Xiang-Yang Bao

Moyamoya Disease in China Its Clinical Features and Outcomes

Background and Purpose— Here we describe the clinical features and outcomes of patients with moyamoya disease who were surgically treated at a single institution in China. Methods— Our cohort included 802 patients with moyamoya disease. Demographic and clinical characteristics were obtained by retrospective chart review; follow-up information and outcome were obtained through clinical visits, telephone, or letter interview. We used the Kaplan-Meier methods to estimate stroke risk by treatment status. Results— The median age for the onset of symptoms was 28 (range, 0.5–77) years. Two definite peaks in age distribution were found. The ratio of women to men was 1:1 (398/404). Familial occurrence of moyamoya disease was 5.2%. The initial symptom was ischemia, hemorrhage, or others in 564, 113, and 125 patients, respectively. Twenty-nine of the 802 patients (3.6%) received conservative management. The remaining 773 patients (96.4%) underwent neurosurgical revascularization procedures, and 502 of these were bilateral. The median follow-up after surgery (n=773) or conservative management (n=26) was 26.3 months (range, 6.0–101.9 months). Most subsequent ischemic events appeared in the first 2 years after surgery. The Kaplan-Meier estimated stroke risk was 10.1% in the first 2 years, and the 5-year-Kaplan-Meier risk of stroke was 12.7% after surgery for all patients treated with surgical revascularization. Conclusions— This study on the clinical features of moyamoya disease in mainland China indicated bimodal incidence distribution with women-to-men ratios of 1:1 and lower rate of hemorrhages in adults compared with in children. Patients had low rates of postoperative ischemic or hemorrhagic strokes, and the majority of patients had preserved functional status after revascularization.

Moyamoya Disease in China

Background and Purpose— Here we describe the clinical features and outcomes of patients with moyamoya disease who were surgically treated at a single institution in China. Methods— Our cohort included 802 patients with moyamoya disease. Demographic and clinical characteristics were obtained by retrospective chart review; follow-up information and outcome were obtained through clinical visits, telephone, or letter interview. We used the Kaplan-Meier methods to estimate stroke risk by treatment status. Results— The median age for the onset of symptoms was 28 (range, 0.5–77) years. Two definite peaks in age distribution were found. The ratio of women to men was 1:1 (398/404). Familial occurrence of moyamoya disease was 5.2%. The initial symptom was ischemia, hemorrhage, or others in 564, 113, and 125 patients, respectively. Twenty-nine of the 802 patients (3.6%) received conservative management. The remaining 773 patients (96.4%) underwent neurosurgical revascularization procedures, and 502 of these were bilateral. The median follow-up after surgery (n=773) or conservative management (n=26) was 26.3 months (range, 6.0–101.9 months). Most subsequent ischemic events appeared in the first 2 years after surgery. The Kaplan-Meier estimated stroke risk was 10.1% in the first 2 years, and the 5-year-Kaplan-Meier risk of stroke was 12.7% after surgery for all patients treated with surgical revascularization. Conclusions— This study on the clinical features of moyamoya disease in mainland China indicated bimodal incidence distribution with women-to-men ratios of 1:1 and lower rate of hemorrhages in adults compared with in children. Patients had low rates of postoperative ischemic or hemorrhagic strokes, and the majority of patients had preserved functional status after revascularization.

Clinical features, surgical treatment, and long-term outcome in pediatric patients with moyamoya disease in China.

Background: There was few detailed demographic and clinical data about Chinese patients with moyamoya disease. Here we describe the clinical features, surgical treatment, and long-term outcome of pediatric patients with moyamoya disease at a single institution in China. Methods: Our cohort included 288 pediatric patients with moyamoya disease. The demographic and clinical characteristics were obtained by retrospective chart review and long-term outcome was evaluated using the stroke status. Univariate and multivariate logistic regression analyses were performed to determine the risk factors for clinical outcome. The risk of subsequent stroke was determined using the Kaplan-Meier method. Results: The median age for the onset of symptoms was 8.0 years. The ratio of female to male patients was 1:1. Familial occurrence of moyamoya disease was 9.4%. The incidence of postoperative complications was 4.2%. Postoperative ischemic events were identified as predictors of unfavorable clinical outcome, while older age of symptom onset was associated with a favorable clinical outcome. The Kaplan-Meier estimate stroke risk was 5% in the first 2 years, and the 5-year-Kaplan-Meier risk of stroke was 9% after surgery for all patients treated with surgical revascularization. Overall, 86% of patients had an independent life with no significant disability. Conclusion: This long-term survey demonstrated that most surgically treated pediatric patients with MMD maintain good outcomes. Our results indicate that an early diagnosis and active intervention before the establishment of irreversible hemodynamic change are essential to achieve a favorable clinical outcome.

Surgical outcomes following encephaloduroarteriosynangiosis in adult moyamoya disease associated with Type 2 diabetes.

OBJECTIVE Debate exists regarding the merits and shortcomings of an indirect bypass procedure for treating adult patients with moyamoya disease (MMD). Considerable variation in neovascularization occurs among different organs in patients with diabetes mellitus. Here, the effect of encephaloduroarteriosynangiosis on MMD associated with Type 2 diabetes mellitus (T2DM) is evaluated. METHODS A retrospective and 1:2 matched case-control study was conducted in moyamoya patients with or without T2DM (n = 180). Postoperative collateral formations were graded according to the Modified Collateral Grading System that originated from the Matsushima Angiographic Stage Classification. Neurological function outcomes before and after the operation were evaluated according to the modified Rankin Scale. Univariate and multivariate logistic regression analyses were performed to determine the risk factors for clinical outcome. RESULTS There was no statistically significant difference in the constituent ratios of initial symptom and preoperative Suzuki stage between patients with and without T2DM. Progression of angiopathy around the circle of Willis was postoperatively observed in bilateral internal carotid arteries in both groups. Patients with T2DM had a higher postoperative Suzuki stage (p < 0.01) and more frequent development of collateral angiogenesis germinating from the external carotid after indirect revascularization procedures in the surgical cerebral hemisphere (82.7% vs 72.2%; p < 0.05). The extent of postoperative collateral formation in patients with diabetes mellitus was significantly higher (p < 0.01). Postoperative clinical improvement in the diabetes group was more common after revascularization procedures (p < 0.05), and the diabetes group had lower modified Rankin Scale scores (p < 0.05) in comparison with the nondiabetes group. Late postoperative stroke and posterior cerebral artery involvement were identified as predictors of unfavorable clinical outcome in both groups, while T2DM was associated with a favorable clinical outcome. CONCLUSIONS Encephaloduroarteriosynangiosis is an efficacious treatment for adult patients with MMD. Patients with T2DM could achieve better collateral circulation and clinical improvement following surgery.

Novel Susceptibility Loci for Moyamoya Disease Revealed by a Genome-Wide Association Study

Background and Purpose— Moyamoya disease (MMD) is a rare cerebral vasculopathy characterized by bilateral internal carotid artery stenosis and often leads to stroke in children or young adults. Although familial inheritance is well recognized, the genetic basis of MMD remains poorly understood. Methods— A 2-stage genome-wide association study was conducted involving 1492 cases and 5084 controls. In the discovery stage, logistic regression was used to test associations, and imputation was conducted based on genotyped single-nucleotide polymorphisms (SNPs). In the validation stage, the top significant SNPs were again genotyped in an independent cohort. Fixed-effects inverse variance-weighted meta-analysis was used in the combined discovery and validation samples. Furthermore, association analysis was conducted in subgroups using patient clinical data. Results— The study identified 10 novel risk loci with genome-wide significance (P<5×10−8) and confirmed a previously reported locus on 17q25. No significant SNP showed evidence of heterogeneity between the 2 stages. Cumulatively, these SNPs explained 14.76% of disease risk variance—a substantial proportion of the 39.02% of risk variance explained by all genome-wide genotyped SNPs. One SNP, rs9916351 in RNF213 (Pcombined=4.57×10−54; odds ratio, 1.96), showed a stronger genetic effect on early-onset than late-onset MMD (P=0.003). Two novel SNPs in genes regulating homocysteine metabolism, rs9651118 in MTHFR (Pcombined=2.49×10−19; odds ratio, 0.65) and rs117353193 in TCN2 (Pcombined=6.15×10−13; odds ratio, 1.43), were associated with high-serum homocysteine in MMD cases. Additionally, another SNP associated with MMD (rs2107595 in HDAC9; Pcombined=1.49×10−29; odds ratio, 1.64) was previously implicated in large-vessel disease. Tissue enrichment analysis showed that the genes of associated loci were highly expressed in the immune system (false discovery rate, <0.05). Conclusions— This study identifies several novel susceptibility genes for MMD. The association with homocysteine metabolism and the immune system enrichment of susceptibility gene expression suggest that therapeutic interventions targeting these pathways may be effective approaches for MMD treatment.

Long-term Outcomes After Encephaloduroarteriosynangiosis in Adult Patients with Moyamoya Disease Presenting with Ischemia

BACKGROUND In adult Moyamoya disease (MMD), there remains controversy about the effectiveness of revascularization surgeries because randomized studies have not been performed to compare the efficacy of surgical techniques. This study was conducted to assess the most appropriate surgical treatment for adult patients with MMD. METHODS Encephaloduroarteriosynangiosis (EDAS) was performed on 247 hemispheres in 145 patients. The clinical and demographic characteristics of patients were obtained via retrospective chart review. Clinical and angiographic states were evaluated retrospectively using quantitative methods. The mean duration of clinical follow up was 141.4 ± 19.5 months. RESULTS A total of 247 EDAS procedures were performed in 145 patients, including 15 EDAS performed using the occipital artery as the donor vessel. The mortality rate was 0%, and the permanent morbidity rates were 1.2% per operation and 2.0% per person. The mean modified Rankin Scale score was 1.21 ± 1.31 postoperatively and 1.01 ± 1.39 at the last follow-up. Of the 109 hemispheres studied, 45% were classified as grade A, 34% as grade B, and 21% as grade C collateral circulation. The annual rates of stroke were calculated to be 0.73% per person-year. Overall, the 1-,5-, and 10-year actuarial stroke rates were 2.1±1.2%, 6.8±2.1%, and 8.9±2.4%, respectively. Bilateral involvement was a common significant factor in any, hemorrhagic, and ischemic strokes. Hypertension was a risk factor for ischemic strokes during follow-up. CONCLUSIONS EDAS is an effective procedure in a Chinese cohort of patients with MMD. EDAS resulted in satisfactory long-term improvement of clinical states and prevention of recurrent strokes.

Cortical Microvascularization in Moyamoya Disease: Characteristics and the Relations with Surgical Outcomes of Encephaloduroarteriosynangiosis

Moyamoya disease (MMD) is a progressive occlusive cerebrovascular disorder of the internal carotid arteries or their branches, with compensatory development of an abnormal basal collateral vascular network [1]. Surgical revascularization has been proposed as effective in preventing clinical events, via either a direct or indirect procedure [2,3]. As a commonly used indirect revascularization method, encephaloduroarteriosynangiosis (EDAS) is considered easier and safer than direct bypass [4]. However, its effectiveness remains controversial [3,4]. Therefore, it is important to identify whether a patient is suitable for EDAS to determine the best surgical approach. Increased and dilated cortical microvasculature is considered a MMD-specific alteration, and it might represent a compensatory mechanism for reduced cerebral blood flow [5,6]. According to our surgical experience in the treatment of MMD, there seems to be a correlation between the cortical microvascular density and the effect of EDAS. Therefore, we sought to verify this hypothesis in this study. We identified all consecutive patients with MMD treated by EDAS at our department from October 2011 to October 2014. The diagnosis of MMDwas made according to the guidelines published in 2012 [2]. All EDAS surgeries were performed on the middle cerebral artery (MCA) territory, and the parietal branch of the superficial temporal artery (STA) was used. General anesthesia was maintained using sevoflurane in oxygen and air, combined infusions of propofol and remifentanil. End-tidal carbon dioxide (ETCO2) was maintained at 38–42 mmHg in all patients during surgery. For the analysis of cortical vascularization, we took photographs of the cerebral cortex during surgery. Postoperatively, we analyzed two suitable regions of interest (ROIs) per cortex image. ROIs were characterized as an area of 5 9 5 or 10 9 10 mm grids without obvious arteries and veins [5]. A microvascular density (MD) was calculated as the percentage of visible microvessel grids and total grids per analyzed ROI, and the final MD scores were represented as the means of the two ROIs in each image. The cases were divided into three groups with the following cutoff points: “low,” MD less than 33%; “medium,” MD between 33% and 66%; and “high,” MD higher than 66% [7] (Figure 1). Postoperative cerebral digital subtraction angiography (DSA) was routinely performed 6–8 months after surgery. The development of collateral circulation through the bypass was graded according to the system described by Matsushima et al. [8]: Grade I, revascularization of less than 1/3 of the MCA distribution; Grade II, between 1/3 and 2/3; and Grade III over 2/3. The extent of collateral formation was dichotomized into favorable (Grade II and Grade III) and unfavorable (Grade I). The long-term outcomes were ascertained during clinical visits and telephone interviews. The overall clinical outcomes were divided into four grades [9]: (1) excellent, preoperative symptoms had totally disappeared without fixed neurological deficits; (2) good, symptoms had markedly decreased, but mild neurological deficits remained; (3) fair, symptoms persisted albeit less frequently; and (4) poor, preoperative symptoms remained unchanged or worsened and with the appearance of new

Circulating endothelial progenitor cells and endothelial cells in moyamoya disease

There is no well‐recognized biomarker for accurately predicting outcome in the presence of moyamoya disease (MMD), a progressive occlusive cerebrovascular disease of the internal carotid arteries or their branches. The aim of this study was to investigate the presence of endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) in MMD and correlate the findings with clinical features.