Multicenter Validation Of Csf Neurofilaments As Diagnostic Biomarkers For ALS
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.
Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
Digital Object Identifier (DOI)
Oeckl, Patrick; Jardel, Claude; Salachas, Francois; Lamari, Foudil; Andersen, Peter M.; Bowser, Robert; Carvalho, Mamede de; Costa, Julia; Damme, Philip van; Gray, Elizabeth; Grosskreutz, Julian; Hernandez-Barral, Maria; Herukka, Sanna Kaisa; Huss, A; Jeromin, Andreas; Kirby, Janine; Kuzma-Kozakiewicz, Magdalena; Mar, Maria del; Mora, Jesus S.; Morelli, Claudia; Muckova, Petra; Petri, Susanne; Poesen, Koen; Rhode, Heidrun; Rikardsson, Anna Karin; Robberecht, Wim; Rodriguez, Ana I.; Shaw, Pamela; Silani, Vincenzo; Steinacker, Petra; Turner, Martin R.; Tuzun, Erdem; Yetimler, Berrak; Ludolph, Albert C.; and Otto, Markus, "Multicenter Validation Of Csf Neurofilaments As Diagnostic Biomarkers For ALS" (2016). Translational Neuroscience. 23.