title: Cerebrospinal fluid levels of neurofilament and tau correlate with brain atrophy in natalizumab-treated multiple sclerosis.
abstract: Brain atrophy is related to clinical deterioration in multiple sclerosis (MS) but its association with intrathecal markers of inflammation or neurodegeneration is unclear. Our aim was to investigate whether cerebrospinal fluid (CSF) markers of inflammation or neurodegeneration are associated with brain volume change in natalizumab-treated MS and whether this change is reflected in non-lesional white matter metabolites.
  
  
  
  About 25 patients with natalizumab-treated MS were followed for 3 years with assessment of percentage brain volume change (PBVC) and absolute quantification of metabolites with proton magnetic resonance spectroscopy (1H MRS). Analyses of inflammatory [interleukin 1β (IL-1β), IL-6, C-X-C motif chemokine 8 (CXCL8), CXCL10, CXCL11, C-C motif chemokine 22] and neurodegenerative [neurofilament light protein (NFL), glial fibrillary acidic protein, myelin basic protein, tau proteins] markers were done at baseline and 1-year follow-up.
  
  
  
  The mean decline in PBVC was 3% at the 3-year follow-up, although mean1H MRS metabolite levels in non-lesional white matter were unchanged. CSF levels of NFL and tau at baseline correlated negatively with PBVC over 3 years (r = -0.564, P = 0.012, and r = -0.592, P = 0.010, respectively).
  
  
  
  A significant 3-year whole-brain atrophy was not reflected in mean metabolite change of non-lesional white matter. In addition, our results suggest that CSF levels of NFL and tau correlate with brain atrophy development and may be used for evaluating treatment response in inflammatory active MS.
authors.affiliation: Department of Neurology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Mellergård
authors.affiliation: Department of Radiation Physics and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.|Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Tisell
authors.affiliation: Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden.|Department of Radiology and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: I
authors.initials: I
authors.lastname: Blystad
authors.affiliation: Department of Radiation Physics and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Grönqvist
authors.affiliation: Clinical Neurochemistry Laboratory, Institution of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Clinical Neurochemistry Laboratory, Institution of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Olsson
authors.affiliation: Department of Clinical Immunology and Transfusion Medicine and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Dahle
authors.affiliation: Department of Neurology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.|Department of Clinical Neurophysiology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Vrethem
authors.affiliation: Department of Radiation Physics and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.|Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden.|Department of Radiology and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Lundberg
authors.affiliation: Department of Clinical Immunology and Transfusion Medicine and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Ernerudh
mesh_terms: D000328:Adult; D001284:Atrophy / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging / Q000473:pathology; D001369:Axons / Q000473:pathology; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007382:Intermediate Filaments; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D000069442:Natalizumab / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D015415:Biomarkers; D007155:Immunologic Factors; D000069442:Natalizumab; D016875:tau Proteins
keywords: brain atrophy; magnetic resonance spectroscopy; multiple sclerosis; natalizumab; neurofilament; quantitative magnetic resonance imaging; tau