Motor phenotypes of amyotrophic lateral sclerosis – a three-determinant anatomical classification based on the region of onset, propagation of motor symptoms, and the degree of upper and lower motor neuron dysfunction
Year: 2025
Type: article
Abstract: BACKGROUND: In amyotrophic lateral sclerosis (ALS), heterogeneity of motor phenotypes is a fundamental hallmark of the disease. Distinct ALS phenotypes were associated with a different progression and survival. Despite its relevance for clinical practice and research, there is no broader consensus on the classification of ALS phenotypes. METHODS: An expert consensus process for the classification of ALS motor phenotypes was performed from May 2023 to December 2024. A three-determinant anatomical classification was proposed which is based on the (1) region of onset (O), (2) the propagation of motor symptoms (P), and (3) the degree of upper (UMN) and/or lower motor neuron (LMN) dysfunction (M). Accordingly, this classification is referred to as the "OPM classification". RESULTS: Onset phenotypes differentiate the site of first motor symptoms: O1) head onset; O2d) distal arm onset; O2p) proximal arm onset; O3r) trunk respiratory onset; O3a) trunk axial onset; O4d) distal leg onset; O4p) proximal leg onset. Propagation phenotypes differentiate the temporal propagation of motor symptoms from the site of onset to another, vertically distant body region: PE) earlier propagation (within 12 months of symptom onset); PL) later propagation (without propagation within 12 months of symptom onset), including the established phenotypes of "progressive bulbar paralysis" (O1, PL), "flail-arm syndrome" (O2p, PL), and "flail-leg syndrome" (O4d, PL); PN) propagation not yet classifiable as time since symptom onset is less than 12 months. Phenotypes of motor neuron dysfunction differentiate the degree of UMN and/or LMN dysfunction: M0) balanced UMN and LMN dysfunction; M1d) dominant UMN dysfunction; M1p) pure UMN dysfunction ("primary lateral sclerosis", PLS); M2d) dominant LMN dysfunction; M2p) pure LMN dysfunction ("progressive muscle atrophy", PMA); M3) dissociated motor neuron dysfunction with dominant LMN and UMN dysfunction of the arms and legs ("brachial amyotrophic spastic paraparesis"), respectively. CONCLUSION: This consensus process aimed to standardize the clinical description of ALS motor phenotypes in clinical practice and research - based on the onset region, propagation pattern, and motor neuron dysfunction. This "OPM classification" contributes to specifying the prognosis, to defining the inclusion or stratification criteria in clinical trials and to correlate phenotypes with the underlying disease mechanisms of ALS.
Authors: Thomas Meyer, Matthias Boentert, Julian Großkreutz, Patrick Weydt, Sarah Bernsen, Peter Reilich, Robert Steinbach, Annekathrin Rödiger, Joachim Wolf, Ute Weyen, Albert C. Ludolph, Jochen Weishaupt, Susanne Petri, Paul Lingor, René Günther, Wolfgang Löscher, Markus Weber, Christoph Münch, André Maier, Torsten Grehl
Institutions: Humboldt-Universität zu Berlin, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Charité - Universitätsmedizin Berlin, University of Münster, University Hospital Münster, University of Lübeck, University of Bonn, German Center for Neurodegenerative Diseases, LMU Klinikum, Ludwig-Maximilians-Universität München, Jena University Hospital, BG University Hospital Bergmannsheil Bochum, Universität Ulm, Medizinische Hochschule Hannover, Diakovere, TUM Klinikum, Technical University of Munich, University Hospital Carl Gustav Carus, German Center for Neurodegenerative Diseases (DZNE) Dresden, Technische Universität Dresden, Innsbruck Medical University, Universität Innsbruck, Muskelzentrum/ALS Clinic, Freie Universität Berlin, Alfried Krupp Hospital
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,190
OpenAlex ID: W4409855427