Our objective was to evaluate the prognostic value of serum NfL levels obtained close to the time of MS onset with long-term clinical outcomes. 

In this prospective cohort study, we identified patients with serum collected within 5 years of first MS symptom onset (baseline) with more than 15 years of routine clinical follow-up. Levels of serum NfL were quantified in patients and matched controls using digital immunoassay (SiMoA HD-1 Analyzer, Quanterix). 

Sixty-seven patients had a median follow-up period of 17.4 years (range:15.1-26.1). Median serum NfL levels were 38.5% higher in MS patients compared to the 37 controls (p=0.004). Patients reaching Expanded Disability Status Scale (EDSS) ≥4had 73.6% higher baseline levels compared to the patients with EDSS<4 (p=0.0001). The best cut-off for predicting progression was 7.62pg/mL; patients with NfL >7.62pg/mL had 8.9-times higher risk of developing progressive MS during follow-up (p = 0.034, 95% CI:1.2-68.1). Patients with the highest NfL levels (3^rd-tertile) progressed most rapidly with an EDSS annual rate of 0.16 (p=0.004), remaining significant after adjustment for sex, age, and disease-modifying treatment (p=0.022). 

This study demonstrates that higher levels of serum NfL detected early in MS are associated with poorer long-term clinical outcomes. These patients may benefit from a more aggressive approach to initial treatment.