The Pathogenetic Mechanism for Moyamoya Vasculopathy Including a Possible Trigger Effect of Increased Flow Velocity

Abstract

Moyamoya disease (MMD), which commonly exhibits moyamoya vasculopathy characterized by chronic progressive steno-occlusive lesions in the circle of Willis with “moyamoya” collateral vessels, has been well known for its unique demographic and clinical features. Although the discovery of the susceptibility gene RNF213 for MMD revealed the factor for its predominance in East Asians, the mechanisms underlying other predominant conditions (females, children, young to middle-aged adults, and anterior circulation) and lesion formation are yet to be determined. As MMD and moyamoya syndrome (MMS), which secondarily produces moyamoya vasculopathy due to pre-existing diseases, have the same vascular lesions despite differences in their original pathogenesis, they may share a common trigger for the development of vascular lesions. Thus, we herein consider a common trigger from a novel perspective on blood flow dynamics. Increased flow velocity in the middle cerebral arteries is an established predictor of stroke in sickle cell disease, which is often complicated by MMS. Flow velocity is also increased in other diseases complicated by MMS (Down syndrome, Graves’ disease, irradiation, and meningitis). In addition, increased flow velocity occurs under the predominant conditions of MMD (females, children, young to middle-aged adults, and anterior circulation), suggesting a relationship between flow velocity and susceptibility to moyamoya vasculopathy. Increased flow velocity has also been detected in the non-stenotic intracranial arteries of MMD patients. In a pathogenetic overview of chronic progressive steno-occlusive lesions, a novel perspective including the trigger effect of increased flow velocity may provide insights into the mechanisms underlying their predominant conditions and lesion formation.

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

“…On the contrary, hemodynamic stress may appropriately explain all the predominant features of vasculopathy. 75 Hemodynamic studies by transcranial Doppler revealed increased flow velocity in females, 76,77 children, 78,79 young to middle-aged adults, 80 and the anterior circulation. 79,81 In addition, a transcranial Doppler study on patients with MMD showed that angiographically nonstenotic, namely, unaffected, arteries in the anterior circulation had significantly higher velocities in patients with MMD than in age-matched controls, suggesting that flow velocity increases in patients with MMD as a premorbid condition.…”