Moyamoya Disease

Moyamoya disease is a chronic cerebrovascular disorder with progressive bilateral stenosis or occlusion of the terminal internal carotid arteries and proximal anterior and middle cerebral arteries, with a network of fragile basal collateral vessels. Moyamoya syndrome describes the same pattern when another disease is present.

Highest incidence is in East Asia (about 1 to 3 cases in every 100,000 people each year in Japan and Korea), with lower rates in Europe and North America. There are two age peaks, one at about 5 years and one at 30 to 45 years, with a female predominance.

Genetics. The RNF213 p.Arg4810Lys variant is a strong risk allele in East Asian populations. About 10% of cases are familial.

Associated conditions. Sickle cell disease, neurofibromatosis type 1, Down syndrome, thyroid disease, cranial irradiation and autoimmune disease.

Staging. Suzuki stages I to VI describe progression from carotid fork narrowing to loss of moyamoya vessels and dominance of external carotid collaterals.

Pathophysiology.

Intimal hyperplasia and smooth muscle proliferation narrow the terminal internal carotid arteries, reducing flow. Collateral vessels dilate but are thin walled, which predisposes to haemorrhage and aneurysm formation.

Hypocapnia from hyperventilation (crying, blowing, exertion) causes vasoconstriction and triggers ischaemia in children.

• Children: recurrent TIAs or strokes, often provoked by crying, coughing, hyperventilation or blowing; headache, seizures and cognitive decline.
• Adults: intracerebral, intraventricular or subarachnoid haemorrhage in about half; also ischaemic events and cognitive impairment.
• Involuntary movements and migraine like headache in a minority.

Red flags.

• Sudden severe headache with deficit (haemorrhage).
• Recurrent TIAs with hypotension or dehydration.
• Fever, vomiting or dehydration in a child with known disease.

• MRI and MR angiography show bilateral stenosis, flow voids at the basal ganglia and decreased flow; ivy sign on FLAIR.
• Digital subtraction angiography is the reference for staging, showing the puff of smoke collateral pattern.
• Perfusion studies (SPECT, PET, CT perfusion or MR perfusion with acetazolamide challenge) assess haemodynamic reserve.
• Exclude secondary causes: sickle cell test, thyroid function, autoimmune screen, neurofibromatosis features.
• Genetic testing for RNF213 in familial disease is optional.

Differential diagnosis. Intracranial atherosclerosis, vasculitis, fibromuscular dysplasia, radiation vasculopathy, sickle cell vasculopathy, reversible cerebral vasoconstriction syndrome and neurofibromatosis arteriopathy.

• Medical measures: avoid hypotension, dehydration, hyperventilation and prolonged fasting; maintain hydration and normocapnia during anaesthesia.
• Aspirin 75 to 100 mg orally once daily, long term, for ischaemic disease. Maximum 100 mg daily in this indication. Monitor for bleeding and dyspepsia and check full blood count. Avoid in children under 16 years unless specialist advice is given (Reye syndrome risk), and in active peptic ulcer or bleeding disorders; avoid in haemorrhagic disease; use caution when eGFR is under 10.
• Surgical revascularisation is the main treatment for symptomatic disease: direct superficial temporal to middle cerebral artery bypass in adults and combined or indirect synangiosis in children. It reduces ischaemic events and, in haemorrhagic disease, reduces rebleeding.
• Seizures: levetiracetam 500 mg orally twice daily, increased as needed to a maximum of 1500 mg twice daily. Monitor mood and renal function. Reduce dose when creatinine clearance is 50 to 80 mL/min (500 to 1000 mg twice daily), 30 to 50 mL/min (250 to 750 mg twice daily) and under 30 mL/min (250 to 500 mg twice daily).
• Haemorrhage: usual acute intracerebral haemorrhage care and neurosurgical review.
• Avoid vasoconstrictors and, where possible, anticoagulants; treat the underlying disease in moyamoya syndrome.

Monitoring. Clinical review and MRI or MR angiography at 6 to 12 months, then every 1 to 2 years; imaging after surgery to confirm graft patency.

Referral and escalation. Specialist cerebrovascular or paediatric neurosurgical centre at diagnosis; emergency review for new deficit.

Special groups. Children: parental advice on avoiding hyperventilation triggers. Pregnancy: plan with obstetric and neurology teams; maintain normocapnia in labour and avoid hypotension.