Jens Kuhle1, Johanna Gaiottino2, David Leppert3, Axel Petzold4, Jonathan P Bestwick5, Andrea Malaspina6, Ching-Hua Lu2, Ruth Dobson2, Giulio Disanto2, Niklas Norgren7, Ahuva Nissim8, Ludwig Kappos3, John Hurlbert9, V Wee Yong9, Gavin Giovannoni2, Steven Casha9. 1. Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK Neurology, University Hospital Basel, Basel, Switzerland. 2. Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK. 3. Neurology, University Hospital Basel, Basel, Switzerland. 4. Department of Molecular Neurosciences, UCL Institute of Neurology, London, UK. 5. Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK. 6. 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. 7. UmanDiagnostics, Umeå, Sweden. 8. Biochemical Pharmacology, John Vane Science Centre, Queen Mary University of London, London, UK. 9. Department of Clinical Neurosciences and the Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Authors: C H Hulme; S J Brown; H R Fuller; J Riddell; A Osman; J Chowdhury; N Kumar; W E Johnson; K T Wright Journal: Spinal Cord Date: 2016-12-20 Impact factor: 2.772
Authors: Brian K Kwon; Ona Bloom; Ina-Beate Wanner; Armin Curt; Jan M Schwab; James Fawcett; Kevin K Wang Journal: Spinal Cord Date: 2019-07-04 Impact factor: 2.772