癫痫大鼠海马神经元和星形胶质细胞的病理演变

目的　探讨癫痫大鼠海马神经元和星形胶质细胞在点燃后各期的病理特点、时序及机制。方法　针对匹罗卡品癫痫大鼠模型,行Nissl、免疫组化和HE染色,观察海马神经元及星形胶质细胞的病理变化。结果　癫痫持续状态后超急性期（4h）,CA3区神经元呈嗜酸性变性、胞浆深染;急性期（24h）,嗜酸性变性最为显著,神经元固缩、核仁消失、突起断裂,星形胶质细胞水肿;缄默期（7d）,CA3、CA1区及门区神经元大量坏死、脱失,胶质增生肥大,海马构筑紊乱;慢性期（6w）,CA3、CA1区出现胶质瘢痕,遗有形态正常的神经元,且颗粒细胞层增厚。结论　癫痫时海马神经元先于星形胶质细胞发生病理改变,二者均参与癫痫发生。     

戊四氮点燃慢性癫痫大鼠海马及颞叶皮质γ-氨基丁酸转运体1及胶质纤维酸性蛋白的表达

BACKGROUND： Gamma-aminobutyric acid transporter plays an important role in gamma-aminobutyric acid metabolism, and is highly associated with epilepsy seizures. Pathologically, astrocytes release active substances that alter neuronal excitability, and it has been demonstrated that astrocytes play a role in epileptic seizures. OBJECTIVE： To observe changes in gamma-aminobutyric acid transporter 1 and glial fibrillary acidic protein expression in the hippocampus and cortex of the temporal lobe in rats with pentylenetetrazol-induced chronic epilepsy. DESIGN, TIME AND SETTING： Randomized, controlled, animal experiment was performed at the Department of Neurobiology, Third Military University of Chinese PLA between January 2006 and December 2007. MATERIALS： Pentylenetetrazol was purchased from Sigma, USA; rabbit anti-rat gammaaminobutyric acid transporter 1 and glial fibrillary acidic protein were from Chemicon, USA. METHODS： A total of 40 Sprague Dawley rats were divided into model and control groups. Rat models of chronic epilepsy were created by pentylenetetrazol kindling, and were subdivided into 3-, 7-, and 14-day kindling subgroups. MAIN OUTCOME MEASURES： Gamma-aminobutyric acid transporter 1 and glial fibrillary acidic protein expression, as well as the number of positive cells in the hippocampus and cortex of temporal lobe of rats, were determined by immunohistochemistry and Western blot analyses. RESULTS： Compared with the control group, the number of gamma-aminobutyric acid transporter 1 and glial fibrillary acidic protein -positive cells in the hippocampus and cortex of rats with pentylenetetrazol-induced epilepsy significantly increased, gamma-aminobutyric acid transporter 1 and glial fibrillary acidic protein expression increased after 3 days of kindling, reached a peak on day 7, and remained at elevated levels at day 14 （P〈 0.05）. CONCLUSION： Astrocytic activation and gamma-aminobutyric acid transporter 1 overexpression may contribute to pentylenetetrazol-induced epilepsy.     

铁离子致创伤后癫痫大鼠模型海马胶质纤维酸性蛋白的动态表达

目的:观察创伤后癫痫大鼠模型海马区胶质纤维酸性蛋白的动态表达,探讨反应性胶质细胞增生在创伤后癫痫发病机制中的作用。方法:应用铁离子颅内注射制作创伤后癫痫模型,采用免疫荧光法染色观察海马各区胶质纤维酸性蛋白的表达。结果:7～15d胶质纤维酸性蛋白反应达高峰,注射侧海马CAl区锥体细胞层神经元大量脱失,30d胶质纤维酸性蛋白仍维持较高水平。结论:反应性胶质细胞增生可能与神经无异常放电环路形成有关,最终诱发创伤后癫痫,并成为慢性复发性癫痫的重要病理学基础。     

MDR-1和GFAP蛋白在难治性癫痫脑组织的表达

目的：观察不同病因的难治性癫痫手术切除脑组织中多药耐药基因蛋白（MDR-1）和胶质纤维酸性蛋白（GFAP）的表达。方法：在对22例难治性癫痫临床病理资料分析的基础上，应用免疫组化和免疫组化双标技术观察脑组织中MDR-1和GFAP蛋白的表达情况。结果：反应性胶质细胞增生是难治性癫痫共同的病理学特征。MDR-1蛋白的表达主要在一些增生性星形胶质细胞和毛细血管壁周围结构，而寡突胶质细胞、小胶质细胞及正常的神经元内无MDR-1蛋白的表达；增生性星形胶质细胞内MDR-1与GFAP具有共存现象。结论：在难治性癫痫的反应必脑胶质细胞内同时具有GFAP和MDR-1蛋白的高表达和共存。     

血清HIF-1α、GFAP表达与脑卒中后继发性癫痫的相关性

目的 探讨血清低氧诱导因子-1α(HIF-1α)、胶质纤维酸性蛋白(GFAP)表达与卒中后继发性癫痫的关系.方法 选取2018年5月至2020年5月芜湖市第五人民医院就诊的卒中后继发癫痫患者73例为癫痫组,卒中后未发生癫痫患者88例为非癫痫组.对比两组患者基础资料及血清HIF-1 α、GFAP水平差异,分析脑卒中继发癫...     

脑立体定向植入海马电极监测颞叶内侧癫痫的临床研究

目的 观察应用脑立体定向微创穿刺技术植入海马电极监测颞叶内侧癫痫的效果.方法 13例耐药性颞叶内侧癫痫患者,主要表现为复杂部分性癫痫发作及继发性全身强直阵挛性发作.根据临床症状、MRI等资料初步确定癫痫灶位于海马区域,在脑立体定向仪引导下于双侧海马植入8-触点深部电极,监测24 ～ 72 h,从而确认癫痫灶是否位于海马区域.结果 13例患者经过72 h监测,共监测到7例有29次临床发作,发作期脑电变化表现为在背景波形基础上出现阵发性高幅慢波或棘尖慢复合波,从某个电极点开始,迅速扩展到同侧其他电极点甚至对侧电极;头皮脑电在延迟1～2s后出现3～4 Hz的高幅δ节律.6例未监测到临床发作的患者,海马电极监测到发作性局灶性高幅慢波或尖慢综合波,而头皮电极未监测到明显异常.13例患者中6例接受选择性海马杏仁核切除或立体定向病灶损毁术,随访3～8个月,效果满意.结论 脑立体定向植入海马电极监测颞叶内侧癫痫是一种安全可靠的方法,可以判断癫痫病灶的起源,为外科进行选择性海马杏仁核切除提供有力依据,对于视频脑电图或其他手段难以记录到癫痫样波形或难以判断癫痫样放电起源的患者可进行脑立体定向深部电极脑电图监测.     

前颞叶切除术或选择性海马杏仁核切除术治疗顽固性内侧颞叶癫痫患者神经心理功能改变的研究

目的 探讨前颞叶切除术(ATL)或选择性海马杏仁核切除术(SAH)治疗顽固性内侧颞叶癫痫(MTLE)患者神经心理功能的改变情况。方法 选择2010年1月-2014年12月来本院接受ATL或SAH治疗的MTLE患者60例; 根据MTLE手术部位分为左颞部MTLE组(n=35)和右颞部MTLE组(n=25); 利用神经心理功能评分系统(DST、VMPT、WMSLM、WMS视觉、BNT、视觉技能、Stroop、WCST、分类、VFT)对患者术前及术后1年神经心理功能进行评分,比较2组患者左右颞部手术前后神经心理测试及手术前后左右颞部神经心理测试差异。结果 60例MTLE患者中35例(58.33%)左颞部MTLE,25例(41.67%)右颞部MTLE; 2组患者在性别、年龄、手术方式、癫痫发作平均年龄、病程、术前WAIS评分方面无显著性差异(P>0.05); 2组患者左右颞部手术前后神经心理测试比较显示,右颞部MTLE组术后在最大学习得分、短时记忆得分、长时记忆得分、第5卡片时间、矫正、转换错误方面与术前比较有显著差异(P<0.05); 左颞部MTLE组术后在合计得分方面与术前比较有显著差异(P<0.05); 2组患者手术前后左右颞部神经心理测试比较显示,左颞部MTLE组在回忆得分、识别得分、短时记忆得分方面显著高于右颞部MTLE组(P<0.05)。结论 尽管ATL或SAH治疗顽固性MTLE患者会引起部分常见的认知副作用,但该手术治疗也可提高患者部分认知功能。     

巢蛋白阳性星形胶质细胞与癫痫持续状态后海马区胶质瘢痕形成的相关性研究

目的 了解癩痫持续状态(SE)后7d海马各区巢蛋白(nestin)阳性星形胶质细胞表达及数目的变化,探讨其与SE导致海马区胶质瘢痕形成的关系.方法 SD大鼠随机分为SE组和对照组,应用匹罗卡品建立SE大鼠模型;在SE后7d处死大鼠行盲法免疫荧光组化实验,观察大鼠海马各区nestin与胶质纤维酸性蛋白单克隆抗体(GFAP...     

海马硬化致耐药性颞叶内侧癫痫的耐药基因蛋白表达及意义

目的 观察耐药性颞叶内侧癫痫硬化海马中有关耐药基因蛋白的表达并探讨其临床意义.方法 对经手术治疗取自16例颞叶内侧癫痫的硬化海马标本进行免疫组化染色观察p-糖蛋白170(p-gp170)、谷胱甘肽硫转移酶-π(GST-π)、拓扑酶Ⅱ(TOP Ⅱ)、胸苷合成酶(TS)及O-6-甲基鸟嘌呤-DNA-甲基转移酶(MGMT)的表达.结果 p-gp170和GST-π在硬化海马组织中神经细胞、血管内皮细胞及胶质细胞均有表达,而以血管内皮细胞和胶质细胞阳性表达尤为突出.TOP Ⅱ、TS和MGMG在硬化海马中无明显阳性表达.结论 长期应用抗癫痫药物可能诱导p-gp170和GST-π表达增强,促进抗癫痫药物的排出与代谢,引起耐药.TOPⅡ、TS和MGMG可能与癫痫耐药机制无关.     

星形胶质细胞、胶质纤维酸性蛋白和抑郁症的关系

对胶质细胞、胶质纤维酸性蛋白在心境障碍神经病理学发病机制中的作用进行综述。     

Outcome of surgical treatment in familial mesial temporal lobe epilepsy

PURPOSE: To describe postoperative outcome in patients with familial mesial temporal lobe epilepsy (FMTLE). METHODS: We studied FMTLE patients who underwent surgical treatment for refractory seizures. FMTLE was defined when at least two individuals in a family had a clinical EEG diagnosis of MTLE. Preoperative investigation included magnetic resonance imaging (MRI), interictal/ictal EEGs, and neuropsychological evaluation. We used Engel's classification for postoperative outcome. RESULTS: To date, 20 FMTLE patients have been operated on, with 1.6 to 9.8 years of follow-up (mean, 5.5 years). Hippocampal atrophy (HA) and other signs of mesial temporal sclerosis (MTS) were present in 18 patients (15 unilateral). Seizures were recorded in 19 patients. Seventeen (85%) patients are in class I. Two patients had normal hippocampal volumes (HcV): one (5%) is in class II and the other (5%) in class IV (extratemporal seizures developed after surgery). One (5%) patient had bilateral HA and is in class III. Qualitative histopathology showed MTS with different degrees of severity. CONCLUSIONS: Refractory FMTLE patients have good surgical outcome when unilateral or clearly asymmetric HA is identified. Preoperative investigation should be the same as that in patients with sporadic refractory MTLE.     

Neuropathological features of mesial temporal sclerosis: Histochemical studies of surgically resected specimens from patients with temporal lobe epilepsy

Mesial temporal sclerosis (MTS) is the most common pathological finding in temporal lobe epilepsy (TLE), but the relationship between MTS and hyperexcitability has not been defined. The neuropathological findings of MTS on the basis of our histochemical investigations using surgically resected specimens from patients with intractable TLE will be reviewed and discussed. Various sclerotic changes including neuronal loss and astrogliosis were observed not only in the hippocampus but also in the other mesial temporal structures such as the amygdala and entorhinal cortex. Moreover, aberrant residual pyramidal neurons were recognized, which showed morphological abnormalities; abnormal distribution of zinc, γ-aminobutyric acid-A receptor and glutamate decarboxy-lase; and disorganization of the granule cell layer (dispersion and bilaminar distribution). Increases in density of the corpora amylacea and peripheral type benzodiazepine receptor binding corresponded with glial proliferation. Histochemical studies demonstrated the association of mossy fiber sprouting with synaptic reorg-anization and changes of several chemically defined inter-neuron systems in the dentate gyrus. Quantitative analysis using in vitro autoradiography showed that neurotrans-mitter receptor bindings related to neuronal excitation (AMPA and NMDA receptor) and inhibition (central type benzodiazepine receptor) were reduced differently as a function of neuronal loss in MTS. These cytochemical changes associated with neurotransmitters and their receptors in the sclerotic hippocampus may constitute the pathological background of epileptogenesis in TLE.     

Association between APOE polymorphisms and mesial temporal lobe epilepsy with hippocampal sclerosis.

To evaluate the hypothetical link between apolipoprotein E (APOE) polymorphisms and mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) and whether presence of APOE epsilon4 allele shortens the latent period between febrile seizures and epilepsy. A further interest is whether presence of APOE epsilon4 allele has an impact on severity of the disease. Forty-seven patients with MTLE-HS were compared with 62 controls. APOE polymorphisms were determined from lymphocytes by standard methods. Eight patients (17%) and 10 controls (16.1%) were demonstrated to have one APOE epsilon4 allele. There was not any statistically significant difference in APOE epsilon4 frequency between patients and controls (P > 0.05). There was not any difference statistically according to onset age of epilepsy and the presence of APOE epsilon4 allele within patient group. APOE epsilon4 polymorphisms did not influence the severity of epilepsy. APOE epsilon4 polymorphisms had no impact on outcome after surgery. Patients with bilateral memory deficits, bilateral hippocampal atrophy and with bilateral epileptiform interictal EEG transients, were independently compared with patients having unilateral features and there were not any statistically significant differences. This study has found no association between APOE epsilon4 polymorphisms and presentation of MTLE-HS in a group of Turkish patients.     

Nonvisual spatial navigation fMRI lateralizes mesial temporal lobe epilepsy in a patient with congenital blindness

Nonvisual spatial navigation functional magnetic resonance imaging (fMRI) may help clinicians determine memory lateralization in blind individuals with refractory mesial temporal lobe epilepsy (MTLE). We report on an exceptional case of a congenitally blind woman with late-onset left MTLE undergoing presurgical memory fMRI. To activate mesial temporal structures despite the lack of visual memory, the patient was requested to recall familiar routes using nonvisual multisensory and verbal cues. Our findings demonstrate the diagnostic value of a nonvisual fMRI task to lateralize MTLE despite congenital blindness and may therefore contribute to the risk assessment for postsurgical amnesia in rare cases with refractory MTLE and accompanying congenital blindness.     

Prognostic factors in patients with mesial temporal lobe epilepsy

Purpose:   To disclose clinical, electrophysiologic, and neuroradiologic factors correlated to prognosis in patients with mesial temporal lobe epilepsy (MTLE).
Methods:   One hundred thirty-six MTLE patients were studied for family history, clinical characteristics, instrumental data [electroencephalography (EEG), video-EEG, neuroimaging], and outcome. The population was divided into drug-resistant (DR: 108 patients, 79.4%) and non–drug-resistant (NDR: 28 patients, 20.6%) groups; all variables were analyzed in the two groups.
Results:   The comparison between the two groups shows a relation between resistance to therapy and febrile seizures (FS) (DR 43.5% vs. NDR 17.8%, p = 0.008), mesial temporal sclerosis (MTS) (DR 64.8% vs. NDR 32.1%, p = 0.0025), early age at seizure onset (DR 23.1% vs. NDR 3.6% p = 0.0160), and epileptiform interictal abnormalities (DR 89.7% vs. NDR 68%, p = 0.010). FS were more frequent in patients with MTS than in patients without (46.28% vs. 26.3%, p = 0.0199). Sixty-nine patients underwent surgery and 85.3% of them had a good outcome.
Conclusion:   MTLE is a heterogeneous syndrome. Establishing the factors responsible for and associated with drug resistance is important for therapeutic purposes, as prompt diagnosis of drug resistance must lead to early surgical management. This study shows that FS, MTS, early age at seizure onset, and epileptiform interictal abnormalities are negative prognostic factors and that FS are related to MTS.     

耐药性颞叶内侧癫痫发作前期海马脑电特征分析

目的 观察耐药性颞叶内侧癫痫患者发作前期海马电极脑电活动特点,为判断和切除癫痫病灶提供神经电生理学依据.方法 对16例非侵入性手段难以明确病灶的耐药性颞叶内侧癫痫患者进行双侧海马电极监测,患者停用抗癫痫药在非麻醉状态下监测48～72 h,分析癫痫发作前期海马电极脑电图资料,探讨耐药性颞叶内侧癫痫发作前期海马电极脑电活动特点.结果 16例发作间期记录到背景活动基础上出现局限于某几个电极点的阵发性高幅慢波1例、发作性快波节律1例、棘波或棘尖慢复合波14例,视为异常脑电活动;经过48～ 72 h监测,10例监测到33次临床癫痫发作,发作起始期海马电极均可记录到清晰可辨的癫痫样脑电波形.结论 颞叶内侧癫痫临床发作起始期海马电极癫痫样放电清晰可辨,部位局限,易于确定癫痫性活动起源部位.对于非侵入性手段难以判断癫痫样放电起源的颞叶内侧癫痫可采用脑立体定向技术植入海马深部电极进行脑电监测.     

Prognostic factors in the surgical treatment of medically intractable epilepsy associated with mesial temporal sclerosis

OBJECTIVES: To assess the prognostic factors determining seizure remission after temporal lobectomy for intractable epilepsy associated with mesial temporal sclerosis (MTS) at pathology. METHODS: The clinical and investigative features of 116 consecutive patients who had temporal lobe surgery for drug-resistant epilepsy and MTS at pathology were assessed using actuarial statistics and logistic regression analysis. RESULTS: At a median follow-up of 63 months the probability of achieving at least a 1-year period of continuous seizure freedom was 67%. Factors contributing to a favourable outcome were interictal EEG localization to the operated lobe and the absence of secondarily generalized seizures. These were also selected in the multivariate analysis, although at lower statistical significance (P=0.08 and 0.09, respectively). Perinatal complications were associated with a significantly worse outcome but overall, complicated febrile convulsions and congruent neuropsychological deficits were not significantly predictive variables. CONCLUSIONS: The present findings may aid in the non-invasive presurgical assessment of patients with intractable TLE and clinical and neuroimaging evidence of MTS.     

Memory in patients with drug-responsive mesial temporal lobe epilepsy and hippocampal sclerosis

PURPOSE: Mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS) is the most common of the antiepileptic drug (AED)-resistant seizure syndromes that are remediable mostly with surgery, although a small group of patients have benign prognosis with fewer seizures. Material-specific memory impairment is an important feature in these patients and may be related to both the structural abnormality and the frequent seizures. In this study, we investigated the relation between memory deficit and HS by taking seizure frequency into account. METHODS: The patients were evaluated according to a standard protocol and divided into two groups, considering their response to AEDs: the good-responder group (GRg, n = 18) and the pharmacoresistant group (PRg, n = 95). They were administered a neuropsychological test battery that included verbal and nonverbal memory tests, compared with each other and with a normal control group (n = 29). The responder group was evaluated by the same battery once again (mean, 23 months; SD, 8.25; range, 14-38 months). RESULTS: Both GR and PR patient groups had poorer memory than the normal controls in all memory tests (p < 0.05). However, the comparison of GRg with PRg revealed that only the digit-span test was significantly worse in PRg (p = 0.0061), and no difference was found in any other memory scores. The reevaluation of the GRg showed no significant difference between the first and second evaluation. CONCLUSIONS: We concluded that the memory impairment in patients with MTLE-HS was permanent and might be related to the direct effect of HS itself. Therefore patients with good response to AEDs can be used as a model for investigating the memory problems in patients with MTLE-HS.