颞叶癫痫患者全脑皮层厚度分析

观察并探讨颞叶癫痫(TLE)患者脑皮层厚度变化。 对71例颞叶癫痫患者(左侧癫痫组40例、右侧癫痫组31例)及17名健康对照组进行三维扰相梯度回波序列(3D-SPGR)扫描,采集数据通过Freesurfer软件进行大脑模型重建;再利用Brainstorm软件配准、平滑,以双样本独立t检验分别比较癫痫组与对照组,和癫痫组间皮层厚度的差异,并将具有统计学意义(P<0.01)的区域在标准脑模板上标注显示。 结果显示,与正常组比较,癫痫组均出现部分颞叶及颞叶意外脑区皮层厚度增大的现象,但异常脑区存在不同(左侧27个,右侧11个);癫痫组间比较,左侧癫痫组患者在左侧额下回眶部皮层增厚现象更为明显。 颞叶癫痫患者的情感及认知等障碍可能与多个脑区皮层增厚的问题有关。     

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...     

Defining clinico-neuropathological subtypes of mesial temporal lobe epilepsy with hippocampal sclerosis

Hippocampal sclerosis (HS) is the most frequent cause of drug-resistant focal epilepsies (ie, mesial temporal lobe epilepsy with hippocampal sclerosis; mTLE-HS), and presents a broad spectrum of electroclinical, structural and molecular pathology patterns. Many patients become drug resistant during the course of the disease, and surgical treatment was proven helpful to achieve seizure control. Hence, up to 40% of patients suffer from early or late surgical failures. Different patterns of hippocampal cell loss, involvement of other mesial temporal structures, as well as temporal neocortex including focal cortical dysplasia, may contribute to the extent of the epileptogenic network and will be discussed. An international consensus is mandatory to clarify terminology use and to reliably distinguish mTLE-HS subtypes. High-resolution imaging with confirmed histopathologic diagnosis, as well as advanced neurophysiologic and molecular genetic measures, will be a powerful tool in the future to address these issues and help to predict each patient's probability to control their epilepsy in mTLE-HS conditions.     

Two electrophysiologically distinct types of granule cells in epileptic human hippocampus

We investigated the electrophysiology of morphologically identified human granule cells with conventional current-clamp recordings. Slices were prepared from 14 human epileptic sclerotic hippocampi. Granule cells appeared to have a diverse electrophysiology. Each cell was distinguished by the shape of the afterhyperpolarization following single action potentials. Two types could be discerned: type I afterhyperpolarizations were monophasic and brief (typically 10–40 ms), whilst type II afterhyperpolarizations were biphasic and long (typically 50–100 ms). The two types also differed in their repetitive firing behaviour and action potential morphology: type I cells had significantly weaker spike frequency adaptation, lower action potential amplitude and smaller action potential upstroke/downstroke ratio. Thus, the firing pattern of type I cells resembled that of rodent dentate interneurons. In contrast, the corresponding parameters of type II cells were comparable to rodent dentate granule cells. Despite the distinct firing patterns, membrane properties were not different. The two types of cells also differed in their synaptic responses to stimulation of the perforant path. At strong suprathreshold stimulation intensity, type I cells always generated multiple action potentials, whereas type II cells usually spiked once only. Slow inhibitory postsynaptic potentials were not detected in type I neurons, but were easily identified in type II neurons. Extracellular recordings of perforant path-evoked field potentials in the cell layer confirmed that the majority of granule cells showed multiple discharges even when we recorded simultaneously from a type II cell that generated one action potential only. The morphology of both types of cells was characteristic of what has been described for primate dentate granule cells.

Based on comparisons with previous studies on rodent and human granule cells, we tentatively hypothesize that: (i) the majority of granule cells from sclerotic hippocampus display an hyperexcitable epileptogenic electrophysiology; (ii) there is a subset of granule cells whose electrophysiology is preserved and is more comparable to granule cells from non-epileptic hippocampus.     

Phase coupling between rhythmic slow activity and gamma characterizes mesiotemporal rapid-eye-movement sleep in humans

In the human sleep literature there is much controversy regarding the existence and the characteristics of hippocampal rhythmic slow activity (RSA). Generally the human RSA is believed to occur in short bursts of theta activity. An earlier study, however, reported mesiotemporal RSA during rapid-eye-movement (REM) sleep that instead of theta fell in the delta frequency band. We conjectured that if this RSA activity is indeed a human analogue of the animal hippocampal theta then characteristics associated with the animal theta should also be reflected in the human recordings. Here our aim was to examine possible phase coupling between mesiotemporal RSA and gamma activity during REM sleep. The study relied on nine epilepsy surgery candidates implanted with foramen ovale electrodes. Positive half-waves of the 1.5–3 Hz RSA were identified by an automatic algorithm during REM sleep. High-frequency activity was assessed for 11 consecutive 20 Hz–wide frequency bands between 20 and 240 Hz. Increase in high frequency activity was phase coupled with RSA in most frequency bands and patients. Such a phase coupling closely resembles that seen between theta and gamma in rodents. We consider this commonality to be an additional reason for regarding delta rather than theta as the human analogue of RSA in animals.     

基于ICA的颞叶癫痫背侧注意网络的研究

很多fMRI研究表明部分癫痫患者缺省模式网络存在中断现象,而对于颞叶癫痫背侧注意网络的研究几乎没有涉及。本研究尝试运用独立成分分析(independent component analysis,ICA)分离出16例单侧颞叶癫痫(temporal lobe epilepsy,TLE)患者和20例正常对照的背侧注意网络,并采用拟合度值(goodness-of-fit scores)分析对感兴趣成分进行挑选,将其结果进行组内分析和组间分析。结果表明:背侧注意网络分布于双侧顶内沟、额中回、额眼区、右侧小脑后叶等区域;颞叶癫痫患者的背侧注意网络相比正常人,大部分区域功能连接度下降,以双侧顶内沟、额中回、右侧小脑后叶区域显著,这可能是由于颞叶癫痫患者的大脑功能内源性组织发生破坏。拟合度值下降表明背侧注意网络激活区域为单侧TLE患者提供了一个灵敏的生物信号特征。     

头孢曲松钠抗颞叶癫痫的效果

目的研究头孢曲松钠(Cef)对颞叶癫痫模型小鼠的抗癫痫效果以及对谷氨酸转运蛋白(GLT-1)表达情况的作用。方法首先构建颞叶癫痫小鼠模型,利用同步视频脑电监测(v EEG)技术,24 h不间断记录小鼠癫痫发作情况。实验组腹腔注射Cef 200 mg/(kg·d),对照组腹腔注射0.9%氯化钠溶液,从癫痫发作频率、间期棘波及海马硬化等方面评价Cef对癫痫发作的控制情况,并用Western blot检测其对谷氨酸转运蛋白GLT-1表达情况的影响。结果单侧海马注射200 ng海人酸(KA)可模拟内侧颞叶癫痫患者反复自发性癫痫发作和海马硬化等两个疾病症状,成功构建内侧颞叶癫痫模型。Cef处理使癫痫发作次数从2.145次/d降低到1.597次/d,平均发作次数降低了31.2%(P0.05)。KA癫痫小鼠较正常小鼠GLT-1表达明显降低,但Cef处理并未明显提升GLT-1的表达。结论腹腔注射Cef部分抑制KA癫痫小鼠的慢性自发性癫痫发作,但无明显提升海马中GLT-1的表达,提示其可能并非是通过提高星形胶质细胞的谷氨酸清除能力而抑制癫痫发作。     

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。     

单侧颞叶癫癎伽玛刀和定向射频热凝术的效果比较

目的探讨深部电极脑电图证实为单侧颞叶内侧的癫癎患者进行伽玛刀和立体定向射频热凝毁损术疗效的区别。方法：2008年3月～2011年8月,深部电极脑电图确认为单侧颞叶内侧癫癎的患者,据深部电极脑电图所显示的异常范围引导,随机进行伽玛刀治疗和立体定向射频热凝毁损术。伽玛刀治疗颞叶内侧结构时,周边剂量8～13 Gy,平均9．3 Gy,中心剂量16～26 Gy,平均18．5 Gy,50％等剂量曲线;立体定向射频热凝毁损术时,毁损温度70～90℃,平均76．3℃,毁损时间90～120s,平均108．5s,毁损间隔3 mm。结果：术后24～65个月,随访可及的21例伽玛刀治疗,其中癫癎完全缓解（Engel Ⅰ级）2例,癫癎发作很少和几乎消失（EngelⅡ级）3例,显著的改善（Engel Ⅲ级）8例,不显著的改善（Engel Ⅳa级）7例,无改变（Ⅳb级）1例;立体定向射频热凝毁损术10例,其中癫癎完全缓解（Engel Ⅰ级）5例,癫癎发作很少或几乎消失（EngelⅡ级）2例,显著的改善（Engel Ⅲ级）0例,不显著的改善（Engel Ⅳa级）2例,癫癎发作更重（ⅣC级）1例。应用SPSS 17．0分析,两组完全缓解（Engel Ⅰ级）率比较差异有统计学意义（P=0．022）,两组完全缓解和癫癎发作很少和几乎消失（Engel Ⅰ级＋Ⅱ级）率比较差异有统计学意义（P=0．021）。结论：对深部电极脑电图证实为单侧颞叶内侧癫癎的患者,SRT的完全缓解率和癫癎基本控制率都高于伽玛刀治疗者。     

Characterising subtypes of hippocampal sclerosis and reorganization: correlation with pre and postoperative memory deficit

Neuropathological subtypes of hippocampal sclerosis (HS) in temporal lobe epilepsy (The 2013 International League Against Epilepsy classification) are based on the qualitative assessment of patterns of neuronal loss with NeuN. In practice, some cases appear indeterminate between type 1 (CA1 and CA4 loss) and type 2 HS (CA1 loss) and we predicted that MAP2 would enable a more stringent classification. HS subtypes, as well as the accompanying alteration of axonal networks, regenerative capacity and neurodegeneration have been previously correlated with outcome and memory deficits and may provide prognostic clinical information. We selected 92 cases: 52 type 1 HS, 15 type 2 HS, 18 indeterminate‐HS and 7 no‐HS. Quantitative analysis was carried out on NeuN and MAP2 stained sections and a labeling index (LI) calculated for six hippocampal subfields. We also evaluated hippocampal regenerative activity (MCM2, nestin, olig2, calbindin), degeneration (AT8/phosphorylated tau) and mossy‐fiber pathway re‐organization (ZnT3). Pathology measures were correlated with clinical epilepsy history, memory and naming test scores and postoperative outcomes, at 1 year following surgery. MAP2 LI in indeterminate‐HS was statistically similar to type 2 HS but this clustering was not shown with NeuN. Moderate verbal and visual memory deficits were noted in all HS types, including 54% and 69% of type 2 HS. Memory deficits correlated with several pathology factors including lower NeuN or MAP2 LI in CA4, CA1, dentate gyrus (DG) and subiculum and poor preservation of the mossy fiber pathway. Decline in memory at 1 year associated with AT8 labeling in the subiculum and DG but not HS type. We conclude that MAP2 is a helpful addition in the classification of HS in some cases. Classification of HS subtype, however, did not significantly correlate with outcome or pre‐ or postoperative memory dysfunction, which was associated with multiple pathology factors including hippocampal axonal pathways, regenerative capacity and degenerative changes.     

Enhanced cyclooxygenase-2 expression in olfactory-limbic forebrain following kainate-induced seizures

Cyclooxygenase-2 is expressed at low levels in a subset of neurons in CNS and is rapidly induced by a multiplicity of factors including seizure activity. A putative relationship exists between cyclooxygenase-2 induction and glutamatergic neurotransmission. Cyclooxygenase-1 is constitutively expressed in glial cells and has been specifically linked to microglia. In this study we evaluated cyclooxygenase-2 protein immunocytochemically and found markedly enhanced immunostaining primarily in olfactory-limbic regions at 2, 6 and 24 h following kainate-induced status epilepticus. Impressive enhanced cyclooxygenase-2 immunoreactivity was localized in anterior olfactory nucleus, tenia tecta, nucleus of the lateral olfactory tract, piriform cortex, lateral and basolateral amygdala, orbital frontal cortex, nucleus accumbens (shell) and associated areas of ventral striatum, entorhinal cortex, dentate gyrus granule cells and hilar neurons, hippocampal CA subfields and subiculum. Alternate sections were processed for dual immunocytochemical analysis utilizing c-Fos and cyclooxygenase-2 antiserum to examine the possibility that the neuronal induction of cyclooxygenase-2 was associated with seizure activity. Neurons that showed a timeline of cyclooxygenase-2 upregulation were found to possess c-Fos immunopositive nuclei. Additional results from all seizure groups showed cyclooxygenase-1 induction in microglia, which was confirmed by Western blot analysis of hippocampus. Western blot and real-time quantitative RT-PCR analysis showed significant upregulation of cyclooxygenase-2 expression, confirming its induction in neurons. These data indicate that cyclooxygenase-2 induction in a neuronal network can be a useful marker for pathways associated with seizure activity.     

颞叶癫痫患者记忆损害的研究

颞叶癫痫 (ＴＬＥ)患者可出现多方面的记忆障碍 ,左右颞叶病变对记忆的影响也不同 ,现将近年来的研究分别介绍如下。1　空间记忆的损害鉴于以往对ＴＬＥ患者空间记忆研究中所测试内容有言语介入或者由于其内容对于受试者来讲抽象、不熟悉等情况 ,出现所得结果不一致 ,为此 ,Ｂａｘ ｅｎｄａｌｅ[1] 等对检查无脑部结构异常的 6 9例术前患者(右ＴＬＥ2 7例 ,左ＴＬＥ32例 )的空间记忆做了全面的测评。结果表明 :右ＴＬＥ组图案学习、复杂图形即时回忆与延迟回忆及图形保留百分比的得分显著低于左ＴＬＥ组 ;右ＴＬＥ组识别图形细节改变较左Ｔ…     

Non-invasive detection of hippocampal sclerosis: correlation between metabolite alterations detected by (1)H-MRS and neuropathology

We assessed (1)H-MRS as a screening tool for detection of hippocampal sclerosis in patients with temporal lobe epilepsy (TLE). (1)H-MRS was carried out in the hippocampus of 23 patients with unilateral TLE. Metabolite alterations detected by (1)H-MRS correlated with degree of segmental neuronal cell loss and amount of astrogliosis. Positive correlation was found between total N-Acetylaspartate (tNAA) reduction and neuronal density in hippocampal CA1 (P < 0.001), CA3 (P = 0.015), and CA4 subfields (P = 0.031) and the dentate gyrus (P = 0.006). Neuronal cell loss in CA1 turned out to be the most predictive and only significant variable for tNAA reduction (P = 0.027). The association between myo-inositol (m-Ins) and astroglial glial fibrillary acidic protein (GFAP) expression revealed significantly increased m-Ins concentrations associated with diffuse astrogliosis (m-Ins = 6.4 +/- 1.1 institutional units) compared with gliosis restricted to isolated sectors of the hippocampus (i.e. hilus) (m-Ins = 5.2 +/- 1.2 institutional units) (P = 0.039). A negative correlation was found between m-Ins and neuronal loss in the CA4 subfield of the hippocampus (P = 0.028). Our results support (1)H-MRS as a suitable non-invasive method for preoperative identification of hippocampal sclerosis in patients with TLE. The extent of tNAA reduction correlates with hippocampal neuronal cell density. Furthermore, m-Ins is associated with the extent of hippocampal astrogliosis.     

Enhanced gamma (30–150 Hz) frequency in the human medial temporal lobe

We performed fast Fourier transformation power spectral analysis of the electrocorticogram in human medial temporal lobe during wakeful rest in six epileptic subjects. Compared with the electrocorticogram wave in the basal temporal lobe, which showed monotonic decline of spectral power across the frequency axis, the electrocorticogram wave in the parahippocampal gyrus was enhanced (or did not decline) in the gamma frequency range (30–150 Hz) in all subjects.

Although it has been suggested that electrical oscillations of the hippocampus have functional roles in higher brain functions, namely learning and memory, the knowledge of hippocampal oscillations is largely limited to animal studies. The present results demonstrate that fast frequency oscillation is also present in the human medial temporal lobe, which has been reported in animal hippocampi. They also demonstrate the importance of recording very fast field potentials in human electrocorticograms. This fast oscillation is likely to play important functional roles related to learning and memory, possibly to induce long-term potentiation in the human medial temporal lobe.     

Hippocampal sclerosis: progress since Sommer

Hippocampal sclerosis (HS) continues to be the most common pathology identified in patients with refractory temporal lobe epilepsy undergoing surgery. Wilhelm Sommer described this characteristic pattern of neuronal loss over 120 years ago through his post-mortem studies on patients with epilepsy. Neuropathological post-mortem studies in the 20th century proceeded to contribute significantly to the understanding of this disease process, with regard to the varying patterns of HS and involvement of adjacent limbic structures. From studies of surgical temporal lobe specimens from the 1950s onwards it was recognized that an early cerebral injury could act as the precipitant for the sclerosis and epilepsy. Modern neuropathological studies have focused on aspects of neuronal injury, loss of specific neuronal groups and cellular reorganization to address mechanisms of epileptogenesis and the enigma of how specific hippocampal neuronal vulnerabilities and glial proliferation are both the effect and the cause of seizures.     

无镁液灌流大鼠海马脑片自发性癫痫样放电的药物敏感性

用常规海马脑片实验方法：撤除人工脑脊液中的Ｍｇ＾２＋、０．５ｈ内ＣＡ１区出现自发性痫样放电,１ｈ内于稳定,约１／３脑片波幅可稳定２ｈ左右,但放电频率呈缓慢增加,无Ｍｇ＾２＋灌流后１￣３ｈ间可以观察抗痫药的作用。苯妥英钠（ＰＨＴ）１００μｍｏｌ／Ｌ,氨甲酰氮卓（ＣＢＺ）１００μｍｏｌ／Ｌ,安定（ＤＺＰ）３０μｍｏｌ／Ｌ,苯巴双妥钠（ＰＢ）１００μｍｏｌ／Ｌ,丙戊酸钠（ＶＰＡ）１０ｍｍｏｌ／Ｌ及乙琥胺     

难治性颞叶癫癎患者海马病理研究

目的:探讨海马硬化和难治性颞叶癫的因果关系。方法:对8例海马硬化患者和7例非海马硬化患者临床资料、手术疗效和海马病理改变进行对比和相关分析。结果:海马硬化组较非海马硬化组病程长,疗效显著,疗效分级与最初脑损伤发生年龄呈正相关。海马硬化组和非海马硬化组均有CA1,CA3锥体细胞和颗粒细胞脱失,海马硬化组更明显。门区神经元脱失仅在海马硬化组可见。海马神经元脱失与脑损伤发生年龄呈正相关。结论:生命早期的脑损害是海马硬化的成因。硬化海马是难治性癫的致灶。以海马结构齿状回门区神经元,颗粒细胞和海马CA3锥体细胞脱失为特点的海马硬化是难治性颞叶癫的主要病理特点和病因,门区细胞的脱失是海马硬化的特征性病理改变,可能在难治性癫的发病机理中起着重要作用。     

颞叶癫痫患者颞叶皮层和海马组织内多药耐药相关蛋白1和胶质原纤维酸性蛋白共表达

目的 观察颞叶癫痫病人多耐药基因1（MDR1）、胶质原纤维酸性蛋白（GFAP）和神经元特异性烯醇化酶（NSE）在颞叶和海马组织内的表达。方法 癫痫组样本来自12例颞叶癫痫病例的手术切除标本,对照组为4例非癫痫病的尸检脑组织。应用双重免疫荧光组织化学方法结合激光共聚焦显微镜技术显示MDR1、GFAP和NSE在颞叶和海马组织内的表达。结果 对照组颞叶皮质和海马齿状回内均可见到许多GFAP表达阳性的星形胶质细胞和NSE表达阳性的神经元,未见到表达MDR1的细胞。癫痫组颞叶皮质和海马齿状回内GFAP阳性星形胶质细胞高于对照组。颞叶皮层和海马组织内可见星形胶质细胞MDR1 和GFAP 共表达现象。结论 颞叶难治性癫痫可能与星形胶质细胞的多药耐药性有关。