Moyamoya Vasculopathy and Moyamoya-Related Systemic Vasculopathy: A Review With Histopathological and Genetic Viewpoints

Systemic vasculopathy has occasionally been reported in cases of moyamoya disease (MMD). Since the pathological relationship between moyamoya vasculopathy (MMV) and moyamoya-related systemic vasculopathy (MMRSV) remains unclear, it was examined herein by a review of histopathologic studies in consideration of clinicopathological and genetic viewpoints. Although luminal stenosis was a common finding in MMV and MMRSV, histopathologic findings of vascular remodeling markedly differed. MMV showed intimal hyperplasia, marked medial atrophy, and redundant tortuosity of the internal elastic lamina, with outer diameter narrowing called negative remodeling. MMRSV showed hyperplasia, mainly in the intima and sometimes in the media, with disrupted stratification of the internal elastic lamina. Systemic vasculopathy has also been observed in patients with non-MMD carrying the RNF213 (ring finger protein 213) mutation, leading to the concept of RNF213 vasculopathy. RNF213 vasculopathy in patients with non-MMD was histopathologically similar to MMRSV. Cases of MMRSV have sometimes been diagnosed with fibromuscular dysplasia. Fibromuscular dysplasia is similar to MMD not only in the histopathologic findings of MMRSV but also from clinicopathological and genetic viewpoints. The significant histopathologic difference between MMV and MMRSV may be attributed to a difference in the original vascular wall structure and its resistance to pathological stress between the intracranial and systemic arteries. To understand the pathogeneses of MMD and MMRSV, a broader perspective that includes RNF213 vasculopathy and fibromuscular dysplasia as well as an examination of the 2- or multiple-hit theory consisting of genetic factors, vascular structural conditions, and vascular environmental factors, such as blood immune cells and hemodynamics, are needed.