DNA 甲基化是人類發現最早的表觀遺傳學修飾之一，具有多種調控功能，參與機體發育過程中干細胞生長、細胞增殖、器官發育、衰老和腫瘤發生等多個生物學過程，而且在突觸重塑、神經細胞分化等神經生物過程中也具有重要作用。近年來，越來越多的研究表明 DNA 甲基化修飾與癲癇的發病機制密切相關，特別是基因啟動子的甲基化改變逐漸受到關注。文章主要對表觀遺傳中基因啟動子區的甲基化在癲癇發生發展中的研究進展進行綜述。
ObjectiveTo determine the outcome of antiepileptic drugs (AEDs) withdrawal in patients who had been seizure-free for more than two years.
MethodsPatients with epilepsy who had been seizure-free for at least two years and decided to stop AEDs therapy gradually were checked on every two months for seizure relapse. The inclusion criteria were:①diagnosis of epilepsy, defined as at least two unprovoked seizures at least 24 hours apart; ②patients remained seizure-free for at least 24 consecutive months during AEDs therapy; ③patients expressed a desire to discontinue AEDs therapy gradually and agreed to return for regular follow-ups; and④electroencephalogram (EEG) showed no epileptic discharge. The time to a seizure relapse and predictive factors were analyzed by survival methods, including sex; age at seizure onset; number of episodes; seizure-free period before AEDs withdrawal; duration of follow-up after AEDs withdrawal; AEDs tapering off period (taper period); results from brain MRI; EEG before seizure-free; EEG before drug withdrawal; seizure type (classified as generalized, partial, or multiple types based on history); the number of AEDs administered for long-term seizure control. A log-rank test was used for univariate analysis, and a Cox proportional hazard model was used for multivariate analysis.
ResultsSixty-eight patients (39 male, 29 female) were admithed. The relapsed rate was 23.5%. Univariate analysis and multivariate Cox regression analysis indicated that multiple AEDs, hippocampal sclerosis and withdrawal time were significantly correlated with seizure recurrence and those were significant independent predictive factors, with hazard ratio were 0.861, 2.223 and 2.137 respectively.
ConclusionsThe relapsed rate in our study was similar to other studies. Distinguishing variables, such as multiple AEDs, hippocampal sclerosis and withdrawal time, need to be considered when decide to withdraw. Therefore, our recommendation is that after two years of being seizure-free, patients could consider withdrawal unless they are hippocampal sclerosis patients.
ObjectiveThrough Sequenom iPEX system analyzed the genetic susceptibility in patients with Medial temporal lobe epilepsy (MTLE) which screening hyperpolarization-activated cyclic nucleotide gated channel (HCN) subunit HCN1 and HCN2 single nucleotide polymorphism blood samples.
MethodsPatients with epilepsy who were diagnosed MTLE in our epileptic clinic from December 2013 to April 2016 were included in this study, total 143 cases. Healthy volunteers who received annual physical checkups were recruited to serve as controls total 120 cases. The group enter criterion according to a 2004 ILAE report mainly:①12~55 years old; ②attack forms:partial onset seizures or secondary tonic-closure-clonus attack, a common onset symptoms such as stomach gas rise feeling, sense of deja vu, automatism etc.; ③with or without febrile convulsions history; ④EEG displayed unilateral or bilateral temporal spike, sharp slow wave, or their spines slow-wave sample such as epilepsy wave; ⑤head MRI displayed hippocampal sclerosis. Exclusion criteria:①tumors; ②head MRI display focal cortical dysplasia (FCD). Using sequenom iPLEX technology platform to detect all the object of study of gene polymorphism sites total ten sites. All statistical tests were conducted using SPSS version 16.0.
Resultsall sites fulfilled Hardy-Weinberg genetic balance. The results showed that HCN1 rs17344896 C/T, rs6451973 A/G and HCN2 rs12977194 A/G three polypeptide sites associated with MTLE, with statistical differences(P < 0.05).
ConclusionHCN1 and HCN2 genetic suscepibility is one of possible mechanism of MTLE.
ObjectiveIn order to evaluate that whether the P-glycoprotein-inhibitor verapamil (VPM) could effect the distribution of antiepileptic drug phenytoin (PHT) in a rat model of mesial temporal lobe epilepsy (MTLE).MethodsThe rat models of MTLE were induced by li-pilocarpine and were randomly divided into two groups (PHT group and VPM+PHT treatment group) to compare the PHT distribution in brain, liver and kidney. Brain dialysate samples were collected by microdialysis technology. And the analysis of samples for PHT concentration was performed by high performance liquid chromatography (HPLC). The comparisons were carried out by t test (or Wilcoxon test).ResultsIn VPM+PHT treatment group, 4 out of 9 rats were dead within 30 minutes after drug administration. The significantly decreased area under the curve (AUC) ratio of brain/plasma in VPM+PHT group was 0.11±0.06 when compared with PHT group 0.21±0.02 (t=3.237, P=0.025), while there were no significant differences in ratios of liver/plasma ［PHT (1.12±0.37) vs. VPM+PHT (0.99±0.27), Z=?0.490, P=0.624］ and kidney/plasma ［PHT (0.74±0.16) vs. VPM+PHT (0.49±0.26), t=1.872, P=0.103］ between two groups.ConclusionsThe P-glycoprotein-inhibitor VPM significantly decreased PHT level in brain of rat with MTLE.
Objectives
The purpose of this study is to verify the phenytoin-resistant mesial temporal lobe epilepsy (MTLE) induced by Li-pilocarpine and screened by antiepilepsy drug (AEDs).
Methods
The rats with MTLE were induced by Li-pilocarpine, which were screened by effect of phenytoin treatment monitored by vedio-EEG. The living microdialysis technology was used for verification of drug concentration in brain of drug-resistant and drug-responsive rat model, and the P-glycoprotein expression was detected by immunohistochemical method.
Results
Sixteen rats with chronic MTLE were successfully induced in total 30 rats, among which, 6 drug-resistant rats with MTLE were screened. The brain/plasma ratio of area under the curve in drug-resistant rats was significantly lower than that of drug-responsive rats (0.15±0.03 vs. 0.28±0.05, P<0.05). In addition, the P-glycoprotein expression in brain of drug-responsive rats was obviously higher than that of drug-responsive rats (P<0.05).
Conclusions
The low concentration of phenytoin in drug-resistant rat model with MTLE was verified that might be related to the over-expressed P-glycoprotein in brain.
