Study On The Risk Factors Of Drug-resistant Epilepsy And The Expression Of Iron Regulatory Transporter 1 And Ceruloplasmin In Peripheral Blood

Objective:To analysis the clinical characteristics and risk factors of drug-resistant epilepsy(DRE);investigate the pathogenesis of drug-resistant epilepsy by examining the expression of iron-regulated transporter 1(IREGl)and ceruloplasmin(Cp)mRNA and protein in peripheral blood of patients with drug-resistant epilepsy and to detect the expression levels of the two indexes in epilepsy patients with different clinical characteristics.Methods:A follow-up study was conducted involving 175 epilepsy patients who were attended in the Department of neurology of the Affiliated Hospital of Youjiang Medical University For Nationalities from May 2015 to January 2017.According to the 2010 International League Against Epilepsy’s definition of drug-resistant epilepsy,divided to 2 groups: the DRE group(involving 102 patients),the AEDs well controlled group(involving 73 patients).The differences between the two groups in the duration,frequency and type of seizure,etiological classification,depressive degree,temporal lobe,encephalitis case,abnormalities of EEG and imaging and the response to AEDs initial were compared,the risk factors of drug-resistant epilepsy were analyzed by Logistic regression analysis.After that,according to CT or MRI examination results,40 drug-resistant epilepsy patients(the no lesion DRE group)and 40 patients with well controlled epilepsy(the no lesion AEDs well controlled group)were screened from the above cases,the difference between the two groups of the above index were compared,then evaluated these indicates by Logistic regression analysis.Blood samples were taken from 32 patients with DRE,30 patients with AEDs well controlled and 34 healthy.The expression of IREG1 and Cp mRNA and protein in peripheral blood was measured by quantitative RT-PCR and western blot.Comparison was made in the expression of the two indexes among epilepsy patients with different frequency and types of epilepsy seizure,abnormalities of EEG,depressive degree,the response to AEDs initia and different medications.Results:(1)Compared with the AEDs well controlled group,the duration,frequency and type of seizure,etiological classification,depressive degree,encephalitis case,abnormalities of EEG and imaging and the response to AEDs initial were significantly differences in the resistance group,with statistical significance(P<0.05),the Logistic regression analysis showed that the duration(OR=1.152,95% CI 1.020~1.302,P=0.023)and seizure frequency of more than four times per month(OR =38.459,95% CI 7.304~202.498,P<0.001)and poor response to AEDs initial(OR= 22.880,95% CI 8.016~65.304,P < 0.001)were the independent risk factors of DRE;(2)Compared with the no lesion AEDs well controlled group,the duration,frequency seizure,abnormalities of EEG,depressive degree and the response to AEDs initial were significantly differences in the resistance group,with statistical significance(P<0.05),Logistic regression analysis showed that seizure frequency of more than four times per month(OR=17.176,95%CI 3.523~83.738,P <0.001)were the independent risk factors of DRE patients without lesion.(3)The expression levels of IREGl mRNAand Cp mRNA were significantly higher in the DRE group(1.326±0.102,1.735±0.189)than the AEDs well controlled group(1.001±0.051,1.014±0.211),(P=0.001,P=0.002);The expression levels of IREGl mRNA and Cp mRNA were significantly higher in the AEDs well controlled group than the normal group(0.643±0.012,0.546±0.053),(P=0.001,P=0.014).(4)The expression levels of IREGl protein and Cp protein were significantly higher in the DRE group(2.092±0.020,1.952±0.035)than the AEDs well controlled group(1.779±0.084,1.767±0.041),(P=0.02,P=0.01);The expression levels of IREGl protein and Cp protein were significantly higher in the AEDs well controlled group than the normal group(1.399±0.083,1.530±0.005),(P=0.012,P=0.005).(5)The relative expression of IREGl gene and Cp gene was positively correlated(r=0.445,P=0.001).(6)Patients with different medications were significantly different in the gene relative expression of IREGl and Cp(P=0.001,P=0.001),patients taking 2 or 3 kinds of medicine higher than patients taking 1 kind of medicine in the gene relative expression of IREGl and Cp,and patients taking 3 kinds of medicine higher than patients taking 2 kinds of medicine in expression of IREGl and Cp(P=0.0 11,P=0.001,P=0.013,P=0.001;P=0.001,P=0.011).(7)Patients with different frequency and types of seizure,abnormalities of EEG,depressive degree and the response to AEDs initia in two groups were no significantly different in the gene relative expression of IREGl and Cp(P>0.05).Conclusion:(1)Epilepsy patients with long duration,high seizure frequency and poor response to AEDs initial may develop into DRE.Early intervention should be taken to reduce the occurrence of drug resistance.(2)Both IREG1 and Cp mRNA and protein level up regulated in peripheral blood of DRE patients,indicated that it may be involved in the occurrence and development of DRE,and can be used as an objective indicator for predicting DRE.(3)IREG1 and Cp mRNA in the peripheral blood of epilepsy patients may have the potential to become drug resistance indexes of the combined drug therapy for DRE.