Objective Phosphorylated neurofilament heavy chain (pNfH) levels are elevated in cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS). Instead of CSF, we explored blood as an alternative source to measure pNfH in patients with ALS.
Methods In this single centre retrospective study, 85 patients with ALS, 215 disease controls (DC) and 31 ALS mimics were included. Individual serum pNfH concentrations were correlated with concentrations in CSF and with several clinical parameters. The performance characteristics of pNfH in CSF and serum of patients with ALS and controls were calculated and compared using receiver operating characteristic (ROC) curves.
Results CSF and serum pNfH concentrations in patients with ALS correlated well (r=0.652, p<0.0001) and were significantly increased compared with DC (p<0.0001) and ALS mimics (p<0.0001). CSF pNfH outperformed serum pNfH in discriminating patients with ALS from DC and ALS mimics (difference between area under the ROC curves: p=0.0001 and p=0.0005; respectively). Serum pNfH correlated inversely with symptom duration (r=−0.315, p=0.0033). CSF and serum pNfH were lower when the disease progression rate was slower (r=0.279, p<0.01 and r=0.289, p<0.01; respectively). Unlike CSF, serum pNfH did not correlate with the burden of clinical and electromyographic motor neuron dysfunction.
Conclusions CSF and serum pNfH concentrations are elevated in patients with ALS and correlate with the disease progression rate. Moreover, CSF pNfH correlates with the burden of motor neuron dysfunction. Our findings encourage further pursuit of CSF and serum pNfH concentrations in the diagnostic pathway of patients suspected to have ALS.
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Contributors Concept and design: MDS, AJ, PVD, KP; drafting of the manuscript and figures: MDS, BG, AJ, VH, BB, PVD, KP; acquisition, analysis or interpretation of data: MDS, BG, KGC, PVD, KP; critical revision of the manuscript for important intellectual content: all authors. PVD and KP contributed equally.
Funding PVD is a senior clinical investigator of the Flemish Fund for Scientific Research (FWO, Fonds voor Wetenschappelijk Onderzoek Flanders, Belgium) and is supported by the Belgian ALS Liga. KP received a start-up grant of the Group of Biomedical Sciences KU Leuven and holds a Clinical Research fund of the University Hospitals Leuven.
Competing interests MDS, BG, KGC, PVD: Nothing to report. KP: ELISA kits were provided by Euroimmun AG (Lübeck, Germany) VH, BB: full time employees of Euroimmun AG (Lübeck, Germany) AJ: Paid employee and stock holder of Iron Horse Diagnostics, Inc. (Scottsdale, AZ, USA) with a pending patent for biomarkers in neuronal injury
Ethics approval Ethical Committee of the University Hospitals Leuven.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement The data used and/or analysed during the current study are available from the corresponding author on reasonable request.
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