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Research paper
Serum neurofilament light chain is a biomarker of human spinal cord injury severity and outcome
  1. Jens Kuhle1,2,
  2. Johanna Gaiottino1,
  3. David Leppert2,
  4. Axel Petzold3,
  5. Jonathan P Bestwick4,
  6. Andrea Malaspina1,5,
  7. Ching-Hua Lu1,
  8. Ruth Dobson1,
  9. Giulio Disanto1,
  10. Niklas Norgren6,
  11. Ahuva Nissim7,
  12. Ludwig Kappos2,
  13. John Hurlbert8,
  14. V Wee Yong8,
  15. Gavin Giovannoni1,
  16. Steven Casha8
  1. 1Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
  2. 2Neurology, University Hospital Basel, Basel, Switzerland
  3. 3Department of Molecular Neurosciences, UCL Institute of Neurology, London, UK
  4. 4Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
  5. 5North-East London and Essex Regional MND Care Centre, London, UK
  6. 6UmanDiagnostics, Umeå, Sweden
  7. 7Biochemical Pharmacology, John Vane Science Centre, Queen Mary University of London, London, UK
  8. 8Department of Clinical Neurosciences and the Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada
  1. Correspondence to Dr Jens Kuhle, Blizard Institute, Barts and the London School of Medicine and Dentistry, 4 Newark Street, Queen Mary University of London, London, UK; j.kuhle{at}


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.


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