ObjectivesTo study surgical outcomes and safety of unilateral anterior temporal lobectomy (ATL) in patients with intractable bilateral temporal lobe epilepsy (TLE) and dominant seizure-onset in unilateral temporal lobe. MethodsTwenty three carefully selected patients with bilaterial TLE and dominant seizure-onset in unilateral temporal lobe were enrolled and divided into surgery and medicine groups according to the treatment.Seizure control were recorded for 2 to 5 years.Changes of full scale of intelligence quotient(IQ),and overall quality of life (QOL),percentage of therapeutic satisfaction,and surgical complications were analyzed 2 years after enrolling. ResultsFavor seizure control (Engel Class I and Class Ⅱ) reached 66.7% (10/15),60% (9/15),and 50% (5/10) at 1,2 and 5 years follow-up after unilateral ATL respectively,the percentages in medicine group is 12.5%,0% and 0% accordingly,and there were significant differences in seizures controls between patients with unilateral ATL and cases with medicine.Significantly differences were also found in changes of patients'QOL and full scale IQ at 2 years follow-up between surgery and medicine groups,and average score of overall QOL improved 5.27±6.45 in surgery group,and declined 1.40±3.58 in medicine group.In ATL group,patients with short preoperative history of seizure presented more favor seizure control than those with long preoperative history,and patients with favor seizure control and short preoperative history of seizure had more chance to improve QOL and IQ after ATL. ConclusionIntracranial EEG is vital in diagnosis of bilateral TLE.Unilateral ATL presents favor seizure control and did not render serious memory and IQ injury in carefully selected patients with true bilateral TLE and dominant seizure-onset in unilateral temporal lobe.
ObjectiveTo study the cytokine changes in the cerebrospinal fluid (CSF) of mesial temporal lobe epilepsy (MTLE) patients, and the mechanism of the development of hippocampal sclerosis. MethodsFifty MTLE patients who sought treatment from January 2013 to March 2014 were included in the study. Clinical features were investigated. All CSF samples of the 59 patients along with 19 samples of the control group were tested for 12 common cytokines using a chemokine magnetic bead panel. Data were statistically analyzed. ResultsClinical features showed no significant difference between hippocampal sclerosis and non-hippocampal sclerosis patients. Interleukin (IL)-1 receptor antagonist (RA), IL-4 and IL-9 expression decreased, and tumor necrosis factor (TNF)-α, IL-3 and IL-5 expression increased. Up-regulation of TNF-α was significantly different between hippocampal sclerosis and non-hippocampal sclerosis patients. ConclusionIL-1RA, IL-3, IL-4, IL-5 and IL-9 changes may be non-specific seizure-related cytokine regulation. TNF-α is associated with hippocampal sclerosis pathology. TNF-α is a possible pathological element in hippocampal sclerosis development.
Objective To discuss the correlation between glutamate receptor 5 (GLUR5) and the pathogenesis of intractable temporal lobe epilepsy (ITLE), through detecting the GLUR5 expression in human with ITLE and Coriaria lactone-induced rhesus monkey temporal lobe epilepsy model. Methods Fifty-four patients with ITLE treated in West China Hospital between January 2007 and December 2015 were regarded as clinical case group in this study. The other 43 patients who underwent temporal lobe removal decompression surgery in the same time period due to trauma, tumor or large area cerebral hemorrhage complicated with cerebral hernia were designated as the clinical control group. Quantitive polymerase chain reaction (PCR) and Western blot methods were used to detect mRNA and protein levels of GLUR5. Western blot was also used to detect the GLUR5 protein level in the hippocampus and temporal lobe tissues of Coriaria lactone-induced rhesus monkey epilepsy model, and the result was compared with that of animal controls. Results Quantitive PCR results showed that the expression ratio (R value) of GLUR5 in the temporal lobe of the clinical case group to the clinical control group was 0.262, without significant difference (P>0.05), while theR value in the hippocampus was 4.896, with a significant difference (P<0.05). The amplification curve showed that the GLUR5 level in the hippocampus of the clinical case group was higher than that of the clinical control group, but the GLUR5 mRNA level in the temporal lobe tissue was not significantly changed. GLUR5 PCR amplified product electrophoresis showed that the amplified fragment was 161 bp. Western blot analysis showed that the GLUR5/actin value of the temporal lobe tissue in the clinical case group was 2.172±0.063, while the value in the clinical control group was 2.142±0.060, and the difference was not statistically significant (P>0.05). The GLUR5/actin value of the hippocampus in the clinial case group was 2.548±0.509, while it was 1.584±0.415 in the clinial control group, and the difference was statistically significant (P<0.05). The GLUR5/actin value of the hippocampus of the rhesus monkey model of epilepsy was 1.007±0.034, and it was 1.001±0.032 in the animal control group, and the difference was not statistically significant (P>0.05). The GLUR5/actin value of the temporal lobe tissue in the animal experimental group of rhesus model of epilepsy was 0.763±0.026, and it was 0.742±0.034 in the animal control group, and the difference was not statistically significant (P>0.05). The target protein bands showed that GLUR5 protein expression in the temporal lobe tissue and hippocampus of the rhesus model of epilepsy and animal controls was not significantly different (P>0.05). Conclusions GLUR5 participates in the pathogenesis of human ITLE by acting on the hippocampus. The expression of GLUR5 in human ITLE is abnormal, but the expression of GLUR5 is not changed in the rhesus model of epilepsy. The abnormal expression of GLUR5 may play a role in the pathogenesis of ITLE.
This study aims to determine the salient brain regions with abnormal changes in white matter structures from diffusion tensor imaging (DTI) images of the patients with temporal lobe epilepsy (TLE), and to discriminate the patients with TLE from normal controls (NCs). Firstly, the DTI images from 50 subjects (28 NCs and 22 TLE) were acquired. Secondly, the four measures including the fractional anisotropy (FA), the mean diffusivity (MD), the axial diffusivity (AD) and the radial diffusivity (RD) were calculated. Thirdly, the tract-based spatial statistics (TBSS) was adopted to extract the measures in brain regions with significant differences between the two compared groups. Fourthly, the obtained measures were used as input features of the support vector machine (SVM) for classification, and the support vector machine-recursive feature elimination (SVM-RFE) was compared with the support vector machine-tract-based spatial statistics (SVM-TBSS) method. Finally, the essential brain regions and their spatial distribution were analyzed and discussed. The experimental results showed that the FA measures of the TLE group decreased significantly in the corpus callosum, superior longitudinal fasciculus, corona radiata, external capsule, internal capsule, inferior fronto-occipital fasciculus, fasciculus uncinatus and sagittal stratum, which were nearly bilaterally distributed, while the MD and RD increased significantly in most of these brain regions of the TLE group. Although the AD also increased, the differences were not statistically significant. The SVM-TBSS classifier obtained accuracies of 82%, 76% and 76% using the FA, MD and RD for classification, respectively, and 80% using combined measures. The SVM-RFE classifier obtained accuracies of 90%, 90% and 92% using the FA, MD and RD respectively, while the highest accuracy was 100% using combined measures. These results demonstrated that the SVM-RFE outperformed the SVM-TBSS, and the dominant characteristic influencing classification in brain regions were in associative and commissural fibers. These results illustrated that the measures of DTI images could reveal the abnormal changes in white matter structure of patients with TLE, providing effective information to clarify its pathological mechanism, localize the focus and diagnose automatically.
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.
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.
Stereo-electroencephalography (SEEG) is widely used to record the electrical activity of patients' brain in clinical. The SEEG-based epileptogenic network can better describe the origin and the spreading of seizures, which makes it an important measure to localize epileptogenic zone (EZ). SEEG data from six patients with refractory epilepsy are used in this study. Five of them are with temporal lobe epilepsy, and the other is with extratemporal lobe epilepsy. The node outflow (out-degree) and inflow (in-degree) of information are calculated in each node of epileptic network, and the overlay between selected nodes and resected nodes is analyzed. In this study, SEEG data is transformed to bipolar montage, and then the epileptic network is established by using independent effective coherence (iCoh) method. The SEEG segments at onset, middle and termination of seizures in Delta, Theta, Alpha, Beta, and Gamma rhythms are used respectively. Finally, the K-means clustering algorithm is applied on the node values of out-degree and in-degree respectively. The nodes in the cluster with high value are compared with the resected regions. The final results show that the accuracy of selected nodes in resected region in the Delta, Alpha and Beta rhythm are 0.90, 0.88 and 0.89 based on out-degree values in temporal lobe epilepsy patients respectively, while the in-degree values cannot differentiate them. In contrast, the out-degree values are higher outside the temporal lobe in the patient with extratemporal lobe epilepsy. Based on the out-degree feature in low-frequency epileptic network, this study provides a potential quantitative measure for identifying patients with temporal lobe epilepsy in clinical.
Objective To identify the most consistent and replicable characteristics of altered spontaneous brain activity in mesial temporal lobe epilepsy patients with unilateral hippocampal sclerosis (MTLE-HS). Methods A systematic literature search was performed in PubMed, Embase, The Cochrane Library, China National Knowledge Infrastructure, Wanfang, and CQVIP databases, to identify eligible whole-brain resting state functional magnetic resonance imaging studies that had measured differences in amplitude of low-frequency fluctuations or fractional amplitude of low-frequency fluctuations between patients with MTLE-HS and healthy controls from January 2000 to January 2019. After literature screening and data extraction, Anisotropic Effect-Size Signed Differential Mapping software was used for voxel based pooled meta-analysis. Results Nine datasets from six studies were finally included, which contained 207 MTLE-HS patients and 239 healthy controls. The results demonstrated that, compared with the healthy controls, the MTLE-HS patients showed increased spontaneous brain activity in right hippocampus and parahippocampal gyrus, right superior temporal gyrus, left cingulate gyrus, right fusiform gyrus, and right inferior temporal gyrus; while decreased spontaneous brain activity in left superior frontal gyrus, right angular gyrus, right middle frontal gyrus, left inferior parietal lobule, left precuneus, and right cerebellum (P<0.005, cluster extent≥10). Conclusion The current meta-analysis demonstrates that patients with MTLE-HS show increased spontaneous brain activity in lateral and mesial temporal regions and decreased spontaneous brain activity in default mode network, which preliminarily clarifies the characteristics of altered spontaneous brain activity in patients with MTLE-HS.
ObjectiveTo investigate the significant genes in Mesio-temporal lobe epilepsy (MTLE) and explore the molecular mechanism of MTLE.MethodsThe microarray data of MTLE were downloaded from the Gene Expression Omnibus (GEO) database and analyzed by bioinformatics methods using GEO2R tool, Venny2.1.0, FUNRICH and Cytoscape software, DAVID and String databases.ResultsOf all the 331 differentially expressed genes(DEGs), 46 genes were down-regulated and 285 genes were up-regulated in dataset GSE88992; Furthermore, the core module genes were identified from those DEGs, which were expressed mostly in plasma membrane and extracellular space; The major molecular funtion were chemokine activity, cytokine activity and chemokine receptor binding; The main biological pathways involved neutrophil chemotaxis, inflammatory response and positive regulation of ERK1 and ERK2 cascade; The KEGG analysis showed DEGs enriched in Chemokine signaling pathway, Cytokine-cytokine receptor interaction and Complement and coagulation cascades. In addition, ten hub genes (Il6, Fos, Stat3, Ptgs2, Ccl2, Timp1, Cd44, Icam1, Atf3, Cxcl1) were found to significantly express in the MTLE.ConclusionThe pathogenesis of MTLE involves multiple genes, and multiple cell signaling pathways. Thus investigations of these genes may provide valuable insights into the mechanism of MTLE.
ObjectiveTo explore the pathogenic mechanism of human herpesvirus 6B (HHV-6B) in the intractable mesial temporal lobe epilepsy (MTLE).Methods42 cases of intractable MTLE and 17 cases of non-MTLE patients who treated in Wuhan Brain Hospital from Jan. 2012 to Dec. 2018 were enrolled in this study. Resected hippocampus, amygdala and mixed uncus samples were examined by real-time polymerase chain reaction (PCR) and reverse-transcriptase PCR to detect viral DNA and message RNA. Comparative analysis was used between the clinical characteristics and the HHV-6 detection.ResultsDetection of HHV-6 DNA was higher in MTLE patients (40.48%) than non-MTLE patients (11.7%). HHV-6B viral DNA was determined in 15/30 HHV-6 DNA-positive samples, and no HHV-6B mRNA were detected in all HHV-6 DNA negative samples. The patient’s age was the only influencing factor of HHV-6 expressing in MTLE. While the patient’s gender, onset age and possible disease cause had no effect on the HHV-6 content.ConclusionsThis study suggests that HHV-6B may play an important role in the pathogenesis of MTLE, but the mechanism needs further study.