Multicenter validation of CSF neurofilaments as diagnostic biomarkers for ALS

Journal article

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.

Authors: Oeckl, P; Jardel, C; Salachas, F; Lamari, F; Andersen, PM

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Taylor and Francis
• Journal: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
• Volume: 17
• Issue: 5-6
• Pages: 403-413
• Publication date: 2016-04-11
• Acceptance date: 2016-02-12
• DOI: 10.3109/21678421.2016.1167913
• EISSN: 2167-9223
• ISSN: 2167-8421
• Language: English
• Keywords: cerebrospinal fluid; neurofilament; biomarker; amyotrophic lateral sclerosis; round robin