Clinical Analysis Of Surgical Treatment Of Temporal Lobe Epilepsy And Experimental Study On The Activation Mechanism Of Hippocampal Glial Cells

Surgery is an indispensable part of the treatment of refractory epilepsy.For the temporal lobe epilepsy(TLE),especially the medial temporal lobe epilepsy(MTLE),the early surgical intervention is better than the effect of antiepileptic drugs.However,not all patients were able to achieve significant remission or complete seizure free after surgery.Glial cell hyperplasia is an important marker of the pathology for refractory epilepsy.Proliferating glial cells can induce seizures by releasing large amounts of glutamate to act on the excitatory N-methyl-D-aspartic acid receptor.The pathological changes of the hippocampal sclerosis are characterized by the degeneration and loss of neurons in the affected area,as well as glial cell proliferation and even fibrogenesis.Glial cell hyperplasia is even found in the temporal cortex.The paper intends to explore the prognosis of surgery by analyzing the clinical data of patients with TLE of different pathological types.To evaluate the value of epileptogenic foci located by magnetoencephalogram in different frequency bands in preoperative evaluation.And to study the activation mechanism of hippocampal glial cells in epileptic rats through in vitro and vivo epileptic models.Part? Prognostic factors of epilepsy surgery for different pathological types of refractory temporal lobe epilepsyObjective: Temporal lobe epilepsy(TLE)is a common type of intractable epilepsy leading to surgery.The predictors of favorable prognostic after epilepsy surgery for TLE are still unclear.The study was intended to analyze the clinical data,prognosis and predictors of well outcome after surgery for different pathological types of temporal lobe epilepsy.Methods: We studied the clinical characteristics,pathological type and prognosis of 92 patients with refractory temporal lobe epilepsy who underwent surgical treatment in our hospital from September 2006 to September 2018.All the patients underwent a resection of anterior temporal lobe combining with partial amygdalohippocampectomy,and were classified into five groups: gliocyte hyperplasia(43 cases),hippocampal sclerosis(16 cases),space-occupying lesion(13 cases),focal cortical dysplasia(11 cases)and dual pathology(9 cases)according to postoperative histopathology results.Seizure outcomes were assessed using the Engel classifications.The relevant factors affecting the surgical effect of refractory temporal lobe epilepsy were analyzed.Results: In the 92 patients,there were 72 cases(78.3%)with a good outcome and 20 cases(21.7%)with a poor outcome.Moreover,the difference was observed between the two groups,except whether or not to conduct intracrania video electroencephalogram(i-VEEG)monitoring.The good outcome rate of patients without i-VEEG monitoring was 85.5%,and the good outcome rate of patients with i-VEEG was 66.7%(?2=4.369,P=0.037).No differences were observed between the groups regarding surgical age,gender,epilepsy course,onset age of epileptic seizures,preoperative AEDs load,preoperative seizure frequency,positive rate of MRI,and surgery side.In addition,the correlation between continuous variables and the Engel's score in all patients was not been observed.Significant differences in the age at onset(P = 0.031),rate of i-VEEG monitoring(P=0.037),and the positive rate of MRI(P=0.001)were observed in the five groups of patients.Among the five groups,the highest rate of a good outcome was 100% in the dual-pathologic group,92.3% in the space-occupying pathological group,87.5% in the hippocampal sclerosis group,81.8% in the FCD group,and 69.8% in the neuron degeneration group,however,there was no statistic difference among the five groups.Conclusions: The well outcome of patients after surgery was most likely to be found in patients with a positive MRI.Patients with FCD were the earlier to experience seizures,patients with space-occupying lesions had seizures later,and patients with neurodegenerative diseases were find to usually have a previous medical history.Although i-VEEG can help to improve the surgical results of patients with inaccurate localization of epileptic foci,it is still worse compared to patients with a positive MRI.Part ? Clinical value of magnetoencephalogram multifrequency analysis in preoperative evaluation of refractory temporal lobe epilepsyObjective: To evaluate the accuracy and value of magnetoencephalography(MEG)multi-frequency analyze in locating epileptogenic foci of refractory temporal lobe epilepsy.Methods: A total of 41 TLE patients were studied during the interictal phase using a 275 channel whole-head magnetoencephalography system.MEG data were studied with multi-frequency range of 4–140 Hz,including the following frequency bands: theta(4–8 Hz),alpha(8–13 Hz),beta(13–30 Hz),gamma(30–90 Hz),and high-frequency oscillations or HFOs(90–140 Hz).The frequency features of the measured MEG data in source space were analyzed with accumulated spectrogram.Sources of MEG signals were localized with accumulated source imaging.The clinical value of MEG multifrequency analysis was analyzed by comparing the relationship between MRI,video electroencephalogram(VEEG)localization and resection range.Results: TLE subjects showed significantly higher concordance between MEG theta activity(4–8 Hz),alpha activity(8–13 Hz)and beta activity(13–30 Hz)with the surgery site.Also,the statistic difference was observed between the five groups(?2 = 40.3,P < 0.0001).Patients with MEG localization consistent with the surgical site had a 59% chance of no seizure after surgery,while patients with video EEG consistent with the surgical site had 51% chance of no seizure after surgery.The MEG findings proved to be valuable for preoperative evaluation.A favorable outcome was seen in 77.3%(17/22)of patients with concordance between the 4-8Hz band results and the surgery spot,and in 95.8%(23/24)and 80.0%(28/35)of patients with concordant MRI and VEEG data,respectively.The seizure-free rate in these three groups was 59.1%,62.5% and 51.4%,respectively.There were no statistically significant differences in terms of favorable operative outcome or seizure-free rate between the 4-8Hz band,MRI and VEEG groups.Conclusions: This study showed that,MEG localization results of most patients were consistent with the resection site,and good surgical results could be obtained even without VEEG monitoring.Consistency among different evaluation methods may indicate better postoperative results.However,VEEG monitoring remains a prerequisite for patients with inconsistent MEG and MRI results.Our results suggest that MEG may provide important information for the localization of epileptic foci in refractory temporal lobe epilepsy.Part ? Expression of Lnc RNA CASC2 in hippocampus of epileptic rats and its effect on astrocyte activation and adenosine metabolismObjective: Growing evidence has indicated that long noncoding RNAs(lnc RNAs)are playing pivotal role in neural development,especially in astrocytes differentiation,and closely implicated in the progress of epilepsy.However,the expression profile and potential function of lnc RNA CASC2 in epilepsy are poorly studied.The aim of this study was to testify the influence of lnc RNA CASC2 on epilepsy in rat and cell models of epileptic seizure.Methods: We adopted q RT-PCR on the hippocampus of rats following pentylenetetrazol(PTZ)-stimulated epilepsy.To further examine the correlation between lnc RNA CASC2 and PTEN,we detected the effects of lnc RNA CASC2 on PTEN expression.Results: We found that lnc RNA CASC2 and PTEN expression were positively correlated in PTZ-induced epileptic rat.Overexpression of lnc RNA CASC2 prolonged the latency and reduced the frequency of epileptic seizure,suppressed the activation of astrocytes and the release of adenosine in epileptic rat,whereas downregulation of lnc RNA CASC2 exhibited the opposite effects.Meanwhile,lnc RNA CASC2 decreased the adenosine metabolism related proteins expression of p38,ENT1 and ADK.In PTZ-treated astrocytes,PTEN was found to be a direct target of lnc RNA CASC2.Additionally,downregulation of PTEN attenuated the protective effect of lnc RNA CASC2 overexpression in epileptic seizure.Conclusions: Our study for the first time demonstrated that lnc RNA CASC2 with co-dysregulated m RNA PTEN were downregulated in the hippocampus of epileptic rats.Specially,lnc RNA CASC2 suppressed PTZ-induced epilepsy by regulating PTEN expression,and thereby suppressed astrocytes activation and adenosine metabolism during epileptogenesis.This study highlights a promising strategy for epilepsy prevention.