Moyamoya Disease Group Research Articles

Genome-Wide DNA Methylation Profiling Reveals Low Methylation Variability in Moyamoya Disease.

Moyamoya disease (MMD) is a chronic cerebrovascular disorder that can lead to stroke and neurological dysfunctions. Given the largely sporadic nature and the role of gene-environment interactions in various diseases, we examined epigenetic modifications in MMD. We performed genome-wide DNA methylation using Illumina 850K Methylation EPIC BeadChip, in two racially distinct adult female cohorts: a non-Asian cohort (13 MMD patients and 7 healthy controls) and an Asian cohort (14 MMD patients and 3 healthy controls). An additional external cohort with both sexes (females: 5 MMD patients and 5 healthy controls, males: 5 MMD patients and 5 healthy controls) was included for validation. Our findings revealed strikingly low DNA methylation variability between MMD patients and healthy controls, in both MMD female cohorts. In the non-Asian cohort, only 6 probes showed increased variability versus 647 probes that showed decreased variability. Similarly, in the Asian cohort, the MMD group also displayed a reduced methylation variability across all 2845 probes. Subsequent analysis showed that these differentially variable probes are located on genes involved in key biological processes such as methylation and transcription, DNA repair, cytoskeletal remodeling, natural killer cell signaling, cellular growth, and migration. These findings mark the first observation of low methylation variability in any disease, contrasting with the high variability observed in other disorders. This reduced methylation variability in MMD may hinder patients' adaptability to environmental shifts, such as hemodynamic stress, thereby influencing vascular homeostasis and contributing to MMD pathology. These findings offer new insights into the mechanisms of MMD and potential treatment strategies.

Long-Term Clinical Outcomes After Cerebral Revascularization in Moyamoya Disease With Extracranial Internal Carotid Artery Occlusion

ObjectiveThe aim of this study is to evaluate the efficacy of cerebral revascularization for Moyamoya disease (MMD) with extra-cranial internal carotid artery occlusion (ICAO). MethodsThis study retrospectively analyzed 37 patients diagnosed with MMD with extra-cranial ICAO who underwent cerebral revascularization surgery. We conducted propensity score matching for MMD patients without extra-cranial ICAO from database of 932 MMD patients. Outcome data, recurrent strokes and modified Rankin Scale (mRS) were collected during follow-up. ResultsA total of 37 MMD patients with extra-cranial ICAO were included in the study. The average follow-up time of MMD patients with extra-cranial ICAO included in the study was 74 months. During the follow-up period, there were 15 hemispheres recurred stroke events. All hemispheres underwent surgery, and the follow-up mRS score was significantly reduced (P <0.001). Kaplan-Meier analysis showed no significant statistical difference in stroke events between the indirect bypass (IB), direct bypass (DB), and combined bypass (CB) groups (P = 0.131). After propensity matching, 48 hemispheres of MMD patients without extra-cranial ICAO were identified from a review of 932 MMD patients. There was no significant statistical difference in stroke events between the MMD patients with extra-cranial ICAO group and the MMD group (P = 0.271). ConclusionsCerebral revascularization can prevent recurrent ischemic and hemorrhagic stroke events for MMD patients with extra-cranial ICAO. There was no difference on long-term clinical outcomes after CB, DB, and IB surgery. The cerebral revascularization has similar effect on the MMD patients with extra-cranial ICAO and MMD patients without.

Moyamoya Disease Increased the Risk of Retinal Vascular Occlusion: A Nationwide Cohort Study in Korea

PurposeTo investigate the risk of retinal vascular occlusion in patients with Moyamoya disease (MMD). DesignRetrospective, longitudinal cohort study using the Korean National Health Insurance Service database. ParticipantsNewly diagnosed MMD patients (n=34,627), who were diagnosed between 2004 and 2022, and their propensity score matched controls (n=136,945) were included. MethodsWe identified retinal vascular occlusion events using diagnostic codes for central retinal artery occlusion, other retinal artery occlusion, and retinal vein occlusion. After a washout-period from 2002 to 2003, information on the diagnosis of retinal vascular occlusion was extracted in both MMD and control group during the follow up period. The association between MMD and the risk of subsequent retinal vascular occlusion was investigated using a time-dependent Cox proportional hazard model and Kaplan-Meier survival analysis with log-rank test adjusted for age, sex, and comorbidities. Main Outcome MeasuresHazard ratios (HRs) and 95% confidence intervals (CIs) for retinal vascular occlusion development according to the MMD. ResultsMMD was associated with an increased risk of subsequent retinal vascular occlusion even after adjusting for confounding variables (HR, 1.22; 95% CI, 1.09–1.36). Among the subtypes of retinal vascular occlusion, central retinal artery occlusion showed a highest HR (2.23; 95% CI, 1.35-3.7). Incidence probability of retinal vascular occlusion was significantly higher among MMD patients than controls (P < 0.001, log-rank test). ConclusionIn this nationwide population-based cohort study, patients with MMD in Korea had an elevated risk of retinal vascular occlusion, suggesting that the MMD is one of the risk factors for retinal vascular occlusion.

Does disease etiology matter in long-term patency in extracranial-intracranial bypass?

OBJECTIVE Extracranial-intracranial (EC-IC) bypass has been well described in chronic vaso-occlusive cerebrovascular diseases, including both moyamoya disease (MMD) and atherosclerotic disease (AD). This study aimed to compare factors associated with bypass occlusion between these two diseases. METHODS An institutional database of 357 patients with intracranial bypass procedures performed between August 2001 and May 2022 was retrospectively reviewed. Patients with MMD and AD were selected for study. Baseline characteristics, surgical technique, and flow-related measurements were compared in relation to the outcome of bypass occlusion. RESULTS A total of 232 patients met inclusion criteria (AD, n = 108; MMD, n = 124). The average age and sex differed significantly between groups (AD 57.2 years, 56.5% male; MMD 36.6 years, 31.5% male; p &lt; 0.001). The modified Rankin Scale scores at surgery and at follow-up were higher in the AD group (p = 0.004 and p &lt; 0.001, respectively), showing a slightly worse baseline functional status, and higher rates of stroke were observed in the AD group by last follow-up (p = 0.005). Patients with AD also were more likely to require an interpositional graft (p &lt; 0.001). At last follow-up, rates of occlusion did not differ between AD and MMD groups (25.2% vs 25.4%, respectively). Of occluded bypasses, the AD group had more occlusions within 1 week compared to MMD (51.9% vs 35.5%, p = 0.176), although the difference was not significant. In patients with more than 1 year of follow-up and in those with more than 2 years of follow-up, MMD tended to have higher rates of occlusion (31.2% vs 26.1% [p = 0.558], and 26.4% vs 20.7% [p = 0.564]). Flow measurements did not differ between AD and MMD groups, but in subgroup analyses of patients with AD and those with MMD, both bypass flow and cut flow index predicted occlusion in both groups. CONCLUSIONS Despite different disease etiologies treated with bypass, rates of occlusion at last follow-up did not vary between groups, although short-term follow-up would suggest earlier bypass failure in AD, and extended follow-up trended toward higher occlusion rates in MMD. Additionally, patients with AD were more likely to have further occurrences of stroke by last follow-up. Importantly, the bypass flow and cut flow index at the time of surgery predicted occlusion in both AD and MMD.

Comprehensive Analysis and In Vitro Verification of Endothelial-Mesenchymal Transition-Related Genes in Moyamoya Disease.

Moyamoya disease (MMD) is a rare, chronic, and progressive cerebrovascular disorder with unclear underlying causes and mechanisms. Previous studies suggest a potential involvement of endothelial-mesenchymal transition (EndMT) in the pathogenesis of MMD. This study aimed to explore the contribution of EndMT-related genes (ERGs) in MMD. Two datasets, GSE141022 and GSE157628, were integrated as the training set after batch effects removal. Differentially expressed ERGs were identified between MMD and control groups. Functional enrichment analysis and immune infiltration analysis were further performed. LASSO regression was used for hub MMD-related ERG selection. Consensus clustering was used for MMD subtype classification based on these hub MMD-related ERGs. Molecular characteristics between MMD subtypes were analyzed using WGCNA. PPI network was used to illuminate the genetic relationship. The hub MMD-related ERGs were validated in an independent testing set, GSE189993. The nomogram model was constructed and evaluated using ROC curves and calibration plots. Additionally, CCK-8, EdU, wound healing, and western blot were performed to confirm the function of the hub MMD-related ERGs. A total of 107 DE-ERGs were identified. Functional enrichment analysis showed these genes were associated with EndMT and immune response. The infiltrating levels of immune cells were commonly higher in the MMD group. LASSO regression identified 12 hub MMD-related ERGs, leading to the identification of two MMD subtypes. Four ERGs emerged as the final hub MMD-related ERGs after validation in the testing set, including CCL21, CEBPA, KRT18, and TNFRSF11A. The nomogram model exhibited excellent discrimination ability. In vitro experiments showed that CCL21, CEBPA, KRT18, and TNFRSF11A could promote proliferation, migration, and EndMT. This study investigated the potential role of EndMT in MMD and identified four hub MMD-related ERGs, providing potential therapeutic targets for MMD treatment.

Identification of oxidative phosphorylation-related genes in moyamoya disease by combining bulk RNA-sequencing analysis and machine learning.

Introduction: Moyamoya disease (MMD) is a chronic cerebrovascular disease that can lead to ischemia and hemorrhagic stroke. The relationship between oxidative phosphorylation (OXPHOS) and MMD pathogenesis remains unknown. Methods: The gene expression data of 60 participants were acquired from three Gene Expression Omnibus (GEO) datasets, including 36 and 24 in the MMD and control groups. Differentially expressed genes (DEGs) between MMD patients MMD and control groups were identified. Machine learning was used to select the key OXPHOS-related genes associated with MMD from the intersection of DEGs and OXPHOS-related gene sets. Gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), gene set enrichment analysis (GSEA), Immune infiltration and microenvironments analysis were used to analyze the function of key genes. Machine learning selected four key OXPHOS-related genes associated with MMD: CSK, NARS2, PTPN6 and SMAD2 (PTPN6 was upregulated and the other three were downregulated). Results: Functional enrichment analysis showed that these genes were mainly enriched in the Notch signaling pathway, GAP junction, and RNA degradation, which are related to several biological processes, including angiogenesis, proliferation of vascular smooth muscle and endothelial cells, and cytoskeleton regulation. Immune analysis revealed immune infiltration and microenvironment in these MMD samples and their relationships with four key OXPHOS-related genes. APC co-inhibition (p = 0.032), HLA (p = 0.001), MHC I (p = 0.013), T cellco- inhibition (p = 0.032) and Type I IFN responses (p < 0.001) were significantly higher in the MMD groups than those in the control groups. The CSK positively correlated with APC co-inhibition and T cell-co-inhibition. The NARS2 negatively correlated with Type I IFN response. The SMAD2 negatively correlated with APC co-inhibition and Type I IFN response. The PTPN6 positively correlated with HLA, MHC I and Type I IFN responses. Discussion: This study provides a comprehensive understanding of the role of OXPHOS in MMD and will contribute to the development of new treatment methods and exploration of MMD pathogenesis.

Effect of moyamoya disease on the basilar artery and adjacent arteries on CTA

BackgroundComputed tomographic angiography (CTA) is rarely used to explore the effect of moyamoya disease (MMD) on the basilar artery (BA) and its adjacent arteries. MethodsParticipants were divided into a control group and an MMD group. The relevant parameters were measured. Statistical analyses included the t-test, chi-squared test, and linear regression analysis. ResultsIn the control group of 100 healthy people, the average age was 54.51 ± 13.40 years, and the ratio of males to females was 0.89:1. In the MMD group of 100 patients, the average age was 53.95 ± 11.31 years, and the ratio of males to females was 1.13:1. In the MMD group, the CTA score of the anterior circulation of the bilateral hemispheres was 7.57 ± 2.36. According to the statistical analyses, (1) in the control group, the BA apex tended to lean to the right in healthy participants; (2) in the MMD group, the BA was closer to the midline, and the angle between the BA and anterior inferior cerebellar artery was reduced, indicating that the BA was relatively elevated; (3) in the MMD group, the diameters of the BA, PCA and vertebral artery were larger than those in the control group; and (4) MMD patients with posterior cerebral atery (PCA) involvement had higher CTA scores of the anterior circulation. ConclusionsMMD can cause the BA to move toward the midline and upward and enlarge major vessels of the posterior circulation. The PCA tends to be involved in MMD patients with higher CTA scores in the anterior circulation.

Circulating immune cell landscape and T-cell abnormalities in patients with moyamoya disease.

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. 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. 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. 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.

106 Characteristics of Cognitive Impairment in Moyamoya Disease

INTRODUCTION: 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 remain largely unknown. 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. In addition, participants underwent arterial spin labeling and resting state fMRI sequences. 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 &lt; 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. The asymptomatic MMD group also showed decreased CBF in the left anterior central and left inferior frontal gyri of the island fap with multiple node abnormalities in the brain network and reduced network connectivity. There was a significant association of these changes with cognitive decline in the MMD group. CONCLUSIONS: In asymptomatic MMD patients, a variety of cognitive impairments precedes the onset of clinical symptoms such as cerebral infarction, which may be a long-term complication of conservative treatment. Besides, disturbance of CBF and impaired brain network connections may be important causes of cognitive decline.

Mass cytometry revealed the circulating immune cell landscape across different Suzuki stages of Moyamoya disease

Moyamoya disease (MMD) is a cerebrovascular disorder marked by progressive arterial narrowing, categorized into six stages known as Suzuki stages based on angiographic features. Growing evidence indicates a pivotal role of systemic immune and inflammatory responses in the initiation and advancement of MMD. This study employs high-dimensional mass cytometry to reveal the immunophenotypic characteristics of peripheral blood immune cells (PBMCs) at various Suzuki stages, offering insights into the progression of MMD. PBMC samples from eight patients with early-stage MMD (Suzuki stages II and III) and eight patients with later-stage MMD (Suzuki stages IV, V, and VI) were analyzed using high-dimensional mass cytometry to evaluate the frequency and phenotype of immune cell subtypes. We identified 15 cell clusters and found that the immunological features of early-stage MMD and later-stage MMD are composed of cluster variations. In this study, we confirmed that, compared to later-stage MMD, the early-stage MMD group exhibits an increase in non-classical monocytes. As the Suzuki stage level increases, the proportions of plasmacytoid DCs and monocyte-derived DCs decrease. Furthermore, T cells, monocytes, DCs, and PMN-MDSCs in the early-stage MMD group show activation of the canonical NF-κB signaling pathway. We summarized and compared the similarities and differences between early-stage MMD patients and later-stage MMD patients. There is a potential role of circulating immune dysfunction and inflammatory responses in the onset and development of MMD.

Abstract WP219: Diffusion Weighted Imaging Characteristics in Deep White and Gray Matter Structures in Pediatric Patients With Moyamoya Disease

Background: Moyamoya Disease (MMD) is a steno-occlusive arteriopathy associated with transient ischemic attacks, stroke, and cognitive impairments. In adult MMD, normal-appearing deep gray and white matter structures (NADWM) show diffusion changes that are associated with cognitive impairments. Apparent diffusion coefficient [ADC] measures the mean diffusion and is sensitive to these changes. The association of ADC changes in NADWM in pediatric MMD is not clear. Our objective is to determine whether ADC is elevated in NADWM in pediatric MMD patients. Hypothesis: ADC values in NADWM will be elevated in MMD patients compared to controls. Methods: Twenty-nine MMD patients and no stroke and 7 healthy controls (HC) were included in a single center, retrospective study. Diffusion and T1-weighted images were analyzed. We constructed a script implementing a convolutional neural network (CNN) based approach to segment and binarize cortical regions of interest (ROI) and allow extraction of ADC values (units =[x10 -6 mm 2 /s]). Segmented ROIs included: 1) all white matter (WM), and NADWM including: 2) thalamus, 3) caudate, 4) putamen, 5) globus pallidus, 6) hippocampus. Mean ADC values were compared for: 1) all ROIs between MMD and controls, and 2) all ROIs in the MMD affected and the contralateral hemispheres within the MMD group. Results: Patients were on average 7.7 + 5.4 years at MMD diagnosis. In all WM, MMD patients had significantly higher ADC values than controls in the left (mean= 865.7 + 101.6 versus 762.4 + 21.6, p=0.01) and right hemispheres (mean= 869.9 + 104.9 versus 761.0 + 21.3, p=.01), respectively. In NADGM, there were no significant differences found between the MMD and control groups in any of the NADGM ROIs. In the NADGM of MMD patients, higher ADC values were found in the putamen (mean= 778.2 + 46.0, p=0.041), hippocampus (mean=1009.5 + 58.6, p=0.005) and all NAWM (mean= 860.3 + 57.0, p&lt;0.0001) in the MMD affected compared to the contra-lesional hemisphere. Conclusions: In pediatric patients with MMD, we found elevated ADC values in deep gray and white matter structures in the diseased hemisphere indicating alterations in the underlying microstructure. Our future analysis will integrate hemodynamic profiles and cognitive outcomes.

Vascular architecture characters and risk factors analysis of unstable moyamoya disease.

In some MMD patients, the digital subtraction angiography (DSA) examination found, occlusion in the ipsilateral internal carotid artery or middle cerebral artery, accompanied by the formation of numerous moyamoya vessels. Conversely, the contralateral internal carotid artery or middle cerebral artery shows signs of stenosis without the presence of moyamoya vessels. Notably, cerebral perfusion studies reveal a similar or even more severe reduction in perfusion on the occluded side compared to the stenotic side. Importantly, clinical symptoms in these patients are typically attributed to ischemia caused by the stenotic side. This condition is referred to as unstable moyamoya disease (uMMD). This clinical research focuses on evaluating risk factors related to MMD and developing strategies to minimize postoperative complications. The study aims to analyze vascular characteristics and identify potential risk factors in patients with uMMD. The authors reviewed consecutive cases with complete clinical and radiological documentation of patients who underwent surgery between January 2018 and June 2023. Univariate analysis and multivariate logistic regression analysis were employed to understand the risk factors and prognosis of postoperative complications in uMMD. Postoperative complications were retrospectively analyzed in 1481 patients (aged 14 to 65). Among them, 1,429 patients were assigned to the conventional treatment group, while 52 were in the unstable moyamoya disease group. The uMMD treatment group showed a significantly higher incidence of early postoperative complications such as RIND, cerebral infarction, and cerebral hemorrhage (p < 0.05). Univariate and multivariate logistic regression analyses were conducted on the postoperative complications of 52 uMMD patients. Initial symptoms of stenosis ≤50% (univariate: p = 0.008, multivariate: p = 0.015; OR [95% CI] =23.149 [1.853-289.217]) and choosing occluded side surgery (univariate: p = 0.043, multivariate: p = 0.018; OR [95% CI] =0.059 [0.006-0.617]) were identified as significant risk factors for postoperative neurological complications. Compared to the conventional treatment group, uMMD has higher complication rates, with vascular stenosis degree and surgical side selection identified as significant risk factors. A comprehensive understanding of preoperative clinical symptoms and vascular characteristics in moyamoya disease patients, coupled with the formulation of rational surgical plans, contributes positively to decreasing postoperative mortality and disability rates in uMMD.

Gut microbiota in adults with moyamoya disease: characteristics and biomarker identification.

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). 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. 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 Fusobacteriota/Actinobacteria was significantly higher/lower in the MMD group than that in the HC group. By MaAsLin2 analysis, the relative abundance of the 2 genera, Lachnoclostridium and Fusobacterium, increased in the MMD group, while the relative abundance of the 2 genera, Bifidobacterium and Enterobacter 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. The gut microbiota was altered in individuals with MMD, and was characterized by increased abundance of Lachnoclostridium and Fusobacterium and decreased abundance of Bifidobacterium and Enterobacter. These 4 genera could be used as biomarkers and predictors in clinical practice.

A Vessel Wall MRI Investigation in Patients With Moyamoya or Quasi-Moyamoya Disease: Diagnosis, Features, and Outcomes.

None of the previous studies have investigated the pathologic authenticity of affected arteries in moyamoya disease (MMD) and Quasi-MMD diagnosed by angiography. This study aimed to confirm the angiographic diagnosis of moyamoya as well as investigate the pathologic mechanisms in angiographically proven MMD and Quasi-MMD using high-resolution magnetic resonance imaging (MRI) in a large sample. We prospectively studied 116 patients who had angiographically proven MMD and Quasi-MMD. Each affected internal carotid artery, and middle cerebral artery was independently evaluated. In addition, clinical features and postoperative outcomes were compared between hemispheres with MMD and moyamoya syndrome (MMS). Among 116 patients analyzed, 88 and 22 patients had angiographically proven MMD and Quasi-MMD, respectively. high-resolution magnetic resonance imaging confirmed bilateral MMD in 73 (83.0%) patients, 1 hemisphere with MMD and the other with intracranial atherosclerotic disease (ICAD) in 10 (11.4%) patients, and bilateral hemispheres with different vasculopathies in 5 (5.7%) patients. Detailed analysis of 204 affected hemispheres showed that several combinations of different vasculopathies were observed in the internal carotid artery and middle cerebral artery of the same hemisphere, such as ICAD-ICAD, ICAD-MMD, dissection-ICAD, and dissection-MMD. Hemispheres were assigned to MMD and MMS groups according to their vasculopathies. Transient ischemic attack occurred more frequently in hemispheres with MMD (48.1% versus 21.1%, P =0.024), whereas symptomatic ischemia was more common in hemispheres with MMS (57.9% versus 24.9%, P =0.002). However, postoperative cerebral infarction, symptom improvement and neo-formative collaterals showed no significant difference between hemispheres with MMD and MMS ( P >0.05). Patients with angiographically proven MMD or Quasi-MMD needed more accurate evaluation combined with high-resolution magnetic resonance imaging. Highly selected patients with MMS might also obtain benefits from surgical revascularization.

Clinical value of the systemic immune-inflammation index in moyamoya disease.

Moyamoya disease (MMD) is a rare cerebrovascular disorder with unknown etiology. The underlying pathophysiological mechanism of moyamoya disease remains to be elucidated, but recent studies have increasingly highlighted that abnormal immune response may be a potential trigger for MMD. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) are inflammatory markers that can reflect the immune-inflammation state of the disease. The purpose of this study was to investigate SII, NLR, and PLR in patients with moyamoya disease. A total of 154 patients with moyamoya disease (MMD group) and 321 age- and sex-matched healthy subjects (control group) were included in this retrospective case-control study. Complete blood count parameters were assayed to calculate the SII, NLR, and PLR values. The SII, NLR, and PLR values in the moyamoya disease group were significantly higher than those in the control group [754 ± 499 vs. 411 ± 205 (P < 0.001), 2.83 ± 1.98 vs. 1.81 ± 0.72 (P < 0.001), and 152 ± 64 vs. 120 ± 42 (P < 0.001), respectively]. The SII in the medium-moyamoya vessels of moyamoya disease was higher than that in the high-moyamoya vessels and low-moyamoya vessels (P = 0.005). Using the receiver operating characteristic (ROC) curve analysis to predict MMD, the highest area under the curve (AUC) was determined for SII (0.76 for SII, 0.69 for NLR, and 0.66 for PLR). Based on the results of this study, patients with moyamoya disease admitted for inpatient care due to acute or chronic stroke have significantly higher SII, NLR, and PLR when compared to blood samples drawn from completely healthy controls in a non-emergent outpatient setting. While the findings may suggest that inflammation plays a role in moyamoya disease, further studies are warranted to corroborate such an association. In the middle stage of moyamoya disease, there may be a more intense imbalance of immune inflammation. Further studies are needed to determine whether the SII index contributes to the diagnosis or serves as a potential marker of an inflammatory response in patients with moyamoya disease.

Long-term outcomes of moyamoya disease versus atherosclerosis-associated moyamoya vasculopathy using high-resolution MR vessel wall imaging

ObjectivesWe aimed to compare the long-term outcomes and surgical benefits between moyamoya disease (MMD) and atherosclerosis-associated moyamoya vasculopathy (AS-MMV) using high-resolution MRI (HRMRI).MethodsMMV patients were retrospectively included and divided into...

Long noncoding RNA profile of the intracranial artery in patients with moyamoya disease.

Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by progressive stenosis of the internal carotid artery (ICA) and secondary formation of collateral vessels. Revascularization surgery is performed in patients with MMD to prevent stroke; however, the pathogenesis of MMD remains unknown. Recently, long noncoding RNAs (lncRNAs) have been found to play a key role in gene regulation and are implicated in various vascular diseases. However, the lncRNA expression profile in MMD lesions has not been investigated. In this study the authors aimed to determine the characteristics of lncRNA expression in MMD lesions. The authors collected microsamples of the middle cerebral artery (MCA) from patients with MMD (n = 21) and patients with control conditions (n = 11) who underwent neurosurgical treatment. Using microarray experiments, the authors compared the profiles of lncRNA expression in the MCAs of the MMD and control patient groups and identified differentially expressed lncRNAs (fold change > 2, q < 0.05). In addition, the neighboring coding genes, whose transcription can be regulated in cis by the identified differentially expressed lncRNAs, were investigated and Gene Ontology (GO) analysis was applied to predict associated biological functions. The authors detected 308 differentially expressed lncRNAs (fold change > 2, q < 0.05), including 306 upregulated and 2 downregulated lncRNAs in the MCA from patients with MMD. Regarding the prediction of biological function, GO analyses with possible coding genes whose transcription was regulated in cis by the identified differentially expressed lncRNAs suggested involvement in the antibacterial humoral response, T-cell receptor signaling pathway, positive regulation of cytokine production, and branching involved in blood vessel morphogenesis. The profile of lncRNA expression in MMD lesions was different from that in the normal cerebral artery, and differentially expressed lncRNAs were identified. This study provides new insights into the pathophysiology of MMD.

Hemodynamic changes of donor artery after combined revascularization in adult Moyamoya disease

To explore the hemodynamic changes of the superficial temporal artery in adult Moyamoya Disease (MMD) who underwent combined revascularization surgery. A number of 40 patients with MMD were enrolled, and all of them underwent a direct superficial temporal artery (STA)-middle cerebral artery (STA-MCA) bypass combined with an encephalo-duro-arterio-synangiosis (EDAS). Hemodynamic parameters were detected by Color Doppler Ultrasonography (CDUS) at the preoperative, perioperative and follow-up time, including peak systolic velocity (PSV), end-diastolic velocity (EDV) and resistance index (RI). The control group were selected randomly during the same period. Researchers applied the SPSS 21 to conduct the two-sample analysis, Chi-Squared test and one-way repeated measures ANOVA between groups. P < 0.05 was considered statistically significant. In this study, 21 males and 19 females with an average age of 44.9 years (Range 28 y–56 y) were enrolled in the MMD group. Among them, 21 patients (52.5%) had perioperative complications, and all symptoms were transient neurological dysfunctions. Intermittent speech disorder was the most common complication during the period of operation. The preoperative hemodynamic of STA showed no significant difference between MMD and the control group. The perioperative hemodynamics had significant carnages compared with preoperative, and there was a trend of fluctuation. The perioperative PSV in the group with complications was significantly higher than the group without complications, except for EDV and RI. In the follow-up (X¯ = 5 months), PSV (60.21 ± 22.24 cm/s, P = 0.712) showed no difference compared with baseline data, while EDV (25.12 ± 9.94 cm/s, P = 0.000) and RI (0.575 ± 0.092, P = 0.000) showed significant difference between MMD and control group. The blood flow spectrogram showed high resistance in preoperative, but most patients showed a low resistance pattern during the follow-up time. It was the first time to demonstrate that the hemodynamic changes of STA fluctuated significantly within one week and eventually remained stable after combined revascularization. The PSV may play a more important role in postoperative complications. In the follow-up, PSV had no significant difference, EDV increased significantly, and RI decreased significantly. The blood flow spectrogram mainly shows a low resistance pattern when the hemodynamic is stable.

RNF213 R4810K Variant in Suspected Unilateral Moyamoya Disease Predicts Contralateral Progression.

BackgroundEarly‐stage unilateral moyamoya disease (MMD) is difficult to discriminate from isolated intracranial atherosclerotic stenosis, and identification of contralateral progression may aid in the diagnosis of MMD. The RNF213 (ring finger protein 213) R4810K variant is a strong genetic susceptibility factor for MMD; however, the role of contralateral progression in unilateral MMD is unknown.Methods and ResultsPatients who had undergone RNF213 R4810K genotyping with suspected unilateral MMD between January 2017 and August 2021 from 2 tertiary university hospitals were retrospectively reviewed. We compared the clinical features and radiographic outcomes of patients with and without this variant. The risk factors of contralateral progression in patients with suspected unilateral MMD were evaluated. The RNF213 R4810K variant was observed in 72 of 123 patients with suspected unilateral MMD, all of which were heterozygous. The allele frequency of the R4810K variant was significantly higher in the suspected unilateral MMD group compared with the historical control group (29.3% versus 1.2%; P<0.0001). Family history of MMD was significantly more common in patients with the variant than in those without (17% versus 4%; P=0.003). Eleven of 72 patients with the variant developed contralateral progression, whereas only 1 of 51 patients without the variant developed contralateral progression during a median follow‐up period of 28 months (log‐rank test; P=0.03). The presence of the RNF213 R4810K variant significantly correlated with contralateral progression (adjusted odds ratio, 6.39 [95% CI, 1.11–36.63]; P=0.04).ConclusionsContralateral progression is more likely to occur in patients with suspected unilateral MMD with the RNF213 R4810K variant than in those without the variant. However, because our study used a small sample size, this finding should be carefully interpreted and requires further studies with more patients and longer follow‐up periods.

Different hemodynamics of basal ganglia between moyamoya and non-moyamoya diseases using intravoxel incoherent motion imaging and single-photon emission computed tomography.

Moyamoya disease (MMD) and non-MMD have different pathogenesis, clinical presentation, and treatment policy. To identify differences in hemodynamics between MMD and non-MMD using intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT). Patients who had undergone 99mTc-ECD or 123I-IMP SPECT, and IVIM imaging were retrospectively studied. IVIM imaging was acquired using six different b-values. Cerebral blood flow ratio (CBFR) in the basal ganglia was calculated using a standardized volume-of-interest template. The cerebellum was used as a reference region. IVIM perfusion fraction (f) was obtained using a two-step fitting algorithm. Elliptical regions of interest were placed in bilateral basal ganglia on the IVIM f map. Patients were classified into MMD and non-MMD groups. The correlation between CBFR and mean IVIM f (fmean) in the basal ganglia was evaluated using Spearman's rank correlation coefficient. In total, 20 patients with MMD and 28 non-MMD patients were analyzed. No significant differences in fmean were observed among MMD, affected hemisphere with non-MMD (non-MMDaff), and unaffected hemispheres with non-MMD (non-MMDunaff). A negative correlation was seen between fmean and CBFR in the MMD group (r = -0.40, P = 0.0108), but not in the non-MMD group (non-MMDaff, r = 0.07, P = 0.69; non-MMDunaff, r = -0.22, P = 0.29). No significant differences were found among MMD and non-MMD patients, irrespective of SPECT tracers. The combination of IVIM MRI and SPECT appears to allow non-invasive identification of differences in hemodynamics between MMD and non-MMD.