What is the management and treatment of Moyamoya disease?

Moyamoya Disease: Comprehensive Management

Overview and Definition

Moyamoya disease is a chronic, progressive cerebrovascular disorder characterized by bilateral stenosis or occlusion of the terminal internal carotid arteries with compensatory development of fragile collateral vessels, requiring surgical revascularization for symptomatic patients to prevent devastating strokes. 1, 2

The disease manifests differently across age groups: children predominantly present with recurrent ischemic strokes or TIAs triggered by hyperventilation, crying, coughing, or fever, while adults in Western countries more commonly present with ischemic events, though hemorrhagic presentation occurs more frequently in Asian populations 2, 3.

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Diagnostic Approach

Essential Imaging Requirements

• Cerebral digital subtraction angiography (DSA) remains the gold standard for diagnosis, particularly for unilateral lesions or cases complicated by atherosclerosis 3
• Three angiographic findings are required: (1) stenosis of the distal ICA bifurcation and proximal ACA/MCA, (2) dilated basal collateral arteries ("puff of smoke" appearance), and (3) bilateral abnormalities 3
• Six angiographic stages exist, from Stage 1 (narrowing of carotid forks) to Stage 6 (moyamoya vessels disappear with collateral circulation solely from external carotid arteries) 4

Functional Assessment

• Perfusion imaging (SPECT, PET, xenon-enhanced CT) and cerebrovascular reactivity assessment are critical for treatment planning and identifying patients with compromised cerebral blood flow reserve 1, 5
• TCD may be useful for evaluation and follow-up 1
• Characteristic EEG finding: slowing of background rhythm after cessation of hyperventilation ("rebuild-up" phenomenon) 2

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Medical Management

Acute and Perioperative Management

Meticulous hemodynamic control is paramount to prevent perioperative stroke, which occurs in 4%-18% of surgical cases. 2, 5

Critical Parameters to Maintain:

• Blood pressure: Maintain systolic BP at or above preoperative baseline; slight elevation may be beneficial 1, 6
• Ventilation: Strict normocapnia with end-tidal CO₂ 35-45 mmHg—even mild hypocapnia causes vasoconstriction and worsens ischemia 1, 2, 6
• Volume status: Euvolemia to mild hypervolemia; administer IV fluids at 1.5 times normal maintenance rate for 48-72 hours postoperatively 1, 3
• Temperature: Maintain normothermia (36-37°C) throughout perioperative period 6
• Avoid: Hypotension, hypovolemia, hyperthermia, and hypocarbia 1, 2

Pain and Anxiety Control

• Minimize crying and hyperventilation in children through perioperative sedation, painless wound dressing techniques, and absorbable suture closures, as these lower PaCO₂ and induce ischemia 1
• Use opioids (fentanyl, alfentanil, remifentanil) and appropriate induction agents to maintain adequate MAP 6

Chronic Medical Therapy

Antiplatelet Therapy

• Aspirin may be reasonable for prevention of ischemic events in both surgical and nonsurgical patients with ischemic moyamoya, though evidence is mixed and practice varies globally (Class IIb recommendation) 1, 2
• Cilostazol (a vasodilator) may improve survival, cerebral blood flow, and cognition compared to other antiplatelet drugs, though requires further validation 1, 2
• Anticoagulants like warfarin are NOT recommended due to hemorrhage risk and difficulty maintaining therapeutic levels, particularly in children (Class III recommendation) 1, 2

Vascular Risk Factor Management

• Diabetes is an independent predictor of recurrent ischemic stroke and requires aggressive management 1, 2
• Hypertension and dyslipidemia are risk factors for cerebrovascular events in asymptomatic moyamoya and must be controlled 1, 2
• Atorvastatin may improve collateral circulation after surgical revascularization 1, 2

Headache Management

• Avoid medications that limit vasodilation or enhance vasoconstriction (triptans, ergots, β-blockers, calcium channel blockers) as they may worsen cerebral perfusion 1
• Consider calcitonin gene-related peptide-targeted therapies 1
• Postoperative improvement of headache is common, though new-onset or worsening headache can occur 1

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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, 3

• Even clinically asymptomatic patients with radiographic or functional evidence of impaired cerebral perfusion should be considered surgical candidates 2, 3
• Surgery markedly reduces stroke risk: preoperative stroke rate of 67% drops to 4.3% at 5-year follow-up after revascularization 1, 2
• Meta-analysis of 1,156 pediatric patients showed 87% derived symptomatic benefit from surgical revascularization 1
• Surgery provides 96% probability of remaining stroke-free over 5-year follow-up 1

Surgical Techniques

Direct Bypass

• Superficial temporal artery to middle cerebral artery (STA-MCA) bypass is the most appropriate intervention, particularly for hemorrhagic moyamoya 2, 3
• The Japan Adult Moyamoya trial demonstrated direct bypass reduces rebleeding from 7.6%/year to 2.7%/year (P=0.04) 2, 3
• Direct bypass shows significant efficacy over indirect surgery in reducing future stroke risk (OR 2.03,95% CI 1.32-3.13, P<0.01) 7
• More pronounced angiographic results compared to indirect techniques (OR 0.20,95% CI 0.06-0.67, P<0.01) 7

Indirect Bypass

• Preferred in children due to small vessel size making direct bypass technically difficult 1, 2, 3
• Techniques include pial synangiosis, encephaloduroarteriosynangiosis (EDAS), encephalomyoarteriosynangiosis (EMAS), and multiple burr holes 1, 2
• Relies on angiogenic proliferation over days to weeks 2
• Pial synangiosis demonstrated marked reductions in stroke frequency: 67% had strokes preoperatively, 7.7% perioperatively, and only 3.2% after ≥1 year follow-up 1

Combined Approaches

• Combined direct and indirect anastomoses show improved results in multiple studies 1
• No significant difference found between direct and combined bypass in some analyses (OR 0.76,95% CI 0.51-1.14, P=0.185) 7
• The key factor in successful outcome is surgeon and institutional experience with moyamoya care 1

Surgical Complications

• Perioperative ischemic stroke: 4%-18% of cases 2, 5
• Cerebral hyperperfusion syndrome (CHS): 16.5% overall (3.8% in pediatric patients, 19.9% in adults) 2
• Spontaneous or traumatic subdural hematoma 1
• Intracranial hemorrhage 1
• Seizures in perioperative period 2

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Long-Term Follow-Up and Surveillance

Monitoring Requirements

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, 3

• Patients with unilateral moyamoya should obtain annual imaging with MRA or CTA to assess for disease progression for at least 3-5 years (Class IIb recommendation) 1
• 27% of patients with unilateral disease eventually develop bilateral involvement 1
• Disease progression is more likely in younger patients 1
• Need for reoperation ranges from 1.8% to 18% 1

Periodic Clinical Assessment

• Annual follow-up visits for 3-5 years by clinicians familiar with moyamoya is supported (Class IIb recommendation) 1
• Techniques to measure cerebral perfusion and blood flow reserve may assist in evaluation and follow-up (Class IIb recommendation) 1, 3
• Monitor for neuropsychological sequelae, headache, and epilepsy 5

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Natural History Without Treatment

• 38.4% of 651 moyamoya patients not initially treated with surgery eventually required surgery due to progressive symptoms 1
• Some patients stabilize without intervention, but this often occurs after sustaining debilitating neurological disability 1
• Annual risk of cerebrovascular events approximately 5% in asymptomatic patients 2, 3
• Posterior circulation involvement is associated with worse clinical presentation and higher recurrent hemorrhages 2

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Key Clinical Pitfalls to Avoid

• Never allow hyperventilation: This is the most common preventable cause of perioperative stroke in moyamoya patients 1, 6
• Do not use hypotonic fluids (5% dextrose, Ringer's lactate, gelatins) as they worsen cerebral edema; use only isotonic fluids (0.9% normal saline) 6
• Avoid routine anticoagulation except in highly selected cases with frequent TIAs or multiple infarctions despite antiplatelet therapy and surgery 1
• Do not delay surgery in symptomatic patients: Conservative management carries high stroke risk, and surgery is more effective than medical therapy alone (OR 0.26,95% CI 0.20-0.33, P<0.001) 7
• Ensure surgery is performed at high-volume centers with experienced surgeons, as institutional experience is the key determinant of successful outcomes 1