Ossemann Michel, de Fays Katalin, Bihin Benoit, Vandermeeren Yves
Université catholique de Louvain (UCL), CHU UCL Namur, Department of Neurology, Avenue Dr G. Thérasse, B5530 Yvoir, Belgium; Université catholique de Louvain (UCL), Institute of NeuroSciences (IoNS), Avenue Hippocrate, 54 Bte 54.10, 1200 Brussels, Belgium.
Université catholique de Louvain (UCL), CHU UCL Namur, Department of Neurology, Avenue Dr G. Thérasse, B5530 Yvoir, Belgium; Université catholique de Louvain (UCL), Institute of NeuroSciences (IoNS), Avenue Hippocrate, 54 Bte 54.10, 1200 Brussels, Belgium.
Epilepsy Res. 2016 Oct;126:78-82. doi: 10.1016/j.eplepsyres.2016.06.004. Epub 2016 Jun 25.
Antiepileptic drugs (AEDs) decrease the occurrence of epileptic seizures and modulate cortical excitability through several mechanisms that likely interact. The modulation of brain excitability by AEDs is believed to reflect their antiepileptic action(s) and could be used as a surrogate marker of their efficacy. Transcranial magnetic stimulation (TMS) is one of the best noninvasive methods to study cortical excitability in human subjects. Specific TMS parameters can be used to quantify the various mechanisms of action of AEDs. A new AED called retigabine increases potassium efflux by changing the conformation of KCNQ 2-5 potassium channels, which leads to neuronal hyperpolarisation and a decrease in excitability.
The purpose of this study is to investigate the effect of retigabine on cortical excitability. Based on the known mechanisms of action of retigabine, we hypothesized that the oral intake of retigabine would increase the resting motor threshold (RMT).
Fifteen healthy individuals participated in a placebo-controlled, double-blind, randomised, clinical trial (RCT). The primary outcome measure was the RMT quantified before and after oral intake of retigabine. Several secondary TMS outcome measures were acquired.
The mean RMT, active motor threshold (AMT) and intensity to obtain a 1mV peak-to-peak amplitude potential (SI1mV) were significantly increased after retigabine intake compared to placebo (RMT: P=0.039; AMT: P=0.014; SI1mV: P=0.019). No significant differences were found for short-interval intracortical inhibition/intracortical facilitation (SICI/ICF), long-interval intracortical inhibition (LICI) or short-interval intracortical facilitation (SICF).
A single dose of retigabine increased the RMT, AMT and S1mV in healthy individuals. No modulating intracortical facilitation or inhibition was observed. This study provides the first in vivo demonstration of the modulating effects of retigabine on the excitability of the human brain, and the results are consistent with the data showing that retigabine hyperpolarizes neurons mainly by increasing potassium conductance.
抗癫痫药物（AEDs）可降低癫痫发作的发生率，并通过几种可能相互作用的机制调节皮层兴奋性。AEDs对脑兴奋性的调节被认为反映了它们的抗癫痫作用，并且可以用作其疗效的替代标志物。经颅磁刺激（TMS）是研究人类受试者皮层兴奋性的最佳非侵入性方法之一。特定的TMS参数可用于量化AEDs的各种作用机制。一种名为瑞替加滨的新型AED通过改变KCNQ 2 - 5钾通道的构象增加钾外流，从而导致神经元超极化并降低兴奋性。
本研究的目的是调查瑞替加滨对皮层兴奋性的影响。基于瑞替加滨已知的作用机制，我们假设口服瑞替加滨会增加静息运动阈值（RMT）。
15名健康个体参与了一项安慰剂对照、双盲、随机临床试验（RCT）。主要结局指标是口服瑞替加滨前后量化的RMT。获取了几个次要的TMS结局指标。
与安慰剂相比，服用瑞替加滨后平均RMT、主动运动阈值（AMT）和获得1mV峰 - 峰值幅度电位的强度（SI1mV）显著增加（RMT：P = 0.039；AMT：P = 0.014；SI1mV：P = 0.019）。在短间隔皮层内抑制/皮层内易化（SICI/ICF）、长间隔皮层内抑制（LICI）或短间隔皮层内易化（SICF）方面未发现显著差异。
单剂量瑞替加滨增加了健康个体的RMT﹑AMT和S1mV。未观察到对皮层内易化或抑制的调节作用。本研究首次在体内证明了瑞替加滨对人脑兴奋性的调节作用，结果与显示瑞替加滨主要通过增加钾电导使神经元超极化的数据一致。
