甲泼尼龙冲击治疗对儿童睡眠中癫痫性电持续状态免疫功能的影响

Effect of methylprednisolone shock therapy on immune function of electrical status epilepticus during sleep in children

目的分析甲泼尼龙冲击治疗儿童睡眠中癫痫性电持续状态(electrical status epilepticus during sleep,ESES)的疗效及免疫功能变化。方法选取2017年10月至2018年10月于中国医科大学附属盛京医院小儿神经内科病房住院治疗的患儿35例,其中初诊颞叶癫痫(temporal lobe epilepsy,TLE)患儿19例(TLE组),初诊TLE伴ESES患儿16例(ESES组);同一时期儿童保健科健康体检儿童21例(正常对照组);比较各组间淋巴细胞亚群及细胞因子变化。口服抗癫痫药治疗无效的ESES患儿,共32例,给予甲泼尼龙冲击治疗3 d,通过治疗前后自身对比,探讨其疗效及患儿免疫功能的变化。结果抗癫痫药治疗无效的ESES患儿病程越长,预后越差。与正常对照组相比,ESES组患儿NK细胞活性降低,差异有统计学意义(P<0.05);与TLE组患儿相比,ESES组患儿IL-6水平更高,差异有统计学意义(P<0.05)。抗癫痫药治疗无效的ESES患儿,予甲泼尼龙冲击治疗后外周血B淋巴细胞比例升高,T淋巴细胞亚群及NK细胞比例均降低,差异均有统计学意义(P均<0.05);IL-2、IL-4、IL-10水平较治疗前升高,IL-6、IL-17、γ干扰素、肿瘤坏死因子水平较治疗前降低,其中IL-6水平变化差异有统计学意义(P<0.05);治疗后脑电图棘波指数(SWI)明显下降,部分患儿生长发育及认知功能得到改善,所有患儿无严重感染、高血压、电解质紊乱等不良反应;治疗效果与免疫指标变化的相关性在NK细胞(r=0.50,P<0.01)、B淋巴细胞(r=0.35,P=0.04)、IL-6(r=0.46,P=0.01)水平有统计学意义,且均为正相关。结论ESES患儿本身即存在免疫功能紊乱,可能存在NK细胞过度失活及IL-6水平升高,先天性免疫及适应性免疫在ESES的发病、病理生理过程中可能均起一定作用。甲泼尼龙冲击治疗可明显降低ESES患儿非快动眼期放电指数,作用机制可能主要与IL-6水平明显降低有关;也可能与重分布各淋巴细胞亚群,影响细胞分化,平衡各种细胞因子有关。

Objective To study the effect of methylprednisolone shock therapy on electrical status epilepticus during sleep(ESES)in children and the changes of immune function before and after methylprednisolone shock therapy.Methods Thirty-five children hospitalized in pediatric neurology ward of Shengjing Hospital of China Medical University from October 2017 to October 2018 were selected,including 19 children with newly diagnosed temporal lobe epilepsy(TLE group)and 16 children with initial diagnosis of TLE with ESES(ESES group),and 21 healthy children in the same period were selected as normal control group.A total of 32 cases with ESES who were taken oral administration of more than 2 anti-epileptic drugs(AEDs)ineffective were given methylprednisolone shock treatment for 3 days.Changes of lymphocyte subsets and cytokines among groups were compared.Results The longer the course of disease,the worse the prognosis of children with ESES.Compared with normal control group,the NK cell activity were significantly lower in children of ESES group(P<0.05).The levels of IL-6 were higher in children of ESES group compared with that in children of TLE group,and there was significant difference between two groups(P<0.05).In children with ESES who had poor therapeutic effect of oral AEDs,the proportion of peripheral blood B lymphocytes increased after methylprednisolone shock treatment,and the proportion of T lymphocyte subsets and NK cells decreased,and the differences were statistically significant(P<0.05).The levels of IL-2,IL-4 and IL-10 were higher than those before treatment,the levels of IL-6,IL-17,INF-γand TNF were lower than those before treatment,and the difference between the level of IL-6 before and after treatment was statistically significant(P<0.05).EEG spike waves index decreased significantly after treatment,some children′s growth and development and cognitive function improved,all children had no serious infection,high blood pressure,electrolyte imbalance and other adverse reactions.The correlation between therapeutic effect and changes of immune indexes was statistically significant in levels of NK cells(r=0.50,P<0.01),B lymphocytes(r=0.35,P=0.04)and IL-6(r=0.46,P=0.01),and all of them were positively correlated(P<0.05).Conclusion Children with ESES have immune dysfunction and may have excessive inactivation of NK cells and elevated levels of IL-6.Congenital immunity and adaptive immunity may play a role in the pathogenesis and pathophysiology of ESES syndrome.Methylprednisolone shock therapy could significantly reduce the non-rapid eye movement discharge index in children with ESES.The mechanism may be related to the significant decrease of IL-6 level.It may also be related to redistribution of lymphocyte subsets,affecting cell differentiation and balancing various cytokines.