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
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 con...
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2025-04-01
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| author | 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 |
| author_facet | 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 |
| author_sort | Thomas Meyer |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-4ebf26de9fe74ad998fa20dd5b3ea8fb |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-04-01 |
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| spelling | doaj-art-4ebf26de9fe74ad998fa20dd5b3ea8fb2025-08-20T03:52:29ZengBMCNeurological Research and Practice2524-34892025-04-017111410.1186/s42466-025-00389-wMotor 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 dysfunctionThomas Meyer0Matthias Boentert1Julian Großkreutz2Patrick Weydt3Sarah Bernsen4Peter Reilich5Robert Steinbach6Annekathrin Rödiger7Joachim Wolf8Ute Weyen9Albert C. Ludolph10Jochen Weishaupt11Susanne Petri12Paul Lingor13René Günther14Wolfgang Löscher15Markus Weber16Christoph Münch17André Maier18Torsten Grehl19Department of Neurology, Center for ALS and other Motor Neuron Disorders, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of HealthDepartment of Neurology, Münster University HospitalDepartment of Neurology, Universitätsmedizin Schleswig-HolsteinDepartment for Neurodegenerative and Neuromuscular Disorders, Bonn UniversityDepartment for Neurodegenerative and Neuromuscular Disorders, Bonn UniversityDepartment of Neurology, LMU University HospitalDepartment of Neurology, Jena University HospitalDepartment of Neurology, Jena University HospitalDepartment of Neurology, Diako MannheimDepartment of Neurology, Berufsgenossenschaftliches Universitätsklinikum BergmannsheilDepartment of Neurology, Ulm UniversityDepartment of Neurology, Ulm UniversityDepartment of Neurology, Diakovere Henriettenstift and FriederikenstiftDepartment of Neurology, Technical University of Munich, Klinikum rechts der IsarDepartment of Neurology, Technische Universität Dresden, University Hospital Carl Gustav CarusDepartment of Neurology, Unit for Neuromuscular Disorders and Clinical Neurophysiology, Medical University of InnsbruckNeuromuscular Diseases Unit/ALS Clinic, HOCH Health OstschweizDepartment of Neurology, Center for ALS and other Motor Neuron Disorders, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of HealthDepartment of Neurology, Center for ALS and other Motor Neuron Disorders, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of HealthDepartment of Neurology, Center for ALS and other Motor Neuron Disorders, Alfried Krupp KrankenhausAbstract 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.https://doi.org/10.1186/s42466-025-00389-wAmyotrophic lateral sclerosisMotor phenotypesClassificationOPM |
| spellingShingle | 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 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 Neurological Research and Practice Amyotrophic lateral sclerosis Motor phenotypes Classification OPM |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Amyotrophic lateral sclerosis Motor phenotypes Classification OPM |
| url | https://doi.org/10.1186/s42466-025-00389-w |
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