Moyamoya Disease
Introduction
Moyamoya disease (MMD) is a chronic, progressive cerebrovascular disorder. It is characterized by stenosis or occlusion of the terminal portions of the internal carotid arteries and their proximal branches. In response to this arterial narrowing, a network of fragile collateral vessels develops at the base of the brain. On angiography, it appears as a “puff of smoke,” giving the disease its Japanese name, moyamoya.
Moyamoya disease refers to the idiopathic form. Similar vascular changes occurring secondary to other conditions, such as Down syndrome, neurofibromatosis type 1, radiation, or sickle cell disease, are classified as Moyamoya syndrome.
Genetics
Moyamoya disease has a strong hereditary base, especially in East Asian populations. Familial cases account for 5–15% of all cases. The most significant susceptibility gene is RNF213 on chromosome 17q25.3. The c.14576G>A (p.R4859K) variant strongly increases disease risk. Other genes, including ACTA2 and GUCY1A3, have been implicated in syndromic forms. The inheritance pattern is complex and multifactorial. There are autosomal-dominant tendencies and incomplete penetrance.
Pathophysiology
The main pathophysiological mechanism is progressive stenosis or occlusion of the intracranial internal carotid arteries, leading to decreased cerebral perfusion. In response, abnormal collateral vessels form at the base of the brain. While these vessels help maintain perfusion relatively, they are fragile and prone to rupture. Chronic ischemia can cause transient ischemic attacks, cerebral infarctions, and cognitive impairment.
Conversely, rupture of fragile collaterals may result in intracerebral or intraventricular hemorrhage. Endothelial proliferation, smooth muscle hyperplasia, and abnormal angiogenesis lead to vascular remodeling, a characteristic feature of the disease.
Epidemiology
Moyamoya disease has a higher prevalence in East Asia, especially Japan, Korea, and China. The prevalence is lower in Europe and North America. The disease has a bimodal age distribution. In childhood, it typically presents between ages 5 and 10 with ischemic events. In adults, it presents around 30 to 40 years with hemorrhagic strokes. The female-to-male ratio is about 2:1.
Clinical manifestations
Patients usually present with recurrent ischemic strokes or transient ischemic attacks. These may manifest as hemiparesis, speech disturbances, diminished consciousness, or seizures. Headaches are also common. Chronic ischemia can cause developmental delay or cognitive deficits. Adults more often present with intracerebral hemorrhage, which often occurs in the basal ganglia or thalamus. Ischemic events can also occur in adults.
Other manifestations include involuntary movements such as chorea. These result from basal ganglia involvement. Rarely, visual symptoms occur if the posterior circulation is affected. Moyamoya disease can be challenging to distinguish from other pediatric or adult stroke syndromes. This can lead to potential delays in diagnosis.
Diagnosis
Diagnosis is based primarily on neuroimaging. Digital subtraction angiography remains the gold standard. It reveals the characteristic “puff of smoke” pattern of collateral vessels. MRI and MRA are used to detect stenosis, infarcts, and collateral vasculatures. CT angiography is an alternative method if MRI is unavailable. Functional imaging, such as SPECT or PET, can evaluate cerebral perfusion and hemodynamic patterns.
Based on the Japanese diagnostic guidelines, stenosis or occlusion of the terminal internal carotid artery or its proximal branches is required. There must be evidence of abnormal vascular networks at the brain base and exclusion of secondary causes.
Biochemical laboratory tests in patients with Moyamoya disease are typically nonspecific and do not establish the diagnosis. However, laboratory evaluation is important to exclude coexisting disorders or secondary causes of moyamoya vasculopathy, such as hematologic, autoimmune, or metabolic conditions, and to guide optimal therapeutic decisions, including the selection of antithrombotic therapy and perioperative management.
Treatment
Treatment of Moyamoya disease is largely supportive and includes antiplatelet therapy, anti epileptic medications, and management of hemorrhagic complications. Definitive treatment is surgical revascularization. Surgery can significantly reduce the risk of future strokes. Surgical options include direct bypass procedures, such as superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis. Encephaloduroarteriosynangiosis (EDAS) is another option to improve collateral circulation, however the choice of procedure depends on patient age, cerebral perfusion status, and surgical expertise.
Prognosis
The prognosis of Moyamoya disease varies depending on the age at onset, severity, and treatment. Without medical or surgical intervention, progressive arterial stenosis leads to recurrent strokes, cognitive decline, and earlier mortality. Early surgical revascularization improves long-term outcomes and reduces the risk of infarction. Children generally show better recovery due to cerebral plasticity. Adults also benefit from prompt intervention. Lifelong monitoring is necessary because of the risk of disease progression or involvement of previously unaffected vessels.
