Background
Moyamoya disease is a progressive, occlusive disease of the cerebral vasculature with particular involvement of the circle of Willis and the arteries that feed it.[1] The image below is a schematic representation of the circle of Willis, the arteries of the brain, and the brainstem. (See Etiology.)
Schematic representation of the circle of Willis, arteries of the brain, and brain stem. The term moyamoya (Japanese for "puff of smoke") refers to the appearance on angiography of abnormal vascular collateral networks that develop adjacent to the stenotic vessels. The steno-occlusive areas are usually bilateral, but unilateral involvement does not exclude the diagnosis. (See Workup.)
Pathologically, moyamoya disease is characterized by intimal thickening in the walls of the terminal portions of the internal carotid vessels bilaterally. The proliferating intima may contain lipid deposits. The anterior, middle, and posterior cerebral arteries that emanate from the circle of Willis may show varying degrees of stenosis or occlusion. This is associated with fibrocellular thickening of the intima, waving of the internal elastic lamina, and thinning of the media. (See Etiology, Workup, Treatment, and Medication.)
Numerous small vascular channels can be seen around the circle of Willis. These are perforators and anastomotic branches. The pia mater may also have reticular conglomerates of small vessels.
Etiology
The cause of moyamoya disease is not known. The disease is believed to be hereditary. Fukui reported a family history in 10% of patients with the disorder. Moreover, Mineharu suggested that familial moyamoya disease is autosomal dominant with incomplete penetrance that depends on age and genomic imprinting factors.[2] Genetically, susceptibility loci have been found on 3p, 6p, 17q, and band 8q23. Mineharu et al have found a specific gene locus, q25.3, on chromosome 17.[3]
People with moyamoya disease have been found to have a higher incidence of elevated thyroid antibodies.[4] While this is an association in some individuals, the significance is not clear. However, it suggests that immune abnormalities may play some role in moyamoya disease.
Associated diseases
Although moyamoya disease may occur by itself in a previously healthy individual, many disease states have been reported in association with moyamoya disease, including the following:
- Immunologic -Graves disease/thyrotoxicosis[5]
- Infections - Leptospirosis and tuberculosis
- Hematologic disorders - Aplastic anemia, Fanconi anemia, sickle cell anemia, and lupus anticoagulant
- Congenital syndromes - Apert syndrome, Down syndrome, Marfan syndrome, tuberous sclerosis, Turner syndrome, von Recklinghausen disease, and Hirschsprung disease
- Vascular diseases - Atherosclerotic disease, coarctation of the aorta and fibromuscular dysplasia, cranial trauma, radiation injury, parasellar tumors, and hypertension
These associated conditions may not be causative, but they do warrant consideration due to their impact on treatment.
Epidemiology
A study indicated that the prevalence of moyamoya disease in California and Washington was 0.086 case per 100,000 population.[6] In this study, the breakdown based on ethnicity as ratio to whites was 4.6 for Asian Americans, 2.2 for African Americans, and 0.5 for Hispanics.
The incidence of moyamoya disease is highest in Japan. The prevalence and incidence of the disorder there has been reported to be 3.16 cases and 0.35 case per 100,000 people, respectively.
Race-, sex-, and age-related demographics
Moyamoya disease occurs primarily in Asians but can also occur (with varying degrees of severity) in whites, blacks, Haitians, and Hispanics.
The female-to-male ratio of moyamoya disease is 1.8:1. Ages for patients with moyamoya disease range from 6 months to 67 years, with the highest peak in the first decade and smaller peaks in the third and fourth decades.
Prognosis
Death from with moyamoya disease is usually from hemorrhage. The outcome of the disease depends on the severity and nature of the hemorrhage; the prognosis depends on recurrent attacks.
Mortality rates from moyamoya disease are approximately 10% in adults and 4.3% in children. About 50-60% of affected individuals experience a gradual deterioration of cognitive function, presumably from recurrent strokes.
Patients with moyamoya disease who present for treatment while symptoms are evolving have a better prognosis than do those who present with static symptoms (which probably indicate a completed stroke).
Janda PH, Bellew JG, Veerappan V. Moyamoya disease: case report and literature review. J Am Osteopath Assoc. Oct 2009;109(10):547-53. [Medline].
Mineharu Y, Takenaka K, Yamakawa H, et al. Inheritance pattern of familial moyamoya disease: autosomal dominant mode and genomic imprinting. J Neurol Neurosurg Psychiatry. Sep 2006;77(9):1025-9. [Medline].
Mineharu Y, Liu W, Inoue K, Matsuura N, Inoue S, Takenaka K. Autosomal dominant moyamoya disease maps to chromosome 17q25.3. Neurology. Jun 10 2008;70(24 Pt 2):2357-63. [Medline].
Kim SJ, Heo KG, Shin HY, Bang OY, Kim GM, Chung CS. Association of thyroid autoantibodies with moyamoya-type cerebrovascular disease: a prospective study. Stroke. Jan 2010;41(1):173-6. [Medline].
Im SH, Oh CW, Kwon OK, et al. Moyamoya disease associated with Graves disease: special considerations regarding clinical significance and management. J Neurosurg. Jun 2005;102(6):1013-7. [Medline].
Uchino K, Johnson A, Claiborne S, Tirschwell DL. Moyamoya disease in Washington State and California. Neurology. 2005;65:956-958. [Medline].
Li H, Zhang ZS, Dong ZN, et al. Increased Thyroid Function and Elevated Thyroid Autoantibodies in Pediatric Patients With Moyamoya Disease: A Case-Control Study. Stroke. Feb 24 2011;[Medline].
Starke RM, Komotar RJ, Hickman ZL, et al. Clinical features, surgical treatment, and long-term outcome in adult patients with moyamoya disease. Clinical article. J Neurosurg. Nov 2009;111(5):936-42. [Medline].
Fung LW, Thompson D, Ganesan V. Revascularisation surgery for paediatric moyamoya: a review of the literature. Childs Nerv Syst. May 2005;21(5):358-64. [Medline].
Scott RM, Smith JL, Robertson RL, et al. Long-term outcome in children with moyamoya syndrome after cranial revascularization by pial synangiosis. J Neurosurg. Feb 2004;100(2 Suppl Pediatrics):142-9. [Medline].
Hoffman HJ. Moyamoya disease and syndrome. Clin Neurol Neurosurg. Oct 1997;99 Suppl 2:S39-44. [Medline].
Cohen N, Berant M, Simon J. Moyamoya and Fanconi's anemia. Pediatrics. Apr 1980;65(4):804-5. [Medline].
Gosalakkal JA. Moyamoya disease: a review. Neurol India. Mar 2002;50(1):6-10. [Medline].

