Serum neurofilament is associated with progression of brain atrophy and disability in early MS

Abstract

Objective: To investigate a potential effect of riluzole on serum neurofilaments (Nf) compared to placebo and the relationship between longitudinal clinical and MRI outcomes and serum Nf levels.Methods: Serum samples were obtained from participants enrolled in a randomized double-blind trial of neuroprotection with riluzole vs placebo as an add-on to weekly interferon-b (IFN-b)-1a IM initiated 3 months after randomization. Nf measurements were performed by ELISA and electrochemiluminescence immunoassay.Results: Longitudinal serum samples were available from 22 riluzole and 20 placebo participants over 24 months. There was no observed treatment effect with riluzole. Nf light chain (NfL) levels decreased over time (p 5 0.007 at 24 months), whereas the Nf heavy chain was unchanged (p 5 0.997). Changes in NfL were correlated with EDSS change (p 5 0.009) and neuropsychological outcomes. Brain volume decreased more rapidly in patients with high baseline NfL (p 5 0.05 at 12 months and p 5 0.008 at 24 months) and this relationship became stronger at 24 months (p 5 0.024 for interaction). Higher and increasing NfL predicted higher number of gadoliniumenhancing lesions (p , 0.001 for both). 1 They determine axonal caliber and transport, and during axonal injury can be measured in the CSF and blood. Immunoassays for both NfL and NfH have been extensively published and have short-term and long-term prognostic value in various neurologic disorders. 2-5The phase II riluzole trial in participants with early multiple sclerosis (MS) was a randomized, double-blind, placebo-controlled study assessing the putative neuroprotective effect of riluzole. The primary outcome of the trial, brain atrophy, was negative. 6 Our goal was to investigate a potential treatment effect on serum NfL and NfH and the longitudinal relationship between serum Nf levels and clinical and MRI outcomes.

Neurofilament light chain serum levels correlate with 10‐year MRI outcomes in multiple sclerosis

“…Short‐term studies have found that in patients with high baseline NfL, brain volume decreased more rapidly ( P = 0.05 at 12 months and P = 0.008 at 24 months) 15. Our BPF measurements of brain atrophy at 10 years consistently correlated with averaged yearly NfL levels, however, limited strength of association was gained by measurements beyond years 1–5.…”

“…Shorter term studies have found correlations between new gadolinium‐enhancing lesions and serum NfL values 13, 15, 31. Patients with either brain, spinal, or both brain and spinal gadolinium‐enhancing lesions had higher serum NfL than those without 13.…”

“…SIMOAbased assays of serum NfL have demonstrated high correlation with CSF values 7,12,13 and potentially provide a more accessible means to monitor MS patients. Serum NfL measurements by SIMOA correlate with disease state as well as short-term outcomes in MS, [12][13][14][15][16][17][18] however, the associations of serum NfL levels in predicting longer term outcomes, have not been explored.…”

Serum neurofilament light chain levels as a marker of upper motor neuron degeneration in patients with Amyotrophic Lateral Sclerosis

“…This might indicate that NfL is shed upon damage of long axons of the UMN. This is further supported by the rise of serum and CSF NfL in other diseases damaging the central nerve axons such as multiple sclerosis .…”

Advancing trial design in progressive multiple sclerosis

“…NfL crosses readily into the blood stream, and recent studies have demonstrated blood NfL to be a good estimate of NfL in the CSF. 14 NfL has been shown to be a good measure of treatment response in RRMS and also correlates with disability progressive in progressive MS. Ongoing studies will define normative values, biologic variability, and optimal testing methods.…”