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.

Q2 Medicine
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
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引用次数: 0

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.

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。
背景:在肌萎缩性侧索硬化症(ALS)中,运动表型的异质性是该疾病的基本标志。不同的ALS表型与不同的进展和生存相关。尽管它与临床实践和研究相关,但对ALS表型的分类没有更广泛的共识。方法:从2023年5月到2024年12月,对ALS运动表型进行了专家共识分类。提出了一个三决定因素的解剖学分类,该分类基于(1)发病区域(O),(2)运动症状的传播(P),以及(3)上(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”。结果:发病表型可区分首次运动症状的部位:1)头部发病;O2d)远端臂发病;O2p)上臂近端发病;O3r)躯干呼吸发作;O3a)干轴向开始;O4d)小腿远端发病;O4p)小腿近端发病。传播表型区分运动症状从发病部位到另一个垂直远处身体区域的时间传播:PE)早期传播(症状发病后12个月内);PL)后期繁殖(在症状出现的12个月内没有繁殖),包括已确定的“进行性球麻痹”(O1, PL)、“连枷臂综合征”(O2p, PL)和“连枷腿综合征”(O4d, PL)等表型;自症状出现以来的传播时间少于12个月,尚未分类。运动神经元功能障碍的表型可区分UMN和/或LMN功能障碍的程度:M0)平衡的UMN和LMN功能障碍;M1d)显性UMN功能障碍;M1p)纯UMN功能障碍(“原发性侧索硬化”,PLS);M2d)显性LMN功能障碍;M2p)纯LMN功能障碍(进行性肌肉萎缩,PMA);M3)分离的运动神经元功能障碍,主要表现为手臂和腿部的LMN和UMN功能障碍(“肱肌萎缩性痉挛性截瘫”)。结论:这一共识过程旨在规范临床实践和研究中ALS运动表型的临床描述——基于发病区域、传播模式和运动神经元功能障碍。这种“OPM分类”有助于明确预后,定义临床试验中的纳入或分层标准,并将表型与ALS的潜在疾病机制联系起来。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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CiteScore
7.40
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0.00%
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14 weeks
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