title: Cerebrospinal fluid levels of chitinase 3-like 1 and neurofilament light chain predict multiple sclerosis development and disability after optic neuritis.
abstract: BACKGROUND
  Cerebrospinal fluid (CSF) biomarkers have been suggested to predict multiple sclerosis (MS) after clinically isolated syndromes, but studies investigating long-term prognosis are needed.
  
  
  OBJECTIVE
  To assess the predictive ability of CSF biomarkers with regard to MS development and long-term disability after optic neuritis (ON).
  
  
  METHODS
  Eighty-six patients with ON as a first demyelinating event were included retrospectively. Magnetic resonance imaging (MRI), CSF leukocytes, immunoglobulin G index and oligoclonal bands were registered. CSF levels of chitinase-3-like-1, osteopontin, neurofilament light-chain, myelin basic protein, CCL2, CXCL10, CXCL13 and matrix metalloproteinase-9 were measured by enzyme-linked immunosorbent assay. Patients were followed up after 13.6 (range 9.6-19.4) years and 81.4% were examined, including Expanded Disability Status Scale and MS functional composite evaluation. 18.6% were interviewed by phone. Cox regression, multiple regression and Spearman correlation analyses were used.
  
  
  RESULTS
  Forty-six (53.5%) developed clinically definite MS (CDMS) during follow-up. In a multivariate model MRI (p=0.0001), chitinase 3-like 1 (p=0.0033) and age (p=0.0194) combined predicted CDMS best. Neurofilament light-chain predicted long-term disability by the multiple sclerosis severity scale (p=0.0111) and nine-hole-peg-test (p=0.0202). Chitinase-3-like-1 predicted long-term cognitive impairment by the paced auditory serial addition test (p=0.0150).
  
  
  CONCLUSIONS
  Neurofilament light-chain and chitinase-3-like-1 were significant predictors of long-term physical and cognitive disability. Furthermore, chitinase-3-like-1 predicted CDMS development. Thus, these molecules hold promise as clinically valuable biomarkers after ON as a first demyelinating event.
authors.affiliation: The MS Clinic, Department of Neurology, Copenhagen University Hospital Glostrup, Glostrup, Denmark signe.modvig.stausboell@regionh.dk.
authors.forename: S
authors.initials: S
authors.lastname: Modvig
authors.affiliation: The MS Clinic, Department of Neurology, Copenhagen University Hospital Glostrup, Glostrup, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Degn
authors.affiliation: Holbaek municipal eye clinic, Denmark.
authors.forename: H
authors.initials: H
authors.lastname: Roed
authors.affiliation: Clinical Eye Research Unit, Department of Ophthalmology, Copenhagen University Hospital Roskilde and The Faculty of Health Sciences, University of Copenhagen, Denmark.
authors.forename: T L
authors.initials: TL
authors.lastname: Sørensen
authors.affiliation: Functional Imaging Unit, Department of Diagnostics, Copenhagen University Hospital Glostrup, Glostrup, Denmark.
authors.forename: H B W
authors.initials: HB
authors.lastname: Larsson
authors.affiliation: Department of Neuroradiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: A R
authors.initials: AR
authors.lastname: Langkilde
authors.affiliation: The MS Clinic, Department of Neurology, Copenhagen University Hospital Glostrup, Glostrup, Denmark.
authors.forename: J L
authors.initials: JL
authors.lastname: Frederiksen
authors.affiliation: Danish MS Research Centre, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: F
authors.initials: F
authors.lastname: Sellebjerg
mesh_terms: D054392:Adipokines / Q000134:cerebrospinal fluid*; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000134:cerebrospinal fluid; D000071451:Chitinase-3-Like Protein 1; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D037102:Lectins / Q000134:cerebrospinal fluid*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid*; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid*; D009902:Optic Neuritis / Q000134:cerebrospinal fluid*; D011379:Prognosis; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D054392:Adipokines; D015415:Biomarkers; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D037102:Lectins; D016900:Neurofilament Proteins; C044882:neurofilament protein L
keywords: Biological markers; CHI3L1 protein; CSF; chitinase; human; multiple sclerosis; neurofilament protein L; optic neuritis; prognosis