title: Assessing tissue damage in multiple sclerosis: a biomarker approach.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Neuroscience, Uppsala University, Uppsala, Sweden; Department of Neurology, Uppsala University Hospital, Uppsala, Sweden; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Burman
authors.forename: H
authors.initials: H
authors.lastname: Zetterberg
authors.forename: M
authors.initials: M
authors.lastname: Fransson
authors.forename: A Si
authors.initials: AS
authors.lastname: Loskog
authors.forename: R
authors.initials: R
authors.lastname: Raininko
authors.forename: J
authors.initials: J
authors.lastname: Fagius
mesh_terms: D000328:Adult; D001253:Astrocytes / Q000473:pathology; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000473:pathology; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000134:cerebrospinal fluid; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000473:pathology*; D004676:Myelin Basic Protein / Q000134:cerebrospinal fluid; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid; D009836:Oligodendroglia / Q000473:pathology; D013116:Spinal Cord / Q000473:pathology
chemical_list: D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; C499048:MBP protein, human; D004676:Myelin Basic Protein; D016900:Neurofilament Proteins; C044882:neurofilament protein L
keywords: glial fibrillary acidic protein; magnetic resonance imaging; multiple sclerosis; myelin basic protein; neurofilament