Multicenter validation of CSF neurofilaments as diagnostic biomarkers for ALS

Patrick Oeckl, Claude Jardel, François Salachas, Foudil Lamari, Peter M. Andersen, Robert Bowser, Mamede de Carvalho, Júlia Costa, Philip van Damme, Elizabeth Gray, Julian Grosskreutz, María Hernández-Barral, Sanna Kaisa Herukka, André Huss, Andreas Jeromin, Janine Kirby, Magdalena Kuzma-Kozakiewicz, Maria del Mar Amador, Jesús S. Mora, Claudia MorelliPetra Muckova, Susanne Petri, Koen Poesen, Heidrun Rhode, Anna Karin Rikardsson, Wim Robberecht, Ana I. Rodríguez Mahillo, Pamela Shaw, Vincenzo Silani, Petra Steinacker, Martin R. Turner, Erdem Tüzün, Berrak Yetimler, Albert C. Ludolph, Markus Otto*

*Corresponding author for this work
64 Citations (Scopus)


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 >568.5 pg/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.

Original languageEnglish
JournalAmyotrophic Lateral Sclerosis and Frontotemporal Degeneration
Issue number5-6
Pages (from-to)404-413
Number of pages10
Publication statusPublished - 17.08.2016
Externally publishedYes

Research Areas and Centers

  • Centers: Center for Neuromuscular Diseases


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