Using electroacupuncture at acupoints to predict the efficacy of hippocampal high-frequency electrical stimulation in pharmacoresistant temporal lobe epilepsy patients

Hippocampal high-frequency electrical stimulation (HFS) shows long-term efficiency in some pharmacoresistant temporal lobe epilepsy patients. However, the success of the procedure varies from patient to patient and neither neurologists nor neurosurgeons are currently unable to pre-operatively predict which patients will respond to the stimulation. Just like electrical stimulation of the hippocampus in the brain, electroacupuncture (EA) at acupoints involves electrical stimulation and is also efficient in treating epilepsy. However, the stimulation targets are acupoints, which are located outside of the brain, and we presume that electrical stimulation of both targets can activate therapeutic neuronal networks, which explains why both stimulations are effective in treating epilepsy. Despite the involvement of different activated positions, the neurotransmitters, including both excitatory and inhibitory amino acids, generated from the stimulation are similar. It has been shown that both hippocampal HFS and EA at acupoints are related to the metabolism of amino acids and thus, we propose the hypothesis that EA at acupoints can predict the curative effect of hippocampal HFS: if EA at acupoints is effective, HFS of hippocampus will also be effective.     

Modelling the temporal region in patients with temporal lobe epilepsy

EEG interictal epileptiform discharges in temporal lobe epilepsy are associated with magnetic fields. The maxima of magnetic spikes recorded over the spherical portions of the head appear fairly symmetric, whereas those over the lower temporal region often have irregular shapes. Furthermore, their magnitude is often unequal with the extremum over the lower temporal region usually of lower magnitude than the extremum over the upper temporal region. This lack of symmetry in shape and magnitude may be due to non-sphericity of the skull over the temporal region or to variations in conductivities of intervening tissues. We present our observation in two patients suggesting that the surface contours of the head contribute to the apparent asymmetries of the field pattern but that the head contours alone may not account for the asymmetries seen in the clinical data.     

Electromyographic responses in leg muscles after electrical stimulation in myelopathy patients with tonic seizures

The electromyographic (EMG) responses in leg muscles after electrical stimulation of the peripheral nerves were examined in patients with myelopathy. The stimuli were delivered to the tibial nerve at the ankle joint. The EMG responses were recorded from the anterior tibial muscle at the latencies of 80-280 ms. In myelopathy patients with tonic seizures in the extremities, the EMG responses evoked both by single and repeated stimulation were frequently observed. Electrical stimulation also provoked the following tonic seizures in the legs. Stimulation of the back of the big toe or of the sural nerve, also produced the EMG responses in the anterior tibial muscle, and tonic seizure in the leg. There was no difference in the appearance of the EMG responses between patients with and without pain sensation during the seizure. A kind of flexor reflex might be related to tonic seizures in patients with myelopathy, at least in part.     

IL-17在药物难治性颞叶外侧型癫痫中的表达

研究白介素17(interleukin 17,IL-17)在药物难治性颞叶外侧型癫痫(lateral temporal lobe epilepsy,LTLE)病灶中的表达和分布,探讨IL-17在TLE发生发展中可能的作用。使用real-time PCR、Western blotting、免疫组化及荧光双标检测12例LTLE致痫灶及8例正常对照脑组织中IL-17的表达。结果提示:IL-17在LTLE中的mRNA和蛋白表达水平较对照组明显增高(P<0.05),且IL-17高表达于LTLE的神经元、星形胶质细胞以及血管内皮细胞。上述研究结果提示,IL-17可能参与了TLE的发生发展。     

颞叶癫癎磁共振波谱研究

目的 :探讨磁共振波谱 (magneticresonancespectrum ,MRS)检查对颞叶癫患者致灶的定位价值。方法 :对 36例颞叶癫患者进行MRS检查 ,主要分析波谱的三个峰 :N—乙酰天门冬氨酸 (NAA)峰位于 2 0 ppm ,总肌酸 (Cr)峰位于 3 0 ppm ,胆碱类物质 (Cho)峰位于 3 2ppm) ,根据波峰曲线下的绝对面积计算出NAA/ (Cr Cho)的比值 ,以NAA(Cr Cho) <0 6 8作为判断异常的标准。结果 :36例病人中 34例NAA/ (Cr Cho)比值 <0 6 8,其中双侧异常 2 1例 ,单侧异常 13例。结论 :MRS能准确反映体内NAA、Cho、Cr等代谢产物的变化 ,对颞叶癫的致灶有定位价值。     

Carboxypeptidase A6 gene (CPA6) mutations in a recessive familial form of febrile seizures and temporal lobe epilepsy and in sporadic temporal lobe epilepsy

Febrile seizures (FS) and temporal lobe epilepsy (TLE) were found in four of the seven siblings born to healthy Moroccan consanguineous parents. We hypothesized autosomal recessive (AR) inheritance. Combined linkage analysis and autozygosity mapping of a genome-wide single nucleotide polymorphism genotyping identified a unique identical by descent (IBD) locus of 9.6 Mb on human chromosome 8q12.1-q13.2. Sequencing of the 38 genes mapped within the linked interval revealed a homozygous missense mutation c.809C>T (p.Ala270Val) in the carboxypeptidase A6 gene (CPA6). Screening all exons of CPA6 in unrelated patients with partial epilepsy (n = 195) and FS (n = 145) revealed a new heterozygous missense mutation c.799G>A (p.Gly267Arg) in three TLE patients. Structural modeling of CPA6 indicated that both mutations are located near the enzyme's active site. In contrast to wild-type CPA6, which is secreted and binds to the extracellular matrix where it is enzymatically active, Ala270Val CPA6 was secreted at about 40% of the level of the wild-type CPA6 and was fully active, while Gly267Arg CPA6 was not detected in the medium or extracellular matrix. This study suggests that CPA6 is genetically linked to an AR familial form of FS and TLE, and is associated with sporadic TLE cases.     

Changes in granule cell firing rates precede locally recorded spontaneous seizures by minutes in an animal model of temporal lobe epilepsy

Although much is known about persistent molecular, cellular, and circuit changes associated with temporal lobe epilepsy, mechanisms of seizure onset remain unclear. The dentate gyrus displays many persistent epilepsy-related abnormalities and is in the mesial temporal lobe where seizures initiate in patients. However, little is known about seizure-related activity of individual neurons in the dentate gyrus. We used tetrodes to record action potentials of multiple, single granule cells before and during spontaneous seizures in epileptic pilocarpine-treated rats. Subsets of granule cells displayed four distinct activity patterns: increased firing before seizure onset, decreased firing before seizure onset, increased firing only after seizure onset, and unchanged firing rates despite electrographic seizure activity in the immediate vicinity. No cells decreased firing rate immediately after seizure onset. During baseline periods between seizures, action potential waveforms and firing rates were similar among the four subsets of granule cells in epileptic rats and in granule cells of control rats. The mean normalized firing rate of granule cells whose firing rates increased before seizure onset deviated from baseline earliest, beginning 4 min before dentate gyrus electrographic seizure onset, and increased progressively, more than doubling by seizure onset. It is generally assumed that neuronal firing rates increase abruptly and synchronously only when electrographic seizures begin. However, these findings show heterogeneous and gradually building changes in activity of individual granule cells minutes before spontaneous seizures.     

Memory for content and source in temporal lobe patients

Left and right temporal lobectomy patients and normal controls were tested in a memory task for which the to-be-remembered items were simple actions involving small objects. Participants either performed the actions, perceived the experimenter performing the actions, or imagined themselves performing the actions. The patients were deficient relative to the controls at remembering the actions and at remembering whether the actions were performed, perceived, or imagined. These results are interpreted as suggesting that the temporal lobes are involved in memory for the source as well as the content of past experiences.     

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。     

Memory for famous people in patients with unilateral temporal lobe epilepsy and excisions

Memory for famous individuals was assessed by the use of a recognition test in which participants first made familiarity judgments, followed by forced-choice decisions to specific probes for identity. Patients with temporal lobe epilepsy (TLE) or excisions, 12 left hemisphere and 12 right hemisphere, and 18 control participants identified famous figures across 3 decades (1970s-1990s). Only patients with right TLE were impaired at familiarity judgments of faces; this deficit was evident only for the most recent decades. Both groups of patients, however, were impaired at naming famous faces and at providing semantic information about famous people. These findings suggest the integrity of temporal structures in both hemispheres is critical for retrieval of detailed semantic information about famous individuals.     

The immunosuppressant cyclosporin A inhibits recurrent seizures in an experimental model of temporal lobe epilepsy

The immunosuppressant, cyclosporin A (CsA), is neuroprotective following brain injury. Previous studies suggest that CsA treatment ameliorates seizure severity during status epilepticus (SE) or cell death following SE. The antiepileptic effects of CsA on recurrent seizures, however, have not been investigated. In the present study, the effects of CsA on spontaneous recurrent seizures (SRSs) in a kainate (KA)-induced mouse model of mesial temporal lobe epilepsy (TLE) were examined. Moreover, the effects of CsA on epileptiform activity in a 4-aminopyridine (4-AP)-induced in vitro seizure model were investigated. A mesial TLE mouse model was generated with a unilateral intrahippocampal injection of KA. SRSs were determined in the ipsilateral hippocampal CA1 region with a long-term video-EEG. CsA was systemically administrated to the epileptic mice exhibiting a stable occurrence of SRSs. A 1-mg/kg dose of CsA did not have any effect on SRSs in the epileptic mice. However, a 5-mg/kg dose of CsA significantly reduced the number of SRSs and decreased the severity of the seizures in the epileptic mice. Additionally, CsA treatment inhibited spontaneous burst discharges in 4-AP-treated hippocampal slices. The results of the present study demonstrate that CsA inhibits recurrent seizures in a mouse model of mesial TLE and suggest that CsA may afford both neuroprotection against SE and antiepileptic effects during the chronic period of epilepsy.     

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。     

Post-treatment with rapamycin does not prevent epileptogenesis in the amygdala stimulation model of temporal lobe epilepsy

Approximately 30% of all epilepsy cases are acquired. At present there is no effective strategy to stop epilepsy development after the precipitating insult. Recent data from experimental models pointed to the mTOR pathway, which can be potently inhibited by rapamycin. However, data on the antiepileptic and antiepileptogenic properties of rapamycin are conflicting. Therefore, we tested whether rapamycin post-treatment influences epileptogenesis in the amygdala stimulation model of temporal lobe epilepsy in rats. Animals were treated with rapamycin (6 mg/kg) or vehicle daily for 2 wks, beginning 24 h after stimulation. Sham-operated animals were treated with rapamycin or vehicle but were not stimulated. Animals were video-EEG monitored to detect spontaneous seizures. Animals were sacrificed 4 wks later and brains were collected for Timm staining. There were no significant differences in the number of stimulated rats developing epilepsy; latency to first spontaneous seizure; number of seizures, or seizure frequency in epileptic animals. The area occupied by mossy fibers was significantly increased in stimulated vs. sham-operated animals but was not different in animals treated with rapamycin vs. vehicle. Collectively, our data suggest that the antiepileptic or antiepileptogenic action of rapamycin is not a universal phenomenon and might be limited to certain experimental models or experimental conditions.     

Heterotopias,cortical dysplasias and glioneural tumors participate in cognitive processing in patients with temporal lobe epilepsy

Focal brain lesions such as cortical dysplasia and glioneural tumors generate epileptic activity and thus may be synaptically connected with normal cortex. To test this hypothesis, we compared event-related potentials recorded directly from the medial temporal lobe (MTL) and a dysplastic lesion in eight patients with intractable temporal lobe epilepsy. The P3 component, related to visual target detection, showed different peak latencies in four patients and a larger intralesional amplitude compared to established anterior-MTL-generators in two patients. Semantic processing was identified by the N400 component and showed a different latency in four patients and larger intralesional amplitudes in two patients. These results are compatible with the hypothesis that cortical lesions interact with synaptic pathways related to cognitive functions such as visual target detection, and verbal processing.     

颞叶癫痫患者语言相关功能区的fMRI研究

目的：通过功能磁共振成像（fMRI）检查,了解颞叶癫痫（TLE）患者语言相关功能区的分布,初步探讨影响其不典型分布的因素,评价fMRI对癫痫患者进行无创语言功能定位检查的临床可操作性。方法：健康对照组和成人发病的左、右一侧性TLE患者组各6例,均为右利手。所有受试者进行动词产生任务fMRI检查,以按键记录受试者的反应。使用统计参数图2（statisticalparametricmap-ping2,SPM2）对fMRI的图像进行个体和组分析。结果：所有受试者顺利完成任务,fMRI的结果显示左侧组较对照组有明显差异,语言激活出现不典型化表现,优势侧有向右侧转移的趋势,其偏侧化指数（1ateralityindex,LI）与病程呈相对的负相关。结论：左侧TLE患者的语言功能区出现不典型分布,偏侧化程度可能与病程有关。fMRI检查评价语言功能相关区结果基本可靠,受试者耐受性好,具有一定的临床可操作性。