Association of Genetic Variants with Postoperative Donor Artery Development in Moyamoya Disease: RNF213 and Other Moyamoya Angiopathy-Related Gene Analysis.

Robust postoperative bypass development is a characteristic of moyamoya disease (MMD); however, genetic factors mediating this phenomenon remain incompletely understood. Therefore, we aimed to elucidate the relationship between postoperative donor artery development and genetic variants. We retrospectively enrolled 63 patients (79 hemispheres) who underwent combined revascularization surgery. Postoperative development of the superficial temporal artery (STA), middle meningeal artery, and deep temporal artery (DTA) was assessed using the caliber-change ratio determined from magnetic resonance angiography measurements. We analyzed RNF213 and 36 other moyamoya angiopathy-related genes by whole-exome sequencing and extracted rare or damaging variants. Thirty-five participants carried RNF213 p.Arg4810Lys (all heterozygotes), whereas 5 had RNF213 rare variants (RVs). p.Arg4810Lys was significantly associated with postoperative DTA development, while age at surgery, hypertension, and hyperlipidemia were inversely associated. Multiple regression analysis revealed that age and p.Arg4810Lys held statistical significance (P = 0.044, coefficient - 0.015, 95% confidence interval (CI) - 0.029 to 0.000 and P = 0.001, coefficient 0.670, 95% CI 0.269 to 1.072, respectively). Those with RNF213 RV without p.Arg4810Lys exhibited a significant trend toward poor DTA development (P = 0.001). Hypertension demonstrated a significant positive association with STA development, which remained significant even after multiple regression analysis (P = 0.001, coefficient 0.303, 95% CI 0.123 to 0.482). Following Bonferroni correction for multiple comparisons, targeted analyses of RNF213 and 36 moyamoya angiopathy-related genes showed a significant association of only RNF213 p.Arg4810Lys with favorable DTA development (P = 0.001). A comprehensive analysis of RNF213, considering both p.Arg4810Lys and RVs, may provide a clearer prediction of postoperative DTA development.

Indirect revascularization for pediatric moyamoya disease.

OBJECTIVE: Indirect revascularization is a common and effective treatment for pediatric moyamoya disease. However, in several cases postoperative angiogenesis is not sufficient. It is not fully understood which factors are involved in the development of postoperative collateral circulation. In this study, the authors aimed to elucidate the factors related to postoperative angiogenesis in indirect revascularization. METHODS: Among the patients who underwent indirect revascularization for moyamoya disease from January 2015 to December 2022, those whose angiogenesis was evaluated using angiography were included. Age, onset symptoms, comorbidities, preoperative imaging findings, surgical details, perioperative complications, postoperative imaging findings, and modified Rankin Scale (mRS) score at the last outpatient visit were retrospectively examined. RESULTS: Ninety cases (53 patients; 37 bilateral, 16 unilateral) were included. Sixty-eight cases (75.6%) were symptomatic. The mean age at surgery was 7.9 years, and the mean postoperative follow-up duration was 48.5 months. Frontotemporal encephalo-duro-arterio-synangiosis (EDAS) was performed in all cases, and simultaneous frontal encephalo-galeo-synangiosis (EGS) was performed in 34 cases. Postoperative angiography revealed insufficient angiogenesis in 14 of 90 cases (15.6%) after frontotemporal EDAS and in 8 of 34 cases (23.5%) after frontal EGS. A high degree of ivy sign depicted on preoperative MRI was found to be significantly correlated with good angiogenesis after both surgical procedures (p = 0.00030 for EDAS and p = 0.0039 for frontal EGS). In addition, an advanced preoperative Suzuki stage was significantly correlated with good postoperative angiogenesis after EDAS (p = 0.00040). Good angiogenesis was significantly correlated with postoperative improvement of the ivy sign in both procedures (p = 0.0005 in EDAS and p = 0.030 in frontal EGS) as well as correlated with a better mRS score at long-term follow-up after EDAS (p = 0.018). CONCLUSIONS: Preoperative ivy sign and Suzuki classification are related to the degree of angiogenesis achieved after indirect revascularization for pediatric moyamoya disease.

Suzuki Stage VI Unilateral Moyamoya Disease Presenting With Massive Intraventricular Hemorrhage.

Moyamoya disease (MMD) is characterized by stenosis of the terminal portion of the internal carotid artery (ICA) and the development of collateral vessels. In late Suzuki stage MMD, ICA almost disappears, and the moyamoya vessels gradually regress. We report a case of late Suzuki stage unilateral MMD presenting with intraventricular hemorrhage. A 76-year-old woman who had previously been diagnosed with right ICA occlusive disease was referred to our hospital due to impaired consciousness. Radiological evaluation revealed massive intraventricular hemorrhage. After endoscopic hematoma removal, digital subtraction angiography (DSA) was performed to examine the vascular anatomy, which revealed numerous basal moyamoya vessels originating from the posterior cerebral artery. Three-dimensional rotational angiography identified a choroidal anastomosis originating from the posterior choroidal artery as the hemorrhage source. The patient had an RNF213 p.Arg4810Lys heterozygous variant in the germline. Based on the DSA findings, MMD was diagnosed, and the patient was transferred to a rehabilitation hospital with good postoperative consciousness. In conclusion, patients diagnosed with ICA occlusive disease may have late Suzuki stage MMD, potentially leading to major hemorrhage; therefore, antithrombotic medications should be administered with caution. In diagnosing ICA occlusive disease, the assessment of periventricular anastomosis should be considered, taking into account the possibility of MMD.