Neuromodulation Program, Department of Neurology, Division of Epilepsy and Clinical Neurophysiology, Boston Children's Hospital, Boston, MA, USA; FM Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Boston, MA, USA.
Behavioral Neuroscience Program, Boston University School of Medicine, Boston, MA, USA.
Clin Ther. 2020 Jul;42(7):1155-1168. doi: 10.1016/j.clinthera.2020.05.016. Epub 2020 Jul 3.
Despite the availability of numerous pharmacologic and nonpharmacologic antiseizure therapies, a fraction of patients with epilepsy remain refractory to current treatment options, underscoring the need for novel drugs and neuromodulatory therapies. Transcranial magnetic stimulation (TMS), coupled with either electromyography or electroencephalography, enables rapid measurement of the cortical excitation/inhibition ratio, which is pathologically shifted toward excess excitability in patients with epilepsy. In this review, we summarize: (1) TMS protocols that have been deployed to identify promising compounds in the antiepilepsy drug (AED)-development pipeline, and (2) the therapeutic potential of TMS in the treatment of drug-resistant seizures.
A focused literature review of the use of TMS in epilepsy, using a PubMed search, was performed. Over 70 articles were included that pertained to: (1) the use of TMS-EMG and TMS-EEG in elucidating the mechanisms of action of AEDs and in discovering potential new AEDs; and (2) the use of repetitive TMS in the treatment of seizures.
Studies from the literature have reported that AEDs alter TMS-derived metrics, typically by leading to a net increase in cortical inhibition with successful therapy. Preclinical TMS work in rodent models of epilepsy has led to the development of novel antiseizure drug compounds. Clinical translational studies of TMS have been used to determine guidelines on the dosages of other agents in the AED pipeline in preparation for clinical trials. Several studies have described the use of therapeutic repetitive TMS in both the ictal and interictal states of epilepsy, with inconsistent results.
TMS has diagnostic and therapeutic potential in epilepsy. TMS-derived markers can enable early-stage measures of AED target engagement, and can facilitate studies of the pharmacokinetic and pharmacodynamic properties of AEDs. TMS may also be used in the early prediction of the efficacy of different AEDs in treating patients, and in direct neuromodulation of epileptic networks. From the therapeutics perspective, despite favorable results in some trials, the optimization of treatment paradigms and the determination of ideal candidates for TMS are still needed. Finally, preclinical experiments of TMS have provided mechanistic insight into its effects on the excitation/inhibition ratio, and may facilitate rational drug-device coupling paradigms. Overall, the capacity of TMS in both the modulation and measurement of changes in cortical excitability highlights its unique role in advancing antiepilepsy therapeutics.
尽管有许多药物和非药物的抗癫痫治疗方法，但仍有一部分癫痫患者对现有治疗方案无反应，这突显了对新型药物和神经调节治疗方法的需求。经颅磁刺激（TMS）结合肌电图或脑电图，可以快速测量皮质兴奋/抑制比，癫痫患者的皮质兴奋/抑制比表现出病理性的过度兴奋。在本综述中，我们总结了：（1）已用于确定抗癫痫药物（AED）开发管道中有前途化合物的 TMS 方案；（2）TMS 在治疗耐药性癫痫中的治疗潜力。
使用 PubMed 进行了针对 TMS 在癫痫中的应用的重点文献回顾。共纳入了 70 多篇与以下内容相关的文章：（1）TMS-EMG 和 TMS-EEG 用于阐明 AED 的作用机制和发现潜在的新 AED；（2）重复 TMS 在治疗癫痫中的应用。
文献中的研究报告称，AED 改变了 TMS 衍生的指标，通常通过成功治疗导致皮质抑制的净增加来实现。癫痫啮齿动物模型中的临床前 TMS 工作导致了新型抗癫痫药物化合物的开发。TMS 的临床转化研究用于确定 AED 管道中其他药物的剂量指南，为临床试验做准备。几项研究描述了在癫痫的发作期和发作间期使用治疗性重复 TMS，结果不一致。
TMS 在癫痫中有诊断和治疗潜力。TMS 衍生的标志物可以实现 AED 靶标结合的早期评估，并有助于研究 AED 的药代动力学和药效动力学特性。TMS 也可用于早期预测不同 AED 治疗患者的疗效，并直接调节癫痫网络。从治疗角度来看，尽管一些试验结果有利，但仍需要优化治疗方案，并确定 TMS 的理想候选者。最后，TMS 的临床前实验提供了对其对兴奋/抑制比影响的机制见解，并可能促进合理的药物-器械耦合模式。总的来说，TMS 调节和测量皮质兴奋性变化的能力突出了其在推进抗癫痫治疗方面的独特作用。
