TUBITAK Destekli Projelerden Çıkan Yayınlar Topluluğu
Published January 1, 2016 | Version v1
Journal article Open

Multicenter validation of CSF neurofilaments as diagnostic biomarkers for ALS

Creators

  • 1. Ulm Univ Hosp, Dept Neurol, Oberer Eselsberg 45, D-89081 Ulm, Germany
  • 2. Hop Univ Pitie Salpetriere Charles Foix, Dept Metab Biochem, F-75651 Paris, France
  • 3. Hop Univ La Pitie Salpetriere Charles Foix, Paris ALS Reference Ctr, Neurol Dis Dept, F-75651 Paris, France
  • 4. Umea Univ, Dept Neurol, S-90185 Umea, Sweden
  • 5. Univ Lisbon, Fac Med, Inst Med Mol, P-1649028 Lisbon, Portugal
  • 6. Univ Nova Lisboa, Inst Tecnol Quim & Biol Antonio Xavier, P-2780157 Oeiras, Portugal
  • 7. Univ Oxford, Nuffield Dept Clin Neurosci, Oxford OX3 9DU, England
  • 8. Jena Univ Hosp, Dept Neurol, D-07747 Jena, Germany
  • 9. Hosp Carlos III Madrid, ALS Unit, Madrid 28029, Spain
  • 10. Iron Horse Diagnost Inc, Scottsdale, AZ 85255 USA
  • 11. Univ Sheffield, Dept Neurosci, Sheffield Inst Translat Neurosci, Sheffield S10 2HQ, S Yorkshire, England
  • 12. Med Univ Warsaw, Dept Neurol, PL-02097 Warsaw, Poland

Description

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 >568.5pg/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.

Files

bib-aa796226-1075-4a8e-abb9-e3ab6e6e976d.txt

Files (440 Bytes)

Name Size Download all
md5:55a68dc1c96f1a70abf507ca34b54fa8
440 Bytes Preview Download