Neurofilament light chain predicts disease activity in relapsing-remitting MS

Abstract

Objective:To investigate whether serum neurofilament light chain (NF-L) and chitinase 3-like 1 (CHI3L1) predict disease activity in relapsing-remitting MS (RRMS).Methods:A cohort of 85 patients with RRMS were followed for 2 years (6 months without disease-modifying treatment and 18 months with interferon-beta 1a [IFNB-1a]). Expanded Disability Status Scale was scored at baseline and every 6 months thereafter. MRI was performed at baseline and monthly for 9 months and then at months 12 and 24. Serum samples were collected at baseline and months 3, 6, 12, and 24. We analyzed the serum levels of NF-L using a single-molecule array assay and CHI3L1 by ELISA and estimated the association with clinical and MRI disease activity using mixed-effects models.Results:NF-L levels were significantly higher in patients with new T1 gadolinium-enhancing lesions (37.3 pg/mL, interquartile range [IQR] 25.9–52.4) and new T2 lesions (37.3 pg/mL, IQR 25.1–48.5) compared with those without (28.0 pg/mL, IQR 21.9–36.4, β = 1.258, p < 0.001 and 27.7 pg/mL, IQR 21.8–35.1, β = 1.251, p < 0.001, respectively). NF-L levels were associated with the presence of T1 gadolinium-enhanced lesions up to 2 months before (p < 0.001) and 1 month after (p = 0.009) the time of biomarker measurement. NF-L levels fell after initiation of IFNB-1a treatment (p < 0.001). Changes in CHI3L1 were not associated with clinical or MRI disease activity or interferon-beta 1a treatment.Conclusion:Serum NF-L could be a promising biomarker for subclinical MRI activity and treatment response in RRMS. In clinically stable patients, serum NF-L may offer an alternative to MRI monitoring for subclinical disease activity.ClinicalTrials.gov identifier:NCT00360906.

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

“…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.…”

Vitamin D supplementation and neurofilament light chain in multiple sclerosis

“…16 The concentration of NFL is elevated in the cerebrospinal fluid (CSF) of MS patients, 17 and it is reduced by effective immunomodulatory treatments such as fingolimod and natalizumab. 22,23 Only one observational study has so far addressed the relationship between vitamin D and NFL in MS, showing that high serum levels of 25-hydroxyvitamin D were associated with low CSF levels of NFL. 22,23 Only one observational study has so far addressed the relationship between vitamin D and NFL in MS, showing that high serum levels of 25-hydroxyvitamin D were associated with low CSF levels of NFL.…”

“…18,19 The concentrations of NFL in serum and CSF are highly correlated, 20,21 and serum NFL also predicts inflammatory disease activity and brain and spinal cord atrophy. 22,23 Only one observational study has so far addressed the relationship between vitamin D and NFL in MS, showing that high serum levels of 25-hydroxyvitamin D were associated with low CSF levels of NFL. 24 We have previously performed a randomized placebo-controlled trial (RCT) of weekly administration of 20 000 IU vitamin D3 in fully ambulatory patients with RRMS living above the Arctic Circle (NCT00785473).…”

Comparison of plasma and cerebrospinal fluid neurofilament light in a multiple sclerosis trial

“…The ratio between plasma and CSF in our study was of the same magnitude as in earlier findings. 22 Our study did not have the prerequisites to explore such aspects further. A recent publication, using serum NFL as a tool for individual follow-up, demonstrated that there was a moderate increased odds ratio of 1.5 of the occurrence of a Gd-positive lesion if an increase of 10 pg/mL in s-NFL was detected.…”

“…A recent publication, using serum NFL as a tool for individual follow-up, demonstrated that there was a moderate increased odds ratio of 1.5 of the occurrence of a Gd-positive lesion if an increase of 10 pg/mL in s-NFL was detected. 22 Our study did not have the prerequisites to explore such aspects further.…”