Temporal lobe epilepsy is a multifactorial neurological dysfunction syndrome that is refractory,resistant to antiepileptic drugs,and has a high recurrence rate.The pathogenesis of temporal lobe epilepsy is complex and...Temporal lobe epilepsy is a multifactorial neurological dysfunction syndrome that is refractory,resistant to antiepileptic drugs,and has a high recurrence rate.The pathogenesis of temporal lobe epilepsy is complex and is not fully understood.Intracellular calcium dynamics have been implicated in temporal lobe epilepsy.However,the effect of fluctuating calcium activity in CA1 pyramidal neurons on temporal lobe epilepsy is unknown,and no longitudinal studies have investigated calcium activity in pyramidal neurons in the hippocampal CA1 and primary motor cortex M1 of freely moving mice.In this study,we used a multichannel fiber photometry system to continuously record calcium signals in CA1 and M1 during the temporal lobe epilepsy process.We found that calcium signals varied according to the grade of temporal lobe epilepsy episodes.In particular,cortical spreading depression,which has recently been frequently used to represent the continuously and substantially increased calcium signals,was found to correspond to complex and severe behavioral characteristics of temporal lobe epilepsy ranging from gradeⅡto gradeⅤ.However,vigorous calcium oscillations and highly synchronized calcium signals in CA1 and M1 were strongly related to convulsive motor seizures.Chemogenetic inhibition of pyramidal neurons in CA1 significantly attenuated the amplitudes of the calcium signals corresponding to gradeⅠepisodes.In addition,the latency of cortical spreading depression was prolonged,and the above-mentioned abnormal calcium signals in CA1 and M1 were also significantly reduced.Intriguingly,it was possible to rescue the altered intracellular calcium dynamics.Via simultaneous analysis of calcium signals and epileptic behaviors,we found that the progression of temporal lobe epilepsy was alleviated when specific calcium signals were reduced,and that the end-point behaviors of temporal lobe epilepsy were improved.Our results indicate that the calcium dynamic between CA1 and M1 may reflect specific epileptic behaviors corresponding to different grades.Furthermore,the selective regulation of abnormal calcium signals in CA1 pyramidal neurons appears to effectively alleviate temporal lobe epilepsy,thereby providing a potential molecular mechanism for a new temporal lobe epilepsy diagnosis and treatment strategy.展开更多
Partial epilepsies, originating in a specific brain region, affect about 60% of adults with epilepsy. Temporal lobe epilepsy (TLE) is the most prevalent subtype within this category, often necessitating surgical inter...Partial epilepsies, originating in a specific brain region, affect about 60% of adults with epilepsy. Temporal lobe epilepsy (TLE) is the most prevalent subtype within this category, often necessitating surgical intervention due to its refractoriness to antiepileptic drugs (AEDs). Hippocampal sclerosis, a common underlying pathology, often exacerbates the severity by introducing cognitive and emotional challenges. This review delves deeper into the cognitive profile of TLE, along with the risk factors for cognitive disorders, depression, and anxiety in this population.展开更多
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
Cognitive impairment is the most common complication in patients with temporal lobe epilepsy with hippocampal scle rosis.There is no effective treatment for cognitive impairment.Medial septum cholinergic neurons have ...Cognitive impairment is the most common complication in patients with temporal lobe epilepsy with hippocampal scle rosis.There is no effective treatment for cognitive impairment.Medial septum cholinergic neurons have been reported to be a potential target for controlling epileptic seizures in tempo ral lobe epile psy.However,their role in the cognitive impairment of temporal lobe epilepsy remains unclear.In this study,we found that patients with temporal lobe epile psy with hippocampal sclerosis had a low memory quotient and severe impairment in verbal memory,but had no impairment in nonverbal memory.The cognitive impairment was slightly correlated with reduced medial septum volume and medial septum-hippocampus tra cts measured by diffusion tensor imaging.In a mouse model of chronic temporal lobe epilepsy induced by kainic acid,the number of medial septum choline rgic neurons was reduced and acetylcholine release was reduced in the hippocampus.Furthermore,selective apoptosis of medial septum cholinergic neurons mimicked the cognitive deficits in epileptic mice,and activation of medial septum cholinergic neurons enhanced hippocampal acetylcholine release and restored cognitive function in both kainic acid-and kindling-induced epile psy models.These res ults suggest that activation of medial septum cholinergic neurons reduces cognitive deficits in temporal lobe epilepsy by increasing acetylcholine release via projections to the hippocampus.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
The pathogenesis of temporal lobe epilepsy(TLE)was originally considered to be acquired.However,some reports showed that TLE was clustered in some families,indicating a genetic etiology.With the popularity of genetic ...The pathogenesis of temporal lobe epilepsy(TLE)was originally considered to be acquired.However,some reports showed that TLE was clustered in some families,indicating a genetic etiology.With the popularity of genetic testing technology,eleven different types of familial TLE(FTLE),including ETL1-ETL11,have been reported,of which ETL9-ETL11 had not yet been included in the OMIM database.These types of FTLE were caused by different genes/Loci and had distinct characteristics.ETL1,ETL7 and ETL10 were characterized by auditory,visual and aphasia seizures,leading to the diagnosis of familial lateral TLE.ETL2,ETL3 and ETL6 showed prominent autonomic symptom and automatism with or without hippocampal abnormalities,indicating a mesial temporal origin.Febrile seizures were common in FTLEs such as ETL2,ETL5,ETL6 and ETL11.ETL4 was diagnosed as occipitotemporal lobe epilepsy with a high incidence of migraine and visual aura.Considering the diversity and complexity of the symptoms of TLE,neurologists enquiring about the family history of epilepsy should ask whether the relatives of the proband had experienced unnoticeable seizures and whether there is a family history of other neurological diseases carefully.Most FTLE patients had a good prognosis with or without anti-seizure medication treatment,with the exception of patients with heterozygous mutations of the CPA6 gene.The pathogenic mechanism was diverse among these genes and spans disturbances of neuron development,differentiation and synaptic signaling.In this article,we describe the research progress on eleven different types of FTLE.The precise molecular typing of FTLE would facilitate the diagnosis and treatment of FTLE and genetic counseling for this disorder.展开更多
Temporal lobe epilepsy is associated with astrogliosis. Notchl signaling can induce astrogliosis in glioma. However, it remains unknown whether Notchl signaling is involved in the pathogenesis of epilepsy. This study ...Temporal lobe epilepsy is associated with astrogliosis. Notchl signaling can induce astrogliosis in glioma. However, it remains unknown whether Notchl signaling is involved in the pathogenesis of epilepsy. This study investigated the presence of Notchl, hairy and enhancer of split-l, and glial fibrillary acidic protein in the temporal neocortex and hippocampus of lithium-pilocar- pine-treated rats. The presence of Notchl and hairy and enhancer of split-1 was also explored in brain tissues of patients with intractable temporal lobe epilepsy. Quantitative electroencephalo- gram analysis and behavioral observations were used as auxiliary measures. Results revealed that the presence of Notchl, hairy and enhancer of split-l, and glial fibriUary acidic protein were en- hanced in status epilepticus and vehicle-treated spontaneous recurrent seizures rats, but remain unchanged in the following groups: control, absence of either status epilepticus or spontaneous recurrent seizures, and zileuton-treated spontaneous recurrent seizures. Compared with patient control cases, the presences of Notch1 and hairy and enhancer of split- 1 were upregulated in the temporal neocortex of patients with intractable temporal lobe epilepsy. Therefore, these results suggest that Notchl signaling may play an important role in the onset of temporal lobe epilepsy via astrogliosis. Furthermore, zileuton may be a potential therapeutic strategy for temporal lobe epilepsy by blocking Notchl signaling.展开更多
Serotonin (5-hydroxytryptamine, 5-HT) influences the cortical and subcortical excitatory/inhibitory balance and participates in the pathophysiological processes of epilepsy. The serotonin transporter (5-HTT) is th...Serotonin (5-hydroxytryptamine, 5-HT) influences the cortical and subcortical excitatory/inhibitory balance and participates in the pathophysiological processes of epilepsy. The serotonin transporter (5-HTT) is the most important factor in serotonin inactivation. We tested whether 5-HTT polymorphisms are involved in the pathogenesis of epilepsy in Chinese Han population. We did not find a significant difference in the frequencies of genotypes and alleles in the 5-HTT gene-linked poLymorphic region (5-H-I-FLPR) in patients with non-lesional temporal lobe epilepsy and normal controls (P〉 0.05). Frequencies of the 5-H1-1- intron 2 variable number tandem repeat (5-HTTVNTR) 12/12 genotype and allele 12 were higher in the patients with non-lesional temporal lobe epilepsy than normal controls (P 〈 0.01). The odds ratio of affecting non-lesional temporal lobe epilepsy was 1.435 (95% Cl, 1.096 1.880) in patients carrying allele 12 (P 〈 0.05). Although the 5-HTTLPR may not be a genetic locus of non-lesional temporal lobe epilepsy in Chinese Hart population, allele 12 in the 5-HTTVNTR may correlate with non-lesional temporal lobe epilepsy. The Stin2.12 allele and 12/12 genotype could be predisposing to non-lesional temporal lobe epilepsy.展开更多
Currently afflicting more than 50 million people worldwide, epilepsy is the spectrum disorder characterizing seizures that occur without other plausible medical explanations. Temporal lobe epilepsy (TLE) is one of the...Currently afflicting more than 50 million people worldwide, epilepsy is the spectrum disorder characterizing seizures that occur without other plausible medical explanations. Temporal lobe epilepsy (TLE) is one of the most common forms of epilepsy. Current clinical methods;including MRI scans, EEG tests, and doctor visits;can take upwards of several months to confirm a TLE diagnosis;during this time, patients may experience additional seizures and are at an increased risk for other psychiatric disorders. The purpose of this study is to identify candidate genetic biomarkers to facilitate the earlier detection and diagnosis of TLE through gene-based testing (e.g., genomic heatmap analysis or genetic and/or microarray testing). It was hypothesized that potential biomarkers could be identified by analyzing genes that are normally significantly overexpressed in the temporal lobe relative to the gray matter. Statistical and functional analysis was performed on significantly overexpressed genes (≥3.000 fold change) in the gene expression profiles of four donors without epilepsy. The experimental-evidence-based STRING protein interactions analysis showed associations between genes found in DAVID keyword search and other genes facilitating network interconnectivity. After evaluation of the genes’ STRING enriched functions, changes in the expression of the genes <em>CAMK2A</em>, <em>NPY</em>, <em>DLG4</em>, <em>MEF2C</em>, and<em> MAPK7</em> were concluded to be potential biomarkers for TLE, confirming the original hypothesis. Specifically, the identification of <em>MEF2C</em> and <em>MAPK7</em> for this purpose is relatively novel in the fields of bioinformatics and neurogenetics. Future work includes investigating the utility of the candidate genes in real-world gene-based diagnostic methods.展开更多
Purpose: To examine the impact of gender and social gender on the level and typology of interictal aggressiveness in patients with temporal lobe epilepsy. Material and Methods: 40 adult patients with Temporal Lobe Epi...Purpose: To examine the impact of gender and social gender on the level and typology of interictal aggressiveness in patients with temporal lobe epilepsy. Material and Methods: 40 adult patients with Temporal Lobe Epilepsy (TLE) and 86 healthy individuals were included. The qualitative and quantitative aggressiveness assess- ment was made with Buss-Durkee Hostility Inventory. The gender role behavior was measured with Bem Sex Role Inventory. Results: Patients with TLE didn’t differ from healthy subjects on the total scores of motor and attitudinal hostility components, but scored higher on subscales “resentment” and “guilt”. The comparative gender analysis showed there were no phenomenological differences in people with TLE. Assault dominated in healthy male subjects, resentment—in healthy female subjects. The prevalence of feminine social gender type was significantly higher in people with TLE in comparison to healthy people (55% vs. 26%, p 0.01). In patients with TLE, the number of masculine traits positively correlated with indirect hostility subscale and attitudinal hostility component scores. In healthy subjects, the masculine traits positively correlated with assault.展开更多
Epilepsy is a common neurological disorder, and its electrophysiology characteristic is abnormally high excitability and synchronization of the neural activity. This paper focuses on the study of medial temporal lobe ...Epilepsy is a common neurological disorder, and its electrophysiology characteristic is abnormally high excitability and synchronization of the neural activity. This paper focuses on the study of medial temporal lobe epilepsy with hippocampal sclerosis. The hippocampus plays an important role in short-term memory. However, little is known about the connectivity between hippocampal structures and adjacent brain regions. The functional and structural connectivity between patients and controls was investigated by using the techniques of functional magnetic resonance imaging and diffusion tensor imaging in the paper. Three pairs of ROIs related to working memory from BOLD-fMRI data were chosen. These ROIs were registrated from MNI space to individual space and the fiber bundle between two ROIs were traced in the DTI images. The results show that the number of fiber bundle of patients reduce among these ROIs, such as left hippocampus and right hippocampus, left hippocampus and left thalamus, left hippocampus and left frontal lobe and so on. And the number of fiber bundle of patients increase among these ROIs, such as left thalamus and right thalamus, right hippocampus and right thalamus. And the FA values of the fiber bundles of patients in some regions related to left hippocampus decrease. The cause of abnormal functional and structural connections due to the damage of hippocampus in medial temporal lobe epilepsy is studied from a new perspective.展开更多
Secondary epileptogenesis is characterized by increased epileptic susceptibility and a tendency to generate epileptiform activities outside the primary focus.It is one of the major resultants of pharmacoresistance and...Secondary epileptogenesis is characterized by increased epileptic susceptibility and a tendency to generate epileptiform activities outside the primary focus.It is one of the major resultants of pharmacoresistance and failure of surgical outcomes in epilepsy,but still lacks effective treatments.Here,we aimed to test the effects of low-frequency stimulation(LFS)at the subiculum for secondary epileptogenesis in a mouse model.Here,secondary epileptogenesis was simulated at regions both contralateral and ipsilateral to the primary focus by applying successive kindling stimuli.Mice kindled at the right CA3 showed higher seizure susceptibilities at both the contralateral CA3 and the ipsilateral entorhinal cortex and had accelerated kindling processes compared with naive mice.LFS at the ipsilateral subiculum during the primary kindling progress at the right CA3 effectively prevented secondary epileptogenesis at both the contralateral CA3 and the ipsilateral entorhinal cortex,characterized by decreased seizure susceptibilities and a retarded kindling process at those secondary foci.Only application along with the primary epileptogenesis was effective.Notably,the effects of LFS on secondary epileptogenesis were associated with its inhibitory effect at the secondary focus through interfering with the enhancement of synaptic connections between the primary and secondary foci.These results imply that LFS at the subiculum is an effective preventive strategy for extensive secondary epileptogenesis in temporal lobe epilepsy and present the subiculum as a target with potential translational importance.展开更多
Neuroinflammation mediated by microglia and oxidative stress play pivotal roles in the development of chronic temporal lobe epilepsy(TLE).We postulated that kainic acid(KA)-Induced status epilepticus triggers microgli...Neuroinflammation mediated by microglia and oxidative stress play pivotal roles in the development of chronic temporal lobe epilepsy(TLE).We postulated that kainic acid(KA)-Induced status epilepticus triggers microglia-dependent inflammation,leading to neuronal damage,a lowered seizure threshold,and the emergence of spontaneous recurrent seizures(SRS).Extensive evidence from our laboratory suggests that dextromethorphan(DM),even in ultra-low doses,has anti-inflammatory and neuroprotective effects in many animal models of neurodegenerative disease.Our results showed that administration of DM(10 ng/kg per day;subcutaneously via osmotic minipump for 4 weeks)significantly mitigated the residual effects of KA,including the frequency of SRS and seizure susceptibility.In addition,DM-treated rats showed improved cognitive function and reduced hippocampal neuronal loss.We found suppressed microglial activation-mediated neuroinflammation and decreased expression of hippocampal gp91^(phox) and p47^(phox) proteins in KA-induced chronic TLE rats.Notably,even after discontinuation of DM treatment,ultra-low doses of DM continued to confer long-term anti-seizure and neuroprotective effects,which were attributed to the inhibition of microglial NADPH oxidase 2 as revealed by mechanistic studies.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
Background Anterior temporal Iobectomy (ATL) is the most common surgical treatment for temporal lobe epilepsy (TLE)although long-term prognosis is often less favorable than short-term outcomes. This study aimed to...Background Anterior temporal Iobectomy (ATL) is the most common surgical treatment for temporal lobe epilepsy (TLE)although long-term prognosis is often less favorable than short-term outcomes. This study aimed to examine the outcomes of patients with TLE 5 years after undergoing ATL, and to seek possible predictors of prognosis. Methods We examined the clinical records of 121 patients with TLE who underwent ATL in our institution between January 2005 and December 2008. The Engel seizure classification was used to divide patients into "seizure free" and "non-seizure free" groups. Univariate and multivariate Logistic regression analyses were used to identify potential prognostic indicators, including history, clinical features of seizures, and magnetic resonance imaging (MRI) and video- electroencephalography (EEG) findings. Results The majority of patients were seizure free during the follow-up period: 71.9% 1 year after surgery; 71.6% after 2 years; 75.8% after 3 years; 78.8% after 4 years after surgery and 68.8% after 5 years. There were significant differences between seizure-free and non-seizure-free groups in terms of preoperative seizure duration, history of febrile seizures, type of seizure, and MRI and video-EEG findings (P 〈0.05), but not in terms of sex, age at seizure onset, age at surgery, side of surgery, auras, family history of seizure, or history of traumatic brain injury, perinatal anoxia or intracranial infection history (P 〉0.05). Multivariate Logistic regression analysis showed that a preoperative seizure duration 〈10 years, a history of febrile seizures, simple complex partial seizures, positive MRI findings, hippocampal sclerosis and unilateral localized video-EEG spikes predicted better outcome (P 〈0.05). Conclusions ATL appears to be an effective means of treating TLE. Patients undergoing ATL for TLE require careful and comprehensive assessment to ensure optimal outcomes and to allow patients to make informed decisions about their treatment.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
Background Tenidap is a liposoluble non-steroidal anti-inflammatory drug that is easily distributed in the central nervous system and also inhibits the production and activity of cyclooxygenase-2 (COX-2) and cytokin...Background Tenidap is a liposoluble non-steroidal anti-inflammatory drug that is easily distributed in the central nervous system and also inhibits the production and activity of cyclooxygenase-2 (COX-2) and cytokines in vitro. This study aimed to evaluate the neuroprotective effect of tenidap in a pilocarpine rat model of temporal lobe epilepsy (TLE). Methods Tenidap was administered daily at 10 mg/kg for 10 days following pilocarpine-induced status epilepticus (SE) in male Wistar rats after which prolonged generalized seizures resulted in TLE. After tenidap treatment, spontaneous recurrent seizures (SRSs) were recorded by video monitoring (for 7 hours per day for 14 days). The frequency and severity of the SRSs were observed. Histological and immunocytochemical analyses were used to evaluate the neuroprotective effect of tenidap and detect COX-2 expression, which may be associated with neuronal death. Results There were 46.88±10.70 survival neurons in tenidap-SE group, while there were 27.60±5.18 survival neurons in saline-SE group at -2.4 mm field in the CA3 area. There were 37.75±8.78 survival neurons in tenidap-SE group, while there were 33.40±8.14 survival neurons in saline-SE group at -2.4 mm field in the CA1 area. Tenidap treatment significantly reduced neuronal damage in the CA3 area (P 〈0.05) and slightly reduced damage in the CA1 area. Tenidap markedly inhibited COX-2 expression in the hippocampus, especially in the CA3 area. Conclusion Tenidap conferred neuroprotection to the CA3 area in a pilocarpine-induced rat model of TLE by inhibiting COX-2 expression.展开更多
Background:Deep brain stimulation(DBS)has seizure-suppressing effects but the molecular mechanisms underlying its therapeutic action remain unclear.This study aimed to systematically elucidate the mechanisms underlyin...Background:Deep brain stimulation(DBS)has seizure-suppressing effects but the molecular mechanisms underlying its therapeutic action remain unclear.This study aimed to systematically elucidate the mechanisms underlying DBS-induced seizure suppression at a molecular level.Methods:We established a macaque model of mesial temporal lobe epilepsy(mTLE),and continuous high-frequency hippocampus DBS(hip-DBS)was applied for 3 months.The effects of hip-DBS on hippocampus gene expression were examined using high-throughput microarray analysis followed by bioinformatics analysis.Moreover,the microarray results were validated using quantitative real-time polymerase chain reaction(qRT-PCR)and Western blot analyses.Results:The results showed that chronic hip-DBS modulated the hippocampal gene expression.We identified 4119 differentially expressed genes and assigned these genes to 16 model profiles.Series test of cluster analysis showed that profiles 5,3,and 2 were the predominant expression profiles.Moreover,profile 5 was mainly involved in focal adhesion and extracellular matrix-receptor interaction pathway.Nine dysregulated genes(Arhgap5,Colla2,Itgbl^Pik3rl,Lama4,Fnl,Col3al,Itga9,and Shc4)and three genes(Colla2,Itgbl,and Flna)in these two pathways were further validated by qRT-PCR and Western blot analyses,respectively,which showed a concordance.Conclusion:Our findings suggest that hip-DBS could markedly reverse mTLE-induced abnormal gene expression.Findings from this study establish the basis for further investigation of the underlying regulatory mechanisms of DBS for mTLE.展开更多
Tuberous sclerosis complex(TSC)is a rare disease that involves multiple organs,including the brain;approximately 80%-90%of TSC patients exhibit TSC-associated epilepsy.Independent temporal lobe epilepsy(TLE),TSC-unrel...Tuberous sclerosis complex(TSC)is a rare disease that involves multiple organs,including the brain;approximately 80%-90%of TSC patients exhibit TSC-associated epilepsy.Independent temporal lobe epilepsy(TLE),TSC-unrelated epilepsy,is particularly rare in patients with TSC.Here,we describe three patients with TSC with independent TLEs that were confirmed by stereo-electroencephalography(EEG),postoperative pathological findings,and seizure outcome at follow-up.The patients were retrospectively enrolled at two centers;their ictal epileptiform discharge onsets were determined using electrode contacts in the hippocampus during stereo-EEG.The three patients underwent anterior temporal lobectomies and remained seizure-free at 1-5 years after surgery.Postoperative pathological examinations confirmed hippocampal sclerosis in all three patients.Furthermore,postoperative intelligence quotient improvement was evident in one patient,while the quality of life was improved in two patients at 12 months after surgery.展开更多
Objective To detect for hippocampal sclerosis presurgically in a group of patients with refractory temporal lobe epilepsy Methods Eighty four consecutive patients with refractory temporal lobe epilepsy were subjec...Objective To detect for hippocampal sclerosis presurgically in a group of patients with refractory temporal lobe epilepsy Methods Eighty four consecutive patients with refractory temporal lobe epilepsy were subjected to brain MRI of hippocampal volumetry A ratio of smaller to larger hippocampal volume was determined and unilateral hippocampal atrophy (HA) was diagnosed if the ratio is less than 0 91 Results Unilateral HA was diagnosed in 42 patients (50%) and bilateral HA in 1 patient Other MRI abnormalities were detected in 18 patients with or without coexisting HA Conclusions Hippocampal sclerosis can be detected presurgically in many patients by brain MRI Additional abnormalities not detected by brain CT can also be demonstrated展开更多
基金supported by the National Natural Science Foundation of China,Nos.62027812(to HS),81771470(to HS),and 82101608(to YL)Tianjin Postgraduate Research and Innovation Project,No.2020YJSS122(to XD)。
文摘Temporal lobe epilepsy is a multifactorial neurological dysfunction syndrome that is refractory,resistant to antiepileptic drugs,and has a high recurrence rate.The pathogenesis of temporal lobe epilepsy is complex and is not fully understood.Intracellular calcium dynamics have been implicated in temporal lobe epilepsy.However,the effect of fluctuating calcium activity in CA1 pyramidal neurons on temporal lobe epilepsy is unknown,and no longitudinal studies have investigated calcium activity in pyramidal neurons in the hippocampal CA1 and primary motor cortex M1 of freely moving mice.In this study,we used a multichannel fiber photometry system to continuously record calcium signals in CA1 and M1 during the temporal lobe epilepsy process.We found that calcium signals varied according to the grade of temporal lobe epilepsy episodes.In particular,cortical spreading depression,which has recently been frequently used to represent the continuously and substantially increased calcium signals,was found to correspond to complex and severe behavioral characteristics of temporal lobe epilepsy ranging from gradeⅡto gradeⅤ.However,vigorous calcium oscillations and highly synchronized calcium signals in CA1 and M1 were strongly related to convulsive motor seizures.Chemogenetic inhibition of pyramidal neurons in CA1 significantly attenuated the amplitudes of the calcium signals corresponding to gradeⅠepisodes.In addition,the latency of cortical spreading depression was prolonged,and the above-mentioned abnormal calcium signals in CA1 and M1 were also significantly reduced.Intriguingly,it was possible to rescue the altered intracellular calcium dynamics.Via simultaneous analysis of calcium signals and epileptic behaviors,we found that the progression of temporal lobe epilepsy was alleviated when specific calcium signals were reduced,and that the end-point behaviors of temporal lobe epilepsy were improved.Our results indicate that the calcium dynamic between CA1 and M1 may reflect specific epileptic behaviors corresponding to different grades.Furthermore,the selective regulation of abnormal calcium signals in CA1 pyramidal neurons appears to effectively alleviate temporal lobe epilepsy,thereby providing a potential molecular mechanism for a new temporal lobe epilepsy diagnosis and treatment strategy.
文摘Partial epilepsies, originating in a specific brain region, affect about 60% of adults with epilepsy. Temporal lobe epilepsy (TLE) is the most prevalent subtype within this category, often necessitating surgical intervention due to its refractoriness to antiepileptic drugs (AEDs). Hippocampal sclerosis, a common underlying pathology, often exacerbates the severity by introducing cognitive and emotional challenges. This review delves deeper into the cognitive profile of TLE, along with the risk factors for cognitive disorders, depression, and anxiety in this population.
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National Natural Science Foundation of China,Nos.82003 729 (to Ying W),82022071 (to YiW)Natural Science Foundation of Shandong Province of China,No.ZR2020QH357 (to Ying W)Public Welfare Technology Research Program of Zhejiang Province,No.LGF20H09001 1 (to JF)。
文摘Cognitive impairment is the most common complication in patients with temporal lobe epilepsy with hippocampal scle rosis.There is no effective treatment for cognitive impairment.Medial septum cholinergic neurons have been reported to be a potential target for controlling epileptic seizures in tempo ral lobe epile psy.However,their role in the cognitive impairment of temporal lobe epilepsy remains unclear.In this study,we found that patients with temporal lobe epile psy with hippocampal sclerosis had a low memory quotient and severe impairment in verbal memory,but had no impairment in nonverbal memory.The cognitive impairment was slightly correlated with reduced medial septum volume and medial septum-hippocampus tra cts measured by diffusion tensor imaging.In a mouse model of chronic temporal lobe epilepsy induced by kainic acid,the number of medial septum choline rgic neurons was reduced and acetylcholine release was reduced in the hippocampus.Furthermore,selective apoptosis of medial septum cholinergic neurons mimicked the cognitive deficits in epileptic mice,and activation of medial septum cholinergic neurons enhanced hippocampal acetylcholine release and restored cognitive function in both kainic acid-and kindling-induced epile psy models.These res ults suggest that activation of medial septum cholinergic neurons reduces cognitive deficits in temporal lobe epilepsy by increasing acetylcholine release via projections to the hippocampus.
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 the National Key R&D Program of China,Precision Medicine Program-Cohort Study on Nervous System Diseases,No.2017YFC0907702。
文摘The pathogenesis of temporal lobe epilepsy(TLE)was originally considered to be acquired.However,some reports showed that TLE was clustered in some families,indicating a genetic etiology.With the popularity of genetic testing technology,eleven different types of familial TLE(FTLE),including ETL1-ETL11,have been reported,of which ETL9-ETL11 had not yet been included in the OMIM database.These types of FTLE were caused by different genes/Loci and had distinct characteristics.ETL1,ETL7 and ETL10 were characterized by auditory,visual and aphasia seizures,leading to the diagnosis of familial lateral TLE.ETL2,ETL3 and ETL6 showed prominent autonomic symptom and automatism with or without hippocampal abnormalities,indicating a mesial temporal origin.Febrile seizures were common in FTLEs such as ETL2,ETL5,ETL6 and ETL11.ETL4 was diagnosed as occipitotemporal lobe epilepsy with a high incidence of migraine and visual aura.Considering the diversity and complexity of the symptoms of TLE,neurologists enquiring about the family history of epilepsy should ask whether the relatives of the proband had experienced unnoticeable seizures and whether there is a family history of other neurological diseases carefully.Most FTLE patients had a good prognosis with or without anti-seizure medication treatment,with the exception of patients with heterozygous mutations of the CPA6 gene.The pathogenic mechanism was diverse among these genes and spans disturbances of neuron development,differentiation and synaptic signaling.In this article,we describe the research progress on eleven different types of FTLE.The precise molecular typing of FTLE would facilitate the diagnosis and treatment of FTLE and genetic counseling for this disorder.
基金funded by the Natural Science Foundation of Hubei Province in China,No.02.02.040458
文摘Temporal lobe epilepsy is associated with astrogliosis. Notchl signaling can induce astrogliosis in glioma. However, it remains unknown whether Notchl signaling is involved in the pathogenesis of epilepsy. This study investigated the presence of Notchl, hairy and enhancer of split-l, and glial fibrillary acidic protein in the temporal neocortex and hippocampus of lithium-pilocar- pine-treated rats. The presence of Notchl and hairy and enhancer of split-1 was also explored in brain tissues of patients with intractable temporal lobe epilepsy. Quantitative electroencephalo- gram analysis and behavioral observations were used as auxiliary measures. Results revealed that the presence of Notchl, hairy and enhancer of split-l, and glial fibriUary acidic protein were en- hanced in status epilepticus and vehicle-treated spontaneous recurrent seizures rats, but remain unchanged in the following groups: control, absence of either status epilepticus or spontaneous recurrent seizures, and zileuton-treated spontaneous recurrent seizures. Compared with patient control cases, the presences of Notch1 and hairy and enhancer of split- 1 were upregulated in the temporal neocortex of patients with intractable temporal lobe epilepsy. Therefore, these results suggest that Notchl signaling may play an important role in the onset of temporal lobe epilepsy via astrogliosis. Furthermore, zileuton may be a potential therapeutic strategy for temporal lobe epilepsy by blocking Notchl signaling.
文摘Serotonin (5-hydroxytryptamine, 5-HT) influences the cortical and subcortical excitatory/inhibitory balance and participates in the pathophysiological processes of epilepsy. The serotonin transporter (5-HTT) is the most important factor in serotonin inactivation. We tested whether 5-HTT polymorphisms are involved in the pathogenesis of epilepsy in Chinese Han population. We did not find a significant difference in the frequencies of genotypes and alleles in the 5-HTT gene-linked poLymorphic region (5-H-I-FLPR) in patients with non-lesional temporal lobe epilepsy and normal controls (P〉 0.05). Frequencies of the 5-H1-1- intron 2 variable number tandem repeat (5-HTTVNTR) 12/12 genotype and allele 12 were higher in the patients with non-lesional temporal lobe epilepsy than normal controls (P 〈 0.01). The odds ratio of affecting non-lesional temporal lobe epilepsy was 1.435 (95% Cl, 1.096 1.880) in patients carrying allele 12 (P 〈 0.05). Although the 5-HTTLPR may not be a genetic locus of non-lesional temporal lobe epilepsy in Chinese Hart population, allele 12 in the 5-HTTVNTR may correlate with non-lesional temporal lobe epilepsy. The Stin2.12 allele and 12/12 genotype could be predisposing to non-lesional temporal lobe epilepsy.
文摘Currently afflicting more than 50 million people worldwide, epilepsy is the spectrum disorder characterizing seizures that occur without other plausible medical explanations. Temporal lobe epilepsy (TLE) is one of the most common forms of epilepsy. Current clinical methods;including MRI scans, EEG tests, and doctor visits;can take upwards of several months to confirm a TLE diagnosis;during this time, patients may experience additional seizures and are at an increased risk for other psychiatric disorders. The purpose of this study is to identify candidate genetic biomarkers to facilitate the earlier detection and diagnosis of TLE through gene-based testing (e.g., genomic heatmap analysis or genetic and/or microarray testing). It was hypothesized that potential biomarkers could be identified by analyzing genes that are normally significantly overexpressed in the temporal lobe relative to the gray matter. Statistical and functional analysis was performed on significantly overexpressed genes (≥3.000 fold change) in the gene expression profiles of four donors without epilepsy. The experimental-evidence-based STRING protein interactions analysis showed associations between genes found in DAVID keyword search and other genes facilitating network interconnectivity. After evaluation of the genes’ STRING enriched functions, changes in the expression of the genes <em>CAMK2A</em>, <em>NPY</em>, <em>DLG4</em>, <em>MEF2C</em>, and<em> MAPK7</em> were concluded to be potential biomarkers for TLE, confirming the original hypothesis. Specifically, the identification of <em>MEF2C</em> and <em>MAPK7</em> for this purpose is relatively novel in the fields of bioinformatics and neurogenetics. Future work includes investigating the utility of the candidate genes in real-world gene-based diagnostic methods.
文摘Purpose: To examine the impact of gender and social gender on the level and typology of interictal aggressiveness in patients with temporal lobe epilepsy. Material and Methods: 40 adult patients with Temporal Lobe Epilepsy (TLE) and 86 healthy individuals were included. The qualitative and quantitative aggressiveness assess- ment was made with Buss-Durkee Hostility Inventory. The gender role behavior was measured with Bem Sex Role Inventory. Results: Patients with TLE didn’t differ from healthy subjects on the total scores of motor and attitudinal hostility components, but scored higher on subscales “resentment” and “guilt”. The comparative gender analysis showed there were no phenomenological differences in people with TLE. Assault dominated in healthy male subjects, resentment—in healthy female subjects. The prevalence of feminine social gender type was significantly higher in people with TLE in comparison to healthy people (55% vs. 26%, p 0.01). In patients with TLE, the number of masculine traits positively correlated with indirect hostility subscale and attitudinal hostility component scores. In healthy subjects, the masculine traits positively correlated with assault.
基金National Natural Science Foundation of Chinagrant number: 6075107
文摘Epilepsy is a common neurological disorder, and its electrophysiology characteristic is abnormally high excitability and synchronization of the neural activity. This paper focuses on the study of medial temporal lobe epilepsy with hippocampal sclerosis. The hippocampus plays an important role in short-term memory. However, little is known about the connectivity between hippocampal structures and adjacent brain regions. The functional and structural connectivity between patients and controls was investigated by using the techniques of functional magnetic resonance imaging and diffusion tensor imaging in the paper. Three pairs of ROIs related to working memory from BOLD-fMRI data were chosen. These ROIs were registrated from MNI space to individual space and the fiber bundle between two ROIs were traced in the DTI images. The results show that the number of fiber bundle of patients reduce among these ROIs, such as left hippocampus and right hippocampus, left hippocampus and left thalamus, left hippocampus and left frontal lobe and so on. And the number of fiber bundle of patients increase among these ROIs, such as left thalamus and right thalamus, right hippocampus and right thalamus. And the FA values of the fiber bundles of patients in some regions related to left hippocampus decrease. The cause of abnormal functional and structural connections due to the damage of hippocampus in medial temporal lobe epilepsy is studied from a new perspective.
基金supported by grants from the National Natural Science Foundation of China(U21A20418 and 82173796)the Natural Science Foundation of Zhejiang Province(LD22H310003)the Research Project of Zhejiang Chinese Medical University(2023JKZDZC04).
文摘Secondary epileptogenesis is characterized by increased epileptic susceptibility and a tendency to generate epileptiform activities outside the primary focus.It is one of the major resultants of pharmacoresistance and failure of surgical outcomes in epilepsy,but still lacks effective treatments.Here,we aimed to test the effects of low-frequency stimulation(LFS)at the subiculum for secondary epileptogenesis in a mouse model.Here,secondary epileptogenesis was simulated at regions both contralateral and ipsilateral to the primary focus by applying successive kindling stimuli.Mice kindled at the right CA3 showed higher seizure susceptibilities at both the contralateral CA3 and the ipsilateral entorhinal cortex and had accelerated kindling processes compared with naive mice.LFS at the ipsilateral subiculum during the primary kindling progress at the right CA3 effectively prevented secondary epileptogenesis at both the contralateral CA3 and the ipsilateral entorhinal cortex,characterized by decreased seizure susceptibilities and a retarded kindling process at those secondary foci.Only application along with the primary epileptogenesis was effective.Notably,the effects of LFS on secondary epileptogenesis were associated with its inhibitory effect at the secondary focus through interfering with the enhancement of synaptic connections between the primary and secondary foci.These results imply that LFS at the subiculum is an effective preventive strategy for extensive secondary epileptogenesis in temporal lobe epilepsy and present the subiculum as a target with potential translational importance.
基金supported by the National Major Scientific and Technological Special Project for Significant New Drugs Development(2019zx09301102)the Project of Liaoning Provincial Department of Education(LJKZ0826)the Open Project of National and Local Joint Engineering Research Center for Drug Research and Development of Neurodegenerative Diseases(2022GCYJZX-YB02).
文摘Neuroinflammation mediated by microglia and oxidative stress play pivotal roles in the development of chronic temporal lobe epilepsy(TLE).We postulated that kainic acid(KA)-Induced status epilepticus triggers microglia-dependent inflammation,leading to neuronal damage,a lowered seizure threshold,and the emergence of spontaneous recurrent seizures(SRS).Extensive evidence from our laboratory suggests that dextromethorphan(DM),even in ultra-low doses,has anti-inflammatory and neuroprotective effects in many animal models of neurodegenerative disease.Our results showed that administration of DM(10 ng/kg per day;subcutaneously via osmotic minipump for 4 weeks)significantly mitigated the residual effects of KA,including the frequency of SRS and seizure susceptibility.In addition,DM-treated rats showed improved cognitive function and reduced hippocampal neuronal loss.We found suppressed microglial activation-mediated neuroinflammation and decreased expression of hippocampal gp91^(phox) and p47^(phox) proteins in KA-induced chronic TLE rats.Notably,even after discontinuation of DM treatment,ultra-low doses of DM continued to confer long-term anti-seizure and neuroprotective effects,which were attributed to the inhibition of microglial NADPH oxidase 2 as revealed by mechanistic studies.
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.
文摘Background Anterior temporal Iobectomy (ATL) is the most common surgical treatment for temporal lobe epilepsy (TLE)although long-term prognosis is often less favorable than short-term outcomes. This study aimed to examine the outcomes of patients with TLE 5 years after undergoing ATL, and to seek possible predictors of prognosis. Methods We examined the clinical records of 121 patients with TLE who underwent ATL in our institution between January 2005 and December 2008. The Engel seizure classification was used to divide patients into "seizure free" and "non-seizure free" groups. Univariate and multivariate Logistic regression analyses were used to identify potential prognostic indicators, including history, clinical features of seizures, and magnetic resonance imaging (MRI) and video- electroencephalography (EEG) findings. Results The majority of patients were seizure free during the follow-up period: 71.9% 1 year after surgery; 71.6% after 2 years; 75.8% after 3 years; 78.8% after 4 years after surgery and 68.8% after 5 years. There were significant differences between seizure-free and non-seizure-free groups in terms of preoperative seizure duration, history of febrile seizures, type of seizure, and MRI and video-EEG findings (P 〈0.05), but not in terms of sex, age at seizure onset, age at surgery, side of surgery, auras, family history of seizure, or history of traumatic brain injury, perinatal anoxia or intracranial infection history (P 〉0.05). Multivariate Logistic regression analysis showed that a preoperative seizure duration 〈10 years, a history of febrile seizures, simple complex partial seizures, positive MRI findings, hippocampal sclerosis and unilateral localized video-EEG spikes predicted better outcome (P 〈0.05). Conclusions ATL appears to be an effective means of treating TLE. Patients undergoing ATL for TLE require careful and comprehensive assessment to ensure optimal outcomes and to allow patients to make informed decisions about their treatment.
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.
基金This study was supported by a grant of National Natural Science Foundation of China (No. 81100964).
文摘Background Tenidap is a liposoluble non-steroidal anti-inflammatory drug that is easily distributed in the central nervous system and also inhibits the production and activity of cyclooxygenase-2 (COX-2) and cytokines in vitro. This study aimed to evaluate the neuroprotective effect of tenidap in a pilocarpine rat model of temporal lobe epilepsy (TLE). Methods Tenidap was administered daily at 10 mg/kg for 10 days following pilocarpine-induced status epilepticus (SE) in male Wistar rats after which prolonged generalized seizures resulted in TLE. After tenidap treatment, spontaneous recurrent seizures (SRSs) were recorded by video monitoring (for 7 hours per day for 14 days). The frequency and severity of the SRSs were observed. Histological and immunocytochemical analyses were used to evaluate the neuroprotective effect of tenidap and detect COX-2 expression, which may be associated with neuronal death. Results There were 46.88±10.70 survival neurons in tenidap-SE group, while there were 27.60±5.18 survival neurons in saline-SE group at -2.4 mm field in the CA3 area. There were 37.75±8.78 survival neurons in tenidap-SE group, while there were 33.40±8.14 survival neurons in saline-SE group at -2.4 mm field in the CA1 area. Tenidap treatment significantly reduced neuronal damage in the CA3 area (P 〈0.05) and slightly reduced damage in the CA1 area. Tenidap markedly inhibited COX-2 expression in the hippocampus, especially in the CA3 area. Conclusion Tenidap conferred neuroprotection to the CA3 area in a pilocarpine-induced rat model of TLE by inhibiting COX-2 expression.
基金grants from the National Natural Science Foundation of China(Nos.81901314,81701251,and 81471315).
文摘Background:Deep brain stimulation(DBS)has seizure-suppressing effects but the molecular mechanisms underlying its therapeutic action remain unclear.This study aimed to systematically elucidate the mechanisms underlying DBS-induced seizure suppression at a molecular level.Methods:We established a macaque model of mesial temporal lobe epilepsy(mTLE),and continuous high-frequency hippocampus DBS(hip-DBS)was applied for 3 months.The effects of hip-DBS on hippocampus gene expression were examined using high-throughput microarray analysis followed by bioinformatics analysis.Moreover,the microarray results were validated using quantitative real-time polymerase chain reaction(qRT-PCR)and Western blot analyses.Results:The results showed that chronic hip-DBS modulated the hippocampal gene expression.We identified 4119 differentially expressed genes and assigned these genes to 16 model profiles.Series test of cluster analysis showed that profiles 5,3,and 2 were the predominant expression profiles.Moreover,profile 5 was mainly involved in focal adhesion and extracellular matrix-receptor interaction pathway.Nine dysregulated genes(Arhgap5,Colla2,Itgbl^Pik3rl,Lama4,Fnl,Col3al,Itga9,and Shc4)and three genes(Colla2,Itgbl,and Flna)in these two pathways were further validated by qRT-PCR and Western blot analyses,respectively,which showed a concordance.Conclusion:Our findings suggest that hip-DBS could markedly reverse mTLE-induced abnormal gene expression.Findings from this study establish the basis for further investigation of the underlying regulatory mechanisms of DBS for mTLE.
基金Beijing Natural Science Foundation of China,Grant/Award Number:7202045National Nature Science Foundation of China,Grant/Award Number:82071488。
文摘Tuberous sclerosis complex(TSC)is a rare disease that involves multiple organs,including the brain;approximately 80%-90%of TSC patients exhibit TSC-associated epilepsy.Independent temporal lobe epilepsy(TLE),TSC-unrelated epilepsy,is particularly rare in patients with TSC.Here,we describe three patients with TSC with independent TLEs that were confirmed by stereo-electroencephalography(EEG),postoperative pathological findings,and seizure outcome at follow-up.The patients were retrospectively enrolled at two centers;their ictal epileptiform discharge onsets were determined using electrode contacts in the hippocampus during stereo-EEG.The three patients underwent anterior temporal lobectomies and remained seizure-free at 1-5 years after surgery.Postoperative pathological examinations confirmed hippocampal sclerosis in all three patients.Furthermore,postoperative intelligence quotient improvement was evident in one patient,while the quality of life was improved in two patients at 12 months after surgery.
文摘Objective To detect for hippocampal sclerosis presurgically in a group of patients with refractory temporal lobe epilepsy Methods Eighty four consecutive patients with refractory temporal lobe epilepsy were subjected to brain MRI of hippocampal volumetry A ratio of smaller to larger hippocampal volume was determined and unilateral hippocampal atrophy (HA) was diagnosed if the ratio is less than 0 91 Results Unilateral HA was diagnosed in 42 patients (50%) and bilateral HA in 1 patient Other MRI abnormalities were detected in 18 patients with or without coexisting HA Conclusions Hippocampal sclerosis can be detected presurgically in many patients by brain MRI Additional abnormalities not detected by brain CT can also be demonstrated