癫痫病人棘波灶的电镜改变

报告２５例癫痫患者在进行手术治疗时，皮层脑电监测下，取棘波最明显最多的大脑皮质层电镜观察，同时对８例病人的胼胝体也做电镜观察，结果发现超微结构下的神经细胞，突触与神经毡，星形胶质细胞，毛细血管及髓鞘均有不同程度的病理变化，突触前轴突末梢及突触后树突均发生不同程度的水肿，尤以突触后树突水肿明显并伴有突触前轴突末梢突触小泡的聚集增多，这些同癫痫的发生有密切关系，在癫痫发病和脑电棘波形成中具有重要意义，     

癫痫病人脑棘波灶轴突、突触和树突的病理学研究

目的研究癫痫病人脑棘波灶内轴突、突触和树突的病理学变化。方法癫痫患者29例,手术治疗时在皮层电图监测下取棘波灶大脑皮质,用βAPP、突触素和MAP2免疫组化方法,分别对轴突、突触和树突的病理变化进行研究,并对突触做了电镜观察。结果棘波灶内轴突病变不明显;突触分布不均,或密集成片,或稀疏淡染,电镜下轴棘非对称性突触前轴突末梢水肿,突触小泡减少或消失;树突屈曲变形,病变严重者树突变得粗细不均,或变成串珠状,多数树突失去分枝,血管周围树突排列紊乱。此外,在5例临床诊断为原发性癫痫的病例,观察到白质内神经细胞异位。结论癫痫棘波灶的病理变化主要发生在突触和树突,突触的增多、重组和丢失,以及白质神经细胞异位可能是癫痫异常放电的病理学基础。     

癫痫患者棘波灶的电镜观察

本文总结２４例癫痫患者在行手术治疗过程中分别在有棘波和无棘波的部位取材进行电镜检查，以探讨癫痫的发病机制。皮层组织取自额叶１２例，颞叶９例，枕叶３例，结果观察到癫痫患者的皮层无论有无棘波，超微结构下的神经细胞、突触与神经毡，星形胶质细胞及毛细血管均有不同程度的病理变化。其变化的特点是水肿，有棘波的部位最严重，尤其是突触前末梢，并有突触小泡减少，这些与癫痫的发生有密切关系，是棘波产生的形态学基础。     

硫酸亚铁制作家兔癫痫模型的病灶光镜和透射电镜研究

对３２只家兔利用ＦｅＳＯ４成功地制作癫痫模型，采取大脑皮层和海马区癫痫点燃病灶作了光镜和透射电镜观察，其脑电图棘波，尖波显示的部位神经元出现损害，突触发生明显病理变化，突触前轴突末梢水肿，突触水泡减少或消失，以上结果提示这些兴奋性突触病变在癫痫发病及脑电图棘波形成中有着重要的意义，脑微血管改变造成血循环障碍可导致大脑皮层和海马区抑制性神经元受损，星形细胞和毛细血管增生，髓鞘松散化，从而引起癫痫的发     

颞叶癫痫脑电图分析及病灶超微结构观察

目的 研究影像学检查无异常的颞叶癫痫患者,电生理异常与皮层棘波灶及海马超微病变的关系.方法 选择经CT或MRI检查未见异常的颞叶癫痫患者7例,术前做脑电图或24h视频脑电监测,术中在脑电监测下取颞叶大脑皮质棘波灶和海马组织,做电镜观察.结果 7例患者电生理检查均可见典型痫样放电.颞叶皮质痫灶和海马可见不同程度的神经元固缩,胶质细胞变性,胶质增生,突触数量及突触结构改变,血脑屏障破坏等改变.结论 影像学无异常的颞叶癫痫患者颞叶皮层痫灶和海马超微结构病理变化明显,特别是突触的变化,是导致癫痫患者脑电生理机能异常及癫痫反复自发性发作的形态学基础.     

癫痫灶的超微结构观察及与癫痫发生机制的关系探讨

目的 观察癫痫患者痫灶的超微结构变化，以探讨癫痫的发生机制。方法 对12例顽固性癫痫患者进行皮质电图监测下手术切除痫灶，电镜下观察痫灶皮质。结果 痫灶有明显的病理变化，包括神经细胞数量减少、神经细胞水肿变性、核浓缩、异染色质边集，线粒体水肿、崩解、嵴排列紊乱，神经突触水肿，小血管或毛细血管扭曲、堵塞或内皮细胞水肿，基底膜增厚或分层，星形胶质细胞突起水肿。结论癫痫的发生均有一定的病理形态学基础，除了神经细胞、突触、星形胶质细胞的变化外，血脑屏障的改变与癫痫的发生及预后天系密切。     

经颅磁刺激结合运动训练与局灶性脑梗死大鼠健侧感觉运动皮质锥体细胞树突和突触结构的改变

经颅磁刺激联合运动训练对脑梗死后健侧大脑感觉运动皮质突触和锥体细胞影响的报道几乎未见,实验拟揭示经颅磁刺激和运动训练促进脑梗死后运动功能恢复的机制。结果显示,经颅磁刺激和运动训练均能改善脑梗死大鼠神经功能,能使动物健侧感觉运动皮质锥体细胞突触界面曲率增加,突触后致密物厚度增加、突触间隙变窄,穿孔突触比例增加。经过4周经颅磁刺激和运动训练后脑梗死大鼠健侧感觉运动皮质区锥体细胞树突总长度、 一级数突分支和单位长度树突的树突棘密度明显增加,这些变化在经颅磁刺激和运动训练联合后更为明显。表明经颅磁刺激和运动训练治疗可以使健侧感觉运动皮质锥体细胞树突和突触结构参数发生改变,从而促使健侧脑的代偿作用,改善脑梗死大鼠的神经功能。     

顽固性颞叶癫(癎)海马超微结构的体视学分析

目的对顽固性颞叶癫痫病人的海马癫痫灶组织和癫痫灶周围正常组织的超微结构进行形态定量观察，以探讨颞叶癫痫的发生机制．方法对45例病人在深部电极监测下手术切除海马．电镜观察癫痫灶组织和癫痫灶周围正常组织中锥体细胞和突触结构的形态学变化：采用体视学分析颞叶癫痫灶组织和癫痫灶周围正常组织锥体细胞线粒体体积密度（Vv）、面积密度（Sv）、数密度（Nv）、比表面积（δ）、平均体积（V）：测量突触间隙的宽度。结果癫痫灶组织锥体细胞线粒体较癫痫灶周围正常组织明显肿胀，且嵴断裂．数量减少，平均截面积增大：线粒体的Vv、V较癫痫灶周围正常组织大，Sv、Nv、8较癫痫灶周围正常组织小。癫痫灶组织中锥体细胞的轴突和树突内线粒体较癫痫灶周围正常组织的锥体细胞肿胀明显；轴棘、轴树突触间隙宽度变窄。结论海马锥体细胞超微结构的改变和细胞线粒体功能变化与顽固性颞叶癫痫的发生关系密切。     

颞叶癫痫患者海马苔藓纤维发芽的实验研究

目的观察颞叶癫痫病人海马齿状回和CA3区苔藓纤维出芽情况。方法癫痫组样本来自12例颞叶癫痫病例的手术切除标本包含海马齿状回和CA3区的脑组织，对照组脑组织样本来自4例非癫痫病的尸检脑组织。应用Timm组织化学染色方法在光镜和电镜水平进行海马结构苔藓纤维发芽的研究。结果光镜下癫痫组可见苔藓纤维穿越海马齿状回颗粒细胞层到达内分子层．CA3区也可见明显的苔藓纤维发芽。癫痫组CA3区和齿状回内分子层苔藓纤维发芽评分高于对照组．统计学上差异有显著性意义。电子显微镜下观察显示癫痫组患者齿状回内分子层可见到银标记的突触末端，主要和树突形成突触连接，所形成的突触为非对称性突触。结论颞叶癫痫可致海马齿状回和CA3区苔藓纤维发芽增加，这可能是难治性癫痫形成的重要机制。     

癫痫发作的基本机理:神经生理和神经生化病因学

神经胶质细胞增生为癫痫发生灶中病变的一个特点,此外还有神经细胞减少以至消失,局部脑循环障碍,显著的树突结构异常。树突的形态改变主要为树突棘消失,树突分支减少产生扭曲和不规则的肿胀。树突棘消失的结果,使突触传入减少导致去神经型过敏(denervation type of Supersensitivity)产生重复放电。神经元全面减少,剩留的神经元为中型到小型的,它们比大的神经元更容易放电。神经胶质细胞增生是癫痫发生灶发展过程中主要现象之一,对说明癫痫发作具有重要意义。     

Combined use of sphenoidal electrodes and the dipole localization method for the identification of the mesial temporal focus

We attempted to sub-classify four cases who show temporal spikes on standard scalp electroencephalogram (EEG), using sphenoidal electrodes and the dipole localization METHOD: In a case with mesial temporal epilepsy, spikes showed phase reversal in a sphenoidal electrode, and the spike dipoles were estimated to be in the mesial temporal lobe. In a case with lateral temporal epilepsy, spikes showed no phase reversal in a sphenoidal electrode, and the spike dipoles were estimated to be in the lateral temporal lobe. In two cases out of four, spikes showed phase reversal in sphenoidal electrodes, whilst the dipoles were estimated to be in the frontal lobe. Clinical features also suggested a diagnosis of frontal lobe epilepsy. In one of the two cases in which frontal lobe epilepsy was suspected, ictal dipoles as well as interictal spike dipoles indicated participation of the frontal lobe in the genesis of seizures. Nevertheless, only mesial temporal lobectomy was performed based on results obtained by invasive subdural electrodes. As a result, seizures were not controlled. Although sphenoidal electrodes were useful for differentiating between mesial and lateral temporal lobe foci, it is advisable to use them in combination with the dipole localization method to identify frontal lobe foci.     

癫痫大鼠海马出芽苔藓纤维突触的超微结构特征

目的:探讨匹罗卡品颞叶癫痫大鼠海马出芽苔藓纤维突触的超微结构特征及其在颞叶癫痫发病机制中的作用。方法:采用Timm组化染色标记出芽苔藓纤维突触末端,在电镜下观察新生突触的类型、比例、定位、以及突触后靶成分。结果:颞叶癫痫大鼠齿状回内分子层可见到银标记的突触末端,出芽苔藓纤维突触主要是轴棘型非对称性突触,其次是轴树型非对称性突触,偶可看到出芽轴突和颗粒细胞体形成突触联系。结论:轴棘型非对称性突触是颞叶癫痫大鼠海马出芽苔藓纤维突触的主要类型,出芽苔藓纤维突触的超微结构特性支持重组突触形成重复的兴奋性环路,而且形成的新的兴奋性环路可能在颞叶癫痫的发生与发展中起重要作用。     

Focal epileptiform spikes in conjuction with K-complexes.

Dyshormia or epileptiform spikes occurring within K-complexes have been described in patients with generalized epilepsy, with one study reporting that generalized spikes occurred frequently in association with K-complexes. We report the rate of focal epileptiform spikes occurring within K-complexes in localization-related epilepsy. Presurgical or diagnostic long-term video-EEG results of 40 consecutive patients with epilepsy (13 patients with right temporal lobe epilepsy, 20 patients with left temporal lobe epilepsy, and 7 patients with frontal lobe epilepsy) were reviewed. Sleep samples were reviewed and the numbers of K-complexes, spikes, and spikes within K-complexes were recorded. The comparison group consisted of 40 consecutive patients with nonepileptic events who were monitored with long-term video EEG. Focal epileptiform spikes occurring within K-complexes occurred in 2 of 13 (15%) patients with right temporal lobe patients, 6 of 20 (30%) patients with left temporal lobe, and 3 of 7 (42%) patients with extratemporal lobe epilepsy. In most patients, spikes occurring during K-complexes were rare. We identified spikes occurring during K-complexes in patients with localization-related epilepsy. The sharply contoured components of K-complexes or associated sleep spindles may obscure focal spikes within K-complexes. Nevertheless, K-complexes may be associated with focal epileptiform discharges.     

Status epilepticus-induced hilar basal dendrites on rodent granule cells contribute to recurrent excitatory circuitry

Mossy fiber sprouting into the inner molecular layer of the dentate gyrus is an important neuroplastic change found in animal models of temporal lobe epilepsy and in humans with this type of epilepsy. Recently, we reported in the perforant path stimulation model another neuroplastic change for dentate granule cells following seizures: hilar basal dendrites (HBDs). The present study determined whether status epilepticus-induced HBDs on dentate granule cells occur in the pilocarpine model of temporal lobe epilepsy and whether these dendrites are targeted by mossy fibers. Retrograde transport of biocytin following its ejection into stratum lucidum of CA3 was used to label granule cells for both light and electron microscopy. Granule cells with a heterogeneous morphology, including recurrent basal dendrites, and locations outside the granule cell layer were observed in control preparations. Preparations from both pilocarpine and kainate models of temporal lobe epilepsy also showed granule cells with HBDs. These dendrites branched and extended into the hilus of the dentate gyrus and were shown to be present on 5% of the granule cells in pilocarpine-treated rats with status epilepticus, whereas control rats had virtually none. Electron microscopy was used to determine whether HBDs were postsynaptic to axon terminals in the hilus, a site where mossy fiber collaterals are prevalent. Labeled granule cell axon terminals were found to form asymmetric synapses with labeled HBDs. Also, unlabeled, large mossy fiber boutons were presynaptic to HBDs of granule cells. These results indicate that HBDs are present in the pilocarpine model of temporal lobe epilepsy, confirm the presence of HBDs in the kainate model, and show that HBDs are postsynaptic to mossy fibers. These new mossy fiber synapses with HBDs may contribute to additional recurrent excitatory circuitry for granule cells.     

Postoperative interictal spikes during sleep contralateral to the operated side is associated with unfavourable surgical outcome in patients with preoperative bitemporal spikes.

PURPOSE: To correlate the persistence of contralateral spikes during sleep after unilateral surgery with seizure outcome in a temporal lobe epilepsy (TLE) population and to test the existing hypotheses about the origin of the contralateral spikes in temporal lobe epilepsy. METHODS: In the 19 patients selected for this study unilateral temporal lobe surgery was performed. To investigate the course of bilateral interictal epileptiform discharges observed before surgery in awake or sleep over the temporal lobe contralateral to surgery, 24 h mobile 12 channel EEG recording was performed at minimum two, in average 4.6 (2-10) years after the surgery. RESULTS: The association of postoperative contralateral spikes and non-seizure free outcome was highly significant. The existence of unilateral pathology before surgery was highly predictive for good outcome and disappearance of contralateral spikes. The association between good seizure outcome, disappearance of contralateral spikes and the existence of unilateral pathology before surgery was also significant. Our data partially satisfies the expectations of both the "seizure induced" and mirror type secondary epileptogenesis hypotheses concerning origin of contralateral spikes, but were not completely congruent with either of them. CONCLUSIONS: Unfavourable surgical outcome in a temporal lobe epilepsy group with preoperative independent bilateral interictal spikes was associated with the persistence of postoperative contralateral spikes and lack of unilateral pathology. Compared with seizure outcome the presence/absence and distribution of postoperative interictal spikes in NREM sleep not entirely fit to the predictions of existing secondary epileptogenesis hypotheses.     

Dipole source localization of interictal epileptiform activity in temporal lobe epilepsy with medial temporal lesion

Dipole sources of interictal epileptiform activities recorded by conventional electroencephalogram (EEG) were estimated using the dipole tracing method. Four cases of temporal lobe epilepsy with medial temporal lesions were studied. Two patients with hippocampal sclerosis, one patient with granulation in the hippocampus and one patient with cavernous angioma were involved in the study. Interictal epileptiform activities were classified into two patterns according to the topography of spikes. They were widespread spikes over the parasagittal electrodes (parasagittal spikes) and restricted spikes at the temporal electrodes (temporal spikes). Dipole sources of parasagittal spikes were localized in the medio-basal temporal lobe with vertically orientated vector moment. Dipole sources of temporal spikes were localized in the medio-basal temporal lobe with horizontally orientated vector moment. Locations of dipoles and directions of vector moments were consistent with topography and polarity of spikes. The difference in the two patterns of interictal epileptiform activities was derived from the difference in the direction of the vector moment of dipole sources. There was no difference in the location of dipole sources. Both the dipole sources and the lesions were localized in the same medio-basal temporal lobe. Dipole tracing was very useful in localizing the dipole sources of interictal epileptiform activities and in understanding the neurophysiological background.     

Upregulation of transmitter release probability improves a conversion of synaptic analogue signals into neuronal digital spikes

ABSTRACT: Action potentials at the neurons and graded signals at the synapses are primary codes in the brain. In terms of their functional interaction, the studies were focused on the influence of presynaptic spike patterns on synaptic activities. How the synapse dynamics quantitatively regulates the encoding of postsynaptic digital spikes remains unclear. We investigated this question at unitary glutamatergic synapses on cortical GABAergic neurons, especially the quantitative influences of release probability on synapse dynamics and neuronal encoding. Glutamate release probability and synaptic strength are proportionally upregulated by presynaptic sequential spikes. The upregulation of release probability and the efficiency of probability-driven synaptic facilitation are strengthened by elevating presynaptic spike frequency and Ca2+. The upregulation of release probability improves spike capacity and timing precision at postsynaptic neuron. These results suggest that the upregulation of presynaptic glutamate release facilitates a conversion of synaptic analogue signals into digital spikes in postsynaptic neurons, i.e., a functional compatibility between presynaptic and postsynaptic partners.     

Comparison of electroencephalographic dipoles of interictal spikes from prolonged scalp video-electroencephalography and magnetoencephalographic dipoles from short-term recording in children with extratemporal lobe epilepsy

We retrospectively compared electroencephalographic (EEG) dipoles of interictal spikes from prolonged video-EEG monitoring with magnetoencephalographic dipoles from short-term recording in four children with extratemporal lobe epilepsy. We analyzed both sets of dipoles using individual interictal spikes and single moving dipole modeling and evaluated the profiles of spike appearance, dipole position, and orientation in EEG and magnetoencephalography. We obtained more than 100 magnetoencephalographic spikes in two patients who manifested frequent interictal EEG spikes throughout both day and night but fewer than 40 magnetoencephalographic spikes in two patients who had interictal EEG spikes mainly during sleep. The dipole positions of EEG and magnetoencephalography were in close proximity and included in the surgical resection area. Most of the dipoles between EEG and magnetoencephalography were oriented perpendicularly. A combination of EEG dipole analysis from prolonged video-EEG monitoring and magnetoencephalographic dipole analysis provides complementary information for presurgical evaluation in children with intractable extratemporal lobe epilepsy.     

Relation between inter-critical and critical stereoelectroencephalographic elements: consequences on the results of cortectomies

Surgical results in 31 cases of cortectomy for epilepsy are reported with stereoelectroencephalographic recordings. The relationships between the cortical area characterized by inter-ictal spikes (irritative area) and the site of the ictal discharge (epileptogenic focus) lead to define two situations: the two areas were considered similar in 11/21 temporal lobe epilepsy and 3/10 frontal lobe epilepsy. Surgical results were then excellent; when the irritative area was not totally included in the cortectomy, surgical results were less good. This situation was more frequent in frontal lobe (70 p. 100) than in temporal lobe epilepsy (47.5 p. 100). However in 7/17 of theses cases, the seizures disappeared or decreased by 90 p. 100. Therefore the irritative area can be considered hetereogeneous. Ictal and interictal stereo-EEG data contain non-redundant information. The inter-ictal EEG patterns contributing to the definition of the epileptogenic area are discussed.     

Magnetoencephalographic localization of epileptic foci using a 37-channel biomagnetometer]

The magnetoencephalography (MEG) and electroencephalography (EEG) were recorded simultaneously from 10 normal subjects using a 37-channel biomagnetometer. No paroxysmal spikelike waveform was observed in MEG at rest with eyes closed. The MEG and EEG were recorded also from 16 patients with primary epilepsy and 24 patients with secondary epilepsy. The examination proved to be safe for both normal subjects and patients with epilepsy. Interictal spikes were observed in 27 cases during the examination. The percentage of spikes identified in MEG but not in EEG was found to be 2. 3% of all spikes. The foci of the spikes identified in MEG were localized and determined in 20 cases. In 10 patients with secondary epilepsy, the localization of the foci were compared with the lesion demonstrated by magnetic resonance imaging (MRI) or computerized tomography (CT) and with the findings of EEG. In 6 cases, the foci by MEG were consistent. In the 4 cases where the MEG foci did not correspond to the MRI or CT findings, MEG foci were supported by the findings of EEG. MEG allows three-dimensional localization and enables us to elucidate the propagation of paroxysms. MEG was very useful in diagnosing epilepsy.