Serum neurofilament light chain (sNfL) levels may help identify multiple sclerosis (MS) patients with no evidence of disease activity-3 (NEDA-3) who are at higher risk of future disease progression, according to a new study published in Multiple Sclerosis.

The results showed that NEDA-3 patients who had sNfL levels greater than the 90th percentile had numerically higher disease activity in the following year, compared to those below the 90th percentile (57.1% vs 31.1%, respectively). However, these results did not reach significance levels (P =.12).

Patients with higher sNfL levels also showed numerically, but not significantly, higher volume loss during the following year in the thalamus and corpus callosum (−1.39 vs −0.49; −0.13 vs −0.06, respectively), as well as an increase in lateral ventricle volume (4.38 vs 2.44) compared to patients with lower levels of sNfL.

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Using multivariable prediction models, researchers were able to show that sNfL levels were associated with higher odds of disease activity in the following year (P =.031). The sNfL level was also found to be of greater prognostic value for disease activity than NEDA-3 status and the number of combined unique active lesions (CUAL) seen on magnetic resonance imaging.

sNfL levels were also associated with whole-brain (WB) volume loss in the preceding year and had a greater predictive value than NEDA-3 status and the number of CUAL in the same model. The model found that every 10% increase in sNfL level resulted in a 0.021% loss in brain volume.

High levels of sNfL were also associated with WB volume loss in the following year, with a 0.015% loss in WB volume for every 10% increase in sNfL level. The prognostic value of sNfL in the year following WB volume loss was greater than NEDA-3 status but similar to the number of CUAL.

“Monitoring of sNfL may thus assist clinicians in decision making by providing more sensitive prognostic information,” the authors concluded.

The study included 369 sNfL measurements from 155 patients in the Czech Republic. Of these measurements, 220 were in patients with EDA-3 status while 149 were in patients who were NEDA-3 during the preceding year.


Uher T, Havrdova EK, Benkert P, et al. Measurement of neurofilaments improves stratification of future disease activity in early multiple sclerosis. Mult Scler. Published online October 6, 2021. doi:10.1177/13524585211047977