Monitoring Multiple Sclerosis: The Role of Serum Neurofilament Light Chain Levels

The biomarker serum neurofilament light chain (sNfL) reflects neuroaxonal damage and is associated with disease activity in multiple sclerosis (MS). However, the precise temporal relationship between sNfL levels and radiologic disease activity, specifically gadolinium-enhancing (Gd+) lesions on MRI, has remained an open question.

A recent study published in Neurology aimed to bridge this knowledge gap by examining the fluctuations in sNfL levels in relation to radiologic findings during a 24-week natalizumab treatment interruption period.

Study Design and Methods

The study was based on data from the exploratory, randomized, partially placebo-controlled RESTORE trial (NCT01071083), which evaluated the impact of natalizumab discontinuation in MS patients.

Participants had been on natalizumab for at least 12 months before being randomized to either continue or suspend therapy. Researchers conducted MRI scans and collected blood samples at four-week intervals up to week 28, with a final assessment at week 52.

In this study, the primary objective was to analyze the correlation between changes in sNfL levels and the appearance of Gd+ lesions, utilizing longitudinal statistical modeling.

Results

Of the 175 participants initially enrolled, 166 had available serum samples for sNfL analysis. Findings showed that sNfL levels were higher in patients with gadolinium-enhancing (Gd+) lesions and there was a positive correlation between sNfL increases and number of lesions. However, 71 percent of those with Gd+ lesions did not exceed the sNfL threshold.

Furthermore, 80 percent of sNfL elevations occurred after the first Gd+ lesions appeared, with a median delay of 8-9 weeks, and remained elevated after the resolution of lesions. Still, even some patients with a high number of lesions had minimal or no sNfL elevation.

This has meaningful implications for clinical practice, particularly in treatment decision-making. The results suggest that sNfL has limited sensitivity as a standalone biomarker for MS activity and that sNfL may be better at ruling disease activity when elevated but not reliable for ruling whether disease activity is stagnant. The delayed sNfL release after Gd+ lesion development is important for healthcare professionals to consider during clinical practice.

Conclusions

While sNfL can provide insight into underlying neuroaxonal damage, its delayed rise and limited sensitivity question sNfl’s use as a standalone marker for MS disease activity.

However, in combination with clinical and radiologic assessments, sNfL may help detect subclinical activity and guide treatment decisions, especially in settings where frequent MRI is impractical.

Reference

Fox RJ, Cree BAC, de Sèze J, et al. Temporal Relationship Between Serum Neurofilament Light Chain and Radiologic Disease Activity in Patients With Multiple Sclerosis. Neurology. 2024;102(9):e209357. doi:10.1212/WNL.0000000000209357