Westmead Clinical School, University of Sydney, Sydney, NSW, Australia.
Brain and Mind Center, University of Sydney, Sydney, NSW, Australia.
Ann Clin Transl Neurol. 2020 May;7(5):733-741. doi: 10.1002/acn3.51039. Epub 2020 Apr 18.
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.
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.
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).
This study established an increase in cortical hyperexcitability with increased disease duration in ALS, mediated by cortical disinhibition and direct increase in corticomotoneuronal excitability.
皮层兴奋性过高已被确立为肌萎缩侧索硬化症（ALS）的早期特征。ALS 进展过程中皮层兴奋性过高的演变仍有待充分阐明。本研究旨在探讨随着疾病进展，ALS 患者皮层功能的变化。
对 444 名疑似 ALS 的患者（345 名 ALS 患者；99 名神经肌肉模拟患者）进行经颅磁刺激（TMS）阈跟踪评估的皮层功能检查，同时进行临床表型分析。疾病分期如下：（1）King 临床分期系统和（2）根据疾病持续时间的比例分为三分之一。
在所有 ALS 阶段均可见皮层兴奋性过高，在 ALS 的晚期更为明显，表现为运动诱发电位幅度增加（P < 0.05），以及随着疾病持续时间的延长，短程皮质内抑制减少（P < 0.05）。随着疾病的进展，中央运动传导时间延长。这些变化伴随着神经生理指数（P < 0.001）和复合肌肉动作电位幅度（P < 0.01）的降低、肌肉无力的进行性加重（P < 0.001）和 ALS 功能评定量表评分的下降（P < 0.001）。
本研究确立了 ALS 患者皮层兴奋性过高与疾病持续时间增加有关，其机制为皮质抑制解除和皮质运动神经元兴奋性直接增加。
