Performance of serum neurofilament light chain in a wide spectrum of clinical courses of amyotrophic lateral sclerosis—a cross‐sectional multicenter study
Thomas Meyer, Erma Salkic, Torsten Grehl, Ute Weyen, Dagmar Kettemann, Patrick Weydt, René Günther, Paul Lingor, Jan Christoph Koch, Susanne Petri, Andreas Hermann, Johannes Prudlo, Julian Großkreutz, Petra Baum, Matthias Boentert, Moritz Metelmann, Jenny Nordén, Isabell Cordts, Jochen H. Weishaupt, Johannes Dorst, Albert C. Ludolph, Yasemin Koc, Bertram Walter, Christoph Münch, Susanne Spittel, Marie Dreger, André Maier, Péter Körtvelyessy
Abstract
BACKGROUND AND PURPOSE: The objective was to assess the performance of serum neurofilament light chain (sNfL) in amyotrophic lateral sclerosis (ALS) in a wide range of disease courses, in terms of progression, duration and tracheostomy invasive ventilation (TIV). METHODS: A prospective cross-sectional study at 12 ALS centers in Germany was performed. sNfL concentrations were age adjusted using sNfL Z scores expressing the number of standard deviations from the mean of a control reference database and correlated to ALS duration and ALS progression rate (ALS-PR), defined by the decline of the ALS Functional Rating Scale. RESULTS: In the total ALS cohort (n = 1378) the sNfL Z score was elevated (3.04; 2.46-3.43; 99.88th percentile). There was a strong correlation of sNfL Z score with ALS-PR (p < 0.001). In patients with long (5-10 years, n = 167) or very long ALS duration (>10 years, n = 94) the sNfL Z score was significantly lower compared to the typical ALS duration of <5 years (n = 1059) (p < 0.001). Furthermore, in patients with TIV, decreasing sNfL Z scores were found in correlation with TIV duration and ALS-PR (p = 0.002; p < 0.001). CONCLUSIONS: The finding of moderate sNfL elevation in patients with long ALS duration underlined the favorable prognosis of low sNfL. The strong correlation of sNfL Z score with ALS-PR strengthened its value as progression marker in clinical management and research. The lowering of sNfL in correlation with long TIV duration could reflect a reduction either in disease activity or in the neuroaxonal substrate of biomarker formation during the protracted course of ALS.