Precision medicine in Moyamoya vasculopathy

Area of Science:

• Neuroscience
• Genetics
• Biomarkers

Background:

• Moyamoya vasculopathy is a progressive cerebrovascular steno-occlusive disease with diverse clinical presentations.
• Advancements in revascularization, antiplatelet therapy, and AI diagnostics offer new avenues for patient management.

Purpose of the Study:

• To refine patient stratification in Moyamoya disease by integrating genetic profiling, neuroimaging phenotypes, and circulating biomarkers.
• To explore emerging diagnostic and therapeutic strategies for Moyamoya vasculopathy.

Main Methods:

• Review of current literature on genetic susceptibility (RNF213, ACTA2, GUCY1A3), molecular pathways (lipid metabolism, nitric oxide signaling, oxidative stress), and proteomic findings.
• Analysis of diagnostic standards including MRI/MRA and digital subtraction angiography (DSA).
• Evaluation of revascularization techniques (direct, indirect, combined bypass) and antiplatelet therapies (e.g., cilostazol).
• Assessment of emerging AI-integrated diagnostic algorithms incorporating multiomic data.

Main Results:

• RNF213 (p.R4810K) is a primary susceptibility allele in East Asian populations; ACTA2 and GUCY1A3 are secondary contributors.
• Dysregulated lipid metabolism, nitric oxide signaling, oxidative stress, and ferroptosis pathways are implicated.
• Proteomic studies reveal disrupted angiogenic and cytoskeletal programs with potential biomarker utility in cerebrospinal fluid and serum.
• Antiplatelet agents like cilostazol show promise in reducing stroke recurrence.
• Direct/combined bypass is superior for adult hemorrhagic Moyamoya, while indirect revascularization is preferred for pediatric cases.
• AI-integrated algorithms show promising diagnostic accuracy.

Conclusions:

• Integrating genotypic and multiomic profiling with hemodynamic assessment can enhance prognostic precision and guide treatment decisions.
• Future research should focus on diverse multicenter registries and trials for targeted/regenerative therapies.
• DSA-guided diagnosis and individualized revascularization remain the clinical standard.