脑局灶性皮层发育不良相关性难治性癫痫的临床病理分析

目的探讨脑局灶性皮层发育不良(FCD)相关性难治性癫痫的临床病理特点。方法对29例2000年1月至2009年8月在本院接受难治性癫痫外科手术并病理诊断为FCD患者的临床资料、神经影像学以及病理学资料进行回顾性分析。并对所有患者进行随访,包括术后服用抗癫痫药物、影像学检查以及癫痫改善或复发的情况。结果 29例患者平均年龄23.5岁,平均病程11.3年,发作形式以复杂部分性发作为主。影像学检查有4例可见海马硬化。病理组织学以FCDⅠ型多见,具体分型为轻微皮层发育不良(mildMCD)3例,FCDⅠa型6例,FCDⅠb型10例,FCDⅡa型5例,FCDⅡb型5例。从发病部位来看,额叶最多见(15例),其次为颞叶(8例),顶叶(6例)。具有双重病理改变的有4例(FCDⅠa型伴海马硬化2例,FCDⅠb型伴海马硬化1例,FCDⅡb伴海马硬化1例)。5例合并胚胎发育不良性神经上皮瘤(DNT)。免疫组化染色示巨大神经元、未成熟神经元、形态异常神经元及白质内异位神经元NeuN均阳性,少数气球细胞呈nestin阳性表达。术后所有病例影像学复查无FCD改变,癫痫控制结果Ⅰa级6例,Ⅰ级5例,Ⅱ级3例,Ⅲ级2例,Ⅳ级13例。手术切除治疗后随访5个月以上,总治愈率为16/29,其中轻型组8/9,重型组8/20。结论 FCD相关性难治性癫痫中FCDⅠb型为最多见类型,分型与预后有关。     

局灶皮层发育不良致难治性癫痫160例临床病理分析

目的探讨局灶皮层发育不良的临床病理学分型及特点。方法收集160例病理诊断为局灶皮层发育不良的难治性癫痫手术治疗患者的病理标本及临床资料。采用HE和免疫组织化学染色,探讨各种类型癫痫病理的临床病理学特点。结果局灶皮层发育不良160例,其中FCDⅠB134例、FCDⅡA16例、FCDⅡB10例。结论局灶皮层发育不良为引发难治性癫痫最常见病因,而亚型中以FCDⅠB型最为多见。免疫组化有助于FCD的诊断与分型。     

癫痫患者切除病灶病理学分析

目的分析癫痫患者切除的致痫灶标本的病理形态学特点。方法将切除的新鲜脑内致痫灶组织标本进行常规处理，HE染色、特殊染色及免疫组化染色，显微镜下观察其病理学改变。结果133例患者中，原发性癫痫58例（43．6％），包括皮质微发育不良15例，局灶性皮层发育不良（FCD）ⅠA14例，FCDⅠB8例，FCDⅡA11例，FCDⅡB6例，皮层发育不良2例，皮层发育畸形2例；继发性癫痫75例（56．4％），包括肿瘤60例，其中胶质瘤41例，其他原发和转移恶性肿瘤9例，良性肿瘤10例；非肿瘤者15例。结论癫痫是多种病因、多种病变引起的一组疾病，其病理形态学最常见的是脑肿瘤，其次是脑原发性结构异常。     

皮层电极监测下切除致痫性脑胶质瘤的临床研究

目的使用皮层电极监测切除致痫性脑胶质瘤，探讨致痫性脑胶质瘤的治疗方法。方法本组病人43例。EEG示轻度异常脑电图9例，巾度异常脑电罔26例，重度异常脑电图8例。CT或MRI检查皆可见占位病变。常规手术开颅显露相应部位脑皮层使用皮层电极对脑电进行监测。确定大体致痫范围，行肿瘤切除。肿瘤切除后再行脑电监测，若仍有癫痫波，根据皮层电极之定位切除致痫灶。结果22例病人行显微镜下肿瘤全切除，15例病人近全切除肿瘤．6例病人次全切除肿瘤。术后随访6个月～6年。34例(79．1％)病人癫痫症状消失，7例(16.3％)病人癫痫发作次数明显减少，2例(4．7％)病人癫痫症状未见好转。总有效率(93．7％)。结论以癫痫为主要症状的脑肿瘤病人．只有在切除胶质瘤时一并切除致痫灶，才是治疗肿瘤并根治癫痫的最佳方法。皮层电极监测下切除致痫性脑胶质瘤是治疗有癫痫症状的脑胶质瘤的有效方法。     

皮层电极监测下切除致痫性脑胶质瘤的临床研究

目的使用皮层电极监测切除致痫性脑胶质瘤,探讨致痫性脑胶质瘤的治疗方法.方法本组病人35例,男19例,女16例.术前行EEG、CT或MRI检查.EEG示轻度异常脑电图7例,中度异常脑电图22例,重度异常脑电图6例.CT或MRI检查皆可见占位改变.其中额叶11例,颞叶8例,额顶叶7例,顶叶5例,颞枕叶3例,岛叶深部1例.常规手术开颅显露相应部位使用VEEG1161型伟思脑电图仪对皮层脑电进行监测.监测范围包括全部肿瘤,重点于肿瘤周边脑组织.确定大体致痫范围,行肿瘤切除.肿瘤切除后再行脑电监测若仍有癫痫波,根据皮层电极之定位切除致痫灶.直至致痫灶全部切除.对疑有深部癫痫灶者,使用深部电极经皮层穿刺对深部脑组织进行监测描记.对重要脑功能区予以保护.结果全部病人皆行显微镜下肿瘤全切除.病理证实星形细胞瘤8例,间变性星形细胞瘤13例,少突胶质细胞瘤7例,间变性少突胶质细胞瘤5例,胶质母细胞瘤2例.术后随访6个月～5年.未再发生癫痫者29例(82.9%);总有效率94.3%.结论只有在切除胶质瘤时一并切除致痫灶,才是治疗肿瘤并根治癫痫的最佳方法.使用皮层电极监测胶质瘤的切除,具体很多优点.     

局灶性皮层发育不良与mTOR信号通路

正局灶性皮层发育不良(focal cortical dysplasia,FCD)是一种最常见的引起难治性癫痫的皮层发育畸形[1]。近年来,对FCD发病机制以及FCD致痫机制的研究,很多集中在哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,m TOR)信号通路的激活与神经元的结构和电生理改变的关系,为将来寻找诊断和治疗FCD的新靶点提供了依据。1 FCD概述FCD的典型特征是局部脑皮层的结构紊乱,伴有细胞形态和排列结构紊乱,如巨大神经元、形态异常神经元和气球细胞等细胞水平的异常。FCD可以     

局灶皮层发育不良51例的病理与临床

目的探讨局灶性皮层发育不良(Focal cortical dysplasia,FCD)的病理与临床特征。方法按照2011年国际抗癫痫联盟(ILAE)的分类标准,对2015年1月—2018年9月中国人民解放军联勤保障部队第988医院收治的51例FCD患者病脑组织进行病理分型,分析不同分型的癫痫发作特征。结果 FCDⅠ型23例(45.1%)、Ⅱ型11例(21.6%)、Ⅲ型17例(33.3%)。Ⅰa型最多(23.5%,12/51),镜下特征为神经元呈微柱状结构排列,免疫组化NF呈紧贴着神经元的线样、瀑布样表达;其次是Ⅲa型(15.7%,8/51),镜下以海马CA4区锥体细胞减少或缺失为主。各类型在双侧大脑半球的发生率无统计学差异,主要是单脑叶发生,颞叶显著多余额叶,超过50%的病例18岁以前出现癫痫症状,主要表现为部分性发作、继发全身强直阵挛,Ⅲ型患者的癫痫首次发作年龄早于Ⅰ、Ⅱ型,癫痫病史也长于其他两型。影像上Ⅰ型阳性率78.3%,其余两型均为100%。结论 FCD是癫痫患者常见的病理特征,仔细的病理检查是各亚型准确分型的前提,Ⅲ型的癫痫发作不同于Ⅰ、Ⅱ型。     

57例皮质发育异常相关性癫痫临床病理分析

目的 探讨皮质发育异常(MCD)相关癫痫的临床病理特征.方法 回顾性分析57例MCD相关癫痫的临床病理资料,分析其病理学特征.结果 MCD相关癫痫占同期手术治疗癫痫的43%.57例MCD相关癫痫中,脑沟回结构紊乱8例;皮质微发育不良(MD)8例;局灶性皮质发育不良(FCD)41例,其中FCD Ⅰ A 13例,FCD Ⅰ B 15例,FCD Ⅱ A7例,FCD Ⅱ B 6例.57例MCD中22例伴海马硬化;1例FCDⅡB伴胚胎发育不良性神经上皮瘤(DNT);1例FCDⅡB局部向神经节神经胶质瘤(GGs)过渡.结论 MCD与难治性癫痫关系密切,以FCD Ⅰ型最为常见,多数病例伴有海马硬化.     

局灶性脑皮层发育不良致顽固性癫痫的外科治疗

目的总结局灶性脑皮层发育不良致顽固性癫痫的诊断、手术治疗方案及效果。方法选取28例局灶性脑皮层发育不良致顽固性癫痫患者,MRI、脑电图（EEG）及正电子发射断层成像（PET）提示癫痫病灶位于发育不良区域,在皮层脑电图监测下切除病灶并进行病理学检查,患者继续服药并随访1年以上。结果局灶性脑皮层发育不良区存在不同程度神经细胞缺失和胶质细胞增生。患者1年预后按Engel标准分级：Ⅰ级12例,Ⅱ级9例,Ⅲ级4例,Ⅳ级3例。结论局灶性脑皮层发育不良区的神经细胞减少和少枝/小胶质细胞增生可能是引起癫痫发作的病理学基础。建议在术中脑电图监测下进行癫痫灶切除术和软膜下横切术,术后1年内75%患者控制良好。     

颞叶结合型局灶性脑皮质发育不良超微结构分析

<正>局灶性脑皮质发育不良(focal cortical dysplasia,FCD)是难治性癫痫的重要病因,经手术治疗的75%以上的儿童癫痫术后病理证实为FCD,是儿童癫痫的首要病因。约20%的成人癫痫存在FCD,全体人群中约50%的癫痫患者是因各种不同类型的FCD所引起[1]。1971年,Taylor等对10例难治性癫痫患者手术切除标本进行显微镜观察,发现了皮层异常结构,系统描述了FCD的病理组织结构特点[2]。以后FCD的概念被广泛应用在解剖学、病理学和影像学等各个领域当中。FCD是一个相对宽泛的概     

局灶性脑皮质发育不良致难治性癫痫病理分型和手术疗效分析

目的 探讨难治性癫痫术后局灶性脑皮质发育不良(FCD)不同病理分型与术后疗效的相巨关系.方法 回顾性分析54例经手术治疗后,病理证实为FCD的药物难治性癫痫患者的临床资料,分析病理分型与手术预后的关系.结果 轻型组(FCD Ⅰ A)24例,重型组(FCD Ⅰ B+ⅡA+ⅡB)30例.术后有效率:轻型组96%,重型组70%,总有效率82%.结论 随着FCD病理改变程度的逐渐加重,手术后疗效越来越差,FCD可能是影响药物难治性癫痫术后疗效的一个重要因素.     

难治性癫(癎)相关耐药蛋白在局灶性皮质发育不良脑组织中的表达

目的 通过对P-糖蛋白、多药耐药相关蛋白和肺耐药相关蛋白在难治性癫痫相关局灶性皮质发育不良脑组织中表达部位的初步研究,以及对其在不同程度病变脑组织中表达量的比较,进一步阐明难治性癫疴的耐药机制,为癫(癎)患者的临床合理用药提供理论依据.方法 选取16例难治性癫(癎)患者手术切除脑组织标本作为患者组(局灶性皮质发育不良Ⅰ型和Ⅱ型患者各8例),5例无癫(癎)发作病史的胶质瘤患者手术切除脑组织标本的非病灶区域作为对照组.应用Envision二步法进行免疫组织化学标记,观察3种耐药蛋白在脑组织中的表达部位和表达强度;应用Western blot法进行SDS-聚丙烯酰胺凝胶电泳,对3种耐药蛋白在脑组织中的表达进行定量分析.结果 P-糖蛋白主要表达于毛细血管内皮细胞,多药耐药相关蛋白主要表达于脑组织内的神经元成分,肺耐药相关蛋白的表达则涌盖了毛细血管内皮细胞、气球细胞及病灶区域部分基质.3种耐药蛋白在局灶性皮质发育不良脑组织中的表达均显著高于对照组脑组织(P-糖蛋白:0.520±0.121,多药耐药蛋白:0.132±0.018,肺耐药相关蛋白:0.092 4-0.018,U=0.000,P<0.01),其中P-糖蛋白和肺耐药相关蛋白在局灶性皮质发育不良Ⅱ型患者的病灶区域(3.809±0.842、0.655±0.303)表达高于病灶周围区域(2.636 4±0.622、0.290±0.096,U=6.000、4.500,P<0.01).结论 P-糖蛋白、多药耐药相关蛋白和肺耐药相关蛋白在不同程度的局灶性皮质发育不良脑组织中具有不同的表达部位和表达量,提示其作用机制和作用强度有所差异.     

脑皮质发育不良继发顽固性癫痫的病理分型及手术治疗

目的 探讨局灶性脑发育不良(FCD)的临床特征、病理学、影像学的特点及手术疗效.方法 42例外科手术切除致痫灶并经病理证实为FCD的患者中,根据Palmini病理学分型进行分类,并对其临床特征、影像学特点及手术疗效进行回顾性分析.结果 42例患者中,按致痫灶部位分类颢叶24例、额叶14例、顶叶6例及枕叶3例,其中多脑叶5例.术前影像学检查阳性率62%.组织学分型FCDⅠA型9例,FCDⅠB型21例,FCDⅡA型5例,FCDⅡB型7例,其中以FCD Ⅰ B型最为常见,多位于颞叶且常伴有海马硬化.所有患者术后至少随访1年以上,癫痫术后治愈率FCD位于颞叶67%,颞叶以外43%(EngleⅠa).结论 FCD是难治性癫痫常见的病理学改变,其病理分型与临床特征和致痫灶部位存在相关性,为制定手术方案和判定手术效果提供了依据.     

难治性癫痫172例临床病理分析

目的 探讨难治性癫痫病灶切除手术患者的临床病理学分型及特点.方法 收集清华大学玉泉医院2008年1月至2009年6月,172例难治性癫痫手术治疗患者的病理标本及临床资料.采用HE和免疫组化染色,探讨各种类型癫痫病灶的临床病理学特点.结果 经病理诊断,局灶皮质发育不良138例(其中FCD Ⅰ B 115例、FCDⅡA 15例、FCDⅡB 8例)、微发育不良2例、胚胎发育不良性神经上皮瘤4例、Rasmussen脑炎7例、瘢痕脑回16例,节细胞瘤、多小脑回畸形、血管畸形、下丘脑错构瘤及结节性硬化各1例.结论 局灶皮质发育不良为引发难治性癫痫最常见病因,其中以FCDⅠ B亚型最为多见.     

Pathophysiologic characteristics of balloon cells in cortical dysplasia

Objects Balloon cells are histopathological hallmarks of cortical malformations, i.e., focal cortical dysplasia (FCD) of the Taylor type or the cortical tubers of tuberous sclerosis, and they are believed to be the epileptogenic substrate and cause therapeutic drug resistant epilepsy in man. This study was carried out to investigate the developmental histogenesis and epileptogenesis of balloon cells in FCD. Materials and methods We used an immunohistochemical approach to examine the expressions of primitive neuroepithelial cell antigens (CD34, nestin, and vimentin), ionotrophic glutamate receptor subunits (NR1, NR2A/B, GluR1, GluR2, GluR3, GluR4, and GluR5/6/7), and P-glycoprotein in balloon cells from FCD and normal cerebral cortex epileptogenic lesions. Conclusion Balloon cells presented in clusters or as scattered cells throughout FCD lesions involving the gray and white matter. We found the balloon cells to be classifiable into three subtypes based on glial fibrillary acidic protein (GFAP) and neurofilament protein (NF-L) immunohistochemistry, i.e., as neuronal, astrocytic, and uncommitted. Immunopositivity for nestin, CD34, and vimentin in balloon cells of FCD suggests that they may be derived from the abnormal development and differentiation of neural stem cells. Moreover, it appears that epileptogenesis in cortical dysplasia is partly caused by the upregulations of some glutamate receptor subunit proteins (NR1, NR2A/B, GluR1, and GluR3) in balloon cells and dysplastic neurons. We speculate that the presence of the drug resistance protein P-glycoprotein in balloon cells might explain medically refractory epilepsy in FCD.     

Clinical and experimental studies of epilepsy associated with focal cortical dysplasia

The results of clinical and experimental studies on epilepsy associated with focal cortical dysplasia (FCD) are presented. We have been interested in the findings of abnormal increases in the numbers of small vessels in specimens of FCD resected from epilepsy patients. In the clinical study of 13 patients with epilepsy, specimens of FCD or dysembryoplastic neuroepithelial tumor (DNT) were examined using immunohistochemistry. The number of vessels in both lesions were greater than those in cortical specimens of autopsy cases without epilepsy. Because the vessels showed negative staining of VEGF, it was thought that the phenomenon of increase in the number of vessels was simply a hypervascularity, not a neovascularity. The local hypervascularity was expected to show local hyperperfusion in CBF-SPECT study, but interictal SPECT demonstrated local hypoperfusion and ictal SPECT showed hyperperfusion. This may have been caused by a functional change in those vessels. In the experimental study, we tried to make a new animal model of FCD to study epileptogenicity of FCD. When kainic acid had been infused into the neocortex in the neonatal rats, FCD was induced in adult Wistar rats. Histopathological examination revealed cortical dyslamination and abnormal neurons. On EEG, local spike bursts were elicited from the lesions, however, clinical seizures were not detected. Although the data are preliminary and observation over a longer period is required to determine whether spontaneous seizures will occur in this model, it is expected that this new model will be useful for studying epilepsy associated with FCD.     

Focal cortical dysplasia: pathophysiological approach

Overview Clinical and experimental studies on focal cortical dysplasia (FCD) were carried out.Materials and methods For the experimental study, an experimental FCD model of rats was developed. Twenty Wistar rats at 0–2 days after birth were used for the study. Kainic acid (KA) solution was injected stereotaxically into medial and lateral sites of the sensori-motor cortex. Bipolar electrodes were inserted in five rats. Their behavior and electroencephalogram (EEG) were recorded using a digital-video-EEG monitoring system. After observation periods of 1, 2, and 6 months, rats were perfused for pathological study. FCD was observed adjacent to the site of KA injection in all rats more than 1 month after the injection.Results and discussions EEG recording demonstrated focal spike discharges in and around the site of injection. However, clinical seizure was not observed. Pathological studies showed decrease in GABA-A receptors and increase in GABA-B receptors not only in the lesion but also in perilesional areas. Fifteen surgical cases of FCD with intractable epilepsy were subjected to the clinical study. Neuro-imaging studies including high-resolution magnetic resonance imaging and single-photon emission computed tomography were performed. Conventional EEG studies demonstrated focal EEG abnormalities with epileptic phenomena. At surgery, intraoperative electrocorticography (ECoG) was performed to localize epileptic foci under neuroleptoanalgesia. Thirteen patients showed epileptiform discharges on preresection ECoG. All foci in non-eloquent areas were resected. Pathological studies including immunohistochemical staining were performed, and the characteristics of the FCD in relation to EEG findings were analyzed. Patients in whom total lesionectomy with complete focus resection was performed had favorable postoperative courses. Nine patients (64.3%) have been seizure-free with reduced medication, and significant improvement was achieved in two patients (14.3%). Electrophysiological examination revealed epileptogenecity not only in the lesions but also in perilesional areas. The immunohistochemical studies showed a decrease in GABA-A receptors and an increase in GABA-B receptors in both the lesions and perilesional areas, but N-methyl-d-aspartate receptors were almost negative in both areas. Glutamate R1 was decreased in both areas, but glutamate R2 was increased in both areas. These findings support the results of a electrophysiological study.Conclusions In conclusion, not only the epileptic property of experimental focal cortical dysplasia but also perilesional epileptogenesis was demonstrated. These findings supported the results of surgery for patients with focal cortical dysplasia. In cases of FCD, total removal of the lesion and resection of the perilesional epileptic focus are needed for a good outcome.     

局灶性皮质发育不良皮质中NMDA受体亚基表达情况

目的探讨N-甲基-D-天冬氨酸(N-methyl-D-aspartate,NMDA)受体亚基NR1、NR2A、NR2B在难治性癫病人局灶性皮质发育不良(focal cortical dysplasia,FCD)皮质中的表达及意义。方法选取20例难治性颞叶癫(术后病理证实为FCD)为FCD组及10例颞叶血管畸形病人为对照组,收集两组病人术中切除的颞叶皮质,利用免疫组化和Syber Green荧光定量PCR技术检测标本中NMDA受体亚基NR1、NR2A、NR2B蛋白和mRNA的表达情况。结果对照组NR1、NR2A和NR2B蛋白表达分别为3.5、3、3,FCD组分别为5、5、5。对照组NR1、NR2A和NR2B mRNA表达分别为1.109、1.079、1.157,FCD组分别为2.176、2.324、2.348。与对照组比较,FCD组NR1、NR2A、NR2B蛋白和mRNA表达显著增加(均P<0.01)。结论 FCD皮质中NMDA受体亚基蛋白及mRNA表达升高,可能是FCD致机制之一。