What is the management of Moyamoya disease?

Moyamoya Disease: Comprehensive Management Overview

Definition and Pathophysiology

Moyamoya disease is a chronic, progressive cerebrovascular disorder characterized by bilateral stenosis or occlusion of the terminal internal carotid arteries (ICA) and proximal anterior cerebral artery (ACA) and middle cerebral artery (MCA), with compensatory development of fragile collateral vessels appearing as a "puff of smoke" on angiography. 1 Patients with associated conditions (sickle cell disease, neurofibromatosis type 1, Down syndrome) are classified as moyamoya syndrome, while those without identifiable risk factors have moyamoya disease. 1, 2

The disease affects approximately 0.086 per 100,000 children in the United States, with highest prevalence in Japan (3 per 100,000). 1 The RNF213 gene variant (R4810K) is strongly associated with severe, early-onset disease in Asian populations. 3

Clinical Presentation

Pediatric Patients

• Predominantly present with ischemic strokes or transient ischemic attacks (TIAs), often multiple and recurrent, involving the carotid circulation with infarctions in watershed territories. 1, 2
• Ischemic symptoms are characteristically triggered by hyperventilation, crying, coughing, straining, or fever due to vasoconstriction in already compromised vessels. 1, 2
• Electroencephalography may show slowing of background rhythm after cessation of hyperventilation ("rebuild-up" phenomenon). 1, 2

Adult Patients

• Adults more commonly present with intracranial hemorrhage compared to children, though recurrent ischemia still occurs. 1, 2
• Hemorrhagic events carry a rebleeding risk of 7.6% per year without surgical intervention. 1, 2
• Headaches with migraine-like features (>50% with aura) or tension-type characteristics are common. 2

Posterior Circulation Involvement

• Occurs in 41.1% of patients and is associated with worse clinical presentation, higher perioperative complications, and increased recurrent hemorrhages. 2, 4
• Disease progression in posterior circulation occurs in 12.6% of patients at mean 6-year follow-up, with 10-year progression-free survival of only 28.3%. 4

Diagnostic Criteria

Diagnosis requires three angiographic findings: (1) stenosis of the distal ICA bifurcation (C1) and proximal ACA (A1) and MCA (M1), (2) dilated basal collateral arteries, and (3) bilateral abnormalities. 1 Unilateral findings constitute "probable" moyamoya. 1

Imaging Modalities

• Cerebral digital subtraction angiography (DSA) remains the gold standard for diagnosis, particularly for unilateral lesions or cases complicated by atherosclerosis. 1
• Magnetic resonance angiography (MRA) can be sufficient when all typical findings are present bilaterally, allowing omission of invasive angiography. 1
• Perfusion imaging and cerebrovascular reactivity assessment are valuable for treatment planning and follow-up. 1, 3
• Transcranial Doppler (TCD) may be useful in evaluation and follow-up (Class IIb recommendation). 1

Medical Management

Acute Management

Maintain optimal cerebral perfusion through euvolemia to mild hypervolemia, normocapnia (end-tidal CO₂ 35-45 mmHg), normothermia, and avoidance of systemic hypotension. 1, 2 Hypocapnia causes vasoconstriction and ischemia in already compromised vessels. 2

Antiplatelet Therapy

• Aspirin may be considered in individuals with moyamoya after revascularization surgery or in asymptomatic individuals for whom surgery is not anticipated (Class IIb recommendation). 1
• Aspirin is commonly prescribed at 81 mg daily in children (weight-based dosing) to prevent microthrombi at stenosis sites. 2
• Evidence supporting antiplatelet therapy is limited, and practice patterns vary globally, with more common use in Western countries than Asia. 2, 3
• Cilostazol (a vasodilator) may improve survival, cerebral blood flow, and cognition compared to other antiplatelet drugs, though requires further validation. 2

Anticoagulation

Anticoagulants such as warfarin are NOT recommended for most individuals with moyamoya because of the risk of hemorrhage and difficulty maintaining therapeutic levels in children (Class III recommendation). 1, 2 Exception: selected individuals with frequent TIAs or multiple infarctions despite antiplatelet therapy and surgery. 1

Risk Factor Management

• Diabetes is an independent predictor of recurrent ischemic stroke and requires aggressive management. 2
• Hypertension and dyslipidemia are risk factors for cerebrovascular events in asymptomatic moyamoya. 2
• Atorvastatin may improve collateral circulation post-revascularization. 2

Surgical Management

Indications for Surgery

All patients with ongoing ischemic symptoms and/or evidence of compromised cerebral perfusion should undergo revascularization surgery (Class I, Level B recommendation). 2 Even clinically asymptomatic patients with radiographic or functional evidence of impaired cerebral perfusion should be considered surgical candidates. 2

Surgery markedly reduces stroke risk: preoperative stroke rate of 67% drops to 4.3% at 5-year follow-up after revascularization. 2

Surgical Techniques

Direct Bypass

Direct bypass (superficial temporal artery to middle cerebral artery) is the most appropriate intervention, particularly for hemorrhagic moyamoya, reducing rebleeding from 7.6% per year to 2.7% per year (P=0.04). 1, 2 The Japan Adult Moyamoya (JAM) trial demonstrated superiority of direct bypass over medical therapy in preventing rebleeding in hemorrhagic moyamoya. 1

Indirect Bypass

• Indirect procedures (pial synangiosis, encephaloduroarteriosynangiosis, multiple burr holes) rely on angiogenic proliferation over days to weeks. 2
• Preferred in children due to small vessel size making direct bypass technically difficult. 2
• Japanese guidelines state that indirect procedure alone is not considered sufficient for adult patients; direct or combined procedure is necessary. 1

Combined Approach

• European guidelines suggest direct/combined revascularization instead of indirect approach alone. 1
• Combined procedures may be more suitable to prevent further ischemia. 5

Endovascular Treatment

Endovascular treatment with angioplasty or stenting is not advisable due to high complication rates, low success rates, and high restenosis rates. 1 The fragility of moyamoya vessels and negative remodeling contribute to poor outcomes. 1

Perioperative Management

Meticulous perioperative management is critical to minimize the 4%-18% risk of perioperative ischemic events. 2, 3

Key Strategies

• Maintain systemic blood pressure at or above preoperative baseline; slight elevation may be beneficial. 1
• Administer intravenous fluids at 1.5 times normal maintenance rate for 48-72 hours postoperatively. 1
• Manage systemic hypotension, hypovolemia, hyperthermia, and hypocarbia during intraoperative and perioperative periods (Class IIb recommendation). 1
• Minimize anxiety and pain through perioperative sedation, painless wound dressing techniques, and absorbable sutures (Class IIb recommendation). 1 Hyperventilation from crying or pain can lower PaCO₂ and induce ischemia. 1

Complications

• Cerebral hyperperfusion syndrome occurs in 16.5% overall (3.8% in pediatric patients, 19.9% in adults). 2
• Perioperative seizures may occur. 2

Long-Term Follow-Up and Surveillance

Serial follow-up is necessary given 5% annual risk of cerebrovascular events in asymptomatic patients and 20% disease progression rate over mean 6-year follow-up. 2

Monitoring Strategies

• Techniques to measure cerebral perfusion and blood flow reserve may assist in evaluation and follow-up (Class IIb recommendation). 1
• Long-term neuroimaging surveillance is essential. 3
• Evaluation of neuropsychological effects, screening for headache, and management of epilepsy are important aspects of chronic care. 3

Screening Recommendations

In the absence of strong family history or medical conditions predisposing to moyamoya syndrome, there is insufficient evidence to justify screening studies in asymptomatic individuals or relatives (Class III recommendation). 1

Common Pitfalls and Caveats

• Avoid hyperventilation in hospitalized patients: Techniques to minimize anxiety and pain reduce stroke risk from hyperventilation-induced vasoconstriction. 1
• Do not overlook posterior circulation involvement: Associated with worse outcomes and requires careful monitoring. 2, 4
• Recognize triggers: Fever, dehydration, and hyperventilation can precipitate ischemic events. 1, 2
• Perioperative vigilance is paramount: The perioperative period carries significant stroke risk requiring meticulous hemodynamic and respiratory management. 2, 3