Expression of multidrug resistance 1 gene and C3435T genetic polymorphism in peripheral blood of patients with intractable epilepsy

BACKGROUND： Increased expression of multidrug resistance 1 （MDR1） mRNA in peripheral blood of patients with intractable epilepsy is not due to epilepsy drugs, but epilepsy behavior. Monitoring MDR1 expression in peripheral blood is a target for MDR1 gene evaluation. OBJECTIVE： To investigate the influence of antiepileptic drugs and seizures on MDR expression in intractable epilepsy, and to analyze the genetic polymorphisms of C3435T in the MDRl gene. DESIGN, TIME AND SETTING： Factorial designs and comparative observations at the experimental center of the Affiliated Hospital of Qingdao Medical College, Qingdao University between October 2003 and October 2004. PARTICIPANTS： A total of 120 subjects were recruited from the epilepsy clinical department of the Affiliated Hospital of Qingdao Medical College. Four groups （n = 30） were classified according to statistical factorial design： intractable epilepsy, treatment response, no treatment, and normal control groups. METHODS： One-step semi-quantitative reverse-transcription polymerase chain reaction technology was used to test expressions of the MDR1 gene in 120 subjects. C3435T polymorphisms in intractable epilepsy group and normal control groups were analyzed by polymerase chain reaction-restriction fragment length polymorphism. MAIN OUTCOME MEASURES： Expression of MDR1 mRNA in the four groups, and C3435T genetic polymorphisms in intractable epilepsy and normal control groups. RESULTS： MDRl gene expression was increased in the intractable epilepsy group, due to the factor seizures, but not the antiepileptic drugs. However, the interaction between the two factors was not statistically significant. Of the 30 subjects in the intractable epilepsy group, the following genotypes were exhibited： 3 （10%） C/C genotype, 9 （30%） C/T genotype, and 18 （60%） T/T genotype at the site of C3435T, while 4 （13%）, 10 （33%）, and 16 （53%） subjects were determined to express these genotypes in the normal control group, respectively. C and T allele frequency were 25% and 75% in the intractable epilepsy group, and 30% and 70% in the normal control group, respectively. However, there was no statistical difference between the groups. CONCLUSION： Results demonstrated that seizures, not antiepileptic drugs, induced MDR1 gene expression in intractable epilepsy. Genetic polymorphisms of C3435T in the MDR1 gene did not contribute to the development of multidrug resistance in patients with intractable epilepsy.

Preliminary analysis of the effect of vagus nerve stimulation in the treatment of children with intractable epilepsy

BACKGROUND Implant vagus nerve stimulation is an adjunctive treatment for intractable epilepsy when patients are not suitable for resective surgery.AIM To identify the safety and efficacy of vagus nerve stimulation in children with intractable epilepsy and analyze the effects on different epilepsy syndromes.METHODS Eligible children with intractable epilepsy were admitted to the study.We collected data from preoperative assessments as the baseline.During the followup time,we recorded the process of seizures(frequency,duration,and seizure type),the changes of drugs or parameters,the complications,etc.The mean reduction rate of seizures,response rate,and McHugh scale were chosen as the outcomes.RESULTS A total of 213 patients were implanted with Tsinghua Pins vagus nerve stimulators,and the average age was 6.6 years.In the follow-up time of postoperative 3 mo,6 mo,12 mo,18 mo,and 24 mo,the average reduction rate was 30.2%,49.5%,56.3%,59.4%,and 63.2%,while the response rate was 21.8%,62.5%,57.1%,69.2%,and 70.7%.In addition,implanted vagus nerve stimulation had different effects on epilepsy syndromes.The reduction rate of West syndrome increased from 36.4%(postoperative 6 m)to 74.3%(postoperative 24 m).The reduction rate of Lennox-Gastaut syndrome improved from 25.4%to 73.1%in 24 mo.The chi-square test of the five efficacy grades showed P<0.05.The comparison between the 3-mo follow-up and the 6-mo follow-up showed P<0.05,and the comparison between the 6-mo follow-up and the 24-mo follow-up showed P>0.05.CONCLUSION Vagus nerve stimulation is safe and effective in children with intractable epilepsy,and the seizure reduction occurred in a time-dependent manner.Moreover,patients with West syndrome may get the most benefits.

Electrocorticography with Direct Cortical Stimulation for a Left Temporal Glioma with Intractable Epilepsy

ELECTROCORTICOGRAPHY (ECoG), the intraoperative recording of cortical potentials, has played an important role in the surgical management of patients with medically intractable epilepsy. This technique is useful in epilepsy surgery to delineate margins of epileptogenic zones, guide resection,

Correlation analysis of Toll-like receptor 3 content in peripheral blood with electroencephalogram parameters and neurotransmitter content in children with intractable epilepsy

Objective:To detect the content of Toll-like receptor 3 (TLR3) in peripheral blood of children with intractable epilepsy, explore the correlation between TLR3 content and EEG parameters, neurotransmitter contents.Methods:37 cases of Intractable epilepsy children in our hospital during September 2016to June 2018 were chosen as Intractable epilepsy group, 30 cases of healthy volunteers who underwent physical examination in our hospital were treated as Normal control group. The levels of TLR3, neurotransmitter [5-hydroxytryptamine (5-HT), dopamine (DA), epinephrine (E), norepinephrine (NE)] and electroencephalogram parameters [alpha, beta, delta, theta] in peripheral blood of two groups were compared. Pearson test was used to evaluate the correlation of TLR3 content in peripheral blood with EEG parameters and neurotransmitter content in children with intractable epilepsy.Results: Content of TLR3 in peripheral blood of Intractable epilepsy group was significantly higher than that of Normal control group;the alpha power and theta power of EEG parameters were lower than those of Normal control group;contents of neurotransmitters such as 5-HT, DA, E and NE were significantly lower than those of Normal control group (P<0.05). The correlation analysis showed that content of TLR3 in peripheral blood of children with intractable epilepsy was negatively correlated with levels of alpha and theta power of EEG, positively correlated with content of neurotransmitters such as 5-HT, DA, E and NE (P<0.05), but had no significant correlation was found with level of beta and delta power (P>0.05).Conclusion: The abnormal increase of TLR3 in peripheral blood of children with intractable epilepsy may be one of the direct causes of neurological impairment in children with intractable epilepsy.

Effects of lamotrigine + sodium valproate therapy on the nerve cell nutrition and apoptosis status as well as inflammatory response in patients with intractable epilepsy

Objective: To investigate the effects of lamotrigine + sodium valproate therapy on the nerve cell nutrition and apoptosis as well as inflammatory response in patients with intractable epilepsy. Methods: A total of 70 patients with intractable epilepsy who were treated in our hospital between August 2013 and October 2016 were divided into routine group (n=35) and study group (n=35) by random number table method, routine group received sodium valproate therapy and study group received lamotrigine combined with sodium valproate therapy. The differences in serum levels of neurotrophy indexes, nerve apoptosis indexes and inflammatory factors were compared between the two groups before and after treatment. Results: Before treatment, there was no statistically significant difference in serum levels of neurotrophy indexes, nerve apoptosis indexes and inflammatory factors between the two groups. After treatment, serum BDNF and NGF levels of study group were higher than those of routine group;serum Bcl-2, Fas and FasL levels of study group were lower than those of routine group whereas Bax level was higher than that of routine group;serum IL-1β, IL-6 and PGE2 levels of study group were lower than those of routine group. Conclusion: Lamotrigine combined with sodium valproate therapy can effectively increase the neurotrophy, inhibit the nerve apoptosis and reduce the systemic inflammatory response in patients with intractable epilepsy.

抗癫痫发作药物的应用进展

癫痫是神经系统中第二大常见疾病,在我国有超过900万的患者。尽管目前已经有超过20种抗癫痫发作药物,仍然有大约1/3的患者对抗癫痫发作药物治疗表现出耐药性。近年来,癫痫治疗领域取得了明显的进展,引入了新的抗癫痫发作药物,为患者提供了更多治疗选择。这些药物不仅在控制癫痫发作方面发挥着作用,而且在减轻药物不良反应和提高患者生活质量方面取得了明显的改善。本文旨在综述近15年来上市的抗癫痫发作药物,以提升临床医师对新上市抗癫痫发作药物的了解,并加深对它们在临床实践中的应用认知水平。

难治性癫痫患儿血清高迁移率族蛋白1与神经递质含量、认知功能的相关性研究

目的 探讨难治性癫痫(IEP)患儿血清高迁移率族蛋白1(HMGB-1)与神经递质含量、认知功能的相关性。方法 选取2018年12月—2022年12月江南大学附属医院就诊的82例IEP患儿及抗癫痫药物控制良好的患儿77例,分别作为IEP组、良好组。检测两组血清HMGB-1、5-羟色胺(5-HT)、γ-氨基丁酸(γ-GABA)、去甲肾上腺素(NE)水平;采用中国-韦氏儿童智力量表修订本(C-WISC)评估患儿认知功能。采用Pearson法分析IEP患儿血清HMGB-1与5-HT、γ-GABA、NE含量及C-WISC评分的相关性。采用多因素逐步Logistic回归模型分析导致IEP患儿认知障碍的危险因素。结果 IEP组血清HMGB-1水平较良好组升高(P <0.05),5-HT、γ-GABA、NE水平及C-WISC评分较良好组降低(P <0.05)。Pearson相关性分析显示,IEP组HMGB-1与5-HT、γ-GABA、NE及C-WISC评分均呈负相关(r=-0.683、-0.648、-0.593和-0.608,均P <0.05)。多因素逐步Logistic回归分析结果显示:年龄[OR=3.080(95%CI:2.014,4.146)]、病程[OR=5.658(95%CI:1.968,3.076)]、海马硬化[OR=2.522(95%CI:1.968,3.076)]、合并情感障碍[OR=1.883(95%CI:1.258,2.509)]和HMGB-1[OR=3.815(95%CI:1.587,6.043)]是导致IEP患儿认知障碍的危险因素(P <0.05)。结论 IEP患儿血清HMGB-1含量较高,与神经递质含量、认知功能密切相关,其高表达是IEP患儿认知功能障碍的危险因素。

丙戊酸钠联合左乙拉西坦治疗小儿难治性癫痫的临床效果

目的 观察丙戊酸钠联合左乙拉西坦治疗小儿难治性癫痫的临床效果。方法 选取2020年1月—2022年12月衡阳市中心医院收治的小儿难治性癫痫患儿80例,采用随机数字表法分为观察组和对照组,各40例。对照组单纯予左乙拉西坦口服溶液治疗,观察组在对照组基础上联合丙戊酸钠口服溶液治疗,2组均持续治疗12周。比较2组治疗效果,治疗前后血清学指标[胰岛素样生长因子-1(IGF-1)、中枢神经特异蛋白(S100β)、神经元特异性烯醇化酶(NSE)]、认知功能评分(包括言语部分和操作部分)、生活质量评分及不良反应。结果 观察组患儿治疗总有效率为95.00%,高于对照组的77.50%(χ^(2)=5.165,P=0.023)。治疗12周后,2组IGF-1、S100β、NSE水平较治疗前降低,且观察组低于对照组(P均<0.01);2组认知功能—语言评分、认知功能—操作评分和生活质量评分均较治疗前提高,且观察组高于对照组(P均<0.01)。观察组与对照组不良反应总发生率比较差异无统计学意义(12.50%vs.15.00%,χ^(2)=0.105,P=0.745)。结论 丙戊酸钠联合左乙拉西坦治疗小儿难治性癫痫的临床效果显著,可改善患儿血清学指标,利于认知功能发育,生活质量提升,且不会增加不良反应发生风险。

基于图论分析法对难治性癫痫脑功能网络的研究

目的:利用静息态fMRI(rs-fMRI)结合图论分析方法研究儿童及青少年难治性癫痫(ITE)脑功能网络拓扑属性的变化,分析异常网络属性指标与病程、智商之间的相关性,探讨ITE患者脑功能网络改变。方法:收集ITE患者23例(ITE组),同期招募23例健康志愿者作为对照组。采用3.0TMRI扫描仪进行扫描,获得T2-FLAIR、3D-T1WI、rs-fMRI数据。利用GRETNA V2.0软件包进行数据预处理并计算网络属性指标,使用SPSS18.0软件分析组间差异。结果:ITE组与对照组年龄、性别及受教育年限差异均无统计学意义(均P>0.05)。ITE组与对照组均有小世界属性,ITE组局部效率及标准化聚类系数减低(P=0.014,0.027)。ITE组节点属性有差异的脑区主要位于默认网络及视觉皮质。ITE组左侧楔前叶节点中心度、左侧楔前叶节点效率均与病程呈负相关(r=-0.564,P=0.005;r=-0.539,P=0.008)。结论:ITE组脑功能网络全局及节点属性均存在异常,脑功能网络改变以局部分离功能降低为主,为ITE脑功能网络研究提供新的视角。

难治性癫痫儿童血浆激肽释放酶、组织蛋白酶B的表达及其临床意义

目的:探讨难治性癫痫儿童血浆激肽释放酶(KLK)、组织蛋白酶B(catB)表达及其临床意义.方法:选取2017年3月至2019年3月河南中医药大学第五临床医学院收治的难治性癫痫患儿43例为研究对象,纳入研究组.选择同期在本院治疗的治疗有效癫痫患儿,同期在本院体检的健康儿童作为对照,分别纳入治疗有效组(n=35)及对照组(n=50).①对3组受试儿血浆KLK、catB,白细胞介素(IL)-6、IL-8、肿瘤坏死因子(TNF)-α水平分别进行统计学分析.②分析研究组患儿血浆KLK、catB水平,分别与其血浆IL-8、IL-6、TNF-α水平的相关关系.③受试者工作特征(ROC)曲线的曲线下面积(AUC),对难治性癫痫的诊断截断值、诊断灵敏度及特异度.④采取多因素非条件Logistic回归分析难治性癫痫临床诊断的独立影响因素.结果:①研究组患儿血浆KLK、catB、IL-6、IL-8、TNF-α水平,均显著高于对照组、治疗有效组,并且差异均有统计学意义(P<0.05).②研究组患儿血浆KLK、catB水平与其IL-6、IL-8、TNF-α水平,均呈正相关关系(r=0.625、0.628、0.657,0.634、0.619、0.664,P<0.05).③血浆KLK、catB水平ROC曲线的AUC分别为0.889、0.856,对难治性癫痫的诊断截断值分别为3.99 U/mL、3.66 U/mL,二者单独诊断难治性癫痫的灵敏度分别为72.10%、72.10%,特异度分别为92.00%、94.00%;二者联合诊断的AUC为0.950,灵敏度为86.00%,特异度为90.70%.④血浆KLK高表达(OR=2.652,95%CI:1.668~4.218,P<0.05),以及catB高表达(OR=2.635,95%CI:1.704~4.075,P<0.05),均是导致患儿发生难治性癫痫的独立危险因素.结论:难治性癫痫儿童血浆KLK、catB水平高表达,对难治性癫痫患儿的临床诊断具有重要参考价值.

Evaluation of P-glycoprotein-targeting circulating microRNAs as peripheral biomarkers for medically intractable epilepsy

Background Early diagnosis of medically intractable epilepsy is challenging in clinical work.P-glycoprotein(P-gp)is one of the most important multidrug efux transporters,which has been demonstrated to contribute to the drug resistance of intractable epilepsy.The present study was aimed to explore the diagnostic value of microRNAs(miRNAs)targeting P-gp for medically intractable epilepsy.Methods Thirty-six patients with intractable epilepsy and 36 epilepsy patients responsive to anti-epilepsy drugs,who visited Jinshan Hospital of Fudan University from September 2014 to September 2016,were enrolled in this study.Clinical information of the patients was obtained by retrospectively reviewing medical records.MiRNAs with diferential serum expression between the two groups of patients were detected by microarray assay.Meanwhile,miRNAs that were confrmed to regulate P-gp in vitro by western blot were selected for further validation.In the validation phase,reverse transcription quantitative PCR(RT-qPCR)was conducted to confrm the diferential expression of the candidate miRNAs in the epilepsy cohorts.Receiver operating characteristic(ROC)curve analysis was carried out to evaluate the diagnostic value of the miRNAs for intractable epilepsy.Results Three miRNAs including miR-6514-3p,miR-6076-5p,and miR-6855-3p were identifed to be candidate miRNAs by microarray assay.The results of western blotting validated that miR-146a-5p and miR-138-5p could regulate P-gp expression in vitro,so they were included in the candidate miRNAs for further validation.In the validation phase,the results of RT-qPCR indicated that compared with drug-responsive patients,the patients with intractable epilepsy showed decreased level of miR-138-5p and increased level of miR-146a-5p.The results of ROC curve analysis indicated that miR-138-5p(AUC=0.877)and miR-146a-5p(AUC=0.866)had high diagnostic value for intractable epilepsy.In addition,the miR-panel composed of miR-138-5p and miR-146a-5p showed higher diagnostic value(AUC=0.926)than the miRNAs selected by microarray assay.Conclusions Our results indicated that the dysregulated miR-138-5p and miR-146a-5p which target P-gp expression have high potential as peripheral biomarkers for medically intractable epilepsy.

Treatment of epilepsy in China Formal or informal?

Antiepileptic drugs are the preferred treatment approach for epileptic patients. However, informal treatment is important for intractable epilepsy. In this study, 500 epileptic patients were recruited from the General Hospital of Beijing Military Area Command of Chinese PLA during the period of October 2009 to January 2012. These involved patients that had been medically treated for at least 1 year. Information on the initial treatment and changes to treatment regimens for each patient was collected through questionnaires. The survey results showed that 52.3% of the epileptic patients searched for treatment after the first seizure, and the mean numbers of seizures was 12.8; 59.8% of the epileptic patients were diagnosed at the first visit, and the mean onset time was 17 months after the first seizure. After diagnosis, patients were treated for an average of 20 days, and the median time was 1 day. Formal anti-epileptic drugs were selected as the first treatment regimen by 67.8% of patients, and 77.5% of these drugs were monotherapies. The mean and median numbers of seizure were respectively 36.9 and 3.0 times before the first regimen was changed. The regimen was changed within the first 6 months by 46.6% of patients, and after the first and second years of treatment, the proportions increased to 54.0% and 71.8%, respectively. In total, 78.5% of the regi- mens were changed to informal treatments. The informal treatment of epilepsy in China is common, being initiated by either patients or physicians. Enhancing epileptic treatment services in hospital, improving physicians＇ professional quality, and strengthening health propaganda may promote the normalization of drug treatment of epilepsy in China.

多模态影像融合联合立体脑电图对多病灶难治性癫痫的术前定位及疗效

目的探讨多模态影像融合联合立体脑电图对难治性癫痫患者术前定位的准确性以及手术效果。方法回顾性分析2021-01-2022-06在湖南省脑科医院行手术治疗的40例难治性癫痫患者,均口服药物效果较差,经磁共振检查确诊为阴性,基于不同的神经成像技术加以分组,其中20例行多模态影像融合为对照组,20例行多模态影像融合联合立体脑电图为观察组。对比2组患者的术前定位准确率与手术治疗效果。结果对照组和观察组阳性检出率分别为95.00%和100.0%,2组比较差异无统计学意义(P>0.05);观察组定位准确率为90.00%,显著高于对照组的75.00%(P<0.05)。观察组骨窗面积为颞叶(14.82±2.55)cm^(2),额叶(14.13±1.34)cm^(2),均显著低于对照组的(17.47±2.75)cm^(2)和(16.23±2.22)cm^(2)(P<0.05)。观察组手术时间为颞叶(3.81±0.91)h,额叶(3.53±0.64)h,顶叶(3.65±0.82)h,均显著低于对照组的(4.52±1.71)h、(4.22±1.15)h和(4.12±1.33)h(P<0.05)。观察组术后感染率为5.00%,显著低于对照组的20.00%(P<0.05)。观察组术后癫痫缓解率为95.00%,显著高于对照组的70.00%(P<0.05)。结论对于多病灶难治性癫痫手术患者,采用多模态影像融合联合立体脑电图可以提升术前定位的准确性,保证手术效果。

基于肾藏精理论探讨大补元煎对难治性癫痫患者免疫功能以及认知功能的影响

目的基于“肾藏精”理论探讨大补元煎对难治性癫痫患者的免疫功能以及认知功能的影响。方法纳入2019年3月—2021年3月收治的难治性癫痫患者104例,随机分两组,对照组采用常规治疗联合认知康复训练;在此基础上,观察组采用基于“肾藏精”理论的大补元煎治疗,持续干预3个月。比较两组的临床疗效及不良反应,治疗前后测定血清CD_(3)^(+)、CD_(4)^(+)、CD_(8)^(+)、CD_(4)^(+)/CD_(8)^(+)和Addenbrooke评估量表(ACE-Ⅲ)。结果对照组的有效率80.77%(42/52)低于观察组94.23%(49/52),差异有统计学意义(P<0.05)。观察组治疗后血清CD_(3)^(+)、CD_(4)^(+)及CD_(4)^(+)/CD_(8)^(+)均高于对照组,CD_(8)^(+)低于对照组,差异有统计学意义(P<0.05)。观察组治疗后注意、记忆力、语言流利、视空间评分均高于对照组,有统计学意义(P<0.05)。两组总不良反应率分析,差异无统计学意义(P>0.05)。结论基于“肾藏精”理论的大补元煎可以进一步提高难治性癫痫的治疗效果,改善免疫功能和认知功能,且安全性高。

左乙拉西坦联合卡马西平治疗难治性局灶性癫痫的临床效果

目的:分析左乙拉西坦联合卡马西平治疗难治性局灶性癫痫的临床效果。方法:选取2021年1月—2022年6月航天中心医院收治的80例难治性局灶性癫痫患者,按照随机数表法将其分为两组,对照组(n=30)患者实施卡马西平治疗,观察组(n=50)患者实施左乙拉西坦联合卡马西平治疗。对比两组患者的临床治疗效果,治疗前后的脑电图棘波指数、癫痫发作频率、血清指标、认知功能及不良反应发生情况。结果:(1)观察组患者的临床治疗总有效率明显高于对照组,差异有统计学意义(P<0.05)。(2)两组患者治疗前的脑电图棘波指数、癫痫发作频率、简易精神状态检查量表(mini-mental state examination,MMSE)对比,差异均无统计学意义(P>0.05);治疗后,观察组患者的脑电图棘波指数、癫痫发作频率均低于对照组,MMSE评分高于对照组,差异有统计学意义(P<0.05)。(3)两组患者治疗前的各项血清指标对比,差异均无统计学意义(P>0.05);治疗后,观察组患者的S-100钙结合蛋白β(S-100 calcium-binding protein β,S-100β)、髓鞘碱性蛋白(myelin basic protein,MBP)、神经元特异性烯醇化酶(neuron-specific enolase,NSE)水平均低于对照组,脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)水平高于对照组,差异有统计学意义(P<0.05)。(4)观察组、对照组的不良反应发生率相近,分别为10.00%、13.33%,组间对比差异无统计学意义(P>0.05)。结论:对难治性局灶性癫痫患者实施左乙拉西坦联合卡马西平的临床效果较为理想,有利于改善患者的脑电图检查结果,减少癫痫发作频率,增强对脑组织的保护作用,提升患者认知功能。

迷走神经刺激通过调控M1/M2小胶质细胞极化减轻神经炎症改善癫痫大鼠认知功能

目的探讨迷走神经刺激(VNS)对难治性癫痫大鼠认知功能的影响及可能机制。方法通过腹腔注射氯化锂-皮罗卡品建立难治性癫痫大鼠模型。模型制作成功大鼠随机分为模型组(18只)与VNS组(15只),另外设对照组(20只)。对照组与模型组只分离迷走神经并植入刺激器,但不给予刺激;VNS组采取连续4周迷走神经电刺激。观察大鼠癫痫发作情况;Morris水迷宫实验检测大鼠认知功能;Nissl染色观察大鼠海马组织病理形态;ELISA检测大鼠海马组织TNF-ɑ、IL-6和IL-10表达;免疫荧光染色法与Western-blot分别检测大鼠海马组织M1型小胶质细胞标记物(iNOS)和M2型小胶质细胞标记物(Arg1)相对表达。结果①与对照组相比,模型组大鼠癫痫发作等级及发作持续时间明显增加(P<0.05);通过VNS连续干预4周后,大鼠癫痫发作等级及发作持续时间明显降低(P<0.05)。②模型组大鼠逃避潜伏期时间明显长于对照组,而穿越原平台的次数明显少于对照组(P<0.05);通过VNS连续干预4周后,癫痫大鼠逃避潜伏期时间明显缩短,而穿越原平台的次数明显增加(P<0.05)。③对照组大鼠海马神经元形态正常;模型组大鼠海马神经元损伤严重,数量明显减少(P<0.05);VNS组大鼠海马神经元损伤相比模型组明显减轻,数量明显增加(P<0.05)。④模型组大鼠海马组织TNF-ɑ、IL-6相对表达明显高于对照组,而IL-10相对表达明显降低(P<0.05);通过VNS连续干预4周后,癫痫大鼠海马组织TNF-ɑ、IL-6相对表达明显降低,而IL-10相对表达明显增加(P<0.05)。⑤与对照组相比,模型组大鼠海马组织iNOS相对表达明显增加,而Arg1相对表达明显减少(P<0.05);与模型组相比,VNS组大鼠海马组织iNOS相对表达明显减少,而Arg1相对表达明显增加(P<0.05)。结论VNS具有改善难治性癫痫大鼠认知功能障碍的作用,其机制可能是通过促进M2型小胶质细胞极化,减轻中枢炎性反应,保护海马神经元。

3同胞的不同遗传缺陷及产前诊断研究

目的通过对3同胞不同遗传缺陷的诊断及干预,探讨遗传咨询及产前诊断策略。方法采用生化、基因及染色体分析明确诊断,通过羊水细胞基因分析对第3胎进行产前诊断。结果先证者,男,2月龄时因发育落后就诊,血液苯丙氨酸>1200μmol/L,PAH基因检出已知致病变异c.728G>A及c.1068C>A,确诊为经典型苯丙酮尿症(PKU),经规范低苯丙氨酸饮食治疗后血液苯丙氨酸浓度控制良好,3月龄后出现难治性癫痫,重度智力损害,14岁时死亡。母亲第2胎孕中期发现胎儿脐膨出,羊水细胞染色体核型异常[45,XN,-21(3)/46,XN(7)],孕28周时终止妊娠。母亲第3胎妊娠早期入院检查,为进一步明确先证者病因,采用冻存的先证者DNA进行全外显子分析,除PAH复合杂合变异外,检出GABRA2基因新发致病变异c.875C>G,证实先证者共患发育性癫痫性脑病78型。第3胎胎龄18周时羊水细胞基因分析发现PAH基因存在与先证者相同的复合杂合变异,GABRA2基因未检出c.875C>G变异。母亲选择继续妊娠,第3胎为男婴,足月顺产出生,于日龄3 d时确诊PKU,遂开始规范低苯丙氨酸饮食与监测,血苯丙氨酸控制在正常范围,目前3岁,智力、运动及体格发育良好。结论PKU为严重的遗传代谢病,经规范治疗后绝大多数患者预后良好。

吡仑帕奈的合成及性能研究进展

吡仑帕奈(Perampanel)是日本卫材公司于2012年10月研发的Fycompa品牌。它是目前为止,唯一对AMPA的受体起效的新一代新药,是第一批用于治疗12岁及以上难治性部分性癫痫发作患者的添加药物,是一种AMPA受体拮抗剂,具有高选择性并调节中枢神经系统中的谷氨酸活性。其药物成分复杂,是经化合物库高通量筛选及后续的结构改造优化而开发的,是以AMPA受体为靶点的首个上市药物。临床上可用于单药或联合用药治疗。常见的不良事件包括头晕、嗜睡、头痛、疲劳、共济失调等。

延续性护理在难治性癫痫患儿生酮饮食治疗中的应用效果

目的:观察延续性护理在难治性癫痫患儿生酮饮食治疗中的应用效果。方法:选取2019年3月至2021年4月该院收治的66例难治性癫痫患儿进行前瞻性研究,按照抽签法将其分为对照组与观察组各33例。对照组实施常规护理,观察组在对照组基础上实施延续性护理,两组均护理至出院后3个月。比较两组护理前后生命质量[癫痫儿童生活质量量表(QOLCE-55)]评分、生酮饮食依从率、患儿家长护理满意度和不良事件发生率。结果:护理后,两组QOLCE-55评分均高于护理前,且观察组高于对照组,差异有统计学意义(P<0.05);观察组生酮饮食依从率为81.82%(27/33),高于对照组的57.58%(19/33),差异有统计学意义(P<0.05);观察组患儿家长护理满意度为96.97%(32/33),高于对照组的75.76%(25/33),差异有统计学意义(P<0.05);两组不良事件发生率比较,差异无统计学意义(P>0.05)。结论:延续性护理应用于难治性癫痫患儿生酮饮食治疗中可提高患儿生命质量、生酮饮食依从率以及患儿家长护理满意度,效果优于常规护理。

MULTIPLE SUBPIAL TRANSECTION FOR TREATMENT OF INTRACTABLE EPILEPSY

On the basis of experimental study, we applied multiple subpial transection (MST) to treat 50 patients with intractable epilepsy in which epileptigenic lesion involved functional areas such as pericentral gyms, postcentral gyrus, Broca's area, Wernicke's area, visual cortex, etc. They were followed up for 6 to 40 months. Complete control of seizures was obtained in 32 patients, significant reduction of seizure (more than 50%) in 13, reduction (less than 50%) in 3, and no effect in 2. The total effective rate was 96%. No functional defect was found in all patients. The mechanism of the disease and surgical technique were discussed in detail. We consider that MST could replace some standard excisional therapy for local epilepsy.