Cortical hyperexcitability evolves with disease progression in ALS
Cortical hyperexcitability evolves with disease progression in ALS
复制标题
DOI：
10.1002/acn3.51039
复制
发表时间：
2020-04-18
影响因子：
5.3
通讯作者：
Vucic, Steve
中科院分区：
文献类型：
--
作者：
Menon, Parvathi;Higashihara, Mana;Vucic, Steve
目的皮质高兴奋性是肌萎缩侧索硬化症(ALS)的早期特征。随着肌萎缩侧索硬化症的进展，皮质超兴奋性的演变仍未完全阐明。本研究旨在探讨ALS患者皮质功能随疾病进展的变化。方法前瞻性地对444例疑似ALS患者(345例ALS；99例神经肌肉模拟物)进行阈值跟踪经颅磁刺激(TMS)和临床分型。结果ALS各期患者均表现出明显的皮质兴奋性，表现为运动诱发电位波幅增高(P<；0.05)，皮质短间期抑制程度降低(P<；0.05)。随着疾病的进展，中枢运动传导时间明显延长。伴随着这些变化的是神经生理指数(P<；0.001)和复合肌肉动作电位波幅(P<；0.001)的下降，进行性肌肉无力(P<；0.001)，以及肌萎缩侧索硬化症功能评定量表(P<；0.001)的下降。解释这项研究证实，随着病程的延长，肌萎缩侧索硬化症患者皮质的过度兴奋性增加，这是由皮质去抑制和皮质运动神经元兴奋性直接增加所介导的。
Objective Cortical hyperexcitability has been established as an early feature of amyotrophic lateral sclerosis (ALS). The evolution of cortical hyperexcitability with ALS progression remains to be fully elucidated. This study aims to investigate changes in cortical function in ALS with disease progression.Methods Cortical function assessed by threshold tracking transcranial magnetic stimulation (TMS) along with clinical phenotyping was prospectively undertaken on 444 patients presenting with suspected ALS (345 ALS; 99 neuromuscular mimics). Disease stage was defined as follows: (1) King's clinical staging system and (2) proportion of disease duration statistically categorized into tertials.Results Cortical hyperexcitability was evident across all ALS stages, being more prominent in later stages of ALS as indicated by increased motor-evoked potential amplitude (P < 0.05), as well as longer disease duration as reflected by reduced short-interval intracortical inhibition (P < 0.05). Prolonged central motor conduction time was evident with disease progression. These changes were accompanied by reduction in neurophysiological index (P < 0.001) and compound muscle action potential amplitude (P < 0.01), progressive muscle weakness (P < 0.001), and decline in the ALS functional rating scale (P < 0.001).Interpretation This study established an increase in cortical hyperexcitability with increased disease duration in ALS, mediated by cortical disinhibition and direct increase in corticomotoneuronal excitability.