Objective:

To evaluate the prognostic utility of neurofilament light chain(NfL) and glial fibrillary acidic protein(GFAP) in serum and CSF from disease onset in predicting long-term clinical outcomes in multiple sclerosis (MS).

Background:

NfL and GFAP in serum and CSF have shown promise as prognostic markers in MS.

Design/Methods:

We identified paired serum and CSF samples from MS patients obtained within 5 years of first MS symptom for whom there was >15 years of routine clinical follow-up. NfL and GFAP were quantified by SiMOA. sNfL was converted to age-adjusted percentiles using normative data (Swiss MS cohort). Clinical outcomes included reaching EDSS≥4 and being diagnosed with clinically progressive MS.

Results:

60 patients met inclusion criteria. Over a mean of 15.8 years(s.d.2.5), 24 patients developed progressive disease and 26 reached EDSS≥4. Serum NfL was strongly correlated to CSF levels (r=0.86, 95% CI 0.78-0.92), while serum GFAP had weaker correlation with CSF (r=0.05, 95% CI 0.29-0.67). Age-adjusted serum NfL (AAsNfL) and CSF GFAP (cGFAP) were the two strongest predictors of reaching EDSS≥4 (AAsNfL AUC 0.72, p=0.0028; cGFAP AUC 0.068 , p=0.017) and clinical progression (AAsNfL AUC 0.66, p=0.036; cGFAP AUC 0.068, p=0.021). The combination of AAsNfL and cGFAP improved prediction of progressive MS compared to either of the markers in isolation. Comparing the patients in the highest versus lowest quintiles for both AAsNfL and cGFAP (i.e. high-high, n=17 vs. low-low, n=13), high-high patients had a 5.5x and 3.6x higher risk of developing EDSS≥4 and progressive MS respectively (p=0.0048 and p=0.012). The combination of AAsNfL and cGFAP quintile groupings improved the prediction of EDSS≥4 (log-rank p=0.0083) or progressive MS (p=0.042) compared to either individual marker.

Conclusions: