What are the diagnostic criteria for moyamoya disease?

Diagnostic Criteria for Moyamoya Disease

Moyamoya disease (MMD) is diagnosed using digital subtraction angiography as the gold standard, requiring bilateral stenosis or occlusion of the terminal internal carotid arteries with characteristic moyamoya collateral vessels, though MRI/MRA can establish diagnosis when all typical findings are present. 1

Core Diagnostic Requirements

Angiographic Criteria (Gold Standard)

Digital subtraction angiography remains the definitive diagnostic modality and must demonstrate: 1

• Stenosis or occlusion at the terminal portion of the intracranial internal carotid artery (centered on the ICA terminus and extending to proximal anterior cerebral artery, middle cerebral artery, and posterior cerebral artery) 1
• Moyamoya vessels (abnormal vascular networks) visible in the arterial phase in the vicinity of the stenotic/occlusive lesions 1
• Both unilateral and bilateral involvement satisfy diagnostic criteria according to the 2015 revision of Japanese criteria, which abolished the previous distinction between "definite" (bilateral) and "probable" (unilateral) cases 1

Alternative MRI/MRA Criteria

MRI/MRA using ≥1.5 Tesla scanners can establish diagnosis without invasive angiography only when ALL of the following are present: 1, 2

• Stenosis/occlusion of the terminal portion of intracranial internal carotid artery 1
• Decreased outer diameter of the terminal ICA and horizontal portion of MCA bilaterally on heavy T2-weighted MRI 1
• At least 2 visible flow voids (unilateral or bilateral) at the basal ganglia or periventricular white matter representing abnormal vascular networks on time-of-flight MRA 1, 2

Critical caveat: MRA misses moyamoya vessels in approximately 17% of cases, so when moyamoya vessels are not clearly visualized on MRA, proceed to digital subtraction angiography 2. MRA is also less reliable for detecting smaller vessel occlusions 1, 2.

Pathognomonic MRI Findings

The combination of diminished flow voids in the ICA, MCA, and ACA coupled with abnormally prominent flow voids from basal ganglia and thalamic collateral vessels is virtually diagnostic of moyamoya syndrome 1, 2. This finding eliminates the need for invasive angiography in typical cases 1.

Essential Exclusion Criteria

MMD is fundamentally an exclusion diagnosis - you must rule out all causes of moyamoya syndrome (MMS) before confirming MMD: 1

Conditions That Define Moyamoya Syndrome (Not Disease):

• Autoimmune diseases: systemic lupus erythematosus, antiphospholipid syndrome, polyarteritis nodosa, Sjögren syndrome 1
• Prior cranial radiation (2-4.3% develop moyamoya vasculopathy; up to 60% in neurofibromatosis type 1 patients receiving radiation) 1
• Genetic syndromes: Down syndrome, neurofibromatosis type 1 1
• Infections: leptospirosis, HIV 1
• Sickle cell disease 1
• Meningitis, brain tumors 1

Note: Atherosclerosis and hyperthyroidism were recently excluded from the MMS list according to the 2021 Japanese criteria revision 1.

Supplementary Imaging Findings

Structural Brain Imaging

• Acute infarcts are best visualized with diffusion-weighted MRI 1
• Chronic infarcts appear in cortical watershed zones, basal ganglia, deep white matter, or periventricular regions 1
• Fluid-attenuated inversion recovery sequences may show linear high signal following sulcal patterns ("Ivy sign"), representing slow flow in poorly perfused cortical circulation 1

Hemodynamic Assessment

Cerebral perfusion studies identify hemodynamic impairment, which predicts stroke risk: 1, 2

• MRI with arterial spin labeling 1, 2
• Brain CT perfusion 1, 2
• Acetazolamide-challenged SPECT or PET 1, 2
• Transcranial Doppler (useful for following blood flow velocities over time) 1

These techniques detect regional perfusion instability and cerebrovascular reserve capacity, though they are poorly validated and variably used depending on local facilities 1.

Disease Staging

The Suzuki classification (Stages 1-6) characterizes angiographic progression but has limited practical application for individual cases based on single examinations without serial temporal evaluations 1. Stage 1 shows narrowing of carotid forks, progressing to Stage 6 where moyamoya vessels disappear and collateral circulation derives solely from external carotid arteries 3.

Clinical Presentation Patterns

While not diagnostic criteria per se, recognizing clinical presentations helps trigger appropriate diagnostic workup: 1

• Ischemic events (transient ischemic attacks, strokes in carotid branches and watershed territories) - triggered by fever, dehydration, physical activity, hyperventilation, hypercoagulable states 1
• Hemorrhagic events (intracerebral or intraventricular, occasionally subarachnoid) from rupture of deep neovascularization collaterals and pseudoaneurysms 1
• Headaches (migraine most common, also tension-type, hemiplegic migraine, cluster) 1
• Neurocognitive impairment from chronic cerebral hypoperfusion 1
• Secondary movement disorders 1

Genetic Testing Considerations

Genetic testing has limited diagnostic utility due to low penetrance and population-specific variants: 1

• RNF213 c.14576G>A polymorphism is found in 95% of familial and 79% of sporadic East Asian cases but shows distinct variants in non-East Asian populations 4, 5
• Genetic testing is not required for diagnosis but may be considered for genetic counseling in familial cases 1
• Patients with Noonan-like symptoms warrant PTPN11 and CBL screening; those with neurofibromatosis type 1 manifestations need NF-1 gene testing 1

Common Diagnostic Pitfalls

• Do not overlook unilateral disease - approximately 20-27% of patients with unilateral moyamoya eventually develop bilateral involvement, and unilateral cases satisfy diagnostic criteria 1, 2
• Do not rely solely on CT scan - it is inadequate to confirm diagnosis but can identify complications like hemorrhage and infarcts 2
• Do not mistake normal flow voids for pathology - the key diagnostic finding is diminished flow voids in major vessels combined with prominent collateral flow voids in basal ganglia/thalamus 2
• Do not skip screening in high-risk populations - consider screening first-degree relatives when multiple family members are affected, and patients with neurofibromatosis type 1, Down syndrome, and sickle cell disease 1