Sheng Wang,1,2,* Qian Jiang,1,2,* Yuan Liu,1,2 Xincheng Zhang,1,2 Yimin Huang,1,2 Huaqiu Zhang1,2 

1Department of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Huaqiu Zhang, Department of Neurosurgery, Tongji hospital of Tongji medical college of Huazhong University of Science and Technology, Wuhan, People’s Republic of China, Email zhanghq@tjh.tjmu.edu.cn

Abstract: Moyamoya Disease (MMD) is a progressive cerebrovascular disorder characterized by the stenosis or occlusion of the terminal portions of the internal carotid arteries and fragile collateral vessel formation. While its etiology remains elusive, emerging evidence strongly implicates infections as key environmental triggers, particularly through immune-mediated vascular injury and interactions with genetic susceptibility (eg, RNF213 variants). This review explores the current understanding of the relationship between infections and MMD, examines epidemiological data, molecular and immunological mechanisms, genetic predispositions, and specific infections implicated in the disease. Critical limitations include causality ambiguity from reliance on anecdotal reports, methodological heterogeneity across studies, and mechanistic gaps in validating infection-endothelial dysfunction relationships. Future research must prioritize prospective cohorts and therapeutic strategies targeting infection-responsive pathways.

Keywords: moyamoya disease, RNF213, infection, second hit