癫痫发作间期alpha波的窄带相位同步分析

神经元同步化放电是癫痫发作的一个重要特征,作者提出并运用窄带相位同步技术对比分析了54个癫痫病人和10个正常成年人的脑电信号(EEG)数据.结果表明,相对于对照组,癫痫组的Alpha波的平均窄带相位同步值有显著下降(P=0.02058).为了更准确地刻画和衡量癫痫组和其对照组在同步模式上的差异,提出了一个新的具体的量化指标,即alpha波的窄带相位同步发散率.分析结果显示,对照组的窄带相位同步发散率明显低于癫痫组(P=0.003060),说明对照组的alpha波振子间互诱导强度更高.这可能反映了癫痫组窄带相位同步发散率的升高及所代表的alpha振子间互诱导强度的减弱与患者在癫痫发作间期的状态有密切的联系.     

左旋组氨酸对匹罗卡品致痫大鼠癫痫发作和海马区神经细胞凋亡的影响

目的:观察左旋组氨酸(L-His)对匹罗卡品(PLO)致痫大鼠皮质脑电图及大鼠海马各区神经细胞凋亡的影响。方法:雄性SD大鼠30只,随机平均分为对照组(匹罗卡品组)、干预组(匹罗卡品+左旋组氨酸组)。各组给予相关干预处理后腹腔注射匹罗卡品建立癫痫模型,行皮质脑电图观察及海马区细胞凋亡染色观察。结果:经皮质脑电图显示,干预组潜伏期延长、痫波频率及大发作次数较对照组明显降低,差异有统计学意义(P<0.05)。凋亡染色显示,对照组的海马各区细胞在各时间点的凋亡数明显高于干预组,差异具有统计学意义(P<0.05)。结论:左旋组氨酸可以延迟匹罗卡品致痫的形成并降低点燃后癫痫发作程度,降低海马各区细胞凋亡数值,提示左旋组氨酸具有抗痫作用。     

Effect of penicillin G-induced epileptic seizures on hemorheological parameters in rats

Normally, cerebral blood flow (CBF) is quantitatively coupled to cerebral metabolic rate like other tissues and maintained basically by altering vascular geometry and appropriate perfusion pressure. However, the rheological properties of the blood are important factors for effective tissue perfusion. Although a lot of studies have reported that hemorheological parameters are affected by a wide range of pathophysiological conditions, to our knowledge no research related to the effects of epileptic seizures on hemorheological parameters has been carried out. Thus, the aim of this study was to explore possible changes in rheological parameters including red blood cell (RBC) deformability, rigidity and aggregation, whole blood and plasma viscosity during epileptic seizures induced by penicillin G in rats. Eighteen female albino rats were divided into three groups that included sham operated controls (Group S), epileptic group (Group E), intraperitoneal penicillin group (Group IPP). Epilepsy was induced by intracortical injections of penicillin G. Hemorheological studies had been carried out 3 h after the induction of epilepsy. Among the studied hemorheological parameters, only RBC deformability was found to be different in the E group compared to S group. Epileptic seizures led to an increase in RBC deformability in the E group. In conclusion, these results suggest that in addition to an increase in CBF, RBC deformability may also improve to better match brain metabolic demands during seizures.     

Increased plasma glutamic acid in a genetic model of epilepsy

A significant increase in the plasma levels of glutamic acid and a significant decrease in aspartic acid and taurine in epileptic patients and their first degree relatives was reported more than a decade ago and an underlying genetic basis for these amino acid changes was suggested. The main objective of the present study was to determine the plasma levels of glutamic acid, aspartic acid and taurine in El mice which are an inbred epileptic mutant mouse strain. The results show a significant increase in plasma glutamic acid but no changes in aspartic acid or taurine in the epileptic mice as compared to controls. The data provide the first evidence of a significant increase in plasma glutamic acid in an animal model of hereditary epilepsy and substantiate the hypothesis that a genetic defect underlies the elevated plasma glutamic acid levels in association with epilepsy. The findings are also compatible with neurochemical and neurophysiological evidence implicating glutamic acid in the mechanism of seizures.     

Quantification of chloride channel 2 (CLCN2) gene isoforms in normal versus lesion- and epilepsy-associated brain tissue

The chloride channel 2 (CLCN2) gene codes for a protein organized in N- and C-terminal regions with regulatory functions and a transmembrane region which forms the ring of the pore. Mutations in the gene have previously been described in patients with idiopathic familial epilepsy. In this study we looked for new isoforms of CLCN2 and we estimated expression levels by real time PCR in brain tissue containing epileptic foci. Samples used in this study were first analyzed and selected to exclude mutations in the coding region of the gene. Four isoforms (skipping exons 3, 16, 22 and 6/7) were identified and quantified by Real Time PCR and compared with total expression of the gene. Expression of the region common to all CLCN2 isoforms was 50% less in epilepsy-associated brain tissue than in controls. The ratio of the various isoforms was slightly greater in epileptic than control tissue. The greatest difference was recorded in the temporal lobe for the isoform with skipped exon 22. Analysis of these isoforms in brain tissue containing epileptic foci suggests that CLCN2 could be implicated in epilepsy, even in the absence of mutations.     

Up-regulation of apelin in brain tissue of patients with epilepsy and an epileptic rat model

Prolonged epileptic seizures or SE can cause neuronal cell death. However, the exact role of neuroprotectant against brain injury during epileptic seizure needs to be further elucidated. The aim of this study was to investigate the expression of the apelin, a novel neuroprotective peptide, in brain tissues of the patients with temporal lobe epilepsy (TLE) and experimental rats using immunohistochemistry, immunofluorescence and Western blotting analysis and to discuss the possible role of apelin in TLE. Thirty temporal neocortical tissue samples from the patients with drug-refractory TLE underwent surgical therapy and nine histologically normal temporal lobes tissues as controls were used in our study. Fifty-six Sprague-Dawley rats were randomly divided into seven groups, including one control group and six groups with epilepsy induced by lithium-pilocarpine. Hippocampus and adjacent cortex were taken from the controls and epileptic rats at 1, 3, 7, 14, 30, and 60 days after onset of seizures. Apelin was mainly expressed in the neurons of TLE patients and controls, and was significantly increased in TLE patients compared with the controls. Apelin was also expressed in the neurons of experimental and control rats, it was gradually increased in the experimental rat post-seizure and reached a stable high level in chronic epileptic phase. Our results demonstrated that the increased expression of apelin in the brain may be involved in human TLE.     

Common ABCB1 polymorphisms associated with susceptibility to infantile spasms in the Chinese Han population

Infantile spasms are a severe epileptic encephalopathy with a variety of etiologies that occur in infancy and early childhood. Subjects with infantile spasms are at a higher risk for evolving into intractable epileptic spasms, tending to be refractory to conventional antiepileptic drugs. Genetic polymorphisms of the P-glycoprotein-encoding gene ABCB1 are suspected to be associated with pharmacoresistance phenotypes in epilepsy patients. Conflicting findings have been reported in different populations; few studies have explored whether this apparent association is affected by other host factors, such as specific epilepsy syndrome. We performed a case-control study to determine whether the risk of infantile spasms is influenced by common ABCB1 polymorphisms in a Han Chinese children's population consisting of 91 patients and 368 healthy individuals. DNA was isolated from whole blood, and three genetic polymorphisms (C1236T, G2677T/A, and C3435T) were assayed by PCR-RFLP. There were significant differences in the distributions of 3435TT [P = 0.001; odds ratio = 2.47; 95% confidence interval (CI) = 1.44-4.27] and 3435CT [P < 0.001; odds ratio = 0.28; 95% CI = 0.15-0.54] genotypes between infantile spasm cases and controls. No significant differences were observed in allelic and haplotypic frequencies of ABCB1 polymorphisms between the two groups. This study demonstrated that variations in the C3435T gene play an important role in the pathogenesis of infantile spasms in the Han Chinese population; 3435TT is associated with increased risk of having this epilepsy syndrome.     

注射用丹参多酚酸盐联合丙戊酸钠治疗脑卒中后癫痫患者的疗效分析

目的:研究注射用丹参多酚酸盐联合丙戊酸钠对脑卒中后癫痫的临床疗效和安全性。方法:选择2016年1月～2019年4月东南大学附属中大医院江北院区神经内科住院的80例脑卒中后癫痫患者,将其随机分为两组。对照组的40例患者仅给予丙戊酸钠治疗,观察组的40例患者给予丹参多酚酸盐联合丙戊酸钠治疗。比较两组治疗后的脑电图检查结果、癫痫症状控制情况。结果:治疗后,观察组总有效率为明显高于对照组(97.50%vs. 80%,P0.05);两组的累及导联数、痫样放电、发作持续时间、发作次数较治疗前以及血清神经元特异性烯醇化酶(Neuron specific enolase,NSE)水平均较治疗前明显降低(P0.05),且观察组以上指标均明显低于对照组(P0.05)。两组的嗜睡、皮疹、头痛、感觉异常、恶心呕吐的发生率比较差异无明显统计学意义(P0.05)。结论:注射用丹参多酚酸盐联合丙戊酸钠治疗脑卒中后癫痫的疗效明显优于单用丙戊酸钠治疗,其可更有效控制癫痫症状,且安全性较高。     

Blood groups in the species survival plan®, European endangered species program,and managed in situ populations of bonobo (Pan paniscus), common chimpanzee (Pan troglodytes), gorilla (Gorilla ssp.), and orangutan (Pongo pygmaeus ssp.)

Blood groups of humans and great apes have long been considered similar, although they are not interchangeable between species. In this study, human monoclonal antibody technology was used to assign human ABO blood groups to whole blood samples from great apes housed in North American and European zoos and in situ managed populations, as a practical means to assist blood transfusion situations for these species. From a subset of each of the species (bonobo, common chimpanzee, gorilla, and orangutans), DNA sequence analysis was performed to determine blood group genotype. Bonobo and common chimpanzee populations were predominantly group A, which concurred with historic literature and was confirmed by genotyping. In agreement with historic literature, a smaller number of the common chimpanzees sampled were group O, although this O blood group was more often present in wild‐origin animals as compared with zoo‐born animals. Gorilla blood groups were inconclusive by monoclonal antibody techniques, and genetic studies were inconsistent with any known human blood group. As the genus and, specifically, the Bornean species, orangutans were identified with all human blood groups, including O, which had not been reported previously. Following this study, it was concluded that blood groups of bonobo, common chimpanzees, and some orangutans can be reliably assessed by human monoclonal antibody technology. However, this technique was not reliable for gorilla or orangutans other than those with blood group A. Even in those species with reliable blood group detection, blood transfusion preparation must include cross‐matching to minimize adverse reactions for the patient. Zoo Biol 30:427–444, 2011. © 2010 Wiley‐Liss, Inc.     

Patient-Specific Detection of Cerebral Blood Flow Alterations as Assessed by Arterial Spin Labeling in Drug-Resistant Epileptic Patients

Electrophysiological and hemodynamic data can be integrated to accurately and precisely identify the generators of abnormal electrical activity in drug-resistant focal epilepsy. Arterial Spin Labeling (ASL), a magnetic resonance imaging (MRI) technique for quantitative noninvasive measurement of cerebral blood flow (CBF), can provide a direct measure of variations in cerebral perfusion associated with the epileptic focus. In this study, we aimed to confirm the ASL diagnostic value in the identification of the epileptogenic zone, as compared to electrical source imaging (ESI) results, and to apply a template-based approach to depict statistically significant CBF alterations. Standard video-electroencephalography (EEG), high-density EEG, and ASL were performed to identify clinical seizure semiology and noninvasively localize the epileptic focus in 12 drug-resistant focal epilepsy patients. The same ASL protocol was applied to a control group of 17 healthy volunteers from which a normal perfusion template was constructed using a mixed-effect approach. CBF maps of each patient were then statistically compared to the reference template to identify perfusion alterations. Significant hypo- and hyperperfused areas were identified in all cases, showing good agreement between ASL and ESI results. Interictal hypoperfusion was observed at the site of the seizure in 10/12 patients and early postictal hyperperfusion in 2/12. The epileptic focus was correctly identified within the surgical resection margins in the 5 patients who underwent lobectomy, all of which had good postsurgical outcomes. The combined use of ESI and ASL can aid in the noninvasive evaluation of drug-resistant epileptic patients.     

The Search for New Screening Models of Pharmacoresistant Epilepsy: Is Induction of Acute Seizures in Epileptic Rodents a Suitable Approach?

Epilepsy, a prevalent neurological disease characterized by spontaneous recurrent seizures (SRS), is often refractory to treatment with anti-seizure drugs (ASDs), so that more effective ASDs are urgently needed. For this purpose, it would be important to develop, validate, and implement new animal models of pharmacoresistant epilepsy into drug discovery. Several chronic animal models with difficult-to-treat SRS do exist; however, most of these models are not suited for drug screening, because drug testing on SRS necessitates laborious video-EEG seizure monitoring. More recently, it was proposed that, instead of monitoring SRS, chemical or electrical induction of acute seizures in epileptic rodents may be used as a surrogate for testing the efficacy of novel ASDs against refractory SRS. Indeed, several ASDs were shown to lose their efficacy on acute seizures, when such seizures were induced by pentylenetetrazole (PTZ) in epileptic rather than nonepileptic rats, whereas this was not observed when using the maximal electroshock seizure test. Subsequent studies confirmed the loss of anti-seizure efficacy of valproate against PTZ-induced seizures in epileptic mice, but several other ASDs were more potent against PTZ in epileptic than nonepileptic mice. This was also observed when using the 6-Hz model of partial seizures in epileptic mice, in which the potency of levetiracetam, in particular, was markedly increased compared to nonepileptic animals. Overall, these observations suggest that performing acute seizure tests in epileptic rodents provides valuable information on the pharmacological profile of ASDs, in particular those with mechanisms inherent to disease-induced brain alterations. However, it appears that further work is needed to define optimal approaches for acute seizure induction and generation of epileptic/drug refractory animals that would permit reliable screening of new ASDs with improved potential to provide seizure control in patients with pharmacoresistant epilepsy.     

拉莫三嗪与丙戊酸钠治疗癫痫合并抑郁障碍患者的疗效比较

目的:探讨拉莫三嗪和丙戊酸钠治疗癫痫合并抑郁障碍的疗效,为其临床治疗提供依据。方法:选择2011年2月~2015年2月在我院接受治疗的癫痫合并抑郁障碍患者60例,根据随机数字表法将患者分为观察组(30例)和对照组(30例),观察组给予拉莫三嗪治疗,对照组给予丙戊酸钠治疗,于治疗前、治疗后8周末和16周末采用HAMD-17和MADRS量表进行评分,并比较两组患者的临床疗效和不良反应。结果:治疗8周末和16周末两组患者的HAMD-17和MADRS量表评分较治疗前均降低,且观察组降低幅度大于对照组,差异均有统计学意义(P0.05)。治疗16周末观察组患者的总有效率为86.67%显著高于对照组的63.33%,差异有统计学意义(P0.05)。两组患者的不良反应主要为皮疹、嗜睡、恶心呕吐等,发生率低,差异无统计学意义(P0.05)。结论:拉莫三嗪和丙戊酸钠均可改善抑郁状态,但拉莫三嗪的疗效优于丙戊酸钠,且不会增加患者不良反应,值得临床推广应用。     

Role of a Neural Cell Adhesion Molecule Found in Cerebrospinal Fluid as a Potential Biomarker for Epilepsy

The neural cell adhesion molecule (NCAM-1) plays an important role in cell adhesion and synaptic plasticity. We designed this study to evaluate NCAM-1 as a potential biomarker for epilepsy. We performed a quantitative evaluation of the levels of NCAM-1 in cerebrospinal fluid (CSF) and serum and noted differences in patients with epilepsy compared to control subjects. We used sandwich enzyme-linked immunosorbent assays to measure NCAM-1 concentrations in CSF and serum samples of 76 epileptic patients (subdivided into the following subgroups: drug-refractory epilepsy, DRE; first-diagnosis epilepsy, FDE; and drug-effective epilepsy, DEE) and 44 control subjects. Our results show that cerebrospinal fluid–NCAM-1 (CSF–NCAM-1) concentrations and NCAM-1 Indices in the epileptic group were lower than in the control group. Both the CSF–NCAM-1 concentration and the NCAM-1 Indices in the drug-refractory epilepsy group were lower than in the drug-effective epilepsy group. These differences were statistically significant (P < 0.05). However, serum–NCAM-1 levels were not statistically different when comparing the epilepsy group to the control group (P > 0.05). Our results indicate that CSF–NCAM-1 is a potential biomarker for drug-effective epilepsy and drug-refractory epilepsy.     

Time-dependent changes in the serum levels of prolactin, nesfatin-1 and ghrelin as a marker of epileptic attacks young male patients

A relationship between hormones and seizures has been reported in animals and humans. Therefore, the purpose of this study was to investigate the association between serum levels of prolactin, nesfatin-1 and ghrelin measured different times after a seizure or non-epileptic event and compared with controls. The study included a total of 70 subjects, and of whom 18 patients had secondary generalized epilepsy (SGE), 16 patients had primary generalized epilepsy (PGE), 16 patients exhibited paroxysmal event (psychogenic) and 20 healthy males were control subjects. The first sample was taken within 5 min of a seizure, with further samples taken after 1, 24, and 48 h so long as the patient did not exhibit further clinically observable seizures; blood samples were taken once from control subjects. Prolactin was measured immediately using TOSOH Bioscience hormone assays. Nesfatin-1 and ghrelin peptides were measured using a commercial immunoassay kit. Patients suffering from focal epilepsy with secondary generalization and primary generalized epilepsy presented with significantly higher levels of serum prolactin and nesfatin-1 and lower ghrelin levels 5 min, 1 and 24 h after a seizure than patients presenting with paroxysmal events (psychogenic) and control subjects; the data were similar but not statistically significant after 48 h. The present study suggests that increased serum prolactin and nesfatin-1 concentrations, decreased ghrelin concentrations could be used as markers to identify patients that have suffered a recent epileptic seizure or other paroxysmal event (psychogenic).     

Genetic dispersion analysis of the relationship of epilepsy to anomalies in brain bioelectrical activity

Estimation of genetic and environmental components of phenotypical dispersion of paroxysmal and nonparoxysmal EEG abnormalities in epilepsy (118 probands and 179 relatives) in two phenotypical model frames has been obtained. The alternative phenotypical model was shown to be more adequate than quasicontinual for EEG abnormalities, and the part of additive genetic component (GA) comprises 15.7% for paroxysmal abnormalities and 49.4% for nonparoxysmal type. In the component type "belonging to one generation" joint influence of genetic and environmental factors on the process of forming EEG abnormalities in ontogeny was observed. The GA value for "epilepsy manifestation" symptom equal to 72.9% in general selection of probands increases to 97.4% in the subgroup of patients with nonparoxysmal abnormalities and 67.4% in the subgroup of patients with paroxysmal EEG abnormalities. It has been suggested that paroxysmal EEG abnormalities reflect their own epileptic process, and as far as nonparoxysmal abnormalities are concerned, they present phenotypical manifestation of the genetic system of predisposition to epilepsy.     

唑尼沙胺单药治疗儿童癫痫疗效及骨代谢的影响

目的:探讨唑尼沙胺(Zonisamide ZNS)对儿童癫痫疗效及骨代谢的影响。方法:选择2013年3月至2014年3月到河北省儿童医院神经内科门诊及病房就诊的新诊断癫痫患儿,其中男性36名,女性24名,年龄在2-14岁,给予唑尼沙胺单药治疗,分别于服药前、服药后6月查血甲状旁腺素、血钙、磷、碱性磷酸酶和骨密度测定,并与对照组进行对比。对照组选择就诊于儿保科年龄、性别相匹配的正常儿童。并分析癫痫患儿发作频率及严重程度,评估疗效。结果:唑尼沙胺治疗53例癫痫患儿中,42例(79.2)无发作,8例(15%)有效,3例(5.7%)无效。且对骨代谢相关血清学指标、骨密度无明显影响。结论:ZNS对儿童癫痫有显著疗效,是一种广谱、耐受良好的抗癫痫药。     

TBC1D24, an ARF6-Interacting Protein, Is Mutated in Familial Infantile Myoclonic Epilepsy

Idiopathic epilepsies (IEs) are a group of disorders characterized by recurrent seizures in the absence of detectable brain lesions or metabolic abnormalities. IEs include common disorders with a complex mode of inheritance and rare Mendelian traits suggesting the occurrence of several alleles with variable penetrance. We previously described a large family with a recessive form of idiopathic epilepsy, named familial infantile myoclonic epilepsy (FIME), and mapped the disease locus on chromosome 16p13.3 by linkage analysis. In the present study, we found that two compound heterozygous missense mutations (D147H and A509V) in TBC1D24, a gene of unknown function, are responsible for FIME. In situ hybridization analysis revealed that Tbc1d24 is mainly expressed at the level of the cerebral cortex and the hippocampus. By coimmunoprecipitation assay we found that TBC1D24 binds ARF6, a Ras-related family of small GTPases regulating exo-endocytosis dynamics. The main recognized function of ARF6 in the nervous system is the regulation of dendritic branching, spine formation, and axonal extension. TBC1D24 overexpression resulted in a significant increase in neurite length and arborization and the FIME mutations significantly reverted this phenotype. In this study we identified a gene mutation involved in autosomal-recessive idiopathic epilepsy, unveiled the involvement of ARF6-dependent molecular pathway in brain hyperexcitability and seizures, and confirmed the emerging role of subtle cytoarchitectural alterations in the etiology of this group of common epileptic disorders.     

Upregulated P2X3 Receptor Expression in Patients with Intractable Temporal Lobe Epilepsy and in a Rat Model of Epilepsy

Purinergic P2X3 receptors (P2X3Rs) play extensive roles in nerve cells in the central nervous system, particularly in hyperexcitability and calcium (Ca²⁺) influx. However, the role of P2X3Rs in epilepsy has not been previously investigated. To determine the relationship between P2X3Rs and epilepsy, the expression and cellular location of P2X3Rs in patients with intractable temporal lobe epilepsy (TLE) and in a lithium chloride-pilocarpine-induced chronic rat model of epilepsy were assessed. Furthermore, the function of P2X3Rs was assessed in vitro. Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis were used to evaluate the expression levels of P2X3Rs in brain tissues from TLE patients and an epileptic rat model, whereas immunofluorescence labeling was applied to determine the distribution of target proteins. Whole-cell recording was subsequently performed to identify the influence of P2X3Rs on seizure-like discharges. P2X3Rs were located at the cell bodies and dendrites of neurons with significantly increased expression in the TLE patients and epileptic rat model. In vitro, P2X3R activation accelerated sustained repetitive firing, whereas P2X3R inhibition led to relatively low-frequency discharges. To the best of our knowledge, this is the first study provide evidence that upregulated P2X3R expression exists in both epileptic humans and rats and may aggravate the epileptic state in vitro. Thus, P2X3Rs may represent a novel therapeutic target for antiepileptic drugs.     

Neuroprotective action of FK-506 (tacrolimus) after seizures induced with pilocarpine: quantitative and topographic elemental analysis of brain tissue

In the present work, X-ray fluorescence microscopy with a synchrotron source for the exciting radiation was applied for topographic and quantitative elemental analysis of rat brain tissue in pilocarpine-induced epilepsy and neuroprotection with FK-506. The mass per unit area of the elements P, S, Cl, K, Ca, Fe, Cu, Zn, Se, Br, and Rb was determined in four fields of the hippocampal formation (sectors 1 and 3 of Ammon’s horn–CA1, CA3; dentate gyrus; hilus of dentate gyrus) and the parietal cortex. The results obtained for epileptic rats treated with FK-506 (SNF) were compared with data obtained previously for epileptic rats (SNS) and a control group. Many statistically significant differences in elemental composition were observed between the SNF and SNS groups. Higher mass per unit area of P was noticed in CA1 and CA3 regions of the hippocampus of SNF rats in comparison with SNS rats. A similar relation was observed for K in all five brain areas analyzed. Also, Fe in CA3 and dentate gyrus, Cu in the parietal cortex, and Zn in CA3 and in the cortex were present at a higher level in the SNF group in comparison with the SNS group. The findings obtained in the present study suggest that the neuroprotective action of FK-506 in epileptic rat brain may involve not only the inhibition of calcineurin but also blockade of the K⁺ channels.     

Relationship Between GABA Concentrations in Cerebrospinal Fluid and Seizure Excitability

Abstract: Various studies suggest that alterations in GABAergic function may be connected to epileptic seizures. Low CSF GABA levels have been reported in epilepsy and also febrile convulsions of children. In this study the pentet-razole seizure threshold of dogs was compared with the concentration of GABA in the CSF and blood plasma. A highly significant positive correlation was found between seizure excitability and CSF GABA level, but not between CSF and plasma GABA concentrations.