Objective:To study the expression of ubiquitin-specific protease 25 (USP25) in the temporal cortex of the kainic acid (KA) induced epilepsy rat model.Methods:Fifty-two male SD rats were randomly divided into the epilepsy model group ( n=39) and sham-operated control group ( n=13) with the random number table. The epilepsy model group was established by injecting KA into the amygdala, then the epileptic rats were randomly divided into 3 groups according to the modeling success time: 1 day for acute period, 7 days for latent period and 30 days for chronic period (13 rats in each group). Those rats were sampled at the end of observation. Rats in the control group were injected with normal saline into the amygdala and sampled together with those in the experimental group. Immunohistochemistry and immunofluorescence double labeling was used to test USP25 expression and its co-expression with neurons (NeuN) and astrocytes (GFAP). Quantitative real-time PCR and Western blot were used to assess the change of USP25 in the temporal cortex of rats. Results:In the ipsilateral temporal cortex, the positive cells of co-expression of USP25 and NeuN were increased in the later stage of epilepsy in the epilepsy model group, and the expression levels of USP25 mRNA and protein in different stages of epilepsy varied significantly ( F= 25.48 and 7.68 respectively, both P<0.05). Compared with the control group (mRNA level: 1.00±0.36, protein level: 1.00±0.46), the expression of USP25 in the latent group (mRNA level: 10.80±4.82, protein level: 1.88±0.32) and the chronic group (mRNA level: 12.97±4.48, protein level: 1.92±0.26) were increased significantly (all P<0.05). In the contralateral temporal cortex, the expression levels of USP25 mRNA and protein in different stages of epilepsy also varied significantly ( F=86.86 and 6.65 respectively, both P<0.05). Conclusions:The increased expression of USP25 in the temporal cortex after the latent period has suggested that the deubiquitination pathway is involved in the chronic pathological process of temporal lobe epilepsy.
Temporal lobe epilepsy is the most common form of epilepsy. However, for this type of condition, antiseizure medication is not effective for children. As miRNAs are involved in the development of temporal lobe epilepsy in children, they may provide potential therapeutic approaches for treatment. The primary aim of this study was to explore the expression and function of miR-135a-5p in children with temporal lobe epilepsy. Hippocampal slices from either normal (control) children or children with temporal lobe epilepsy were used to detect the expression of miR-135a-5p and its target gene caspase activity and apoptosis inhibitor 1. To further explore the role of miR-135a-5p in the development of temporal lobe epilepsy in children, primary hippocampal neurons from newborn rats were cultured in vitro in a magnesium-free medium to mimic the temporal lobe epilepsy condition in children. The effect of transfection of miR-135a-5p inhibitor into cells was also assessed. Apoptosis and proliferation of hippocampus cells was respectively assessed by flow cytometry or 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The level of miR-135a-5p was significantly increased in both children with temporal lobe epilepsy and the epileptiform discharge model that employed newborn rat hippocampal neurons; whereas, the expression of caspase activity and apoptosis inhibitor 1 was down-regulated by overexpression of miR-135a-5p. Moreover, miR-135a-5p mediated the pro-apoptotic effect of temporal lobe epilepsy via repressing caspase activity and apoptosis inhibitor 1 expression. Additionally, miR-135a-5p reduced cell survival in the temporal lobe epilepsy condition. Overexpression of miR-135a-5p induced cell apoptosis through inhibition of caspase activity and apoptosis inhibitor 1 expression and suppressed cell survival in children with temporal lobe epilepsy.
Objective To compare the behavioral manifestations, electroencephalogram ( EEG ) monitoring and hippocampal pathological changes in two rat epilepsy models induced by kainic acid ( KA) injected into hippocampus and amygdala respectively. Methods Male adult Sprague-Dawley rats(n=24) were randomly divided into hippocampus model group ( n=9 ) , amygdala model group ( n=9 ) and control group (n=6). Two epilepsy models were established by kainic acid (0. 6 μg,1. 0 μg/μl) stereotactically injected into hippocampus CA3 region (hippocampus model) or amygdala (amygdala model). The status epilepticus ( SE ) of rats was observed by behavioral manifestations and EEG monitoring. Following successful modeling, those rats were randomly divided into 3 groups, including 1-day ( acute phase) , 7-day ( latent phase) and 30-day ( chronic phase) post SE groups ( n=3 in each group) . Rats in the control group were injected with an equal volume of saline in the hippocampal CA3 or amygdala. Immunohistochemistry was used for observing the pathological changes of neuron (NeuN), astrocyte (GFAP) and microglia (Iba1) in the rat hippocampus. Results Behavioral and EEG monitoring showed that rats from both models had typical seizure behaviors and EEG characteristics in the acute and chronic phases. However, there were different seize types and onset time between the 2 models in the acute phase. The hippocampus model group had partial seizures at 63. 33 ± 4. 41 min post KA injection with intermittent generalized tonic-clonic seizures. Multi-phase spikes were recorded in acute phase. Amygdala model group had severe generalized tonic-clonic seizures at 28. 67 ± 3. 48 min post KA injection, and the main cortical EEG form was sharp wave rhythm. Immunohistochemical staining revealed gradual hippocampal neuron death from acute to chronic phases in both models, which resulted in serious neuronal loss. Meanwhile, the aggravation of astrocyte proliferation and accumulation of microglia occurred in hippocampus in both models. Remarkably, compared with hippocampus model, the amygdala model in chronic phase had more neuronal loss in CA1 region ( 10. 83 ± 1. 52 vs. 22. 43 ± 5. 16, P<0. 01) and CA4 region (12. 87 ± 2. 13 vs. 25. 81 ± 4. 60, P <0. 05), more astrocyte proliferation in CA1 region (61. 20 ± 7. 33 vs. 14. 65 ± 0. 12, P<0. 01) and CA4 region (76. 73 ± 5. 40 vs. 43. 01 ± 1. 35, P<0. 01) as well as more widespread accumulation of microglia in CA1 region (13. 70 ± 3. 88 vs. 1. 08 ± 0. 01, P<0. 01). Conclusions Our results have indicated that both rat epilepsy models simulated human temporal lobe epilepsy. The differences in the behavior, EEG performances and particularly pathological changes of hippocampus between two models should be taken into consideration in the future study.
Background/Aims: Circular RNAs (circRNAs) are a class of long noncoding RNAs with a closed loop structure that regulate gene expression as microRNA sponges. CircRNAs are more enriched in brain tissue, but knowledge of the role of circRNAs in temporal lobe epilepsy (TLE) has remained limited. This study is the first to identify the global expression profiles and characteristics of circRNAs in human temporal cortex tissue from TLE patients. Methods: Temporal cortices were collected from 17 TLE patients and 17 non-TLE patients. Total RNA was isolated, and high-throughput sequencing was used to profile the transcriptome of dysregulated circRNAs. Quantitative PCR was performed for the validation of changed circRNAs. Results: In total, 78983 circRNAs, including 15.29% known and 84.71% novel circRNAs, were detected in this study. Intriguingly, 442 circRNAs were differentially expressed between the TLE and non-TLE groups (fold change≥2.0 and FDR≤0.05). Of these circRNAs, 188 were up-regulated, and 254 were down-regulated in the TLE patient group. Eight circRNAs were validated by real-time PCR. Remarkably, circ-EFCAB2 was intensely up-regulated, while circ-DROSHA expression was significantly lower in the TLE group than in the non-TLE group (P<0.05). Bioinformatic analysis revealed that circ-EFCAB2 binds to miR-485-5p to increase the expression level of the ion channel CLCN6, while circ-DROSHA interacts with miR-1252-5p to decrease the expression level of ATP1A2. Conclusions: The dysregulations of circRNAs may reflect the pathogenesis of TLE and circ-EFCAB2 and circ-DROSHA might be potential therapeutic targets and biomarkers in TLE patients.
患者女性,37岁,汉族,于2007年首次无诱因出现肢体抽搐,意识丧失,持续约2~3 min后自行缓解,当地医院行“脑电图”检查后以“癫痫”给予药物治疗.此后患者仍有发作,临床形式多样.发作频率每年4~6次不等.近1个月,患者发作极频繁,并出现癫痫持续状态1次,为进一步诊治于2017年5月24日来我院.入院查体:神清语利,对答切题,智力正常,头部毛发及皮肤无异常.12对颅神经检查无异常,四肢肌力、肌张力正常,腱反射存在,病理反射未引出.我院头颅平片示颅内4枚针状金属异物,长短不等,平均长约4.0 cm,1枚位于左侧,另3枚位于右侧,且胸腔内亦有1针(图1).
Objective To investigate the expression changes of astrocytic syntrophin in hippocampus from human mesial temporal lobe epilepsy (MTLE). Methods From April, 2015 to July, 2016, 17 cases of hippocampus, collected from temporal lobectomy, were divided into MTLE group (n=13) and non-MTLE group (n=4) according to hematoxylin and eosin staining, glial fibrillary acidic protein and neuronal nu-clei immunohistochemical staining. Immunofluorescence double labeling and immunofluorescence histochemistry were used to observe the expression of syntrophin. Results The proliferation of astrocytes increased and neurons reduced in the hippocampus of MTLE group. Syntro-phin was found in the membrane and foot processes of astrocyte, that was enriched along perivascular astrocyte end-feet domain in non-MTLE group, but lost in MTLE group. While the whole expression of syntrophin was more in MTLE group than in non-MTLE group (t=5.421, P<0.001). Conclusion The distribution of syntrophin in hippocampus astrocytes may be related to the development of MTLE.
癫痫外科是功能神经外科的重要组成部分,针对神经外科研究生在癫痫外科学习中存在的各种问题,本文探讨了研究生在癫痫外科学习中的培养策略,提出理论与临床实践相结合、强化临床实践能力和科研能力培养等对策,以加强神经外科研究生的综合素质.
Objective To study factors impacting on the outcome of surgery in intractable temporal lobe epilepsy with hippocampal sclerosis in children.Methods Between June 2010 and June 2012,clinical data of 25 pediatric patients with temporal lobe epilepsy haboring hippocampal sclerosis were collected in neurosurgical department of Beijing Tiantan Hospital.Seizure outcome was evaluated with Engel class.The correlation among age at seizure onset,sex,seizure frequency,duration of seizure,age at operation,MRI findings,pathological features and seizure outcome were assessed.Results Seven patients were confirmed as FCD Ⅲ a by neuropathology and others were hippocampal sclerosis only.Duration of seizure is a risk factor to affect the outcome of operation (P < 0.05),but other factors have minor impact on the outcome of operation(P > 0.05).Conclusion Early operation of temporal lobe epilepsy with hippocampal sclerosis in children predicts a better outcome.The correlation between the pathological lesions and surgical effects should be paid more attention for further study.
Background: Some recent studies suggest that some imaging-negative temporal lobe epilepsy (TLE) had significant amygdala enlargement (AE). Contradictory data were also reported in previous studies regarding the association between AE and TLE. The present study was to investigate the clinical characters of a group of TLE with AE and compare the amygdala volume of the same patient before and after antiepileptic drugs treatment by a larger sample size.Methods: This study recruited 33 mesial TLE patients with AE and 35 healthy volunteers. The clinical history, seizure semiology, electroencephalogram (EEG), fluorodeoxyglucose-positron emission tomography (FDG-PET) and amygdala volume were investigated. The amygdala volume were compared between ipsilateral and contralateral sides, TLE patients and 35 healthy controls, and patients at first and follow-up visit by 3.0 T MRI.Results: Average seizure onset age was 42.0 years (SD 14.3). All patients had complex partial seizures, fourteen had occasional generalized tonic-clonic seizures which often happened during sleep. Ninety percent patients suffered from anxiety or depression. Thirty percent patients had memory decline. Interictal epileptiform discharges appeared predominantly in the anterior or inferior temporal area ipsilateral to AE. Interictal FDG-PET showed regional glucose hypometabolism in the ipsilateral temporal lobe. No hippocampal sclerosis (HS) was suspected in all patients. 22 patients demonstrated good seizure control and significantly reduced volume of the enlarged amygdala after treatment (P < 0.01). The other 11 patients showed initial response to treatment, followed by a gradual increase in seizure frequency over time, and no volume change of the enlarged amygdala after treatment.Conclusions: TLE with AE probably represents a distinct nosological and probably less homogeneous syndrome which is most likely a subtype of TLE without ipsilateral HS. The chronic and long lasting inflammatory processes or focal cortical dysplasia could lead to amygdala enlargement possibly.
Purpose: This study aimed to discuss the clinical features of seizure semiology and electroencephalography (EEG) in young children with lesional temporal lobe epilepsy (TLE).Method: Children with lesional TLE received presurgical evaluation for intractable epilepsy. They were followed up for more than one year after temporal lobectomy. We reviewed the medical history and video-EEG monitoring of children with TLE to analyze the semiology of seizures and EEG findings and compared the semiology of seizures and EEG findings of childhood TLE and adult TLE.Results: A total of 84 seizures were analyzed in 11 children (aged 23-108 months). The age of seizure onset was from 1 month to 26 months (a mean of 17.6 months). All of the patients exhibited prominent motor manifestations including epileptic spasm, tonic seizure, and unilateral clonic seizure. Seven children manifested behavioral arrest similar to an automotor seizure in adult TLE but with a shorter duration and higher frequency. The automatisms were typically orofacial, whereas manual automatisms were rarely observed. The EEG recordings revealed that diffuse discharge patterns were more common in younger children, whereas focal or unilateral patterns were more typical in older children. All of the patients were seizure-free after temporal lobectomy with more than one-year follow-up. All of the children had a mental development delay or regression; however, there was improvement after surgery, especially in those with surgery performed early.Conclusion: In contrast to TLE in adults, young children with lesional TLE probably represent a distinct nosological and probably less homogeneous syndrome. Although they had generalized clinical and electrographic features, resective epilepsy surgery should be considered as early as possible to obtain seizure control and improvement in mental development. (C) 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Objective To discuss the clinical features of postictal psychiatric disorders in epilepsy patients.Methods Ninety-eight patients receiving presurgical evaluation from 2007 to 2009 were reviewed.The significant psychiatric disorders were reported in three epilepsy patients while they received video EEG montoring for presurgical evaluation.All the clinical data were retrospectively analyzed including semiology,EEG,MRI and the treatment.Results All the patients suffered from postictal psychiatric disorders after a cluster of epileptic seizures.There was a lucid interval between seizures and psychiatric symptoms in all patients.The psychiatric disorders were characterized by auditory and visual hallucinations,mania,depression and aggression.Conclusion Postictal psychiatric disorders are common psychiatric complication of chronic epilepsy.Recognition of this disorder is critical to initiate treatment and avoid severe accidental injury.
Objective To reviewe the operated temporal lobe epilepsy(TLE) with hypermotor seizures(HMS) in our center and to discuss the clinical decision-making for this type patients.Methods One hundred and two operated TLE patients from 2007-2009 were reviewed.All presurgical evaluation data of these patients including history,MRI,scalp video-electroencephalography(VEEG),PET and intracranial EEG recording were analyzed,retrospectively.HMS behavior was recognized according to Luders's description.Results Two patients exhibited typical hypermotor seizures.The scalp-EEG suggested temporal lobe onset although their semiological feature of frontal orign.One patient was given intracranial monitoring and another was directly performed operation without invasive examination for his positive finding of MRI.These two patients were seizure-free for more than two years after undergoing anterior temporal lobe resection.Conclusions Hypermotor seizure semiology may occasionally occur in patients with TLE.If scalp EEG patterns and neuroimaging findings are correspond,the postoperative seizure outcome is favorable in such patients.
Objective To investigate the distribution of aquaporin 4(AQP4) and inwardly rectifying potassium channel 4.1(Kir4.1) in the astrocytes from human mesial temporal lobe epilepsy(MTLE).Methods Hippocampal specimens,including 10 cases of MTLE and 6 cases of non-MTLE,were observed under optical and transmission electron microscopy.The distribution of AQP4 and Kir4.1 in astrocytes was investigated with immunoflurescence.Results Compared with non-MTLE hippocampus,the main structural changes of MTLE included remarkable hyperplasia astrocytes,serious swelling astrocytes and distinguished astrophy neurons.In non-MTLE hippocampus,immunoflurescence signals of AQP4 and Kir4.1 were enriched along perivascular astrocyte end-feet domain.However,it reveals significant loss of AQP4 and Kir4.1 in perivascular astrocyte end-feet domain in MTLE.Conclusion Loss of perivascular AQP4 and Kir4.1 in the human MTLE may help to understand the roles of astrocyte in MTLE.
OBJECTIVE To explore the application of intracranial electrodes (IE) for temporal lobe epilepsy (TLE) surgery and assess the clinical utility of intracranial video electroencephalography (IVEEG). METHODS The clinical data of 60 TLE patients undergoing implantation of IE were reviewed retrospectively. Cortical subdural strip, grids and depth electrodes were implanted by sphenotresia, bone disc craniotomy or stereotactic technology. RESULTS The implanted electrodes were as follows: frontal-temporal lobe cortical strip (n = 34), frontal-anterior temporal-occipitotemporal lobe cortical strip (n = 7), bilateral temporal lobe cortical strip (n = 7), combined temporal lobe strip & depth (n = 7), anterior temporal-occipitotemporal junction cortical strip (n = 3) and combined strip & grid (n = 2). The following procedures were performed: anterior temporal lobectomy (ATL) (n = 50), combined ATL & frontal focal cortical resection (n = 7), combined ATL & callosotomy (n = 1) and combined neocortex epileptogenic focus resection & amygdalohippocampectomy (n = 2). CONCLUSION IVEEG is effective and important for the localization of epileptogenic focus in patients with intractable temporal lobe epilepsy.
Objective To set up the new lab examination method for 1p,19q and 10q loss of heterozygosity(LOH) in glioma.Methods Thirty-eight cases of oligodendroglioma were enrolled into the study.Real-time quantitative polymerase chain reaction-based microsatellite analysis was performed on tumor tissues in order to study the status of chromosomes 1p,19q and 10q.Results Among the 38 cases of oligodendroglioma,25 cases(65.7%) showed 1p LOH,26 cases(68.4%) showed 19q LOH,while 5 cases(13.2%) showed 10q LOH.Conclusion Real-time quantitative polymerase chain reaction-based microsatellite analysis is a rapid and specific for detecting LOH in glioma tissues.
Objective In the present study, the correlation of MRI features and pathological changes was studied and the impact of MRI changes on seizure outcome was analyzed. Methods Between Jan. 2005 and Dec. 2008, clinical data of 121 temporal lobe epilepsy (TLE) patients were collected in our institute. Correlation of MRI features and pathological changes was analyzed statistically. According to MRI features, three subtypes of TLEs including medial (MTLE), lesion - related (LTLE) and paradoxical temporal lobe epilepsy (PTLE) were diagnosed. Postoperatively, patients were divided into seizure - free and non - seizure - free group according to Engel seizure classification. Differences of seizure outcome from surgery among different TLE subgroups were compared. Results Among the 121 TLE patients, 101 showed positive MRI findings and 107 showed positive pathological changes. No difference existed. There was a positive correlation between MRI findings and pathological changes. Seizure outcome of PTLE patients was much poorer than that of MTLE and LTLE patients, while no difference existed between the latter two subtypes. Conclusions MRI was one of the most important examinations for the diagnosis of TLE and plays a major role in predicting seizure outcome from surgery among TLE patients.
Objective To study the methods of implantation of intracranial electrodes (IE) for epilepsy surgery,and assess the evaluation of intracranial video electroencephalography (iVEEG).Method The clinical data for 112 patients undergoing implantation of IE were retrospectively reviewed,including position,category,modus operandi and complication.Results Cortical subdural strip electrodes were implanted in 87 cases,combined strip and depth electrodes in 9,grids electrodes in 13,combined strip and grids electrode in 3.The duration of monitoring was 24-192 hours.The complications included leakage of cerebrospinal fluid in 15 cases,nausea and vomiting in 9,cerebral abscess in 2,epidural hematoma and subdural hematoma in 1 each.There was no death in this group.Conclusions Implantation of IE is considerable for identification of epileptogenic focus.Intracranial subdural monitoring is a useful diagnostic technique for surgical localization in patients with intractable epilepsy.
Objective To investigate the clinical characteristics of dysembryoplastic neuroepithelial tumor(DNET) and to improve the comprehension of the lesions.Method The clinical presentation,imaging characteristics,surgical treatment and histopathologic outcomes of fourty-two cases with a confirmed diagnosis of DNET were restrospoctively reviewed.Results The first symptom of DNET was epilepsy in 40 cases (40/42,95%).The characteristics of MRI examination of DNET included decreased signal on the T1-weighted images and a hyper-intense signal on T2-weighted images in 37 cases,and intermix T1 and T2 in 5 patients.Thirty cases were type A and 12 cases were type B.Conclusions Epilepsy is the first and foremost symptom of DNET.CT and MRI are most important diagnostic methods for DNET before operation.Extended resection including mass lesion and epilepsy focus should be performed to relieve seizure attack.
Objective To study the operative technique of transpetrosal-presigmoid approach in microsurgical treatment of petroclival tumors.Methods The clinical features,operative methods,results of operation and postoperative complications of 10 cases of petroclival tumors resected via the transpetrosal-presigmoid approach were analyzed retrospectively.Results Total resection of the tumor was achieved in 10 cases.The main postoperative complications were the transient aphasia and the decrease in muscle strength because of temporal edema in 2 patients,the CSF collection under the skin flap in 2 patients.They were all successfully recovered after management.Conclusions The transpetrosal presigmoid approach is a preferable method for petroclival tumors because of several predominant advantages.