PDF(Pubmed)
Abstract：
Progressive myoclonic epilepsy type 1 (EPM1) is caused by biallelic alterations in the CSTB gene, most commonly dodecamer repeat expansions. Although transcranial magnetic stimulation (TMS)-induced long-interval intracortical inhibition (LICI) was previously reported to be normal in EPM1, short-interval intracortical inhibition (SICI) was reduced. We explored the association between these measures and the clinical and genetic features in a separate group of patients with EPM1.
TMS combined with electromyography was performed under neuronavigation. LICI was induced with an inter-stimulus interval (ISI) of 100 ms, and SICI with ISIs of 2 and 3 ms, and their means (mSICIs) were expressed as the ratio of conditioned to unconditioned stimuli. LICI and mSICI were compared between patients and controls. Nonparametric correlation was used to study the association between inhibition and parameters of clinical severity, including the Unified Myoclonus Rating Scale (UMRS); among patients with EPM1 due to biallelic expansion repeats, also the association with the number of repeats was assessed.
The study protocol was completed in 19 patients (15 with biallelic expansion repeats and 4 compound heterozygotes), and 7 healthy, age- and sex-matched control participants. Compared to controls, patients demonstrated significantly less SICI (median mSICI ratio 1.18 vs 0.38; p < .001). Neither LICI nor SICI was associated with parameters of clinical severity. In participants with biallelic repeat expansions, the number of repeats in the more affected allele (greater repeat number [GRN]) correlated with LICI (rho = 0.872; p < .001) and SICI (rho = 0.689; p = .006).
Our results strengthen the finding of deranged γ-aminobutyric acid (GABA)ergic inhibition in EPM1. LICI and SICI may have use as markers of GABAergic impairment in future trials of disease-modifying treatment in this condition. Whether a higher number of expansion repeats leads to greater GABAergic impairment warrants further study.
TMS combined with electromyography was performed under neuronavigation. LICI was induced with an inter-stimulus interval (ISI) of 100 ms, and SICI with ISIs of 2 and 3 ms, and their means (mSICIs) were expressed as the ratio of conditioned to unconditioned stimuli. LICI and mSICI were compared between patients and controls. Nonparametric correlation was used to study the association between inhibition and parameters of clinical severity, including the Unified Myoclonus Rating Scale (UMRS); among patients with EPM1 due to biallelic expansion repeats, also the association with the number of repeats was assessed.
The study protocol was completed in 19 patients (15 with biallelic expansion repeats and 4 compound heterozygotes), and 7 healthy, age- and sex-matched control participants. Compared to controls, patients demonstrated significantly less SICI (median mSICI ratio 1.18 vs 0.38; p < .001). Neither LICI nor SICI was associated with parameters of clinical severity. In participants with biallelic repeat expansions, the number of repeats in the more affected allele (greater repeat number [GRN]) correlated with LICI (rho = 0.872; p < .001) and SICI (rho = 0.689; p = .006).
Our results strengthen the finding of deranged γ-aminobutyric acid (GABA)ergic inhibition in EPM1. LICI and SICI may have use as markers of GABAergic impairment in future trials of disease-modifying treatment in this condition. Whether a higher number of expansion repeats leads to greater GABAergic impairment warrants further study.
摘要：
目的：进行性肌阵挛性癫痫1型（EPM1）是由CSTB基因的双等位基因改变引起的，最常见的是十二聚体重复扩增。尽管先前报道了经颅磁刺激（TMS）诱导的长间隔皮质内抑制（LICI）在EPM1中正常，但短间隔皮质内抑制（SICI）却降低了。我们在一组单独的EPM1患者中探索了这些措施与临床和遗传特征之间的关联。
方法：在神经导航下进行TMS联合肌电图检查。诱导LICI的刺激间隔（ISI）为100毫秒，以及ISI为2和3ms的SICI，它们的均值（mSICIs）表示为条件刺激与非条件刺激的比率。在患者和对照组之间比较LICI和mSICI。非参数相关性用于研究抑制与临床严重程度参数之间的关联，包括统一肌阵风评定量表（UMRS）；在由于双等位基因扩增重复而患有EPM1的患者中，还评估了与重复次数的相关性.
结果：在19例患者中完成了研究方案（15例具有双等位基因扩增重复和4个复合杂合子），7、健康年龄和性别匹配的对照参与者。与对照组相比，患者的SICI明显减少（mSICI比值中位数为1.18vs0.38；p<.001）。LICI和SICI均与临床严重程度参数无关。在双等位基因重复扩展的参与者中，受影响较大的等位基因中的重复数(较大的重复数[GRN])与LICI(rho=0.872;p<.001)和SICI(rho=0.689;p=.006)相关。
结论：我们的结果加强了EPM1中γ-氨基丁酸（GABA）能抑制的发现。在这种情况下，LICI和SICI可能在未来的疾病修饰治疗试验中用作GABA能损伤的标志物。更高的扩增重复次数是否会导致更大的GABA能损害值得进一步研究。
方法：在神经导航下进行TMS联合肌电图检查。诱导LICI的刺激间隔（ISI）为100毫秒，以及ISI为2和3ms的SICI，它们的均值（mSICIs）表示为条件刺激与非条件刺激的比率。在患者和对照组之间比较LICI和mSICI。非参数相关性用于研究抑制与临床严重程度参数之间的关联，包括统一肌阵风评定量表（UMRS）；在由于双等位基因扩增重复而患有EPM1的患者中，还评估了与重复次数的相关性.
结果：在19例患者中完成了研究方案（15例具有双等位基因扩增重复和4个复合杂合子），7、健康年龄和性别匹配的对照参与者。与对照组相比，患者的SICI明显减少（mSICI比值中位数为1.18vs0.38；p<.001）。LICI和SICI均与临床严重程度参数无关。在双等位基因重复扩展的参与者中，受影响较大的等位基因中的重复数(较大的重复数[GRN])与LICI(rho=0.872;p<.001)和SICI(rho=0.689;p=.006)相关。
结论：我们的结果加强了EPM1中γ-氨基丁酸（GABA）能抑制的发现。在这种情况下，LICI和SICI可能在未来的疾病修饰治疗试验中用作GABA能损伤的标志物。更高的扩增重复次数是否会导致更大的GABA能损害值得进一步研究。
