High serum neurofilament light chain levels correlate with brain atrophy and physical disability in multiple sclerosis

Abstract

Background and purpose Serum neurofilament light chain (sNfL) is a promising biomarker of neuroaxonal damage in persons with multiple sclerosis (pwMS). In cross‐sectional studies, sNfL has been associated with disease activity and brain magnetic resonance imaging (MRI) changes; however, it is still unclear to what extent in particular high sNfL levels impact on subsequent disease evolution. Methods sNfL was quantified by an ultrasensitive single molecule array (Simoa) in 199 pwMS (median age = 34.2 years, 64.3% female) and 49 controls. All pwMS underwent 3‐T MRI to assess global and compartmental normalized brain volumes, T2‐lesion load, and cortical mean thickness. Follow‐up data and serum samples were available in 144 pwMS (median follow‐up time = 3.8 years). Linear and binary logistic models were used to estimate the independent contribution of sNfL for changes in MRI and Expanded Disability Status Scale (EDSS). Age‐corrected sNfL z‐scores from a normative database of healthy controls were used for sensitivity analyses. Results High sNfL levels at baseline were associated with atrophy measures of the whole brain (standardized beta coefficient βj = −0.352, p < 0.001), white matter (βj = −0.229, p = 0.007), thalamus (βj = −0.372, p = 0.004), and putamen (βj = −1.687, p = 0.012). pwMS with high levels of sNfL at baseline and follow‐up had a greater risk of EDSS worsening (p = 0.007). Conclusions Already single time point elevation of sNfL has a distinct effect on brain volume changes over a short‐term period, and repeated high levels of sNfL indicate accumulating physical disability. Serial assessment of sNfL may provide added value in the clinical management of pwMS.

Cerebrospinal fluid neurofilament light and cerebral atrophy in younger‐onset dementia and primary psychiatric disorders

“…Although NfL has classically been associated with WM tract damage, 5,6 which is in keeping with the results from the MPRAGE group, NfL had a weak relationship with GM volume loss in the FSPGR group. NfL associations with GM volume have been demonstrated in multiple sclerosis 27,28 . This may in part be driven by Wallerian degeneration of WM contributing to loss of GM or by an independent process 29 …”

“…NfL associations with GM volume have been demonstrated in multiple sclerosis. 27,28 This may in part be driven by Wallerian degeneration of WM contributing to loss of GM or by an independent process. 29 A relative strength of our study is the use of biascorrected and accelerated 95% CIs, a conservative measure of significance.…”

Baseline serum neurofilament light chain levels differentiate aggressive from benign forms of relapsing–remitting multiple sclerosis: a 20-year follow-up cohort

“…Baseline serum NfL levels have been associated with worsening of EDSS in the first year, number of relapses, and progression of brain atrophy, as measured by cerebral magnetic resonance imaging (MRI) [ 52 – 55 ] in short-term prognosis studies. Regarding long-term prognosis, both baseline and longitudinal measures of NfL levels have been linked to greater cerebral MRI-based brain atrophy [ 25 , 53 , 56 – 60 ]; however, their association with disability progression is inconsistent [ 23 ]. In fact, studies with longer clinical follow-up periods found no relationship between baseline NfL levels and disability progression [ 24 , 25 ].…”