Moyamoya Disease: Stages, Causes, Symptoms, Treatment

Moyamoya disease is a condition where there is chronic and progressive narrowing of walls of internal carotid arteries characterized by thickening of the walls, resulting in a narrowed or stenosed internal diameter of the artery. This progressive narrowing may gradually cause complete blockage in the arteries and result in stroke. In order to compensate for the decreased blood flow in the narrowed arteries, our brain forms collateral blood vessels, so that the deprived areas of the brain can receive oxygen-rich blood. Moyamoya disease was discovered by the Japanese and they termed these collateral vessels as “moyamoya,” which means “puff of smoke,” in Japanese. The collateral vessels are tiny and have a hazy appearance when seen on an angiogram. The tiny moyamoya collateral vessels are more fragile than the normal blood vessels and can easily rupture and bleed into the brain resulting in hemorrhages. Both sides of the brain are commonly affected by Moyamoya and this disease is also usually associated with aneurysms.

When the carotid arteries become narrowed and the blood flow becomes slow, it increases the risk of clot formation and transient ischemic attacks (TIA) or a full-fledged stroke. In order to compensate for the decreased blood flow, our brain slowly forms “detours” in the form of small collateral blood vessels to supply blood to the affected regions of the brain. As mentioned before, these tiny blood vessels resemble a wisp of smoke when seen on an angiogram thus giving this disease its name “Moyamoya” which means a “puff of smoke” in Japanese.

When the process of blockage starts, it tends to worsen the same way. As of now, there are no known medications to help reverse the blockage. If the patient suffers bleeding or a major stroke, then there may be permanent loss of function in the patient. It is important that this condition is diagnosed as early as possible and the treatment started immediately. Surgical treatment is often recommended in Moyamoya disease.

Moyamoya disease is classified into the following stages depending on its progression and angiographic findings:

Stage I: There is narrowing of the internal carotid arteries.

Stage II: The moyamoya vessels develop at the base of the brain.

Stage III: There is worsening of the moyamoya vessels and increase in the narrowing of the internal carotid arteries. The diagnosis of this disease is usually made at this stage.

Stage IV: There is increase in the collateral vessels from the scalp and reduction of moyamoya vessels.

Stage V: Reduction of moyamoya vessels and significant internal carotid artery narrowing.

Stage VI: The moyamoya vessels disappear completely and the internal carotid arteries are completely blocked with significant collateral vessels from the scalp.

Transient ischemic attack which consists of hemorrhagic stroke, ischemic stroke or mini-stroke in the patient is the initial symptom of moyamoya disease. This occurs because of hindrance in the oxygen rich blood flow to the brain. Hemorrhagic stroke occurs when the tiny blood vessels burst and the blood leaks into the brain. The symptoms of hemorrhagic stroke as well as ischemic stroke consist of numbness or weakness in the arm or leg, difficulty in speaking, or paralysis which can affect one side of the body. Headache is also a common symptom in hemorrhagic stroke. Patient can experience other symptoms also such as cognitive or learning impairments and seizures.

Given below is a list of symptoms of Moyamoya disease which need immediate medical attention:

Symptoms of Stroke Consist of: Blurry or disturbed vision, weakness or paralysis affecting one side of the body, headaches, slurred speech, loss of sense of taste or smell, difficulty in speaking, inability to walk, inability to stand upright and seizures.

Symptoms of a Brain Hemorrhage Which Require Immediate Medical Attention Include: Nausea, vomiting, lethargy, fatigue, vision changes, severe headache, weakness/numbness in some part of the body, sudden loss of consciousness, loss of coordination/balance, difficulty speaking, difficulty in understanding speech, feeling of a “strange” taste in the mouth and seizures.

• The exact cause of moyamoya disease is not known. Having a family history of this disease or hereditary factors can play a role, particularly if the patient is of Japanese origin.
• Girls are at a slightly higher risk for developing moyamoya disease than boys.
• Moyamoya disease is more commonly found in Japan and people of Asian ethnicity; however, people from any country or ethnicity can suffer from this condition.
• A traumatic injury to the brain can also trigger Moyamoya disease.
• An inherited gene defect can also cause Moyamoya disease.
• Moyamoya disease is often diagnosed in children aged from 5 to 15 years and in adults who are between the ages of 30 to 45 years.
• Moyamoya-like changes are also seen in patients who have undergone radiation therapy to the neck and head for treatment of craniopharyngiomas and pituitary tumors.
• There are many diseases which are associated with changes resembling moyamoya disease. Moyamoya syndrome can also develop in patients who are suffering from sickle cell disease, neurofibromatosis type I, and Down’s syndrome.

If the patient is having symptoms resembling a stroke then patient is referred to a neurosurgeon. The surgeon then asks questions regarding the symptoms of the patient and also patient’s previous medical history, family history and the medications which the patient is taking. After medical history is taken, a physical exam is performed. Imaging tests are done to help diagnose this condition, as they reveal the characteristic narrowing of the arteries and the collateral blood vessels of moyamoya, which have the hazy appearance of a “puff of smoke.” Diagnostic imaging tests can also show multiple small strokes in the patient. A correct diagnosis of moyamoya disease can be made if the MRI scan images show decreased blood flow in the internal carotid artery, the anterior and middle cerebral arteries; and increased collateral blood flow at the base of the brain. Angiogram is often needed to confirm the diagnosis of moyamoya disease.

Magnetic Resonance Imaging (MRI) scan uses radio-frequency and magnetic field waves to generate detailed images of the soft tissues of the brain. Magnetic Resonance Angiogram (MRA) can also be done during the MRI scan by injecting a contrast agent into the patient’s blood, which can reveal a clearer image of the arteries of the brain. Magnetic Resonance Imaging is a noninvasive test.

Angiogram is a procedure where a catheter is introduced into the artery and passed via the blood vessels to the brain. After the catheter is in place, the doctor injects a contrast dye into the blood after which x-rays are taken. Angiogram helps in examining all the vital arteries to the brain including the internal carotid arteries, external carotid arteries and vertebral arteries. Imaging tests are important to identify any pre-existing collateral vessels, in case if the surgery is done then the surgeon can take care to avoid disrupting these collateral vessels. Arteriovenous malformations or aneurysms can often be seen with moyamoya disease and they can also be detected during an angiogram. Angiogram is an invasive procedure.

Computed Tomography (CT) Perfusion Imaging helps in detecting blood flow in the brain. This test also helps the surgeon in planning the surgery. A contrast agent is injected into the blood stream, which allows the doctors to assess the amount of blood flow that is reaching the brain and to determine the parts of the brain that are at a higher risk for stroke. When Computed Tomography Perfusion imaging is done, Diamox, a medication, is given to dilate the arteries which also act as a “stress test” for the brain.

Computed Tomography Angiography (CTA) scan uses x-rays to generate detailed images of anatomical structures of the brain. A contrast agent is injected into the blood stream to view the arteries of the brain more clearly. CTA scan is a very good test in providing pictures of both the soft tissues as well as blood vessels. Computed Tomography Angiography is a noninvasive test.

Cerebral Blood Flow Studies including the Xenon-Enhanced CT scan, Transcranial Doppler Ultrasonography (TCD), Single Photon Emission Computed Tomography (SPECT) scan, and Positron Emission Tomography (PET) scan also can be done to help with the diagnosis and treatment of moyamoya disease.

Presently, there are no medications which can reverse the narrowing of the arteries in moyamoya disease. The aim of treatment for moyamoya disease is cutting down the risks of recurrent strokes by doing an arterial bypass or by forming a new blood supply to the affected parts of the brain. Anti-platelet agents, which include medicines like aspirin, are given to prevent the formation of clots. In patients who are suffering from TIAs and strokes, aspirin helps in reducing the risk of occurrence of a damaging stroke. According to studies, aspirin used alone is not effective in treatment of moyamoya disease. Surgery is commonly recommended for treatment of moyamoya disease.

Treatment for patients suffering from long-term damage from strokes consists of physical therapy, occupational therapy and speech therapy to help the patient regain function and cope with their disability.

Surgery is commonly recommended for patients with moyamoya disease who are having progressive or recurrent strokes or TIAs. There are various surgical procedures available for moyamoya disease with the goal of preventing more strokes by revascularization or restoring the blood flow to the affected parts of the brain. The surgical procedures can be divided into two groups; one which involves direct connection between the blood vessels and the other which involves indirect connection between the blood vessels. Generally, direct bypass procedures are done in older children and adults; whereas indirect procedures are done in children below the age of 10 years.

Cerebral Bypass Procedure is a surgical procedure, which involves the direct method of revascularization by connecting a blood vessel present outside the brain to a blood vessel present inside the brain. This will reroute or bypass the blood flow around the damaged narrowed/blocked artery. Superficial temporal artery to middle cerebral artery or STA-MCA is the commonest bypass procedure used and gives an immediate improvement in the blood flow. In cases where the superficial temporal artery is not sufficiently big or is not available to use for bypass, then a different artery needs to be used. This is determined after the surgeon has reviewed the images of the arteries from CT angiogram or angiogram.

Encephalo-Myo-Synangiosis (EMS) is a surgical procedure that is also an indirect method of revascularization where the surgeon dissects the temporalis muscle and places it onto the surface of the brain through an opening in the skull. Gradually there is formation of new vessels between the brain and the blood-rich muscle.

Encephalo-Duro-Arterio-Synangiosis (EDAS) is a procedure which involves the indirect method of revascularization where the superficial temporal artery is put in contact with the surface of the brain. The surgeon makes a hole in the skull directly under the artery and the artery is then sutured to the brain’s surface after which the bone is replaced. As time goes, angiogenesis occurs where there is formation of small arterial vessels to the brain.

Encephalo-Duro-Arterio-Myo-Synangiosis (EDAMS) is a surgical procedure which is also an indirect method of revascularization and which combines the technique of EMS and EDAS.

Omental Transposition is a procedure that is another indirect method of revascularization where the omentum, which is very abundant in blood supply, is placed on the brain’s surface and eventually it is expected that the vessels will grow into the brain and enhance the blood supply.

Multiple Burr Holes Procedure is another indirect method of revascularization where the surgeon drills multiple small holes in the skull, so that new vessels can grow into the brain from the scalp.

It is difficult to predict the prognosis and life expectancy of the patient having moyamoya disease as the natural history of this condition is not clear. The progression of Moyamoya disease can be slow with the patient suffering from occasional strokes or TIAs; or there can be rapid worsening of this disease where the patient’s health declines. The prognosis and life expectancy of the patient having moyamoya disease depends on the speed and the degree of the narrowing and blockage in the arteries. Prognosis also depends on the ability of the patient to form effective collateral circulation, the age of the patient when the symptoms started, whether one or both sides of the brain are affected, whether the patient has suffered a stroke, patient’s general health, the extent of disability which the patient has as a result of a stroke and how soon the treatment started after the diagnosis. The neurologic condition of the patient is also important in determining the recovery and life expectancy of the patient.

According to studies, about 50 to 60% of patients who do not seek treatment for moyamoya disease will have progression of the disease and have decreased life expectancy and poor prognosis whereas surgical treatment of patients has revealed a great decrease in the progression of this disease.

As far as recovery from Moyamoya disease is concerned, it is important for family members to understand that this is a progressive disease and there is continuous worsening of the narrowing of the blood vessels of the brain. Symptoms can become gradually severe over a period of time and patient can also suffer multiple strokes in a short span of time. Surgery is done to provide a new and healthy source of blood circulation to the brain and to cut down the risk of a life-threatening stroke.

The prognosis tends to be excellent if there is surgical treatment done in patients before a disabling stroke and even in severe moyamoya disease. In patients who do not have any symptoms, surgical treatment helps in protecting against stroke and also increases the life expectancy of the patient. However, if the patient is not treated, then there is worsening of moyamoya disease with clinical deterioration in the patient along with potentially irreversible neurological impairments.