局灶性皮质发育不良癫癎患者头皮脑电图的特点及其定位意义

目的:探讨头皮脑电图(EEG)在局灶性皮质发育不良(focal cortical dysplasia,FCD)癫癎中的表现特点及定位致癎灶的意义.方法:选择自2005年4月至2006年8月我研究所收治的22例术前采用长程颅内电极埋置,术后病理证实为FCD的患者为研究对象.将发作间期皮层电图(ECoG)癎样异常放电(interictal epileptiform discharge,IED)分为四种类型:A:独立棘波,B:重复棘慢波,C:多棘波,D:快波,以a、b、C、d分别表示头皮EEG与上述分类相对应的IED波形.发作期癫癎异常放电(ictal discharge,ID)被分为:Ⅰ型:节律性快波,Ⅱ型:棘波节律,Ⅲ型:小于8 Hz的节律性电活动.将22例患者术前头皮EEG与ECoG的数字资料进行分析比较.结果:22例FCD患者头皮EEG的IED分型中,a型占50%,ECoG的IED中,A型占36%,D型与C型各占23%.头皮EEG a型中,45%来自ECoG类型1ED.头皮EEG表现为C和d型IED的均来自ECoG的C与D型.头皮EEG的ID中Ⅰ型有7例,Ⅱ型有4例,Ⅲ型有9例;头皮EEG的ID中的Ⅲ型明显多于ECoG的Ⅲ型(X2=7.02,P=0.03).头皮EEG局限型Ⅰ型与Ⅱ型ID的部位与手术部位一致性好.结论:FCD患者头皮EEG的IED以棘波,尖波波形较多见,且表现范围较ECoG上的IED广泛.头皮EEG的ID表现以Ⅲ型为主,且定位意义不如ECoG上的ID类型.经过由皮层到头皮的传导,不论是IED还是ID,异常放电形式均有可能发生改变.当头皮EEG的IED与ID同时为局限型且部位彼此相一致时,定位可靠性较高.     

局灶性皮质发育不良患者的磁共振波谱分析与临床相关性研究

目的:应用多体素氢质子磁共振波谱(MRS)研究局灶性皮质发育不良(FCD)患者脑代谢特点,并进一步探讨(癎)性发作的机制.方法:收集来自贵阳医学院附属医院和重庆医科大学临床学院神经科门诊及住院明确诊断的20例大脑FCD伴有(癎)性发作患者和20名健康受试者进行多体素MRS扫描,测量患者病灶区、病灶比邻区和远离病灶区皮质氮-乙酰门冬氨酸(NAA)与肌酸(Cr)的比值(NAA/Cr),并与对照组受试者相对应皮质区NAA/Cr值比较.结果:FCD患者病灶区、病灶比邻区较对照组皮质区NAA/Cr比值显著降低(P＜0.01),远侧病灶区皮质区与对照组皮质区NAA/Cr比值之间比较差异无统计学意义(P＞0.05);病灶区皮质NAA/Cr比值与临床(癎)性发作次数之间未见相关性.结论:多体素MRS可无创观察FCD患者脑代谢改变,为手术治疗FCD伴有难治性癫(癎)患者提供了一个重要的参考指标.     

局灶性皮质发育畸形的分类进展

皮质发育畸形（malformations of cortical de‐velopment ，MCD）是一组局限性或广泛性大脑皮质结构的异常，是导致癫?、神经发育迟滞等常见病的病因［1‐2］。而局灶性皮质发育畸形（focal cortical dy splasia ，FCD ）是M CD的一种特殊亚型，是M CD所致难治性癫?的常见病因，超过50％的患者经手术切除的病灶病理学诊断为 FCD［3］。神经细胞的增殖、迁移、分化在FCD亚型形成的病理学机制中占有重要作用［4］。     

癫癎发作期PET定位药物难治性癫癎1例并文献复习

目的：探讨药物难治性癫癎患儿在注射18F-DG药物时发生癫癎发作后所查正电子发射断层扫描（PET）显示局灶性高代谢灶的意义，并复习相关文献。方法：1例1岁零2个月女性患儿有发作性抽搐伴意识丧失13个月，智能发育落后于正常同龄儿童，视频脑电图显示左颁局限性癎样放电，MRI显示左侧颁叶局灶病变，在注射18F-DG药物时发生癫癎发作，斯时所查PET-CT显示左颁局灶性高代谢灶，因为与无创检查结果定位一致，遂行左侧颁叶后部癎灶切除术加中央前回软脑膜下横纤维切断术。结果：术前服用抗癫癎药物状态下每日发作数10次，术后6个月患儿癫癎完全缓解，切除组织病理学提示局灶性皮质发育不良（FCDIIb），手术后13d视频脑电图正常，6个月脑电图左侧额区尖波。患儿手术后6个月时智力有所进步，但仍落后于正常同龄儿。有文献显示在癫癎发作期注射18F-DG后PET在局灶性癫痂患者中一般显示局灶高代谢灶，并能定位政癎灶。结论：癫癎发作期注射18F-DGPET所显示的局灶高代谢区对致癎灶定位有很大帮助。     

儿童顽固性癫(癎)术前致(癎)灶的评估与手术疗效

儿童是癫(癎)病的高发人群,其中约30％的患儿即使经过系统正规的药物治疗,其发作也得不到有效的控制,最终将发展为顽固性癫(癎)[1].文献报告[2]约50％的顽固性癫(癎)患者可以通过手术治疗使发作得到彻底根除或有效的控制.     

基于VBM-DARTEL的局灶性皮质发育不良脑灰质体积异常检测方法

目的:局灶性皮质发育不良(Focal Cortical Dysplasia,FCD)是导致药物难治性癫痫的重要病因之一。如何应用磁共振影像探究FCD全脑解剖结构的异常变化部位和定位,对临床诊断和治疗具有重要意义。方法:本文建立一种基于VBM-DARTEL的FCD脑灰质异常检测方法。该方法包括对磁共振结构像进行图像分割、DARTEL模板制作、图像标准化等,最后使用双样本独立t检验统计分析患者组和对照组全脑灰质体积的差异,从而得到FCD脑灰质的病变特征。结果:与正常对照组相比,FCD患者组双侧大脑半球存在广泛脑区的灰质体积异常;FCD患者的脑灰质存在萎缩,并伴有灰质体积异常增大的脑区,且多集中在额叶和颞叶等区域。结论:基于DARTEL的VBM方法可以有效地检测FCD患者脑灰质体积的异常变化,且能准确定位FCD病灶。     

局灶性癫癎发作间期和发作期的脑电图在致癎灶定侧中的意义

目的:探讨局灶性癫癎发作间期和发作期脑电图变化特点及其在致癎灶定侧中的作用。方法:分析100例局灶性癫癎患者的发作间期、发作期脑电图及发作症状所提供的致癎灶侧别信息。结果:在这100例局灶性癫癎发作患者中,发作间期、发作期脑电图和发作症状可提供明确的致癎灶定侧的信息者分别为53例、76例和73例。结论:在致癎灶定侧诊断中,发作期与发作间期脑电图相比,可提供较高比例的侧别信息;综合分析发作间期、发作期脑电图和发作症状,可以使大部分局灶性癫癎发作的患者获得致癎灶的定侧信息,并为进一步埋置颅内电极,精确定位癫癎灶提供重要的参考。     

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。     

NGF对局灶性脑缺血再灌注后大鼠皮质IL-1β表达的调控作用

目的:探讨外源性神经生长因子(NGF)对局灶性脑缺血再灌注大鼠皮质白细胞介素1β(IL-1β)表达的影响.方法:线栓法制作大鼠局灶性腩缺血再灌注模型,应用免疫组织化学显色、免疫印迹分析方法,结合图像分析技术检测大鼠缺血侧顶叶皮质 IL-1β蛋白表达变化.结果:假手术组大鼠顶叶皮质IL-1β没有表达,缺血再灌注组顶叶皮质IL-1β蛋白在各时间点明显表达,IL-1β蛋白阳性产物的光密度值高于假手术组;NGF组IL-1β蛋白阳性产物的光密度值低于缺血冉灌注组.结论:脑缺血再灌注损伤后诱导 IL-1β蛋白表达,NGF 明显降低缺血再灌注大鼠顶叶皮质IL-1β蛋白表达,这可能是 NGF发挥神经保护作用的分子机制之一.     

Apelin-13对局灶性脑缺血再灌注后大鼠皮质Akt和磷酸化Akt表达的调节

目的探讨外源性Apelin-13对局灶性脑缺血再灌注大鼠皮质Akt及p-Akt表达的影响。方法 Wistar大鼠132只,按随机数字表法均分为假手术组、脑缺血再灌注组、脑缺血再灌注后Apelin-13干预组。线栓法制备大鼠局灶性脑缺血再灌注模型,Moor VMS-LDF1激光多普勒血流仪检测模型组脑缺血前、后脑血流变化,免疫组织化学显色、免疫印迹分析方法检测顶叶皮质Akt和p-Akt表达变化。结果模型组大鼠脑缺血后脑血流量明显低于缺血前,脑缺血模型建立成功。缺血再灌注组皮质Akt表达较假手术组少,Apelin-13干预组皮质Akt表达高于缺血再灌注组。缺血再灌注组皮质pAkt表达高于假手术组,Apelin-13干预组p-Akt表达高于缺血再灌注组。结论外源性Apelin-13上调了脑缺血再灌注损伤大鼠皮质Akt和p-Akt蛋白表达。     

脑皮质发育不良性难治性癫痫57例临床病理分析

目的探讨难治性癫痫病灶手术切除患者,经病理诊断为脑皮质发育不良病例的临床病理特点。方法对57例手术切除脑癫痫病灶新鲜标本先进行测量,后切开用10％中性缓冲福尔马林溶液固定,石蜡切片,常规染色、特染及免疫组化染色,详细形态学观察。按脑皮质发育不良的病理诊断标准进行分类,探讨各种类型临床病理学特点。结果在57例中,皮质轻度发育不良（mildMCD）9例;局灶性皮层发育不良（FCD）33例（ⅠA14例,ⅠB14例,ⅡA8例,ⅡB7例）;皮层瘢痕性小脑回畸形5例。应用免疫组化和特染指标协助诊断。结论本组脑皮质发育不良以FCDⅠA和ⅠB型为常见类型;类型与手术疗效有关。一些免疫组化和特染指标有助于诊断与分型。     

Detection of cortical malformations using enhanced synthetic contrast images derived from quantitative T1 maps

The detection of cortical malformations in conventional MR images can be challenging. Prominent examples are focal cortical dysplasias (FCD), the most common cause of drug‐resistant focal epilepsy. The two main MRI hallmarks of cortical malformations are increased cortical thickness and blurring of the gray (GM) and white matter (WM) junction. The purpose of this study was to derive synthetic anatomies from quantitative T1 maps for the improved display of the above imaging characteristics in individual patients. On the basis of a T1 map, a mask comprising pixels with T1 values characteristic for GM is created from which the local cortical extent (CE) is determined. The local smoothness (SM) of the GM‐WM junctions is derived from the T1 gradient. For display of cortical malformations, the resulting CE and SM maps serve to enhance local intensities in synthetic double inversion recovery (DIR) images calculated from the T1 map. The resulting CE‐ and/or SM‐enhanced DIR images appear hyperintense at the site of cortical malformations, thus facilitating FCD detection in epilepsy patients. However, false positives may arise in areas with naturally elevated CE and/or SM, such as large GM structures and perivascular spaces. In summary, the proposed method facilitates the detection of cortical abnormalities such as cortical thickening and blurring of the GM‐WM junction which are typical FCD markers. Still, subject motion artifacts, perivascular spaces, and large normal GM structures may also yield signal hyperintensity in the enhanced synthetic DIR images, requiring careful comparison with clinical MR images by an experienced neuroradiologist to exclude false positives.     

Vascular endothelial growth factor‐C modulates cortical NMDA receptor activity in cortical lesions of young patients and rat model with focal cortical dysplasia

Emergence of dysmorphic neurons is the primary pathology in focal cortical dysplasia (FCD) associated pediatric intractable epilepsy; however, the etiologies related to the development and function of dysmorphic neurons are not fully understood. Our previous studies revealed that the expression of vascular endothelial growth factor‐C (VEGF‐C) and corresponding receptors VEGFR‐2, VEGFR‐3 was increased in the epileptic lesions of patients with tuberous sclerosis complex or mesial temporal lobe epilepsy. Here, we showed that the expression of VEGF‐C, VEGFR‐2, and VEGFR‐3 was increased at both mRNA and protein levels in patients with cortical lesions of type I, IIa, and IIb FCD. The immunoreactivity of VEGF‐C, VEGFR‐2 and VEGFR‐3 was located in the micro‐columnar neurons in FCD type I lesions, dysplastic neurons (DNs) in FCD type IIa lesions, balloon cells (BCs) and astrocytes in FCD type IIb lesions. Additionally, the amplitude of evoked‐EPSCs (eEPSC) mediated by NMDA receptor, the ratio of NMDA receptor‐ and AMPA receptor‐mediated eEPSC were increased in the dysmorphic neurons of FCD rats established by prenatal X‐ray radiation. Furthermore, NMDA receptor mediated current in dysmorphic neurons was further potentiated by exogenous administration of VEGF‐C, however, could be antagonized by ki8751, the blocker of VEGFR‐2. These results suggest that VEGF‐C system participate in the pathogenesis of cortical lesions in patients with FCD in association with modulating NMDA receptor–mediated currents.     

额叶癫癎患者的临床特点及脑电分析

目的：观察额叶癫痫患者的临床特点、EEG表现、治疗方法及效果。方法：回顾性分析62例额叶癫痫患者的临床表现、发作期及发作间期EEG改变和抗癫痫药物的治疗效果。结果：额叶癫痫常见的发作形式为复杂部分性发作（82％），主要表现为假自主运动，发声及重复语言，姿势性强直，并伴有发作持续时间短、频繁发作、发作后神志恢复快等特点。发作期EEG痫样放电检出率100％，但能定位额区仅占74％，发作新时期EEG8例无阳性发现。经抗癫痫药物治疗，有效率达93％，其中50％完全控制发作，主要用药为卡马西平。随访2-5年，仍有效者占88％。结论：额叶癫痫为一组以运动症状为主要表现的特征性癫痫综合征，卡马西平治疗效果满意。     

Variable histopathology features of neuronal dyslamination in the cerebral neocortex adjacent to epilepsy‐associated vascular malformations suggest complex pathogenesis of focal cortical dysplasia ILAE type IIIc

Focal cortical dysplasia type IIIc (FCD‐IIIc) is histopathologically defined by the International League Against Epilepsy''s classification scheme as abnormal cortical organization adjacent to epilepsy‐associated vascular malformations (VM). However, the incidence of FCD‐IIIc, its pathogenesis, or association with the epileptogenic condition remains to be clarified. We reviewed a retrospective series of surgical brain specimens from 14 epilepsy patients with leptomeningeal angiomatosis of Sturge‐Weber syndrome (LMA‐SWS; n = 6), cerebral cavernous malformations (CCM; n = 7), and an arteriovenous malformation (AVM; n = 1) to assess the histopathological spectrum of FCD‐IIIc patterns in VM. FCD‐IIIc was observed in all cases of LMA‐SWS and was designated as cortical pseudolaminar sclerosis (CPLS). CPLS showed a common pattern of horizontally organized layer abnormalities, including neuronal cell loss and astrogliosis, either manifesting predominantly in cortical layer (L) 3 extending variably to deeper areas with or without further extension to L2 and/or L4. Another pattern was more localized, targeting mainly L4 with extension to L3 and/or L5. Abnormal cortical layering characterized by a fusion of L2 and L3 or L4–L6 was also noted in two LMA‐SWS cases and the AVM case. No horizontal or vertical lamination abnormalities were observed in the specimens adjacent to the CCM, despite the presence of vascular congestion and dilated parenchymal veins in all VM. These findings suggest that FCD‐IIIc depends on the type of the VM and developmental timing. We further conclude that FCD‐IIIc represents a secondary lesion acquired during pre‐ and/or perinatal development rather than following a pathomechanism independent of LMA‐SWS. Further studies will be necessary to address the selective vulnerability of the developing cerebral neocortex in LMA‐SWS, including genetic, encephaloclastic, hemodynamic, or metabolic events.     

额叶癫癎发作的临床特征及脑电图分析

目的：探讨额叶癫癎发作的临床特征、脑电图（EEG）特点及临床意义.方法：回顾性分析30例经手术证实发作起源于额叶的药物难治性额叶癫癎患者87次临床发作症状、发作期及发作间期的头皮EEG特点.结果：额叶癫癎发作形式复杂多样,常见的发作形式有姿势性强直发作、过度运动性自动症、扭转性强直、阵挛性发作、发声、失神等,有时出现发作性情绪改变或自主神经症状等少见症状.额叶癫癎常见以下发作特点：发作频繁,常成簇出现,发作起止突然,持续时间短暂,发作后意识恢复快,以睡眠中发作为主.额叶癫癎发作间期EEG阳性率较低,额区棘波、尖波出现率相对较低,且波形不典型,发作期额叶限局性或弥漫性的改变与背景活动的差别不明显.结论：额叶癫癎临床和EEG不典型是导致额叶癫癎发作临床诊断困难的主要原因,认识额叶癫癎发作的临床特点,延长EEG记录时间,认真分析发作症候学、发作期同步EEG有助于明确诊断.     

Experimentally induced laminar necrosis,status verrucosus,focal cortical dysplasia reminiscent of microgyria,and porencephaly in the rat

Different types of cortical malformation were produced, following focal cortical freezing, electrocoagulation, focal cortical aspiration or gentle brushing of uncovered meninges, in newborn or 1-to 3-day-old rats. Malformations included laminar necrosis of the cerebral cortex, status verrucosus, focal cortical dysplasia reminiscent of microgyria, and porencephaly. Similar procedures from postnatal day 4 onwards, at a time when a reactive astrogliosis is possible, produced cavitating infarcts and tissue scars. Cytoarchitectonic studies revealed an abnormal distribution of different types of pyramidal and nonpyramidal neurons in these malformations. These indicated three subtypes of focal cortical dysplasia, which probably depend on different pathogenic mechanisms. Autoradiographic studies with [³H] methylthymidine showed normal positioning of late-generated neuroblasts in the cerebral cortex, thus suggesting preserved migration. The present experimentally induced cortical malformations are useful models of similar cortical abnormalities in humans.     

Molecular diagnostics in drug‐resistant focal epilepsy define new disease entities

Structural brain lesions, including the broad range of malformations of cortical development (MCD) and glioneuronal tumors, are among the most common causes of drug‐resistant focal epilepsy. Epilepsy surgery can provide a curative treatment option in respective patients. The currently available pre‐surgical multi‐modal diagnostic armamentarium includes high‐ and ultra‐high resolution magnetic resonance imaging (MRI) and intracerebral EEG to identify a focal structural brain lesion as epilepsy underlying etiology. However, specificity and accuracy in diagnosing the type of lesion have proven to be limited. Moreover, the diagnostic process does not stop with the decision for surgery. The neuropathological diagnosis remains the gold standard for disease classification and patient stratification, but is particularly complex with high inter‐observer variability. Here, the identification of lesion‐specific mosaic variants together with epigenetic profiling of lesional brain tissue became new tools to more reliably identify disease entities. In this review, we will discuss how the paradigm shifts from histopathology toward an integrated diagnostic approach in cancer and the more recent development of the DNA methylation‐based brain tumor classifier have started to influence epilepsy diagnostics. Some examples will be highlighted showing how the diagnosis and our mechanistic understanding of difficult to classify structural brain lesions associated with focal epilepsy has improved with molecular genetic data being considered in decision making.