Moyamoya disease

Did You Know?

• Patients usually present with TIA, ischemic/hemorrhagic stroke, seizure, or idiopathic stroke-like symptoms, with a bimodal age distribution in young adolescence or mid-forties.
• The natural history of the disorder is not well known, but long-term outlook seems good when direct bypass is used.
• A case report established that both moyamoya disease and dural arteriovenous fistulas are associated with dural angiogenesis.

Cause

About 10-15% of moyamoya disease cases are familial, and some arise from specific genetic mutations. Susceptibility to moyamoya disease-2 is caused by variation in the RNF213 gene on chromosome 17q25, though mutation alone may not be sufficient. Moyamoya disease-5 results from mutation in the ACTA2 gene on 10q23.3, and moyamoya disease-6 with achalasia from mutation in the GUCY1A3 gene on 4q32. Loci have been mapped to chromosome 3p (MYMY1) and 8q23 (MYMY3). An X-linked recessive syndromic form (MYMY4) involves moyamoya, short stature, hypergonadotropic hypogonadism, and facial dysmorphism. The molecular causes of both familial and sporadic cases remain unclear. Inflammatory cytokines and matrix metalloproteinases have been proposed as contributors, but their significance is unknown. Hemoglobinopathies like sickle cell disease can cause a clinically similar syndrome through arterial occlusion rather than constriction. Rarely, atherosclerotic changes in distal intracranial carotid arteries produce a vasoocclusive form.

Pathophysiology

The disease derives its name from the smoke-like appearance on angiographs caused by a tangle of tiny vessels that form in response to stenosis. Blood leaking from these arteries can press on the brain and cause headaches. The pathogenesis has remained elusive, though the RNF213 gene has been implicated. A proposed mechano-biological theory suggests multifactorial pathogenesis involving factors such as vascular anatomy differences that lead to broad cerebral vessel occlusion and shifts in vessel connections. Once vascular occlusion begins, it tends to continue despite medical management, potentially causing transient ischemic attacks, repeated strokes, or death, though some people remain asymptomatic. The internal carotid artery is primarily constricted, often extending to the middle and anterior cerebral arteries. When the internal carotid becomes completely blocked, the fine collateral circulation it supplies is obliterated, and patients may survive on posterior circulation from the basilar artery. Unlike atherosclerosis, where arterial walls are damaged by fat and immune cell deposits, moyamoya involves proliferation of the inner layer of the carotid artery within the lumen, along with blood clots that can cause strokes.

Treatment

Antiplatelet drugs such as aspirin are typically given to prevent clots, but surgery is usually recommended. Because moyamoya primarily affects the internal carotid artery and adjacent sections of the anterior and middle cerebral arteries, surgeons can redirect other arteries like the external carotid or superficial temporal artery to replace circulation. The most favored indirect procedures are EDAS, EMS, and multiple burr holes; the direct procedure is STA-MCA. Combined revascularization, including direct superficial temporal artery to middle cerebral artery bypass with indirect procedures, is considered the treatment of choice, though its efficacy for hemorrhagic disease remains uncertain. The EDAS procedure involves dissecting a scalp artery, opening the skull beneath it, and suturing the artery to a branch of the middle cerebral artery. The EMS procedure places the temporalis muscle onto the brain surface through a skull opening. Multiple burr holes allow new vessel growth from the scalp. The STA-MCA procedure directly sutures the superficial temporal artery to the middle cerebral artery.