Adult Moyamoya Disease and Moyamoya Syndrome: What Is New?

Abstract

Background: Recent advances are in the genetics, diagnosis, pathophysiology, and management of moyamoya disease (MMD), and moyamoya syndrome (MMS), a term used to describe moyamoya-like vasculopathy associated with various systemic diseases or conditions.

Summary: Ring finger protein (RNF213) has been reported to be a susceptibility gene not only for MMD but also for atherosclerotic intracranial arterial stenosis and ischemic stroke attributable to large artery atherosclerosis. The latest guidelines by the Research Committee on MMD of the Japanese Ministry of Health, Labor, and Welfare, removed limitations of the previous definition that required bilateral involvement of the intracranial carotid artery to make the diagnosis, given the increasing evidence of progression to bilateral involvement in unilateral MMD. 3-dimensional constructive interference in steady-state MRI is useful for the differential diagnosis of MMD from atherosclerosis. Recent advances in the pathophysiology of MMD suggest that genetic and environmental factors play important roles in vascular angiogenesis and remodeling via complex mechanisms. The latest Japanese Guidelines and American Scientific Statement described that antiplatelet therapy can be considered reasonable. Endovascular interventional stent placement fails to prevent ischemic events and does not halt MMD progression. In the Japan Adult Moyamoya trial, a randomized controlled trial for bilateral extracranial-intracranial direct bypass versus conservative therapy in patients with MMD, who had intracranial hemorrhage, recurrent bleeding, completed stroke, or crescendo transient ischemic attack was significantly fewer with direct bypass than with conservative care.

Key messages: This review presents updated information on genetics, diagnosis, pathophysiology, and treatment of adult MMD and MMS. Despite recent advances, many mysteries still exist in the etiologies of moyamoya vasculopathy. The diagnostic criteria and treatment guidelines have been updated but not yet been globally established. Ongoing and future studies investigating underlying pathophysiological mechanisms of MMD and MMS may clarify potentially effective medical, surgical, or endovascular treatments.

Keywords: Guidelines; Intracranial arterial stenosis; Moyamoya disease; Moyamoya syndrome; RNF213.

Fig. 1.

Diagram for the development of MMD (modified from [19]). The phenomenon is that the involved arteries decrease their luminal diameter because of intimal thickening and their outer diameter because of medial degeneration and the waving of elastic lamina during disease progression in the early stage of MMD. Shrinkage of involved arteries progresses in parallel with the progression of luminal stenosis.

Fig. 2.

Demographic view of the possible mechanism underlying the development of MMD. Internal carotid-external carotid (IC-EC) conversion as a compensatory physiological reorganization system for MMD.

Fig. 3.

A case of MMD (presented as case 1 in [21]). a MRI shows a watershed infarction in the right cerebral hemisphere. b On MRA, the right ICA was poorly visualized (white arrow), and the left ICA was not visible. c SPECT at rest shows extremely reduced blood flow in the right cerebral hemisphere (left side). d Steal phenomenon was induced by Diamox administration in the right cerebral hemisphere (left side). e A good patency was confirmed after STA-MCA double bypass surgery on MRA (white arrows). ICA, internal carotid artery; MCA, middle cerebral artery; MRA, magnetic resonance angiography; SPECT, single-photon computerized tomography; STA, superficial temporal artery.

Fig. 4.

A middle-aged patient with ischemic-onset MMD, who was associated with Graves’ disease. a Magnetic resonance angiography indicates steno-occlusive changes at bilateral terminal internal carotid arteries with abnormal vascular network formation at the base of the brain. b Heavy T2-weighted imaging indicates outer diameter narrowing at bilateral terminal internal carotid arteries (yellow arrows).