Moyamoya disease is a noninflammatory, non-vasculitic and nonatherosclerotic condition characterized by progressive stenosis of intracranial arteries. The intracranial arteries usually involved are the terminal internal carotid artery and the proximal portions of the anterior cerebral and middle cerebral arteries. There is a slowly progressive occlusion which permits the development of the unique small anastomotic collateral pathways causing the "puff of smoke" appearance on the angiogram or "cerebral basal rete mirabile". Moyamoya disease is the term used when the internal carotid artery stenosis and associated collaterals are observed bilaterally and when no associated diseases are identified (i.e., idiopathic). Moyamoya phenomenon is the term used to describe extensive collateralization of the circle of Willis arteries associated with severe unilateral or bilateral internal carotid artery stenosis or occlusion in the presence of certain conditions [1
The list of conditions and causes associated with moyamoya phenomenon is long an includes neurofibromatosis, craniopharyngioma, optic glioma, distal internal carotid artery compression by tumor, chronic meningitis, leptospiral infections, atherosclerosis, sickle cell disease, antiphospholipid syndrome or lupus anticoagulant, Alagille syndrome (an autosomal dominant disorder associated with abnormalities of the liver, heart, skeleton, eye, and kidneys and characteristic facial morphology, osteogenesis imperfecta, Costello syndrome (a rare genetic disorder that affects multiple organs), and cocaine use. Moyamoya phenomenon has also been associated with extracranial and peripheral arterial disease, essential thrombocythemia, and birth control pills (possibly in combination with cigarettes). Cases of moyamoya vessels developing around the stenosis of a vessel supplying an arteriovenous malformation have been reported. Recent case reports suggest an association between thyrotoxicosis (Grave disease) and severe moyamoya disease [Please see reference 1 for an excellent review].
Moyamoya was first described in the late 1950's with most cases being reported from Japan. Clinical presentation is variable and age dependent. In childhood strokes tend to be ischemic, whereas in adults they are more often hemorrhagic. It occurs with a bimodal onset, peaking in the first and fourth decades of life. Children are more likely to present with acute transitory hemiplegia secondary to recurrent cerebrovascular episodes [2
]. Down syndrome in association with moyamoya has been reported since the 1980's and ischemic vascular pathologies in general are common. Infact, new-onset focal weakness is not uncommon in Down syndrome and moyamoya syndrome is one of the more common causes [3
The exact etiology of moyamoya is unknown. It has been speculated that there is a genetic mode of inheritance based on a higher incidence of the disease in Asian populations and on familial occurrence in both Asians and whites and this has been supported by genetic linkage analysis. Various connective tissue, angiogenesis, and inflammatory mediators have been implicated including fibroblast growth factor, transforming growth factor β1
, elastin, and prostaglandin E2
The association of moyamoya with Down syndrome is also not fully understood. The incidence of moyamoya syndrome in patients with trisomy 21 is approximately three times the general population [5
]. Moyamoya is characterized by elastopathic vascular damage, and patients with Down syndrome are in general predisposed to vascular diseases, including abnormal nail bed capillary morphology, high pulmonary vascular resistance, retinal vessel abnormalities, renovascular hypertension, and primary intimal fibroplasias [5
]. There has also been a reported association of elastosis perforans serpiginosa (a dermatologic disease characterized by transepithelial elimination of abnormal elastic fibers, and focal dermal elastosis) with both Down syndrome and moyamoya [7
]. Chromosome 21 encodes proteins that affect arterial physiology and elasticity, including superoxide dismutase 1, interferon γ receptor, cystathionine β-synthetase, and collagen type IV (found in the intima of large arteries). It has been postulated that these proteins may be abnormally expressed when three copies of chromosome 21 are present [2
]. Pathologic studies are limited but support this notion [8
Various treatments have been explored, although none are ideal. Medical therapy in ischemic moyamoya conditions include aspirin and hydration [2
]. Surgical treatment includes both direct and indirect revascularization procedures, and one review concludes no difference between the two techniques [9
]. The largest and most recent study to date of long-term outcome of surgical revascularization in Downs syndrome patients with moyamoya (ages ranging from 1 to 29 years old) suggests that clinical, radiologic, and angiographic features of moyamoya phenomenon associated with Down syndrome are comparable to those of idiopathic moyamoya disease. Cerebral revascularization surgery with the pial synangiosis technique seems to confer long-lasting protection against additional strokes in this patient population [10
In summary, the presence of moyamoya syndrome should be considered in the evaluation of patients with Down syndrome who present with transient ischemic attack-like symptoms of fluctuating hemiparesis even in the very young. Surgical revascularization with encephalomyosynangiosis apparently confers long-term benefits.