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Baseline neurofilament light levels track with brain volume loss in MS



Baseline levels of neurofilament light (NfL) in cerebrospinal fluid (CSF) correlated well with imaging findings in patients with multiple sclerosis (MS) over the course of 10 years, according to a recent study. The correlation between CSF NfL at baseline and the percent of total brain volume change was statistically significant and persisted over time, said Alok Bhan, MD, in an interview at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.

“We found a significant correlation between loss of total brain volume with baseline CSF NfL at the 5- and 10-year follow-up,” reported Dr. Bhan. At the 5-year mark, the correlation coefficient (r) was –0.430 (P = .003); at 10 years, the correlation coefficient was –0.395 (P = .042).

Higher CSF levels of the neuropeptide “thereby predicted steeper loss of brain volume over a 10-year disease course, and baseline CSF NfL could thus be a prognostic factor for later MRI-confirmed progression,” reported Dr. Bhan, of the department of neurology at Stavanger (Norway) University Hospital, and his coinvestigators.

Magnetic resonance imaging, the current standard in tracking MS lesions, has limitations, noted the investigators. “MRI pathology is only revealed after the injury has manifested itself, and as it is commonly being conducted no more frequent[ly] than annually, lesions may have developed up to a year” before they are evident on MRI scans, they said.

Concerns about long-term effects of the gadolinium deposition that results from frequent scans are rising as well, said Dr. Bhan. For these reasons, he said, MRI is an imperfect biomarker for MS progression.

NfL is a polypeptide in neurons that has been proposed as prognostic in MS, but “longitudinal data regarding its prognostic value” are still scarce, said Dr. Bhan.

To help fill that knowledge gap, the study aimed to assess how NfL obtained from CSF at the time of MS diagnosis correlated with MRI-determined loss of brain volume over a period of 10 years.

Participants’ brain atrophy was assessed using MRI performed at baseline and at 5 and 10 years using the same protocol on a 1.5 Tesla scanner. The protocol included dual spin echo T2-weighted imaging, 3-D T1-weighted imaging, and dual spin echo T1-weighted imaging. In addition to obtaining both global and regional changes in brain volume, the investigators also calculated regional volumes for subcortical deep gray matter.

Cerebrospinal fluid obtained from the lumbar puncture performed at the time of baseline assessment was the source for the single NfL value, obtained by use of a commercially available enzyme-linked immunosorbent assay.

Looking at volume loss in specific brain regions, significant correlations were seen between volume loss in the deep gray matter at both 5 and 10 years (r = –0.430 and –0.395; P = .006 and .042, respectively). At 10 years, pallidal nuclei and hippocampal volume losses also correlated significantly with baseline CSF NfL (r = –0.445 and –0.472; P = .020 and .013, respectively).

Attrition was substantial in the cohort, with the initial 44 patients dropping to 39 at 5 years and 27 by 10 years. Of those 44 initial enrollees, 30 were female, and the mean age was about 42 years at baseline. Duration of MS was a median 60 months at the time of enrollment, and the mean Extended Disability Status Scale (EDSS) score was 3.5 at baseline. Most patients (n = 35) had relapsing-remitting MS.

Just 16% of enrollees were on disease-modifying therapy at baseline, but this figure climbed to 52% by the end of the study period, said Dr. Bhan, a trend that in part reflected changes in practice patterns over the study period.

“Our study is yet another report that supports the use of CSF NfL in the routine work-up of newly diagnosed MS,” noted Dr. Bhan and his coauthors. Having a baseline CSF NfL level “would give patients an indication of future disease burden 10 years in advance,” thereby adding to the prognostic toolkit, they said.

Dr. Bhan reported receiving research funding from Novartis Norway, and two other coauthors reported several financial relationships with pharmaceutical companies.

SOURCE: Bhan A et al. ECTRIMS 2019, Abstract P592.

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