Validation and Extension Study Exploring the Role of RNF213 p.R4810K in 2,877 Chinese Moyamoya Disease Patients.

OBJECTIVE: To validate, update, and extend the role of RNF213 p.R4810K (G>A) for predicting the phenotype of moyamoya disease (MMD) patients and explore the different effects on pediatric and adult groups. METHODS: A total of 2,877 patients conducted from 2004 to 2018 were included. Review Manage 5.3 and SPSS 20.0 were applied to complete all statistical analyses. Information on age at onset, sex, initial symptom, family history and complications were obtained via retrospective chart review. Angiographic records were evaluated. RESULTS: In China, geographic proximity to Korea or Japan may affect the carrying rate of RNF213 p.R4810K. The proportion of patients with the following characteristics was significantly higher (P <0.017) in the GA than in the GG group: female, age at onset < 18 years, infarct after transient ischemic attack, family history of MMD, and posterior cerebral artery involvement. For pediatric patients, GA showed more cerebral hemorrhage (CH) (odds ratios (ORs) [95% confidence intervals (CIs)] = 3.99 (1.61-9.88), P = 0.003), more patients were in the Suzuki early and intermediate stage (P = 0.001; P = 0.001, respectively), while for the adult group, GA indicated more female (OR [95% CIs] = 1.43 [1.15-1.79], P = 0.001), fewer patients with diabetes (0.58 [0.38-0.86], P = 0.007) and intermediate Suzuki stage (P = 3.70 × 10-4). CONCLUSIONS: The incidence and carrying rates of RNF213 p.R4810K in various regions for Chinese MMD patients were obviously different. RNF213 p.R4810K has different predictive effects on phenotypes of pediatric and adult patients.

Clinical and Genetic Risk Factors of Long-Term Outcomes after Encephaloduroarteriosynangiosis in Moyamoya Disease in China.

OBJECTIVES: This retrospective study was conducted to analyze the associations between ring finger protein 213 p.R4810K variant, clinical features and long-term outcomes in patients with moyamoya disease (MMD) after encephaloduroarteriosynangiosis treatment. MATERIALS AND METHODS: A total of 2,545 patients with MMD in China were included in this study (median of follow-up duration: 32.00 months). Multiple Cox regression models were used to assess the associations between p.R4810K variant, clinical features and long-term outcomes. RESULTS: For all patients, in multivariate Cox analysis, no association was observed between p.R4810K and long-term outcomes. Pediatric onset (HR, 0.38; 95%CI, 0.25-0.59) and headache (HR, 0.26; 95%CI, 0.08-0.83) were inversely and hypertension (HR, 1.43 95%CI, 1.06-1.94), diabetes (HR, 1.55; 95%CI, 1.00-2.40), bilateral lesions (HR, 2.73; 95%CI, 1.12-6.65) and posterior cerebral artery involvement (HR, 1.44; 95%CI, 1.08-1.90) were positively associated with follow-up stroke (all P < 0.05). Pediatric onset (HR, 0.46; 95%CI, 0.26-0.82) was inversely and hyperlipidemia (HR, 1.83; 95%CI, 1.23-2.73), smoking (HR, 1.86; 95%CI, 1.13-3.07), high Suzuki angiographic stage (HR, 1.71, 95%CI, 1.09-2.70), poor admission neurologic status (HR, 8.93; 95%CI, 6.49-12.29) and follow-up stroke (HR, 8.31; 95%CI, 6.01-11.49) were positively associated with poor neurologic outcome at the last follow-up visit (all P < 0.05). The factors were not consistent in the different groups of age at onset. CONCLUSIONS: In our study, p.R4810K may play no role in long-term outcomes in Chinese MMD. Clinical features including age at onset, initial symptoms, risk factors of stroke, imaging, poor admission neurologic status were associated with poor outcomes in MMD after EDAS.

Predictive role of heterozygous p.R4810K of RNF213 in the phenotype of Chinese moyamoya disease.

OBJECTIVE: Precise genetic analyses were conducted with ring finger protein 213 (RNF213) in relation to a particular clinical phenotype in Chinese patients with moyamoya disease (MMD) to determine whether heterozygosity is responsible for the early-onset and severe form of this disease. METHODS: A case-control study for RNF213 p.R4810K involving 1,385 Chinese patients with MMD and 2,903 normal control participants was performed. Correlation analyses between genotype and phenotype or different clinical features were also statistically explored. RESULTS: An obvious trend was observed: the carrying rate of RNF213 p.R4810K gradually decreased when moving from coastal cities in northeast, north, and east China to southern cities or inland areas. Higher frequencies of p.R4810K were observed in patients with MMD compared with control participants (odds ratio, 48.1; 95% confidence interval, 29.1-79.6; p = 1.6 × 10-141). In addition, the onset age of all patients with the GA and AA genotypes were lower than with the GG genotype, and the median onset age was 40.0, 36.0, and 11.5 years with GG, GA, and AA, respectively, thereby confirming that those with GA or AA could acquire MMD during early life stages. Patients with MMD with the GA genotype were more susceptible to posterior cerebral artery (PCA) involvement compared to those with the GG genotype (38.4% vs 23.3%, p = 8.3 × 10-7). CONCLUSIONS: Strong evidence suggests that the carrying rate of RNF213 p.R4810K is closely related MMD risk in China and has given rise to an earlier onset age and more severe PCA involvement.

Clinical characteristics and leptomeningeal collateral status in pediatric and adult patients with ischemic moyamoya disease.

AIM: Previous studies have found significant differences in clinical characteristics between pediatric and adult moyamoya disease (MMD) patients, but few studies have focused on the factors underlying these differences. We aimed to investigate the differences in leptomeningeal collateral (LMC) status between pediatric and adult MMD patients and to analyze the effects of LMCs on clinical characteristics and therapeutic prognosis. METHODS: We retrospectively analyzed 214 MMD patients from January 2014 to January 2016. Clinical characteristics and LMC status were compared between the pediatric and adult patients. LMC status was graded as good or poor depending on the retrograde flow from the posterior cerebral artery (PCA) on digital subtraction angiography (DSA). RESULTS: A total of 83 pediatric and 131 adult (1:1.6) MMD patients were analyzed. Pediatric patients were more likely to experience a transient ischemic attack (81%), whereas adult patients were more likely to experience infarction (51%). Regarding the different MMD stages (the early, medium, and advanced stages corresponded to Suzuki stages 1-2, 3-4, and 5-6, respectively), the prevalence of good LMC status was higher for pediatric patients than for adult patients in the early stage (P = 0.047) and the medium stage (P = 0.001), but there were no differences between these patient groups in the advanced stage (P = 0.547). Worse postoperative angiographic outcomes (P = 0.017) were found in adult patients than in pediatric patients in the medium stage. Poor LMC status had strong correlations with infarction (P < 0.001 and P = 0.017) and poor postoperative outcomes (P = 0.003 and P = 0.043) in both pediatric and adult patients. CONCLUSIONS: Pediatric MMD patients have greater patency and a greater ability to establish good LMC status than adult patients, and poor LMC status has a strong correlation with severe clinical symptoms and poor postoperative outcomes. LMC status may be an important factor in the differences in clinical characteristics and prognosis between pediatric and adult MMD patients.

Meta-analysis of topical vancomycin powder for microbial profile in spinal surgical site infections.

OBJECTIVES: To systematically evaluate the impact of topical vancomycin powder for microbial profile in spinal surgical site infections. METHODS: All available literature regarding the topical use of vancomycin powder to prevent postoperative spinal infections was retrieved from the MEDLINE, EMBASE, and Cochrane databases starting from the creation date and up until September 30, 2018. RESULTS: A total of 21 studies involving 15,548 patients were reviewed. The combined odds ratio showed that topical use of vancomycin powder was effective for reducing the incidence of gram-positive bacterial infections in spinal surgical sites (OR 0.41, P < 0.00001) without affecting its efficacy in the prevention of polymicrobial infections (OR 0.30, P = 0.03). Additionally, it could significantly reduce the infection rate of methicillin-resistant staphylococcus (OR 0.34, P < 0.0001). However, topical vancomycin powder showed no advantage for preventing gram-negative bacterial infections (OR 0.94, P = 0.75). CONCLUSIONS: Topical administration of vancomycin powder may not increase the rates of gram-negative bacterial or polymicrobial infections in spinal surgical sites. On the contrary, it can significantly reduce the infection rates of gram-positive bacteria, methicillin-resistant staphylococcus (MRS) and microorganism. Of course, the topical vancomycin powder cannot change the rates of gram-negative bacterial infections, which may be related to the antimicrobial spectrum of vancomycin. Due to the limited number of articles included in this study, additional large-scale and high-quality studies are needed to provide more reliable clinical evidence.

Gene dysregulation in peripheral blood of moyamoya disease and comparison with other vascular disorders.

OBJECTIVE: Moyamoya disease (MMD) is a chronic occlusive cerebrovascular disease with unknown etiology, sharing many similar clinical symptoms with other vascular disorders. This study aimed to investigate gene dysregulation in peripheral blood of MMD and compare it with other vascular disorders. METHODS: Transcriptomic profiles of 12 MMD patients and 8 healthy controls were obtained using RNA sequencing. Differentially expressed genes (DEGs) were identified and several were validated by quantitative real-time PCR in independent samples. Biological pathway enrichment analysis of DEGs and deconvolution of leukocyte subsets in peripheral blood were performed. Expression profiles for other vascular diseases were downloaded from public database and consistent DEGs were calculated. Gene set enrichment analysis (GSEA) was conducted to compare gene dysregulation pattern between MMD and other vascular diseases. RESULTS: A total of 533 DEGs were identified for MMD. Up-regulated genes were mainly involved in extracellular matrix (ECM) organization, whereas down-regulated genes were primarily associated with inflammatory and immune responses. As for cell populations, significantly increased naïve B cells and naïve CD4 cells as well as obviously decreased resting natural killer cells were observed in peripheral blood of MMD patients. GSEA analysis indicated that only up-regulated genes of ischemic stroke and down-regulated genes of coronary artery disease and myocardial infarction were enriched in up-regulated and down-regulated genes of MMD, respectively. CONCLUSION: Dysregulated genes in peripheral blood of MMD mainly played key roles in ECM organization, inflammatory and immune responses. This gene dysregulation pattern was specific compared with other vascular diseases. Besides, naïve B cells, naïve CD4 cells and resting natural killer cells were aberrantly disrupted in peripheral blood of MMD patients. These results will help elucidate the complicated pathogenic mechanism of MMD.

Collateral Circulation in Moyamoya Disease: A New Grading System.

Background and Purpose- Predicting the risk of stroke and determining intervention indications are highly important for patients with Moyamoya disease (MMD). Here, we evaluated a novel MMD grading system based on collateral circulation and Suzuki stage to evaluate symptoms and predict prognosis. Methods- In total, 301 idiopathic MMD patients were retrospectively analyzed between 2014 and 2016. A collateral circulation grading system with scores ranging from 1 to 12 was established: the anatomic extent of pial collateral blood flow from posterior cerebral artery to middle cerebral artery and anterior cerebral artery was scored from 1 to 6; perforator collateral and internal cerebral artery flow were scored as 6 to 1, which corresponded to Suzuki stages 1 to 6. Dynamic susceptibility contrast-magnetic resonance imaging was used to evaluate hemodynamic status. We assessed the association between the grading system and clinical characteristics. Results- We analyzed 364 symptomatic hemispheres of 301 patients (146 males, 28±16 years). Ischemic patients who presented with infarction were more likely to score <8 points (P<0.001), whereas those with ischemia symptoms (transient ischemic attack and headache) were more likely to score >8 points. Hemorrhagic patients who presented with intraparenchymal hemorrhage were more likely to score <8 points, whereas those who presented with intraventricular hemorrhage were more likely to score >8 points (P<0.001). According to dynamic susceptibility contrast-magnetic resonance imaging, lower scores were correlated with more severe time to peak delay (P<0.001) and worse relative cerebral blood volume ratio (P=0.016) and cerebral flow ratio (P=0.002). Encephaloduroarteriosynangiosis was performed in 348 symptomatic hemispheres. Patients who had collateral scores <4 points were more likely to have a postoperative stroke and a worse prognosis during the follow-up. Conclusions- This new MMD collateral grading system correlated well with clinical symptoms, hemodynamic status, and therapeutic prognosis and may facilitate risk stratification and prognosis predictions in patients with MMD.

Epidemiology of Moyamoya Disease in China: Single-Center, Population-Based Study.

BACKGROUND: To our knowledge, no previous study has described the nationwide epidemiologic features of moyamoya disease (MMD) in China. We describe the epidemiologic features including the relative prevalence, age distribution, gender distribution, and initial clinical manifestations of patients with MMD treated at a single institution in China. METHODS: Our cohort included 4128 patients with MMD. Their demographic and clinical characteristics were obtained by retrospective chart review. RESULTS: The median age for the onset of symptoms was 30.36 years. The age distribution of patients with MMD was bimodal, with the highest peak detection rate at 35-45 years of age and a smaller peak at 5-9 years of age. The ratio of female-to-male patients was 1:1. The disease occurred mainly in the Han people and was rarely seen in minority nationalities. In our cohort, transient ischemic attack was the most common initial clinical manifestation (48.13%). The other initial manifestations included infarction (22.62%), hemorrhage (16.45%), and headache 230/4128 (5.57%). In north and northeast China, the ischemic type was more predominate while the hemorrhagic type was relatively rare. However, the percentage of hemorrhagic type in East China was higher than anywhere else in China. CONCLUSIONS: This study confirmed some unique epidemiologic features as the studies previously reported in China, but it also revealed some new sight and tendency about moyamoya in China. As a lack of national epidemiologic studies, this study indicated the outline of moyamoya in China.

Management of Dumbbell and Paraspinal Tumors of the Thoracic Spine Using a Single-stage Posterolateral Approach: Case Series.

This study investigated the surgical results of a single-stage posterolateral approach with arc incision, unilateral laminectomy, and costotransversectomy for the management of dumbbell tumors and paraspinal tumors of the thoracic spine. From January 2010 to March 2017, 14 patients with dumbbell tumors or paraspinal tumors of the thoracic spine who underwent resection with single-stage posterolateral approach were followed up and analyzed retrospectively. The operations were performed using a single-stage posterolateral approach with arc incision, unilateral laminectomy, and costotransversectomy without any instrumentation. We reviewed the scores of clinical symptoms and imaging results, including postoperative MRI and reconstructed 3D-CT images. Gross total removal was achieved in 13 patients, and subtotal removal was achieved in 1 case. Histopathology revealed schwannoma in 9 patients, angiolipoma in 1 patient, and paraganglioma and mixed hemangioma in 2 patients each. No significant operative or postoperative complications occurred in any patient. The 14 patients were followed up for 14-68 months (mean 39.4 months). At the final follow-up, no obvious spinal deformity or tumor recurrence was found in any patient except one with paraganglioma. Single-stage posterolateral approach is a good alternative surgical method for removing dumbbell tumors and paraspinal tumors of the thoracic spine without necessitating a subsequent anterior operation.

Encephaloduroarteriosynangiosis for pediatric moyamoya disease: long-term follow-up of 100 cases at a single center.

OBJECTIVE The object of this study was to summarize the long-term effect of encephaloduroarteriosynangiosis (EDAS) for the treatment of pediatric moyamoya disease (MMD) and to investigate factors influencing the clinical outcomes of EDAS. METHODS Clinical features, angiographic findings, and clinical outcomes were analyzed among MMD patients younger than 18 years who had been treated with EDAS between 2002 and 2007 at the authors' institution. The Kaplan-Meier method was used to estimate stroke risk after EDAS. Predictors of neurological outcome were assessed. RESULTS One hundred fifteen patients were identified. The mean age at symptom onset was 7.3 ± 4.0 years. The incidence of familial MMD was 11.3%. The female/male ratio was 1:1.16. A total of 232 EDAS procedures were performed, and the incidence of postoperative complications was 3%. Postoperative digital subtraction angiography was performed in 54% of the patients, and about 80% of the hemispheres showed good or excellent results. Neovascularization showed significant correlations with delay time (from symptom onset to first operation), Suzuki stage, and preoperative stroke (all p < 0.05). Clinical follow-up was available in 100 patients with a mean follow-up of 124.4 ± 10.5 months. Ten-year cumulative survival was 96.5% after surgery, and the risk of stroke was 0.33%/person-year. An independent life with no significant disability was reported by 92% of the patients. A good outcome correlated with a low Suzuki stage (p = 0.001). Older children and those without preoperative stroke had better clinical outcomes (p < 0.05). CONCLUSIONS On the basis of long-term follow-up data, the authors concluded that EDAS is a safe and effective treatment for pediatric MMD, can reduce the risk of subsequent neurological events, and can improve quality of life. The risk of ischemia-related complications was higher in younger patients, and older children showed better outcomes. Compensation was greater with more prominent cerebral ischemia. The long-term clinical outcome largely depended on the presence and extent of preoperative stroke.

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.

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.

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.

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.

Prospective screening of family members with moyamoya disease patients.

BACKGROUND: Genetic factors play an important role in the pathogenesis of moyamoya disease (MMD). Previous studies concentrated on familial MMD patients. In this study, we focused on family members of sporadic MMD patients, and aimed to gain a clearer understanding of the role that genetic factors play in MMD. METHODS: The immediate family members of MMD patients were initially screened by transcranial Doppler sonography (TCD) and positive cases were verified by magnetic resonance angiography (MRA). RESULTS: From July 2011 to March 2013, there were 527 MMD patients managed in our hospital, including 38 familial MMD cases. In this study, 285 immediate family members of 245 sporadic MMD patients were screened. Another 41 cases of familial MMD cases were identified, which included 21 family members and 20 corresponding sporadic MMD patients who had family members confirmed positive with MMD. As a result, the proportion of familial MMD patients increased from 7% (38/527) to 15% (79/527) in this period. For the main segments of the circle of Willis, Kappa values between TCD and MRA for the anterior cerebral arteries, middle cerebral arteries and posterior cerebral arteries were 0.91, 0.72, and 0.47, respectively. Familial cases confirmed by our screening showed a significantly higher percentage of asymptomatic patients (57%) compared with 9% from the control group who had a clear family history before. CONCLUSIONS: Familial MMD patients may account for a higher percentage among all cases than previously thought. Some family members of MMD patients may also have MMD, but not have any obvious symptoms. Routine screening should be implemented for all family members of MMD patients to improve the detection rate for this part of the patient base. TCD has a high diagnostic agreement with MRA for MMD. TCD may be the preferred choice for screening because it is inexpensive and safe.

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

BACKGROUND: Moyamoya disease (MMD) develops mostly in Asian countries including Japan, Korea, mainland China and Taiwan. However, there are few detailed demographic and clinical data about Chinese patients with MMD. Currently, the most effective treatment in adult patients with MMD is unknown. There have only been a few small case series reporting on encephaloduroarteriosynangiosis (EDAS) in an adult population. Here we describe the clinical features, surgical treatment and long-term outcome of adults with MMD treated at a single institution in China. METHODS: Our cohort included 470 adult patients with MMD. The demographic and clinical characteristics were obtained by retrospective chart review and long-term outcome was evaluated using the stroke status. The modified Rankin Scale (mRS) was used to determine the neurological functional outcome. Univariate and multivariate logistic regression analyses were performed to determine risk factors for postoperative morbidity and functional outcome. The risk of subsequent stroke was determined using the Kaplan-Meier method and Cox regression was used to determine risk factors for postoperative or subsequent strokes. RESULTS: The median age for the onset of symptoms was 36.8 (range, 18-59) years. The ratio of female to male patients was 1:1 (231/239). Familial occurrence of MMD was 2.3%. The most common initial symptom was a cerebral ischemic event. The incidence of postoperative ischemic events or hemorrhage was 5.9% (9.8% of patients). Older age at symptom onset, posterior cerebral artery (PCA) involvement and the presence of transient ischemic attack (TIA) were identified as predictors of adverse postoperative events. The Kaplan-Meier estimate stroke risk was 10.1% in the first 2 years, and the 5-year Kaplan-Meier risk of stroke was 13% after surgery for all patients treated with surgical revascularization. Older age at symptom onset, PCA involvement and the presence of TIA were identified as predictors of postoperative or subsequent strokes. Overall, 73.2% of patients had an independent life with no significant disability, with the strongest predictor being the preoperative mRS score. CONCLUSION: Clinical characteristics of adult MMD in China are different from those in other Asian countries. EDAS in adult patients with MMD carries a low risk, is effective at preventing future ischemic events and improves quality of life.

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.

Increased thyroid function and elevated thyroid autoantibodies in pediatric patients with moyamoya disease: a case-control study.

BACKGROUND AND PURPOSE: The purpose of this study was to investigate whether thyroid function and thyroid autoantibodies were associated with the risk of moyamoya disease in pediatric subjects. METHODS: Thyroid function and thyroid autoantibodies were evaluated in patients with moyamoya disease and control subjects, and their associations with moyamoya disease were estimated using multivariate analysis. RESULTS: We included 114 pediatric patients and 114 healthy control subjects. The patients displayed higher prevalence of increased thyroid function and elevated thyroid autoantibodies in comparison with control subjects. These remained significant after multivariate adjustment; the ORs (95% CI) for increased thyroid function and evaluated thyroid autoantibodies were evaluated as 12.47 (1.55 to 100.51) and 4.33 (1.29 to 14.59), respectively. CONCLUSIONS: Increased thyroid function and elevated thyroid autoantibodies are associated with moyamoya disease and therefore monitoring of thyroid function and thyroid autoantibodies in patients with moyamoya disease is suggested, which might help to guide subsequent clinical management.