The Moyamoya Disease pathophysiology
Moyamoya disease is a rare, progressive cerebrovascular disorder characterized by the narrowing or occlusion of the terminal portions of 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 network that develops at the base of the brain as the body attempts to compensate for reduced blood flow. Understanding the pathophysiology of moyamoya disease involves examining the underlying vascular changes, genetic and molecular factors, and the body’s response to chronic cerebral ischemia.
At the core of moyamoya disease is the progressive stenosis or occlusion of the distal intracranial internal carotid arteries and their proximal branches, such as the anterior and middle cerebral arteries. This narrowing results from abnormal thickening of the arterial intima, the innermost layer of the blood vessel wall. Unlike typical atherosclerotic processes that involve lipid deposits, moyamoya-associated arterial changes are primarily due to proliferative thickening and fibrosis within the arterial wall, leading to luminal narrowing. This constriction significantly diminishes cerebral blood flow, predisposing affected individuals to ischemic strokes, transient ischemic attacks, or hemorrhages.
As the primary arteries become occluded, the brain‘s autoregulatory mechanisms activate to maintain adequate perfusion. In response, a network of fragile collateral vessels forms at the base of the brain. These vessels, which develop in an attempt to bypass the occluded arteries, are thin-walled and prone to rupture, explaining the increased risk of hemorrhagic strokes in moyamoya patients. The abnormal vascular network appears as a “puff of smoke” on angiographic imaging, reflecting the proliferation of small, tangled vessels.
Genetic and molecular factors play a significant role in the disease’s pathogenesis. Moyamoya disease shows a higher prevalence among East Asian populations, particularly in Japan, Korea, and China, suggesting a genetic predisposition. Mutations in the RNF213 gene have been identified as a major susceptibility factor, although the exact molecular mechanisms remain under investigation. These genetic alterations likely influence vascular development and integrity, contributing to the abnormal arterial remodeling seen in the disease.
Inflammatory processes and abnormal angiogenic signaling also contribute to moyamoya pathophysiology. Inflammatory mediators may promote endothelial cell proliferation and fibrosis within the arterial wall, exacerbating luminal narrowing. Simultaneously, increased expression of angiogenic factors such as vascular endothelial growth factor (VEGF) encourages the formation of collateral vessels. However, these newly formed vessels are often structurally weak and inefficient, failing to adequately compensate for the reduced blood flow and increasing the risk of hemorrhagic events.
Clinically, the progressive nature of moyamoya disease reflects the ongoing vascular changes. The chronic ischemia stimulates a cycle where arterial stenosis worsens, collateral vessels enlarge, and the risk of stroke persists or escalates. Surgical revascularization procedures aim to restore adequate cerebral blood flow by bypassing the occluded arteries, highlighting the importance of understanding the disease’s vascular pathology.
In summary, moyamoya disease’s pathophysiology involves complex vascular remodeling driven by genetic predisposition, abnormal arterial proliferation, and compensatory collateral formation. These processes collectively lead to a fragile vascular network that predisposes individuals to ischemic and hemorrhagic strokes, underscoring the importance of early diagnosis and intervention.
