Assessing tissue damage in multiple sclerosis: a biomarker approach

Acta Neurol Scand. 2014 Aug;130(2):81-9. doi: 10.1111/ane.12239. Epub 2014 Feb 24.

Abstract

Objectives: Magnetic resonance imaging (MRI) of the brain and spinal cord is the gold standard for assessing disease activity in multiple sclerosis (MS). MRI is an excellent instrument for determination of accumulated damage to the brain and spinal cord, but tells us little about ongoing tissue damage. In this study, biomarkers of oligodendrocyte, axonal and astrocyte injury were related to MRI and clinical findings and used to assess tissue damage in MS.

Materials and methods: Cerebrospinal fluid from 44 patients with relapsing-remitting MS, 20 with secondary progressive MS and 15 controls were investigated with ELISA to determine levels of myelin basic protein (MBP), neurofilament light (NFL) and glial fibrillary acidic protein (GFAp). Patients underwent MRI of the brain and spinal cord, and gadolinium enhancing lesions, T1 lesions and T2 lesions were counted.

Results: Patients in clinical relapse and patients with nonsymptomatic gadolinium enhancing lesions had high levels of MBP and NFL, indicating ongoing damage to oligodendrocytes and axons. The level of MBP dropped quickly within a week from the onset of a relapse, whereas NFL remained elevated for several weeks and GFAp slowly rose during the course of a relapse. Relapsing-remitting MS patients without gadolinium enhancing lesions had values of MBP, NFL and GFAp similar to controls, while patients with secondary progressive disease had moderately increased values of all biomarkers.

Conclusions: Analysis of MBP, NFL and GFAp provides direct means to measure tissue damage and is a useful addition to our methods for evaluation of MS.

Keywords: glial fibrillary acidic protein; magnetic resonance imaging; multiple sclerosis; myelin basic protein; neurofilament.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Astrocytes / pathology
  • Biomarkers / cerebrospinal fluid
  • Brain / pathology
  • Case-Control Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Glial Fibrillary Acidic Protein / cerebrospinal fluid
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Multiple Sclerosis / cerebrospinal fluid*
  • Multiple Sclerosis / pathology*
  • Myelin Basic Protein / cerebrospinal fluid
  • Neurofilament Proteins / cerebrospinal fluid
  • Oligodendroglia / pathology
  • Spinal Cord / pathology

Substances

  • Biomarkers
  • Glial Fibrillary Acidic Protein
  • MBP protein, human
  • Myelin Basic Protein
  • Neurofilament Proteins
  • neurofilament protein L