Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies

Epilepsy is a severe,relapsing,and multifactorial neurological disorder.Studies regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy.The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota composition.Satisfactory results are lacking for conventional treatments for epilepsy.Surgical resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy.Non-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research focus.This review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of epilepsy.It also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation.Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures.Additionally,many new technologies for the diagnosis and treatment of epilepsy are being explored.However,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.

The role of axon guidance molecules in the pathogenesis of epilepsy

Current treatments for epilepsy can only manage the symptoms of the condition but cannot alter the initial onset or halt the progression of the disease. Consequently, it is crucial to identify drugs that can target novel cellular and molecular mechanisms and mechanisms of action. Increasing evidence suggests that axon guidance molecules play a role in the structural and functional modifications of neural networks and that the dysregulation of these molecules is associated with epilepsy susceptibility. In this review, we discuss the essential role of axon guidance molecules in neuronal activity in patients with epilepsy as well as the impact of these molecules on synaptic plasticity and brain tissue remodeling. Furthermore, we examine the relationship between axon guidance molecules and neuroinflammation, as well as the structural changes in specific brain regions that contribute to the development of epilepsy. Ample evidence indicates that axon guidance molecules, including semaphorins and ephrins, play a fundamental role in guiding axon growth and the establishment of synaptic connections. Deviations in their expression or function can disrupt neuronal connections, ultimately leading to epileptic seizures. The remodeling of neural networks is a significant characteristic of epilepsy, with axon guidance molecules playing a role in the dynamic reorganization of neural circuits. This, in turn, affects synapse formation and elimination. Dysregulation of these molecules can upset the delicate balance between excitation and inhibition within a neural network, thereby increasing the risk of overexcitation and the development of epilepsy. Inflammatory signals can regulate the expression and function of axon guidance molecules, thus influencing axonal growth, axon orientation, and synaptic plasticity. The dysregulation of neuroinflammation can intensify neuronal dysfunction and contribute to the occurrence of epilepsy. This review delves into the mechanisms associated with the pathogenicity of axon guidance molecules in epilepsy, offering a valuable reference for the exploration of therapeutic targets and presenting a fresh perspective on treatment strategies for this condition.

改进YOLOv5su模型检测桃树缩叶病

为实现自然环境下桃树缩叶病的检测,该研究提出了一种基于YOLOv5su的桃树缩叶病识别改进模型DLLYOLOv5su。首先,针对桃树缩叶病目标特征变化较大的问题,在骨干网络最后一层C3模块中加入可变形自注意力模块(deformable attention,DA),使模型更加关注目标区域,降低背景对模型的影响,提高模型在复杂背景下的拟合能力。其次在SPPF(fast spatial pyramid pooling)模块中引入LSKA(large separable kernel attention)结构,大核卷积增大了模型的感受野,使模型能够关注更多信息。最后,提出了LAWD(lightweight adaptive weighted downsampling)模块,使用轻量化的下采样结构替换卷积模块,减少计算开销。在桃树缩叶病数据集上进行试验,结果显示,DLL-YOLOv5su模型权重大小为17.6 MB,检测速度为83帧/s。识别准确率P、召回率R和平均精度均值mAP_(50)分别达到了80.7%、73.1%和80.4%,相较于原始YOLOv5su分别提高了4.2、2.4和4.3个百分点。与YOLOv3-tiny、Faster R-CNN、YOLOv7和YOLOv8相比mAP_(50)分别高出了28.5、11.8、2.1和4.1个百分点。改进模型识别精度高,误检、漏检率低,检测速度满足实时检测的要求,可以为桃树缩叶病的实时监测和预警提供参考。

小麦SUS基因家族鉴定与生物信息学分析

【目的】对小麦蔗糖合成酶(sucrose synthase,SUS)基因家族进行鉴定和生物信息学分析,为探究小麦SUS(TaSUS)基因家族的作用机制提供理论参考。【方法】采用生物信息学方法在小麦全基因组上鉴定TaSUS基因家族成员,并对其系统进化关系、染色体位置、基因结构、保守结构域、启动子顺式作用元件和基因表达模式进行分析。【结果】在小麦基因组中共鉴定到分布于14条染色体上的24个TaSUS基因,可分为3个亚组。TaSUS基因含有多个外显子,但部分基因缺失非翻译区结构。TaSUS基因家族成员启动子区域包含45种顺式作用元件,涉及植物生长发育和逆境胁迫响应。大多数TaSUS基因在小麦穗中显著表达,在叶、茎和根中的相对表达量较低。【结论】研究结果有助于了解小麦SUS基因家族的进化,为后期小麦SUS基因家族的生物功能研究奠定理论基础。

Correlation Study on Expression of GST-π Protein in Brain Tissue and Peripheral Blood of Epilepsy Rats Induced by Pilocarpine

Previous studies have suggested that glutathione-S-transferase π （GST-π） over-expression in the brain tissue is associated with refractory epilepsy. However, whether the change in GST-π level in the peripheral blood is in line with that in brain tissue remains unknown. This study examined the correlation between GST-π in brain tissue and that in peripheral blood in rat models of pilocarpine-induced refractory epilepsy. The animals were divided into drug-resistant group and drug-responsive group according to the response to anti-epileptic drugs. GST-π expression in brain tissue was immunohistochemically determined, while the expression of GST-π in peripheral blood was analyzed by Western blotting. In the hippocampus and cortex, GST-π was mainly found in the cytoplasm and membrane of neurons, and the GST-π expression level was higher in drug-resistant group than in the drug-responsive group and saline control group （P〈0.05）. Moreover, there was no significant difference between responders and saline control animals （P〉0.05）. The change in expression of GST-π in peripheral blood showed the same pattern as that in brain tissues, suggesting GST-π might contribute to drug resistance in epilepsy. Importantly, the GST-π over-expression in peripheral blood could be used as a marker for resistance to anti-epileptic agents.

Effects of topiramate versus other antiepileptic drugs on the cognitive function of patients with epilepsy

BACKGROUND： Only very large dose of topiramate has neurotoxicity, indicating that topiramate has low neurotoxicity and high safety. The residual rate of topiramate is affected by many cognitive-related adverse effects. Patients who take topiramate often accompany with thought slowness, difficulty in finding words, dyscalculia, blunt reaction, attention decreasing, memory deterioration, etc. OBJECTIVE： To compare the effects of topiramate with traditional anti-epileptic drugs （including carbamazepine and Valproic acid （VPA） on cognitive function of patients with epilepsy. DESIGN： Observational experiment, self-control and intergroup comparison. SETTING： Sichuan Academy of Medical Science. PARTICIPANTS： Eighty-seven inpatients and outpatients with newly diagnosed epilepsy who received preliminary diagnosis and follow-up in the Department of Neurology, Sichuan People＇s Hospital between January 2004 and June 2006 were involved in this survey. They were diagnosed according to disease history and electroencephalogram （EEG）. The onset type was diagnosed following the definition of epilepsy and epileptic syndrome in 1989 International Anti-epileptic League. The involved patients and their relatives were informed of detection and therapeutic regimen. The patients were assigned into two groups according to table of random digit： traditional antiepileptic drugs group （AEDs group, n =44） and topiramate （TPM） group （n =43）. METHODS： （1）Among the patients in AEDs group, carbamazepine was the first choice for 21 patients with partial seizures or partial secondarily generalized seizures, and VPA for 23 patients with generalized seizures. The initial dose of carbamazepine was 300 mg/d, and that of VPA was 500 mg/d. Patients in the TPM group took TPM with the initial dose of 25 mg/d, increased by 25 mg/d each week to target dose 150 mg/d within 8 weeks. （2） Curative effect was graded into 4 degrees： markedly effective, effective, ineffective and aggravated. Total effective rate was calculated. （3） Cognitive function of patients was tested before and 6 months after administration by using Wechsler Adult Intelligence Scale（WAIS） or Wechsler Intelligence Scale for Children （WISC, Chinese edition）, （Higher scores indicated better cognitive function）, Stroop color word interference, test of memory of past numbers, test of telling the names of fruits and vegetables within 1 minute （Shorter time for reading word, telling color and memory of past numbers demonstrated better cognitive function. Less errors in reading words, telling colors and memory of past numbers, numbering and telling the names of fruits and vegetables within 1 minute indicated better cognitive function）, etc. totally 22 items. （4） t test and paired t test were used for measurement data. MAIN OUTCOME MEASURES： Clinical curative effects and adverse reactions as well as neurological tests. RESULTS： Eighty-four pationts praticipated final analysis and 3 dropped out. （1） Inthe AEDS group and TPM group, total effective rate was 86% and 99%, respectively. （2） In the AEDs group, there were no significant changes in the scores of each test of WIS before and after treatment （P 〉 0.05）. In the TPM group, total IQ, word scores, verbal IQ and digit span scores were significantly decreased （ t =2.097 - 4.423, P 〈 0.05 - 0.01 ） .Following treatment, the time for reading word and telling color for patients in the AEDs group was prolonged in Stroop color interference test （ t = - 2.304, - 2.454, P 〈 0.05 ）, and time for reading word and memory of past numbers for patients in the topiramate group was significantly prolonged （ t = - 3.054, 2.272, P 〈 0.01, 0.05 ）. （3）There were no significant differences in scores of WIS before and after treatment in AEDs group and TPM group （P 〉 0.05）. Following treatment, verbal IQ, word scores, total IQ, digit span of patients in the TPM group were significantly lower than those in the AEDs group （t =2.052 - 3.297, P 〈 0.05- 0.01 ） .There were no significant differences in Stroop color word interference, memory of past numbers and telling the names of fruits and vegetables within 1 minute before and after treatment in AEDs group and TPM group （P 〉 0.05）. CONCLUSION： （1） Moderate and small doses of both TPM and AEDs may lead to mild cognitive function impairment of patients, mainly presenting delayed reaction and decreased sensitivity. （2）TPM mainly influences attention, language comprehension ability and fluency, while AEDs cause delayed reaction easily, but influence executive function mainly.

Stereotactic surgery for refractory epilepsy complicated by mental disorders A retrospective case analysis

BACKGROUND： Anti-epilepsy and anti-psychosis drugs have traditionally been used in the clinic to treat epilepsy complicated by mental disorders. However, there is still no effective therapy for refractory epilepsy patients suffering from persistent mental disorders. OBJECTIVE： To explore the therapeutic effects of stereotactic multi-element localization and multi-target radiofrequency ablation on patients with refractory primary epilepsy and mental disorders. DESIGN： A retrospective case analysis. SETTING： Department of Neurosurgery, the 454 Hospital of Chinese PLA. PARTICIPANTS： Between June and November 2004, 13 patients with refractory primary epilepsy complicated by persistent mental disorders were admitted to the Department of Neurosurgery, the 454 Hospital of Chinese PLA. The patient group consisted of nine males and four females, with an average age of 25 years （range 18-39 years）, and a course of disease ranging 3-11 years. Diagnosis of mental disorders was in accordance with Chinese Classification of Mental Disorders. Written informed consent was obtained from all patients and their families, and the treatment protocol was approved by the Ethics Committee of the Hospital. METHODS： Under venous inhalation anesthesia, the disease targets, including bilateral corpus callosum, bilateral amygdala, and bilateral medial septal area, as well as unilateral Forel-H area, were coagulated by RFG-3CF radiofrequency thermocoagnlation at 75-80 ℃ for 60-70 seconds. During thermocoagulation, the targets were identified using deep-brain microelectrodes and localized according to electrophysiology and electric resistance values. MAIN OUTCOME MEASURES： One year post-surgery, epileptic seizures were assessed on the basis of the Tan classification, and psychogenic （non-epileptic） seizures were evaluated using a 5-grade system. RESULTS： All enrolled 13 epileptic patients were included in the final analysis. The results of follow-up evaluations demonstrated that epilepsy was well-controlled. In total, nine patients did not experience relapse, and the frequency of seizures was reduced by 75% in two patients, and 50%-74% in another two patients. Psychogenic seizures were ameliorated in 11 cases （class 1, recovery） and improved significantly in two cases （class 2, significant improvement）. CONCLUSION： Radiofrequency ablation of bilateral corpus callosum, bilateral amygdala, bilateral medial septal area, and unilateral Forel-H area exhibits certain efficacy in treating epileptic patients suffering from persistent mental disorders.

Electrocorticography-Guided Surgical Treatment of Solitary Supratentorial Cavernous Malformations with Secondary Epilepsy

Objective To evaluate the efficacy of electrocorticographic(ECoG) monitoring and the application of different surgical approaches in the surgical treatment of solitary supretentorial cavernous malformations with secondary epilepsy. Methods This study enrolled a consecutive series of 36 patients with solitary supratentorial cavernous malformations and secondary epilepsy who underwent surgery with intraoperative ECoG monitoring in the Department of Neurosurgery between January 2004 and January 2008. The patients were composed of 15 males and 21 females, aged between 8 and 52 years(mean age 27.3±2.8 years) at the time of surgery. Epilepsy history, the type of epilepsy at the presentation, lesion location, the incidence of residual epileptiform discharges, and postoperative outcomes were evaluated. Results Histopathological examination indicated cavernous malformations and hippocampal sclerosis in 36 and 5 cases, respectively. Neuronal degeneration, glial cell proliferation, and neurofibrillary tangles were found in all the resected cerebral tissues of extended lesionectomy of residual epileptic foci. Lesionectomy, anterior temporal lobectomy, anterior temporal lobectomy plus cortical thermocoagulation, extended lesionectomy, extended lesionectomy plus cortical thermocoagulation were performed in 4, 4, 1, 14, and 13 cases, respectively. Residual epileptiform discharges were captured in 9 out of the 14 patients who had additional cortical thermocoagulation. According to Engle class for postoperative outcomes, 27 cases were class I(75.00%), 5 were class II(13.89%), 2 were class III(5.56%), and 2 were class IV(5.56%), thus the total effective rate(class I+class II) was 88.89%. Neither of epilepsy history, the type of epilepsy, and the location of cavernous malformation was significantly related to outcomes(P>0.05). A significant relationship was found between the incidence of residual epileptiform discharges and outcomes(P=0.041). Conclusions Intraoperative ECoG monitoring, the application of different surgical approaches, and the resection of residual epileptic foci could produce good result in the surgical treatment of supratentorial cavernous malformation with secondary epilepsy. Postoperative residual epileptiform discharges could be a useful predictor for evaluating the outcomes.

Microsurgical Treatment of Epilepsy with Parenchymal Neurocysticercosis

Parenchymal neurocysticercosis is the most common form of neurocysticercosis in the central nervous system(CNS),which mainly causes epilepsy and usually responses well to routine medications.However,there are appreciable cases of relapses refractory to medical treatment.We investigated microsurgical treatment of epilepsy with parenchymal neurocysticercosis.Nine cases of epilepsy caused by parenchymal neurocysticercosis from 2002 to 2018 were analyzed retrospectively.Cysts in 7 cases were completely removed.No case died of operation and no new dysfunction of the nervous system was observed after surgery.Among the other 9 cases,8 cases became seizure-free or controlled by medicine according to the postoperative follow­up for 6 months to 9 years.One case was lost for followup.It was suggested that epilepsy with parenchymal neurocysticercosis can usually be controlled after routine medications.However,surgery is still indicated in some cases and careful microsurgery is associated with satisfactory clinical outcomes in appropriately selected cases.

Epilepsy versus non-epileptic attack disorder: A diagnostic and therapeutic challenge

Epilepsy and non-epileptic attack disorder (NEAD) share a vast number of clinical features, however the aetiology and management are very different. Video-EEG is the gold standard diagnostic tool and relies on the occurrence of seizure activity during assessment to make a diagnosis. Added complexity arises from the co-existence of epilepsy and NEAD, occurring in a significant proportion of patients. Comprehensive assessment and investigation is therefore required to prevent gross mistreatment in this diagnostically difficult subgroup. We present a case of NEAD with co-existing epilepsy and the challenges that this may present in clinical practice.

Posterior quadrantic disconnection maintains the activity of isolated temporal-parietal-occipital nerve tissue: neuroprotective measures in the surgical treatment of epilepsy

Extensive lesions involving the posterior quadrant of the cerebral hemisphere （temporal, parietal, and occipital lobes） induce intractable epilepsy. These patients are potential candidates for surgical treatmenttu. Maintenance of isolated nerve tissue activity after surgery plays a crucial role in the neuroprotective effects of neurosurgery treatment. Disconnection surgery of the posterior quadrant is used to completely isolate nerve fibers, while blood supply at the isolated lobes is maintained. Subsequently, cavities caused by cystic or necrotic nerve tissues should be reduced as much as possible,

Clinical Observation on 930 Child Epilepsy Cases Treated with Anti-epilepsy Capsules

1090 cases of child epilepsy were divided randomly into two groups: the treatment group (930 cases treated with anti-epilepsy capsules) and the control group (160 cases treated with luminal). The results showed that in the treatment group, 534 cases were markedly effective, 241 effective, 96 improved, 46 ineffective, and 13 aggravated, with a total effective rate of 83.33%; while in the control group, 64 cases were markedly effective, 19 effective, 38 improved, 29 ineffective, and 10 aggravated, with a total effective rate of 51.88%. The treatment group showed an obviously higher total effective rate than that in the control group (P<0.01). After treatment, cases in the two groups all had lower frequency of epilepsy attacks and shorter duration of each attack as compared with that before treatment (P<0.01), but the situation was obviously better in the treatment group. The anti-epilepsy capsules had very good effect on various types of epilepsy, especially on autonomic epilepsy and on epilepsies due to wind, phlegm, or terror as differentiated in TCM. After treatment, the recovery rate shown by EEG examination was 54.3% in the treatment group, while 38.4% in the control group, the former being obviously higher than the latter (P<0.01).

Clinical Characteristics and Current Medical Practice in a Group of Sudanese Patients with Epilepsy: A Cross Sectional Hospital Based-Study

Introduction: The epilepsy classification in under developed countries faces many difficulties in reporting, work-up and management strategies. Exploring local practice in general hospitals will positively add to the welfare of patients with epilepsy. The objectives of this study were to assess the current medical practice in epilepsy work up and to study the selection of AEDs as per ILAE guidelines. Methods: This was a cross sectional-retrospective hospital based study, conducted between April and September 2016 in Omdurman Teaching Hospital, Khartoum, Sudan. Patients aged 18 years old and above were enrolled. Epilepsy was defined as having at least two non-provoked seizures in the least 6 months in a patient who was assessed by clinical review and electroencephalogram (EEG). Epilepsy was classified as generalized, focal or unclassified. Medications refer to all internationally licensed antiepileptic medications (AEDs) in 2016. Results: One hundred adult Sudanese patients were enrolled for this study. The most common event described during the ictal phase was tongue biting in 50% of participants followed by body stiffness in 46%. Epilepsy was classified as generalized in 84%, focal in 11% and unclassified in 5% patients. In generalized epilepsy, the MRI detected 23.3% abnormal findings higher than the CT which detected 14.8% (4/27), p value = 0.032. In focal epilepsy, the CT detected 75% abnormal findings higher than the MRI which detected 33.3%, p value = 0.02. The AEDs used were as follows: Carbamazepine (CBZ) 48%, Na valproate (VP) 33%, Lamotrigine (LMT) 2%, Levetricetan (LVT) 1%, CBZ + VP 14% and CBZ + Oxcarbazepine (OXC) 2%. Conclusion: The current medical practice in Omdurman teaching hospital should be modified to match the international league against epilepsy (ILAE) guidelines in workup, management, AEDs selection and classification of epilepsy.

Surgical treatment of refractory epilepsy, secondary to central nervous system infection

Previous studies have focused on medial temporal lobe epilepsy secondary to central nervous system infections. Several large-sample analyses of multi-lobe injuries or complications of medial temporal lobe epilepsy have been reported. The present study selected 29 patients （10 males and 19 females with a mean age of 18 years） with refractory epilepsy secondary to central nervous system infections （meningitis in 8, encephalitis in 21） from Beijing Functional Neurosurgical Institute from May 2006 to August 2008. All patients underwent computer tomography or magnetic resonance imaging, as well as electroencephalogram examinations; cortical electrodes were embedded in 11 patients. In addition, 13 （45%） patients underwent anterior temporal Iobectomy, and 16 （56%） underwent extratemporal corcticectomy. Results showed that 18 （62%） patients obtained favorable outcomes following surgical treatment, including 80% with temporal lobe epilepsy and 50% with extratemporal epilepsy. Central nervous system infection was not a contraindication for epilepsy treatment, and identification of epileptic foci proved to be crucial. In addition, a young age at infection, as well as prolonged latent period from time of infection to initial afebrile seizure, were 2 predictive factors for all patients. Cortical electrodes significantly increased the detection rate of epileptic foci, but did not improve prognosis of foci excision.

Subicular pyramidal neurons gate drug resistance in temporal lobe epilepsy

OBJECTIVE To understand the underlying mechanisms of drug resistant temporal lobe epilepsy(TLE).METHODS In vivo and vitro electrophysiology,optogenetics and chemogenetics were used in a classic multi-drug resistant TLE model.RESULTS Subicular pyramidal neuron activity was not inhibited by the anti-epileptic drug phenytoin in drug resistant rats.This phenomenon was specific to the subiculum,but did not involve surrounding temporal lobe regions.Selective inhibition of subicular pyramidal neurons by both optogenetics and chemogenetics reversed drug resistance.In contrast,selective activation of subicular pyramidal neurons directly induced drug resistance in drug responsive rats.Furthermore,long-term low frequency stimulation at the subiculum,which is clinically feasible,inhibited the activity of subicular pyramidal neurons and reversed drug resistance.CONCLUSION Subicular pyramidal neurons might be a key ″ switch″ mediating drug resistance in TLE and represent a new potential target for more precise treatment of drug resistant TLE.

A SURVEY OF EPILEPSY TREATED WITH ACUPUNCTURE AND MOXIBUSTION IN RECENT YEARS

In this paper,we have introduced the developing tendencies and features of the treat-ment of epilepsy with acupuncture and moxibustion.studies on the naechanism of the therapeutic ef-fect.the evaluation of the clinical effect and some problems in the last 10 years.Moreover,we haveput forward our opinions for improving the treatment in future.

Comparisons of drug efficacy and time-effect among magnesium valproate,sustained-release magnesium valproate tablet and depakine chrono for epilepsy An experiment of determining cortical convulsive threshold in rats undergoing electrical stimulation

BACKGROUND： Scholars have investigated the differences in drug metabolism and pharmacodynamics between valproate and its sustained-release tablets only from the angle of pharmaceutical sciences or clinical practice. Whether the fact that differences in drug efficacy and time-effect of different doses of valproate and different types of sustained-release valproate tablets at the same concentration can be quantitatively reflected by determining the changes in convulsive threshold pre- and post-administration in rat models of determining the convulsive threshold developed by direct cortical electrical stimulation remains unclear. OBJECTIVE： This study aimed to compare the drug efficacy and time-effect among magnesium valproate, sustained-release magnesium valproate tablet and depakine chrono in the treatment of epilepsy by determining the convulsive threshold of rat models created by direct cortical electrical stimulation, and human serum drug concentration before and after administration. DESIGN： A controlled observational experiment. SETTING： Research Institute of Epilepsy, Shanxi Medical University. MATERIALS： Adult health male SD rats of clean grade, weighing 200 - 220 g, provided by the Laboratory Animal Center of Shanxi Medical University. The protocol was carried out in accordance with requests from Animal Ethics Committees for guidance. Magnesium valproate （Lot No. 041004） and sustained-release magnesium valproate tablet （Lot No. 050501） were produced in Hunan Xiangzhong Pharmaceutical Co., Ltd. METHODS： This study was carried out in the Laboratory for Epilepsy, Shanxi Medical University between June and August 2005. （1）All the SD rats were created into models for determining cortical convulsive threshold. They were randomly divided into 4 groups with 20 rats in each： magnesium valproate tablet group, sustained-release magnesium valproate tablet group, depakine chrono group and control group. After being modeled, the rats in the first 3 groups were intragastrically administrated with magnesium valproate, sustained-release magnesium valproate tablet and depakine chrono, respectively, while the control group were intragastrically administrated with the same volume of normal saline. （2）Convulsive threshold of each fasting rat was determined 0.5 hour before, and 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14 and 24 hours after single administration, separately. （3） Convulsive threshold was determined repeatedly 2 weeks after single administration. Each rat was administrated two times daily successively. Convulsive threshold was determined 0.5 hour before, and 0.5, 2.5, 7 and 12 hours after administration, separately. （4）Hepatic and renal tissues were harvested for pathological examination after 1 month of administration. （5）Nine healthy voluntary medical stuffs were recruited in this study. Written informed consents of experiment were obtained each involved subject. The study was given an approval by the Ethics Committee of Shanxi Medical University. According to the scheme, the 9 volunteers were randomly assigned into 3 groups, in which, volunteers were asked to take magnesium valproate 500 g, sustained-release magnesium valproate tablet 500 g and depakine chrono 500 g, respectively, in the morning under the condition of fasting. Serum drug concentration of each drug was determined by fluorescence polarization immunoassay at different time points. MAIN OUTCOME MEASURES： （2） Rat convulsive threshold after single and repeated administrations. （2）Hepatic and renal pathological examination results. （3） Serum drug concentration in vivo. RESULTS：（4）Rat convulsive threshold after single and repeated administrations： Drug efficacy in the magnesium valproate tablet group reached to a peak level 1 to 2 hours after single administration, and was obviously higher than that in the other groups 1 hour after administration （P 〈 0.05）. Drug efficacy in the sustained-release magnesium valproate tablet group and depakine chrono group both reached to a peak level 7 hours after administration, and was significantly higher than that in the control group （P 〈 0.05）. After repeated administrations, the average peak valley deviation of the convulsive threshold in the magnesium valproate tablet group was 120- 150 μ A, which was 2 and 2.5 times as that in the sustained-release magnesium valproate tablet group and depakine chrono group, respectively. After repeated administrations for 10 times, convulsive threshold was increased by 440 μ A in the sustained-release magnesium valproate tablet group, and by 230 μ A in the depakine chrono group in comparison with before administration. （2） Hepatic and renal pathological examination results： No obvious differences in hepatic and renal impairment were found among the 4 groups after I month of administration successively. （3） Serum drug concentration in vivo： Serum-drug concentration of magnesium valproate was increased fast and reached to a peak level 0.5 - 2 hours after administration, remained at a relatively stable level 2 - 4 hours after administration, and then was slowly decreased. The drug efficacy of sustained-release magnesium valproate tablet and depakine chrono was slowly released 1 - 6 hours after administration, reached to a peak level at about 7 hours, and could last for about 16 hours. CONCLUSION： Magnesium valproate has a rapid onset and offset of action. Sustained-release magnesium valproate tablet has a slow onset but long duration of drug efficacy. Depakine chrono can be easier to be absorbed than sustained-release magnesium valproate tablet, but its long-term effect on improving the convulsive threshold is inferior to sustained-release magnesium valproate tablet.

N-methyl-D-aspartate receptor subunit 1 protein expression in the hippocampus and temporal cortex of kainic acid-induced epilepsy rats

BACKGROUND： The N-methyl-D-aspartate receptor subunit 1 （NMDAR1） contributes to the incidence of epilepsy. However, the relationship between epilepsy-induced brain injury and NMDAR1 remains poorly understood. OBJECTIVE： To investigate changes in NMDAR1 protein expression in the hippocampus and temporal cortex of kainic acid-induced epilepsy rats. DESIGN, TIME AND SETFING： A randomized, controlled, animal experiment was performed at the Department of Physiology and Department of Pathology, Basic Medical College of Jilin University from March 2002 to March 2003. MATERIALS： Rabbit anti-NMDAR1 antibody was purchased from Wuhan Boster Biological Technology, China. METHODS： A total of 80 healthy, male, Wistar rats, aged 22 weeks, were randomly assigned to sham-surgery （n = 10） and model （n = 70） groups. Epilepsy models were established by injecting kainic acid （1μL） into the right amygdala, and rats were sacrificed at 2, 6, 24, 72 hours, and 7, 15, 30 days after surgery, with 10 animals at each time point. The rats in the sham-surgery group were injected with 1μL phosphate buffered saline into the right amygdala. MAIN OUTCOME MEASURES： NMDAR1 protein expression in the hippocampus and temporal cortex at 2, 6, 24, 72 hours and 7, 15, 30 days after epilepsy was detected using immunohistochemistry and flow cytometry analysis. RESULTS： In the sham-surgery group, a few NMDARl-positive cells were distributed in the hippocampus and temporal cortex. In the model group, NMDARl-positive cells were increased in the hippocampus and temporal cortex at 2 hours following kainic acid-induced epilepsy. They were significantly increased at 6 hours, and slightly decreased at 7 days （CA3 region and temporal cortex）, but remained greater than the sham-surgery group. This continued until day 30 （P 〈 0.01 ）. In addition, there were more NMDAR1 positive cells in the hippocampal CA3 and dentate gyrus than the temporal cortex （P 〈 0.01）. CONCLUSION： In epilepsy model rats, NMDAR1 protein expression was upregulated in the hippocampus and temporal cortex, and in particular in the hippocampal CA3 and dentate gyrus. NMDAR1 may participate in epilepsy and the excitation process of the epileptic brain.

Sudden cardiac arrest in a patient with epilepsy induced by chronic inflammation on the cerebral surface

The present study analyzed a patient with epilepsy due to chronic inflammation on the cerebral surface underwent sudden cardiac arrest. Paradoxical brain discharge, which occurred prior to epileptic seizures, induced a sudden cardiac arrest. However, when the focal brain pressure was relieved, cardiac arrest disappeared. A 27-year-old male patient underwent pre-surgical ram monitoring for 160 hours. During monitoring, secondary tonic-clonic seizures occurred five times. A burst of paradoxical brain discharges occurred at 2-19 seconds （mean 8 seconds） prior to epileptic seizures. After 2-3 seconds, sudden cardiac arrest occurred and lasted for 12-22 seconds （average 16 seconds）. The heart rate subsequently returned to a normal rate. Results revealed arachnoid pachymenia and adhesions, as well as mucus on the focal cerebral surface, combined with poor circulation and increased pressure, lntracranial electrodes were placed using surgical methods. Following removal of the arachnoid adhesions and mucus on the local cerebral surface, paradoxical brain discharge and epileptic seizures occurred three times, but sudden cardiac arrest was not recorded during 150-hour monitoring. Post-surgical histological examination indicated meningitis. Experimental findings suggested that paradoxical brain discharge led to cardiac arrest instead of epileptic seizures; the insult was associated with chronic inflammation on the cerebral surface, which subsequently led to hypertension and poor blood circulation in focal cerebral areas.

Risks of suicidality in adult patients with epilepsy

AIM: To determine the prevalence and risks of suicidality in a group of patients with epilepsy. METHODS: Included were 200 adult patients and 100 matched healthy subjects. The clinical interview using The Diagnostic and Statistical Manual of Mental Disorders(4th edition), Beck Depression Inventory(2nd edition)(BDI-Ⅱ), Hamilton Anxiety Rating Scale(HAM-A), Yale-Brown Obsessive Compulsive Scale(Y-BOCS) and Eysenck Personality Questionnaire-Revised Rating Scale testings were used for diagnosis and assessment of severity of psychiatric symptoms. Blood concentrations of serotonin, catecholamines and dopamine were also measured.RESULTS: Suicidality was reported in 35%(compared to 9% for controls), of them 80%, 72.86%, 55.71% and 52.9% had depression, anxiety, obsession and aggression respectively. Patients with suicidality had higher scores of BDI-Ⅱ(P = 0.0001), HAM-A(P = 0.0001), and Y-BOCS(P = 0.037) and lower scores of psychotic(P = 0.0001) and extroversion(P = 0.025) personality traits. Regardless the presence or absence of suicidality, patients with epilepsy had low serotonin(P = 0.006), noradrenaline(P = 0.019) and adrenaline(P = 0.0001) levels. With suicidality, significant correlations were identified between:(1) age and scores of BDI-Ⅱ(r = 0.235, P = 0.0001) and HAM-A(r = 0.241, P = 0.046);(2) age at onset and concentrations of noradrenaline(r =-0.502, P = 0.024);(3) duration of illness and scores of BDI-Ⅱ(r = 0.247, P = 0.041), Y-BOCS(r = 0.270, P = 0.025) and neurotic personality trait(r =-0.284, P = 0.018); and(4) doses of antiepileptic drugs and scores of psychotic personality traits(r =-0.495, P = 0.006 for carbamazepine; r =-0.508, P = 0.0001 for valproate).CONCLUSION: This is the first study which systematically estimated the prevalence and risks of suicidality in a homogenous group of patients with epilepsy. This study emphasizes the importance of epilepsy itself as a risk for suicidality and not its treatment.