What is the cause of moyamoya syndrome?

The cause of the syndrome 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 first 100 patients in our own operative series, we have seen the syndrome in association with Asian birth (13 children), neurofibromatosis -- the congenital condition that cases tumors to grow on nerves -- (13), following cranial x-ray or chemotherapy treatments (10 children), Down Syndrome (a chromosome defect -- 9 children), etc. There is also an association with a previous history of surgery for congenital heart disease, suggesting that there may be a genetic defect in the blood vessel wall in these patients. But around 50% of our children have no known cause for their moyamoya syndrome. Our adult patients have usually had no definite cause detected either, but there have been some 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.

Is the disease a progressive one, and will my child's condition worsen with time?

All patients with moyamoya syndrome will develop progressive narrowing of their brain blood vessels over time, and I have never seen an exception to this rule after more than three decades studying and following these patients. Along with this progressive narrowing of the brain blood vessels, the patient's clinical condition will also worsen; this is why 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 and fulminating course over less than a year, and others a slow and desultory progression which may take decades to evolve.

What is my child's prognosis now that the moyamoya syndrome has been diagnosed?

Our data suggest that the patient's prognosis is very definitely linked to clinical status at the time the diagnosis is first made and surgical treatment instituted. Many of the authors who write about moyamoya link prognosis to age at diagnosis, but I don't believe that this indicator is an accurate one. For example, if a three year-old child is diagnosed with the syndrome, 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 is at the time of diagnosis and 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.

How many patients with moyamoya syndrome have you actually taken care of?

Since 1983 and up to December 31, 2001, I have operated on more than 150 children with the syndrome. There are roughly twice as many girls than boys in the group, and the average age at surgery has been a little more than 7 years of age, although patients have been as young as 4 months at the time of operation. Since 1985, all patients (142) have been operated upon using the same surgical technique, "pial synangiosis."

What is actually done during the surgical procedure "pial synangiosis" that you have recommended for my child?

This operation is designed to take advantage of the tendency of the brains of children with moyamoya syndrome to attract new blood vessels from any source that is made available by the surgeon. We make an incision on the scalp over an artery supplying blood only to the skin over the head. We separate this artery 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 it in contact with the brain. Then the bone window is replaced securely, and the skin incision closed. In some patients, we may also place an extra small hole (a "burr hole") in the skull remote from the first incision, and at this hole we also make tiny openings in all of the coverings of the brain before closing the incision. In about 75% of patients, new blood vessels will also grow into the brain through this small opening, and the short additional operating time required to do this extra procedure seems worthwhile. 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.

What is the difference between an operation like a pial synangiosis and the other operations that are recommended for moyamoya syndrome in children?

The pial synangiosis differs from the EDAS (encephaloduroarteriosynangiosis), EMS (encephalomyosynangiosis), omental transposition or transfer, dural inversion procedures, etc., in that the surgical technique of pial synangiosis use 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 and disadvantages to 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 particular technique that has been recommended. All of the above procedures are so-called "indirect revascularization" surgical procedures, in that they induce new blood vessel growth to the brain over time. Another type of surgery frequently recommended for moyamoya syndrome has been the direct arterial bypass, or superficial temporal to middle cerebral artery anastomosis (STA-MCA bypass). I believe that this technique is a very valuable one to treat certain adults 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 impossible. I 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, as occurs in the indirect surgical procedures.

My doctor has recommended a surgical procedure different from the pial synangiosis to treat the condition. Does it matter which procedure is used?

A detailed answer to this question is beyond the scope of this question and answer format, because there are many different surgical procedures, with varying technical considerations and implications in various patient groups. No one surgical technique is the right answer for every patient with the syndrome, 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.

Is it dangerous to operate on both sides of the brain at once?

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 syndrome have a very tenuous 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 essential for the child 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. 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 either to correct a potential problem. 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.

How many patients have undergone bilateral surgery, and what have been the results?

Of the pediatric patients with moyamoya syndrome operated on as of December 31, 2001, 95 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 13 patients for various reasons, 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.

What is the chance of another stroke during or following the operation?

The surgery has been safe, and has a low complication rate, but approximately 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 these patients 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. In four patients, I thought that unstable blood pressure or medication problems were the likely causes of the new post-operative strokes. Some patients have had new strokes while waiting for surgery that had to be delayed or postponed for various reasons; because of the way operative complications are reported, these patients are also included in this group. Most of these patients, by the way, have made excellent recoveries.

Why does the surgery work?

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. That is why even making a small skull opening (the "burr hole" mentioned above) can also help these patients. We are not sure what makes these new blood vessels sprout and grow, and this response is usually not seen in patients having brain surgery for other reasons. Our research work has demonstrated that in the fluid surrounding the brain (CSF) of patients with moyamoya syndrome are growth factors which seem to induce the development of the new blood vessels. Our research work in this area is ongoing, and we have recently reported on the results of some of this work involving growth factors and other substances in the cerebrospinal fluid that seem to be related to a chronic inflammation of some type in these patients. 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.

What diagnostic studies need to be done prior to carrying out the surgery?

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 skull, 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 quite 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. If time is available, we may also obtain MRI perfusion studies and occasionally SPECT scans or other cerebral blood flow studies. These tests are usually safe, but they are still of theoretical value only. They will demonstrate areas in the brain where blood flow is diminished or unstable, and we hope that they will be of benefit in planning surgery and demonstrating its long-term benefit.

How long will the hospital stay be?

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 are taken out by the family physician or pediatrician ten days following the procedure; recently we have begun to use sutures that will dissolve on their own and that do not require removal.

What is the usual follow-up of the operated patients?

If distance permits, I see patients again in four to six weeks after the procedure. Many patients live too far away for this visit to be practicable, and a visit to the patient's local neurologist can serve as a substitute. I ask that all patients return to Boston in one year for follow up studies, which include another cerebral arteriogram and repeats of any pre-op cerebral blood flow studies. The arteriogram is usually the last one that the patient will need to undergo, with subsequent follow-ups consisting of yearly MRI-MRA studies only (which can be carried out locally). I believe that the single follow-up arteriogram is important for a number of reasons. Most importantly, it documents the success of the surgery, and helps to determine if any additional treatment needs to be considered. It serves as a baseline from which to compare subsequent MRI and MRA studies, and also enables us to learn more about the moyamoya evolution in the patient. I ask that all my patients stay in contact with me on a yearly basis. Follow-up in patients with moyamoya syndrome is extraordinarily important and really forms the basis of our knowledge regarding prognosis and ultimate outcome of the condition, and I rely on my patients to help me in this effort.

Does my child's activity need to be restricted after the surgery?

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 restrict the patient's activities after surgery until the new blood vessels begin to grow into the brain to lessen stroke risk. 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. I permit the patients then to gradually return to full activities over a 3 to 6 month period, with careful supervision during the early part of this normalization schedule. 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, 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.

What will happen to a patient with moyamoya syndrome decades from now? Will there be problems with bleeding in the brain or further strokes? Will my daughter ever be able to marry and raise a family?

No one knows whether the form of moyamoya syndrome prevalent in most children, which causes strokes and TIA's, will be replaced in adulthood by the bleeding form seen occasionally in adults. The evidence in my 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. I do have three patients now, treated surgically in the 1980's and 1990's, who have married and had uncomplicated pregnancies and deliveries. In my own series, I have patients followed for up to 17 years after surgery. There have been only five late strokes in this series, 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.

Does moyamoya syndrome run in families? Do my affected child's brothers and sisters need to be checked for the presence of the syndrome?

In my own series, I now have 8 patients (four families) where there are either siblings with the syndrome, or a mother-child syndrome. One woman has two children, one of whom has the moyamoya syndrome. The mother of another patient has also had two other children who have the syndrome. In general, however, a familial or genetically transmitted form of moyamoya syndrome is extremely rare in the Western Hemisphere, and unusual in my own population. There is no current method of determining before birth whether the developing fetus is likely to have the syndrome. As of December 31, 2001, 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 regions of the brain, stroke, seizures, and so on.

My doctor has recommended medical treatment of the syndrome. Are medications effective?

Certain medications can be very helpful in the treatment of the symptoms caused by moyamoya syndrome. I believe that the basis for some of the strokes and TIA's in this condition is sludging of blood 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 downstream blood vessels -- which blocks them off temporarily or permanently. Medicines which prevent this micro-clot formation, such as aspirin, are essential in moyamoya syndrome, and I 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, I believe, by the consistent long-term benefit of the aspirin administration. In children exposed to chickenpox, however, aspirin should probably be stopped until the incubation period of the illness has passed. We have also recommended the chicken pox vaccination for children with moyamoya 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 syndrome. These medications are often helpful in reducing the headache 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 I firmly believe that surgery is the mainstay of treatment for the syndrome. 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 in the patients.

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