High NfL levels seen in children near times of disease activity: Study

Blood levels of the nerve damage marker NfL seem to spike to very high levels around times of disease activity in children with multiple sclerosis (MS), a new study reports.

The findings support using NfL as a biomarker of disease activity, in the form of relapses or lesions, in children with the disease.

The study, “High serum neurofilament levels are observed close to disease activity events in pediatric-onset MS and MOG antibody-associated diseases,” was published in Multiple Sclerosis and Related Disorders.

NfL, or neurofilament light chain, is a structural protein inside nerve fibers. When nerves are damaged, NfL gets released into blood serum (the non-cell part) and other bodily fluids, serving as a general marker of nerve damage.

Studies in adults with MS have suggested serum NfL may be a useful biomarker of disease activity. Less is known about its utility as a biomarker in children, however.

A research team led by scientists at the University of California, San Francisco evaluated how serum NfL (sNfL) varied with disease activity in children with pediatric-onset MS (POMS) at their clinic.

“Although sNfL associations in adult-onset MS studies are promising, the temporal dynamics of increased sNfL levels following overt disease activity in POMS … has not been determined. Such information could advance our understanding of sNfL levels over time and may allow its use as a disease activity biomarker,” the researchers wrote.

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The study included data on 142 children with POMS, as well as 201 children without a neurological disease. The team also evaluated data for 20 children with another autoimmune neurological disorder called myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).

At the initial evaluation, average sNfL levels were significantly higher in the children with POMS or MOGAD than those without a neurological disease.

Over time, the researchers noted high levels of sNfL (100 picograms per milliliter or higher) were only seen in children with POMS at times close to new disease activity, including a relapse, new or enlarging lesions on MRI scans, or a new lesion with active inflammatory activity. The levels tended to decrease as time passed following a relapse or new MRI activity, however.

“High sNfL levels were only observed within four months of disease onset or a clinical relapse in POMS,” the researchers wrote, adding the MOGAD cases showed “a similar pattern.”

While high sNfL levels were associated with relapse activity, some children with POMS had relapses without sNfL levels higher than the cutoff.

Children with high or low sNfL levels near a relapse were comparable for factors like disease duration, demographics, and treatments, analyses showed. Children with high sNfL levels near a relapse tended to have more severe disability scores at the time of sampling, however.

The researchers said that the results “further reinforce the association of sNfL level with disease activity events and neuronal injury in demyelinating disorders” such as MS and MOGAD. “Our findings support [serum NfL] as a biomarker of disease activity in pediatric demyelinating disorders,” they wrote.