Surgical Aspects of Moyamoya Disease

Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by unilateral or bilateral steno-occlusion of the main trunks of the circle of Willis and the development of basal collateral channels, including hypertrophy of the lenticulostriate and thalamoperforating arteries, which results in the characteristic appearance of moyamoya vessels. Takeuchi first described the disease in 1957 as hypoplasia of the bilateral internal carotid arteries . In 1969, Suzuki first employed the term “moyamoya” to describe the angiographic appearance of the enlarged collaterals, meaning “puff of smoke” in Japanese .

MMD is now known to affect people of diverse ethnicities, including Europeans, Americans, Japanese, Koreans, and Chinese. MMD is reported most often in Japan, with an estimated incidence of 0.54–0.94 per 100,000 and a prevalence of 6.03 per 100,000 population . In Europe and North America, partly due to underdiagnosis or misdiagnosis, the true incidence is still unknown. A 2005 study estimated an incidence of 0.086 per 100,000 population in California and Washington . However, a 2012 study reported an incidence of 0.57/100,000 in the United States , which is closer to the Asian incidence. MMD has a bimodal age distribution with the first peak in the pediatric population around 5–9 years, and the second peak in mid-adulthood around 45–49 years. In the first decade of life, the diagnosis is equally common in males and females, but subsequently, females predominate with a ratio of 2–3:1 .

Familial occurrence has been reported in 5–10% of cases. Although genetic factors have a role in MMD, they remain to be fully elucidated. In Japan, it has been established that familial MMD is transmitted in an autosomal dominant fashion with incomplete penetrance. RNF213 was the first identified susceptibility gene for MMD, and was found to be mutated in 95% of Japanese patients with familial MMD, 73% of those with nonfamilial MMD, and only 1.4% of controls .

Histologically, the affected vessels show eccentric fibrocellular intimal thickening, smooth muscle cell proliferation in the media, and abnormalities of the internal elastic lamina, with no evidence of inflammation or atheroma . The resulting steno-occlusion leads to hypoperfusion of cerebral vascular territories, and the watershed areas are particularly susceptible to ischemia. In response to hypoperfusion, thin-walled moyamoya collateral arteries (including the lenticulostriate) proliferate and enlarge. Moyamoya collaterals also lack smooth muscle cells, have incomplete internal elastic lamina, and may harbor aneurysmal dilatation, which could lead to hemorrhagic presentations (intracerebral, intraventricular, or subarachnoid hemorrhage).

In children, the most common presentation is cerebral ischemia. In a large Asian population study, 40% of those younger than 10 years of age presented with TIA and nearly 30% presented with cerebral infarction. Hemorrhagic presentation occurred in 3–9% of pediatric patients in both Asian and North American series. Other less common presentations include seizures, movement disorders, learning difficulties, and developmental delays. In adults, nearly 50% presented with intracranial hemorrhage in the Japanese series . In the North American cohort, adult MMD still largely presented with cerebral ischemia (about 80%) .