Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications(ASMs),a condition known as pharmacoresistant epilepsy.The management of pharmacoresistant epilepsy remains an intract...Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications(ASMs),a condition known as pharmacoresistant epilepsy.The management of pharmacoresistant epilepsy remains an intractable issue in the clinic.Its early prediction is important for prevention and diagnosis.However,it still lacks effective predictors and approaches.Here,a classical model of pharmacoresistant temporal lobe epilepsy(TLE)was established to screen pharmacoresistant and pharmaco-responsive individuals by applying phenytoin to amygdaloid-kindled rats.Ictal electroencephalograms(EEGs)recorded before phenytoin treatment were analyzed.Based on ictal EEGs from pharmacoresistant and pharmaco-responsive rats,a convolutional neural network predictive model was constructed to predict pharmacoresistance,and achieved 78% prediction accuracy.We further found the ictal EEGs from pharmacoresistant rats have a lower gamma-band power,which was verified in seizure EEGs from pharmacoresistant TLE patients.Prospectively,therapies targeting the subiculum in those predicted as“pharmacoresistant”individual rats significantly reduced the subsequent occurrence of pharmacoresistance.These results demonstrate a new methodology to predict whether TLE individuals become resistant to ASMs in a classic pharmacoresistant TLE model.This may be of translational importance for the precise management of pharmacoresistant TLE.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
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
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
BACKGROUND Gelastic seizure(GS)is a rare type of epilepsy that most commonly appears in patients with hypothalamic hamartoma.It is rarely associated with other types of brain damage.This particular type of epilepsy is...BACKGROUND Gelastic seizure(GS)is a rare type of epilepsy that most commonly appears in patients with hypothalamic hamartoma.It is rarely associated with other types of brain damage.This particular type of epilepsy is relatively rare and has few links to other brain lesions.Temporal lobe malacia is mostly caused by cerebral infarction or cerebral hemorrhage,which can lead to seizures.We report a case of GS in a woman with temporal lobe malacia which was reported for the first time in the literature.CASE SUMMARY A 73-year-old female,diagnosed case of GS,presented with repetitive stereotyped laughter a month prior to presentation,happening multiple times daily and with each time lasting for 5-15s.Electroencephalogram displayed a focal seizure seen in the right temporal region.Magnetic resonance imaging head with contrast showed a right temporal lobe malacia.The patient was started on levetiracetam daily.The patient indicated that they had fully recovered and were not experiencing any recurrent or stereotyped laughter during their daily routines.These results remained consistent even after a one-year follow-up period.CONCLUSION GS can be caused by temporal lobe malacia,which is an uncommon but potentially grave condition.The outcome of this present case exhibited the importance of the temporal lobe in the genesis of GS.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
BACKGROUND： Kainic acid can be used to induce a model of epilepsy by systemic injection, such as intraperitoneal or subcutaneous injection. Individual rats have different responses to kainic acid, therefore high dose...BACKGROUND： Kainic acid can be used to induce a model of epilepsy by systemic injection, such as intraperitoneal or subcutaneous injection. Individual rats have different responses to kainic acid, therefore high doses of drug are required and the success rate of model induction is low. It is necessary to develop an improved method to establish a temporal lobe epilepsy （TLE） animal model. OBJECTIVE： To explore an economic, stable and efficient method of establishing a TLE animal model. DESIGN, TIME AND SETTING： A completely randomized, controlled study. The experiments were performed in the Cellular Function Laboratory of the Physiology Department, Anhui Medical University from March to July 2007. MATERIALS： Twenty adult male Wistar rats, weighing 230-260 g, were provided by the Experimental Animal Centre of Nanjing Medical University. Kainic acid was purchased from Sigma in USA. Type SN-2 stereotaxic apparatus was made by Narishge in Japan. METHODS： Wistar rats were randomly divided into a kainic acid （KA） group （n = 12） and a normal saline （NS） group （n = 8）. For intrahippocampal microinjection, a burr hole was drilled in the skull at the following stereotaxic coordinates： anteroposterior （AP） 4.1 mm caudal to bregma; lateral （ML） 4.2 mm right lateral to the midline. Rats in the KA group were injected with 2.5 μL KA （0.4 g/L） into the center of the CA3 region, while in the NS group the same volume of NS was injected into the same site. MAIN OUTCOME MEASURES： Both groups were monitored under a video capture system for 12 weeks to record spontaneous seizures. Intracranial eletroencepholograph （IEEG） recordings in vivo were performed after the behavioral observations. After the IEEG recordings, hippocampi were processed into coronal sections. Nissl and Timm stainings were then performed to observe and confirm pathology. RESULTS： Twenty rats were involved in the final analysis. Behavioral observations： the eadiest spontaneous onset of epilepsy appeared 2 weeks after injection of KA. Eight rats had spontaneous onset of epilepsy 3-12 weeks after treatment. None of rats in the NS group had spontaneous onset of epilepsy. IEEG recordings： Epileptic-form waves, such as sharp waves and spike waves, were calculated by artificial analysis The number of epileptic-form waves in the KA group increased significantly compared to those of the NS group （P 〈 0.01）. Morphology results： In the KA group, Nissl staining and Timm staining revealed typical pathology in the hippocampal temporosphenoid lobe. In the NS group, no pathology was observed. CONCLUSION： Intrahippocampal microinjection of KA is a reliable method to establish a temporal lobe epilepsy animal model, requiring low doses of kainic acid and giving a high rate of success.展开更多
Objective To explore the ability of interictal diffusion-weighted imaging(DWI)to localize the temporal lobe of seizure origin and to predict postoperative seizure control in patients with temporal lobe epilepsy(TLE).M...Objective To explore the ability of interictal diffusion-weighted imaging(DWI)to localize the temporal lobe of seizure origin and to predict postoperative seizure control in patients with temporal lobe epilepsy(TLE).Methods Twenty-seven patients with intractable TLE considered for surgery and 19 healthy volunteers were studied with conventional magnetic resonance imaging(MRI)and DWI.Apparent diffusion coefficients(ADCs)of bilateral hippocampi in both TLE patients and control subjects were obtained.Lateralization to either temporal lobe with hippocampal ADC was based on the threshold values derived from ±1SD of right/left ratios in normal subjects.And the postoperative pathology was reviewed.Results Hippocampal ADCs were higher on the side of surgery compared with those on the contralateral side as well as the ipsilateral side in control subjects [resected side(109.8±7.3)×10-5 cm2/s,contralateral side(91.7±4.7)×10-5 cm2/s,control subjects(81.6±5.2)×10-5 cm2/s,all P<0.01].Right/left hippocampal ADC ratio and conventional MRI lateralized to the operated temporal lobe in 21 of 27(77.8%)and in 18 of 27(66.7%)patients.Lateralization to the surgical side was not associated with postoperative seizure control with right/left hippocampal ADC ratio(P>0.05).Conclusions Conventional MRI is a sensitive method to detect hippocampal sclerosis.Accuracy of the right/left hippocampal ADC ratio for lateralizing to the side of surgery is very high,but it isn't a better predictor of surgical outcome.展开更多
Objective To evaluate metabolic abnormalities in patients with mesial temporal lobe epilepsy （MTLE） with proton magnetic resonance spectroscopy （MRS） using a 3.0T MR scanner. Methods Sixty-three patients （32 wom...Objective To evaluate metabolic abnormalities in patients with mesial temporal lobe epilepsy （MTLE） with proton magnetic resonance spectroscopy （MRS） using a 3.0T MR scanner. Methods Sixty-three patients （32 women and 31 men） with diagnosed MTLE underwent diagnostic MR imaging （MRI） and proton MRS using a 3.0T MR scanner. The clinical history and interictal epileptiform discharges （IEDs） were recorded. Sixteen healthy volunteers served as control. The results of proton MRS were compared with the findings of electroencephalogram and structural MRI findings. Results Twenty-seven of the 63 patients with MTLE showed unilateral hippocampal sclerosis, and 9 showed bilateral hippocampal sclerosis. The concentration ratio of N-acytelaspartate （NAA） / [ creatine （ Cr ） ＋ choline （Cho） ] in the hippocampal region of MTLE patients （0. 64±0. 07） was significantly lower than control （0. 80±0. 05, P = 0.023）. In the patients with unilateral hippocampal sclerosis, NAA/（Cr ＋ Cho） in the hippocampal region ipsilateral to the sclerotic hippocampus （0.56±0.06） was significantly lower than the ratio in the contralateral hippocampal region （0.69±0.07, P 〈 0. 001 ）. There was significant difference in hippocampal NAA/（ Cr ＋ Cho） between the refractory patients and the non-refractory patients （0. 64±0. 05 vs.0.71±0. 07, P =0. 04）. Forty-five patients were lateralized by IEDs, while 49 patients were lateralized by metabolite ratio. And lateralization determined by proton MRS and IEDs was concordant in 33 patients. Conclusions MRS as a noninvasive tool adds helpful metabolite information to routine MRI in evaluation of MTLE. The method is well established and should be a routine clinical application in the investigation of epilepsy.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 human brain is known to be influenced by environmental stimuli（Feeney et al.,1982;Kaplan,1988）.Therefore,research on the brain activation pattern by external stimuli has been an important topic in neuroscience（...The human brain is known to be influenced by environmental stimuli（Feeney et al.,1982;Kaplan,1988）.Therefore,research on the brain activation pattern by external stimuli has been an important topic in neuroscience（Kaplan,1988）.Chewing gum has been known to have a positive effect on cognition,including alertness,attention,cognitive processing speed,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
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
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
Objective To explore the effect and mechanism of Chaihu Longgu Muli Decoction(柴胡龙骨牡蛎汤,CHLGMLD)in rats with temporal lobe epilepsy(TLE).Methods A total of 80 Sprague-Dawley(SD)male rats were randomized into cont...Objective To explore the effect and mechanism of Chaihu Longgu Muli Decoction(柴胡龙骨牡蛎汤,CHLGMLD)in rats with temporal lobe epilepsy(TLE).Methods A total of 80 Sprague-Dawley(SD)male rats were randomized into control(CON),model(MOD),carbamazepine(CBZ,0.1 g/kg),CHLGMLD low dose(CHLGMLD-L,12.5 g/kg),and high dose(CHLGMLD-H,25 g/kg)groups,with 16 rats in each group.TLE rat models were established in the four groups with the use of lithium-pilocarpine except for the CON group.After the successful establishment of TLE models,all drugs were administered through gavage,and distilled water was given to rats in the CON and MOD groups for four weeks.The frequency and duration of seizures before and after treatment were recorded for the evaluation of the alleviation degree.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect the expression levels of miR-146a-3p and miR-146a-5p.The expression levels of toll-like receptor 4(TLR4),interleukin-1 receptor-associated kinase 1(IRAK1),tumor necrosis factor(TNF)receptor-associated factor 6(TRAF6),TAK1-binding protein(TAB),nuclear factor-kappa B(NF-κB),and interleukin-1 beta(IL-1β)in hippocampus were tested by immunofluorescence assay.Correlation analysis between the above factors and expressions of miR-146a-3p and miR-146a-5p were performed separately.Results CHLGMLD decreased the frequency(P<0.05)and duration(P<0.01)of seizures in rats.CHLGMLD down-regulated the expression levels of miR-146a-5p and miR-146a-3p(P<0.05),and inhibited the expression levels of TLR4,IRAK1,TRAF6,TAB,NF-κB,and IL-1β(P<0.01).The correlation analysis revealed that the expression levels of TLR4,IRAK1,TRAF6,TAB,NF-κB,and IL-1β were positively correlated with the expression levels of miR-146a-3p and miR-146a-5p detected by qRT-PCR,respectively(P<0.01).Conclusion CHLGMLD can inhibite the TLR4 signaling pathway by lowering the expression levels of miR-146a-3p and miR-146a-5p to alleviate hippocampal dentate gyrus inflammation in TLE rats,thus relieving seizures.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
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
Objective To investigate the difference in interictal perfusion patterns between refractory and non-refractory temporal lobe epilepsies evaluated with flow-sensitive alternating inversion recovery (FAIR) magnetic reso...Objective To investigate the difference in interictal perfusion patterns between refractory and non-refractory temporal lobe epilepsies evaluated with flow-sensitive alternating inversion recovery (FAIR) magnetic resonance (MR) sequence. Methods Nine patients with refractory temporal lobe epilepsy, 21 patients with non-refractory temporal lobe epilepsy, and 13 normal volunteers underwent FAIR MR scanning. The relative cerebral blood flow (rCBF) in bilateral hemispheres and mesial temporal lobes were measured. And we also calculated the asymmetry index (AI) values. Results The AI values of bilateral hemispheres in refractory and non-refractory epilepsy patients were both significantly different from those of volunteers (P=0.012 and 0.029, respectively). There was significant difference in AI values of bilateral mesial temporal lobes between non-refractory epilepsy patients and volunteers (P=0.049), while no significant difference between refractory epilepsy patients and volunteers. Conclusions The hypoperfusion pattern of interictal refractory temporal lobe epilepsy patients is different from that of non-refractory patients. Although the hypoperfusion tends to extend out of temporal lobes in all patients, the refractory epilepsy patients have a preference of bilateral mesial temporal hypoperfusion, which may be valuable for evaluating prognosis.展开更多
OBJECTIVE To review the clinical features and surgical treatment for patients with temporal lobe gangliogliomas. METHODS Patients with temporal lobe gangliogliomas who underwent resection of temporal lobe tumors, conf...OBJECTIVE To review the clinical features and surgical treatment for patients with temporal lobe gangliogliomas. METHODS Patients with temporal lobe gangliogliomas who underwent resection of temporal lobe tumors, confirmed by surgical pathology, seen between September 1998 and November 2004 at the West China hospital, were selected. Medical records were reviewed for age at diagnosis, age at onset of seizures, delay between seizure onset and tumor diagnosis, types and frequencies of seizures, EEG results, extent of surgery, and pathologic diagnosis. The follow-up periods varied from 12 to 60 months （mean 30 months）. RESULTS Eighteen patients were identified, including 14 males and 4 females. Age at operation ranged from 4 years to 34 years （mean 17.6 years）. All patients underwent at least one surgical procedure. Fifteen tumors were classified as WHO Grade I lesions, and 3 as WHO Grade Ⅱ lesions. None of patients experienced a tumor recurrence. Among the patients, 85% had complete and sustained seizure relief. CONCLUSION Complex partial seizures and auras were the common presenting symptom of these patients. The follow-up suggested good relief from the seizures after surgery and a low risk for tumor recurrence and malignant progression.展开更多
基金supported by grants from the National Key R&D Program of China(2020YFA0803900)the National Natural Science Foundation of China(82173796 and U21A20418)+1 种基金the Natural Science Foundation of Zhejiang Province(LD22H310003)the Key R&D Plan of Zhejiang Province(2021C03116).
文摘Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications(ASMs),a condition known as pharmacoresistant epilepsy.The management of pharmacoresistant epilepsy remains an intractable issue in the clinic.Its early prediction is important for prevention and diagnosis.However,it still lacks effective predictors and approaches.Here,a classical model of pharmacoresistant temporal lobe epilepsy(TLE)was established to screen pharmacoresistant and pharmaco-responsive individuals by applying phenytoin to amygdaloid-kindled rats.Ictal electroencephalograms(EEGs)recorded before phenytoin treatment were analyzed.Based on ictal EEGs from pharmacoresistant and pharmaco-responsive rats,a convolutional neural network predictive model was constructed to predict pharmacoresistance,and achieved 78% prediction accuracy.We further found the ictal EEGs from pharmacoresistant rats have a lower gamma-band power,which was verified in seizure EEGs from pharmacoresistant TLE patients.Prospectively,therapies targeting the subiculum in those predicted as“pharmacoresistant”individual rats significantly reduced the subsequent occurrence of pharmacoresistance.These results demonstrate a new methodology to predict whether TLE individuals become resistant to ASMs in a classic pharmacoresistant TLE model.This may be of translational importance for the precise management of pharmacoresistant TLE.
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.
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 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.
基金the Natural Science Foundation of the Fujian Province,No.2021J01876.
文摘BACKGROUND Gelastic seizure(GS)is a rare type of epilepsy that most commonly appears in patients with hypothalamic hamartoma.It is rarely associated with other types of brain damage.This particular type of epilepsy is relatively rare and has few links to other brain lesions.Temporal lobe malacia is mostly caused by cerebral infarction or cerebral hemorrhage,which can lead to seizures.We report a case of GS in a woman with temporal lobe malacia which was reported for the first time in the literature.CASE SUMMARY A 73-year-old female,diagnosed case of GS,presented with repetitive stereotyped laughter a month prior to presentation,happening multiple times daily and with each time lasting for 5-15s.Electroencephalogram displayed a focal seizure seen in the right temporal region.Magnetic resonance imaging head with contrast showed a right temporal lobe malacia.The patient was started on levetiracetam daily.The patient indicated that they had fully recovered and were not experiencing any recurrent or stereotyped laughter during their daily routines.These results remained consistent even after a one-year follow-up period.CONCLUSION GS can be caused by temporal lobe malacia,which is an uncommon but potentially grave condition.The outcome of this present case exhibited the importance of the temporal lobe in the genesis of GS.
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Funds for the Excellent Talent of Anhui Province of China, No.06043090National Century Excellent Talents in University of China, No.NCET-06-0557Natural Science Foundation of Anhui Province Department of Education, No. KJ2007A028
文摘BACKGROUND： Kainic acid can be used to induce a model of epilepsy by systemic injection, such as intraperitoneal or subcutaneous injection. Individual rats have different responses to kainic acid, therefore high doses of drug are required and the success rate of model induction is low. It is necessary to develop an improved method to establish a temporal lobe epilepsy （TLE） animal model. OBJECTIVE： To explore an economic, stable and efficient method of establishing a TLE animal model. DESIGN, TIME AND SETTING： A completely randomized, controlled study. The experiments were performed in the Cellular Function Laboratory of the Physiology Department, Anhui Medical University from March to July 2007. MATERIALS： Twenty adult male Wistar rats, weighing 230-260 g, were provided by the Experimental Animal Centre of Nanjing Medical University. Kainic acid was purchased from Sigma in USA. Type SN-2 stereotaxic apparatus was made by Narishge in Japan. METHODS： Wistar rats were randomly divided into a kainic acid （KA） group （n = 12） and a normal saline （NS） group （n = 8）. For intrahippocampal microinjection, a burr hole was drilled in the skull at the following stereotaxic coordinates： anteroposterior （AP） 4.1 mm caudal to bregma; lateral （ML） 4.2 mm right lateral to the midline. Rats in the KA group were injected with 2.5 μL KA （0.4 g/L） into the center of the CA3 region, while in the NS group the same volume of NS was injected into the same site. MAIN OUTCOME MEASURES： Both groups were monitored under a video capture system for 12 weeks to record spontaneous seizures. Intracranial eletroencepholograph （IEEG） recordings in vivo were performed after the behavioral observations. After the IEEG recordings, hippocampi were processed into coronal sections. Nissl and Timm stainings were then performed to observe and confirm pathology. RESULTS： Twenty rats were involved in the final analysis. Behavioral observations： the eadiest spontaneous onset of epilepsy appeared 2 weeks after injection of KA. Eight rats had spontaneous onset of epilepsy 3-12 weeks after treatment. None of rats in the NS group had spontaneous onset of epilepsy. IEEG recordings： Epileptic-form waves, such as sharp waves and spike waves, were calculated by artificial analysis The number of epileptic-form waves in the KA group increased significantly compared to those of the NS group （P 〈 0.01）. Morphology results： In the KA group, Nissl staining and Timm staining revealed typical pathology in the hippocampal temporosphenoid lobe. In the NS group, no pathology was observed. CONCLUSION： Intrahippocampal microinjection of KA is a reliable method to establish a temporal lobe epilepsy animal model, requiring low doses of kainic acid and giving a high rate of success.
文摘Objective To explore the ability of interictal diffusion-weighted imaging(DWI)to localize the temporal lobe of seizure origin and to predict postoperative seizure control in patients with temporal lobe epilepsy(TLE).Methods Twenty-seven patients with intractable TLE considered for surgery and 19 healthy volunteers were studied with conventional magnetic resonance imaging(MRI)and DWI.Apparent diffusion coefficients(ADCs)of bilateral hippocampi in both TLE patients and control subjects were obtained.Lateralization to either temporal lobe with hippocampal ADC was based on the threshold values derived from ±1SD of right/left ratios in normal subjects.And the postoperative pathology was reviewed.Results Hippocampal ADCs were higher on the side of surgery compared with those on the contralateral side as well as the ipsilateral side in control subjects [resected side(109.8±7.3)×10-5 cm2/s,contralateral side(91.7±4.7)×10-5 cm2/s,control subjects(81.6±5.2)×10-5 cm2/s,all P<0.01].Right/left hippocampal ADC ratio and conventional MRI lateralized to the operated temporal lobe in 21 of 27(77.8%)and in 18 of 27(66.7%)patients.Lateralization to the surgical side was not associated with postoperative seizure control with right/left hippocampal ADC ratio(P>0.05).Conclusions Conventional MRI is a sensitive method to detect hippocampal sclerosis.Accuracy of the right/left hippocampal ADC ratio for lateralizing to the side of surgery is very high,but it isn't a better predictor of surgical outcome.
文摘Objective To evaluate metabolic abnormalities in patients with mesial temporal lobe epilepsy （MTLE） with proton magnetic resonance spectroscopy （MRS） using a 3.0T MR scanner. Methods Sixty-three patients （32 women and 31 men） with diagnosed MTLE underwent diagnostic MR imaging （MRI） and proton MRS using a 3.0T MR scanner. The clinical history and interictal epileptiform discharges （IEDs） were recorded. Sixteen healthy volunteers served as control. The results of proton MRS were compared with the findings of electroencephalogram and structural MRI findings. Results Twenty-seven of the 63 patients with MTLE showed unilateral hippocampal sclerosis, and 9 showed bilateral hippocampal sclerosis. The concentration ratio of N-acytelaspartate （NAA） / [ creatine （ Cr ） ＋ choline （Cho） ] in the hippocampal region of MTLE patients （0. 64±0. 07） was significantly lower than control （0. 80±0. 05, P = 0.023）. In the patients with unilateral hippocampal sclerosis, NAA/（Cr ＋ Cho） in the hippocampal region ipsilateral to the sclerotic hippocampus （0.56±0.06） was significantly lower than the ratio in the contralateral hippocampal region （0.69±0.07, P 〈 0. 001 ）. There was significant difference in hippocampal NAA/（ Cr ＋ Cho） between the refractory patients and the non-refractory patients （0. 64±0. 05 vs.0.71±0. 07, P =0. 04）. Forty-five patients were lateralized by IEDs, while 49 patients were lateralized by metabolite ratio. And lateralization determined by proton MRS and IEDs was concordant in 33 patients. Conclusions MRS as a noninvasive tool adds helpful metabolite information to routine MRI in evaluation of MTLE. The method is well established and should be a routine clinical application in the investigation of epilepsy.
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 Medical Research Center Program(2015R1A5A2009124)through the National Research Foundation of Korea(NRF)funded by the Ministry of Science,ICT and Future Planning
文摘The human brain is known to be influenced by environmental stimuli（Feeney et al.,1982;Kaplan,1988）.Therefore,research on the brain activation pattern by external stimuli has been an important topic in neuroscience（Kaplan,1988）.Chewing gum has been known to have a positive effect on cognition,including alertness,attention,cognitive processing speed,
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.
基金National Natural Science Foundation of China(81874429)Natural Science Foundation of Hunan Province(2020JJ5294)+3 种基金Traditional Chinese Medicine Science&Research Project of Hunan Province(202145)Excellent Youth Program of Hunan Education Department(21B0081)Hunan Provincial Administration of Traditional Chinese Medicine(D2022027)Changsha Natural Science Foundation of China(KQ2202255).
文摘Objective To explore the effect and mechanism of Chaihu Longgu Muli Decoction(柴胡龙骨牡蛎汤,CHLGMLD)in rats with temporal lobe epilepsy(TLE).Methods A total of 80 Sprague-Dawley(SD)male rats were randomized into control(CON),model(MOD),carbamazepine(CBZ,0.1 g/kg),CHLGMLD low dose(CHLGMLD-L,12.5 g/kg),and high dose(CHLGMLD-H,25 g/kg)groups,with 16 rats in each group.TLE rat models were established in the four groups with the use of lithium-pilocarpine except for the CON group.After the successful establishment of TLE models,all drugs were administered through gavage,and distilled water was given to rats in the CON and MOD groups for four weeks.The frequency and duration of seizures before and after treatment were recorded for the evaluation of the alleviation degree.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect the expression levels of miR-146a-3p and miR-146a-5p.The expression levels of toll-like receptor 4(TLR4),interleukin-1 receptor-associated kinase 1(IRAK1),tumor necrosis factor(TNF)receptor-associated factor 6(TRAF6),TAK1-binding protein(TAB),nuclear factor-kappa B(NF-κB),and interleukin-1 beta(IL-1β)in hippocampus were tested by immunofluorescence assay.Correlation analysis between the above factors and expressions of miR-146a-3p and miR-146a-5p were performed separately.Results CHLGMLD decreased the frequency(P<0.05)and duration(P<0.01)of seizures in rats.CHLGMLD down-regulated the expression levels of miR-146a-5p and miR-146a-3p(P<0.05),and inhibited the expression levels of TLR4,IRAK1,TRAF6,TAB,NF-κB,and IL-1β(P<0.01).The correlation analysis revealed that the expression levels of TLR4,IRAK1,TRAF6,TAB,NF-κB,and IL-1β were positively correlated with the expression levels of miR-146a-3p and miR-146a-5p detected by qRT-PCR,respectively(P<0.01).Conclusion CHLGMLD can inhibite the TLR4 signaling pathway by lowering the expression levels of miR-146a-3p and miR-146a-5p to alleviate hippocampal dentate gyrus inflammation in TLE rats,thus relieving seizures.
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.
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.
文摘Objective To investigate the difference in interictal perfusion patterns between refractory and non-refractory temporal lobe epilepsies evaluated with flow-sensitive alternating inversion recovery (FAIR) magnetic resonance (MR) sequence. Methods Nine patients with refractory temporal lobe epilepsy, 21 patients with non-refractory temporal lobe epilepsy, and 13 normal volunteers underwent FAIR MR scanning. The relative cerebral blood flow (rCBF) in bilateral hemispheres and mesial temporal lobes were measured. And we also calculated the asymmetry index (AI) values. Results The AI values of bilateral hemispheres in refractory and non-refractory epilepsy patients were both significantly different from those of volunteers (P=0.012 and 0.029, respectively). There was significant difference in AI values of bilateral mesial temporal lobes between non-refractory epilepsy patients and volunteers (P=0.049), while no significant difference between refractory epilepsy patients and volunteers. Conclusions The hypoperfusion pattern of interictal refractory temporal lobe epilepsy patients is different from that of non-refractory patients. Although the hypoperfusion tends to extend out of temporal lobes in all patients, the refractory epilepsy patients have a preference of bilateral mesial temporal hypoperfusion, which may be valuable for evaluating prognosis.
文摘OBJECTIVE To review the clinical features and surgical treatment for patients with temporal lobe gangliogliomas. METHODS Patients with temporal lobe gangliogliomas who underwent resection of temporal lobe tumors, confirmed by surgical pathology, seen between September 1998 and November 2004 at the West China hospital, were selected. Medical records were reviewed for age at diagnosis, age at onset of seizures, delay between seizure onset and tumor diagnosis, types and frequencies of seizures, EEG results, extent of surgery, and pathologic diagnosis. The follow-up periods varied from 12 to 60 months （mean 30 months）. RESULTS Eighteen patients were identified, including 14 males and 4 females. Age at operation ranged from 4 years to 34 years （mean 17.6 years）. All patients underwent at least one surgical procedure. Fifteen tumors were classified as WHO Grade I lesions, and 3 as WHO Grade Ⅱ lesions. None of patients experienced a tumor recurrence. Among the patients, 85% had complete and sustained seizure relief. CONCLUSION Complex partial seizures and auras were the common presenting symptom of these patients. The follow-up suggested good relief from the seizures after surgery and a low risk for tumor recurrence and malignant progression.
