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Serum neurofilament light chain in distinct phenotypes of amyotrophic lateral sclerosis: a longitudinal, multicenter study

Objective To assess the performance of serum neurofilament light chain (sNfL) in clinical phenotypes of amyotrophic lateral sclerosis (ALS). Methods In 2949 ALS patients at 16 ALS centers in Germany and Austria, clinical characteristics and sNfL were assessed. Phenotypes were differentiated for two...

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Main Authors: Meyer, Thomas (Author) , Dreger, Marie (Author) , Grehl, Torsten (Author) , Weyen, Ute (Author) , Kettemann, Dagmar (Author) , Weydt, Patrick (Author) , Günther, René (Author) , Lingor, Paul (Author) , Petri, Susanne (Author) , Koch, Jan Christoph (Author) , Großkreutz, Julian (Author) , Rödiger, Annekathrin (Author) , Baum, Petra (Author) , Hermann, Andreas (Author) , Prudlo, Johannes (Author) , Boentert, Matthias (Author) , Weishaupt, Jochen H. (Author) , Löscher, Wolfgang N. (Author) , Dorst, Johannes (Author) , Koc, Yasemin (Author) , Bernsen, Sarah (Author) , Cordts, Isabell (Author) , Vidovic, Maximilian (Author) , Steinbach, Robert (Author) , Metelmann, Moritz (Author) , Kleinveld, Vera E. (Author) , Norden, Jenny (Author) , Ludolph, Albert C. (Author) , Walter, Bertram (Author) , Schumann, Peggy (Author) , Münch, Christoph (Author) , Körtvélyessy, Péter (Author) , Maier, André Sascha (Author)
Format: Article (Journal)
Language:English
Published: September 2024
In: European journal of neurology
Year: 2024, Volume: 31, Issue: 9, Pages: 1-13
ISSN:1468-1331
DOI:10.1111/ene.16379
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1111/ene.16379
Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/ene.16379
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Author Notes:Thomas Meyer, Marie Dreger, Torsten Grehl, Ute Weyen, Dagmar Kettemann, Patrick Weydt, René Günther, Paul Lingor, Susanne Petri, Jan Christoph Koch, Julian Großkreutz, Annekathrin Rödiger, Petra Baum, Andreas Hermann, Johannes Prudlo, Matthias Boentert, Jochen H. Weishaupt, Wolfgang N. Löscher, Johannes Dorst, Yasemin Koc, Sarah Bernsen, Isabell Cordts, Maximilian Vidovic, Robert Steinbach, Moritz Metelmann, Vera E. Kleinveld, Jenny Norden, Albert Ludolph, Bertram Walter, Peggy Schumann, Christoph Münch, Péter Körtvélyessy, André Maier

MARC

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520 |a Objective To assess the performance of serum neurofilament light chain (sNfL) in clinical phenotypes of amyotrophic lateral sclerosis (ALS). Methods In 2949 ALS patients at 16 ALS centers in Germany and Austria, clinical characteristics and sNfL were assessed. Phenotypes were differentiated for two anatomical determinants: (1) upper and/or lower motor involvement (typical, typMN; upper/lower motor neuron predominant, UMNp/LMNp; primary lateral sclerosis, PLS) and (2) region of onset and propagation of motor neuron dysfunction (bulbar, limb, flail-arm, flail-leg, thoracic onset). Phenotypes were correlated to sNfL, progression, and survival. Results Mean sNfL was - compared to typMN (75.7 pg/mL, n = 1791) - significantly lower in LMNp (45.1 pg/mL, n = 413), UMNp (58.7 pg/mL n = 206), and PLS (37.6 pg/mL, n = 84). Also, sNfL significantly differed in the bulbar (92.7 pg/mL, n = 669), limb (64.1 pg/mL, n = 1305), flail-arm (46.4 pg/mL, n = 283), flail-leg (53.6 pg/mL, n = 141), and thoracic (74.5 pg/mL, n = 96) phenotypes. Binary logistic regression analysis showed highest contribution to sNfL elevation for faster progression (odds ratio [OR] 3.24) and for the bulbar onset phenotype (OR 1.94). In contrast, PLS (OR 0.20), LMNp (OR 0.45), and thoracic onset (OR 0.43) showed reduced contributions to sNfL. Longitudinal sNfL (median 12 months, n = 2862) showed minor monthly changes (<0.2%) across all phenotypes. Correlation of sNfL with survival was confirmed (p < 0.001). Conclusions This study underscored the correlation of ALS phenotypes - differentiated for motor neuron involvement and region of onset/propagation - with sNfL, progression, and survival. These phenotypes demonstrated a significant effect on sNfL and should be recognized as independent confounders of sNfL analyses in ALS trials and clinical practice. 
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