Temporal lobe epilepsy is the most common form of focal epilepsy in adults,accounting for one third of all diagnosed epileptic patients,with seizures originating from or involving mesial temporal structures such as th...Temporal lobe epilepsy is the most common form of focal epilepsy in adults,accounting for one third of all diagnosed epileptic patients,with seizures originating from or involving mesial temporal structures such as the hippocampus,and many of these patients being refractory to treatment with anti-epileptic drugs.Temporal lobe epilepsy is the most common childhood neurological disorder and,compared with adults,the symptoms are greatly affected by age and brain development.Diagnosis of temporal lobe epilepsy relies on clinical examination,patient history,electroencephalographic recordings,and brain imaging.Misdiagnosis or delay in diagnosis is common.A molecular biomarker that could distinguish epilepsy from healthy subjects and other neurological conditions would allow for an earlier and more accurate diagnosis and appropriate treatment to be initiated.Among possible biomarkers of pathological changes as well as potential therapeutic targets in the epileptic brain are micro RNAs.Most of the recent studies had performed micro RNA profiling in body fluids such as blood plasma and blood serum and brain tissues such as temporal cortex tissue and hippocampal tissue.A large number of micro RNAs were dysregulated when compared to healthy controls and with some overlap between individual studies that could serve as potential biomarkers.For example,in adults with temporal lobe epilepsy,possible biomarkers are miR-199a-3p in blood plasma and miR-142-5p in blood plasma and blood serum.In adults with mesial temporal lobe epilepsy,possible biomarkers are miR-153 in blood plasma and miR-145-3p in blood serum.However,in many of the studies involving patients who receive one or several anti-epileptic drugs,the influence of these on micro RNA expression in body fluids and brain tissues is largely unknown.Further studies are warranted with children with temporal lobe epilepsy and consideration should be given to utilizing mouse or rat and non-human primate models of temporal lobe epilepsy.The animal models could be used to confirm micro RNA findings in human patients and to test the effects of targeting specific micro RNAs on disease progression and behavior.展开更多
The Na＋-K＋-CI- cotransporter 1 and K＋-CI- cotransporter 2 regulate the levels of intracellular chloride in hippocampal cells. Impaired chloride transport by these proteins is thought to be involved in the pathophys...The Na＋-K＋-CI- cotransporter 1 and K＋-CI- cotransporter 2 regulate the levels of intracellular chloride in hippocampal cells. Impaired chloride transport by these proteins is thought to be involved in the pathophysiological mechanisms of mesial temporal lobe epilepsy. Imbalance in the relative expression of these two proteins can lead to a collapse of CI- homeostasis, resulting in a loss of gamma-aminobutyric acid-ergic inhibition and even epileptiform discharges. In this study, we investigated the expression of Na＋-K＋-CI- cotransporter 1 and K＋-CI- cotransporter 2 in the sclerosed hippocampus of patients with mesial temporal lobe epilepsy, using western blot analysis and immunohistochemistry. Compared with the histologically normal hippocampus, the sclerosed hippocampus showed increased Na＋-K＋-Cl- cotransporter 1 expression and decreased K＋-CI- cotransporter 2 expression, especially in CA2 and the dentate gyrus. The change was more prominent for the Na＋-K＋-CI- cotransporter 1 than for the K＋-CI- cotransporter 2. These experimental findings indicate that the balance between intracellular and extracellular chloride may be disturbed in hippocampal sclerosis, contributing to the hyperexcitability underlying epileptic seizures. Changes in Na＋-K＋-CI-cotransporter 1 expression seems to be the main contributor. Our study may shed new light on possible therapies for patients with mesial temporal lobe epilepsy with hippocampal sclerosis.展开更多
Objective To determine the spatio-temporal expression of p70S6k activation in hippocampus in mesial temporal lobe epilepsy. Methods Temporal lobe epilepsy model was established by stereotaxically unilateral and intrah...Objective To determine the spatio-temporal expression of p70S6k activation in hippocampus in mesial temporal lobe epilepsy. Methods Temporal lobe epilepsy model was established by stereotaxically unilateral and intrahip-pocampal injection of kainite acid (KA) in adult male C57BL/6 mice. Latent and chronic epileptogenesis were represented by mice 5 days after KA injection (n=5) and mice 5 weeks after KA injection (n=8), respectively. Control mice (n=5) were injected with saline. Immunohistochemical assays were performed on brain sections of the mice. Results Hippocampus both ipsilateral and contralateral to the KA injection displayed significantly up-regulated pS6 immunoreactivity in dispersed granule cells in 5-day and 5-week model mice. Conclusion The activation of p70S6k is mainly located in the dentate gyrus in KA-induced mouse model of temporal lobe epilepsy, indicating that the activation may be related with the disperse degree and hypertrophy of granule cells.展开更多
Background Autophagy plays essential roles in the development and pathogenesis of mesial temporal lobe epilepsy(mTLE).In this research,we aim to identify and validate the autophagy-related genes associated with mTLE t...Background Autophagy plays essential roles in the development and pathogenesis of mesial temporal lobe epilepsy(mTLE).In this research,we aim to identify and validate the autophagy-related genes associated with mTLE through bioinformatics analysis and experimental validations.Methods We obtained the dataset GSE143272 and high-throughput sequencing results of mTLE from public data-bases.Potential differentially expressed autophagy-related genes related to mTLE were identified using R software.Subsequently,genomes pathway enrichment analysis,protein-protein interactions(PPIs),and the gene ontology(GO)enrichment were performed for the selected autophagy-related genes.The mRNA expression profiles of hub genes were then used to establish a least absolute shrinkage and selection operator(LASSO)model.Finally,seven hub candidate autophagy-related genes were confirmed in hippocampus using the lithium-pilocarpine chronic epilepsy model.Results A total of 40 differential expression genes(DEGs)among the core autophagy-related genes were identified.The analysis results of PPI revealed that interactions among these DEGs.KEGG pathway and GO analysis of selected candidate autophagy-related genes indicated that those enriched terms mainly focused on macroautophagy,regula-tion of autophagy,cellular response to extracellular stimulus and mitochondrion disassembly.The results suggested that SQSTM1,VEGFA,BNIP and WIPI2 were consistent with the bioinformatics analysis.The expression levels of SQSTM1 and VEGFA in epilepsy model samples were significantly higher than those in normal control,while BNIP and WIPI2 expression levels were notably decreased.The final hub gene-based LASSO regression model accurately predicted the occurrence of epilepsy(AUC=0.88).Conclusions Through bioinformatics analysis of public data,we identified 40 candidate autophagy-related genes associated with mTLE.SQSTM1,VEGFA,BNIP and WIPI2 may play significant roles in autophagy,influencing the onset and development of mTLE by regulating autophagy pathway.These findings deepen our understanding of mTLE,and may serve as sensitive and valuable indicators for the prognosis and diagnosis of this condition.展开更多
Background There is a lack of further exploration of the epileptogenic network of specific types of epilepsy,such as unilateral hippocampal sclerosis(HS),and there is an urgent need to find exact evidence to confirm t...Background There is a lack of further exploration of the epileptogenic network of specific types of epilepsy,such as unilateral hippocampal sclerosis(HS),and there is an urgent need to find exact evidence to confirm the consistency of its brain network changes.Methods We enrolled 22 mesial temporal lobe epilepsy with hippocampal sclerosis(mTLE-HS)patients to compare the differences in brain activity between 22 healthy controls(HCs)and them.Resting-state electroencephalography(EEG)was also measured.Then,we calculated the power spectral density and phase locking values in and between these electrodes.Results The results showed the increased theta power was related to the high severity of epilepsy in the temporal,parietal,and central regions in mTLE-HS patients,and there were positive correlations between theta power in the contralateral temporal region and seizure frequency.Theta power in the ipsilateral parietal lobe is positively correlated with the number of anti-seizure medications(ASMs),but not with the usage of third-generation ASMs.Meanwhile,the temporal lobe of mTLE-HS patients had more connectivity with parietal lobe and central region.展开更多
Background: Many studies have emphasized that selective resection of epileptic lesions in temoral lobe is associated with better preservation of cognition function;whether this applies to patients with refractory mesi...Background: Many studies have emphasized that selective resection of epileptic lesions in temoral lobe is associated with better preservation of cognition function;whether this applies to patients with refractory mesial temporal lobe epilepsy (MTLE) remains unknown. The objective of this study was to evaluate changes in cognitive functions, mood status, and quality of life after anterior temporal lobectomy in patients with refractory MTLE. Methods: This single-arm cohort study assessed cognitive function, mood status, and quality of life, as well as electroencephalography findings, in patients with refractory MTLE who underwent anterior temporal lobectomy at Xuanwu Hospital from January 2018 to March 2019. Pre- and post-operative characteristics were compared to evaluate the effects of surgery. Results: Anterior temporal lobectomy significantly reduced the frequencies of epileptiform discharges. The overall success rate of surgery was acceptable. Anterior temporal lobectomy did not result in significant changes in overall cognitive functions (P > 0.05), although changes in certain domains, including visuospatial ability, executive ability, and abstract thinking, were detected. Anterior temporal lobectomy resulted in improvements in anxiety and depression symptoms and quality of life. Conclusions: Anterior temporal lobectomy reduced epileptiform discharges and incidence of post-operative seizures as well as resulted in improved mood status and quality of life without causing significant changes in cognitive function.展开更多
Mesial temporal lobe epilepsy(mTLE),the most common type of focal epilepsy,is associated with functional and structural brain alterations.Machine learning(ML)techniques have been successfully used in discriminating mT...Mesial temporal lobe epilepsy(mTLE),the most common type of focal epilepsy,is associated with functional and structural brain alterations.Machine learning(ML)techniques have been successfully used in discriminating mTLE from healthy controls.However,either functional or structural neuroimaging data are mostly used separately as input,and the opportunity to combine both has not been exploited yet.We conducted a multimodal ML study based on functional and structural neuroimaging measures.We enrolled 37 patients with left mTLE,37 patients with right mTLE,and 74 healthy controls and trained a support vector ML model to distinguish them by using each measure and the combinations of the measures.For each single measure,we obtained a mean accuracy of 74%and 69%for discriminating left mTLE and right mTLE from controls,respectively,and 64%when all patients were combined.We achieved an accuracy of 78%by integrating functional data and 79%by integrating structural data for left mTLE,and the highest accuracy of 84%was obtained when all functional and structural measures were combined.These findings suggest that combining multimodal measures within a single model is a promising direction for improving the classification of individual patients with mTLE.展开更多
Objective To investigate the lateralizing value of ictal face wiping(FW)in patients with refractory mesial temporal lobe epilepsy(MTLE).Methods Presurgical video types were retrospectively reviewed among 96 patients w...Objective To investigate the lateralizing value of ictal face wiping(FW)in patients with refractory mesial temporal lobe epilepsy(MTLE).Methods Presurgical video types were retrospectively reviewed among 96 patients who were seizure-free for at least 3 years after temporal lobectomy between 1997 and 2012.Attention展开更多
Human herpes virus 6(HHV-6)is a ubiquitous and most common pathogen that affects humans.Human herpes virus 6B(HHV-6B)is a wide spread human herpesvirus that infects most people when they are children,establishes laten...Human herpes virus 6(HHV-6)is a ubiquitous and most common pathogen that affects humans.Human herpes virus 6B(HHV-6B)is a wide spread human herpesvirus that infects most people when they are children,establishes latent infections in the central nervous system(CNS),especially in the hippocampus and amygdala,and induces neurologic diseases.HHV-6 can establish a latent infection and be reactivated by various stimuli.Recently,viral genomic DNA of HHV-6B has been detected in surgically removed brain tissues of intractable epilepsy patients,suggesting the involvement of HHV-6B in the pathogenesis of epilepsy.Temporal lobe epilepsy(TLE)has been shown to be closely related with HHV-6B.TLE patients with HHV-6B in their brains suffer from reiterative attacks of febrile seizures and hippocampal sclerosis.However,the mechanisms underlying the contribution of this virus to the development of TLE remains unknown.The direct damage and immune activation caused by the virus are involved in the process of neuron damage,abnormal neural circuit formation and glial cell proliferation.In addition,some cytokines like interleukin-17A(IL-17A),nuclear factor-kappa B(NF-κb),transforming growth factor-β(TGF-β),mitogen-activated protein kinase(MAPK)and phospholipase A2 are up-regulated and involved in the pathological process of TLE.More studies are needed to clarify the mechanisms underlying the link between HHV-6B and epilepsy,and identify biomarkers to recognize different patient groups for anti-inflammatory or immunomodulatory therapies.展开更多
文摘Temporal lobe epilepsy is the most common form of focal epilepsy in adults,accounting for one third of all diagnosed epileptic patients,with seizures originating from or involving mesial temporal structures such as the hippocampus,and many of these patients being refractory to treatment with anti-epileptic drugs.Temporal lobe epilepsy is the most common childhood neurological disorder and,compared with adults,the symptoms are greatly affected by age and brain development.Diagnosis of temporal lobe epilepsy relies on clinical examination,patient history,electroencephalographic recordings,and brain imaging.Misdiagnosis or delay in diagnosis is common.A molecular biomarker that could distinguish epilepsy from healthy subjects and other neurological conditions would allow for an earlier and more accurate diagnosis and appropriate treatment to be initiated.Among possible biomarkers of pathological changes as well as potential therapeutic targets in the epileptic brain are micro RNAs.Most of the recent studies had performed micro RNA profiling in body fluids such as blood plasma and blood serum and brain tissues such as temporal cortex tissue and hippocampal tissue.A large number of micro RNAs were dysregulated when compared to healthy controls and with some overlap between individual studies that could serve as potential biomarkers.For example,in adults with temporal lobe epilepsy,possible biomarkers are miR-199a-3p in blood plasma and miR-142-5p in blood plasma and blood serum.In adults with mesial temporal lobe epilepsy,possible biomarkers are miR-153 in blood plasma and miR-145-3p in blood serum.However,in many of the studies involving patients who receive one or several anti-epileptic drugs,the influence of these on micro RNA expression in body fluids and brain tissues is largely unknown.Further studies are warranted with children with temporal lobe epilepsy and consideration should be given to utilizing mouse or rat and non-human primate models of temporal lobe epilepsy.The animal models could be used to confirm micro RNA findings in human patients and to test the effects of targeting specific micro RNAs on disease progression and behavior.
基金supported by the Science and Technology Foundation of Guangdong Province,No.2008B060600063the National Natural Science Foundation of China,No. 81071050the Natural Science Foundation of Guangdong Province,No. S2011020005483
文摘The Na＋-K＋-CI- cotransporter 1 and K＋-CI- cotransporter 2 regulate the levels of intracellular chloride in hippocampal cells. Impaired chloride transport by these proteins is thought to be involved in the pathophysiological mechanisms of mesial temporal lobe epilepsy. Imbalance in the relative expression of these two proteins can lead to a collapse of CI- homeostasis, resulting in a loss of gamma-aminobutyric acid-ergic inhibition and even epileptiform discharges. In this study, we investigated the expression of Na＋-K＋-CI- cotransporter 1 and K＋-CI- cotransporter 2 in the sclerosed hippocampus of patients with mesial temporal lobe epilepsy, using western blot analysis and immunohistochemistry. Compared with the histologically normal hippocampus, the sclerosed hippocampus showed increased Na＋-K＋-Cl- cotransporter 1 expression and decreased K＋-CI- cotransporter 2 expression, especially in CA2 and the dentate gyrus. The change was more prominent for the Na＋-K＋-CI- cotransporter 1 than for the K＋-CI- cotransporter 2. These experimental findings indicate that the balance between intracellular and extracellular chloride may be disturbed in hippocampal sclerosis, contributing to the hyperexcitability underlying epileptic seizures. Changes in Na＋-K＋-CI-cotransporter 1 expression seems to be the main contributor. Our study may shed new light on possible therapies for patients with mesial temporal lobe epilepsy with hippocampal sclerosis.
基金Supported by National Natural Science Foundation of China (31021091, 30971001)Beijing Natural Science Foundation (7102109)Fok Ying Tong Education Foundation (121024)
文摘Objective To determine the spatio-temporal expression of p70S6k activation in hippocampus in mesial temporal lobe epilepsy. Methods Temporal lobe epilepsy model was established by stereotaxically unilateral and intrahip-pocampal injection of kainite acid (KA) in adult male C57BL/6 mice. Latent and chronic epileptogenesis were represented by mice 5 days after KA injection (n=5) and mice 5 weeks after KA injection (n=8), respectively. Control mice (n=5) were injected with saline. Immunohistochemical assays were performed on brain sections of the mice. Results Hippocampus both ipsilateral and contralateral to the KA injection displayed significantly up-regulated pS6 immunoreactivity in dispersed granule cells in 5-day and 5-week model mice. Conclusion The activation of p70S6k is mainly located in the dentate gyrus in KA-induced mouse model of temporal lobe epilepsy, indicating that the activation may be related with the disperse degree and hypertrophy of granule cells.
基金the National Natural Science Foundation of China(82071447,81571266,81771405)the Sanming Project of Medicine in Shenzhen(No.SZSM201911003).
文摘Background Autophagy plays essential roles in the development and pathogenesis of mesial temporal lobe epilepsy(mTLE).In this research,we aim to identify and validate the autophagy-related genes associated with mTLE through bioinformatics analysis and experimental validations.Methods We obtained the dataset GSE143272 and high-throughput sequencing results of mTLE from public data-bases.Potential differentially expressed autophagy-related genes related to mTLE were identified using R software.Subsequently,genomes pathway enrichment analysis,protein-protein interactions(PPIs),and the gene ontology(GO)enrichment were performed for the selected autophagy-related genes.The mRNA expression profiles of hub genes were then used to establish a least absolute shrinkage and selection operator(LASSO)model.Finally,seven hub candidate autophagy-related genes were confirmed in hippocampus using the lithium-pilocarpine chronic epilepsy model.Results A total of 40 differential expression genes(DEGs)among the core autophagy-related genes were identified.The analysis results of PPI revealed that interactions among these DEGs.KEGG pathway and GO analysis of selected candidate autophagy-related genes indicated that those enriched terms mainly focused on macroautophagy,regula-tion of autophagy,cellular response to extracellular stimulus and mitochondrion disassembly.The results suggested that SQSTM1,VEGFA,BNIP and WIPI2 were consistent with the bioinformatics analysis.The expression levels of SQSTM1 and VEGFA in epilepsy model samples were significantly higher than those in normal control,while BNIP and WIPI2 expression levels were notably decreased.The final hub gene-based LASSO regression model accurately predicted the occurrence of epilepsy(AUC=0.88).Conclusions Through bioinformatics analysis of public data,we identified 40 candidate autophagy-related genes associated with mTLE.SQSTM1,VEGFA,BNIP and WIPI2 may play significant roles in autophagy,influencing the onset and development of mTLE by regulating autophagy pathway.These findings deepen our understanding of mTLE,and may serve as sensitive and valuable indicators for the prognosis and diagnosis of this condition.
基金National Key R&D Program of China(2022YFC2503801)Cadre Health Care Project of the Sichuan Provincial Department of Health(2023–110)National College Student Innovation and Entrepreneurship Training Program(C2024131786).
文摘Background There is a lack of further exploration of the epileptogenic network of specific types of epilepsy,such as unilateral hippocampal sclerosis(HS),and there is an urgent need to find exact evidence to confirm the consistency of its brain network changes.Methods We enrolled 22 mesial temporal lobe epilepsy with hippocampal sclerosis(mTLE-HS)patients to compare the differences in brain activity between 22 healthy controls(HCs)and them.Resting-state electroencephalography(EEG)was also measured.Then,we calculated the power spectral density and phase locking values in and between these electrodes.Results The results showed the increased theta power was related to the high severity of epilepsy in the temporal,parietal,and central regions in mTLE-HS patients,and there were positive correlations between theta power in the contralateral temporal region and seizure frequency.Theta power in the ipsilateral parietal lobe is positively correlated with the number of anti-seizure medications(ASMs),but not with the usage of third-generation ASMs.Meanwhile,the temporal lobe of mTLE-HS patients had more connectivity with parietal lobe and central region.
文摘Background: Many studies have emphasized that selective resection of epileptic lesions in temoral lobe is associated with better preservation of cognition function;whether this applies to patients with refractory mesial temporal lobe epilepsy (MTLE) remains unknown. The objective of this study was to evaluate changes in cognitive functions, mood status, and quality of life after anterior temporal lobectomy in patients with refractory MTLE. Methods: This single-arm cohort study assessed cognitive function, mood status, and quality of life, as well as electroencephalography findings, in patients with refractory MTLE who underwent anterior temporal lobectomy at Xuanwu Hospital from January 2018 to March 2019. Pre- and post-operative characteristics were compared to evaluate the effects of surgery. Results: Anterior temporal lobectomy significantly reduced the frequencies of epileptiform discharges. The overall success rate of surgery was acceptable. Anterior temporal lobectomy did not result in significant changes in overall cognitive functions (P > 0.05), although changes in certain domains, including visuospatial ability, executive ability, and abstract thinking, were detected. Anterior temporal lobectomy resulted in improvements in anxiety and depression symptoms and quality of life. Conclusions: Anterior temporal lobectomy reduced epileptiform discharges and incidence of post-operative seizures as well as resulted in improved mood status and quality of life without causing significant changes in cognitive function.
基金This study was supported by the National Natural Science Foundation of China(Nos.81501452,81621003,81761128023,81220108031,and 81227002)the Program for Innovative Research Team in University(PCSIRT,No.IRT16R52)of China+1 种基金the Scholar Professorship Award(No.T2014190)of Chinathe CMB Distinguished Professorship Award(No.F510000/G16916411)administered by the Institute of International Education.
文摘Mesial temporal lobe epilepsy(mTLE),the most common type of focal epilepsy,is associated with functional and structural brain alterations.Machine learning(ML)techniques have been successfully used in discriminating mTLE from healthy controls.However,either functional or structural neuroimaging data are mostly used separately as input,and the opportunity to combine both has not been exploited yet.We conducted a multimodal ML study based on functional and structural neuroimaging measures.We enrolled 37 patients with left mTLE,37 patients with right mTLE,and 74 healthy controls and trained a support vector ML model to distinguish them by using each measure and the combinations of the measures.For each single measure,we obtained a mean accuracy of 74%and 69%for discriminating left mTLE and right mTLE from controls,respectively,and 64%when all patients were combined.We achieved an accuracy of 78%by integrating functional data and 79%by integrating structural data for left mTLE,and the highest accuracy of 84%was obtained when all functional and structural measures were combined.These findings suggest that combining multimodal measures within a single model is a promising direction for improving the classification of individual patients with mTLE.
文摘Objective To investigate the lateralizing value of ictal face wiping(FW)in patients with refractory mesial temporal lobe epilepsy(MTLE).Methods Presurgical video types were retrospectively reviewed among 96 patients who were seizure-free for at least 3 years after temporal lobectomy between 1997 and 2012.Attention
基金funded by the Science&Technology Department of Sichuan Province(No.2019YFH0145)National Natural Science Foundation of China(No.81571272).
文摘Human herpes virus 6(HHV-6)is a ubiquitous and most common pathogen that affects humans.Human herpes virus 6B(HHV-6B)is a wide spread human herpesvirus that infects most people when they are children,establishes latent infections in the central nervous system(CNS),especially in the hippocampus and amygdala,and induces neurologic diseases.HHV-6 can establish a latent infection and be reactivated by various stimuli.Recently,viral genomic DNA of HHV-6B has been detected in surgically removed brain tissues of intractable epilepsy patients,suggesting the involvement of HHV-6B in the pathogenesis of epilepsy.Temporal lobe epilepsy(TLE)has been shown to be closely related with HHV-6B.TLE patients with HHV-6B in their brains suffer from reiterative attacks of febrile seizures and hippocampal sclerosis.However,the mechanisms underlying the contribution of this virus to the development of TLE remains unknown.The direct damage and immune activation caused by the virus are involved in the process of neuron damage,abnormal neural circuit formation and glial cell proliferation.In addition,some cytokines like interleukin-17A(IL-17A),nuclear factor-kappa B(NF-κb),transforming growth factor-β(TGF-β),mitogen-activated protein kinase(MAPK)and phospholipase A2 are up-regulated and involved in the pathological process of TLE.More studies are needed to clarify the mechanisms underlying the link between HHV-6B and epilepsy,and identify biomarkers to recognize different patient groups for anti-inflammatory or immunomodulatory therapies.
