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

NfL amyotrophic lateral sclerosis biomarker phenotype serum neurofilament light chain

Journal

European journal of neurology
ISSN: 1468-1331
Titre abrégé: Eur J Neurol
Pays: England
ID NLM: 9506311

Informations de publication

Date de publication:
10 Jun 2024
Historique:
revised: 01 05 2024
received: 25 02 2024
accepted: 21 05 2024
medline: 11 6 2024
pubmed: 11 6 2024
entrez: 11 6 2024
Statut: aheadofprint

Résumé

To assess the performance of serum neurofilament light chain (sNfL) in clinical phenotypes of amyotrophic lateral sclerosis (ALS). 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. 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). 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.

Identifiants

DOI: 10.1111/ene.16379 PMID: 38859579
pubmed: 38859579
doi: 10.1111/ene.16379
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e16379

Subventions

Organisme : Bosis Canessa ALS Stiftung, Düsseldorf, Germany

Informations de copyright

© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.

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Auteurs

Thomas Meyer (T)

Department of Neurology, Center for ALS and Other Motor Neuron Disorders, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
Ambulanzpartner Soziotechnologie APST GmbH, Berlin, Germany.
ORCID: 0000-0002-2736-7350

Marie Dreger (M)

Department of Neurology, Center for ALS and Other Motor Neuron Disorders, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.

Torsten Grehl (T)

Department of Neurology, Center for ALS and Other Motor Neuron Disorders, Alfried Krupp Krankenhaus, Essen, Germany.

Ute Weyen (U)

Department of Neurology, Center for ALS and Other Motor Neuron Disorders, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil, Bochum, Germany.

Dagmar Kettemann (D)

Department of Neurology, Center for ALS and Other Motor Neuron Disorders, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.

Patrick Weydt (P)

Department for Neuromuscular Disorders, Bonn University, Bonn, Germany.
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany.
ORCID: 0000-0003-2344-5662

René Günther (R)

Department of Neurology, Technische Universität Dresden, University Hospital Carl Gustav Carus, Dresden, Germany.
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Dresden, Germany.
ORCID: 0000-0003-0329-5644

Paul Lingor (P)

Department of Neurology, Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Munich, Germany.
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Munich, Germany.

Susanne Petri (S)

Department of Neurology, Hannover Medical School, Hannover, Germany.

Jan Christoph Koch (JC)

Department of Neurology, Universitätsmedizin Göttingen, Göttingen, Germany.

Julian Großkreutz (J)

Department of Neurology, Universitätsmedizin Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.

Annekathrin Rödiger (A)

Department of Neurology, Jena University Hospital, Jena, Germany.
Zentrum für Seltene Erkrankungen (ZSE), Jena University Hospital, Jena, Germany.

Petra Baum (P)

Department of Neurology, University Hospital Leipzig, Leipzig, Germany.

Andreas Hermann (A)

Translational Neurodegeneration Section "Albrecht-Kossel", Department of Neurology, University of Rostock, University Medical Center, Rostock, Germany.
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Greifswald, Germany.

Johannes Prudlo (J)

Translational Neurodegeneration Section "Albrecht-Kossel", Department of Neurology, University of Rostock, University Medical Center, Rostock, Germany.
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Greifswald, Germany.

Matthias Boentert (M)

Department of Neurology, Münster University Hospital, Münster, Germany.

Jochen H Weishaupt (JH)

Division for Neurodegenerative Diseases, Neurology Department, Mannheim Center for Translational Medicine, University Medicine Mannheim, Heidelberg University, Mannheim, Germany.

Wolfgang N Löscher (WN)

Department of Neurology, Medical University Innsbruck, Innsbruck, Austria.

Johannes Dorst (J)

Department of Neurology, Ulm University, Ulm, Germany.
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Ulm, Germany.

Yasemin Koc (Y)

Department of Neurology, Center for ALS and Other Motor Neuron Disorders, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.

Sarah Bernsen (S)

Department of Neurology, Center for ALS and Other Motor Neuron Disorders, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
Department for Neuromuscular Disorders, Bonn University, Bonn, Germany.
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany.

Isabell Cordts (I)

Department of Neurology, Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Munich, Germany.
ORCID: 0000-0002-2078-1997

Maximilian Vidovic (M)

Department of Neurology, Technische Universität Dresden, University Hospital Carl Gustav Carus, Dresden, Germany.
ORCID: 0000-0003-1453-1681

Robert Steinbach (R)

Department of Neurology, Jena University Hospital, Jena, Germany.
ORCID: 0000-0003-3936-6010

Moritz Metelmann (M)

Department of Neurology, University Hospital Leipzig, Leipzig, Germany.

Vera E Kleinveld (VE)

Department of Neurology, Medical University Innsbruck, Innsbruck, Austria.

Jenny Norden (J)

Department of Neurology, Center for ALS and Other Motor Neuron Disorders, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.

Albert Ludolph (A)

Department of Neurology, Ulm University, Ulm, Germany.
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Ulm, Germany.

Bertram Walter (B)

Department of Neurology, Center for ALS and Other Motor Neuron Disorders, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.

Peggy Schumann (P)

Department of Neurology, Center for ALS and Other Motor Neuron Disorders, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
Ambulanzpartner Soziotechnologie APST GmbH, Berlin, Germany.

Christoph Münch (C)

Department of Neurology, Center for ALS and Other Motor Neuron Disorders, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
Ambulanzpartner Soziotechnologie APST GmbH, Berlin, Germany.

Péter Körtvélyessy (P)

Department of Neurology, Center for ALS and Other Motor Neuron Disorders, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
ORCID: 0000-0003-1262-6169

André Maier (A)

Department of Neurology, Center for ALS and Other Motor Neuron Disorders, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.

Classifications MeSH