pressure meticulously, especially during intracerebral hemorrhage, with recommendations and protocols varying based on the patient's hypertension status. Additionally, lipid-lowering therapeutic strategies, particularly employing statins, are appraised for their possible beneficial role in MMD management, even as comprehensive data from disease-specific clinical trials remains elusive. Comprehensive guidelines and protocols to navigate the multifaceted therapeutic avenues for MMD, while maintaining a delicate balance between efficacy and safety, warrant further meticulous research and development. This protocol manuscript seeks to elucidate the various aspects and challenges imbued in managing and navigating through the complex landscape of MMD treatment.
PubMed: 38322475
DOI: 10.12998/wjcc.v12.i3.466 -
Neuropsychiatric Disease and Treatment 2023Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by the progressive narrowing and occlusion of the intracranial internal carotid arteries, leading... (Review)
Review
Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by the progressive narrowing and occlusion of the intracranial internal carotid arteries, leading to the formation of abnormal collateral vessels. MMD primarily affects the cerebrovascular system, and evidence suggests it is associated with various neuropsychiatric outcomes. This manuscript aims to provide an overview of the current understanding of MMD, including its epidemiology, pathophysiology, clinical manifestations, and diagnosis. Furthermore, it explores the emerging research on the neuropsychiatric sequelae of MMD, such as cognitive impairment, psychiatric disorders, and quality of life. The manuscript concludes with the challenges in managing MMD-related neuropsychiatric outcomes and potential avenues for future research.
PubMed: 38090021
DOI: 10.2147/NDT.S402375