MRI phenotypes in MS: Longitudinal changes and miRNA signatures.

Area of Science:

• Neurology
• Immunology
• Biomarker Discovery

Background:

• Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system.
• Brain lesions and atrophy are key indicators of MS progression.
• Understanding distinct MS phenotypes is crucial for targeted treatment strategies.

Purpose of the Study:

• To classify and immunologically characterize individuals with MS based on brain lesion and atrophy patterns.
• To identify associated microRNA (miRNA) profiles for each MRI-defined phenotype.
• To investigate the dynamic changes and conversion rates between phenotypes over time.

Main Methods:

• Quantified cerebral T2-hyperintense lesion volume (T2LV) and brain parenchymal fraction (BPF) in a large cohort of MS patients.
• Defined four MRI phenotypes (I-IV) based on T2LV and atrophy levels.
• Assessed serum miRNAs in a separate cohort with stable MRI phenotypes.

Main Results:

• One-third of patients exhibited lesion-atrophy dissociation.
• All phenotypes showed progressive atrophy over 5 years, with Type II exhibiting the most significant BPF reduction.
• Type IV was the only phenotype to worsen in physical disability.
• Phenotypes I and II had higher conversion rates (33% and 46%) compared to III and IV (>90% stability).
• Age and baseline BPF predicted 5-year phenotype conversion.
• Distinct miRNA signatures were identified for each MRI phenotype, with hsa.miR.22.3p, hsa.miR.361.5p, and hsa.miR.345.5p being key differentiators.

Conclusions:

• MRI-defined MS phenotypes demonstrate dynamic conversion patterns, reflecting distinct underlying pathological processes (neurodegeneration vs. inflammation).
• The identified miRNA signatures suggest a role for blood-brain barrier integrity in MS pathogenesis and progression.
• These findings support the partial independence of neurodegeneration and inflammation measures in MS.