title: Serum neurofilament light chain is a biomarker of human spinal cord injury severity and outcome.
abstract: BACKGROUND
  Neurofilaments (Nf) are major structural proteins that occur exclusively in neurons. In spinal cord injury (SCI), the severity of disease is quantified by clinical measures that have limited sensitivity and reliability, and no blood-based biomarker has been established to further stratify the degree of injury. We aimed to examine a serum-based NfL immunoassay as predictor of the clinical outcome in SCI.
  
  
  METHODS
  Longitudinal measurement of serum NfL was performed in patients with central cord syndrome (CCS, n=4), motor-incomplete SCI (iSCI, n=10), motor-complete SCI (cSCI, n=13) and healthy controls (HC, n=67), and correlated with clinical severity, neurological outcome, and neuroprotective effect of the drug minocycline.
  
  
  RESULTS
  Baseline NfL levels were higher in iSCI (21 pg/mL) and cSCI (70 pg/mL) than in HC (5 pg/mL, p=0.006 and p<0.001) and CCS (6 pg/mL, p=0.025 and p=0.010). Levels increased over time (p<0.001) and remained higher in cSCI versus iSCI (p=0.011) and than in CCS (p<0.001). NfL levels correlated with American Spinal Injury Association (ASIA) motor score at baseline (r=-0.53, p=0.004) and after 24 h (r=-0.69, p<0.001) and 3-12-month motor outcome (baseline NfL: r=-0.43, p=0.026 and 24 h NfL: r=-0.72, p<0.001). Minocycline treatment showed decreased NfL levels in the subgroup of cSCI patients.
  
  
  CONCLUSIONS
  Serum NfL concentrations in SCI patients show a close correlation with acute severity and neurological outcome. Our data provide evidence that serum NfL is of prognostic value in SCI patients for the first time. Further, blood NfL levels may qualify as drug response markers in SCI.
authors.affiliation: Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK Neurology, University Hospital Basel, Basel, Switzerland.
authors.forename: Jens
authors.initials: J
authors.lastname: Kuhle
authors.affiliation: Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: Johanna
authors.initials: J
authors.lastname: Gaiottino
authors.affiliation: Neurology, University Hospital Basel, Basel, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Leppert
authors.affiliation: Department of Molecular Neurosciences, UCL Institute of Neurology, London, UK.
authors.forename: Axel
authors.initials: A
authors.lastname: Petzold
authors.affiliation: Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Bestwick
authors.affiliation: Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK North-East London and Essex Regional MND Care Centre, London, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Malaspina
authors.affiliation: Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: Ching-Hua
authors.initials: CH
authors.lastname: Lu
authors.affiliation: Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: Ruth
authors.initials: R
authors.lastname: Dobson
authors.affiliation: Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: Giulio
authors.initials: G
authors.lastname: Disanto
authors.affiliation: UmanDiagnostics, Umeå, Sweden.
authors.forename: Niklas
authors.initials: N
authors.lastname: Norgren
authors.affiliation: Biochemical Pharmacology, John Vane Science Centre, Queen Mary University of London, London, UK.
authors.forename: Ahuva
authors.initials: A
authors.lastname: Nissim
authors.affiliation: Neurology, University Hospital Basel, Basel, Switzerland.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kappos
authors.affiliation: Department of Clinical Neurosciences and the Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Hurlbert
authors.affiliation: Department of Clinical Neurosciences and the Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: V Wee
authors.initials: VW
authors.lastname: Yong
authors.affiliation: Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: Gavin
authors.initials: G
authors.lastname: Giovannoni
authors.affiliation: Department of Clinical Neurosciences and the Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Steven
authors.initials: S
authors.lastname: Casha
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D008911:Minocycline / Q000627:therapeutic use; D016900:Neurofilament Proteins / Q000097:blood*; D009460:Neurologic Examination / Q000187:drug effects; D011379:Prognosis; D012016:Reference Values; D013119:Spinal Cord Injuries / Q000097:blood* / Q000175:diagnosis* / Q000188:drug therapy
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers; D016900:Neurofilament Proteins; C044882:neurofilament protein L; D008911:Minocycline
keywords: NEUROSURGERY