丙戊酸钠联合左乙拉西坦治疗儿童癫痫的疗效及其对血清S-100β与高迁移率族蛋白-1的影响

目的探讨丙戊酸钠联合左乙拉西坦治疗儿童癫痫(children epilepsy)的疗效，以及对患儿血清S-100β与高迁移率族蛋白(HMGB)-1的影响。 方法选择2016年7月至2018年10月，在内蒙古包钢医院诊断为儿童癫痫的160例患儿为研究对象。采用随机数字表法，将其随机分为研究组(n＝80)与对照组(n＝80)，对其癫痫发作分别采取丙戊酸钠联合左乙拉西坦治疗与仅用丙戊酸钠的治疗策略。治疗16周后，评价2组患儿癫痫发作治疗有效率及改善脑电图痫样放电治疗有效率，并采用χ²检验进行统计学比较。治疗前、后，对2组患儿炎症相关指标进行检测，包括血清肿瘤坏死因子(TNF)-α，高敏C反应蛋白(hs-CRP)，同型半胱氨酸(Hcy)水平及血细胞比容(HCT)与红细胞沉降率(ESR)，以及血清S-100β与HMGB-1水平。对上述指标治疗前、后组内比较，采用配对t检验；组间比较，采用成组t检验。2组患儿治疗过程中不良反应率比较，采用χ²检验。本研究遵循的程序符合内蒙古包钢医院伦理委员会要求，并获得批准(审批文号：BG201606073)，与所有受试儿监护人签署临床研究知情同意书。2组患儿性别构成比、年龄、病程、治疗前癫痫每年发作次数、治疗前脑电图痫样放电发生率及癫痫发作类型构成比等一般临床资料比较，差异均无统计学意义(P>0.05)。 结果①治疗后，研究组患儿癫痫发作的治疗有效率、改善脑电图痫样放电治疗有效率分别为92.5%(74/80)与85.0%(68/80)，显著优于对照组的68.8%(55/80)与58.8%(47/80)，并且差异均有统计学意义(χ²＝14.444、13.635，P<0.001)。②治疗后，研究组患儿的血清TNF-α、hs-CRP、Hcy水平及HCT与ESR分别为(53.1±14.0)pg/mL、(5.0±2.5)mg/L、(12.5±3.1)μmol/L、(38.1±5.1)%与(3.0±0.5)mm/h，显著低于其治疗前的(107.9±17.8)pg/mL、(10.1±2.5)mg/L、(42.2±5.8)μmol/L、(45.3±4.5)%与(5.2±0.6)mm/h，并且差异均有统计学意义(t＝21.644、12.902、40.393、9.468、25.194，P<0.001)；对照组患儿的血清TNF-α、hs-CRP、Hcy水平及HCT与ESR分别为(60.6±17.8)pg/mL、(8.2±2.2)mg/L、(15.2±3.1)μmol/L、(40.2±3.4)%与(4.5±0.6)mm/h，显著低于其治疗前的(112.4±14.3)pg/mL、(9.3±3.8)mg/L、(41.1±2.8)μmol/L、(44.6±5.5)%与(5.4±0.8)mm/h，并且差异均有统计学意义(t＝20.292、2.241、55.456、3.320、8.050，P<0.05)。治疗后组间比较，研究组患儿的上述指标均显著低于对照组，并且差异均有统计学意义(t＝2.962、8.595、5.508、3.064、17.178，P<0.05)。③治疗后，研究组患儿的血清S-100β与HMGB-1水平分别为(0.65±0.38)μg/L与(5.3±2.4)μg/L，显著低于治疗前的(0.91±0.32)μg/L与(8.1±2.0)μg/L，并且差异均有统计学意义(t＝4.681、8.020，P<0.001)；对照组患儿的血清S-100β与HMGB-1水平分别为(0.78±0.27)μg/L与(6.4±2.2)μg/L，显著低于治疗前的(0.88±0.25)μg/L与(7.9±1.7)μg/L，并且差异均有统计学意义(t＝2.431、P＝0.016，t＝4.826、P<0.001)。治疗后，研究组患儿的上述指标，均显著低于对照组，并且差异均有统计学意义(t＝2.495、P＝0.014，t＝2.840、P＝0.005)。④2组患儿治疗过程中恶心呕吐、纳差、头晕、嗜睡及肝、肾功能损伤等不良反应率比较，差异无统计学意义(P>0.05)。 结论丙戊酸钠联合左乙拉西坦治疗癫痫患儿的疗效，显著优于仅用丙戊酸钠者，而且患儿血清S-100β及HMGB-1降低更显著，导致的不良反应率更低，具有一定临床应用价值。

Effects of sodium valproate combined with levetiracetam in treatment of children epilepsy and its influences on serum S-100βand high mobility group box-1

Objective To explore the effects of sodium valproate combined with levetiracetam in treatment of children epilepsy,and influences of treatment on serum S-100βand high mobility group box(HMGB)-1 in children with epilepsy.Methods A total of 160 children who were diagnosed as epilepsy in Inner Mongolia Baogang Hospital from July 2016 to October 2018 were selected as research subjects,and they were randomly sorted into study group(n=80)and control group(n=80)by random digits table method.Their seizures were treated with sodium valproate combined with levetiracetam and sodium valproate alone,respectively.After 16 weeks of treatment,the effective rates of seizure disorder treatment and improvement of epileptiform discharge of electroencephalography were evaluated,and chi-square test was used for statistical comparison.Levels of serum tumor necrosis factor(TNF)-α,hyper sensitive C-reactive protein(hs-CRP)and homocysteine(Hcy),and hematocrit(HCT)and erythrocyte sedimentation rate(ESR),and the levels of serum S-100βand HMGB-1 were detected before and after treatment.Paired-samples t test was used for intra-group comparison before and after treatment among the above indexes,independent-samples t test was used for inter-group comparison.Chi-square test was used to compare the rate of adverse reactions during treatment between two groups.The study was approved by the Ethics Committee of Inner Mongolia Baogang Hospital(Approval No.BG201606073),and all guardians of children signed the informed consent forms for clinical study.There were no significant differences between two groups in general clinical data,such as gender constituent ratio,age,course of disease,frequency of seizure disorder per year before treatment,incidence of epileptiform discharge of electroencephalography and constituent ratio of epileptiform discharge types before treatment,etc.(P>0.05).Results①The effective rate of seizure disorder treatment and improvement of epileptiform discharge of electroencephalography in study group were 92.5%(74/80)and 85.0%(68/80),respectively,which both were significantly higher than those in control group 68.8%(55/80)and 58.8%(47/80),and both the differences were statistically significant(χ2=14.444,13.635;P<0.001).②In study group,the levels of serum TNF-α,hs-CRP and Hcy,and HCT and ESR after treatment were(53.1±14.0)pg/mL,(5.0±2.5)mg/L,and(12.5±3.1)μmol/L,(38.1±5.1)%and(3.0±0.5)mm/h,respectively,which all were significantly lower than(107.9±17.8)pg/mL,(10.1±2.5)mg/L,(42.2±5.8)μmol/L,(45.3±4.5)%and(5.2±0.6)mm/h before treatment,and all the differences were statistically significant(t=21.644,12.902,40.393,9.468,25.194;P<0.001).In control group,the levels of serum TNF-α,hs-CRP and Hcy,and HCT and ESR after treatment were(60.6±17.8)pg/mL,(8.2±2.2)mg/L,(15.2±3.1)μmol/L,(40.2±3.4)%and(4.5±0.6)mm/h,respectively,which all were significantly lower than(112.4±14.3)pg/mL,(9.3±3.8)mg/L,(41.1±2.8)μmol/L,(44.6±5.5)%and(5.4±0.8)mm/h before treatment,and all the differences were statistically significant(t=20.292,2.241,55.456,3.320,8.050;P<0.05).After treatment,the above indexes in study group all were statistically lower than those in control group,and all the differences were statistically different(t=2.962,8.595,5.508,3.064,17.178;P<0.05).③In study group,levels of serum S-100βand HMGB-1 after treatment were(0.65±0.38)μg/L and(5.3±2.4)μg/L respectively,which were significantly lower than those before treatment(0.91±0.32)μg/L and(8.1±2.0)μg/L,and both the differences were statistically significant(t=4.681,8.020;P<0.001).In control group,levels of serum S-100βand HMGB-1 after treatment were(0.78±0.27)μg/L and(6.4±2.2)μg/L respectively,which were significantly lower than those before treatment(0.88±0.25)μg/L and(7.9±1.7)μg/L,and both the differences were statistically significant(t=2.431,P=0.016;t=4.826,P<0.001).After treatment,levels of serum S-100βand HMGB-1 in study group were significantly lower than those in control group,and both the differences were statistically significant(t=2.495,P=0.014;t=2.840,P=0.005).④There was no significant difference between two groups in rate of adverse reactions,such as nausea,vomiting,anorexia,dizziness,drowsiness,liver and kidney injury during treatment(P>0.05).Conclusions The efficacy of sodium valproate combined with levetiracetam is obviously better than that of sodium valproate alone in treatment of children with epilepsy.The children′s serum S-100βand HMGB-1 are more significantly reduced,resulting in a lower rate of adverse reactions,which has certain clinical values.