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
{"title":"肌萎缩性侧索硬化症的运动表型——基于发病区域、运动症状的传播和上下运动神经元功能障碍程度的三决定因素解剖学分类。","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","doi":"10.1186/s42466-025-00389-w","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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\".</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":94156,"journal":{"name":"Neurological research and practice","volume":"7 1","pages":"27"},"PeriodicalIF":0.0000,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036282/pdf/","citationCount":"0","resultStr":"{\"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.\",\"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\",\"doi\":\"10.1186/s42466-025-00389-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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\\\".</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":94156,\"journal\":{\"name\":\"Neurological research and practice\",\"volume\":\"7 1\",\"pages\":\"27\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-04-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036282/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neurological research and practice\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1186/s42466-025-00389-w\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurological research and practice","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1186/s42466-025-00389-w","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}
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.
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.