NORD gratefully acknowledges Edward R. Smith, MD, Department of Neurosurgery, Children's Hospital Boston/Harvard Medical School, and R. Michael Scott, MD, Neurosurgeon-in-Chief, The Children's Hospital, Boston, for assistance in the preparation of this report.
Moyamoya disease is a progressive disorder that affects the blood vessels in the brain (cerebrovascular). It is characterized by the narrowing (stenosis) and/or closing (occlusion) of the carotid artery inside the skull, a major artery that delivers blood to the brain. At the same time, tiny blood vessels at the base of the brain open up in an apparent attempt to supply blood to the brain distal to the blockage. These tiny vessels are the "moyamoya" vessels for which the disease was named. Inadequate blood supply then leads to reduced oxygen delivery to the brain, and it is this oxygen deprivation that causes the signs of moyamoya. One of the symptoms is typically stroke, which results in paralysis of the face, arms or legs, loss of speech, etc., or temporary loss of neurologic function of body parts or speech (transient ischemic attacks, or “TIA”). Other symptoms that may result include headaches, visual disturbances, developmental delay, and seizures. Approximately 10% of cases of moyamoya in Asian countries have a genetic cause. Patients with this arteriopathy that occurs either on a familial or idiopathic basis are said to have moyamoya disease. Patients in whom the artery changes occur in association with another process such as sickle cell disease or Down syndrome are said to have moyamoya disease. In this report, we use the term "moyamoya disease" as shorthand for both forms.
Although moyamoya disease may occur at any age, there are two peak incidence periods –between the ages of five and ten years in children, and between 30 to 50 years in adults. Children with moyamoya disease may present with a variety of symptoms, but most present with those related to reduced brain blood supply, including stroke, TIAs, headaches, seizures, involuntary movements, or occasionally progressive developmental delay.
Although adults with moyamoya also present with signs and symptoms of brain ischemia, they also have a greater tendency to suffer intracranial hemorrhage than children, presumably due to rupture of the tiny moyamoya blood vessels possibly in the setting of higher blood pressures seen in adulthood.
The causes of moyamoya disease are unknown. However, it is known that the disorder may appear as an isolated, primary disorder that may have genetic determinants or may occur in association with a number of different underlying disorders, as noted above. It is likely that the phenotypic arteriopathy of moyamoya actually represents a common end-pathway of a number of pathophysiologically distinct processes.
Primary moyamoya disease may be genetically transmitted as an autosomal recessive trait, and accounts for approximately 10% of all cases in Japan. Recently, two major mutations have been reported to be associated with specific subpopulations of moyamoya patients. The first, R179 mutations in the ACTA2 gene, correlate with a radiographically distinct subtype of moyamoya disease, identified in a very small cohort of patients related to a larger group of ACTA2 mutations that cause cardiac and aortic disorders. (Munot, 2012) More significantly, mutations in RNF213 are strongly associated with the classic East Asian, bilateral, idiopathic familial disease presenting in adulthood and may be present in up to 70% of all East Asian familial cases of moyamoya. (Kamada, 2011)
Secondary moyamoya disease 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 Down syndrome, although there is now a long list of conditions now published in the medical literature with which moyamoya disease is associated. In susceptible patients, the disease may occur following radiation therapy to the brain to treat certain brain tumors such as optic glioma or craniopharyngioma. Unlike primary moyamoya disease, the disease can occasionally present with angiographic changes involving only on one side. This process can remain unilateral, or – in about 30% of patients – progress to involve the other side. (For more information on these disorders, use “neurofibromatosis type I,” “sickle cell,”, etc., as your search terms in the Rare Disease Database.)
In Japan, moyamoya disease typically occurs in females under the age of 20. In Japan, the disease is estimated to occur in 1 per 300,000 people. Although moyamoya was originally reported in individuals of Japanese ancestry, cases have been reported from elsewhere in Asia as well as from Europe, North and South America, and most series reported in the western hemisphere have a minority of patients of Asian descent. Of note, most patients in North America are isolated cases, with recent literature suggesting that less than 4% of cases in this population are familial. (Gaillard 2017)
In most patients, the diagnosis of moyamoya can be made from a careful assessment of an MRI and MRA. Cerebral arteriography will confirm the diagnosis, establish the exact degree of blood vessel narrowing, demonstrate the existing blood flow patterns to various areas of the brain, and allow treatment decisions to be made; for these reasons, it is the standard diagnostic tool for this condition. In particular, catheter angiography can help with the identification of important blood vessels called “transdural collaterals,” which are present in some cases and can markedly influence surgical planning and prognosis. (Storey 2017)
Medical treatment of moyamoya disease has been utilized to treat many of the symptoms of moyamoya, and is often an important part of the patient’s management. Treatment measures include aspirin (to prevent or reduce the development of small blood clots developing within the narrowed vessels) and anti-seizure medications (when indicated because of a patient’s seizure disorder). In rare instances, anticoagulants such as lovenox or coumadin are administered in very unstable patients having frequent symptoms, but because of the obvious risk of cerebral bleeding in this condition, they are rarely indicated as long-term measures. Calcium channel blockers are sometimes used to help reduce headache and, in some patients, reduce symptoms related to transient ischemic attacks, However, calcium channel blockers need to be used carefully, as they can also lower blood pressure, which may increase stroke risk. There is no medication available which will stop the progression of the cerebral artery narrowing and the disease will continue to progress in the vast majority of patients regardless of treatment.
Surgical procedures are designed to reestablish blood supply to the brain by diverting scalp blood supply to the brain surface and thereby circumventing the progressive loss of brain hemisphere blood flow. There are many surgical procedures proposed to treat moyamoya, and they have been divided into so-called “indirect” and “direct” operations. Indirect procedures, usually carried out in children and younger patients, include pial synangiosis, encephalomyosynangiosis (EMS), encephaloduroarteriosynangiosis (EDAS), dural inversion, and other similar variants. These operations involve the placement of vascularized structures from the scalp and/or the membranes that surround the brain onto the brain surface, which in most moyamoya patients will induce the growth of new blood vessels into the brain. The most common direct procedure involves the direct suturing of a scalp blood vessel, the superficial temporal artery, to a middle cerebral artery branch on the brain surface. Long-term results following surgery of either type have been quite good, with long-term prevention of strokes seen in published series of both pediatric and adult patients.
Importantly, recent data demonstrates that the most important factor predicting a successful surgical outcome is to receive treatment at a center that performs a high volume of moyamoya cases every year. (Titsworth 2016)
Genetic counseling may be of benefit for patients and their families if they have a hereditary form of moyamoya disease.
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