What is Moya Moya syndrome and how is it managed?

Moyamoya Syndrome: Diagnosis and Management

Moyamoya syndrome is a progressive cerebrovascular disorder characterized by chronic stenosis of the distal internal carotid arteries and their proximal branches, with formation of abnormal collateral vessels that appear as a "puff of smoke" on angiography, requiring surgical revascularization for optimal management of symptomatic cases to prevent stroke and improve quality of life. 1

Definition and Classification

Moyamoya is classified into two categories:

• Moyamoya Disease (MMD): Idiopathic form with no known associated conditions
• Moyamoya Syndrome (MMS): When the moyamoya pattern occurs in association with other conditions 1

The 2021 Research Committee on Moyamoya Disease Guidelines expanded the definition to include:

• Unilateral disease (previously required bilateral involvement)
• Involvement of proximal middle cerebral artery or anterior cerebral artery 1

Epidemiology

• Prevalence:

  • Japan: 3 per 100,000 (highest worldwide)
  • United States: 0.086 per 100,000 children 1
  • Recent US data shows increasing diagnosis (0.57 per 100,000 people/year) 1

• Demographics:

  • Female predominance (female:male ratio of 1.9:1 to 2.6:1) 1
  • Bimodal age distribution with peaks at age 10 and 30-40 years 1, 2
  • Higher prevalence in Asian populations, particularly Japanese 2
  • Family history present in 11-12% of cases 1

Associated Conditions (Moyamoya Syndrome)

Common conditions associated with moyamoya syndrome include:

• Autoimmune diseases (systemic lupus erythematosus, antiphospholipid syndrome)
• Meningitis
• Brain tumors
• Down syndrome
• Neurofibromatosis type 1
• Head irradiation
• Sickle cell disease 1

Pathophysiology and Genetics

• Progressive stenosis of distal internal carotid arteries and proximal branches
• Development of collateral vessels at the base of the brain
• Genetic component: RNF213 gene on chromosome 17q25-ter identified as a major susceptibility gene, particularly in East Asian populations 2
• Different genetic variants may explain ethnic differences in prevalence 1

Clinical Presentation

The clinical presentation varies by age:

Children

• Predominantly ischemic symptoms (stroke, TIAs)
• Intellectual decline
• Seizures
• Involuntary movements 2
• Symptoms may be triggered by hyperventilation, crying, coughing, straining, or fever 1

Adults

• Higher incidence of hemorrhagic stroke
• Intracerebral hemorrhage often accompanied by intraventricular hemorrhage 2
• Headaches (often migraine-like) 1

Diagnostic Criteria and Imaging

Japanese Research Committee diagnostic guidelines include:

1. Stenosis involving distal ICA bifurcation and proximal portions of ACA and MCA
2. Appearance of dilated basal collateral arteries
3. Bilateral abnormalities (though unilateral disease now accepted in updated criteria) 1

Recommended Imaging Studies:

• Catheter angiography: Gold standard for diagnosis 2
• MRI/MRA: Preferred noninvasive imaging modality 1
  • T2-weighted FLAIR may show "ivy sign" (high signal in sulci indicating slow flow)
  • SWI can demonstrate microhemorrhages
  • Vessel wall imaging helpful for evaluating arteriopathy 1
• CTA: Alternative to MRA for initial diagnosis and follow-up 1
• Perfusion studies: Helpful to assess cerebral blood flow and reserve 1

Management

Medical Management

1. Antiplatelet therapy:

   • Aspirin may be considered in asymptomatic patients or after revascularization 1
   • Limited evidence for efficacy but commonly used 1

2. Avoid medications that cause vasoconstriction or lower blood pressure 1

3. Anticoagulants generally not recommended due to risk of hemorrhage, except in selected cases with frequent TIAs or multiple infarctions 1

Surgical Management

Surgical revascularization is the mainstay of treatment for symptomatic moyamoya and can be categorized as:

1. Direct bypass:

   • Creation of direct extracranial-intracranial anastomosis (typically superficial temporal artery to middle cerebral artery)
   • Provides immediate revascularization
   • More technically demanding with higher risk of complications
   • Japan Adult Moyamoya trial showed benefit for hemorrhagic moyamoya 1

2. Indirect bypass:

   • Apposition of extracranial tissues onto brain surface to form synangiosis
   • Relies on angiogenic proliferation over weeks
   • Technically simpler with fewer immediate complications

3. Combined approaches:

   • Utilizing both direct and indirect techniques

Perioperative Management

Critical considerations during surgery:

• Maintain normocapnia (end-tidal CO2 35-45 mmHg)
• Avoid hypotension and maintain euvolemia to mild hypervolemia
• Set blood pressure goals at or above patient's asymptomatic baseline
• Avoid systolic blood pressure >180 mmHg
• Avoid mannitol 1

Special Considerations

• Children with hyperventilation-induced symptoms: Techniques to minimize anxiety and pain during hospitalizations may reduce stroke risk 1
• Screening: Not recommended for asymptomatic individuals or relatives without strong family history 1
• Monitoring: TCD may be useful for evaluation and follow-up 1

Prognosis

Without treatment, moyamoya is progressive with high risk of recurrent stroke. Approximately 38% of untreated patients eventually require surgery due to progressive symptoms 1. Surgical revascularization significantly reduces stroke risk and improves quality of life when performed in appropriate candidates.