构建海人酸诱导的内侧颞叶癫痫小鼠模型

目的 建立C57BL/6颞叶癫痫小鼠模型,观察其在行为学和病理学上的变化.方法 将C57BL/6小鼠随机分为空白对照组、0.9%氯化钠注射组(35μL/g)和海人酸注射组(12 mg/kg),进行单侧海马注射.注射5 d或5周后,取小鼠脑进行HE染色,观察海马病理结构改变;检测海马组织中mTOR通路标志物P-S6蛋白质...     

颞叶内侧癫痫患者记忆损害研究进展

认知障碍在癫痫患者中是常见的现象,癫痫的群体化研究表明癫痫患者的认知障碍高达30％～40％,及时诊断和治疗有助手减少其对患者生活质量的影响。     

海马电刺激治疗难治性颞叶癫痫的机制

大多数颞叶癫痫（TLE）是药物耐受性的难治性癫痫。对于药物控制不好又不适宜手术的TLE患者来说，脑的深部海马电刺激（hippocampus electrical stimulation，HES）是一种可供选择的有效的治疗手段。癫痫动物模型及人体临床实验均发现HES可显著减少癫痫发作频率或使发作间期棘波数量减少。其产生抗癫痫作用的机制可能是电极周围神经元被抑制的结果，也可能是抑制性神经递质释放的结果，或是多种机制的协同作用。本文就此作一综述。     

伴海马硬化的颞叶癫痫发作期心动过缓及心脏停搏1例

心率改变是颞叶内侧癫痫发作期的重要变化。曾有研究显示64％～100％的颞叶癫痫发作伴随心动过速,而心动过缓发生较少,仅在〈6％部分性发作期可出现,主要在颞叶癫痫发作出现,额叶癫痫发作也可出现。在大的癫痫中心进行视频脑电图（V-EEG）监测的患者中仅有0．1％～0．4％出现发作期心脏停搏。发作期心动过缓或心脏停搏可能是癫痫发作所致猝死（SUDEP）的重要因素,应引起高度重视。我中心监测到1例伴海马硬化的颞叶癫痫的发作期心动过缓及心脏停搏现象,现将其特点报告如下。     

IL-1β和NF-κB在慢性内侧颞叶癫痫模型中的相互作用

目的:观察白介素1β(IL-1β)与核因子-κB(NF-κB)在大鼠内侧颞叶癫痫(mesial temporal lobe epilepsy,MTLE)模型中的表达变化;体外培养的星形胶质细胞经IL-1β和吡咯烷二硫氨基甲酸(PDTC)预处理后,观察其增殖和NF-κB表达变化。方法:利用匹罗卡品诱导SD大鼠发作癫痫制成MTLE模型,根据自发发作出现和稳定时间分为急性期对照组(AC,制模后2 h)、急性期癫痫组(AS)、潜伏期对照组(LC,制模后3周)、潜伏期癫痫组(LS)、慢性期对照组(CC,制模后8周)和慢性期癫痫组(CS)。体外培养的星形胶质细胞分为对照组、IL组和PDTC+IL组,利用凝胶迁移电泳(EMSA)、免疫印迹(WB)、酶联免疫吸附(ELISA)和免疫组织化学(IHC)的方法观察IL-1β和NF-κB的表达变化;MTT检测星形胶质细胞的增殖活化程度。结果:匹罗卡品诱导的MTLE模型大鼠海马内IL-1β和NF-κB在急性期、潜伏期和慢性期表达均增加,但以急性期和慢性期明显;IL-1β可以促进体外培养的星形胶质细胞增殖、上调星形胶质细胞内NF-κB的表达,而PDTC可以明显抑制IL-1β的上述作用。结论:IL-1β通过NF-κB促进大鼠星形胶质细胞的活化增殖,这一改变可能与MTLE发病密切相关,探讨其机制可能为MTLE的治疗提供新的靶点。     

海人酸诱导成年大鼠颞叶癫痫中海马异常神经发生机制研究进展

神经发生(neurogenesis)是指神经干细胞(neural stem cells,NSCs)或神经前体细胞(neural precursor cells,NPCs)的增殖、分化以及新生神经元的存活、成熟和迁移整合的过程.实验证实~([1]),成年动物及人类的室管膜与室管膜下区、嗅球、海马、中隔、纹状体及皮质与脊髓广泛分布有多潜能的NSCs与NPCs,这些细胞能分化为有完整功能的神经元并整合入神经环路,提示中枢的神经发生不仅限于胚胎期,在生后乃至成年的整个发育期均能观察到神经发生.     

颞叶内侧及外侧癫痫蝶骨电极长程视频脑电图监测

目的：比较颞叶内侧癫痫（MTLE）及颞叶外侧癫痫（颞叶新皮层癫痫,NCTLE）蝶骨电极长程视频脑电（V-EEG）的特点。方法：根据国际抗癫痫联盟（ILAE）癫痫综合征的诊断标准,从发作类型、临床特征以及解剖部位、病因等方面,将112例难治性颞叶癫痫分为MTLE89例,NCTLE23例,对其蝶骨电极长程V—EEG监测结果进行回顾分析。结果：MTLE组和NCTLE组均具有高先兆出现率,蝶骨电极发作间期EEG棘波、棘慢波、尖波、尖慢波总检出率分别为83．1％和30．4％,其间差异具有显著意义（P〈0．01）。发作期蝶骨电极EEG定位准确率较高,MTLE定侧率为70．8％（63／89）,临床发作形式以手口自动症为主。结论：MTLE与NCTLE具有相应EEG及临床发作特征,蝶骨电极长程V—EEG监测能有效鉴别诊断MTLE与NCTLE,在一定程度上可为准确定位致痫灶提供可靠依据,进而有利于指导手术。     

基于Granger因果性的功能磁共振成像对内侧颞叶癫痫活动的研究

在内侧颞叶癫痫(mTLE)中,内侧颞叶与皮层及皮层下结构参与了癫痫活动的起源与传播.基于Granger因果性(GC)检验方法,对脑电联合功能磁共振(EEG-fMRI)数据进行分析,研究内侧颞叶在mTLE中的作用.以内侧颞叶激活区域为参考区域,计算参考区域与大脑其余每个体素点之间的Granger因果关系,并映射到全脑,形成Granger因果图(GCM).结果表明,内侧颞叶将癫痫活动传播到外侧颞叶、额叶、顶叶及丘脑等区域,同时受到脑岛、壳核以及丘脑等区域脑活动的影响,提示内侧颞叶在mTLE痫样发放的传播环路中具有关键作用.     

痫样放电偶极子对颞叶内侧型顽固性癫痫的定位价值

目的：探讨痫样放电偶极子分析结合临床特征和其它无创检查对颞叶内侧型顽固性癫痫的定位价值。方法：对21例发作间期主要在颞区存在痴样放电且每月致残性发作1次以上的顽固性癫痫患者,结合临床特征和其它无创检查确诊为颞叶内侧型癫病并定侧后,进行机器人辅助立体定向射频热凝毁损颞叶内侧结构治疗。结果：术后12～37个月,按照Engel分级系统：Ⅰ级6例（29％,其中Ⅰa级5例,Ⅰd级1例）,Ⅱb级3例（14％）,Ⅳa级4例（19％）,Ⅳb级7例（30％）,Ⅳc级1例（5％）。术后患者的神经功能均无明显下降。结论：机器人辅助立体定向系统射频热凝毁损术安全、有效、方便、快捷,部分颞叶内侧型顽固性癫痫患者对立体定向射频热凝治疗反应良好。     

Impaired attention network in temporal lobe epilepsy: A resting FMRI study

Attention deficit is a common symptom in the patient with mesial temporal lobe epilepsy (mTLE). Although presumption has been proposed by the previous study that mTLE may have impaired attention networks, no fMRI study has addressed the alteration of the dorsal attention network in mTLE. Twenty-four patients with bilateral mTLE and the same number of gender- and age-matched healthy controls participated in the current fMRI study. The resting-state network corresponding to the dorsal attention network (DAN) was extracted by using independent component analysis (ICA) from each participant. Functional connectivity in the DAN was then compared between the patients and controls. In addition, the scores of Trail Making Test (TMT) in the patients were correlated to the z-score of the voxels showing significant difference between the two groups. Compared with the controls, the patients with mTLE presented decreased functional connectivity in almost all the regions within the DAN. Moreover, there were negative correlations between the TMT scores and the z-scores in the voxels showing decreased or increased functional connectivity in mTLE. Our results suggested that the alteration of DAN might underpin the impairment of top-down attention function in mTLE. Our fMRI study may contribute to the understanding of neuro-pathophysiological mechanism of attention impairments in patients with mTLE.     

1H magnetic resonance spectroscopy at 3 T in cryptogenic and mesial temporal lobe epilepsy

The objectives of this work were to compare concentrations of N-acetylaspartate (NAA), glutamate (Glu), glutamine (Gln), Glx (=Glu + Gln), myo-inositol (mI), total creatine (Cre) and other metabolites in the temporal lobes of patients with mesial temporal lobe epilepsy (mTLE), cryptogenic TLE (cTLE), who show no abnormalities in high-resolution MRI, and healthy controls using single voxel (1)H MRS at 3 T. Twelve patients with mTLE, nine with cTLE and 22 controls were investigated using a short echo time STEAM protocol. Voxels were positioned bilaterally in the medial and lateral temporal lobes. Spectra were processed with LCModel. Significantly lower mean NAA were detected in mTLE patients (P < 0.001) and a trend towards lower NAA in cTLE patients compared to controls (P = 0.053). Glx was not different between groups. Estimates of Glu showed a different metabolic pattern in mTLE with elevated Glu in lateral compared with medial voxels on the ipsilateral side to seizure onset (P = 0.019). MI concentrations were significantly lower in cTLE (P < 0.001) and in mTLE patients (P = 0.005) compared with healthy controls. MI/Cre was significantly reduced in cTLE patients only (P = 0.004). The results confirm low NAA in mTLE and to a lesser extent in cTLE patients. MI and mI/Cre were identified as potential metabolic indicators of the epileptogenic area in cTLE.     

RCAN1/CaNA在颞叶癫痫患者及戊四氮动物模型中的表达变化

目的观察钙调神经磷酸酶调节因子1(RCAN1)及钙调神经磷酸酶A(CaNA)在颞叶癫痫患者及戊四氮(PTZ)致癫动物模型中的表达变化。方法收集颞叶癫痫患者手术切除的皮质,并纳入癫痫组(n=18);收集脑外伤患者手术切除的皮质,并纳入对照组(n=11)。30只SD大鼠随机分为模型对照组(MC)和PTZ组。分别应用Western blot和免疫组织化学染色检测RCAN1和CaNA的表达情况;应用免疫荧光染色对RCAN1进行定位;应用免疫共沉淀分析RCAN1与CaNA的相互作用。结果 RCAN1定位于神经元的细胞膜;在颞叶癫痫患者及癫痫模型中,RCAN1的表达水平较对照组明显下降(P<0.01),CaNA的表达水平较对照组明显增高(P<0.01);RCAN1与CaNA具有相互作用。结论在颞叶癫痫患者及癫痫模型中,RCAN1低表达,而CaNA高表达,提示RCAN1可能通过调控CaNA参与癫痫的形成。     

耐药性颞叶癫痫患者记忆功能损害的多因素分析

目的：观察耐药性颞叶癫痫患者记忆功能的损害并分析其影响因素。方法：采用韦氏记忆量表对32例耐药性颞叶癫痫患者记忆功能进行评估,并与32例普通癫痫患者进行比较,同时对可能的影响因素如发病年龄、发作频度、海马体积、脑电图异常放电范围、病程持续时间等进行相关性分析。结果：与普通癫痫患者比较,耐药性颞叶癫痫患者记忆功能普遍降低,尤其以短时记忆为明显。在其各种可能因素中,起病年龄、发作频度、抗癫痫药的种类和海马痫样放电的范围对记忆商（MQ）具有显著影响。结论：耐药性颞叶癫痫患者有明显记忆损害,起病年龄、发作频度、服用抗癫痫药的种类和海马痢样放电的范围是影响记忆功能的主要因素。     

GABAA receptor subunits in the rat hippocampus II: Altered distribution in kainic acid-induced temporal lobe epilepsy

Intraperitoneal injection of kainic acid in the rat represents a widely used animal model of human temporal lobe epilepsy. Injection of kainic acid induces acute limbic seizures which are accompanied by seizure-induced brain damage and late spontaneous recurrent seizures. There is considerable evidence for an altered transmission of GABA in human temporal lobe epilepsy and in the kainic acid model. We therefore investigated by immunocytochemistry the distribution of 13 GABA receptor subunits in the hippocampus of rats 12 h, 24 h, and two, seven and 30 days after injection of kainic acid. Within the molecular layer of the dentate gyrus, decreases in α₂- and δ- and slight increases in α₁-, β₂- and β₃-immunoreactivities were observed at early intervals (12 to 24 h) after kainic acid injection. These changes were succeeded by marked increases in α₁-, α₂-, α₄-, α₅-, β₁-, β₃-, γ₂- and δ-immunoreactivities in the same area after seven to 30 days. Within the hippocampus proper, changes in expression of GABA_A receptor subunits were demarcated by considerable neurodegeneration of CA1 and CA3 pyramidal neurons. All subunits present within dendritic areas of CA1 and CA3 were affected. These were α₁, α₂, α₅, β₁–β₃, γ₂ and α₄ (present only in CA1). Decreases in these subunits were followed by increased expression of α₂-, α₅-, β₃-, γ₂- and δ-subunits in the hippocampus proper notably in CA3 at later intervals (up to 30 days). α₁-, β₂-, γ₂- and δ-subunits were found in presumed GABA containing interneurons throughout the hippocampus. Their immunoreactivity was augmented after two to seven days. Some α₄-, γ₃- and δ-immunoreactivity was also found in astrocytes 48 h after kainic acid injection.Our data indicate an impairment of GABA-mediated neurotransmission due to a lasting loss of GABA_A receptor containing cells after kainic acid-induced seizures. The seizure-induced loss in GABA_A receptors within the hippocampus may in part be compensated by increased expression of GABA_A receptor subunits within the molecular layer of the dentate gyrus and in pyramidal cells.     

颅内电极V-EEG对难治性颞叶癫痫致痫灶的定位价值

目的：探讨颅内埋藏电极同步录像脑电图监测（V-EEG）对难治性颞叶癫痫致痫灶的定位作用。方法：对临床、影像学检查及头皮电极脑电图（EEG）不能明确癫痫致痫灶的3例难治性颞叶癫痫患者,采用颅骨钻孔方法埋置硬膜下电极和深部电极,经长程颅内电极V—EEG监测进一步定位致痫灶。结果：3例难治性颡叶癫痫患者通过颅内电极V-EEG监测,并依据发作初始期的EEG异常放电特征确定了致痫灶,并进行病灶切除。结论：依据发作初始期颅内电极EEG痫样放电的部位和范围,能够为难治性癫痫外科手术治疗提供更可靠的定位指标。     

视频脑电图对颞叶内侧癫癎致癎灶定侧价值探讨

目的：探讨视频脑电图（V—EEG）对颞叶内侧癫癎（MTLE）致痼灶定侧的价值。方法：回顾性分析34例MTLE患者的发作间期及发作期V—EEG提供的致癎灶的侧别信息,并与术中深部电极检测到颞叶内侧部位的痫样放电的侧别进行比较。结果：发作间期、发作期V-EEG能定侧的分别是23例（68％）,29例（85％）。与术中深部电极检查定侧符合的分别是20例（87％）,26例（90％）,两者的定侧符合率比较差异无统计学意义（P〉0．05）。结论：MTLE患者发作间期痫样放电呈单侧分布或分布有绝对的侧别优势时,定侧意义较大,与发作期EEG对致癎灶定侧意义相当。     

颞叶外侧癫痫患者脑组织NHE1及凋亡相关蛋白的表达

目的　检测颞叶外侧癫痫患者手术切除脑组织标本中钠氢交换体1（Na+/H+ exchanger-1,NHE1）的表达及凋亡相关蛋白的表达,初步探讨其致病机制。 方法　收集16例颞叶外侧癫痫患者手术切除脑组织标本作为癫痫组,10例颞叶肿瘤和脑出血患者手术切除脑组织标本作为对照组,HE染色观察脑组织病理学变化,免疫组化染色法以及免疫荧光法检测NHE1表达特点,Western blot等方法半定量分析NHE1蛋白表达特点,并检测凋亡相关蛋白Bcl-2与Bax表达特点。 结果　HE染色可见癫痫组颞叶组织中神经元明显减少,吞噬现象明显增多,小胶质细胞过度活跃,而对照组标本无类似表现;免疫荧光及免疫组化染色提示NHE1定位于神经元上,癫痫组NHE1染色较对照组增强（P<0.05）;癫痫组NHE1蛋白半定量表达较对照组增高（P<0.05）;凋亡相关蛋白检测显示癫痫组Bcl-2蛋白表达较对照组降低（P<0.05）,Bax蛋白表达较对照组增高（P<0.05）。 结论　NHE1与颞叶外侧癫痫的形成和发展密切相关,其机制可能是NHE1增高参与调控神经元凋亡。