Advanced search
Publication Cover
Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration Volume 17, 2016 - Issue 5-6
Submit an article Journal homepage
1,174
Views
74
CrossRef citations to date
0
Altmetric
Research Article

Multicenter validation of CSF neurofilaments as diagnostic biomarkers for ALS

Patrick OecklDepartment of Neurology, Ulm University Hospital, 89081Ulm, Germany;
, PHD,
Claude JardelDepartment of Metabolic Biochemistry, Hôpitaux universitaires Pitié Salpétrière-Charles Foix, 75651Paris, France,
, PharmD, PhD,
François SalachasParis ALS Reference Center, Neurological Diseases Department, Hôpitaux universitaires La Pitié Salpêtrière-Charles Foix, 75651Paris, France,
, MD,
Foudil LamariDepartment of Metabolic Biochemistry, Hôpitaux universitaires Pitié Salpétrière-Charles Foix, 75651Paris, France,
, MD,
Peter M. AndersenDepartment of Neurology, University of Umea, 90185Umea, Sweden,
, MD, PhD,
Robert BowserIron Horse Diagnostics, Inc., 85255Scottsdale, Arizona, USA, ;Divisions of Neurology and Neurobiology, Barrow Neurological Institute, 85013Phoenix, Arizona, USA,
, PhD,
Mamede de CarvalhoFaculty of Medicine - Instituto de Medicina Molecular, University of Lisbon, 1649-028Lisbon, Portugal,
, PhD,
Júlia CostaInstituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, 2780-157Oeiras, Portugal,
, PhD,
Philip van DammeUniversity Hospitals Leuven, Department of Neurology, 3000Leuven, Belgium, ;KU Leuven - University of Leuven, Department of Neurosciences, VIB - Vesalius Research Center, Experimental Neurology - Laboratory of Neurobiology, Leuven, Belgium,
, MD, PhD,
Elizabeth GrayNuffield Department of Clinical Neurosciences, University of Oxford, OX3 9DUOxford, UK,
, PhD,
Julian GrosskreutzDepartment of Neurology, Jena University Hospital, 07747Jena, Germany,
, MD,
María Hernández-BarralALS Unit, Hospital Carlos III, Madrid, 28029Madrid, Spain,
, MD,
Sanna-Kaisa HerukkaDepartment of Neurology, University of Eastern Finland and Kuopio University Hospital, 70211Kuopio, Finland,
, PhD, MD,
André HussDepartment of Neurology, Ulm University Hospital, 89081Ulm, Germany;
, MSc,
Andreas JerominIron Horse Diagnostics, Inc., 85255Scottsdale, Arizona, USA,
, PhD,
Janine KirbyDepartment of Neuroscience, Sheffield Institute for Translational Neuroscience, University of Sheffield, S10 2HQSheffield, UK,
, PhD,
Magdalena Kuzma-KozakiewiczDepartment of Neurology, Medical University of Warsaw, 02-097Warsaw, Poland,
, MD, PhD,
Maria del Mar AmadorParis ALS Reference Center, Neurological Diseases Department, Hôpitaux universitaires La Pitié Salpêtrière-Charles Foix, 75651Paris, France,
, MD,
Jesús S. MoraALS Unit, Hospital Carlos III, Madrid, 28029Madrid, Spain,
, MD,
Claudia MorelliIRCCS Istituto Auxologico Italiano, Department of Neurology and Laboratory of Neuroscience, 20149 Milano, Italy,
, MD,
Petra MuckovaInstitute of Biochemistry I, Jena University Hospital, 07743Jena, Germany,
, PhD,
Susanne PetriDepartment of Neurology, Hannover Medical School, 30625Hannover, Germany,
, MD,
Koen PoesenLaboratory of molecular neurobiomarker research, University of Leuven and Laboratory Medicine, University Hospitals of Leuven, 3000Leuven, Belgium,
, PharmD, PhD,
Heidrun RhodeInstitute of Biochemistry I, Jena University Hospital, 07743Jena, Germany,
, MD,
Anna-Karin RikardssonDepartment of Neurology, University of Umea, 90185Umea, Sweden,
,
Wim RobberechtKU Leuven - University of Leuven, Department of Neurosciences, VIB - Vesalius Research Center, Experimental Neurology - Laboratory of Neurobiology, Leuven, Belgium,
, MD, PhD,
Ana I. Rodríguez MahilloALS Unit, Hospital Carlos III, Madrid, 28029Madrid, Spain,
, PhD,
Pamela ShawDepartment of Neuroscience, Sheffield Institute for Translational Neuroscience, University of Sheffield, S10 2HQSheffield, UK,
, MD,
Vincenzo SilaniIRCCS Istituto Auxologico Italiano, Department of Neurology and Laboratory of Neuroscience, 20149 Milano, Italy, ;Department “Dino Ferrari” Center, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20122Milano, Italy
, MD,
Petra SteinackerDepartment of Neurology, Ulm University Hospital, 89081Ulm, Germany;
, PhD,
Martin R. TurnerNuffield Department of Clinical Neurosciences, University of Oxford, OX3 9DUOxford, UK,
, PhD,
Erdem TüzünNeuroscience Department, Institute of Experimental Medical Research, Istanbul University, 34393Istanbul, Turkey, and
, MD, PhD,
Berrak YetimlerNeuroscience Department, Institute of Experimental Medical Research, Istanbul University, 34393Istanbul, Turkey, and
, MSc,
Albert C. LudolphDepartment of Neurology, Ulm University Hospital, 89081Ulm, Germany;
, MD &
Markus OttoDepartment of Neurology, Ulm University Hospital, 89081Ulm, Germany; Correspondence[email protected]
, MD show all
Pages 404-413 | Received 13 Jan 2016, Accepted 12 Feb 2016, Published online: 11 Apr 2016
 
Sample our Medicine, Dentistry, Nursing & Allied Health journals, sign in here to start your FREE access for 14 days

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.

Acknowledgement

We are grateful to the excellent technical assistance of Imen Ben Younes, Dagmar Schattauer, Sandra Hübsch and Mehtap Bulut-Karac.

This study was supported by the JPND networks SOPHIA (01ED1202A) and BiomarkAPD (01ED1203F), the German Federal Ministry of Education and Research (FTLDc O1GI1007A, KKMS, MND-Net 01GM1103A, PYRAMID 01GM1304), the EU (NADINE 246513, FAIR-PARK II 633190), the foundation of the state Baden-Württemberg (D.3830), BIU (D.5009), the Scientific and Technological Research Council of Turkey (TUBITAK 112S362) and the E-rare grant PYRAMID (E-rare 12-093). MRT is funded by a Medical Research Council & Motor Neurone Disease Association Lady Edith Wolfson Senior Clinical Fellowship (MR/K01014X/1)

Declaration of interest

PVD holds a senior clinical investigatorship of FWO-Vlaanderen. The other authors report no conflicts of interest.

Log in via your institution

Access through your institution

Log in to Taylor & Francis Online

Restore content access

Restore content access for purchases made as guest
Purchase options * Save for later

PDF download + Online access

  • 48 hours access to article PDF & online version
  • Article PDF can be downloaded
  • Article PDF can be printed
USD 65.00 Add to cart

Issue Purchase

  • 30 days online access to complete issue
  • Article PDFs can be downloaded
  • Article PDFs can be printed
USD 478.00 Add to cart

* Local tax will be added as applicable

Related Research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.