作者：龙苹苹，范嘉佳，樊军，舒怡，刘丽娟

单位：

1.610000 四川省成都市，四川省妇幼保健院 四川省妇女儿童医院功能检查 2.610000 四川省成都市，四川省妇幼保健院 四川省妇女儿童医院耳鼻喉科 3.610000 四川省成都市，四川省妇幼保健院 四川省妇女儿童医院小儿内科二病区 通信作者：龙苹苹，E-mail：longiov626@126.com

Units：

1.Department of Function Check, Sichuan Provincial Maternity and Child Health Care Hospital/Sichuan Provincial Womenand Children's Hospital, Chengdu 610000, China 2.Department of Ear-nose-throat, Sichuan Provincial Maternity and Child Health Care Hospital/Sichuan Provincial Womenand Children's Hospital, Chengdu 610000, China 3.Department of Two Wards of Internal Medicine Pediatric, Sichuan Provincial Maternity and Child Health Care Hospital/Sichuan Provincial Women and Children's Hospital, Chengdu 610000, China Corresponding author: LONG Pingping, E-mail: longiov626@126.com

关键词：

癫痫; 难治性癫痫; miR-145-5p; 倾向性评分匹配;

Keywords：

Epilepsy; Refractory epilepsy; miR-145-5p; Propensity score matching

CLC：

DOI：

10.12114/j.issn.1008-5971.2022.00.004

Funds：

摘要：

背景难治性癫痫患者例数占癫痫患者总数的20%～30%,其病因复杂多样,故临床诊治困难。随着相关研究的进一步深入,发现大脑在癫痫条件下,可以表达特定的微小核糖核酸(miRNAs),而miRNAs通过调控神经元凋亡、胶质细胞增生等参与癫痫的发生发展,这为难治性癫痫的靶向治疗提供了新的方向。目的通过倾向性评分匹配探讨miR-145-5p表达水平与小儿难治性癫痫的关系。方法前瞻性选取2019年1月至2021年4月四川省妇幼保健院收治的癫痫患儿291例为研究对象。根据患儿是否为难治性癫痫,将其分为难治组(难治性癫痫,72例)和可控组(非难治性癫痫,219例)。收集患儿基线资料、临床资料{包括发病年龄、每次发作持续时间、初次治疗前发作次数、初始脑电图情况、病因、是否存在影像学改变、首次抗癫痫药物(AEDs)治疗反应、实验室检查指标[神经节苷脂抗体(GM1-A)、谷氨酸脱羧酶抗体(GADA)、miR-145-5p表达水平]}。对基线资料进行倾向性评分匹配后,采用多因素Logistic回归分析探讨难治性癫痫的影响因素。结果匹配前,两组患儿性别、病程、癫痫家族史比较,差异有统计学意义(P <0.05)。经倾向性评分匹配后,共有61对患儿配对成功。匹配后,两组患儿年龄、性别、病程、体质指数、癫痫家族史、癫痫发作类型、热性惊厥史、脑炎史、新生儿缺氧缺血性脑病史比较,差异无统计学意义(P> 0.05)。匹配后,难治组患儿发病年龄小于可控组,每次发作持续时间长于可控组,首次AEDs治疗反应佳者所占比例、miR-145-5p表达水平低于可控组(P <0.05)。多因素Logistic回归分析结果显示,发病年龄[OR=0.492,95%CI(0.338,0.717)]、每次发作持续时间[OR=1.229,95%CI(1.060,1.424)]、首次AEDs治疗反应[OR=0.293,95%CI(0.119,0.724)]、miR-145-5p表达水平[OR=0.032,95%CI(0.005,0.193)]是难治性癫痫的影响因素(P <0.05)。结论miR-145-5p表达水平升高是小儿难治性癫痫的保护因素,其可作为难治性癫痫患儿潜在的治疗靶点和诊断及病情评估的生物标志物。

Abstract：

【Abstract】　Background The number of patients with refractory epilepsy accounts for 20%-30% of the total numberof patients with epilepsy. Its etiology is complex and diverse, so it is difficult to make clinical diagnosis and treatment. With thefurther deepening of relevant research, it is found that the brain can express specific microRNAs (miRNAs) under the conditionof epilepsy, and miRNAs participate in the occurrence and development of epilepsy by regulating neuronal apoptosis and glialcell proliferation, which provides a new direction for the targeted treatment of refractory epilepsy. Objective To explore therelationship between the expression level of miR-145-5p and refractory epilepsy in children by propensity score matching.MethodsA total of 291 children with epilepsy treated in Sichuan Provincial Maternity and Child Health Care Hospital fromJanuary 2019 to April 2021 were prospectively selected as the research objects. According to whether the children had refractoryepilepsy, they were divided into refractory group (refractory epilepsy, 72 cases) and controllable group (non-refractory epilepsy,219 cases) . The baseline data and clinical data {including age of onset, duration of each seizure, number of seizures before initialtreatment, initial EEG status, etiology, whether there are imaging changes, response to the first antiepileptic drugs (AEDs) treatment,laboratory examination indexes [antibodies to GM1 ganglioside (GM1-A) , glutamic acid decarboxylase antibody (GADA) , miR-145-5p expression level] } of children were collected. After propensity score matching of baseline data, multivariate Logistic regressionanalysis was used to explore the influencing factors of refractory epilepsy.Results Before matching, there was statisticallysignificant difference in gender, course of disease, and family history of epilepsy between the two groups (P< 0.05) . Afterpropensity score matching, a total of 61 pairs of children were successfully matched. After matching, there was no statisticallysignificant difference in age, gender, course of disease, body mass index, family history of epilepsy, type of seizure, history offebrile seizures, history of encephalitis, and history of neonatal hypoxic-ischemic encephalopathy between the two groups (P >0.05) . After matching, the age of onset of children in the refractory group was younger than that in the controllable group, theduration of each episode was longer than that in the controllable group, the proportion of patients with good response to the firstAEDs treatment and the expression level of miR-145-5p were lower than those in the controllable group (P < 0.05) . MultivariateLogistic regression analysis showed that age of onset [OR=0.492, 95%CI (0.338, 0.717) ] , duration of each episode [OR=1.229,95%CI (1.060, 1.424) ] , response to the first AEDs treatment [OR=0.293, 95%CI (0.119, 0.724) ] , miR-145-5p expression level[OR=0.032, 95%CI (0.005, 0.193) ] were the influencing factors of refractory epilepsy (P < 0.05) .ConclusionThe elevatedexpression level of miR-145-5p is a protective factor for children with refractory epilepsy, which can be used as a potentialtherapeutic target and a biomarker for diagnosis and disease evaluation.

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