Neurofilament levels are associated with blood-brain barrier integrity, lymphocyte extravasation, and risk factors following the first demyelinating event in multiple sclerosis.

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 locus gene ()*1501, anti-Epstein-Barr virus (EBV) antibodies, and 25-hydroxy vitamin D, were also measured.

RESULTS

Higher serum NfL (sNfL) levels were associated with higher albumin quotient ( < 0.001), CSF CD80+ ( = 0.012), and CD80+ CD19+ ( = 0.015) cell frequency. sNfL levels were also associated with contrast-enhancing and T2 lesions on brain magnetic resonance imaging (MRI; all  ⩽ 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 ( = 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.