The Moyamoya Disease pathophysiology explained
Moyamoya disease is a rare, progressive cerebrovascular disorder characterized by the narrowing or occlusion of arteries at the base of the brain, specifically the internal carotid arteries and their main branches. The term “moyamoya” is Japanese for “puff of smoke,” which describes the appearance of the abnormal vascular networks that develop as the disease advances. Understanding its pathophysiology involves examining the complex processes that lead to arterial stenosis, collateral vessel formation, and the resulting clinical consequences.
At the core of moyamoya disease lies an abnormal proliferation of smooth muscle cells within the arterial walls, leading to thickening and narrowing of the affected arteries. The exact cause of this proliferative process remains unknown, but it is believed to involve genetic factors, inflammatory responses, and endothelial dysfunction. The narrowing primarily affects the terminal portions of the internal carotid arteries and the proximal segments of the anterior and middle cerebral arteries. As these arteries progressively constrict, blood flow to vital areas of the brain diminishes, resulting in ischemia.
In response to reduced blood flow, the brain initiates a compensatory process by developing a network of tiny, fragile collateral vessels. These vessels emerge from the leptomeningeal arteries and other nearby arteries, attempting to bypass the occlusion and restore perfusion. However, these collateral vessels are abnormal, dilated, and prone to rupture, which can lead to hemorrhagic strokes. The proliferation of these vessels creates the characteristic “puff of smoke” appearance seen on angiograms.
The progression of moyamoya disease involves a cycle of arterial narrowing, collateral vessel formation, and potential vessel rupture. The stenosis reduces cerebral perfusion, leading to ischemic symptoms such as transient ischemic attacks, strokes, or neurological deficits. Simultaneously, the fragile collateral vessels are vulnerable to rupture, contributing to intracranial hemorrhages. The dynamic balance between ischemia and hemorrhage complicates management and underscores the importance of early detection.
On a molecular level, abnormalities in growth factors such as vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) may promote abnormal vessel proliferation. Additionally, genetic mutations, particularly in the RNF213 gene, have been linked to moyamoya disease, especially in East Asian populations, suggesting a hereditary component to its pathogenesis.
In summary, moyamoya disease involves a cascade of pathological processes starting with progressive arterial stenosis, likely driven by abnormal cellular proliferation and genetic predisposition. The body’s attempt to compensate through collateral vessel formation results in a delicate and abnormal vascular network that can lead to both ischemic and hemorrhagic events. Understanding these mechanisms is vital for early diagnosis, management, and the development of potential targeted therapies to improve outcomes for affected individuals.
