Information on the following diseases can be found in the Related Disorders section of this report:

• Cerebrovascular Accident (CVA) or (Stroke)
• Cerebral Vascular Malformations

Although Moyamoya syndrome may occur at any age, it most often occurs between the ages of five and ten years and during the third and fourth decades of life. Symptoms vary with age of onset.

Children with Moyamoya syndrome may have convulsions, headaches, involuntary muscle movements, paralysis of one side of the body (hemiplegia), or paralysis of one limb. Some children may show signs of mental retardation. Affected children tend to develop one or more of the following visual disturbances: blindness in one half of the visual field of one or both eyes (hemianopia), double vision (diplopia), bilaterally (right and left) decreased visual clearness (acuity), and the inability to recognize objects. Affected children may develop mini-strokes (transient ischemic attacks) or complete strokes.

Later onset is characterized by bleeding (hemorrhaging) or stroke. Adults are more prone to intracranial bleeding below the middle covering of the brain (subarachnoid). This may be followed by accumulation of excessive amounts of watery fluid in the optic disks (papilledema) and fainting. Neurosis (mainly anxiety) usually occurs in adults with Moyamoya syndrome. Affected individuals usually have sudden interruptions of the blood supply to the brain (cerebral infarctions), which can lead to brain tissue death.
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The causes of Moyamoya syndrome are unknown. However, it is known that the disorder may appear as an isolated, primary disorder that is genetically determined or it may occur due to, or in association with, one of a number of different underlying disorders (secondary).

Primary Moyamoya syndrome is genetically transmitted as an autosomal recessive trait. It accounts for approximately 10% of all cases. Two genetic locations have been identified as significant in primary Moyamoya syndrome: 3p26-p24.2 and 17q25. The interaction of the two has not as yet been determined.

Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 17q25” refers to band 25 on the long arm of chromosome 17. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Genetic diseases are determined by the combination of genes for a particular trait which are on the chromosomes received from the father and the mother.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

Secondary Moyamoya syndrome occurs in association with a number of different underlying disorders or conditions, including certain infections involving the central nervous system, neurofibromatosis type I, sickle cell disease, and tuberous sclerosis. (For more information on these disorders, use "Neurofibromatosis Type I," "Sickle Cell," and "Tuberous Sclerosis" as your search terms in the Rare Disease Database.). In addition, secondary Moyamoya syndrome has been associated with meningitis, retinitis pigmentosa, fibromuscular dysplasia, atherosclerosis, Down syndrome, Fanconi’s anemia, and following radiation therapy to the skull base of children.
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Moyamoya syndrome typically occurs in females of Japanese origin under the age of 20. It occurs in females almost twice as often as in males. In Japan, the syndrome is estimated to occur in 1 individual per 1 million people. Although most cases occur in individuals of Japanese ancestry, cases have been reported from elsewhere in Asia as well as from Europe, North and South America.

Although it typically occurs among Asian women, cases have been reported involving Afro-Americans, Haitians, Hispanics, and Caucasians.
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Symptoms of the following disorders can be similar to those of Moyamoya Disease. Comparisons may be useful for a differential diagnosis:

A cerebrovascular accident (stroke) occurs because the blood supply to the brain has been cut off or decreased. Thrombotic strokes occur when a clot has narrowed or completely closed an artery in the neck or head. This is the result of the buildup of fat-containing materials and calcium (plaque) on the inner linings of the blood vessels. Embolic strokes occur when a clot breaks away from the diseased artery in another part of the body and clogs a smaller artery in the brain. Hemorrhagic strokes occur when a blood vessel ruptures in or around the brain, depriving that area of blood. Each type of stroke has its own symptoms, progression, and prognosis. Clumsiness, headaches, speech difficulties, weakness or complete paralysis of one or both sides of the body may occur. Stiff neck, nausea, vomiting, and unconsciousness are also common symptoms.

Vascular malformations (abnormal blood vessels) of the brain are classified into arteriovenous malformations (abnormal arteries and veins), cavernous malformations (enlarged channels of blood vessels), venous malformations (abnormal veins), and the telangiectasias (enlarged capillary- sized vessels). Malformations in the brain may cause recurrent headaches, seizures, and hemorrhaging. Hemorrhaging in the brain may cause cerebrovascular accidents (strokes).

Diagnosis
Cerebral angiography supplemented by magnetic resonance imaging (MRI) are diagnostic tests used to determine the condition of the brain's blood vessels and, hence, to see if Moyamoya syndrome is present.

Treatment
Medical treatment of Moyamoya syndrome has been unsuccessful in the past. However, surgical treatment has been reasonably successful, especially among children, and various surgical approaches have been developed.

Five surgical treatments are currently in use. Each of these is designed to reestablish blood supply to the brain. They are: Encephalomyosynangiosis (EMS), Encephaloduroarteriosynangiosis (EDAS), Encephalomyoarteriosynangiosis (EMAS), Superficial Temporal-to-Middle Cerebral Artery (STA-MA) Bypass, and Indirect Non-Bypass Revascularization. Response of patients to these complex and very complicated surgeries varies.

For patients experiencing mini-strokes, aspirin, vasodilators (calcium- channel blockers) and/or anticoagulants may be prescribed.

The disease may also stabilize after a progressive course.

Genetic counseling may be of benefit for patients and their families if they have the hereditary form of Moyamoya syndrome. Other treatment is symptomatic and supportive.
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An adult Moyamoya disease research study is being conducted at Columbia University Medical Center. The study is called "Outcomes of Revascularization in Moyamoya." The purpose of this study is to examine the effects of neurosurgery on mental, psychological, neurological, and daily functions among persons with Moyamoya disease. People with Moyamoya disease who undergo EDAS neurosurgery and those who do not undergo neurosurgery can participate in this study. For more information, contact the investigator, Joanne Festa, PhD, at (212) 305-5860. Dr. Festa is Assistant Professor of Clinical Neuropsychology at Columbia University College of Physicians & Surgeons.

McKusick VA, Ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Moyamoya Disease. Entry Number; 252350: Last Edit Date; 12/10/2002.

McKusick VA, Ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Moyamoya Disease 2. Entry Number; 607151: Last Edit Date; 8/15/2002.

TEXTBOOKS
Scott RM. Moyamoya Syndrome. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:559.

Fauci AS, et al., eds. Harrison's Principles of Internal Medicine, 14th Ed. New York, NY: McGraw-Hill, Inc; 1998:2342.

Bennett JC, Plum F. Eds. Cecil Textbook of Medicine. 20th ed. W.B. Saunders Co., Philadelphia, PA; 1996:888.

Behrman RE, Kliegman RM, Arvin AM. Eds. Nelson Textbook of Pediatrics. 15th ed. W.B. Saunder Company. Philadelphia, PA; 1996:1729.

REVIEW ARTICLES
Seol HJ, Kim DG, Oh CW, et al. Radiosurgical treatment of cerebral arteriovenous malformation in a patient with moyamoya disease: case report. Neurosurgery.2002;51:478-81; discussion 481-2.

De Borchgrave V, Saussu F, Depre A, et al. Moyamoya disease and Down syndrome: case report and review of the literature. Acta Neurol Belg. 2002;102:63-66.

Smith ER, Butler WE, Ogilvy CS. Surgical approaches to vascular anomalies of the child’s brain. Curr Opin Neurol. 2002;15:165-71.

Losken A, Carlson GW, Culbertson JH, et al. Omental free flap reconstruction in complex head and neck deformities. Head Neck. 2002;24:326-31.

JOURNAL ARTICLES
Morioka M, Hamada J, Todaka T, et al. High-risk age for rebleeding in patients with hemorrhagic Moyamoya disease: long-term follow-up study. Neurosurgery. 2003;52:1049-55.

Oya S, Tsutsumi K, Ueki K. Adult-onset moyamoya disease with repetitive ischemic attacks successfully treated by superficial temporal-middle cerebral artery by-pass—case report. Neurol Med Chir (Tokyo). 2003;43:138-41.

Marioka M, Hamada J, KawanoT, et al. Angiographic dilatation and branch extension of the anterior choroidal and posterior communicating arteries are predictive of hemorrhage in adult moyamoya patients. Stroke. 2003;34:90-95.

Zafeiriou DI, et al. Familial moyamoya disease in a Greek family. Brain Dev. 2003;25:288-90.

Asumal KB, et al. Moyamoya disease: an elusive diagnosis. J Pak Med Assoc. 2003;53:160-2.

Dobson SR, Holden KR, Nietert PJ, et al. Moyamoya syndrome in childhood sickle cell disease: a predictive factor for recurrent cerebrovascular events. Blood. 2002;99:3144-50.

Soriano SG, Cowan DB, Proctor MR, et al. Levels of soluble adhesion molecules are elevated in the cerebrospinal fluid of children with moyamoya syndrome. Neurosurgery. 2002;50:54-49.

Isono M, Ishii K, Kamida T, et al. Long-term outcomes of pediatric moyamoya disease treated by encephalo-duro-arterio-synangiosis. Pediatr Neurosurg. 2002;36:14-21.

FROM THE INTERNET
NINDS Moyamoya Disease Information Page. Reviewed 12-14-2001.
www.ninds.nih.gov/health_and_medical/disorders/moyamoya.htm?format=printable

Sucholeiki R, Chawla J. Moyamoya Disease. eMedicine. Last Updated: January 18, 2002. 11pp.
www.emedicine.com/neuro/topic616.htm

Children’s Hemiplegia and Stroke Association. Moyamoya Disease. nd. 2pp.
www.chasa.or/moyamoya.htm

Scott RM. FAQs About Moyamoya Syndrome. Boston Neurological Foundation. nd. 6pp.
www.boston-neurosurg.org/amphitheater/online/html

UCLA Neurosurgery. Cerebrovascular & Stroke Diseases & Disorders. Moya-moya Disease. nd. 2pp.
www.neurosurgery.medsch.ucla.edu/Diagnoses/Cerebrovascular/CetrebroDis_7.html

Columbia Pediatric Neurosurgery. Moya-moya. nd. 2pp.
www.cpmcnet.columbia.edu/dept/nsg/PNS/moyamoya.html

Moyamoya Disease. Varius subjects. Nd.
http://www003.upp.so-net.ne.jp/moya-moya/world_map.htm
http://www003.upp.so-net.ne.jp/moya-moya/age_distribution.htm
http://www003.upp.so-net.ne.jp/moya-moya/cure.htm
http://www003.upp.so-net.ne.jp/moya-moya/JAM_trial.htm
http://www003.upp.so-net.ne.jp/moya-moya/prognosis.htm
http://www003.upp.so-net.ne.jp/moya-moya/asymptomatic.htm

Laurent JP. Moyamoya Disease: Moyamoya Syndrome/Stroke in Children. nd. 2pp.
www.bcm.tmc.edu/pednsurg/disorder/moyamoya.htm