Is It Necessary to Distinguish Moyamoya Disease and Syndrome?
Yes, it is absolutely necessary to distinguish between moyamoya disease (MMD) and moyamoya syndrome (MMS) because they differ fundamentally in their underlying causes, which directly impacts treatment approaches—specifically, MMS requires tailored therapeutic management of the associated underlying condition in addition to addressing the cerebrovascular pathology. 1
Key Distinction: Idiopathic vs. Secondary
The critical difference lies in etiology:
Moyamoya Disease (MMD): Idiopathic cerebrovascular stenotic-occlusive condition with progressive stenosis of the terminal internal carotid artery and abnormal collateral vessel formation, occurring in the absence of other identifiable causes. 1
Moyamoya Syndrome (MMS): The same characteristic angiographic vascular pattern, but occurring secondary to specific associated conditions such as autoimmune diseases (SLE, antiphospholipid syndrome, polyarteritis nodosa, Sjögren syndrome), meningitis, brain tumors, Down syndrome, neurofibromatosis type 1, head irradiation, and sickle cell disease. 1
Why This Distinction Matters Clinically
Treatment Implications
Despite sharing identical angiographic appearances and similar stroke risks (both ischemic and hemorrhagic), MMS differs from MMD in requiring tailored therapeutic approaches based on the associated underlying conditions. 1 For example:
- A patient with MMS secondary to SLE requires immunosuppressive therapy in addition to cerebrovascular management 1
- MMS from sickle cell disease necessitates hematologic management 1
- MMS from autoimmune conditions may respond to disease-specific treatments that could potentially modify the vascular pathology 1
Prognostic Differences
The natural history and response to revascularization surgery may differ between MMD and MMS, though both conditions carry significant morbidity and mortality risk. 1 Understanding whether moyamoya is primary or secondary helps predict disease behavior and surgical outcomes.
Genetic Considerations
MMD has strong genetic associations, particularly with RNF213 gene mutations (especially the R4810K variant in East Asian populations), with up to 12% having positive family history. 1 This genetic component is typically absent in MMS, making the distinction important for genetic counseling and family screening.
Diagnostic Approach
When evaluating a patient with characteristic moyamoya angiographic findings:
- Screen systematically for associated conditions listed in the MMS criteria to determine if the vasculopathy is primary or secondary 1
- Note that atherosclerosis and hyperthyroidism were excluded from the 2021 Japanese Research Committee criteria for MMS-associated conditions, though international consensus is still evolving 1
- Perform comprehensive workup including autoimmune serologies, assessment for genetic syndromes, and history of radiation exposure or meningitis 1
Current Limitations
A significant challenge exists: no data exist on the sensitivity and specificity of diagnostic codes in differentiating MMD from MMS, limiting the ability to distinguish their respective epidemiological characteristics. 1 This represents a critical gap in our understanding of these conditions.
Important Caveat
No specific treatment recommendations for MMS have been published by the European Stroke Organization (ESO), Japanese guidelines, or the American Heart Association (AHA) statement, highlighting an urgent need for research specifically addressing MMS management. 1 However, the fundamental principle remains: treat the underlying associated condition while managing the cerebrovascular pathology.