Moyamoya angiopathy

« Moyamoya » angiopathy 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 stenosis 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 at 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 used when no specific disorder is associated with the arterial abnormalities.

This document was created by ORPHANET in collaboration with the Tanguy Moya-Moya association and CERVCO (D. Hervé, H. Chabriat).
Source: CADASIL, Orphanet Public Encyclopedia, April 2008
http://www.orpha.net/data/patho/Pub/fr/MoyaMoya-FRfrPub2373.pdf

The Disease

What is Moyamoya disease?
Moyamoya disease is a rare condition affecting the blood vessels that supply the brain. It is characterized by the gradual narrowing, or even blockage, of the arteries located at the base of the skull, leading to an insufficient supply of blood, and therefore oxygen, to the brain. The resulting symptoms are usually paralysis of an arm or leg, headaches, vision and speech disturbances, or epileptic seizures. These symptoms may be permanent or temporary. Moyamoya disease usually occurs without any apparent cause. When it appears in association with another condition that causes a gradual narrowing of the arteries at the base of the brain, it is referred to as « Moyamoya syndrome » or secondary Moyamoya.

How many people does this disease affect?
The prevalence of Moyamoya disease (the number of people affected in a given population at a certain time) varies by population. In France, it is estimated to affect approximately 1 in 300,000 people. In Japan, where the disease was initially described, it is believed to be 10 times more frequent, with approximately 1 case in 30,000 people.

Who can be affected? Is it present everywhere in France and the world?
The disease affects all populations, but it is much more common in Japan and among people of Asian origin. Moyamoya disease primarily affects children between the ages of 5 and 15, but it can also occur in adults, particularly between the ages of 30 and 40. Girls seem to be affected more often than boys.

What causes this disease?
The exact cause of Moyamoya disease is unknown. It can occur in isolation (with no associated illness), and in such cases, it is referred to as Moyamoya disease. In a small number of cases, it runs in families, meaning that several family members have the disease. This suggests that genetic factors are involved, though no specific gene has been identified yet. Familial cases are very rare (see « Genetic Aspects »).

During the disease, the large arteries that supply blood to the brain (figure 1) gradually narrow (stenosis), which prevents blood from flowing normally. To compensate for this slowdown in blood circulation, other, finer vessels gradually develop. It is somewhat like a highway being congested and secondary roads being built to bypass the traffic jam. When observed through arteriography (see further details below), the network of newly formed small collateral vessels has a cloudy or « puff of smoke » appearance, which is referred to as « moyamoya » in Japanese.

Figure 1: The internal carotid artery is the main artery that supplies blood to the brain. It is generally affected in Moyamoya disease. It divides into the anterior cerebral artery and the middle cerebral artery, which can also become narrowed. (http://radiologynotes.servehttp.com/vascular/vascular.htm)
Sometimes, it is a consequence of another condition, such as sickle cell disease, Down syndrome, or a tumor at the base of the skull that has been treated with radiotherapy. In such cases, it is referred to as Moyamoya syndrome.

Is it contagious?
No, Moyamoya disease is not a contagious illness.

What are the symptoms?
The symptoms of the disease vary greatly from person to person.
In both children and adults, the disease mainly manifests through strokes (often referred to as « attacks » in common language). These occur when a part of the brain is suddenly deprived of blood supply (called ischemic stroke or cerebral infarction) or when a small blood vessel bursts and blood leaks into the brain (called hemorrhagic stroke or cerebral hemorrhage).
Strokes can cause various symptoms that appear suddenly. Often, this includes weakness or paralysis of a limb or one side of the body (hemiplegia), or a loss of sensation in part of the body (numbness, abnormal tingling). In practice, this may result in the person being unable to hold a fork, one or both legs giving way, or a sudden inability to move one arm, for example. In children, these issues sometimes occur when they are upset or crying.
Strokes can also cause speech or language problems (difficulty speaking or regression of speech), vision problems, and issues with balance and coordination (making walking clumsy).
These problems may be permanent or temporary (referred to as transient ischemic attacks).
Children may also suffer from severe headaches, dizziness, and experience academic delays due to learning or memory difficulties.
Finally, some patients may also have epileptic seizures. The symptoms of these seizures vary: movements or convulsions (muscle jerks, tremors, stiffness), sensory disturbances (tingling, numbness, auditory or visual hallucinations), psychological issues (panic, memory problems, confusion, loss of consciousness, blackouts), or even excessive salivation, urinary incontinence, etc. The seizures can affect the entire body (generalized seizures), usually accompanied by loss of consciousness, or just one part of the body (a limb, for example) or one side of the body (partial seizures).
In some cases, repeated strokes can eventually damage intellectual functions, and some children may become « slower » or begin to experience learning difficulties. Others may lose some of the skills they had previously acquired (such as language). Similarly, in adults, intellectual abilities may decline due to the disease.
Adults with Moyamoya disease experience the same symptoms as children, but strokes are most often caused by cerebral hemorrhage. However, as in children, they may also be caused by cerebral infarction.

What explains the symptoms?
Most symptoms are caused by insufficient blood flow to the brain. Certain areas of the brain do not receive enough oxygen to function properly. The symptoms depend on the affected area: vision problems, motor issues, sensory disturbances, etc. Repeated episodes of oxygen deprivation can permanently damage the affected areas, explaining why some effects are lasting.

Additionally, particularly in adults, while the newly formed small supplementary blood vessels provide a minimum blood supply, they are more fragile than normal vessels. There is, therefore, an additional risk of bleeding in these vessels, which can lead to cerebral hemorrhages. Moreover, these abnormal small vessels can also become blocked.

What is the progression of the disease?
The narrowing of the arteries supplying blood to the brain is progressive: without treatment, the symptoms worsen, and the risk of stroke increases.
The main risk of the disease is the development of permanent neurological problems, particularly the possible occurrence of intellectual impairment due to brain damage. Loss of speech or movement disorders are also common, but rehabilitation can sometimes help reduce the severity of the aftereffects. About half of the patients may experience intellectual deterioration.
In some cases, Moyamoya disease can be fatal (about 10% of adults and 4% of children), usually due to a cerebral hemorrhage.

Diagnosis

How is Moyamoya angiopathy diagnosed?
When the first symptoms appear, brain imaging through magnetic resonance imaging (MRI) is often performed first. This painless examination involves obtaining detailed images of the brain by placing the patient in a machine that produces a magnetic field. It allows doctors to detect brain lesions (hemorrhage or infarction).
However, the examination that confirms the diagnosis of Moyamoya disease is cerebral angiography. This is a radiological examination using X-rays, which allows observation of the blood vessels after injecting a « contrast agent » into the blood to make the vessels more visible. In individuals with Moyamoya disease, the images of the brain’s blood vessels are very telling: they reveal the presence of an abnormal network of « smoke-like » vessels (see figure 2).

Figure 2: On the left, an angiogram of a person with Moya Moya disease. Small « smoke-like » vessels appear to compensate for the narrowing of the internal carotid artery or its branches (anterior or middle cerebral arteries). On the right, an angiogram shows normal arteries.
MCA: Middle cerebral artery
ACA: Anterior cerebral artery
ICA: Internal carotid artery
This examination also helps to assess the severity of arterial narrowing.

What do additional tests consist of? What are they for?

The discovery of Moya Moya disease requires investigating any possible cause to determine if there is an underlying condition that could explain it, or if it is an idiopathic form (i.e., without an apparent cause).

A brain MRI can already rule out certain causes, such as congenital brain vessel malformations or the presence of a tumor. However, other tests are generally conducted. Blood tests can help detect blood disorders (such as protein C deficiency, which promotes the formation of blood clots – small plugs formed by blood platelets – or sickle cell disease, a condition characterized by abnormal red blood cells that can block blood vessels). Together with urine tests, these tests can also help detect metabolic diseases (such as homocystinuria, which can sometimes cause strokes).

Moya Moya syndrome can be associated with other diseases, such as neurofibromatosis type 1 (or Recklinghausen disease), a genetic disorder characterized by café-au-lait spots, « freckles » in the armpits and groin, small skin growths, or lumps under the skin (neurofibromas). If the diagnosis of neurofibromatosis has not already been made, it is based on ophthalmological and dermatological examinations.

Can this disease be confused with other conditions? Which ones? How can you tell the difference?

Strokes are relatively common in the general population, especially among older people, smokers, or those with high blood pressure, diabetes, or high cholesterol. In adults, Moya Moya disease may not necessarily be considered at the onset of stroke symptoms. However, cerebral angiography can direct the physician towards a diagnosis of Moya Moya disease.

In children, on the other hand, strokes are extremely rare. They can be caused by several diseases, which will be systematically investigated, as explained above.

Genetic aspects

What are the risks of transmission to children? What are the risks for other family members?
In the vast majority of cases, Moya Moya disease is sporadic, meaning there is only one case within a family.
Very rarely, the disease is familial (with at least two cases occurring in the same family). Familial forms are, however, exceptional in Europe (around 2%). In Japan, where the disease is more common, about 10% of Moya Moya cases are familial. In these families, the mode of transmission from one generation to another is not clearly determined. Researchers believe that the risk of relatives developing the disease is slightly increased, but it cannot be precisely evaluated.
However, when Moya Moya syndrome is a consequence of an inherited genetic disease (such as neurofibromatosis), there is a risk that siblings may also have this genetic disease (though it is impossible to predict if they will also develop Moya Moya syndrome).

Can this disease be detected in at-risk individuals before it manifests?
In exceptional cases, a brain MRI performed for a completely different reason (such as trauma) may reveal narrowing of the cerebral arteries before any symptoms appear.

Can prenatal diagnosis be made?
No, prenatal diagnosis is not possible.

Treatment, management, prevention

Is there a treatment for this condition? What benefits can be expected from the treatment?

There is no treatment to prevent the narrowing of the brain arteries, but there are ways to limit the symptoms.

Surgery
Most often, a surgical operation can be considered, especially in early forms of the disease. The choice of such an intervention can be difficult and is made after consultation between the family and the medical teams, based on the patient’s age, condition, and symptoms. However, not all patients are good « candidates » for surgery, which can sometimes be more dangerous than beneficial.
The goal of the operation is to provide blood to areas of the brain suffering from a lack of oxygen. This is done by « redirecting » vessels that supply other regions (such as the scalp, temporal muscles, etc.) and bringing them to the brain. These redirected vessels will then develop and provide « palliative » irrigation, bypassing the narrowed cerebral arteries (this is referred to as revascularization). Several surgical techniques are used to redirect the vessels:

• Multicraniosotomy involves making several small holes in the skull bones to allow scalp vessels to develop towards poorly perfused areas of the brain.
• Temporo-sylvian anastomosis connects the temporal artery (located at the temple outside the skull) to the middle cerebral artery within the brain.
• Additionally, some surgeons also perform an anastomosis or bypass of the obstructed carotid artery, which involves placing a small conduit (a piece of vessel or plastic tube) that bypasses the narrowed area of the internal carotid artery, redirecting blood flow. This operation is the most delicate and is therefore performed less frequently.

The difference in efficacy between these surgical techniques is not well established, and surgeons generally choose the least aggressive and most easily feasible solution, especially for young children. In case of failure, another surgical approach may be considered. Each operation is discussed on a case-by-case basis.

Medications
Since some cerebral vessels are narrower due to the disease, there is a higher risk of blood clots forming and contributing to the obstruction of these vessels. Medications that prevent platelet aggregation and thus the formation of clots (antiplatelet agents), such as aspirin, are sometimes given to patients as a preventive measure, but their efficacy is not clearly proven. Moreover, these medications can increase the risk of bleeding in the brain.
In certain cases, vasodilator medications (calcium channel blockers) may be prescribed. They cause the blood vessels to dilate (widen), allowing blood to flow more easily. They can sometimes help alleviate headaches.
In the event of seizures, antiepileptic medications may be prescribed.

Rehabilitation
After a stroke, rehabilitation should be organized by a multidisciplinary team to try to recover as many faculties as possible, including language, movement, and cognitive abilities. Both children and adults often have impressive recovery capabilities that must be fully exploited through appropriate exercises.
Thus, physiotherapy is essential for managing any motor disorders (walking, balance, coordination of movements, etc.). In cases of speech disorders, speech therapy is recommended. Physiotherapy and speech therapy sessions are reimbursed by Social Security.
In cases of significant sequelae, psychomotor therapy sessions can help the patient cope with their disability and accept their body image, allowing them to adapt to their environment.
Regarding the management of intellectual disorders, it can involve participation in group sessions (with other patients, for example), stimulating the patient, preventing isolation, and limiting the feeling of being a burden to those around them.
In cases of loss of autonomy (intellectual slowdown, behavioral disorders, significant motor difficulties), the patient may need specialized home assistance or even hospitalization in a specialized medical facility to assist with daily living (hygiene, nutrition).

What are the benefits and risks of treatment?
Generally, children respond better to surgery than adults.
The prognosis for operated individuals is quite good, although some improvements may only be visible 6 to 12 months after the procedure. Multiple interventions may sometimes be necessary.
However, these are heavy operations, and the risks associated with anesthesia are higher in patients due to poor brain vascularization and vessel fragility (high risk of hemorrhage). It is important to discuss this with the anesthetist before the operation to assess the risks involved.
Additionally, when a patient has suffered a severe and prolonged stroke, the damaged areas of the brain are unfortunately permanently affected. Even if the patient can « recover » certain abilities, they may present permanent sequelae on which surgical intervention will have no effect.

Is psychological support advisable?
At various times, both the family and the patient may feel the need for psychological support.
The announcement of the diagnosis is a difficult moment, as it concerns a disease that affects the brain and can potentially be disabling both physically and mentally. Moreover, the evolution of the disease is unpredictable, and the fear of a significant stroke (which can cause serious irreversible damage, such as paralysis, vision problems, etc.) contributes to plunging some patients or their parents into anxiety that is difficult to bear. For this reason, the support of a psychologist can be greatly helpful.
When the disease occurs in a child, it is particularly difficult for parents to learn how to care for the child without overprotecting them, to maintain communication within the couple and family, and to manage feelings of jealousy or even guilt that the siblings of the sick child may experience. Additionally, the decision-making process regarding a possible operation can be difficult, and parents need guidance and support.
Various relaxation methods can also be useful for learning to manage anxiety and coping with the illness.

What can one do on their own to help with recovery?
There are no specific recommendations, but it is advisable to maintain a good lifestyle, and for adults, to avoid smoking (as it increases the risk of stroke).
Similarly, contraceptive pills or hormone treatments given during menopause can increase the risk of cardiovascular diseases (in addition to the risk related to Moya Moya disease). Generally, to avoid any unnecessary risk-taking, hormone treatment is only maintained if it provides real benefits for menopause-related symptoms (such as treatment for hot flashes), and this for a limited duration.
Additionally, a pill containing only progestogens (without estrogens) is generally preferred over the conventional pill

How to get follow-up care?
Follow-up for individuals with Moya Moya disease is conducted in specialized hospital neurology consultations. The frequency of visits and examinations is determined by the medical team.
However, certain symptoms should alert the patient or their parents and prompt them to seek emergency care.
For instance, a stroke may manifest as sudden vision or speech disturbances, sudden difficulties in moving a limb (for example, it may become difficult to write), or coordination issues. Likewise, in the case of severe headaches, it is advisable to consult a doctor promptly.

What information should be known and communicated in an emergency?
In an emergency, it is crucial to inform the doctors about the diagnosis of Moya Moya disease. Given the significant risks associated with anesthesia, it is necessary for the patient to be managed by an experienced anesthetist familiar with this disease and its specifics.
Finally, it is imperative to inform the healthcare staff about the ongoing treatments and their dosages. This precaution helps avoid incompatible drug combinations and potential overdoses.

Can this disease be prevented?
No, as of now, there is no way to prevent the occurrence of Moya Moya disease.

Living with the disease

What are the consequences of the disease on family, professional, social, school, and sports life?
Being affected by a disease that impacts the brain, associated with the risk of physical and/or intellectual disability, is extremely challenging. However, it is impossible to predict whether patients will have permanent sequelae and which functions will be affected (vision, speech, walking, etc.). The consequences of the disease vary significantly from one person to another.
It is entirely possible to lead a normal life while having Moya Moya disease.
However, in some individuals, strokes may leave debilitating sequelae, compromising the patient’s autonomy.
Thus, in some cases for adults, ceasing professional activity may become necessary, or at least a reorientation or reorganization of work hours. Additionally, in the event of a stroke, hospitalization followed by often lengthy rehabilitation is essential to enable patients to recover and regain as many functions as possible.
For many children, normal schooling can be ensured and adapted through an Individualized Reception Project (PAI) or a Personal Schooling Project (PPS). This is an agreement involving the family, the school, and the school doctor, aimed at meeting the child’s needs and informing teachers about the disease.
For children with significant deficits (vision and speech disorders, significant learning difficulties), schooling in a class for disabled students (CLIS), with fewer students and adapted teaching, may be necessary and more reassuring. CLIS also allows for time for essential sessions of speech therapy, psychomotricity, or physiotherapy.
In certain cases, education and care can take place at home through the Special Education and Home Care Service (SESSAD).

Pregnancy
It is possible to have children while affected by Moya Moya disease, with appropriate medical follow-up. Given the risks associated with anesthesia, necessary precautions must be taken. It is therefore important to discuss any desire for pregnancy or an ongoing pregnancy with your doctor.

Learn more

Where is research currently?
Research aims to better understand the mechanisms responsible for the narrowing of the cerebral arteries. The rare familial cases are studied to try to identify one or more genes responsible for the disease.
Clinically, therapeutic trials are being considered, particularly to evaluate the effectiveness of « vasodilator » or « neuroprotective » medications.

Definition

« Moyamoya » angiopathy 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 use when no disease is associated with the arterial abnormalities..

Epidemiology

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 by a radiological examination of the brain without any symptoms in one 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, 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.

Clinical Description

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 haemorrhagesin 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 seizureswhich 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
• Movement’s disordersbut 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 vasculitisin 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 vasculitisor 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 anaemia, diabetes, abnormal thyroid function etc.

Etiology – Pathophysiology

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” appearance.

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.

Diagnosis

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 occlusionof 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 Moyamoyasyndrome: arteriosclerosis 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

Treatment of Moyamoya disease is complex and must be discussed by multidisciplinary teams involving, in particular, neurologists, neurosurgeons and anaesthetists.

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 anastomosis (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 thought 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.

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