Multicenter validation of CSF neurofilaments as diagnostic biomarkers for ALS
Yazar
van Damme, Philip
de Carvalho, Mamede
Costa, Julia
Gray, Elizabeth
Grosskreutz, Julian
Hernandez-Barral, Maria
Herukka, Sanna-Kaisa
Huss, Andre
Jeromin, Andreas
Kirby, Janine
Kuzma-Kozakiewicz, Magdalena
Amador, Maria del Mar
Mora, Jesus S.
Morelli, Claudia
Muckova, Petra
Petri, Susanne
Poesen, Koen
Rhode, Heidrun
Rikardsson, Anna-Karin
Robberecht, Wim
Rodriguez Mahillo, Ana I.
Shaw, Pamela
Silani, Vincenzo
Steinacker, Petra
Turner, Martin R.
Ludolph, Albert C.
Otto, Markus
Yetimler, Berrak
Tuzun, Erdem
Oeckl, Patrick
Jardel, Claude
Salachas, Francois
Lamari, Foudil
Andersen, Peter M.
Bowser, Robert
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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 (p568.5pg/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.
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