Cortical excitability, as measured by transcranial magnetic stimulation combined with electromyography, is a potential biomarker for the diagnosis and follow-up of epilepsy. We report on long-interval intracortical inhibition data measured in four different centres in healthy controls (n = 95), subjects with refractory genetic generalized epilepsy (n = 40) and with refractory focal epilepsy (n = 69). Long-interval intracortical inhibition was measured by applying two supra-threshold stimuli with an interstimulus interval of 50, 100, 150, 200 and 250 ms and calculating the ratio between the response to the second (test stimulus) and to the first (conditioning stimulus). In all subjects, the median response ratio showed inhibition at all interstimulus intervals. Using a mixed linear-effects model, we compared the long-interval intracortical inhibition response ratios between the different subject types. We conducted two analyses; one including data from the four centres and one excluding data from Centre 2, as the methods in this centre differed from the others. In the first analysis, we found no differences in long-interval intracortical inhibition between the different subject types. In all subjects, the response ratios at interstimulus intervals 100 and 150 ms showed significantly more inhibition than the response ratios at 50, 200 and 250 ms. Our second analysis showed a significant interaction between interstimulus interval and subject type (P = 0.0003). Post hoc testing showed significant differences between controls and refractory focal epilepsy at interstimulus intervals of 100 ms (P = 0.02) and 200 ms (P = 0.04). There were no significant differences between controls and refractory generalized epilepsy groups or between the refractory generalized and focal epilepsy groups. Our results do not support the body of previous work that suggests that long-interval intracortical inhibition is significantly reduced in refractory focal and genetic generalized epilepsy. Results from the second analysis are even in sharper contrast with previous work, showing inhibition in refractory focal epilepsy at 200 ms instead of facilitation previously reported. Methodological differences, especially shorter intervals between the pulse pairs, may have contributed to our inability to reproduce previous findings. Based on our results, we suggest that long-interval intracortical inhibition as measured by transcranial magnetic stimulation and electromyography is unlikely to have clinical use as a biomarker of epilepsy.

中文翻译：

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长间隔皮质内抑制作为癫痫生物标志物：经颅磁刺激研究


通过经颅磁刺激结合肌电图测量的皮质兴奋性是癫痫诊断和随访的潜在生物标志物。我们报告了在四个不同中心测量的健康对照 ( n = 95)、难治性遗传性全身性癫痫 ( n = 40) 和难治性局灶性癫痫 ( n = 69) 受试者的长间隔皮质内抑制数据。长间隔皮质内抑制是通过施加两次阈上刺激（刺激间隔为 50、100、150、200 和 250 毫秒）并计算对第二个（测试刺激）和第一个（条件刺激）的响应之间的比率来测量的。 ）。在所有受试者中，中位反应比在所有刺激间隔均显示抑制。使用混合线性效应模型，我们比较了不同受试者类型之间的长间隔皮质内抑制反应比。我们进行了两项分析；一种包括来自四个中心的数据，另一种不包括来自中心 2 的数据，因为该中心的方法与其他中心不同。在第一个分析中，我们发现不同受试者类型之间的长间隔皮质内抑制没有差异。在所有受试者中，刺激间隔 100 和 150 毫秒的反应比显示出比 50、200 和 250 毫秒的反应比明显更多的抑制作用。我们的第二次分析显示刺激间隔和受试者类型之间存在显着的交互作用（ P = 0.0003）。事后测试显示，刺激间隔为 100 毫秒（ P = 0.02）和 200 毫秒（ P = 0.04）时，对照组和难治性局灶性癫痫之间存在显着差异。 对照组和难治性全身性癫痫组之间或者难治性全身性癫痫组和局灶性癫痫组之间没有显着差异。我们的结果并不支持之前的研究结果，即长间隔皮质内抑制在难治性局灶性和遗传性全身性癫痫中显着减少。第二次分析的结果与之前的研究形成了更鲜明的对比，显示 200 毫秒时对难治性局灶性癫痫有抑制作用，而不是之前报道的促进作用。方法上的差异，尤其是脉冲对之间较短的间隔，可能导致我们无法重现以前的发现。根据我们的结果，我们认为通过经颅磁刺激和肌电图测量的长间隔皮质内抑制不太可能在临床上用作癫痫的生物标志物。