颞叶癫痫致痫灶的病理学研究进展

癫痫是由多种不同病因引起的慢性脑部疾病。临床主要表现为短暂、突然、反复的的痫性发作，长期、频繁的癫痫发作会导致大脑功能紊乱。颞叶癫痫占难治性癫痫病人的60％-70％，是局限性癫痫的代表。颞叶癫痫致痫灶的最主要病理改变是海马硬化，其次是低级别胶质细胞瘤、血管性疾病等“占位性”病变和先天性皮质发育异常等。以下就颞叶癫痫致痫病变及其病理学研究进展予以综述。     

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。     

功能性大脑半球切除术治疗婴儿偏瘫综合征伴难治性癫痫

目的：探讨功能性大脑半球切除术治疗婴儿偏瘫综合征伴难治性癫痫的临床疗效。方法：对3例婴儿偏瘫综合征伴难治性癫痫患者采用功能性大脑半球切除术行手术治疗，切除感觉运动皮质和颞叶，切开胼胝体，孤立残留的额叶及顶枕叶部分脑组织，术后随访观察其临床治疗效果。结果：3例婴儿偏瘫综合征患者的癫痫发作均得到完全控制，行为改善，且神经功能缺失症状未加重。结论：对婴儿偏瘫综合征伴难治性癫痫患者行病侧功能性大脑半球切除术，可使癫痫发作得到良好的控制。     

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。     

小儿癫痫及其发作类型、频率与脑细胞葡萄糖代谢的相关性研究

目的： 探讨小儿癫痫及其发作类型、频率与癫痫灶脑细胞葡萄糖代谢的相关性。方法: 对经临床、EEG及MRI检查确诊的86例癫痫患儿进行脑18F-FDG PET显像检测,以反映癫痫灶脑细胞葡萄糖代谢情况。结果: 与对照组比,癫痫组脑PET显像异常 (P<0.01);异常率为89.9% (77/86), 其中72例发作间期为低代谢显像,5例发作期为高代谢显像。不同发作类型癫痫患儿脑PET显像异常的脑区不同,婴儿痉挛症和Lennox-Gastaut syndrome 脑PET显像异常部位主要在双侧皮质,呈双侧大脑弥漫性皮质低代谢改变,复杂部分性发作患儿则主要为颞叶。脑PET显像异常与发作频率或病情呈正相关(P<0.01),即脑PET显像异常愈重,发作频率愈高或病情愈重;但与发病年龄无关(P>0.05)。结论: 癫痫患儿脑细胞葡萄糖代谢异常;不同发作类型的癫痫患儿脑细胞葡萄糖代谢异常的脑区不同;脑PET显像异常与发作频率或病情呈正相关。     

海仁酸诱导癫痫模型海马的形态学改变

癫痫症是最常见的神经系统疾病之一，海仁酸是脑内兴奋性氨基酸递质—谷氨酸的结构类似物，脑内或系统给予惊厥剂量的海仁酸，可选择性的激活边缘系统，引起急性癫痫发作。目前，海仁酸模型已广泛用于癫痫发作的研究，其特点是具有与人类颞叶癫痫极为相似的癫痫发作行为特征和海马硬化的神经病理学改变。本文对海仁酸癫痫模型出现的海马形态学的改变及其可能的机制进行了综述。     

难治性癫痫体外反搏作辅助治疗的体会

现代影像学技术发现癫痫病灶为一低血流灌注区,为此作者对8例难治性癫痫在原抗痫药不变情况下,加用体外反搏治疗取得一定效果,特作报告如下。 患者男7名,女1名,年龄28～67岁,癫痫病史已8～37年,有全身强直阵挛发作6例,颞叶癫痫1例,顶叶癫痫1例。体外反搏每日1次,每次50分钟,15次为一疗程。计完成2个疗程2例,3个疗程3例,4     

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。     

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。     

基于Granger因果分析的癫痫发作间歇期EEG在δ频段的功能连接模式

目的 应用频域Granger因果分析方法,研究颞叶癫痫发作间歇期16导脑电图(EEG)在与癫痫发作相关的δ频段的过度放电功能连接特性.方法 实验数据来自颞叶癫痫9例患者(6例左颞叶癫痫,3例右颞叶癫痫),9例正常对照受试者.记录每例颞叶癫痫受试者在发作间歇期的痫样放电、非痫样放电以及正常对照组的共3个状态的16导EEG;每个状态下各记录10个EEG数据段,每个数据段长度为20s,采样频率为200 Hz;应用带通滤波提取EEG的δ分量(1～4 Hz).应用频域Granger因果分析方法,分别计算痫样放电组、非痫样放电组和正常组10次记录的16通道EEGδ频段分量之间的频域因果度量平均值Iδ;分析以上3个组颞叶区(左颞叶癫痫:T3、T5,右颞叶癫痫:T4、T6)与额区(Fp1、Fp2、F3、F4)和顶区(C3、C4)之间EEG在δ频段的功能连接模式.结果 痫样放电组:下颞叶区(左下颞叶区T5,右下颞叶区T6)与额区、顶区之间Iδ在0.1323±0.0329～0.1670±0.0289;非痫样放电组:下颞叶区与额区、顶区之间的Iδ在0.0300±0.0130～0.0420±0.0072;正常对照组:下颞叶区与额区、顶区之间的Iδ在0.0153±0.0028～0.0193±0.0057.统计结果表明:痫样放电组下颞叶区与额区、顶区之间的Iδ值与非痫样放电组相比差异有统计学意义(P＜0.05),与正常对照组相比差异有统计学意义(P＜0.01);非痫样放电组下颞叶区与额叶、顶叶之间的Iδ值和正常对照组相比差异无统计学意义(P＞0.05).结论 颞叶癫痫发作间歇期在痫样放电状态下,EEGδ频段在下颞叶区与额区、顶区之间存在较强连接,过度放电从下颞叶区传递到额区和顶区.非痫样放电组和正常组的EEGδ频段,下颞叶区与额叶、顶叶之间连接弱,下颞叶区不是EEG信号传导的起始区.     

Functional neuroimaging in epilepsy: FDG PET and ictal SPECT.

Epileptogenic zones can be localized by F-18 fluorodeoxyglucose positron emission tomography (FDG PET) and ictal single-photon emission computed tomography(SPECT). In medial temporal lobe epilepsy, the diagnostic sensitivity of FDG PET or ictal SPECT is excellent, however, the sensitivity of MRI is so high that the incremental sensitivity by FDG PET or ictal SPECT has yet to be proven. When MRI findings are ambiguous or normal, or discordant with those of ictal EEG, FDG PET and ictal SPECT are helpful for localization without the need for invasive ictal EEG. In neocortical epilepsy, the sensitivities of FDG PET or ictal SPECT are fair. However, because almost a half of the patients are normal on MRI, FDG PET and ictal SPECT are helpful for localization or at least for lateralization in these non-lesional epilepsies in order to guide the subdural insertion of electrodes. Interpretation of FDG PET has been recently advanced by voxel-based analysis and automatic volume of interest analysis based on a population template. Both analytical methods confirmed the performance of previous visual interpretation results. Ictal SPECT was analyzed using subtraction methods(coregistered to MRI) and voxel-based analysis. Rapidity of injection of tracers, HMPAO versus ECD, and repeated ictal SPECT, which remain the technical issues of ictal SPECT, are detailed.     

Brain fluorodeoxyglucose (FDG) PET in dementia

The purpose of this article is to present a selective and concise summary of fluorodeoxyglucose (FDG) positron emission tomography (PET) in dementia imaging. FDG PET is used to visualize a downstream topographical marker that indicates the distribution of neural injury or synaptic dysfunction, and can identify distinct phenotypes of dementia due to Alzheimer's disease (AD), Lewy bodies, and frontotemporal lobar degeneration. AD dementia shows hypometabolism in the parietotemporal association area, posterior cingulate, and precuneus. Hypometabolism in the inferior parietal lobe and posterior cingulate/precuneus is a predictor of cognitive decline from mild cognitive impairment (MCI) to AD dementia. FDG PET may also predict conversion of cognitively normal individuals to those with MCI. Age-related hypometabolism is observed mainly in the anterior cingulate and anterior temporal lobe, along with regional atrophy. Voxel-based statistical analyses, such as statistical parametric mapping or three-dimensional stereotactic surface projection, improve the diagnostic performance of imaging of dementias. The potential of FDG PET in future clinical and methodological studies should be exploited further.     

影响颞叶癫癎预后的危险因素分析

目的：探讨影响颞叶癫癎预后的危险因素,为临床合理治疗颞叶癫癎和判断预后提供依据。方法：采用病例对照研究,回顾性分析两组颞叶癫癎患者即药物难治组102例,药物控制良好组166例的临床资料,采用单因素分析和多因素Logistic回归模型分析影响颞叶癫癎预后的相关因素。结果：单因素分析表明合理药物治疗前病程长、初期发作频繁（〉4次／月）、围产期损伤、服药依从性差、具有神经系统疾患和有影像学异常等6个因素对颞叶癫癎的预后有不利影响（均P〈0．05）,进一步进行多因素Logistic回归分析,筛选出合理治疗前病程长（OR=1．989,95％CI：1．071～3．692）、初期发作频率高（OR=10．393,95％CI：5．355～20．170）、服药依从性差（OR=5．151,95％CI：2．916～8．615）、具有神经系统疾患（OR=1．113,95％CI：0．564-4．448）和有影像学异常（OR=4．032,95％CI：2．160～7．526）是影响颞叶癫癎预后的独立危险因素。结论：合理药物治疗前病程长、初期发作频繁（〉4次／月）、患者服药依从性差、具有神经系统疾患和影像学异常是药物治疗颞叶癫癎的重要危险因素,具有这些因素的患者易发展成难治性癫癎。     

Neural correlates of dementia: regional brain metabolism (FDG-PET) and the CERAD neuropsychological battery.

The present Investigation examined the biological correlates of the cognitive deficits of Alzheimer's disease and related dementias using the neuropsychological assessment battery of the Consortium to Establish a Registry of Alzheimer's Disease (CERAD) and positron emission tomography (PET). Resting state cerebral glucose metabolism was measured using the labelled radiotracer, [18F] Fluoro-2-deoxyglucose (FDG), in a sample of patients with mild to moderate dementia (n = 66). Specific and predictable relationships were seen between regional brain metabolism (left and right, frontal, temporal, and parietal lobes) and the neuropsychological measures of verbal fluency, constructional praxis, and verbal list learning. On tests of naming and delayed verbal recall only diminished FDG uptake in the left frontal lobe and the left temporal lobe, respectively, approached significance. This study demonstrates the expected relationships between neuropsychological performance and regional cerebral metabolism, thereby providing support for the CERAD battery as a valid measure in the clinical evaluation of dementia and for the use of FDG-PET in brain-behavior studies of dementia.     

难治性癫痫与多药耐药基因

难治性癫痫的耐药机制尚不十分清楚。多药耐药基因(MDR)是首个被发现与难治性癫痫相关的基因,其表达产物P-糖蛋白(Pgp)在难治性癫痫脑组织中表达增强,颞叶癫痫耐药机制则可能与MDR-1a mRNA及MDR-1b mRNA的高表达相关,特异性Pgp抑制剂能显著提高部分抗癫痫药物在难治性癫痫中的作用。对它们的深入研究可能会为难治性癫痫的治疗提供新途径及为新的抗癫痫药物的研究提供靶点。     

PET脑显像及其他显像技术在放射性脑损伤诊断的对比性研究

目的 探讨^18F－脱氧葡萄糖（FDG）正电子发射型计算机断层显影（PET）脑显像和其他医学影像方法对早期诊断放射性脑损伤的价值，以达到预防、减少脑放射损伤的目的。方法 静脉注射^18F-FDG后行脑显像，获得横断面、冠状面、矢状面断层显像。所有病人均进行CT检查。结果 20例正常人脑PET显像图像可见大脑皮质各叶、基底神经节、丘脑及小脑放射性分布均匀对称。12例完成头颈部恶性肿瘤放疗后有临床症状者均检出不同程度局灶性脑组织葡萄糖代谢下降，显像阳性率100％；其中10例鼻咽癌放疗后PET结果提示放射脑损伤病灶共23处，最常见于颞叶病灶13处、脑干4处、小脑4处以及顶叶2处。2例脑胶质细胞瘤放疗病人，PET结果提示病灶：顶叶2处、颞叶1处、枕叶1处。12例放疗后病人CT检查仅10例提示放射性脑损伤。结论 PET脑显像能准确、早期诊断脑放射损伤，是头颈部恶性肿瘤肿瘤放疗后的非常重要的监测手段。     

Computer-assisted lateralization of unilateral temporal lobe epilepsy using Z-score parametric F-18 FDG PET images

Background

To evaluate the use of unbiased computer-assisted lateralization of temporal lobe epilepsy (TLE) by z-score parametric PET imaging (ZPET).

Methods

38 patients with histologically proven unilateral TLE due to pure hippocampal sclerosis, referred for pre-surgical PET evaluation of intractable seizure over a 5-year period, were included. The F-18 FDG images were oriented along temporal long axis and then transformed into ZPET images on a voxel by voxel basis. Multiple regions of interests (21 in total) were placed on cortical, subcortical and cerebellar structures on twenty-eight out of 38 patients with totally seizure-free (class I) outcome. Paired t-tests with Bonferroni correction were used to determine the location of the most asymmetric regions as variables for subsequent discriminant analysis of the entire group of the patients.

Results

The computer program identified the anterior half of the temporal lobe (p < 0.0005) and thalami (p = 0.021) as the most asymmetric regions in TLE patients with Class I outcome. Discriminant analysis using z-scores from a total of 8 ROIs (in 4 pairs) on these structures correctly lateralized thirty-seven out of 38 (97%) patients (sensitivity = 94%; specificity = 100%). The only false localization came from a patient with equivocal z-scores on the temporal lobes and this patient turned out to have poor outcome.

Conclusion

The computer-assisted lateralization of TLE using ZPET provides an accurate, fast and objective way of seizure evaluation.     

Development of Korean standard brain templates

We developed age, gender and ethnic specific brain templates based on MR and Positron-Emission Tomography (PET) images of Korean normal volunteers. Seventy-eight normal right-handed volunteers (M/F=49/29) underwent 3D T1-weighted SPGR MR and F-18-FDG PET scans. For the generation of standard templates, an optimal target brain that has the average global hemispheric shape was selected for each gender. MR images were then spatially normalized by linear transformation to the target brains, and normalization parameters were reapplied to PET images. Subjects were subdivided into 2 groups for each gender: the young/midlife (<55 yr) and the elderly groups. Young and elderly MRI/PET templates were composed by averaging the spatially normalized images. Korean templates showed different shapes and sizes (mean length, width, and height of the brains were 16.5, 14.3 and 12.1 cm for man, and 15.6, 13.5 and 11.4 cm for woman) from the template based on Caucasian (18.3, 14.2, and 13.3 cm). MRI and PET templates developed in this study will provide the framework for more accurate stereotactic standardization and anatomical localization.     

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。