Moyamoya disease

Overview

Moyamoya disease is a rare, progressive cerebrovascular disorder characterized by the narrowing or occlusion of the internal carotid arteries and their main branches at the base of the brain. As the major arteries constrict, the brain attempts to compensate by creating a network of tiny, fragile blood vessels to bypass the blockage. These collateral vessels appear hazy on angiographic imaging, resembling a “puff of smoke,” which is what “moyamoya” means in Japanese.

The disease can lead to repeated strokes, transient ischemic attacks (TIAs or “mini-strokes”), headaches, cognitive decline, and seizures. Moyamoya is most commonly diagnosed in children around age 5 and in adults in their 30s or 40s, with higher prevalence in East Asian populations, particularly in Japan, Korea, and China. However, it occurs worldwide and can affect individuals of all ethnic backgrounds.

Causes

The exact cause of Moyamoya disease is not fully understood. It is considered a chronic, non-atherosclerotic, non-inflammatory, and idiopathic arteriopathy, but genetic and environmental factors are believed to contribute to its development.

Possible Causes and Risk Factors

• Genetic mutations: Mutations in the RNF213 gene have been associated with familial and sporadic cases, particularly in East Asians.

• Familial inheritance: About 10–15% of cases are familial, indicating a genetic predisposition.

• Associated conditions: Moyamoya syndrome (a secondary form) can occur in association with other disorders, such as:

  • Neurofibromatosis type 1

  • Sickle cell disease

  • Graves' disease

  • Radiation therapy to the head and neck

When Moyamoya arises independently, it is termed "Moyamoya disease." When it is associated with other conditions, it is often referred to as "Moyamoya syndrome."

Symptoms

Symptoms of Moyamoya disease result from reduced blood flow to the brain and the rupture of fragile collateral vessels. The presentation can differ by age group, with children more likely to experience ischemic symptoms and adults more prone to hemorrhagic strokes.

Common Symptoms in Children

• Transient ischemic attacks (TIAs)

• Ischemic stroke

• Seizures

• Weakness or numbness on one side of the body

• Speech or vision disturbances

• Involuntary movements (chorea or dystonia)

Common Symptoms in Adults

• Hemorrhagic stroke (bleeding in the brain)

• Severe headaches

• Memory problems or cognitive decline

• Seizures

• Motor deficits or paralysis

Symptoms may be triggered or worsened by hyperventilation, stress, crying, or fever, especially in children. The progression of the disease can be variable and unpredictable, with increasing risk of permanent neurological damage over time.

Diagnosis

Diagnosis of Moyamoya disease relies on a combination of clinical evaluation, neuroimaging, and exclusion of other potential causes of arterial stenosis. Early diagnosis is critical to prevent strokes and long-term neurological deficits.

Imaging Studies

• Magnetic Resonance Imaging (MRI): Detects past strokes or ischemic areas in the brain.

• Magnetic Resonance Angiography (MRA): Non-invasive way to view blood vessel narrowing and collateral circulation.

• Cerebral Angiography: The gold standard for diagnosis; reveals stenosis of the internal carotid arteries and the characteristic “puff of smoke” appearance from collateral vessels.

Additional Tests

• CT Angiography (CTA): Alternative imaging modality to visualize blood vessels.

• Single-photon emission computed tomography (SPECT) or PET scan: To assess cerebral blood flow and perfusion.

• Electroencephalogram (EEG): May be used in children with seizures.

• Genetic testing: In familial cases, especially for RNF213 mutation.

Diagnostic criteria require narrowing or occlusion of the terminal portion of the internal carotid arteries and the presence of abnormal vascular networks, typically without signs of inflammation or atherosclerosis.

Treatment

Treatment for Moyamoya disease focuses on preventing strokes and improving cerebral blood flow. While medications may help manage symptoms and reduce stroke risk, surgical intervention is the most effective approach to restoring blood supply to the brain.

1. Surgical Treatment

• Direct revascularization: Involves connecting a branch of an external artery (e.g., superficial temporal artery) directly to an internal cerebral artery (e.g., middle cerebral artery). This provides immediate increased blood flow.

• Indirect revascularization: Involves placing vascularized tissue (e.g., dura mater or muscle) onto the brain surface to stimulate new vessel growth over time (e.g., encephaloduroarteriosynangiosis, EDAS).

• Combined procedures: Utilize both direct and indirect techniques for maximum benefit.

2. Medical Management

• Antiplatelet therapy: Such as aspirin, to reduce the risk of clot formation and ischemic stroke.

• Antiepileptic drugs: For seizure control in affected patients.

• Control of risk factors: Managing hypertension, diabetes, and avoiding smoking.

3. Supportive Care

• Rehabilitation therapy after stroke to regain motor or speech functions.

• Speech, physical, and occupational therapy as needed.

Surgical treatment significantly reduces the risk of recurrent strokes and improves long-term outcomes. Early intervention is associated with better prognosis, especially in children.

Prognosis

The prognosis of Moyamoya disease varies based on the age of onset, severity of symptoms, and the timeliness of treatment. Without intervention, the disease is progressive and can lead to recurrent strokes, cognitive impairment, and disability.

Prognostic Factors

• Early diagnosis and prompt surgical revascularization are associated with improved outcomes.

• Children generally have better long-term outcomes with early surgery.

• Delayed treatment or lack of surgical intervention increases the risk of irreversible neurological damage.

With appropriate treatment, many individuals with Moyamoya disease can lead full and active lives. Lifelong follow-up is recommended to monitor for progression and manage any complications. Advances in imaging and surgical techniques continue to improve the outlook for patients with this rare condition.