Neurofilament levels, disease activity and brain volume during follow-up in multiple sclerosis

Irene Håkansson,Charlotte Dahle,Henrik Zetterberg,Anders Tisell,Jan Ernerudh,Kaj Blennow,Magnus Vrethem,Petra Cassel,Peter Lundberg

doi:10.1186/s12974-018-1249-7

Abstract

BackgroundThere is a need for clinically useful biomarkers of disease activity in clinically isolated syndrome (CIS) and relapsing remitting MS (RRMS). The aim of this study was to assess the correlation between neurofilament light chain (NFL) in cerebrospinal fluid (CSF) and serum and the relationship between NFL and other biomarkers, subsequent disease activity, and brain volume loss in CIS and RRMS.MethodsA panel of neurodegenerative and neuroinflammatory markers were analyzed in repeated CSF samples from 41 patients with CIS or RRMS in a prospective longitudinal cohort study and from 22 healthy controls. NFL in serum was analyzed using a single-molecule array (Simoa) method. “No evidence of disease activity-3” (NEDA-3) status and brain volume (brain parenchymal fraction calculated using SyMRI®) were recorded during 4 years of follow-up.ResultsNFL levels in CSF and serum correlated significantly (all samples, n = 63, r 0.74, p < 0.001), but CSF-NFL showed an overall stronger association profile with NEDA-3 status, new T2 lesions, and brain volume loss. CSF-NFL was associated with both new T2 lesions and brain volume loss during follow-up, whereas CSF-CHI3L1 was associated mainly with brain volume loss and CXCL1, CXCL10, CXCL13, CCL22, and MMP-9 were associated mainly with new T2 lesions.ConclusionsSerum and CSF levels of NFL correlate, but CSF-NFL predicts and reflects disease activity better than S-NFL. CSF-NFL levels are associated with both new T2 lesions and brain volume loss. Our findings further add to the accumulating evidence that CSF-NFL is a clinically useful biomarker in CIS and RRMS and should be considered in the expanding NEDA concept. CSF-CXCL10 and CSF-CSF-CHI3L1 are potential markers of disease activity and brain volume loss, respectively.

Highlights

There is a need for clinically useful biomarkers of disease activity in clinically isolated syndrome (CIS) and relapsing remitting Multiple sclerosis (MS) (RRMS)
This study aimed to assess the correlation between S-neurofilament light chain (NFL) and cerebrospinal fluid (CSF)-NFL, to evaluate NFL levels in relation to other biomarkers and disease activity parameters and to identify parameters associated with number of new T2 lesions and brain volume loss during 4 years of follow-up in a longitudinal cohort of patients with newly diagnosed CIS and relapsing remitting MS (RRMS)
S-NFL levels, just like recently reported for CSF-NFL levels [13] in this cohort, did not differ between CIS patients and RRMS patients (p = 0.9 for S-NFL and p = 0.4 for CSF-NFL) or between patients with and without a relapse starting within 2 months prior to sample collection at baseline (p = 0.7 for S-NFL and p = 0.1 for CSF-NFL)

Summary

Introduction

There is a need for clinically useful biomarkers of disease activity in clinically isolated syndrome (CIS) and relapsing remitting MS (RRMS). The aim of this study was to assess the correlation between neurofilament light chain (NFL) in cerebrospinal fluid (CSF) and serum and the relationship between NFL and other biomarkers, subsequent disease activity, and brain volume loss in CIS and RRMS. New T2 lesions, and disability progression are conventional signs of disease activity in MS. Brain atrophy is present early in the disease course [5, 6] and associated with disability progression [7]. Neurofilament light chain (NFL) in CSF correlates with long-term prognosis in MS [9], is a risk factor for conversion from clinically isolated syndrome (CIS) to relapsing remitting

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