Transcranial magnetic stimulation (TMS), a non-invasive procedure, stimulates the cortex evaluating the central motor pathways. The response is called motor evoked potential (MEP). Polyphasia results when the response crosses the baseline more than twice (zero crossing). Recent research shows MEP polyphasia in patients with generalized genetic epilepsy (GGE) and their first-degree relatives compared with controls. Juvenile Myoclonic Epilepsy (JME), a GGE type, is not well studied regarding polyphasia. In our study, we assessed polyphasia appearance probability with TMS in JME patients, their healthy first-degree relatives and controls. Two genetic approaches were applied to uncover genetic association with polyphasia.

20 JME patients, 23 first-degree relatives and 30 controls underwent TMS, obtaining 10–15 MEPs per participant. We evaluated MEP mean number of phases, proportion of MEP trials displaying polyphasia for each subject and variability between groups. Participants underwent whole exome sequencing (WES) via trio-based analysis and two-case scenario. Extensive bioinformatics analysis was applied.

We identified increased polyphasia in patients (85%) and relatives (70%) compared to controls (47%) and significantly higher mean number of zero crossings (i.e., occurrence of phases) (patients 1.49, relatives 1.46, controls 1.22; p < 0.05). Trio-based analysis revealed a candidate polymorphism, p.Glu270del,in SYT14 (Synaptotagmin 14), in JME patients and their relatives presenting polyphasia. Sanger sequencing analysis in remaining participants showed no significant association. In two-case scenario, a machine learning approach was applied in variants identified from odds ratio analysis and risk prediction scores were obtained for polyphasia. The results revealed 61 variants of which none was associated with polyphasia. Risk prediction scores indeed showed lower probability for non-polyphasic subjects on having polyphasia and higher probability for polyphasic subjects on having polyphasia.

Polyphasia was present in JME patients and relatives in contrast to controls. Although no known clinical symptoms are linked to polyphasia this neurophysiological phenomenon is likely due to common cerebral electrophysiological abnormality. We did not discover direct association between genetic variants obtained and polyphasia. It is likely these genetic traits alone cannot provoke polyphasia, however, this predisposition combined with disturbed brain-electrical activity and tendency to generate seizures may increase the risk of developing polyphasia, mainly in patients and relatives.

经颅磁刺激 (TMS) 是一种非侵入性程序，可刺激评估中枢运动通路的皮层。该反应称为运动诱发电位 (MEP)。当反应超过基线两次（零交叉）时，就会出现多相。最近的研究表明，与对照组相比，全身性遗传性癫痫 (GGE) 患者及其一级亲属的 MEP 多相。青少年肌阵挛性癫痫 (JME) 是一种 GGE 类型，关于多相症的研究并不充分。在我们的研究中，我们用 TMS 评估了 JME 患者、他们的健康一级亲属和对照的多相出现概率。应用了两种遗传方法来揭示与多相症的遗传关联。

20 名 JME 患者、23 名一级亲属和 30 名对照组接受了 TMS，每位参与者获得 10-15 个 MEP。我们评估了 MEP 平均阶段数、显示每个受试者多相的 MEP 试验比例以及组间变异性。参与者通过基于三人组的分析和两例情景进行了全外显子组测序（WES）。应用了广泛的生物信息学分析。

我们发现，与对照组 (47%) 相比，患者 (85%) 和亲属 (70%) 的多相症增加，过零的平均数显着增加（即阶段的发生）（患者 1.49，亲属 1.46，对照 1.22；p< 0.05)。基于 Trio 的分析揭示了一个候选多态性 p.Glu270del,inSYT14（突触结合蛋白 14），在 JME 患者及其亲属中出现多相症。其余参与者的 Sanger 测序分析显示没有显着关联。在两种情况下，机器学习方法应用于从优势比分析中识别的变体，并获得多相症的风险预测分数。结果揭示了 61 个变体，其中没有一个与多相症相关。风险预测分数确实显示非多相受试者患多相症的概率较低，而多相受试者患多相症的概率较高。

与对照组相比，JME 患者和亲属中存在多相。尽管没有已知的临床症状与多相症有关，但这种神经生理现象可能是由于常见的脑电生理异常所致。我们没有发现获得的遗传变异与多相症之间的直接关联。单凭这些遗传特征很可能不会引起多相症，然而，这种易感性与脑电活动紊乱和癫痫发作的倾向相结合，可能会增加患多相症的风险，主要发生在患者和亲属中。