Clinical Course, Therapy, and Long-Term Outcomes of Children With Moyamoya Disease and Posterior Cerebral Artery Involvement.

BACKGROUND AND OBJECTIVES: Posterior cerebral artery involvement (PCAi) has been identified as an important factor related to poor prognosis in moyamoya disease (MMD). This study summarized the characteristics of children with MMD and PCAi, clarified the clinical course, identified prognostic predictors, and investigated the long-term effect of encephaloduroarteriosynangiosis for posterior circulation (EDAS-p). METHODS: We retrospectively reviewed all our pediatric MMD cases with follow-up angiograms from November 2003 to December 2016. PCAi was classified as early-onset at initial diagnosis and delayed-onset after anterior circulation revascularization. Multivariable data including clinical features, radiographic findings, and surgical outcomes were analyzed. RESULTS: Among 570 children with MMD, 246 (43.2%) had PCAi, with 176 (30.9%) classified as early-onset PCAi. During a median follow-up period of 10 years, 17.8% (70/394) of patients without initial PCAi developed delayed-onset PCAi. The median time to detection of a new PCA lesion was 15.5 (range 7-110) months from initial diagnosis, with a median age of 10.5 (3-22). Younger age at onset, familial occurrence, advanced Suzuki stages, and preoperative infarctions were predictors of delayed-onset PCAi. EDAS-p was performed on 294 hemispheres of 195 patients with PCAi. Stroke-free survival was significantly higher in the EDAS-p group than in the non-EDAS-p group (99.0% vs 90.2%; p < 0.001 [Breslow test]; p = 0.001 [log-rank test]; median follow-up: 101 months). DISCUSSION: PCAi is not uncommon in children with MMD, underscoring the need for long-term close clinical monitoring, especially in patients with high-risk factors for PCA progression. EDAS-p may be a safe and effective procedure for preventing subsequent stroke in children with MMD and PCAi.

High Level of Serum Complement C3 Expression is Associated with Postoperative Vasculopathy Progression in Moyamoya Disease.

Background: The immune system plays an important role in the onset and development of moyamoya disease (MMD), but the specific mechanisms remain unclear. This study aimed to explore the relationship between the expression of complements and immunoglobulin in serum and progression of MMD. Methods: A total of 84 patients with MMD and 70 healthy individuals were enrolled. Serum immunoglobulin and complement C3 and C4 expression were compared between healthy individuals and MMD patients. Follow-up was performed at least 6 months post-operation. Univariate and multivariate analysis after adjusting different covariates were performed to explore predictive factors associated with vasculopathy progression. A nomogram basing on the results of multivariate analysis was established to predict vasculopathy progression. Results: Compared to healthy individuals, MMD patients had significantly lower expression of serum complements C3 (P = 0.003*). Among MMD patients, C3 was significantly lower in those with late-stage disease (P = 0.001*). Of 84 patients, 27/84 (32.1%) patients presented with vasculopathy progression within a median follow-up time of 13.0 months. Age (P=0.006*), diastolic blood pressure (P=0.004*) and serum complement C3 expression (P=0.015*) were associated with vasculopathy progression after adjusting different covariables. Conclusion: Complement C3 is downregulated in moyamoya disease and decreases even further in late-Suzuki stage disease. Age, diastolic blood pressure and serum complement C3 expression are associated with vasculopathy progression, suggesting that the complement might be involved in the development of moyamoya disease.

Isolated anterior cerebral artery occlusion: an atypical form of moyamoya disease.

BACKGROUND: The relationship between anterior cerebral artery (ACA) occlusion and moyamoya disease (MMD) has rarely been studied. In this study, we focused on a special type of MMD: isolated ACA-occlusive MMD. We investigated clinical attributes, genotypes and progression risk factors in patients with ACA-occlusive MMD, providing initial insights into the relationship between ACA occlusion and MMD. METHODS: We retrospectively analysed digital subtraction angiography (DSA) from 2486 patients and diagnosed 139 patients with ACA-occlusive MMD. RNF213 p.R4810K (rs112735431) mutation analysis was performed. Patients were categorised into progression and non-progression groups based on whether they progressed to typical MMD. Differences in clinical characteristics, neuropsychological assessment, radiological findings and genotypes were evaluated. Logistic regression analyses identified risk factors for ACA-occlusive MMD progression. RESULTS: The median age of patients with ACA-occlusive MMD was 36 years, and the primary symptom was transient ischaemic attack (TIA). 72.3% of ACA-occlusive MMD patients had cognitive decline. Of 116 patients who underwent RNF213 gene mutation analysis, 90 patients (77.6%) carried the RNF213 p.R4810K GG allele and 26 (22.4%) carried the GA allele. Of 102 patients with follow-up DSA data, 40 patients (39.2%) progressed. Kaplan-Meier curve estimates indicated a higher incidence of ischaemic stroke in the progression group during follow-up (p=0.035). Younger age (p=0.041), RNF213 p.R4810K GA genotype (p=0.037) and poor collateral compensation from the middle cerebral artery (MCA) to ACA (p<0.001) were risk factors of ACA-occlusive MMD progression to typical MMD. CONCLUSIONS: Cognitive decline and TIA might be the main manifestations of ACA-occlusive MMD. Isolated ACA occlusion may be an early signal of MMD. The initial lesion site of MMD is not strictly confined to the terminal portion of the internal carotid artery. Younger patients, patients with RNF213 p.R4810K GA genotype or those with inadequate MCA-to-ACA compensation are more likely to develop typical MMD.

Association of cognitive function and hypoperfusion in Moyamoya disease patients without stroke.

The influence of hypoperfusion on cognition in patients with Moyamoya disease (MMD) is unclear. This study investigated cognitive function changes in MMD patients without stroke and illustrated the relationship between cognitive impairment and hypoperfusion. We prospectively performed a structured battery of seven neurocognitive tests on 115 adult MMD patients without stroke and 82 healthy controls. Hemodynamic assessment was performed using dynamic susceptibility contrast-enhanced MRI. The best subset regression (BSR) strategy was used to identify risk factors. Global cognition (MoCA), speed of information processing (TMT-A), executive function (TMT-B), visuospatial function (CDT), and verbal memory (CAVLT) were significantly poorer in MMD patients without stroke than in healthy controls. The TMT-B score significantly correlated with cerebral blood flow (CBF) in the bilateral lateral frontal lobes, centrum semiovale, and temporal lobes. The TMT-A and CAVLT scores significantly correlated with CBF in the left centrum semiovale (L-CSO) and temporal lobes. According to the BSR results, age, education, white matter lesions, and hypoperfusion of the L-CSO were risk factors for cognitive impairment. Hypoperfusion leads to multiple cognitive impairments in MMD patients without stroke. The perfusion of particular areas may help evaluate the cognitive function of MMD patients and guide therapeutic strategies.

Wavelet Analysis of Cerebral Oxygenation Signal Measured by Near-Infrared Spectroscopy in Moyamoya Disease.

BACKGROUND: Spontaneous low-frequency oscillations (LFOs) have been widely studied in cerebrovascular disease, but little is known about their role in moyamoya disease (MMD). The objective of this study was to assess the value of spontaneous LFOs in MMD based on wavelet analysis of near-infrared spectroscopy signals. METHODS: Sixty-four consecutive idiopathic adult patients were prospectively enrolled. The regional tissue oxygenation index (TOI) obtained from continuous near-infrared spectroscopy signals. Five frequency intervals of spontaneous LFOs (I, 0.0095-0.02 Hz; II, 0.02-0.06 Hz; III, 0.06-0.15 Hz; IV, 0.15-0.40 Hz; and V, 0.40-2.00 Hz) were extracted based on wavelet analysis. The data were compared between the patients and healthy control groups. Clinical features, cognitive function, and disease progression of MMD were analyzed using TOI and frequency interval data. RESULTS: Compared with the healthy control group, patients with MMD had a higher cerebral TOI in both hemispheres. Based on wavelet analysis, the spontaneous LFO of TOI was found to be significantly lower for patients with MMD in frequency intervals II to IV than that for the controls. The spontaneous LFO of TOI is also related to the Suzuki stages in intervals II to IV, stroke in interval III, and cognitive impairment in intervals III to Ⅳ. CONCLUSIONS: There were significant differences in spontaneous LFO between patients with MMD and healthy controls. The change in spontaneous LFO in MMD is related to Suzuki stage, cerebral infarction, and cognitive impairment. This might be an effective method for evaluating the severity and monitoring the progression of MMD.

Identification of moyamoya disease based on cerebral oxygen saturation signals using machine learning methods.

Moyamoya is a cerebrovascular disease with a high mortality rate. Early detection and mechanistic studies are necessary. Near-infrared spectroscopy (NIRS) was used to study the signals of the cerebral tissue oxygen saturation index (TOI) and the changes in oxygenated and deoxygenated hemoglobin concentrations (HbO and Hb) in 64 patients with moyamoya disease and 64 healthy volunteers. The wavelet transforms (WT) of TOI, HbO and Hb signals, as well as the wavelet phase coherence (WPCO) of these signals from the left and right frontal lobes of the same subject, were calculated. Features were extracted from the spontaneous oscillations of TOI, HbO and Hb in five physiological activity-related frequency segments. Machine learning models based on support vector machine (SVM), random forest (RF) and extreme gradient boosting (XGBoost) have been built to classify the two groups. For 20-min signals, the 10-fold cross-validation accuracies of SVM, RF and XGBoost were 87%, 85% and 85%, respectively. For 5-min signals, the accuracies of the three methods were 88%, 88% and 84%, respectively. The method proposed in this article has potential for detecting and screening moyamoya with high proficiency. Evaluating the cerebral oxygenation with NIRS shows great potential in screening moyamoya diseases.

Imaging features of adult moyamoya disease patients with anterior intracerebral hemorrhage based on high-resolution magnetic resonance imaging.

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 mm2) compared with ischemic group (2.29 ± 1.17 mm2) or asymptomatic group (3.00 ± 1.34 mm2). 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.