General Information: Moyamoya disease 1. What is moyamoya? In the late 1950's, clinical entity of moyamoya disease is noticed by Japanese neurosurgeons at that time. Since its etiology was not known (even now), many names were designated to this disease. Officially, it is named as the "spontaneous occlusion of the circle of Willis". The artery (the internal carotid artery) which supplies blood to the brain becomes stenotic (narrowing) or occluded at the base of the brain. Consequently, the small arteries in the deep brain become larger (enlarged) as a collateral pathway to supplement the reduced blood. These abnormal arteries look like the puff of the cigarette and it is called "moyamoya" appearance in Japanese language. Finally, the name "moyamoya disease" becomes popular instead of the "spontaneous occlusion of the circle of Willis". 2. Symptoms Two major events occur in moyamoya disease. One is cerebral ischemia (lack of blood to the brain). The other is cerebral hemorrhage (bleeding, rupture of the brain artery). Age distribution of the onset of moyamoya disease has two peaks. Children below the age of 10, cerebral ischemia is common. Adults between 30 and 40 years of age, hemorrhage is common. Of course, hemorrhage in the children and ischemia in adults may occur, but is less common. Male/female ratio is 1:1.8, which means female dominance. Incidence is 3.16/100,000, and about 400 new patients are diagnosed annually in Japan. Moyamoya disease is noted everywhere in the world, but is fairly common in the east Asia, above all, in Japan. The etiology is still not known. Once, the congenital theory such as congenital vascular anomaly or the acquired theory such as infection is proposed. Family history, i.e., about 10% incidence among brothers/sisters and parents /children, and high incidence among Japanese indicate genetic factors. At present, speculated etiologies are both congenital and acquired: genetic factors as well as environmental factors may play an important role in the presentation of moyamoya disease. It is obvious that bacteria or virus are not the cause, thus there is no chance of transmission of the disease from one to another. Symptoms of moyamoya disease include hemiparesis and hemi-corporeal sensory deficits (motor and sensory deficits of the half side of the body), seizure, involuntary movement, gait disturbance, monoparesis (weakness of the arm or foot), dysarthria (speech disturbance), aphasia, visual disturbance (narrowing of the visual field). These symptoms may be present in the other disease. There are atypical symptoms which delays the diagnosis of the disease, which include learning difficulty, vertigo, abnormal behavior, restless, paraparesis (weakness of the legs), collapse, syncope, headache, vomit, nausea, etc. Cerebral ischemia is either temporary or permanent. Transient ischemic attack (TIA) is defined as disappearance of the symptoms within 24 hours, but usually TIA lasts several minutes or disappears within 30 minutes. When eating noodle, playing musical instrument such as flute, singing loudly, crying, running fast, blood concentration of bicarbonate decreases, and cerebral arteries become spastic (narrowing), and the blood supply to the brain reduces, thus cerebral ischemia occurs. This ischemia may result in consciousness disturbance, weakness of the arm and/or foot, speech disturbance, involuntary movement of the arm or leg. Other symptoms include headache, seizure, abnormal sensation, psychosis, and decline of school performance. In children, minor symptoms are not noticed even by the parents, leading to the delay of the diagnosis. They may learn automatically to avoid shouting or hyperventilation to prevent ischemic events. In the case of cerebral hemorrhage, symptoms depend upon the location and size of the hemorrhage. When cerebral aneurysm is associated and ruptures, subarachnoid hemorrhage may occur, but in the majority of the cases with hemorrhage, intracerebral hemorrhage or intraventricular hemorrhage occurs. This results in consciousness disturbance (coma, stupor), paresis, sensory disturbance, or seizure. Fatal stroke is often associated with brain hemorrhage, and this hemorrhage often recurs. 3. Diagnosis Diagnosis is made by clinical observation and imaging methods. When the patient complains weakness during eating noodles, paresis during crying, diagnosis is usually straightforward. In the case of seizure or involuntary movement, diagnosis is sometimes delayed. When the clinical diagnosis is epilepsy and anti-convulsant is given, and then ischemic events are followed, it takes a long time to reach the diagnosis of moyamoya disease. Mis-diagnosis of mental disease is not rare at the beginning of the disease. If moyamoya disease is suspected, the patient has to visit neurosurgeon, neurologist, or pediatric neurologist. When there are severe headache, nausea, vomit, loss of consciousness, paresis, speech disturbance or visual disturbance, immediate medical check is required. Diagnostic imaging There are three diagnostic methods for moyamoya disease. 1. catheter angiography, 2. magnetic resonance (MR) imaging and MR angiography, and 3. computerized tomographic (CT) scan and CT angiography. Catheter angiography used a small tube (1.3 mm in diameter called a catheter) which is inserted from the femoral artery. This catheter is navigated in the artery to the neck (carotid) artery. Using contrast material, arterial anatomy is visualized. This method has a potential risk such as cerebral infarction, thus its indication should be strict. In adults, this catheter angiography can be done under local anesthesia, but for children, general anesthesia is required. MR imaging and angiography are risk-free diagnostic methods, but its diagnostic ability is often inferior to catheter angiography. MR examination requires only 30 minutes without pain. Sedation during MR examination is required for small children. CT scan is especially valuable in emergency to differentiate between hemorrhage and infarction. CT can tell the presence or absence of hemorrhage, but can not depict moyamoya disease. Recent advance of CT angiography allows the diagnosis of moyamoya disease when the CT scanner is modern enough to create three-dimensional arterial images. Diagnostic criteria of moyamoya disease (1) Stenosis and/or occlusion of terminal portion of the intracranial internal carotid artery and its vicinity, and so-called "moyamoya vessels" at the base of the brain are observed. (2) the above-mentioned changes are observed bilaterally. When the lesions are bilateral, the diagnosis is "definite", but when the lesion is unilateral, the diagnosis is "probable". 4. Treatment A. Emergency treatment In the acute stage, treatment is essentially the same as in the cerebral infarction or hemorrhage due to other causes. In cerebral infarction, brain protective drug, anti-thrombotic drug may be given by a drip infusion. In cerebral hemorrhage, conservative management including blood pressure control is usually done when the hematoma is small. In the case of ventricular hemorrhage, drainage operation (insertion of the small tube to the ventricle) is performed. If the hematoma is large enough, open surgery to remove it has to be done. Drip infusion to control the brain pressure and brain swelling is also required. There is no reason to perform anastomosis surgery in the acute stage. Anti-convulsant to control seizure is frequently required. B. Treatment in the chronic stage 1. Patients with cerebral ischemia Anti-platelet drugs, anti-coagulants, vaso-dilating drugs are occasionally given. Some doctors believe these drugs are necessary, but others do not (including me). In the seizure case, anti-convulsant is necessary. In order to prevent recurrent ischemic stroke, anastomotic surgery (bypass surgery) is believed to be effective.Anastomosis between the superficial temporal artery (STA) and middle cerebral artery (MCA) is carried out under a microscope. This anastomosis is called "direct bypass". On the other hand, "indirect bypass" is the surgery to place a dura mater (envelope which surrounds the brain) or temporal muscle or its fascia is placed over the ischemic brain surface. The latter method expects a new spontaneous anastomosis and some period is required to establish such an anastomosis. It is common to add an indirect bypass more or less when "direct bypass" is scheduled. In moyamoya disease, both right and left brains are ischemic, thus bypass surgery is required bilaterally. Usually, one-side operation for more ischemic brain is performed. And, then bypass surgery for the opposite side is scheduled in several months. Surgical complication rates are not high, but possible complications include cerebral infarction, cerebral hemorrhage, wound infection, seizure, fever, neurological deterioration. The surgical effects do not appear immediately, but the frequency of the ischemic events may gradually reduce, and then disappear. Postoperative time course is variable and depends upon the cerebral blood flow, method of operation, etc. Bypass surgery is performed under general anesthesia. Catheter angiography for children also requires general anesthesia. General anesthesia for moyamoya disease has a low risk of cerebral infarction. 2. Patients with cerebral hemorrhage It is believed that hemorrhage occurs as the results of breakthrough by overload to the fine collateral arteries in the deep brain. To reduce this overload, bypass surgery is performed. However, the surgical benefit is not proved. To disclose the true efficacy of bypass surgery for hemorrhagic cases, clinical trial is under way in Japan. For hypertensive patients, anti-hypertensive drugs are given, Anti-platelet drugs are not given. 3. Rehabilitation Rehabilitation is required for hemiparesis, gait disturbance, aphasia, etc caused by cerebral infarction or hemorrhage. There are three kinds of rehabilitation; physical therapy (PT), occupational therapy (OT), and speech therapy (ST). Rehabilitation is not aimed at the initial state before the stroke. Functional full recovery is impossible because there is brain damage. The purpose of rehabilitation is how to cope with the impairment and adapt the social life, or occasionally how to reduce the necessary assistance of the family members. C. Incidentally discovered moyamoya disease Familial incidence of moyamoya disease is about 10%. Screening MR examination is occasionally performed to the family members who are completely disease free. Examination for headache or vertigo, or that for minor head trauma may disclose moyamoya disease incidentally. The patient with incidentally discovered moyamoya disease will not always develop neurological deficits in the future. In many case, no treatment is given to such patients. 6. Prognosis In the case of ischemic presentation, transient ischemic attack (TIA) is not always results in cerebral infarction. Children with moyamoya disease sometimes have mental retardation or motor weakness. The frequency of TIA decreases with time. In the rare occasion, bleeding occurs in the patients with the initial ischemic presentation. Recurrent hemorrhage in the patients with initial hemorrhagic presentation is common, and prognosis is poor especially for the middle-aged or elders. Fatal stroke in moyamoya disease is in most cases attributable to recurrent hemorrhage. 2004.2.7