Patrick Oeckl1, Claude Jardel2, François Salachas3, Foudil Lamari2, Peter M Andersen4, Robert Bowser5,6, Mamede de Carvalho7, Júlia Costa8, Philip van Damme9,10, Elizabeth Gray11, Julian Grosskreutz12, María Hernández-Barral13, Sanna-Kaisa Herukka14, André Huss1, Andreas Jeromin5, Janine Kirby15, Magdalena Kuzma-Kozakiewicz16, Maria Del Mar Amador3, Jesús S Mora13, Claudia Morelli17, Petra Muckova18, Susanne Petri19, Koen Poesen20, Heidrun Rhode18, Anna-Karin Rikardsson4, Wim Robberecht10, Ana I Rodríguez Mahillo13, Pamela Shaw15, Vincenzo Silani17,21, Petra Steinacker1, Martin R Turner11, Erdem Tüzün22, Berrak Yetimler22, Albert C Ludolph1, Markus Otto1. 1. a Department of Neurology , Ulm University Hospital , 89081 Ulm , Germany ; 2. b Department of Metabolic Biochemistry , Hôpitaux universitaires Pitié Salpétrière-Charles Foix , 75651 Paris , France . 3. c Paris ALS Reference Center, Neurological Diseases Department , Hôpitaux universitaires La Pitié Salpêtrière-Charles Foix , 75651 Paris , France . 4. d Department of Neurology , University of Umea , 90185 Umea , Sweden . 5. e Iron Horse Diagnostics, Inc. , 85255 Scottsdale , Arizona , USA . 6. f Divisions of Neurology and Neurobiology , Barrow Neurological Institute , 85013 Phoenix , Arizona , USA . 7. g Faculty of Medicine - Instituto de Medicina Molecular , University of Lisbon , 1649-028 Lisbon , Portugal . 8. h Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa , 2780-157 Oeiras , Portugal . 9. i University Hospitals Leuven , Department of Neurology , 3000 Leuven , Belgium . 10. s KU Leuven - University of Leuven , Department of Neurosciences, VIB - Vesalius Research Center, Experimental Neurology - Laboratory of Neurobiology , Leuven , Belgium . 11. j Nuffield Department of Clinical Neurosciences , University of Oxford , OX3 9DU Oxford , UK . 12. k Department of Neurology , Jena University Hospital , 07747 Jena , Germany . 13. t ALS Unit, Hospital Carlos III, Madrid , 28029 Madrid , Spain . 14. l Department of Neurology , University of Eastern Finland and Kuopio University Hospital , 70211 Kuopio , Finland . 15. m Department of Neuroscience , Sheffield Institute for Translational Neuroscience, University of Sheffield , S10 2HQ Sheffield , UK . 16. n Department of Neurology , Medical University of Warsaw , 02-097 Warsaw , Poland . 17. o IRCCS Istituto Auxologico Italiano, Department of Neurology and Laboratory of Neuroscience, 20149 Milano, Italy . 18. p Institute of Biochemistry I, Jena University Hospital , 07743 Jena , Germany . 19. q Department of Neurology , Hannover Medical School , 30625 Hannover , Germany . 20. r Laboratory of molecular neurobiomarker research , University of Leuven and Laboratory Medicine, University Hospitals of Leuven , 3000 Leuven , Belgium . 21. v Department "Dino Ferrari" Center, Department of Pathophysiology and Transplantation , Università degli Studi di Milano , 20122 Milano , Italy. 22. u Neuroscience Department , Institute of Experimental Medical Research, Istanbul University , 34393 Istanbul , Turkey , and.
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 >568.5 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.
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 ALSpatients 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.
Entities:
Keywords:
Cerebrospinal fluid; amyotrophic lateral sclerosis; biomarker; neurofilament; round robin
Authors: Mariah L Hoye; Erica D Koval; Amy J Wegener; Theodore S Hyman; Chengran Yang; David R O'Brien; Rebecca L Miller; Tracy Cole; Kathleen M Schoch; Tao Shen; Tomonori Kunikata; Jean-Philippe Richard; David H Gutmann; Nicholas J Maragakis; Holly B Kordasiewicz; Joseph D Dougherty; Timothy M Miller Journal: J Neurosci Date: 2017-04-17 Impact factor: 6.167
Authors: Michael Benatar; Lanyu Zhang; Lily Wang; Volkan Granit; Jeffrey Statland; Richard Barohn; Andrea Swenson; John Ravits; Carlayne Jackson; Ted M Burns; Jaya Trivedi; Erik P Pioro; James Caress; Jonathan Katz; Jacob L McCauley; Rosa Rademakers; Andrea Malaspina; Lyle W Ostrow; Joanne Wuu Journal: Neurology Date: 2020-05-08 Impact factor: 9.910