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.     

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。     

难治性癫(癎)273例的临床病理学分析

目的 研究难治性癫(癎)的临床病理学特点.方法 对2005年1月至2007年12月在首都医科大学宣武医院接受致(癎)灶外科手术切除治疗的连续273例患者的临床及病理学资料进行回顾性分析.结果 273例患者的平均发病年龄为11.0岁,平均病程为11.2年.组织学具体分型:皮质发育畸形(MCD)158例,搬痕性脑回63例,肭肿瘤26例,中枢神经系统炎症性病变13例,血管畸形3例,囊肿3例,胆脂瘤1例,其他分类未明6例.其中MCD又包括局灶性皮质发育不良(FCD)Ⅰ型104例(平均发病年龄11.1岁,平均病程11.2年),FCDⅡ型30例(平均发病年龄7.9岁,平均病程12.7年),轻微皮质发育不良(mild MCD)6例,结节性硬化6例,多小脑回3例,其余皮质发育不良9例.158例MCD中有31例伴有海马硬化的病理学表现.134例FCD中FCD Ⅰ B型占86例(64.2%),多位于颢叶(45例).脑肿瘤26例(平均发病年龄14.5岁,平均病程6.3年),其中20例为混合性神经元-胶质肿瘤(76.9%),常见于颞叶,多数周边伴有皮质发育不良的病理学改变.结论 难治性癫(癎)中最常见的病理学类型依次分别为MCD、瘢痕性脑回和肿瘤.FCD最常见的病理学类型为FCD Ⅰ B型,多位于颞叶,常伴有海马硬化.难治性癫(癎)相关的脑肿瘤多为位于颞叶且生长缓慢的混合性神经元-胶质肿瘤.     

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.     

磁共振阴性的局灶性脑皮质发育不良的手术治疗

目的探讨磁共振难以确定病灶的致痫性局灶性脑皮质发育不良的诊断和定位方法,提高手术治疗效果。方法回顾性分析联合应用视频脑电图(VEEG)、脑磁图(MEG)及术中皮层电极脑电图监测(ECo G)检查,诊断、定位并经手术后病理证实为局灶性皮质发育不良(FCD)的24例磁共振检查阴性的难治性癫痫患者的临床资料。结果 24例癫痫患者行手术治疗,病理FCDⅠa型5例,FCDⅠb型3例,FCDⅠc型5例,FCDⅡa型6例,FCDⅡb型5例。术后随访1~5年,EngelⅠ级9例,EngelⅡ级5例,EngelⅢ级8例,EngelⅣ级2例。结论联合应用VEEG、MEG和(或)ECo G技术有助于准确诊断和定位磁共振阴性的FCD,提高FCD致难治性癫痫的手术疗效。     

难治性癫痫46例患者大脑半球或多脑叶切除标本的临床病理学分析

目的 研究难治性癫痫患者大脑半球或多脑叶切除标本的临床病理学特点.方法 对2005-2009年在首都医科大学宣武医院接受大脑半球(行功能性大脑半球切除术)或多脑叶切除的46例难治性癫痫患者临床病理学资料进行回顾性分析.结果 46例患者的平均发病年龄3.9岁,平均病程为10.2年.其中行大脑半球切除33例,多脑叶切除13例,且颞叶全部受累.组织学分型:继发性瘢痕脑回31例,皮质发育畸形7例,中枢神经系统感染8例.31例瘢痕脑回标本镜下可见皮质结构消失、神经元减少、反应性胶质细胞增生及淀粉样小体出现;此外还可观察到含铁血黄素(13例)、钙化(9例)以及岛状分布的神经元(5例).瘢痕脑回均伴不同程度的皮质发育不良,并有7例伴海马硬化.7例脑回发育畸形中,局灶性皮质发育不良(FCD)5例(其中FCDⅠB型3例,FCDⅠA型1例,FCDⅡA型1例),多小脑回畸形及穿通脑畸形各1例.8例中枢神经系统感染中Rasmussen脑炎5例、巨细胞病毒性脑炎1例、结核性脑膜炎1例、囊虫感染1例.结论 大脑半球或多脑叶切除的脑组织病理学主要是多种原因(比如外伤、缺氧等)引起的继发性瘢痕脑回,颞叶病变明显.中枢神经系统感染以Rasmussen脑炎为主,皮质发育畸形主要以FCDⅠB型为主.

Abstract：

Objective To investigate the clinicopathologic features of the brain tissue from multilobar resection or hemispherectomy for refractory epilepsy. Methods The clinical and pathologic findings of 46 cases seen at Xuanwu hospital from 2005 to 2009 were reviewed retrospectively. Results The mean age of seizure onset and disease duration were 3.9 years and 10.2 years, respectively. There were 33 cases of hemispherectomy and 13 cases of multilobar resection. Temporal lobe abnormality was seen in all cases. The pathologic subgroups were as follows: ulegyria (31/46), malformation of cortical development (MCD, 7/46 ) and infection (8/46). Microscopic examination of ulegyria showed cortical architectural disturbances, neuronal loss, reactive gliosis and appearance of corpora amylacea. We also noted deposition of hemosiderin (13 cases), calcification (9 cases) and island-like neurons (5 cases). All ulegyria cases were accompanied by varying degree of cortical dysplasia, and hippocampus sclerosis were identified in 7 cases. MCD comprised of 5 cases of focal cortical dysplasia ( FCD), including 3 cases of FCDⅠB, 1 case of FCDⅡA and 1 case of FCDⅠA, 1 case of polymicrogyria and 1 case of porencephaly. Among 8 infection eases, there were 5 cases of Rasmussen encephalitis ( RE), l case of cysticercosis, 1 case of tuberculous meningitis and l case of Cytomegalovirus encephalitis. Conclusions The most common pathological category of specimens from hemispherectomy or multilobar resection is ulegyria with obvious temporal lobe abnormality. This is followed by MCD ( with FCDⅠB as the main type) and central nervous system infection (RE as the most frequent abnormality).     

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.     

重度局灶性皮层发育不良和皮层错构性肿瘤病变的临床病理分析

目的 观察癫痫手术切除脑病变中,重度局灶性脑皮层发育不良(FCD Ⅱ B)与皮层错构性癫痫相关肿瘤(神经元和混合性神经元-胶质瘤)的临床病理特点.探讨两者的形态学变化及相瓦关系.方法 手术切除脑癫痫病灶,新鲜标本进行测量、切开、照相,显微镜下形态学观察.按脑皮质发育不良的病理诊断标准分类.应用一组免疫组化和特染指标协助诊断.结果 在133例癫痫脑病变切除病例中,典型FCD Ⅱ B者5例,皮层错构性癫痫相关肿瘤6例.在5例FCDⅡB中,存在重度脑皮层分层紊乱,典型的不成熟神经元、巨大神经元、异常神经元和气球样细胞.在6例脑皮层错构性癫痫相关肿瘤中,同样有以上病变,另外出现胶质神经元瘤样增生,DNT有黏液性背景、胶质增生及神经元减少.结论 FCD Ⅱ B与皮层错构性癫痫相关肿瘤有许多相似的病理变化,两者可能是癫痫脑病理谱系的连续病变,有待深入研究.     

合并海马硬化的颞叶内侧型癫痫的网络分析

目的在只有海马硬化为可见核磁共振病灶的颞叶内侧癫痫中,很多患者合并新皮质的局灶性皮质发育不良(FCD)。本文旨在探讨两者的癫痫网络差异。方法回顾性分析79例颞叶内侧型癫痫患者。所有患者行前颞叶切除术,术后随访至少1年无癫痫发作。根据病理将其分为单纯海马硬化组(HS)和合并新皮质FCD(FCD Ⅲa)组。将每个病人的术前发作间期~(18)FDG-PET数据标准化后,利用Matlab下的SPM(statistical parametric mapping)工具包分析两组间的代谢差异。结果 FCD Ⅲa组和HS组,无论是左侧还是右侧,其发病年龄、病史、性别以及发作期的主要症状学出现的频率均无明显差异。而FCD Ⅲa组的癫痫网络明显大于HS组,有差异的脑区主要在颞叶新皮质、额叶内侧面,缘上回和中央前后回。结论 FCD Ⅲa的癫痫网络要比单纯海马硬化所致的颞叶癫痫范围要大而且更复杂。遇到海马硬化所致的颞叶癫痫,要充分考虑到FCD Ⅲa的可能性,必要时行立体脑电明确新皮质的切除范围。     

局灶性皮质发育不良癫痫患者的临床及脑电图特征分析

目的探讨局灶性皮质发育不良(FCD)癫痫患者的临床和视频脑电图(VEEG)特征。方法分析39例FCD癫痫患者的临床资料,并对患者的临床特征及VEEG结果进行分析。结果 39例患者首次癫痫发作年龄2d至23岁,平均年龄(7.49±3.32)岁,头颅MRI检查27例(69.2%)异常,12例(30.8%)阴性。术后病理按2011年ILAE制定了新的FCD分类标准,结果为FCDⅠ型13例(33.3%),Ⅱ型16例(41.0%),Ⅲ型10例(25.6%)。39例患者VEEG监测中共发作187次,平均每例4.8次,FCDⅠ型组和FCDⅡ型组发作频率高于FCDⅢ型组(P0.05),FCDⅠ型组与FCDⅡ型组比较无明显差异(P0.05)。发作间期6例(15.4%)FCD癫痫患者VEEG阴性,癫痫样放电区域性24例(61.5%),广泛性9例(23.1%),3型比较无明显差异(P0.05);26例(66.7%)有节律性癫痫样放电,FCDⅡ型组高于FCDⅠ型组和FCDⅢ型组(P0.05),FCDⅠ型组与FCDⅢ型组比较无明显差异(P0.05)。发作期起始癫痫样放电呈区域性31例(79.5%),广泛性8例(20.5%),3型比较(P0.05)。结论 FCD癫痫患者首次癫痫发作多见于儿童期;FCDⅠ型和FCDⅡ型临床发作频率高;发作间期具有特征性节律性癫痫样放电FCDⅡ型最多见;发作间期及发作期起始癫痫样放电主要呈区域性。     

Interobserver and intraobserver reproducibility in focal cortical dysplasia (malformations of cortical development)

Purpose: Malformations of cortical development (MCD) (cortical dysplasias) are well‐recognized causes of intractable epilepsy. Although a histologic classification system for MCD has been proposed by Palmini et al. (Neurology; 2004; 62:S2), studies to date have not assessed reproducibility. The purpose of this study was to analyze inter‐ and intraobserver agreement among eight experienced neuropathologists (NPs) with respect to this classification system. Methods: Sections from 26 epilepsy resections were selected to represent the range of pathologies described by Palmini et al. Recuts of single sections from each case were sent to the NPs to classify. The slides were resent at a later date for reclassification. Kappa analysis for both inter‐ and intraobserver concordance was performed. Results : Interobserver agreement was moderate (κ = 0.4968). There was ≥62.5% (5 of 8 NPs) agreement for 19 of 26 cases. The greatest concordance was present when making focal cortical dysplasia (FCD) types IIA/B classifications (12 of the 14 cases with ≥75% consensus). Mild MCD (types I/II) and FCD types IA/B classifications were the least reproducible, and used most frequently in cases without consensus. Intraobserver concordance was moderate to very good (range κ = 0.4654–0.8504). The category with the fewest classification changes made on reevaluation was FCD type IIB (4.2%), whereas that with the most changes was mild MCD (types I/II) (52.9%). Discussion : Interobserver concordance using this approach was moderate. The classification categories with the greatest concordance were FCD type IIA/B, and the least, mild MCD and FCD types IA/B. In addition, difficulty in differentiating Mild MCD/FCD type I lesions from normal and/or gliotic tissue was noted.     

Epilepsy

MR is a fundamental step in the diagnostic path of patients with medically refractory partial epilepsy (MRPE) potentially amenable to surgery. The most frequent lesions harboured by these patients are: malformations of cortical development (MCD), mainly focal cortical dysplasias (FCD); epileptogenic tumours, such as dysembryoplastic neuroepithelial tumours (DNT) and gangliogliomas (GG); and mesial temporal sclerosis (MTS).     

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.     

Surgical pathology of epilepsy‐associated non‐neoplastic cerebral lesions: A brief introduction with special reference to hippocampal sclerosis and focal cortical dysplasia

Among epilepsy‐associated non‐neoplastic lesions, mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE‐HS) and malformation of cortical development (MCD), including focal cortical dysplasia (FCD), are the two most frequent causes of drug‐resistant focal epilepsies, constituting about 50% of all surgical pathology of epilepsy. Several distinct histological patterns have been historically recognized in both HS and FCD, and several studies have tried to perform clinicopathological correlations. However, results have been controversial, particularly in terms of post‐surgical seizure outcome. Recently, the International League Against Epilepsy constituted a Task Forces of Neuropathology and FCD within the Commission on Diagnostic Methods, to establish an international consensus of histological classification of HS and FCD, respectively, based on agreement with the recognition of the importance of defining a histopathological classification system that reliably has some clinicopathological correlation. Such consensus classifications are likely to facilitate future clinicopathological studies. Meanwhile, we reviewed the neuropathology of 41 surgical cases of mTLE, and confirmed three type/patterns of HS along with no HS, based on the qualitative evaluation of the distribution and severity of neuronal loss and gliosis within hippocampal formation, that is, HS type 1 (61%) equivalent to “classical” Ammon's horn sclerosis, HS type 2 (2%) representing CA1 sclerosis, HS type 3 (17%) equivalent to end folium sclerosis, and no HS (19%). Furthermore, we performed a neuropathological comparative study on mTLE‐HS and dementia‐associated HS (d‐HS) in the elderly, and confirmed that neuropathological features differ between mTLE‐HS and d‐HS in the distribution of hippocampal neuronal loss and gliosis, morphology of reactive astrocytes and their protein expression, and presence of concomitant neurodegenerative changes, particularly Alzheimer type and TDP‐43 pathologies. These differences may account, at least in part, for the difference in pathogenesis and epileptogenicity of HS in mTLE and senile dementia. However, the etiology and pathogenesis of most epileptogenic lesions are yet to be elucidated.     

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。