TY - JOUR
T1 - Multicenter validation of CSF neurofilaments as diagnostic biomarkers for ALS
AU - Oeckl, Patrick
AU - Jardel, Claude
AU - Salachas, François
AU - Lamari, Foudil
AU - Andersen, Peter M.
AU - Bowser, Robert
AU - de Carvalho, Mamede
AU - Costa, Júlia
AU - van Damme, Philip
AU - Gray, Elizabeth
AU - Grosskreutz, Julian
AU - Hernández-Barral, María
AU - Herukka, Sanna Kaisa
AU - Huss, André
AU - Jeromin, Andreas
AU - Kirby, Janine
AU - Kuzma-Kozakiewicz, Magdalena
AU - Amador, Maria del Mar
AU - Mora, Jesús S.
AU - Morelli, Claudia
AU - Muckova, Petra
AU - Petri, Susanne
AU - Poesen, Koen
AU - Rhode, Heidrun
AU - Rikardsson, Anna Karin
AU - Robberecht, Wim
AU - Rodríguez Mahillo, Ana I.
AU - Shaw, Pamela
AU - Silani, Vincenzo
AU - Steinacker, Petra
AU - Turner, Martin R.
AU - Tüzün, Erdem
AU - Yetimler, Berrak
AU - Ludolph, Albert C.
AU - Otto, Markus
N1 - Publisher Copyright:
© 2016 World Federation of Neurology on behalf of the Research Group on Motor Neuron Diseases.
PY - 2016/8/17
Y1 - 2016/8/17
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84962905616
U2 - 10.3109/21678421.2016.1167913
DO - 10.3109/21678421.2016.1167913
M3 - Journal articles
C2 - 27415180
AN - SCOPUS:84962905616
SN - 2167-8421
VL - 17
SP - 404
EP - 413
JO - Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
JF - Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
IS - 5-6
ER -
SDG 3 – Gesundheit und Wohlergehen