BACKGROUND: Increased blood brain barrier (BBB) permeability, CNS inflammation 
and neuroaxonal damage are pathological hallmarks in early multiple sclerosis 
(MS).
OBJECTIVE: To investigate the associations of neurofilament light chain (NfL) 
levels with measures of BBB integrity and central nervous system (CNS) 
inflammation in MS during the first demyelinating event.
METHODS: Blood and cerebrospinal fluid (CSF) were obtained from 142 MS (McDonald 
2017) treatment-naive patients from the SET study (63% female; age: 
29.7 ± 7.9 years) following the disease onset. NfL, albumin, immunoglobulin G 
(IgG), and immunoglobulin M (IgM) levels were measured in CSF and blood samples. 
Albumin quotient was computed as a marker of BBB integrity. Immune cell subset 
counts in CSF were measured using flow cytometry. MS risk factors, such as Human 
leukocyte antigen DRB1 locus gene (HLA DRB1)*1501, anti-Epstein-Barr virus (EBV) 
antibodies, and 25-hydroxy vitamin D3, were also measured.
RESULTS: Higher serum NfL (sNfL) levels were associated with higher albumin 
quotient (p < 0.001), CSF CD80+ (p = 0.012), and CD80+ CD19+ (p = 0.015) cell 
frequency. sNfL levels were also associated with contrast-enhancing and T2 
lesions on brain magnetic resonance imaging (MRI; all p ⩽ 0.001). Albumin 
quotient was not associated with any of the MS risk factors assessed. sNfL 
levels were associated with anti-EBV viral capsid antigen (VCA) IgG levels 
(p = 0.0026).
CONCLUSION: sNfL levels during the first demyelinating event of MS are 
associated with greater impairment of BBB integrity, immune cell extravasation, 
and brain lesion activity on MRI.