目的 探讨拉莫三嗪与左乙拉西坦联合治疗小儿难治性癫痫的疗效及对患儿血清高迁移率族蛋白1（HMGB1）、神经节苷脂抗体（GM1-A）的影响。方法 回顾性选择2017年6月—2020年6月在昆明市儿童医院治疗的难治性癫痫患儿120例为研究对象，根据患儿的治疗方案分为对照组和试验组。对照组给予左乙拉西坦片治疗，初始剂量为10～20 mg·kg^-1·d^-1，每周增加5～10 mg·kg^-1·d^-1，增加剂量至20～40 mg·kg^-1·d^-1，加量期3～7周，连续治疗6个月。试验组在对照组基础上给予拉莫三嗪片治疗，初始剂量为0.3～0.6 mg·kg^-1·d^-1，12 h服药1次，每周加量0.3～0.6 mg·kg^-1·d^-1，目标剂量5～10 mg·kg^-1·d^-1，治疗6个月。观察两组患者的治疗效果，比较治疗前及治疗6个月后两组患儿认知功能、血清炎症因子水平、血清免疫球蛋白水平、血清HMGB1、GM1-A、神经元特异性烯醇化酶（NSE）、神经肽Y（NPY）水平。记录治疗期间患儿不良反应发生情况。结果 试验组总有效率（88.33%）显著高于对照组总有效率（70%），两组比较差异有统计学意义（P<0.05）；治疗前两组患儿的言语智商、操作智商评分比较差异无统计学意义（P>0.05），治疗后两组患儿的言语智商、操作智商评分均显著升高（P<0.05），且试验组升高更显著（P<0.05）；治疗前两组患儿的免疫球蛋白A（IgA）、免疫球蛋白M（IgM）、免疫球蛋白G（IgG）水平比较差异无统计学意义（P>0.05），治疗后两组患者的IgA、IgM、IgG水平均显著升高（P<0.05），且试验组升高更显著（P<0.05）；治疗前两组患儿的GM1-A、NSE、NPY水平比较差异无统计学意义（P>0.05），治疗后两组患儿的GM1-A、NSE水平均显著下降（P<0.05），NPY水平均显著升高（P<0.05），且试验组改善更显著（P<0.05）；治疗前两组患儿的HMGB-1、肿瘤坏死因子-α（TNF-α）、超敏C反应蛋白（hs-CRP）、白细胞介素-6（IL-6）水平比较差异无统计学意义（P>0.05），治疗后两组患儿的HMGB-1、TNF-α、hs-CRP、IL-6水平均显著下降（P<0.05），且试验组下降更显著（P<0.05）；两组患儿的不良反应发生率比较，差异无统计学意义（P>0.05）。结论 拉莫三嗪联合左乙拉西坦治疗难治性癫痫的治疗效果较好，可改善患儿的认知功能和免疫功能，降低炎症反应，改善HMGB-1、GM1-A水平，并且安全性较好。

Objective To investigate the efficacy of lamotrigine combined with levetiracetam in the treatment of refractory epilepsy in children and its effects on serum high mobility group protein 1 (HMGB-1) and ganglioside antibody (GM1-A). Methods Total 120 children with refractory epilepsy treated in Kunming Children's Hospital from June 2017 to June 2020 were selected retrospectively and divided into control group and experimental group according to the treatment scheme. Children in the control group were treated with Levetiracetam Tablets, with an initial dose of 10-20 mg·kg^-1·d^-1, an increase of 5-10 mg·kg^-1·d^-1 per week and an increase of dose to 20-40 mg·kg^-1·d^-1, the dosage period was 3-7 weeks, and the treatment lasted for six months. The experimental group was treated with lamotrigine tablets on the basis of the control group, with an initial dose of 0.3-0.6 mg·kg^-1·d^-1, once every 12 hours, an additional dose of 0.3-0.6 mg·kg^-1·d^-1per week, and a target dose of 5-10 mg·kg^-1·d^-1 for six months. The therapeutic effects of the two groups were observed, and the cognitive function ang the levels of serum inflammatory factor level, serum immunoglobulin level, serum HMGB-1, GM1-A, neuron specific enolase (NSE) and neuropeptide Y (NPY) were recorded. The incidence of adverse reactions in children during treatment was recorded. Results The total effective rate of the experimental group (88.33%) was significantly higher than that of the control group (70%), and there was significant difference between the two groups (P < 0.05). There was no significant difference in the scores of verbal IQ and operational IQ between the two groups before treatment (P > 0.05), the scores of verbal IQ and operational IQ of children in the two groups increased significantly after treatment (P < 0.05), and the scores of children in the experimental group increased more significantly (P < 0.05). There was no significant difference in the levels of immunoglobulin A (IgA), immunoglobulin M (IgM) and immunoglobulin G (IgG) (P > 0.05). After treatment, the levels of IgA, IgM and IgG in the two groups increased significantly (P < 0.05), and more significantly in the experimental group (P < 0.05). There was no significant difference in the levels of GM1-A, NSE and NPY between the two groups before treatment (P > 0.05). After treatment, the levels of GM1-A and NSE in the two groups decreased significantly (P < 0.05), the levels of NPY increased significantly (P < 0.05), and the improvement in the experimental group was more significant (P < 0.05). There was no significant difference in the levels of HMGB-1, tumor necrosis factor-α (TNF-α), high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) in the two groups before treatment (P > 0.05). After treatment, the levels of HMGB-1, TNF-α, hs-CRP and IL-6 in the two groups decreased significantly (P < 0.05), especially in the experimental group (P < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups. Conclusion Lamotrigine combined with levetiracetam is effective in the treatment of refractory epilepsy, which can improve children's cognitive and immune function, reduce inflammatory response, improve the levels of HMGB-1 and GM1-A, and has good safety.

R985

昆明市科学技术局科技保障民生发展计划（2017-1-S-15138）