To investigate whether serum levels of neurofilament light protein (NfL) or glial fibrillary acidic protein (GFAP) in people with radiologically isolated syndrome (pwRIS) correlate with imaging measures associated with poor clinical outcomes in people with multiple sclerosis.

Currently, there are no specific, evidence-based recommendations for managing pwRIS. However, imaging and blood biomarkers may offer valuable prognostic insights.

We quantified serum levels of two proteins, NfL and GFAP, in 52 individuals with RIS and 21 healthy controls (HC). We assessed the relationships between these blood biomarkers and magnetic resonance imaging (MRI) disease progression measures at baseline and the 12-month follow-up.

Our findings revealed that pwRIS exhibited significantly higher levels of NfL than HC (median 10.8 vs. 8.5 pg/ml, p=0.03), while GFAP levels did not differ significantly between the two groups. In a cross-sectional analysis, baseline NfL showed correlations with the number of black holes (r=0.4, p=0.01), the number of spinal cord lesions (r=0.33, p=0.03), and the number of central vein sign positive (CVS+) lesions (r=0.31, p=0.05). Baseline GFAP correlated with the number of black holes (r=0.46, p=0.002), the number of infratentorial lesions (r=0.35, p=0.02), and the number of CVS+ lesions (r=0.33, p=0.03). In the longitudinal analysis, baseline GFAP correlated with the development of white matter lesions (WML, r=0.5, p=0.02), black holes (r=0.4, p=0.045), and CVS+ lesions (r=0.4, p=0.049) at 12-month follow-up. Baseline NfL did not correlate significantly with MRI measures at 12-month follow-up.

These results suggest that in pwRIS, sGFAP may be a prognostic marker for the development of WMLs, black holes, and CVS+ lesions. Of particular interest is the association of high sGFAP with future CVS+ lesions, as these lesions are believed to be more specific for MS than WMLs without the CVS. Prospective validation is currently underway to confirm the prognostic value of sGFAP in pwRIS.