我国儿童癫痫的年发病率约为15.1/万人，其中30%左右无法用抗癫痫药物控制，为难治性癫痫。癫痫患者的自主神经系统功能受损，影响心脏活动，心率变异性昼夜节律扁平。儿童癫痫不仅影响身心健康，其频繁发作更不利于患儿的生长发育和生活技能学习，尤其是处于快速发育期的3-6岁学龄前儿童，因此治疗、控制癫痫发作尤为重要。迷走神经刺激能够控制部分难治性癫痫的发作，但疗效个体差异大，疗法的临床推广和进一步发展受到一定限制。本文从3-6岁儿童癫痫的心率变异性昼夜节律出发，研究迷走神经刺激的影响；针对疗效不同的患儿，探寻迷走神经刺激影响心率变异性昼夜节律的不同模式，希望以相关发现为基础，支持迷走神经刺激的疗法研究。首先，分析了46名3-6岁健康儿童的24小时心电数据，结果表明健康儿童的心率变异性昼夜节律呈现夜间高、白天低的特征，验证了儿童心率变异性昼夜节律的存在。同时，对92名同年龄段难治性癫痫患儿的研究显示，其昼夜节律相对于健康儿童有显著的数值降低、扁平化现象，尤其是夜间差异巨大，但评估迷走-交感神经功能平衡性的指标并没有显著改变；难治性癫痫患儿的自主神经功能受损，但仍处于相对平衡的状态。其次，对接受迷走神经刺激治疗的92名患儿，分析研究其术前与术后26周不同访视期采集的共6次24小时动态心电进行。结果表明，迷走神经刺激植入术短期内使得儿童的心率变异性昼夜节律严重降低，显著低于术前水平，此抑制效果在8周时间内快速恢复至略高于术前水平。此后，迷走神经刺激持续修复患儿心率变异性昼夜节律，26周随访结果显示相比术前有显著提高，且恢复了部分节律变化细节，但整体上与健康儿童仍有显著差异。进一步地，针对迷走神经刺激疗效不同的患儿，分组对比其在迷走神经刺激下的心率变异性昼夜节律变化情况。发现“癫痫发作完全控制”的患儿，心率变异性昼夜节律术前水平显著高于其他患儿，但26周后与其自身术前相比无显著变化；“癫痫发作没有改善”的患儿，26周后心率变异性昼夜节律反而有了显著改善。这一发现不仅为术前筛选疗效佳的患者提供了客观依据，也为迷走神经刺激控制癫痫发作的机制研究提供了新的思路。
The annual incidence of epilepsy in children in our country is about 15.1 per 10,000. About 30% of them can’t be controlled by antiepileptic drugs, which is refractory epilepsy. Patients with epilepsy have impaired autonomic nervous system (ANS) function, which affects heart activity and leads to flattening of circadian rhythm (CR) of heart rate variability (HRV). Children's epilepsy not only affect physical and mental health, but also do harm to their growth, development and life skills learning, especially for the 3-6 year-old preschool children who are in the rapid development period. So treatment and control of epilepsy are particularly important. Vagus nerve stimulation (VNS) can control the seizures of some refractory epilepsy, but the individual efficacy varies greatly, which is not conducive to the clinical promotion. This article starts from the CR of HRV in 3-6 years old children with epilepsy, to study the effect of VNS to them. For children with different therapeutic effects, explores different patterns of VNS affecting CR of HRV. First, the 24-hour ECG data of 46 healthy children aged 3-6 years were analyzed. The results showed that the HRV of healthy children showed high nighttime and low daytime characteristics, which verified the existence of children's CR of HRV. At the same time, a study of 92 children with refractory epilepsy of the same age showed that their CR of HRV has a significant reduction and flattening compared with healthy children. The difference is huge, especially at night. But the indicator of the balance of vagal sympathetic function doesn’t change significantly. Children with refractory epilepsy have impaired autonomic nerve function, but are still in a relatively balanced state.Secondly, for 92 children who received VNS treatment, this article studied a total of 6 times 24-hour dynamic electrocardiograms collected during different periods before and after surgery. The results showed that VNS implantation severely inhibited CR of HRV in children at a short term. This inhibitory effect quickly recovered to slightly higher than the preoperative level within 8 weeks. Since then, VNS has continued to repair the CR of children’s HRV. Compared with preoperative, the CR of HRV of 26-week follow-up has significantly improved. And some details of rhythm changes have been restored. There are still significant differences from healthy control standards overall.Furthermore, for children with different VNS effects, the CR changes of HRV under VNS were compared in sub-groups. Children with complete-seizure- control were found to have significantly higher pre-operative HRV than others, but there was no significant change after 26 weeks compared with pre-operation of themselves. Instead, children with seizure-did-not-improve have significant improvement in CR changes of HRV after VNS. Such findings not only provide objective evidence for preoperative screening of patients with good outcome, but also provide new ideas for the study of the mechanism of that how VNS control seizures
