title: Acute axonal damage predicts clinical outcome in patients with multiple sclerosis.
abstract: The objectives of this study were (1) to determine how cerebrospinal fluid (CSF) neurofilament heavy chain (NfH(SM134) and NfH(SM135)) levels relate to clinical outcome in optic neuritis (ON) and multiple sclerosis (MS) relapse patients treated with high dose oral methylprednisolone; and (2) to correlate neurofilament and myelin basic protein (MBP) concentrations, particularly as the latter was previously associated with clinical disability. Fifty subjects participated in two double-blind, randomized, placebo-controlled clinical trials. Eight/18 patients in the ON trial and 15/32 subjects in the MS attack trial were treated with oral methylprednisolone. In the MS attack trial group, CSF NfH(SM134) and NfH(SM135) measured at week 3 and deltaCSF NfH(SMI34) levels from baseline to week 3 were predictive of clinical outcome at week 8 and 52. In the ON group, no such association was seen. When both groups were combined, baseline CSF NfH(SHM134) and NfH(SM135) correlated positively with baseline enhancing lesion volume (ELV) (r(s) =0.50, P <0.01 and rS =0.53, P <0.01, respectively). Levels of NfH(SM135) at baseline and week 3 also strongly correlated with the MBP concentration. This study supports the view that acute inflammation in ON and MS results in axonal pathology and that the latter has a role in determining functional impairment.
authors.affiliation: Department of Neuroinflammation, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK. e.lim@ion.ucl.ac.uk
authors.forename: E T
authors.initials: ET
authors.lastname: Lim
authors.forename: F
authors.initials: F
authors.lastname: Sellebjerg
authors.forename: C V
authors.initials: CV
authors.lastname: Jensen
authors.forename: D R
authors.initials: DR
authors.lastname: Altmann
authors.forename: D
authors.initials: D
authors.lastname: Grant
authors.forename: G
authors.initials: G
authors.lastname: Keir
authors.forename: E J
authors.initials: EJ
authors.lastname: Thompson
authors.forename: G
authors.initials: G
authors.lastname: Giovannoni
mesh_terms: D000208:Acute Disease; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001369:Axons / Q000473:pathology*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D004185:Disability Evaluation; D006801:Humans; D008279:Magnetic Resonance Imaging; D008775:Methylprednisolone / Q000008:administration & dosage*; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000188:drug therapy* / Q000473:pathology; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid*; D009902:Optic Neuritis / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000473:pathology; D011237:Predictive Value of Tests; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D016900:Neurofilament Proteins; D008775:Methylprednisolone