Increased Serum NfL Indicates Ongoing Neuroinflammation, May Predict Neurodegeneration in Early MS

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“Medicine, blood samples in the laboratory”
Serum NfL levels are indicative of ongoing neuroinflammation and may be predictive of neurodegeneration in patients with early MS.

Serum neurofilament light chain (sNfL) levels are indicative of ongoing neuroinflammation and may be predictive of potential neurodegeneration in patients with early multiple sclerosis (MS), according to a study published in Multiple Sclerosis.

Previous studies have depicted a strong relationship between sNfL levels and lesion burden, as well as future development of brain volume loss in patients with MS. However, few have investigated the dynamics of this relationship between sNfL levels and imaging measures in a longitudinal study with follow-up periods at multiple points. Moreover, it is unclear whether sNfL is a marker of ongoing inflammation or of preceding neurodegeneration.

As such, researchers designed a study that included 172 patients with MS who were enrolled in the SET cohort (Study of Early Interferon beta-1a Treatment) after a first demyelinating event, with the goal of determining the longitudinal relationship between sNfL levels and brain imaging markers including lesion burden and brain atrophy.

Levels of sNfL were collected and measured before the initiation of corticosteroid treatment, the day of initiation of IFNb-1a, at 1 month, and then annually during a 36-month period. During a 48-month period, participants underwent brain magnetic resonance imaging scans annually. The predictive role of sNfL levels, compared with lesional pathology, was explored throughout the study.

Investigators noted a strong association between percentage changes of sNfL and lesion burden accumulation as assessed by T1 lesion volume (P <.001), as well as T2 lesion number (P <.001). A similar association was not observed between percentage changes of sNfL and brain volume loss during the 36-month period (P >.1). Early levels of sNfl, especially from baseline to the first month, were associated with delayed brain volume loss after the 48-month study period (P <.001). Higher sNfL levels were observed over follow-up for patients who lost No Evidence of Disease Activity (NEDA-3) status within 36 months vs patients with sustained NEDA-3 status.

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Limitations of the study included a focus on patients with early-stage MS and patients who were treated primarily with interferons.

In this study of early-stage MS, higher levels of sNfL appeared to reflect “neuropathological processes driven mainly by ongoing neuroinflammation as indirectly assessed by the accumulation of lesion burden.” Moreover, they suggest that sNfL levels “have a stronger association with future development of brain atrophy than with actual or previous brain volume loss.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Srpova B, Uher T, Hrnciarova T, et al. Serum neurofilament light chain reflects inflammation-driven neurodegeneration and predicts delayed brain volume loss in early stage of multiple sclerosis [published online January 21, 2020]. Mult Scler. doi: 10.1177/1352458519901272