#ACTRIMS2022 – Blood NfL Levels May Help Quantify Relapse Severity

Measuring levels of the neurofilament light chain (NfL) protein in blood may be a way to “quantify” relapse severity and predict future disability in people with relapsing-remitting multiple sclerosis (RRMS).

“Higher [blood] NfL levels during periods of active inflammation predicted more [brain] atrophy,” researchers wrote in an abstract titled “Serum neurofilament as a predictor of 10-year gray matter atrophy and clinical disability in multiple sclerosis – a longitudinal study.”

The findings were shared at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2022 by Ingrid Anne Lie, a PhD student in the department of clinical medicine at the University of Bergen, in Norway.

RRMS is characterized by relapses — times when new symptoms suddenly appear, or old symptoms worsen — interspersed with periods of less severe symptoms called remissions. Relapses are generally thought to be driven by new inflammation in the nervous system.

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Neurofilament light chain, called NfL, is a structural protein in nerve cells that gets released into the blood when these cells are damaged. NfL levels in serum, the non-cellular part of blood, are known to spike around the time of disease relapses, but the prognostic implications of this biomarker remain incompletely understood.

“Our aim for this study was to investigate how periods of acute disease activity compare to periods of remission in early RRMS in predicting clinical disability and grey matter atrophy measures after 10 years,” Lie said. Of note, grey matter is the portion of brain tissue containing the bodies of neurons, or nerve cells.

In the study, the researchers examined data from a clinical trial called OFAMS, which was conducted in the mid-2000s. A total of 92 people with early RRMS were included in the study, of whom 78 were followed for up to 10 years and had available NfL measurements collected over the first two years. At the end of follow-up, the median age was 50, and median disease duration was about 14 years.

“We looked at NfL levels during the OFAMS trial, and their association with MRI and clinical measures after 10 years,” Lie said.

For each patient, the researchers calculated the mean overall NfL level from all available measurements, as well as the “mean inflammatory level,” referring to samples taken close to the appearance of a new inflammatory brain lesion on MRI scans. A “mean non-inflammatory level,” including all samples collected at least two months after or two weeks before the appearance of a new lesion, also was calculated.

The team then used statistical analyses to look for associations between NfL levels and outcomes later on.

Results showed that a higher mean overall NfL over the first two years was significantly associated with lower grey matter volume and more brain lesions after 10 years.

Higher mean inflammatory NfL levels showed similar associations, and also were significantly associated with higher (worse) scores on the nine hole peg test, a measure of manual dexterity, after 10 years. But notably, non-inflammatory NfL levels showed no such correlation.

“We found that higher NfL levels during periods of early active inflammation, but probably not during remission, in patients with early RRMS predicted grey matter atrophy and clinical disability after 10 years,” Lie concluded.

Given that NfL levels only were significantly predictive of clinical measures during disease relapses, Lie proposed that measuring levels of the protein “may be a way to quantify the severity of the relapse, and indicate the risk of permanent or future disability.”

Unexpectedly, high inflammatory NfL levels were associated with a lower change in the expanded disability status scale (EDSS) — that is, less substantial accumulation of disability — from years 2–10. Lie noted that this finding is likely influenced by the fact that there were relatively few patients in this analysis, and EDSS is not very sensitive to small changes in disability. Differences among clinicians rating EDSS over time also may have contributed.

This study is limited by its small size, Lie said. She also noted that therapeutic interventions “varied considerably” between and among patients over follow-up, which likely affected the results.

Editor’s note: The Multiple Sclerosis News Today team is providing in-depth coverage of the ACTRIMS Forum 2022 Feb. 24–26. Go here to see the latest stories from the conference.