Multicenter validation of CSF neurofilaments as diagnostic biomarkers for ALS


Oeckl P., Jardel C., Salachas F., Lamari F., Andersen P. M. , Bowser R., ...More

AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION, vol.17, pp.404-413, 2016 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 17
  • Publication Date: 2016
  • Doi Number: 10.3109/21678421.2016.1167913
  • Title of Journal : AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
  • Page Numbers: pp.404-413

Abstract

OBJECTIVE: Neurofilaments are leading neurochemical biomarkers for amyotrophic lateral sclerosis (ALS). Here, we investigated the effect of preanalytical factors on neurofilament concentrations in cerebrospinal fluid (CSF) in a reverse round-robin with 15 centers across Europe/U.S. METHODS: Samples from ALS and control patients (5/5 each center, n=150) were analyzed for phosphorylated neurofilament heavy chain (pNfH) and neurofilament light chain (NfL) at two laboratories. RESULTS: CSF pNfH was increased (p<0.05) in ALS in 10 out of 15 centers and NfL in 5 out of 12 centers. The coefficient of variation (CV%) of pNfH measurements between laboratories was 18.7 +/- 19.1%. We calculated a diagnostic cut-off of >568.5pg/mL for pNfH (sensitivity 78.7%, specificity 93.3%) and >1,431pg/mL for NfL (sensitivity 79.0%, specificity 86.4%). CONCLUSION: Values in ALS patients are already comparable between most centers, supporting eventual implementation into clinical routine. However, continuous quality control programs will be necessary for inclusion in the diagnostic work-up.