Calma Aicee Dawn, van den Bos Mehdi, Pavey Nathan, Santos Silva Cláudia, Menon Parvathi, Vucic Steve
Brain and Nerve Research Center, The University of Sydney, Sydney 2139, Australia.
Department of Neurosciences and Mental Health, Unidade Local de Saúde de Santa Maria, 1649-028 Lisbon, Portugal.
Brain Sci. 2024 Jul 29;14(8):760. doi: 10.3390/brainsci14080760.
Upper motor neuron (UMN) dysfunction is an important feature of amyotrophic lateral sclerosis (ALS) for the diagnosis and understanding of pathogenesis. The identification of UMN signs forms the basis of ALS diagnosis, although may be difficult to discern, especially in the setting of severe muscle weakness. Transcranial magnetic stimulation (TMS) techniques have yielded objective physiological biomarkers of UMN dysfunction in ALS, enabling the interrogation of cortical and subcortical neuronal networks with diagnostic, pathophysiological, and prognostic implications. Transcranial magnetic stimulation techniques have provided pertinent pathogenic insights and yielded novel diagnostic and prognostic biomarkers. Cortical hyperexcitability, as heralded by a reduction in short interval intracortical inhibition (SICI) and an increase in short interval intracortical facilitation (SICF), has been associated with lower motor neuron degeneration, patterns of disease evolution, as well as the development of specific ALS clinical features including the split hand phenomenon. Reduction in SICI has also emerged as a potential diagnostic aid in ALS. More recently, physiological distinct inhibitory and facilitatory cortical interneuronal circuits have been identified, which have been shown to contribute to ALS pathogenesis. The triple stimulation technique (TST) was shown to enhance the diagnostic utility of conventional TMS measures in detecting UMN dysfunction. Resting-state EEG is a novel neurophysiological technique developed for directly interrogating cortical neuronal networks in ALS, that have yielded potentially useful physiological biomarkers of UMN dysfunction. The present review discusses physiological biomarkers of UMN dysfunction in ALS, encompassing conventional and novel TMS techniques developed to interrogate the functional integrity of the corticomotoneuronal system, focusing on pathogenic, diagnostic, and prognostic utility.
上运动神经元（UMN）功能障碍是肌萎缩侧索硬化症（ALS）诊断和理解发病机制的重要特征。UMN体征的识别是ALS诊断的基础，尽管可能难以辨别，尤其是在严重肌肉无力的情况下。经颅磁刺激（TMS）技术已产生了ALS中UMN功能障碍的客观生理生物标志物，能够对具有诊断、病理生理和预后意义的皮质和皮质下神经元网络进行研究。经颅磁刺激技术提供了相关的致病见解，并产生了新的诊断和预后生物标志物。皮质兴奋性过高，表现为短间隔皮质内抑制（SICI）降低和短间隔皮质内易化（SICF）增加，与下运动神经元变性、疾病演变模式以及包括裂手现象在内的特定ALS临床特征的发展有关。SICI降低也已成为ALS的一种潜在诊断辅助手段。最近，已确定了生理上不同的抑制性和易化性皮质中间神经元回路，这些回路已被证明与ALS发病机制有关。三重刺激技术（TST）被证明可提高传统TMS测量在检测UMN功能障碍方面的诊断效用。静息态脑电图是一种新开发的神经生理学技术，用于直接研究ALS中的皮质神经元网络，已产生了UMN功能障碍的潜在有用生理生物标志物。本综述讨论了ALS中UMN功能障碍的生理生物标志物，包括为研究皮质运动神经元系统功能完整性而开发的传统和新型TMS技术，重点关注其致病、诊断和预后效用。
