What is Moyamoya Disease?
Moyamoya disease is a rare disorder that affects the blood vessels that supply blood to the brain. In the course of the disease, the carotid artery, one of the main blood vessels in the skull, is narrowed and can’t provide an adequate supply of blood to the brain. As a result, a disorganized mass of small blood vessels develops at the base of the skull, apparently in an attempt to compensate for the loss of blood flow through the carotid artery. The disease is named for the Japanese word “moyamoya,” meaning “puff of smoke,” referring to the appearance of the mass of small blood vessels.
Typically, the tangle of new blood vessels isn’t able to supply enough blood to the brain. When the brain can’t get enough oxygen and nutrients via the blood, patients suffer from a variety of complications, including strokes, bleeding in the brain, and declines in cognitive function.
Symptoms of Moyamoya Disease
The first symptoms of moyamoya can appear at any age, but they most often initially occur in children between the ages of 5 and 10. Another peak of initial symptoms occurs in adults between the ages of 30 and 50.
The most common initial symptom of the disease in children is an ischemic stroke (sudden decrease in blood flow to the brain caused by a blood vessel blockage) or a transient ischemic attack (TIA), also called a “ministroke.”
Adults also sometimes experience a hemorrhagic stroke, a loss of blood supply to the brain caused by bleeding. It’s not clear why adults are more prone to brain bleeding, but it might be related to the fact that blood pressure is, in general, higher in adults.
Other symptoms related to blood flow include:
- Weakness, numbness, or paralysis in the face or limbs, often on one side of the body
- Problems with speech or understanding others’ speech
- Vision disturbances
- Uncontrollable muscle movements
What Causes Moyamoya Disease?
Scientists do not yet know what causes moyamoya disease. Some cases clearly have an inherited component, but many cases occur in patients with no family history of the disease. Moyamoya also commonly occurs in association with many other disorders, leading some scientists to believe that the blood vessel formation characteristic of moyamoya is the end result of many different disease processes.
Moyamoya can be classified into two different forms, primary and secondary moyamoya disease.
Primary Moyamoya Disease
Primary moyamoya disease occurs on its own and seems to have a strong inherited component.
Secondary Moyamoya Disease
Secondary moyamoya occurs at the same time as another disease, disorder, or condition. Moyamoya is often associated with Down syndrome, sickle cell disease, and neurofibromatosis type 1, but there are many other disorders that seem to be linked to moyamoya.
Secondary moyamoya also sometimes occurs following radiation treatment for some brain tumors.
Unlike primary moyamoya disease, secondary moyamoya sometimes affects the arteries on one side of the brain. In about a third of these cases, however, the disease eventually progresses to include arteries on both sides of the brain.
Risk Factors for Moyamoya Disease
Although the cause of moyamoya is unknown, certain risk factors put an individual at an increased risk of developing the disease:
- Geographic descent. The prevalence of moyamoya is much higher in East Asian countries than it is elsewhere in the world. People of Asian descent have a higher incidence of the disease even when they are living in other countries.
- Family history. People with a family history are as much as 40 times more like to develop moyamoya than are people without a family history.
- Age. Children younger than 15 are at the highest risk of developing the disease.
- Sex. Women are at a higher risk than men.
- Associated medical conditions. Those with disorders or conditions associated with moyamoya have a higher risk.
Is Moyamoya Disease Hereditary?
The prevalence of moyamoya disease in certain populations makes it very likely that the disease, in some cases, has a strong genetic component. The disease was first observed in Japan, and it affects approximately 5 in every 100,000 people in the country. That rate is 10 times higher than the frequency of the disease in Europe. In the United States, people of Asian descent are 4 times more likely to be affected than are those from other parts of the world.
In Japan, as many as 15% of primary moyamoya cases occur in people with a family history of the disease. In the past decade, researchers have identified two gene variations that appear to be associated with moyamoya. The disease seems to follow an autosomal dominant pattern, meaning an individual can develop the disease if they inherit one of the gene variations from only one parent. Sometimes, however, the disease doesn’t develop even when an individual possesses one of the gene variations.
Many cases of moyamoya are not associated with a family history of the disease. In populations outside Asia, these sporadic cases are more common than familial cases. For example, only 4% of cases in North America occur in people with a family history of moyamoya.
How Is Moyamoya Disease Detected?
The most common first symptom of moyamoya disease is a stroke, which can itself be fatal or cause permanent neurological damage. It’s vital to seek immediate medical attention when you notice the first sign of a stroke, even if the symptoms seem to improve or disappear.
The acronym “FAST” can help you remember how to identify the warning signs of a stroke:
- Face. Watch for drooping on one side of the face, such as a drooping eyelid or a lopsided smile.
- Arms. The sufferer may have trouble raising their arms or keeping their raised arms held high.
- Speech. Slurred or garbled speech is a stroke warning sign.
- Time. A quick response to the warning signs is essential. Permanent damage or death can occur within minutes.
If you notice any of the warning signs, call for emergency medical help immediately.
How Is Moyamoya Disease Diagnosed?
Diagnosis of moyamoya disease will begin with a physical exam, personal and family medical histories, and possible laboratory tests to rule out other potential causes of your symptoms.
A definitive diagnosis of moyamoya comes from imaging exams that can show the blood vessel development characteristic of the disease. Imaging scans can also show the state of blood supply to the patient’s brain, which can be used to make decisions about treatment options.
Imaging technologies commonly used to diagnose moyamoya disease include:
- Magnetic resonance imaging (MRI)
- Magnetic resonance angiography (MRA)
- Computerized tomography (CT)
- Positron emission tomography (PET)
- Transcranial Doppler ultrasound
- Cerebral angiogram
An electroencephalogram (EEG), which measures the brain’s electrical activity, may also be used in the diagnostic process.
PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.
How Is Moyamoya Disease Treated?
Treatment for moyamoya disease focuses on improving blood flow to the brain and preventing future strokes or bleeding in the brain. Medications can decrease the risk of stroke and manage other symptoms. In cases where blood flow to the brain is severely limited or is getting substantially worse over time, surgery may be recommended.
Medications commonly used to treat moyamoya and its symptoms include:
- Blood thinners. Aspirin or other blood-thinning medication is often recommended to prevent the formation of small blood clots that can block restricted blood vessels.
- Antiseizure medications. Drugs may be used to control seizures in those individuals who experience them as a result of the disease.
- Calcium channel blockers. These drugs may be used to treat headaches associated with moyamoya. They must be used with caution because they may also decrease blood pressure, which can increase stroke risk.
Surgical interventions can decrease the risk of stroke by creating new routes for blood flow to the brain. The procedures, known as revascularization surgeries, bypass the blood vessels restricted by moyamoya and deliver more blood directly to the brain.
There are two broad types of revascularization surgery:
- Direct revascularization. In this procedure, surgeons connect an artery from the side of the head directly to an artery that delivers blood to the brain, thereby bypassing the carotid artery that has been narrowed by moyamoya. This surgery can be difficult to perform on children because the arteries involved are too small.
- Indirect revascularization. In this procedure, surgeons remove a small section of the blood vessel, muscle, or other tissue from another part of the head and attach the tissue directly to the surface of the brain. Over time, the blood vessel structure of the attached tissue forms new blood vessels in the brain tissue. The new blood vessels increase overall blood flow to the brain and are often effective at preventing future strokes.
How Does Moyamoya Disease Progress?
Moyamoya disease is progressive. Without surgical intervention, most sufferers will continue to experience strokes and/or bleeding in the brain. In the long term, these events are likely to cause mental and physical impairments, and they can be fatal.
How Is Moyamoya Disease Prevented?
There is no way to prevent moyamoya disease, and no drug treatments are available that will reverse or halt the progressive narrowing of the affected arteries. Treatment of the disease is aimed at preventing life-threatening or debilitating strokes or bleeding in the future.
Surgical interventions have proven to be effective in preventing future complications. Many patients, both children, and adults, have experienced long-term relief from strokes after undergoing revascularization procedures.
Moyamoya Disease Caregiver Tips
Moyamoya Disease Brain Science
Scientists continue to search for the cause of moyamoya disease. It seems likely that the disease can arise from a variety of causes. Some areas in which researchers are looking for possible causes include:
- Genetics. Studies have found more than one gene that appears to be associated with moyamoya. It is likely that in some cases, the disease is triggered by the interaction of multiple genetic factors. It’s also possible that different gene variations create a disposition for different forms of the disease.
- Abnormal blood vessel development factors. Studies have found evidence of abnormal levels of certain proteins in the cerebrospinal fluid and blood of moyamoya patients. These proteins play a role in the development of blood vessels and other tissues, and they may be a key to understanding the cause of the disease.
- Infection and immune system factors. Some studies have suggested a connection between moyamoya and certain infections, as well as the immune system’s responses to those infections.
- Radiation. Studies have shown a link between moyamoya and radiation treatments for some types of cancer.
Moyamoya Disease Research
Title: Vessel Wall MR Imaging to Explore Sex-Differences of Intracranial Arterial Wall Changes After Suspected Stroke
Contact: Jae W Song, MD
Hospital of the University of Pennsylvania
Despite advances in stroke care, women continue to face worse outcomes after stroke than men. This disparity in outcomes may be related to biologic sex-differences that manifest in the development and progression of atherosclerosis. Decades of cyclic changes in the hormonal milieu lead to different metabolic profiles in women. These changes may also explain sex-differences in risk factor profiles of atherogenesis and plaque composition. The investigators’ objective is to conduct a cross-sectional MR imaging study of suspected stroke patients to compare the burden and composition of intracranial atherosclerosis and risk factors between men and women. Results from this study are expected to show that sex and sex-specific risk factors should be considered at the outset of stroke evaluation for risk-stratification. In the era of precision medicine, the investigators propose the role of sex should be a starting point in the clinical evaluation of stroke.
Title: Stroke and Cerebrovascular Diseases Registry
Principal investigator: Atif Zafar, MD
Department of Neurology, University of New Mexico
Stroke is the fifth cause of all-cause mortality in the US http://www.cdc.gov/stroke/facts.htm Early identification and treatment not only prevent mortality but also morbidity. Recent advancement in the imaging and diagnostic technique and novel therapeutic modalities has dramatically helped to downgrade stroke from the list of top mortality index in the last 3 years. However, studies determining factors which help predict stroke outcome are still underway and much work needs to be done in this direction. Many factors currently are used to predict stroke outcomes with varying results, for e.g. NIHSS is a good predictor of stroke outcome at 3 months; however, the investigators need better predictors, outcome scales or outcome measures which are easy, reliable and has better specificity and sensitivity.
Acute Brain injury, Transient Ischemic Attack is a special category of a neurological condition wherein there is an impending devastating outcome if workup is not completed in a timely fashion. There is an urgent need to do investigations with high-risk patients to prevent stroke and further mortality and morbidity. The abcd2 score can help us to risk stratify the TIA and to predict the chances of stroke in this specific cohort. However, investigators need better identifiers than already present, to improve the patient changes in secondary prophylaxis of stroke prevention.
There is also some correlation of clinical and biochemical predictors in subarachnoid, cerebral venous thrombosis including Hunt and Hess, SAH score, WFNS-SAH grading among others with variable predictive quality. (Rosen et al; Neurocritical Care; April 2005, Volume 2, Issue 2, pp 110-118: Subarachnoid hemorrhage grading scales).
Title: The Role of Cerebral Hemodynamics in Moyamoya Disease
Principal investigator: Colin Derdeyn, MD
Washington University School of Medicine
Saint Louis, MO
Moyamoya disease is a rare medical disorder that affects the blood vessels (pipes that transport blood) in the brain. In Moyamoya disease, the large blood vessels in the middle of the brain close down over time. The cause of this disorder is unknown. In order to compensate for this narrowing, the body grows new small blood vessels around the blockage. These small branches grow larger (and maybe more numerous) to give the disorder its name. “Moyamoya” is the Japanese term for “puff of smoke” and is used to describe the hazy appearance of these small blood vessels on an angiogram.
Treatment for moyamoya is difficult because so little is known about the disease. Some people never have a stroke while others may have several. It is likely that the strokes are due to insufficient blood flow to the brain. There are surgical procedures that may improve blood flow to the brain, however, these procedures may cause complications and may not always improve the blood flow.
The main purpose of this study is to determine if people with moyamoya disease who have insufficient blood flow are at a higher risk for stroke. In this study, researchers will learn more about the risks and potential benefits of surgical treatment. This information will help decide if there are people at higher risk for stroke who might benefit from surgery or if there are those at a lower risk who might not benefit.
In this study, participants will undergo baseline clinical and laboratory evaluations. Measurements of blood flow to the brain and oxygen use will be obtained using positron emission tomography (PET). Participants will be followed for up to 5 years. PET studies will be conducted one and three years after enrollment to determine if blood flow improves over time. Participants treated with surgery (at the discretion of their treating physicians) will also be followed for perioperative complications, improvement in blood flow, and long term risk of stroke.