Moyamoya Disease

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 results from 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 many other disorders 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 live in other countries.
• Family history. People with a family history are as much as 40 times more likely to develop moyamoya than 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 specific populations makes it very likely that the condition, in some cases, has a strong genetic component. The disease was first observed in Japan, affecting approximately 5 in every 100,000 people in the country. That rate is ten times higher than the frequency of the disease in Europe. In the United States, people of Asian descent are four 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 condition 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 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 in one side of the face, such as a drooping eyelid or a crooked 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. 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. An imaging scan 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. If blood flow to the brain is severely limited or is getting substantially worse over time, surgery may be recommended.

Medications

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 who experience them due to 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, increasing stroke risk.

Surgery

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 challenging to perform on children because the arteries involved are too small.
• Indirect revascularization. In this procedure, surgeons remove a small section of a blood vessel, muscle, or other tissue from another part of the head and attach the tissue directly to the brain’s surface. Over time, the attached tissue’s blood vessel structure 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 effective at 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 condition can arise from a variety of causes. Some areas in which researchers are looking for possible sources include:

• Genetics. Studies have found more than one gene that appears to be associated with moyamoya. The disease is likely triggered by the interaction of multiple genetic factors in some cases. 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 specific 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

Stage: Recruiting

Contact: Jae W. Song, MD

Hospital of the University of Pennsylvania

Philadelphia, PA 

Despite advances in stroke care, women continue to face worse outcomes after stroke than men. This disparity in results 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

Stage: Recruiting

Principal investigator: Atif Zafar, MD

Department of Neurology, University of New Mexico

Albuquerque, NM

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 prevents mortality but also morbidity. Recent advancements in imaging and diagnostic techniques and novel therapeutic modalities have dramatically helped to downgrade stroke from the top mortality index list in the last 3 years. However, studies determining factors that 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 outcome with varying results, e.g., NIHSS is a good predictor of stroke outcome at 3 months; however, the investigators need better predictors, outcome scales, or outcome measures that 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).