Cortical Excitability as a Prognostic and Phenotypic Stratification Biomarker in Amyotrophic Lateral Sclerosis.

IF 8.1 1区医学 Q1 CLINICAL NEUROLOGY

Annals of Neurology Pub Date : 2025-06-25 DOI:10.1002/ana.27305

Federico Ranieri, Gianmaria Senerchia, Luigi Bonan, Stefania Casali, Corrado Cabona, Mariagiovanna Cantone, Fabiola De Marchi, Luca Diamanti, Alberto Doretti, Nicola Fini, Massimiliano Filosto, Andrea Fortuna, Aniello Iovino, Valentina Virginia Iuzzolino, Giuseppe Lanza, Christian Lunetta, Luca Maderna, Jessica Mandrioli, Letizia Mazzini, Gabriella Musumeci, Andi Nuredini, Gianni Sorarù, Antonella Toriello, Nicola Ticozzi, Massimiliano Todisco, Veria Vacchiano, Lucia Zinno, Vincenzo Silani, Simone Rossi, Vincenzo Di Lazzaro, Raffaele Dubbioso

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引用次数: 0

Abstract

Objective: Despite its clinical heterogeneity, amyotrophic lateral sclerosis is unified by early and prominent alterations in cortical excitability, increasingly recognized as contributors to disease progression. This study assessed whether the ratio between motor evoked potential (MEP) amplitude, reflecting upper motor neuron integrity, and compound muscle action potential (CMAP) amplitude, indexing lower motor neuron function, could provide an accessible marker of corticospinal excitability to stratify patients by phenotype, stage, and survival.

Methods: In this multicenter retrospective study, 743 amyotrophic lateral sclerosis patients from 16 tertiary centers in Italy were analyzed. The MEP:CMAP ratio, recorded from upper limb muscles, was categorized as hyperexcitable, normal, or hypoexcitable. Phenotypes included progressive muscular atrophy (or lower motor neuron), flail arm/leg, classic, bulbar, patient with predominant upper motor neuron signs (or pyramidal), and primary lateral sclerosis. Disease stage was assessed using King's staging. Survival was analyzed using Kaplan-Meier curves and Cox regression models.

Results: The MEP:CMAP ratio differed significantly across phenotypes (p < 0.0001), with hyperexcitability predominating in lower motor neuron, flail, classic, and bulbar forms, and hypoexcitability in pyramidal and primary lateral sclerosis. Hypoexcitability increased in advanced King's stages (p < 0.0001). Hyperexcitable patients had shorter survival (p = 0.004), including when tested within 1 year of onset (p = 0.006). Cox regression identified the MEP:CMAP ratio as an independent survival predictor (HR 1.84, 95% CI 1.12-3.03, p = 0.016).

Interpretation: This real-world study supports the clinical value of the MEP:CMAP ratio as a scalable biomarker of cortical excitability in amyotrophic lateral sclerosis, with prognostic relevance across phenotypes and disease stages. ANN NEUROL 2025.

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皮质兴奋性作为肌萎缩性侧索硬化症的预后和表型分层生物标志物。

目的：尽管其临床异质性，肌萎缩侧索硬化症是由早期和显著的皮质兴奋性改变统一的，越来越多地认识到这是疾病进展的因素。本研究评估了反映上运动神经元完整性的运动诱发电位（MEP）振幅与反映下运动神经元功能的复合肌肉动作电位（CMAP）振幅之间的比值，是否可以为皮质脊髓兴奋性提供一个可访问的标志物，以按表型、分期和生存对患者进行分层。方法：在这项多中心回顾性研究中，对意大利16个三级中心的743例肌萎缩侧索硬化症患者进行了分析。从上肢肌肉记录的MEP:CMAP比率分为过度兴奋、正常和低兴奋。表型包括进行性肌肉萎缩（或下运动神经元），连枷臂/腿，典型，球型，以上运动神经元体征为主的患者（或锥体）和原发性侧索硬化。采用King分期法评估疾病分期。生存率分析采用Kaplan-Meier曲线和Cox回归模型。结果：MEP:CMAP比值在不同表型之间存在显著差异(p)。解释：这项现实世界的研究支持MEP:CMAP比值作为肌萎缩性侧索硬化症皮质兴奋性的可扩展生物标志物的临床价值，具有不同表型和疾病分期的预后相关性。Ann neurol 2025。

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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来源期刊

Annals of Neurology 医学-临床神经学

CiteScore

18.00

自引率

1.80%

发文量

270

审稿时长

3-8 weeks

期刊介绍： Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.