Precision medicine in Moyamoya vasculopathy

Moyamoya vasculopathy is a progressive cerebrovascular steno-occlusive disease with variable presentation. As revascularization techniques, antiplatelet therapies, and imaging-based artificial intelligence (AI) diagnostics continue to advance, there is an emerging opportunity to refine patient stratification by integrating genetic profiling, neuroimaging phenotypes, and circulating biomarkers.

The RNF213 locus (particularly p.R4810K) represents the primary susceptibility allele in East Asian cohorts, with secondary contributors including ACTA2 and GUCY1A3 showing incomplete penetrance. Emerging. data reveal dysregulated lipid metabolism, impaired arginine-arginine-nitric oxide (NO) and methionine signaling, heightened oxidative stress, and ferroptotic pathways. Proteomic studies identify disrupted angiogenic and cytoskeletal programs with potential biomarker utility in cerebrospinal fluid and serum. Current diagnostic standards employ MRI/MRA and digital subtraction angiography. Observational data support antiplatelet agents, including cilostazol, in reducing stroke recurrence and mortality. Direct and combined bypass approaches demonstrate superior outcomes in adult hemorrhagic disease, whereas indirect revascularization predominates in pediatric populations. Emerging AI-integrated diagnostic algorithms incorporating imaging and multiomic data exhibit promising diagnostic accuracy.

Systematic integration of genotypic and multiomic profiling with hemodynamic assessment could enhance prognostic precision, optimize surgical timing, and guide antiplatelet selection in Moyamoya. Next step priorities include studying ethnically diverse multicenter registries and rigorous trials evaluating targeted and regenerative therapeutic strategies. Digital subtraction angiography (DSA)-guided diagnosis and individualized revascularization strategies remain the clinical standard.