Moyamoya Disease

Recognised in Japan in the 1960s, this is a progressive occlusive cerebral arteritis affecting the distal internal carotid arteries near the Circle of Willis. Moyamoya is Japanese for "puff of smoke" and describes the appearance of the resultant network of abnormal small collateral vessels seen on angiography.¹ There is a familial form (about 15% of patients²) which links to a gene on chromosome 17q25 - though the exact underlying cause remains unknown.

Recent research has identified the presence of increased numbers of endothelial progenitor cells (specifically outgrowth cells) compared to controls. This could be developed as a diagnostic test in the future.³

Moyamoya Disease (MMD) is a rare condition, although asymptomatic patients may remain undetected. A four year study in Japan from 2002-2006 found that the detection rate per year was 0.94 patients per 100,000 people. The prevalence was 10.5 patients per 100,000. There was a female to male ratio of 2.18:1. The incidence of asymptomatic patients was 17.8%. There were two peaks of onset between 45 and 49 years and between 5 and 9 years.

Initially thought to be a disease occurring primarily in Asian countries, the number of patients diagnosed in Europe is increasing due to increased awareness of the condition.⁵

Generally the clinical features are those associated with transient ischaemic attacks (more common with children) and stroke (haemorrhagic more typical in adults). They include headache, hemiparesis, seizures, disturbed consciousness, speech deficits (aphasia), sensory and cognitive impairments, involuntary movements and vision problems.

• Anterior circulation stroke
• Basilar artery thrombosis
• Posterior cerebral artery stroke
• Subarachnoid haemorrhage
• Blood dyscrasias
• Cavernous sinus syndromes
• Cerebral aneurysms
• Craniopharyngioma
• Dissection syndromes
• Fibromuscular dysplasia
• Intracranial haemorrhage
• Fabry Disease
• Homocystinuria/homocysteinaemia
• Hyperglycaemia/hypoglycaemia
• MELAS (mitochondrial myopathy, encephalopathy, lactacidosis, stroke)
• Methylmalonic acidaemia
• Propionic acidaemia
• Neurofibromatosis types 1 & 2
• Pituitary tumours
• Polyarteritis nodosa
• Temporal/giant cell arteritis
• Tolosa-Hunt Syndrome (painful ophthalmoplegia caused by nonspecific inflammation of the cavernous sinus or superior orbital fissure)

Associations have been made with leptospirosis, TB, certain anaemias and vascular disorders causing intimal thickening including hypertension and atherosclerosis.

MMD also commoner in association with a mixed bag of congenital syndromes (Down's, Turner's, Marfan's, Apert's) and diseases (neurofibromatosis type I, tuberous sclerosis, Hirschsprung).

• If a patient has had a stroke and the aetiology is unclear, a hypercoagulability profile should be arranged including Protein C, Protein S, Antithrombin III, homocysteine and Factor V Leiden levels.
• A raised erythrocyte sedimentation rate (ESR) may rule out vasculitis, but a normal ESR does not exclude this diagnosis.
• The gold standard test is radio-imaging.
• Findings suggestive of the diagnosis of MMD on CT scanning or magnetic resonance angiography (MRA) include:
  • Stenosis or occlusion at the terminal portion of the internal carotid artery or the proximal portion of the anterior or middle cerebral arteries
  • Abnormal vascular networks in the vicinity of the occluded or stenosed areas
  • The presence of these findings bilaterally
• An enhancement of MRI, which produces a whole-brain histogram of diffusion tensor imaging (WBH-DTI), may be helpful in identifying Moyamoya patients who have had a cerebral infarction from those who have not.⁷

Medical

There is little evidence that the disease process per se can be modified by drug therapy. If cerebral haemorrhage has occurred, strict control of blood pressure should be instituted. Patients who have sustained an ischaemic stroke or TIA should have the appropriate antiplatelet or anticoagulant therapy.⁶

Surgical

Procedures to enhance cerebral flow produce variable results.⁸ One study suggested that the surgical technique needs to be tailored to the needs of the individual patient.⁹ Indirect revascularisation techniques, which rely on the development of collateral vessels to circumvent the block, seem to produce the best results in paediatric patients. The commonest technique, known as encephalomyoduroarteriosynangiosis (EMDAS) involves repositioning the richly vascularised temporalis muscle and the temporal artery along the lateral brain surface and suturing them to the dura. For adult patients, the best technique seems to be direct shunting between the superficial temporal artery and the middle cerebral artery.¹⁰

Surgery improves the prognosis for patients presenting with cerebral ischaemia. However, for patients presenting with haemorrhage, the prognosis is poor. Progressive neurological deterioration and disability occur.

One study found that 30% of patients with unilateral disease developed arteriopathy on the other side within an average period of 2.2 years. Risk factors included contralateral abnormalities on initial imaging, congenital cardiac anomaly, previous cranial irradiation, Asian ancestry, and familial disease. The study recommended monitoring by using MR imaging and MR angiography at regular intervals for such patients.¹¹

Death is generally from haemorrhage in approximately 5% of children and 10% of adults.⁶