Cerebrovascular Disorders

Epidemiology and Demographics

• Moyamoya disease has a bimodal age distribution, with peaks around 10 years and 30-40 years, and a higher prevalence in East Asian populations, with an ethnicity-specific incidence rate ratio of 4.6 compared to whites, and a female predominance with a female-to-male ratio up to 2.6:1 1, 2
• The disease has a higher incidence in Asian Americans (4.6 times higher), Black Americans (2.2 times higher), and a lower incidence in Hispanic Americans (0.5 times lower) compared to whites 1, 2

Clinical Presentation

• Children with Moyamoya disease predominantly present with ischemic symptoms, including transient ischemic attacks (TIAs), ischemic stroke, intellectual decline, seizures, and involuntary movements, often triggered by hyperventilation, crying, coughing, straining, or fever 2
• Adults more commonly present with intracranial hemorrhage, ischemic events (strokes or TIAs), and headaches, with posterior circulation involvement associated with worse clinical presentation and higher risk of hemorrhage 1, 2
• Characteristic electroencephalographic finding in children is the slowing of background rhythm after hyperventilation cessation ("rebuild-up" phenomenon) 2

Diagnosis

• Definitive diagnosis requires demonstration of stenosis of distal internal carotid artery bifurcation and proximal portions of ACA and MCA, appearance of dilated basal collateral arteries, and bilateral abnormalities, with catheter angiography as the gold standard and MRA and CTA as acceptable non-invasive alternatives 1, 2, 3

Genetics and Risk Factors

• Moyamoya disease has a strong genetic component, with up to 12% of patients having a positive family history, and the RNF213 gene as the primary susceptibility gene, with the R4810K variant predominant in East Asian populations (Japanese and Korean) 1, 2
• Penetrance rates vary significantly, with heterozygotes of RNF213 R4810K having approximately 0.67% (1 per 150) and homozygotes having more than 78%, and transmission is predominantly maternal, with affected mothers more often producing female offspring 1
• Genetic screening has limited benefit in the general population due to incomplete penetrance, and its role in non-Asian populations where Moyamoya disease incidence is low is uncertain 1

Management and Prevention

• Early diagnosis is critical, especially in children, as diagnosis may be delayed due to communication limitations, and different age groups require different management approaches due to varying clinical presentations, with surgical revascularization procedures showing benefit for symptomatic patients 1, 2, 3
• Understanding the genetic basis of Moyamoya disease may help identify potential therapeutic targets, and the disease involves gradual conversion of cerebral blood supply from internal carotid system to external carotid system, with progression through Suzuki stages (I-VI) reflecting increasing stenosis and collateral formation followed by regression of collaterals 1