What Causes Moyamoya Disease? Exploring the Triggers and Risk Factors

Moyamoya disease is a rare, progressive cerebrovascular disorder characterized by the narrowing or blockage of arteries in the brain, particularly the internal carotid arteries. As these vessels become obstructed over time, the brain compensates by forming a network of tiny collateral blood vessels that resemble a "puff of smoke" on imaging scans—hence the name "moyamoya," which means "puff of smoke" in Japanese. While the exact cause of this condition remains unclear, ongoing research continues to shed light on potential triggers and underlying mechanisms.

Possible Causes and Contributing Factors

Although the precise etiology of moyamoya disease has not been fully established, several theories have emerged based on clinical observations and scientific studies. One prominent theory suggests that the condition may stem from an inflammatory process affecting the blood vessels, sometimes referred to as vasculitis. However, evidence linking moyamoya directly to autoimmune or allergic-type reactions remains limited and inconclusive.

Infection-Related Triggers

Emerging data indicate a stronger association between moyamoya disease and various infectious agents. Researchers have observed higher incidence rates in patients with prior exposure to certain pathogens, including viruses, bacteria, tuberculosis, and even parasitic infections like schistosomiasis. These infections may trigger chronic inflammation within the cerebral vasculature, leading to gradual vessel deterioration and the development of abnormal blood vessel networks. In some cases, post-infectious immune responses could contribute to endothelial damage, further accelerating vascular occlusion.

Genetic and Hereditary Components

Another compelling line of investigation focuses on genetic predisposition. A growing body of evidence supports the idea that moyamoya disease can be inherited, with certain familial clusters reported across different populations—particularly in East Asian countries such as Japan and Korea. Specific gene mutations, including those in the RNF213 gene, have been identified in many affected individuals, suggesting a hereditary component. This genetic link helps explain why some families experience multiple cases, although not everyone with the mutation will develop the disease.

Autoimmune Links: A Weaker Connection

While early hypotheses proposed that allergic or autoimmune conditions might play a central role in moyamoya pathogenesis, recent clinical findings suggest otherwise. Studies analyzing patient histories show minimal correlation between moyamoya and classic allergic disorders or systemic autoimmune diseases. Instead, the focus has shifted toward understanding how localized vascular inflammation—possibly initiated by infection or genetic susceptibility—leads to long-term structural changes in the brain's blood supply.

Environmental and Regional Influences

Geographic patterns also provide valuable clues. The disease appears more frequently in certain regions, especially in Asia, implying that environmental factors—such as regional infections, dietary habits, or even climate-related variables—might interact with genetic backgrounds to influence disease onset. Additionally, secondary forms of moyamoya syndrome are often seen in patients with pre-existing conditions like neurofibromatosis type 1, sickle cell disease, or after cranial radiation therapy, highlighting the complexity of its development.

In summary, while the definitive cause of moyamoya disease remains elusive, current research emphasizes a multifactorial origin involving genetic vulnerability, infectious triggers, and chronic vascular inflammation. Understanding these interrelated factors is crucial for improving early diagnosis, developing targeted treatments, and potentially preventing progression in at-risk individuals.