The Factors Influencing Prognosis Of Drug Refractory Temporal Lobe Epilepsy And Serum Marker Screening And Validation Studies

Objectives:Epilepsy is a global neural disease,whose key points of treatment are qualitative and localization diagnosis.However,there are no reliable biomarkers in this area,especially in drug refractory epilepsy(DRE).How to objectively evaluate the epilepsy control state after surgery of drug-resistant temporal lobe epilepsy is also absent,because clinician can only judge that according to Engel or ILAE classificatin.Therefore,the purpose of this study is to sort out and analyze the prognosis of patients with temporal lobe epilepsy treated by surgery,as well as how the preoperative EEG form and MRI performance of patients affect the surgical prognosis.And then to screen and validate the potential clinical valuable serum biomarkers of epilepsy control station after surgery from randomized 29 seizure-freedom temporal lobe epilepsy surgery patients,taking advantage of proteomics technology.Methods:From October 2010 to October 2014,129 patients with temporal lobe epilepsy were treated with functional neurosurgery in shengjing hospital affiliated to China medical university,of which 115 were treated with surgery.All patients were evaluated according to ILAE or Engel grading criteria and followed up for 1 to 4 years.The cases treated by surgery were classified according to the intermittent discharge form of preoperative electroencephalogram and MRI manifestations.To analyze the difference between different forms of interictal discharge and MRI in seizure-free rate.Twenty-nine patients with anterior temporal lobe and hippocampal amygdalectomy were randomly selected and met the criteria of ILAE or Engel grade I(complete seizure control)after surgery.Venous serum samples from pre-operation and different post-operation follow-up times including 3months,6months,1year,18months,and 2years were used.The self control methods were used in this study.The sequential protein screening test,PRM test,absolute quantification of peptide“VGAHAGEYGAEALER”,and hippocampal cerebrospinal fluid(CSF)microdialysis of temporal lobe epilepsy model rat,to name a few,were applied in this study.Results:In 115 cases of temporal lobe epilepsy treated by surgery,according to the4-year follow-up period,the total control rates of postoperative seizures were 90.2%,79.8%,75.2%and 72.5%,respectively.The difference between unilateral anterior head discharge and bilateral discharge was statistically significant(P<0.001).For MRI positive patients,the overall prognosis was relatively good regardless of the form of intermittent eeg.However,for patients with negative MRI,intermittent eeg discharge was limited to unilateral anterior head,and the overall prognosis after surgery was relatively good.Ten changed proteins including HBA(P=0.0080)?HBB(P=0.0417)?PRDX2(P=0.0052)?BLVRB(P=0.0108)?ALDOA(P=0.0266)?CA1(P=0.0042)?CAT(P=0.0036)?BPGM(P=0.0166)?YWHAE(P=0.0178),HSPA8(P=0.0408)of Pre/Post-operation have been found in the first screening test from 9 patients No.1-9.The P-value and declining positive rates of these proteins were HBA(P=0.005,87.50%)?HBB(P=0.005,87.50%)?PRDX2(P=0.015,75.00%),BLVRB(P=0.02,87.50%)?ALDOA(P=0.02,70.83%)?CA1(P=0.02,87.50%)?CAT(P=0.006,87.50%)?BPGM(P=0.03,84.21%)?YWHAE(P=0.02,75.00%)?HSPA8(P=0.02,87.50%))after PRM test including 24 patients.Nine of ten proteins(HBA?HBB?PRDX2?BLVRB?ALDOA?CA1?BPGM?YWHAE?HSPA8)have also been found changed in the subject/control rats hippocampal CSF proteomics.Some proteins changed quickly after surgery with no statistic difference between 3month and 1year of post-operation.Average serum concentrations of Pre/Post-operation from selected peptide“VGAHAGEYGAEALER”splitting from HBA protein are 1*10~3-1*10~4pmol/ml/1*10~2-1*10~3pmol/ml(P<0.001).Another study have discovered differernt phenomenon of these proteins in other epilepsy types including frontal epilepsy,which means that these ten proteins may have the potential to become the serum biomarkers of localization diagnosis of drug-resistant temporal lobe epilepsy.Conclusion:Surgery is an effective treatment for temporal lobe epilepsy.The prognosis of patients with intermittent eeg discharge confined to unilateral anterior head is better.The prognosis of patients with abnormal MRI was better regardless of the discharge form during the intermission before surgery.The ten proteins including HBA?HBB?PRDX2?BLVRB?ALDOA?CA1?CAT?BPGM?YWHAE and HSPA8 could become the candidates of serum biomarkers of epileptic status evaluation after drug refractory temporal lobe epilepsy surgery.The biomarkers forms maybe the peptide.