Research Progresses in Understanding the Pathophysiology of Moyamoya Disease

Abstract

Background: The pathogenesis of moyamoya disease (MMD) is still unknown. The detection of inflammatory molecules such as cytokines, chemokines and growth factors in MMD patients' biological fluids supports the hypothesis that an abnormal angiogenesis is implicated in MMD pathogenesis. However, it is unclear whether these anomalies are the consequences of the disease or rather causal factors as well as these mechanisms remain insufficient to explain the pathophysiology of MMD. The presence of a family history in about 9-15% of Asian patients, the highly variable incidence rate between different ethnic and sex groups and the age of onset support the role of genetic factors in MMD pathogenesis. However, although some genetic loci have been associated with MMD, few of them have been replicated in independent series. Recently, RNF213 gene was shown to be strongly associated with MMD occurrence with a founder effect in East Asian patients. However, the mechanisms leading from RNF213 mutations to MMD clinical features are still unknown. Summary: The research on pathogenic mechanism of MMD is in its infancy. MMD is probably a complex and heterogeneous disorder, including different phenotypes and genotypes, in which more than a single factor is implicated. Key Message: Since the diagnosis of MMD is rapidly increasing worldwide, the development of more efficient stratifying risk systems, including both clinical but also biological drivers became imperative to improve our ability of predict prognosis and to develop mechanism-tailored interventions.

Prolonged Mean Transit Time Detected by Dynamic Susceptibility Contrast Magnetic Resonance Imaging Predicts Cerebrovascular Reserve Impairment in Patients with Moyamoya Disease

“…The pathophysiological mechanisms of MMD remain poorly understood. MMD is probably a complex and heterogeneous disorder, including different phenotypes and genotypes, in which more than a single factor is implicated [3] . Patients with MMD show various grades of hemodynamic insufficiency and ischemic symptoms.…”

Proposal for a Prospective Registry for Moyamoya Disease in Japan

“…Part of the data items will be employed from the stroke version of (CDE) proposed by NINDS (NIN https://commondataelements.ninds.nih.gov/#page=Default), which will ensure that our disease registry meets with the international standards and will facilitate international co-operation. 18) It is also important to utilize the data from the past as well as ongoing clinical research; therefore, data items collected in JAM, AMORE and COSMO-Japan studies will be included in the registry, which will enable continuous follow-up of the patients who participated in these studies. 11–13) Open registry is ideal for collecting as much data as possible.…”

“…Participants of this meeting come from Japan, Europe, North America, China and South Korea, representing key institutions for the treatment of MMD. 15,16) …”

GEN-O-MA project: an Italian network studying clinical course and pathogenic pathways of moyamoya disease—study protocol and preliminary results

“…MA is sub-classed in moyamoya disease (MMD) when MA is bilateral and it is the sole disease manifestation, or moyamoya syndrome (MMS) when MA is associated with a well-defined acquired or genetic condition. MA occurring unilaterally has been recently defined as unilateral moyamoya disease (uMMD) [1].…”

“…Anomalies in angiogenesis and vasculogenesis, due to the detection of increased cytokine and growth factor concentrations have been invoked as potential disease mechanisms. Also genetic factors, given the high familial rate and the ethnic differences, are believed to be involved [1,2].…”