目的 探討拉莫三嗪與左乙拉西坦聯(lián)合治療小兒難治性癲癇的療效及對患兒血清高遷移率族蛋白1（HMGB1）、神經(jīng)節(jié)苷脂抗體（GM1-A）的影響。方法 回顧性選擇2017年6月—2020年6月在昆明市兒童醫(yī)院治療的難治性癲癇患兒120例為研究對象，根據(jù)患兒的治療方案分為對照組和試驗組。對照組給予左乙拉西坦片治療，初始劑量為10～20 mg·kg^-1·d^-1，每周增加5～10 mg·kg^-1·d^-1，增加劑量至20～40 mg·kg^-1·d^-1，加量期3～7周，連續(xù)治療6個月。試驗組在對照組基礎(chǔ)上給予拉莫三嗪片治療，初始劑量為0.3～0.6 mg·kg^-1·d^-1，12 h服藥1次，每周加量0.3～0.6 mg·kg^-1·d^-1，目標(biāo)劑量5～10 mg·kg^-1·d^-1，治療6個月。觀察兩組患者的治療效果，比較治療前及治療6個月后兩組患兒認(rèn)知功能、血清炎癥因子水平、血清免疫球蛋白水平、血清HMGB1、GM1-A、神經(jīng)元特異性烯醇化酶（NSE）、神經(jīng)肽Y（NPY）水平。記錄治療期間患兒不良反應(yīng)發(fā)生情況。結(jié)果 試驗組總有效率（88.33%）顯著高于對照組總有效率（70%），兩組比較差異有統(tǒng)計學(xué)意義（P<0.05）；治療前兩組患兒的言語智商、操作智商評分比較差異無統(tǒng)計學(xué)意義（P>0.05），治療后兩組患兒的言語智商、操作智商評分均顯著升高（P<0.05），且試驗組升高更顯著（P<0.05）；治療前兩組患兒的免疫球蛋白A（IgA）、免疫球蛋白M（IgM）、免疫球蛋白G（IgG）水平比較差異無統(tǒng)計學(xué)意義（P>0.05），治療后兩組患者的IgA、IgM、IgG水平均顯著升高（P<0.05），且試驗組升高更顯著（P<0.05）；治療前兩組患兒的GM1-A、NSE、NPY水平比較差異無統(tǒng)計學(xué)意義（P>0.05），治療后兩組患兒的GM1-A、NSE水平均顯著下降（P<0.05），NPY水平均顯著升高（P<0.05），且試驗組改善更顯著（P<0.05）；治療前兩組患兒的HMGB-1、腫瘤壞死因子-α（TNF-α）、超敏C反應(yīng)蛋白（hs-CRP）、白細(xì)胞介素-6（IL-6）水平比較差異無統(tǒng)計學(xué)意義（P>0.05），治療后兩組患兒的HMGB-1、TNF-α、hs-CRP、IL-6水平均顯著下降（P<0.05），且試驗組下降更顯著（P<0.05）；兩組患兒的不良反應(yīng)發(fā)生率比較，差異無統(tǒng)計學(xué)意義（P>0.05）。結(jié)論 拉莫三嗪聯(lián)合左乙拉西坦治療難治性癲癇的治療效果較好，可改善患兒的認(rèn)知功能和免疫功能，降低炎癥反應(yīng)，改善HMGB-1、GM1-A水平，并且安全性較好。

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

昆明市科學(xué)技術(shù)局科技保障民生發(fā)展計劃（2017-1-S-15138）