Serum neurofilament light chain is a biomarker of human spinal cord injury severity and outcome

Jens Kuhle, Johanna Gaiottino, David Leppert, Axel Petzold, Jonathan P. Bestwick, Andrea Malaspina, Ching Hua Lu, Ruth Dobson, Giulio Disanto, Niklas Norgren, Ahuva Nissim, Ludwig Kappos, John Hurlbert, V. Wee Yong, Gavin Giovannoni, Steven Casha

Research output: Contribution to journalArticlepeer-review

95 Scopus citations

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), motorcomplete 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.

Original languageEnglish (US)
Pages (from-to)273-279
Number of pages7
JournalJournal of Neurology, Neurosurgery and Psychiatry
Volume86
Issue number3
DOIs
StatePublished - Mar 1 2015
Externally publishedYes

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology
  • Psychiatry and Mental health

Fingerprint

Dive into the research topics of 'Serum neurofilament light chain is a biomarker of human spinal cord injury severity and outcome'. Together they form a unique fingerprint.

Cite this