Serum and cerebrospinal fluid brain damage markers neurofilament light and glial fibrillary acidic protein correlate with tick-borne encephalitis disease severity-a multicentre study on Lithuanian and Swedish patients

Eur J Neurol. 2023 Oct;30(10):3182-3189. doi: 10.1111/ene.15978. Epub 2023 Jul 23.

Abstract

Background and purpose: Our aim was to examine the correlation between biomarkers of neuronal and glial cell damage and severity of disease in patients with tick-borne encephalitis.

Methods: One hundred and fifteen patients with tick-borne encephalitis diagnosed in Lithuania and Sweden were prospectively included, and cerebrospinal fluid (CSF) and serum samples were obtained shortly after hospitalization. Using pre-defined criteria, cases were classified as mild, moderate or severe tick-borne encephalitis. Additionally, the presence of spinal nerve paralysis (myelitis) and/or cranial nerve affection were noted. Concentrations of the brain cell biomarkers glial fibrillary acidic protein (GFAP), YKL-40, S100B, neurogranin, neurofilament light (NfL) and tau were analysed in CSF and, in addition, NfL, GFAP and S100B levels were measured in serum. The Jonckheere-Terpstra test was used for group comparisons of continuous variables and Spearman's partial correlation test was used to adjust for age.

Results: Cerebrospinal fluid and serum concentrations of GFAP and NfL correlated with disease severity, independent of age, and with the presence of nerve paralysis. The markers neurogranin, YKL-40, tau and S100B in CSF and S100B in serum were detected, but their concentrations did not correlate with disease severity.

Conclusions: Neuronal cell damage and astroglial cell activation with increased NfL and GFAP in CSF and serum were associated with a more severe disease, independent of age. Increased GFAP and NfL concentrations in CSF and NfL in serum were also indicative of spinal and/or cranial nerve damage. NfL and GFAP are promising prognostic biomarkers in tick-borne encephalitis, and future studies should focus on determining the association between these biomarkers and long-term sequelae.

Keywords: central nervous system; neurofilament; neuroglia; tick-borne encephalitis; viral encephalitis.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Brain
  • Brain Injuries*
  • Chitinase-3-Like Protein 1
  • Encephalitis, Tick-Borne*
  • Glial Fibrillary Acidic Protein / cerebrospinal fluid
  • Humans
  • Intermediate Filaments
  • Lithuania
  • Neurofilament Proteins
  • Neurogranin
  • Patient Acuity
  • Sweden

Substances

  • Chitinase-3-Like Protein 1
  • Glial Fibrillary Acidic Protein
  • Neurogranin
  • Biomarkers
  • Neurofilament Proteins