Moyamoya Disease - Causes, Symptoms, Risk Factors, Diagnosis and Treatment

What Is Moyamoya Disease?

Moyamoya disease is a sparse vascular disorder in which the carotid arteries in the skull become very narrow and eventually blocked. This drastically reduces the smooth flow of blood to the brain, and the miniature blood vessels present at the base of the brain enlarge to compensate for the shortage of blood supply.

Moyamoya disease can cause a mini-stroke or bleeding within the brain. Additionally, it may affect the regular functioning of the brain and cause delays or disabilities in the cognitive development of the individual.

Where Is Moyamoya Disease Prevalent?

Moyamoya disease generally affects children. Moyamoya disease is documented to prevail worldwide, but it is comparatively common in East Asian countries, such as Korea, Japan, and China. Genetic factors may be the reason for such a geographical concentration of moyamoya disease.

What Are the Causes of Moyamoya Disease?

The precise cause that leads to the development of moyamoya disease remains unknown. Genetic factors in Asian countries have contributed to the cause of moyamoya disease, but more research and analysis need to be done in this aspect. Vascular changes in an individual may also trigger Moyamoya disease. It should also be known that Moyamoya syndrome is usually associated with specific syndromes and conditions, such as Down syndrome, hyperthyroidism, neurofibromatosis type 1, and sickle cell anemia.

What Is the Pathophysiology of Moyamoya Disease?

The exact pathophysiology of moyamoya disease (MMD) is not well understood, but a genetic predisposition is suggested in East Asian populations. Mutations in the BRCC3/MTCP1 and GUCY1A3 genes have been linked to moyamoya syndrome. Affected individuals exhibit concentric and eccentric fibrocellular thickening of the intima in the intracranial portion of the internal carotid artery (ICA). In a study, a high prevalence of type 1 diabetes, autoimmune thyroid disorders, and other autoimmune conditions was observed in those with moyamoya, suggesting a possible autoimmune connection. Chronic brain ischemia from arterial narrowing is thought to cause overexpression of proangiogenic factors like fibroblast growth factor and hepatocyte growth factor, leading to the formation of a fragile network of collateral vessels.

Several types of MMD have been identified, associated with specific chromosomes:

• MYMY1: Chromosome 3p.

• MYMY2: RNF213 gene on chromosome 17q25.

• MYMY3: Chromosome 8q23.

• MYMY4: An X-linked recessive disorder marked by moyamoya disease (MMD), hypergonadotropic hypogonadism, short stature, and facial dysmorphism.

• MYMY5: ACTA2 gene on chromosome 10q23.

• MYMY6 With Achalasia: The GUCY1A3 gene is located on chromosome 4q32.

What Is the Inheritance Pattern of Moyamoya Disease?

Japanese individuals (up to 15 percent) with moyamoya disease have relatives who also have the condition, indicating a familial transmission. However, the specific inheritance pattern is unclear. Studies suggest that moyamoya disease may follow an autosomal dominant pattern, meaning a single copy of the altered gene in each cell can cause the disorder. Despite this, some people with the altered gene do not develop the disease, a phenomenon known as reduced penetrance.

What Are the Signs and Symptoms of Moyamoya Disease?

Moyamoya disease generally occurs in children but is also recorded to have been found in adults. Symptoms of all age groups are not the same, and there is significant variation in age. In children, the initial symptom is mostly an episode of stroke or repeated transient ischemic attacks. Adults also may experience the initial sign of a stroke, but this is in addition to bleeding in the brain called a hemorrhagic stroke sourced from abnormal brain vessels. Mentioned below are some of the clinical manifestations of moyamoya disease:

• Headache.

• Seizures.

• Weakness.

• Numbness.

• Paralysis of the face.

• Paralysis of arm or leg.

• Paralysis of only one side of the body.

• Visual disturbances.

• Difficulties with speech.

• Difficulty in understanding others.

• Cognitive development delays.

• Overall delayed growth.

• Involuntary movements of the body.

• Sudden jerks.

• Tremors.

• Drooping of saliva.

• Redness of the eyes.

• Dizziness.

• Loss of balance.

• Trouble walking on a straight path.

• Sudden onset of confusion.

• Overactive reflexes.

• Stiff muscles.

• Reduced sensation of touch and feel.

• Pins and needles all over the body.

• Fatigue.

• Vertigo.

• Difficulty in coordination.

• Slurred speech.

• Difficulty in swallowing.

• Rapid involuntary eye movements.

• Fever.

What Are the Risk Factors for Moyamoya Disease?

The cause of moyamoya disease is unknown, but some factors may risk a patient and make them more prone to developing moyamoya disease. Mentioned below are some of the risk factors:

• Asian heritage.

• Family history of Moyamoya disease.

• Neurofibromatosis type 1.

• Sickle cell disease.

• Down syndrome.

• Being female (females have a higher incidence rate of moyamoya disease).

What Are the Stages of Moyamoya Disease?

The Suzuki stages of moyamoya disease are described as follows:

• Stage 1: Narrowing of a carotid fork.

  • Angiographic examination shows stenosis only in the terminal portion of the internal carotid artery (ICA).

• Stage 2: Initiation and emergence of basal moyamoya.

  • This reveals stenosis in all terminal branches of the ICA (anterior cerebral artery (ACA) or middle cerebral artery (MCA)) along with the presence of deep moyamoya vessels during angiographic examination.

• Stage 3: Intensification of basal moyamoya.

  • An angiographic examination will show an increase in deep moyamoya vessels. Magnetic resonance angiography (MRA) during this stage displays a ‘puff of smoke’ appearance, with a deflection in the ACA and MCA.

• Stage 4: Minimization of basal moyamoya.

  • Angiographic examination indicates regression of deep moyamoya vessels and the emergence of transdural collaterals, with deflection noted in the posterior cerebral artery (PCA).

• Stage 5: Reduction of moyamoya.

  • Angiographic examination shows further regression of deep moyamoya vessels and the progression of transdural collateral vessels.

• Stage 6: Disappearance of Moyamoya.

  • Angiographic examination reveals the disappearance of deep moyamoya vessels and complete occlusion of the ICA, with the blood supply to the ACA and MCA areas mainly coming from the external carotid artery.

How to Diagnose Moyamoya Disease?

Early diagnosis is crucial to avoid any complications or permanent damage. Specific tests may prove to be efficient diagnostic tools for moyamoya disease.

Mentioned below are some of them:

• Electroencephalogram.

• Neuroimaging.

• Computed tomography or CT.

• Magnetic resonance imaging or MRI.

• Angiography.

• Ultrasound.

When to Consult a Doctor?

Seek immediate medical attention if one experiences any symptoms of a stroke or mini-stroke, even if they are intermittent or seem to disappear.

All the signs and symptoms can easily be triggered by day-to-day activities such as exercise, coughing, crying, and others. Healthcare professionals generally use “FAST” to determine the presence of moyamoya disease, where F stands for face, A stands for arms, S stands for speech, and T stands for time. Questions are asked concerning the face, arms, speech, and time. An example is mentioned below:

• Face - Ask the patient to smile wide. Does one side of the lips droop?

• Arms - Ask the patient to raise both hands. Does one hand drift downward? Or is one hand unable to rise?

• Speech - Ask the patient to keep repeating a simple phrase. Is the speech slurred?

• Time - If any of these are observed, immediate action must be taken.

How to Treat Moyamoya Disease?

The treatment of Moyamoya disease involves symptomatic management. The main aim of the treatment is to improve the flow of blood to the brain and control recurrent episodes of seizures. Prescribing blood thinners may aid in avoiding the formation of blood clots or other forms of arterial blockages, but it also poses the risk of excessive bleeding. Therefore, the healthcare provider generally assesses each patient’s manifestation and recommends medicines. In a few cases, revascularization can be a successful management strategy.

Conclusion:

Moyamoya disease is a chronic, progressive condition. It affects the arteries in the brain by narrowing them, thus blocking the healthy flow of blood. This can eventually lead to ischemic stroke, seizures, and hemorrhagic stroke. Surgical intervention has proven to be one of the best treatment modalities for moyamoya disease. This wards off the possibility of mental decline and multiple strokes. It is always advised to get an early diagnosis, even if there is a single sign or symptom. Early diagnosis and prompt treatment can help the individual live everyday life at ease.