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Moyamoya disease is a very rare condition in which the walls of the internal carotid arteries - which supply blood to important areas of the brain - become thickened. This gradually slows the flow of blood to the brain and increases the likelihood of blood clot formation, both of which can lead to strokes and transient ischemic attacks.
In this condition, small blood vessels also form a network of "side roads" trying to supply oxygen to the oxygen-starved areas of the brain once served by the narrowed arteries. These many tiny blood vessels show up clearly on an angiogram, explaining the name for the disease; in Japanese, "moyamoya" means puff of smoke.
More fragile than normal blood vessels, arteries in this network can also break and bleed into the brain, causing hemorrhages (In the brain, hemorrhage can be even more dangerous than elsewhere in the body, as brain tissue becomes irritated and inflamed and the pressure inside the skull increases), in certain patients.
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The cause of moyamoya disease is unknown. The process of narrowing of the brain arteries seems to be a non-specific reaction of the brain's blood vessels to a wide variety of stimuli, injuries, or genetic defects.
For example, in the more than 300 patients in the operative series of my colleague Edward Smith and myself seen from 1985 to the present, the disease has been associated with:
Neurofibromatosis -- the congenital condition that cases tumors to grow on nerves (24 children)
Asian ancestry (28 children)
Down Syndrome -- a chromosome defect (22 children)
Hematologic disorder--like sickle cell disease (12 children)
There is also an association with a previous history of surgery for congenital heart disease (14 patients), suggesting that there may be a genetic defect in blood vessel structure in these patients. But around 50% of our children have no known cause for their moyamoya disease. Our adult patients have usually had no definite cause detected either, but there have been some other associations -- heavy cigarette smoking, the use of birth control pills in young women, and in one patient a long history of cocaine abuse. Cocaine is a powerful constrictor of blood vessels throughout the body, so the association makes some sense.
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Children with moyamoya disease usually come into the hospital or emergency room with symptoms of stroke - weakness on one side of the body, slurred speech or impaired vision. These symptoms may occur and then gradually subside or they may appear suddenly and remain permanent.
Sometimes the disease will cause headaches or seizures (a sudden change in consciousness or behavior, due to changes in brain electrical activity. Seizures may result in loss of consciousness, involuntary movements such as twitching or shaking, abnormal sensations or visual disturbances. Possible causes include epilepsy, trauma, meningitis, tumor, stroke and hydrocephalus).
Brain hemorrhages are a rare occurrence for children with moyamoya disease, although they occur more frequently in young adults with the disease. Most patients have one form of the condition, and it is extremely rare to see the childhood form of the disease evolve later in life to the hemorrhagic form. Symptoms of hemorrhage include:
nausea
vomiting
intense headache
lethargy
vision changes
weakness
numbness on one side or in one part of the body.
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Magnetic resonance imaging (MRI and MRA) and occasionally computed tomography (CT) scans give the initial indications of moyamoya disease. The standard - both for diagnosing the disease and for planning surgery - is a cerebral angiogram. A dye that shows up on x-rays is fed into the carotid artery and a series of x-ray images are taken. Both the narrowed artery and the proliferation of new blood vessels (the "puff of smoke," for which the disease is named) show up in sharp relief. All angiograms carry some risks, which are slightly greater in children with moyamoya, so a highly-skilled angiographic team is essential.
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All patients with moyamoya disease will develop progressive narrowing of their brain blood vessels over time, and we have never seen an exception to this rule after more than three decades of studying these patients. Along with this progressive narrowing of the brain blood vessels, the patient's clinical condition also worsens; this is why we believe that surgery to increase the brain's borderline blood supply is so important for most patients.
The rate of progression is extremely variable from patient to patient, however, with some patients experiencing a rapid course with many strokes over less than a year, and others a slow and desultory progression which may take decades to evolve.
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Our data suggest that the patient's prognosis is very definitely linked to clinical status at the time the diagnosis is first made and when surgical treatment is instituted. Many of the authors who write about moyamoya feel that prognosis is linked to age at diagnosis, but I don't believe that this indicator is a strictly accurate one. For example, if a three year-old child is diagnosed with the disease, we have found that the youngster's ultimate outcome is dependent on whether there have been strokes in both sides of the brain and how badly impaired the child when the diagnosis is first made and treated by surgery. A young child's prognosis seems to be just the same as an older youngster with a similar scan and clinical history, in other words.
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From January 1985 up to March 1, 2008 Dr. Smith and I have operated on 300 patients up to 21 years of age with the disease. There are roughly one-and-a-half as many girls than boys in the group, and the average age at surgery has been around 7 years of age, although patients have been as young as 4 months at the time of operation. Since 1985, all patients have been operated upon using the same surgical technique, "pial synangiosis," with minor modifications over the years.
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This operation is designed to take advantage of the tendency of the brains of children with moyamoya disease to attract new blood vessels from any source that is made available by the surgeon. We make an incision on the scalp to expose a healthy blood vessel (the superficial temporal artery), and then separate it from the tissues around it, keeping blood flowing through it. We open up a window of bone beneath the artery, and then use a microscope to carefully open all of the coverings of the brain right down to the brain surface. The artery is then placed directly onto the brain, and the tissues surrounding its walls are sewn to the brain surface with tiny sutures to keep the artery in contact with the brain. Then the bone window is replaced securely, and the skin incision closed. To operate on one side of the brain takes about 3 to 4 hours; in many patients, we will try to do both sides of the brain on the same day, under the same anesthesia.
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The surgery works by inducing the development of new blood vessels from the donor scalp artery in the area of the area of the synangiosis, which provides an additional source of blood to the underlying brain. These blood vessels develop not only from the scalp artery, which is the major source of new blood, but also from blood vessels which sprout from the coverings of the brain around the skull opening. We are not sure what makes these new blood vessels sprout and grow. Our research work has demonstrated that in the fluid (CSF) surrounding the brain of patients with moyamoya disease there are growth factors which seem to induce the development of the new blood vessels. We have recently reported on research on other substances in the CSF that seem to be elevated in patients with moyamoya, and we hope that eventually it might be possible to enhance the effect of surgery by treating patients before or during surgery with some of these substances.
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The pial synangiosis differs from the so-called "indirect" procedures like EDAS (encephaloduroarteriosynangiosis), EMS (encephalomyosynangiosis), omental transposition or transfer, dural inversion procedures, etc., in that the surgical technique of pial synangiosis uses a wide opening of all of the membranes covering the brain and the fixing of the donor tissue - the scalp artery - directly to the brain surface with tiny sutures to promote more rapid development of arterial ingrowth to nourish the brain. There are numerous technical considerations, advantages and disadvantages of each surgical technique used in this condition, and it is beyond the scope of this FAQ to review them in detail. You should discuss these issues with the surgeon you have consulted, particularly to determine why a particular technique is being recommended and what the surgical results have been with the recommended procedure.
All of these procedures are called "indirect" because they induce new blood vessel growth to the brain over time. Another type of surgery frequently recommended for moyamoya disease has been the direct arterial bypass, or superficial temporal to middle cerebral artery anastomosis ("STA-MCA bypass"). We believe that this technique is a very valuable one to treat certain patients with the condition. In children, however, the diameter of the superficial temporal scalp artery is often less then 0.5 mm., and the diameter of blood vessels on the surface of the brain even less. The amount of new blood that can reach the brain through such a tiny single blood vessel channel is small, and the operation is often technically very difficult. We suspect that the major clinical benefit from such operations comes from the indirect collateralization that eventually reaches the brain through blood vessels growing into the craniotomy area from the scalp and membranes lining the inner part of the skull, similar to that which occurs in the indirect surgical procedures like pial synangiosis. No one surgical technique is the right answer for every patient with the disease, and the patient needs to review the surgical recommendation with the involved surgeon, determine his or her rationale for the recommendation, and inquire about the surgeon's results and experience with the technique recommended.
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Operating on both sides of the brain during the same anesthesia probably reduces the patient's risk of having a stroke with surgery. Most of the patients with moyamoya disease have a very unstable blood supply to their brain that can be reduced very easily. Anesthesia can alter brain blood flow, and in particular, the starting and ending of the anesthesia are critical times when blood flow to the brain can be dramatically changed. It is our belief that reducing the number of anesthetic inductions is probably a good idea for many children with moyamoya. We also monitor the patient's brain waves ("EEG") throughout the procedure using small button electrodes placed over the scalp except in the areas where we are operating, and will on occasion monitor blood flow using a microprobe through a separate skull opening. As we are carrying out the surgery, we can tell whether our anesthetic or surgical techniques are affecting the patient's brain function, and alter our surgical protocol to correct any problems noted with either cerebral blood flow or brain electrical activity. If all is going well after the first side is completed, we will immediately operate on the other side to avoid having to administer another anesthetic on a separate occasion.
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Of the pediatric patients with moyamoya disease operated on as of March 1, 2008, 167 patients have undergone synangiosis on both sides of the head under the same anesthetic and using EEG monitoring. We have had to stop the operation after the first side was completed in 19 patients because of monitoring changes or other technical concerns, and the surgery was completed later safely in all of these. Depending on the patient's status and the reasons for stopping the surgery, the opposite side will be done in a period ranging from several days to three months from following the first operation. In certain patients, we recommend from the start that surgery be carried pit on one side at a time for clinical and/or technical reasons.
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The surgery has been safe, but approximately 4 to 7% of patients will suffer new strokes of varying degrees of severity either at the time of surgery or during the first post-operative month. Most of the patients who suffer strokes had been neurologically unstable before surgery, having frequent strokes or numerous transient ischemic attacks ("TIA's") -- brief periods of neurological dysfunction that are often warning signs of an impending stroke - in the months or weeks before the operation. We believe that such patients are at a higher risk for stroke during a surgical procedure than patients who have had no recent events of this type. For this reason, we usually wait for four to six weeks after any stroke before we proceed with surgery.
Some patients have had new strokes while waiting for surgery that had to be delayed or postponed for various reasons, but because of the way operative complications are reported, these patients are also included in this percentage figure. Most of these patients, by the way, have made excellent recoveries. Two patients have died during the first week after surgery. Both had minimal blood supply to their brain prior to the operation, and we believe that the cause of their fatal massive strokes was a complete blockage of a major artery trunk during the post-operative period. These are the only two deaths in our patients due to stroke, but one patient died of an aneurysm rupture years after surgery.
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Studies to document the extent of preexisting strokes and brain injury need to be obtained -- an MRI of the brain, and if possible, an MRA (MR angiogram, which demonstrates some of the brain blood vessels). Because we need to know flow patterns of blood around the brain, and also to determine whether any blood flow is getting to the brain from arteries outside the brain, all patients need to undergo formal cerebral arteriography (or angiography). This test involves the placement of a small tube ("catheter") through an artery in the groin up to the neck where its tip is placed in the individual blood vessels supplying the brain, x-ray visible dye is injected, and x-ray pictures taken. This part of the diagnostic evaluation is extremely important in planning the surgery and estimating its risk.
In the past, it has been thought that this study was very risky in children with marginal blood flow to the brain, but our radiology group has recently published data regarding arteriogram complications in our own patients, and the complication rate is in fact very low, with only one post-arteriogram stroke and minimal minor problems in what is now a large number of patients. For this reason, if at all possible, we prefer that patients undergo arteriography at The Children's Hospital in Boston, unless there are significant practical reasons why this cannot be done. We may also obtain MRI perfusion studies and occasionally SPECT scans or other cerebral blood flow studies if there are major questions as to whether or not surgery should be performed. These tests are still of theoretical value only. They will demonstrate areas in the brain where blood flow is diminished or unstable, and are occasionally of benefit in planning surgery and in late follow-up.
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Most patients are admitted the night before surgery for intravenous administration of fluids to ensure adequate volume of fluid within the body's blood vessels. The night following the operation, the patient stays in the intensive care unit so that blood pressure and body hydration status can be carefully assessed and maintained, and to make sure that the child's pain management is optimal. The patients are then transferred to our patient floor, where the usual hospital stay is another three to four days. There are no restrictions on airplane travel after surgery, and patients and their families can usually return home one week after the operation. The skin sutures that we use will dissolve on their own and do not require removal later.
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If distance permits, we see patients again in four to six weeks after the procedure. Many patients live too far away for an office visit in Boston to be practicable, and a visit to the patient's local neurologist can serve as a substitute. We ask the patients to undergo a follow-up cerebral arteriogram in one year, in Boston if possible, so that the efficacy of the surgery can be assessed, and a satisfactory baseline for the future established. An MRI and MRA are also carried out at the same time, and plans for appropriate follow-up made with the family.
We ask that all of our patients stay in contact with us on a yearly basis. Follow-up in patients with moyamoya disease is extraordinarily important and forms the basis of our knowledge regarding prognosis and ultimate outcome of the condition. We rely on our patients to help us in this effort.
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Moyamoya symptoms are often brought on or worsened by activities that involve overbreathing (hyperventilation), reduction in blood pressure, or by dehydration. For this reason, it makes sense to lessen stroke risk by restricting the patient's activities after surgery until the new blood vessels begin to grow into the brain. As a basic guideline, patients can usually return to school or regular activities within 2 to 4 weeks of the operation, but cannot participate in gym or sports involving the likelihood of heavy exertion for three months. We permit patients to gradually return to full activities over a 3 to 6 month period, with careful supervision during the early part of this period. Dehydration must be carefully avoided at all times. The area of the surgical incision should be protected against trauma in all sports and activities - for example, by wearing a bicycle helmet when bike-riding, a batting helmet in baseball, etc. - and heading the ball in soccer is not permitted until 6 months following surgery. The bone window that is opened at the time of surgery, by the way, is secured quite tightly after the operation in most patients with a construct of titanium plating. It is very strong and resistant to trauma almost immediately after the operation.
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No one knows whether the form of moyamoya disease prevalent in most children, which causes strokes and TIA's, will be replaced in adulthood by the bleeding form seen in adults. The evidence in our own series suggests that this change in pattern is unlikely, since most adult patients don't have histories of stroke and TIA when they were younger. We do have several patients now, treated surgically in the 1980's and 1990's, who have married and had uncomplicated pregnancies and deliveries. In our own series, we have patients followed for more than 20 years after surgery. There have been only five late strokes in all of these patients, two involving the territory of the brain supplied by arteries that go to the back of the head ("posterior circulation") and three that seemed to involve the frontal lobes. In four of these patients, reoperations were required, because these areas of the brain were not well supplied by the blood flow supplied to the brain by the synangiosis procedures. In general, however, the patients have done exceedingly well over the long-term, with more than two-thirds of the patients leading normal lives with no noticeable neurological deficits.
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In our own series, we have 19 patients (twelve families) where there are either siblings with the disease, or a parent-child syndrome. One operated patient has two children, one of whom has the moyamoya disease. One patient has two other siblings who have the disease. In general, however, a familial or genetically transmitted form of moyamoya disease is rare in the Western Hemisphere. There is no current method of determining before birth whether the developing fetus is likely to have the disease. As of March 2008, we have not recommended that siblings of affected patients be studied by MRI/A or angiography unless there are compelling reasons to do so, such as symptoms that suggest temporary loss of blood flow to the brain, such as stroke, TIAs, seizures, and so on. We have recommended that identical twins be studied, as well as siblings where there is a strong family history of stroke at an early age. Although the average age for the development of symptoms is around 7 years, no one know when the artery narrowing first begins, and it is certainly conceivable that an MRI/A during the first year of life might not detect the potential presence of the disease.
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Certain medications can be very helpful in the treatment of the symptoms caused by moyamoya disease. We believe that the basis for some of the strokes and TIA's in this condition is slowing of blood flow within the narrowed arteries at the base of the brain, the formation of tiny blood clots at these areas, and the subsequent breaking off of these clots into brain blood vessels. Medicines which prevent clot formation, such as aspirin, are essential in moyamoya disease, and we believe that all moyamoya patients need to be on the medication permanently. The small risk of Reye's Syndrome -- an inflammatory swelling of the brain following chicken pox infection that can develop when aspirin is given at the same time as the infection occurs -- is outweighed, we believe, by the consistent long-term benefit of the aspirin administration. In children exposed to chickenpox, however, aspirin should be stopped until the incubation period of the illness has passed. We have also recommended the chicken pox vaccination for children with moyamoya who are taking aspirin, although the vaccination has not been uniformly effective in preventing infection in some of our patients.
Calcium channel blockers such as verapamil are also often prescribed for patients with moyamoya disease. These medications are often helpful in reducing the headache or TIAs that certain patients may suffer during various stages of the illness, but these medications need to be given under the supervision of a neurologist. It is important to understand, however, that no medications prevent the arterial narrowing process from progressing or keep the moyamoya vessels from developing, and we firmly believe that surgery is the mainstay of treatment for the disease. There is no rationale for the administration of steroids or other anti-inflammatory medications in moyamoya, since there is no direct evidence of inflammation in the blood, cerebrospinal fluid, or arteries of affected patients.
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We have had a longstanding interest in trying to learn more about moyamoya disease in the hopes of ultimately developing better treatments for children affected by this disease, including ongoing research initiatives in collaboration with many other scientists and physicians at Children's Hospital, Harvard Medical School, and elsewhere. Current projects include learning about how the blood vessels change in response to the disease and its treatment, how cerebral blood flow is altered in patients with moyamoya, and what factors in the blood or cerebrospinal fluid might be involved in the development and progression of this disease. If you are interested in learning more about these research initiatives, please let us know and we would be glad to discuss them with you in more detail. We welcome contributions to our Moyamoya research fund -- such contributions are becoming more and more necessary in these years of diminishing federal support for medical research.
If you have any questions, please contact us for more information.
R. Michael Scott, M.D.
Edward R. Smith, M.D.
Department of Neurosurgery
The Children's Hospital, Boston
300 Longwood Avenue; Bader 319
Boston, MA 02115
PHONE: 617 355-6011
FAX: 617 730-0906
michael.scott@childrens.harvard.edu
edward.smith@childrens.harvard.edu
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