Genetic and nongenetic factors for contralateral progression of unilateral moyamoya disease: the first report from the SUPRA Japan Study Group

OBJECTIVE Although many studies have analyzed risk factors for contralateral progression in unilateral moyamoya disease, they have not been fully elucidated. The aim of this study was to examine whether genetic factors as well as nongenetic factors are involved in the contralateral progression. METHODS The authors performed a multicenter cohort study in which 93 cases with unilateral moyamoya disease were retrospectively reviewed. The demographic features, RNF213 R4810K mutation, lifestyle factors such as smoking and drinking, past medical history, and angiographic findings were analyzed. A Cox proportional hazards model was used to find risk factors for contralateral progression. RESULTS Contralateral progression was observed in 24.7% of cases during a mean follow-up period of 72.2 months. Clinical characteristics were not significantly different between 63 patients with the R4810K mutation and those without it. Cox regression analysis showed that the R4810K mutation (hazard ratio [HR] 4.64, p = 0.044), childhood onset (HR 7.21, p < 0.001), male sex (HR 2.85, p = 0.023), and daily alcohol drinking (HR 4.25, p = 0.034) were independent risk factors for contralateral progression. CONCLUSIONS These results indicate that both genetic and nongenetic factors are associated with contralateral progression of unilateral moyamoya disease. The findings would serve to help us better understand the pathophysiology of moyamoya disease and to manage patients more appropriately.

Clinical Course of Unilateral Moyamoya Disease

BACKGROUND The natural history of unilateral moyamoya disease (MMD) progressing to bilateral MMD remains an enigma in modern vascular neurosurgery. Few, small series with limited follow-up have reported relatively high rates of contralateral stenosis progression. OBJECTIVE To review our large series of unilateral MMD patients and evaluate radiographic and surgical progression rates, and identify any factors associated with progression. METHODS We included all unilateral MMD cases treated from 1991 to 2017 in an observational study. We examined time to contralateral radiographic progression and contralateral progression requiring surgery. Using Cox regression analysis, we evaluated factors potentially associated with contralateral progression. RESULTS There were 217 patients treated for unilateral MMD. About 71% were female, and the average age at first surgery was 33.8 yr. Average follow-up was 5.8 yr (range 1-22 yr). A total of 18 patients (8.3%) developed contralateral progression. And 8 of these (3.7%) developed progression requiring bypass surgery. Baseline stenosis and hyperlipidemia (HLD) were significantly associated with radiographic progression (hazard ratio [HR] = 9.7, P = .006; HR = 4.0, P = .024). Baseline stenosis was associated with surgical progression (HR = 44.2, P = .002). Results were similar when controlling for possible confounders using multivariate regression. CONCLUSION Previous series showed relatively high rates of progression in unilateral MMD (15%-30%), but these studies were small and long-term follow-up was rarely available. Our large series indicates that the rate of progression is lower than previously reported but still warrants yearly noninvasive screening. These data may provide indirect support for statin therapy in MMD.

Patterns of Acute Intracranial Hemorrhage in Adult Patients with Bilateral and Unilateral Moyamoya Disease

Background: Moyamoya disease (MMD) is a rare cerebrovascular disease. The difference of hemorrhagic patterns in adult patients with bilateral and unilateral MMD is still unclear. Objective: For a better understanding of their characteristics, we compared the patterns of acute intracranial hemorrhage in adult patients with bilateral and unilateral MMD. Method: Adult MMD patients with acute intracranial hemorrhage were retrospectively included. Clinical and radiological characteristics of adult patients with bilateral and unilateral MMD were collected and analyzed. Chi-square test, t-test, or rank sum test were used for statistical analyses. Results: A total of 107 patients were included. Among 74 patients with bilateral MMD, 9 (12.2%) were at Suzuki Stage 2, 48 (64.9%) were at Stage 3, 16 (21.6%) were at Stage 4, and another (1.4%) was at Stage 5. However, in patients with unilateral MMD, 8 (24.2%) were at Stage 2, 23 (69.7%) were at Stage 3, and 2 (6.1%) were at Stage 4. Intraparenchymal hemorrhage was found in 40 (54.1%) patients with bilateral MMD and 16 (48.5%) patients with unilateral MMD (P=0.594). Intraventricular hemorrhage was shown in 65 (87.8%) patients with bilateral MMD and 19 (57.6%) patients with unilateral MMD (P<0.001). Subarachnoid hemorrhage was observed in 17 (23.0%) patients with bilateral MMD and 18 (54.5%) patients with unilateral MMD (P=0.001). Conclusion: Unilateral MMD patients with acute intracranial hemorrhage are at the earlier Suzuki stage than the bilateral MMD patients. Intraventricular hemorrhage occurs more frequently in bilateral MMD, while subarachnoid hemorrhage is more frequent in unilateral MMD.