Meyer Thomas, Boentert Matthias, Großkreutz Julian, Weydt Patrick, Bernsen Sarah, Reilich Peter, Steinbach Robert, Rödiger Annekathrin, Wolf Joachim, Weyen Ute, Ludolph Albert C, Weishaupt Jochen, Petri Susanne, Lingor Paul, Günther René, Löscher Wolfgang, Weber Markus, Münch Christoph, Maier André, Grehl Torsten
Department 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 Health, Augustenburger Platz 1, 13353, Berlin, Germany.
APST Research GmbH, Berlin, Germany.
Neurol Res Pract. 2025 Apr 28;7(1):27. doi: 10.1186/s42466-025-00389-w.
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.
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".
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.
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.
在肌萎缩侧索硬化症（ALS）中，运动表型的异质性是该疾病的一个基本特征。不同的ALS表型与不同的疾病进展和生存期相关。尽管其对临床实践和研究具有重要意义，但对于ALS表型的分类尚未达成更广泛的共识。
于2023年5月至2024年12月开展了一项关于ALS运动表型分类的专家共识过程。提出了一种基于三个决定因素的解剖学分类方法，该方法基于：（1）起病部位（O）；（2）运动症状的传播（P）；（3）上运动神经元（UMN）和/或下运动神经元（LMN）功能障碍的程度（M）。因此，这种分类被称为“OPM分类”。
起病表型区分首发运动症状的部位：O1）头部起病；O2d）手臂远端起病；O2p）手臂近端起病；O3r）躯干呼吸肌起病；O3a）躯干轴向起病；O4d）腿部远端起病；O4p）腿部近端起病。传播表型区分运动症状从起病部位到另一个垂直距离较远的身体区域的时间传播情况：PE）早期传播（症状出现后12个月内）；PL）晚期传播（症状出现后12个月内无传播），包括已确定的“进行性延髓麻痹”（O1，PL）、“连枷臂综合征”（O2p，PL）和“连枷腿综合征”（O4d，PL）等表型；PN）由于症状出现时间少于12个月，传播情况尚无法分类。运动神经元功能障碍表型区分UMN和/或LMN功能障碍的程度：M0）UMN和LMN功能障碍平衡；M1d）UMN功能障碍为主；M1p）纯UMN功能障碍（“原发性侧索硬化症”，PLS）；M2d）LMN功能障碍为主；M2p）纯LMN功能障碍（“进行性肌肉萎缩”，PMA）；M3）解离性运动神经元功能障碍，分别以手臂和腿部的LMN和UMN功能障碍为主（“臂丛性肌萎缩性痉挛性截瘫”）。
这一共识过程旨在基于起病区域、传播模式和运动神经元功能障碍，规范临床实践和研究中ALS运动表型的临床描述。这种“OPM分类”有助于明确预后，确定临床试验中的纳入或分层标准，并将表型与ALS的潜在疾病机制相关联。
