"Moyamoya" syndrome or disease is the term used to define the presence of an abnormal vascular network which develops because of gradual stenosis (narrowing) of the arteries at the base of the brain (upper end of the internal carotid artery or beginning of its branches anterior cerebral artery or middle cerebral artery).The abnormal vascular network appears gradually, to compensate for the reduction in blood flow downstream from the stenoses in the arteries at the base of the brain. It often has a "cloudy" or "hazy puff of smoke" appearance which in Japanese, is translated by "moyamoya".
The abnormal vascular network can develop when the arteries in the base of the skull narrow as a result of an already known general or localized disease.These patients are described as having the "Moyamoya syndrome". The term "Moyamoya disease" is usek when no disease is associated with the arterial abnormalities..
The frequency of the disease varies according to the population. In Japan, where the disease is most commonly found, the diagnosis of Moyamoya is suggested bya radiological examination of the brain without any symptoms in 1 in 2000 cases. The prevalence of Moyamoya is estimated at approximately 3 out of 100,000 cases and its incidence (number of new cases) is estimated at 0.35 cases in 100,000 people per year.
In Europe or the USA, Moyamoya disease is thought to be 10 times less frequent. The estimated frequency is approximately 0.3 cases per 100,000 people in France, a total of approximately 180 cases. The number of new cases in the USA is 0.086 cases/100,000 people per year but it varies between 0.03 among non-Asians and 0.3 cases/100,000 people per year among Asians.
In both Asia and Europe, the disease appears to be more frequent in women (1.3 to 2.4 women for one affected man).
The frequency of the familial forms varies between 2% and 20% in Japan depending on the series. Familial forms are rare in Europe.
The onset of clinical signs occurs before the age of 10 in one-half of all cases (Children form of Moyamoya disease). It then occurs most frequently between the ages of 25 and 50 (adult form of the disease).
In adults, Moyamoya disease can cause the following:
- transient ischemic attacks (TIA) or cerebral infarction in approximately one-half of cases (they may, for example, cause sudden hemiplegia, speech disorders, etc.). They often result from hyperventilation (blowing into a musical instrument or a balloon, high temperatures or hot drinks) and, in extreme cases, may worsen if there is any drop in blood pressure.
- cerebral haemorrhages in 2 out of 3 cases
- headache which can be sudden and may accompany a cerebral infarction or a cerebral haemorrhage. Headache is observed in 30% to 60% of cases when the disease is diagnosed
- epileptic seizures which are most frequent after a cerebral haemorrhage or infarction in approximately 1 in 5 cases
- cognitive disorders (loss of concentration, language, memory etc.) which may appear suddenly during an infarct or a cerebral haemorrhage or gradually as a result of cerebral atrophy
- movements discorders but this is rare.
Hereditary forms of Moyamoya disease have been observed mainly in Japan where familial cases represent 10% of cases. They are unusual in Europe.
Moyamoya syndrome in adults produces a combination of neurological disorders associated with the cerebral abnormal vascular network and signs of the associated general disease.
The commonest general pathology associated with Moyamoya syndrome is:
- Sickle-cell disease
- Down syndrome
- Intracranial arteriosclerosis
- post-radiation cerebral vasculitis in the arteries at the base of the skull (frequently observed in Type I neurofibromatosis because of the irradiation of this zone to treat optic nerve tumours)
- infectious or toxic vasculitis or observed in certain inflammatory diseases affecting the arteries at the base of the skull
- tumors at the base of the skull
Other associations have been reported but some of them may have occurred randomly: arterial trauma, cranial trauma, congenital or acquired heart defects, aortic coarctation, arterial aneurysm, polycystic kidneys, Fanconi's anemia, diabetes, abnormal thyroid function etc.
Moyamoya syndrome has been very seldom reported in association with a number of rare diseases e.g. homocysteinuria, Fabry's disease, NADHCoQ reductase deficiency, mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), retinitis pigmentosa, hyperthyroidism, Apert's Syndrome, Marfan's Syndrome, tuberous sclerosis (Bourneville-Pringle syndrome), Turner Syndrome,Hirschsprung disease, Noonan Syndrome, Alalagille Syndrome, and Type I Glycogenosis
Moyamoya disease begins with stenosis (or narrowing) of the large arteries at the base of the skull. The innermost layer of the artery wall (intima) thickens, where the muscle cells, which are usually located in the centre of the wall, have migrated and proliferated. This thickening is associated with changes in the fibrillary components of the vessel wall. Unlike the Moyamoya syndrome which can be associated with inflammation in the vessel wall, in Moyamoya disease there is no inflammatory damage to the wall. In Moyamoya disease, the exact mechanisms leading to the thickening of the vascular wall remain unknown. The very slow, gradual thickening of the arteries at the base of the skull are thought to cause: 1) dilation of the existing vessels downstream from the stenosis (the existing vessels dilate to the maximum to compensate for the drop in blood supply) and 2) development of new vessels through the production of angiogenic factors (factors stimulating the growth of new vessels e.g. bFGF or basic Fibroblast Growth Factor) in the poorly-supplied cerebral tissue.
It is the development of this new "abnormal" vascular network that produces the very specific appearance observed during arteriography which is typical of Moyamoya disease (development of numerous small vessels grouped together to form the"hazy puff of smoke" appreance.
Despite the development of this "neo-vascularisation", cerebral blood supply can remain inadequate, causing cerebral infarcts. "Neo-vascularisation", consisting mainly of small, very fragile vessels, can also lead to cerebral haemorrhage.
A diagnosis of Moyamoya disease or syndrome is always suggested by the results of a brain scan, an MRI of the brain or an examination of the vessels using an angioscanner or arteriography of the brain. The examination is most commonly carried out in patients with neurological deficiencies or headache.
According to the Japanese Ministry of Health, diagnosing Moyamoya disease with certainty is based on the presence of the following criteria on the arteriography, MRI (magnetic resonance imaging) with MRA (magnetic resonance angiography) or autopsy:
- stenosis or occlusion of the terminal section of the internal carotid artery, the first part (A1) of the anterior carotid artery or the first part (M1) of the middle cerebral artery
- presence of an abnormal arterial network
- bilateral nature of the first two criteria
- absence of any cause of the Moyamoya syndrome: arterioclerosis of the arteries at the base of the skull, autoimmune disease, meningitis, tumour (at the base of the skull). Down syndrome, Type 1 neurofibromatosis, cranial trauma, irradiation of the head, other disease
A "probable" diagnosis of Moyamoya disease is considered when the vascular abnormalities are not bilateral.
Unilateral forms of Moyamoya disease ("probable" disease) are more frequent in adults. In a Japanese study, 7% of forms that were unilateral at the time of diagnosis became bilateral during the 6-year monitoring period.
Treatment of Moyamoya disease is complex and must be discussed by multidisciplinary teams involving, in particular, neurologists, neurosurgeons and anesthesist.
Depending on the patient's age and general condition, the type of cerebral lesions (infarction or haemorrhage) and the stage reached by the disease, various therapeutic options are available:
- no medical or surgical treatment
- medical treatment: vasodilator medication to improve the blood supply to the brain, anti-epileptic drugs in patients suffering from epilepsy, and, in certain circumstances, platelet antagonist medication (although this increases the risk of haemorrhage)
- surgical treatment: it is proposed to improve the blood supply to the brain (when certain areas of the brain are being damaged or risk damage as a result of inadequate blood supply). A number of surgical techniques may be considered but they should be discussed by a multidisciplinary team in a specialist centre.
- multicraniostomy (term meaning the drilling of several holes in the skull): a large number of small holes are drilled in the skull to enable the vessels in the scalp to grow through the holes on the surface of the skull and down into the interior of the brain to supply those areas which have a poor blood supply)
- temporal artery-middle cerebral artery anatomosis (anastomosis = communication between 2 tubes) consists of joining the temporal artery outside the skull to the middle cerebral artery within the brain to provide blood from outside the skull into the brain to improve its supply
- other surgical techniques are sometimes used. They consist of placing tissue taken from elsewhere in the body and containing a large number of blood vessels in contact with the brain so that the vessels develop in the areas of the brain that lack a good blood supply.
These various treatments may be combined. They are discussed against the background of the stage of the illness, the patient's age, the technical possibilities and the progress of the disease.
Familial forms - Genetic counselling
In Japan, 10% of Moyamoya cases appear to be familial in origin (at least two relatives have been diagnosed in the same family). In a small number of families, transmission is autosomal dominant (the genetic abnormality responsible for the disease affects as many men as women and adults have a one in two chance of passing it on to their children) but penetrance is weak. The number of cases within a family is therefore low (often two or three cases). In most families, there is probably some polygenic susceptibility. In Japan, when a case of Moyamoya disease has been diagnosed, the likelihood of identifying another case within the patient's family is thought to be 34 times higher than the risk of the onset of the disease among the general population.
No gene responsible for Moyamoya disease has yet been identified. A number of chromosome locations have been reported, in chromosomes 3, 6, 8, 12 and 17 but none of these has been confirmed.
In Europe, familial forms seem to be extremely rare. A very small number of familial cases have been observed in Italy, Belgium and France (fewer than 5 families in all). The risk of finding another case within the same family remains unknown.
Development - Prognosis
In adults, after diagnosis, the disease develops very slowly in most cases, over several decades. The prognosis depends mainly on the severity of the sequelae from cerebral vascular accidents occurring as part of the illness. When Moyamoya disease is confirmed (bilateral damage) and has already caused a cerebral infarct, the risk of a further cerebral vascular accident is though to be approximately 10% per year in the absence of any surgical treatment. Certain studies suggest that the risk would be reduced two- or threefold, approximately, by surgical treatment aimed at improving the blood supply to the brain.