局灶性皮质发育不良相关癫痫的诊疗进展

局灶性皮质发育不良（FCD）是临床中常见的局灶性癫痫的病理类型之一,多数FCD患者在癫痫起病后即表现出耐药性,成为难治性癫痫。2011年国际抗癫痫联盟提出了新的FCD病理分型后,让大家对FCD有了更进一步的认识。近几年随着医学检测技术、病理研究及神经影像技术的发展,针对不同病理亚型的研究使得临床医生对FCD致病机制及治疗措施的决策有了新的理解。该文综合近年相关文献,对FCD不同亚型临床特点、治疗方法及相关预后作一综述,以期为临床决策提供帮助。     

局灶性皮质发育不良与难治性癫痫

局灶性皮质发育不良是难治性癫痫的重要病因,近年来,随着影像学和脑电生理学的发展,分子生物学和病理生理学在癫痫发病机制研究中的应用,人们对局灶性皮质发育不良的遗传和病理生理学特点的认识产生了浓厚的兴趣.本文对大脑皮质的发育过程、局灶性皮质发育不良的发病及致痫机制分类及影像学的特征、手术治疗进行综述.     

局灶性皮质发育不良继发难治性癫痫的外科治疗进展

局灶性皮质发育不良(Focal Cortical Dysplasias,FCDs)是一种先天性皮质发育不良,也是儿童和成人难治性癫痫的一种常见病因。随着结构及功能神经影像学技术的发展,该类癫痫发作逐渐被证实为难治性癫痫患者需行手术治疗的重要原因之一。各种具有特征性表现的FCDs的病理分型可以帮助我们对其作为癫痫病因的理解。而对FCDs及相关的癫痫起源灶的全切除可以为绝大多数癫痫患者带来理想的治疗效果。     

局灶性皮质发育不良合并难治性癫痫患者头部MRI融合PET-CT进行术前评估的价值

目的探讨颅脑PET-MRI融合图像在表现为局灶性皮质发育不良(focal cortical dysplasia,FCD)的应用价值,并总结患者治疗后的预后,为广大癫痫患者寻求一个更合理的诊治方案。方法回顾性分析2017年1月～2018年8月我院神经内外科、儿科收治的23例表现为难治性癫痫的FCD患者临床表现、影像学特点、视频脑电图特点以及手术疗效。结果表现为难治性癫痫的FCD患者的发作类型多种多样,但以局灶性发作继发全面性发作为主;病灶多见于颞叶15例、额叶6例、顶叶2例; 20例患者癫痫序列MRI及视频脑电发现病灶,3例患者行癫痫序列磁共振及视频脑电未能确定明确的致痫灶,完善PET-MRI融合成像发现致痫灶,病变部位主要在额叶,因此对于头部MRI阴性的患者,则主要通过PET-MRI发现病灶;视频脑电图(EEG)痫样放电部位与PET-MRI融合成像发现的病灶部位有较高一致性,且放电及发作形式对于FCD分型没有明显的相关性; 23例患者术后癫痫发作次数明显减少,有的未再发作。结论表现为难治性癫痫的FCD患者可通过PET-MRI融合成像结合视频脑电脑电进行术前评估,找准致痫灶,手术切除癫痫灶的治疗可取得良好的预后。     

局灶性皮质发育不良所致难治性癫痫的微创神经外科治疗

目的应用神经导航结合术中皮质电极描记,微创治疗局灶性皮质发育不良(focal cortical dysplasia,FCD)所致的难治性癫痫。方法 26例局灶性皮质发育不良所致的难治性癫痫患者,术前常规使用CT、磁共振成像(magnetic resonanceimaging,MRI)、长程视频脑电图(digital video signal and electroencephalogram,VEEG)、磁共振波谱分析(MR Spectroscopy,MRS)等检查,如病灶位于功能区则行功能性磁共振成像(functional magnetic resonance imaging,fMRI)。术中通过神经导航确定的病灶与ECoG确定的致痫灶位置及范围进行对比,了解两者的吻合程度及差异,综合分析后精确并标记出癫痫波的起源位置和范围,将局灶性皮质发育不良病灶和周边的致痫皮质切除;如致痫灶位于功能区或附近,在保留功能区皮质的基础上,给予低功率皮质热灼。结果术后病理结果:26例患者病理标本符合FCD。术后患者无明显并发症出现。根据Engel术后效果分级进行评估,Ⅰ级23例,Ⅱ级2例,Ⅲ级1例。结论神经导航结合术中皮质电极描记在局灶性皮质发育不良所致的难治性癫痫手术中,具有定位准确、损伤少的优点,在切除致痫灶的同时能最大程度保护脑功能。     

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。     

影响局灶性皮质发育不良所致难治性癫痫手术疗效的相关因素分析

目的分析影响局灶性皮质发育不良(FCD)所致药物难治性癫痫手术疗效的相关因素。方法收集2015年9月至2018年7月在中国科学技术大学附属第一医院神经外科接受手术治疗并经病理确诊为FCD的50例药物难治性癫痫患者的临床资料,包括病史、发作频率、病灶位置、视频脑电结果、头颅MRI表现、术前服药种类、手术切除范围、术后早期癫痫发作情况,采用Engel分级评估患者手术疗效,并将其分为预后良好组和预后不良组。运用统计学方法分析FCD所致难治性癫痫的手术疗效相关影响因素。结果共有50例患者接受手术,其中致痫灶位于颞叶31例,额叶14例,顶叶2例,枕叶2例,颞枕叶1例,手术完整切除致痫灶44例,未完整切除6例,术后病理分型为FCDⅠ、Ⅱ、Ⅲ型分别有19例、17例、14例,术后随访时间为12～46个月,平均(20.7±7.9)个月,术后EngelⅠ级34例、EngelⅡ级3例、EngelⅢ级5例、EngelⅣ级8例,预后良好组34例,预后不良组16例。单因素分析显示病程≥10年、术后出现早期癫痫发作、致痫灶未完全切除者手术疗效较差(均P0.05)。二分类Logistic回归分析结果显示,致痫灶是否完全切除和术后是否出现早期癫痫发作是FCD所致难治性癫痫手术疗效的独立影响因素(均P0.05)。结论致痫灶是否完整切除和术后是否出现早期癫痫发作与FCD致难治性癫痫的手术疗效密切相关。患者的病程也是FCD致难治性癫痫手术疗效的重要预测因素。     

局灶性皮质发育不良所致难治性癫痫的手术预后影响因素分析

目的探讨影响局灶性皮质发育不良（FCD）所致药物难治性癫痫患者手术预后的相关因素。方法回顾性分析2011年6月至2013年d月北京丰台医院癫痫中心一首都医科大学附属北京天坛医院医疗联盟收治的43例药物难治性癫痫患者的临床资料。所有患者均行手术治疗,且术后病理证实为FCD。分析患者的临床发作类型、视频脑电、MRI表现、正电子发射断层显像术（PET）-CT表现、病灶部位、手术切除范围以及术后病理分型。根据Engel分级评估患者的预后。采用单因素分析和多因素Logistic回归分析探讨影响FCD所致药物难治性癫痫患者手术预后的相关因素。结果43例患者术后随访3．8～5．5年,平均（4．3±1．2）年。单因素分析结果显示,部分性发作、PET—CT阳性、病灶位于颞叶以及完全切除病灶的患者预后更佳（均P〈0．05）。多因素Logistic回归分析结果显示,手术切除范围与FCD所致难治性癫痫的手术预后密切相关（OR=6．857,95％CI：1．583—29．707,P=0．010）。结论手术切除范围与FCD所致难治性癫痫患者的手术预后相关。术前临床发作类型、PET-CT表现、病灶部位可能能够作为评估患者手术预后的重要指标。     

静息态功能磁共振在局灶性皮质发育不良癫痫患者中定位致痫区的价值

目的 基于局部一致性(regional homogeneity,ReHo)、低频振幅(amplitude of low frequency fluctua-tion,ALFF)和部分性低频振幅(fractional ALFF)三项指标,探究静息态功能磁共振成像(resting—state function MRI,rs...     

局灶性皮质发育不良不同病理类型的MRI表现及预后

局灶性皮质发育不良(focal cortical dysplasia,FCD)是由于早期神经元和神经胶质细胞的增生与分化受到影响而阻碍了大脑皮质的局部发育,使局部皮质出现一系列改变的疾病.据统计报道,成人手术中至少20%的患者经病理证实为FCD[ 1-3] ,而在儿童手术病例中高达50%[4-6].在临床上,FCD多表现为药物难治性癫,约占所有局灶性难治性癫的30%.随着神经影像学技术的进步,特别是MRI的使用,FCD的诊断率已日益提高.     

Characteristics of epilepsy in focal cortical dysplasia in infancy

To describe the poorly known characteristics of epilepsy during infancy in focal cortical dysplasia (FCD), one of the most frequent cause of infantile epilepsy. All 28 patients with FCD referred to two specialized centres were retrospectively studied regarding seizure characteristics, psychomotor evaluation, and response to medical and surgical treatment. All patients presented with early partial seizures. Semiology, but not the age of onset, depended on the topography of the dysplasia, with abnormal eye movements in all cases of posterior FCD. Eleven patients also developed infantile spasms (IS), mainly asymmetrical. IS were easily controlled with Vigabatrin or ACTH, but no partial seizures could be medically controlled except in one patient. All patients except one had abnormal neuropsychological findings. Fifteen patients had surgery, eight became seizure free, and seven were significantly improved regarding psychomotor development. Very early and refractory partial seizures, but easily controlled IS are the main characteristics of FCD in infancy. Only the focal ictal semiology may help differentiate the localization of FCD. Its intrinsic epileptogenicity could sustain this clinical pattern. Since the chances for medical control and normal neurodevelopment are poor, surgical treatment should be considered early in infants with FCD.     

The clinical spectrum of focal cortical dysplasia and epilepsy

Focal cortical dysplasia is an important pathologic substrate in patients with epilepsy, but its clinical spectrum has not yet been completely defined. We retrospectively studied 30 epilepsy surgery patients with focal abnormalities of neuronal migration as the only histopathologic finding in resected tissue. Patients comprised two clinical groups. Seventeen patients with extratemporal epilepsy had early (median age, 7.0 years) extratemporal resection or hemispherectomy for severe epilepsy (47% of patients with > 10 partial seizures a day) that began in infancy or early childhood (median age, 1.0 year), usually in the setting of mental retardation or developmental delay (59% of patients), and often with magnetic resonance imaging (MRI) evidence of focal neuronal migration abnormality (44% of patients). In contrast, 13 patients with temporal lobe epilepsy were significantly older at age of seizure onset (median, 8.0 years; p = 0.001) and surgery (median, 22.0 years; p = 0.001), with less severe epilepsy (no patients with an average of > 10 seizures a day; p = 0.004), and without mental retardation or MRI evidence of neuronal migration abnormality (p = 0.001). In both groups, positron emission tomography (PET) was more sensitive than MRI and showed focal hypometabolism in seven patients with normal MRI. Seizure-free outcome tended to be more common after temporal lobectomy (77%) than after extratemporal resection or hemispherectomy (53%). Pathologic abnormalities were more severe in patients with extratemporal epilepsy than in patients with temporal lobe epilepsy. The clinical spectrum of focal cortical dysplasia included not only infants and children with severe extratemporal epilepsy and mental retardation, but also older patients with temporal lobe epilepsy and at least boderline IQ. Preoperative diagnosis may be difficult in cases with less severe pathologic abnormality, but high-resolution MRI and PET can increase the yield.     

Usefulness of focal rhythmic discharges on scalp EEG of patients with focal cortical dysplasia and intractable epilepsy

We examined the significance and frequency of occurrence of rhythmic epileptiform discharges (REDs) on the scalp EEGs of 74 patients with intractable partial epilepsy. We also analyzed the relationship of this abnormality to the continuous epileptiform discharges (CEDs) recorded on ECoG. Both REDs and CEDs had been found to be highly specific and sensitive indicators of focal cortical dysplastic lesions. Thirty-four patients (group I) had focal cortical dysplastic lesions (FCDLs) and 40 (group II) had non-dysplastic structural lesions. REDs were observed in 15 (44%) of the 34 patients of group I and in none of group II. REDs did not occur in isolation, were associated with more intermittent interictal spikes involving other regions, but had a greater (P < 0.05) significance for the localization of the epileptogenic area. A strong relationship was observed between the presence of REDs on scalp EEG and the occurrence of CEDs on ECoG recordings. Twelve (80%) of 15 patients with REDs had CEDs. Focal cortical dysplastic lesions are likely to be present when rhythmic epileptiform discharges are found.     

Interictal regional polyspikes in noninvasive EEG suggest cortical dysplasia as etiology of focal epilepsies

Purpose: To evaluate the clinical significance of interictal regional polyspikes in focal epilepsies secondary to cortical dysplasia.
Methods: We performed a data search for the term "regional polyspikes" in the database of our epilepsy-monitoring unit. Patients with generalized epilepsies including Lennox-Gastaut syndrome were excluded. Regional interictal epileptiform discharges were recorded in 513 patients with noninvasive EEG.
Results: We identified 29 patients with interictal regional polyspikes and focal epilepsies. Another 484 patients showed regional epileptiform discharges other than polyspikes. The etiology of the epilepsy was significantly more frequently cortical dysplasia in the group of patients with regional polyspikes (35%, 10 of 29 patients) than in the patients with other regional epileptiform discharges (5%, 24 of 484 patients) (p < 0.01). The polyspikes were significantly more frequently localized to the extratemporal (72%; n = 21) than temporal (28%; n = 8) regions (p < 0.01). In contrast, regional epileptiform discharges other than polyspikes were significantly more frequently localized to the temporal lobe (75%; n = 362) than extratemporal regions (25%; n = 122) (p < 0.01). Eight of the 10 patients with focal cortical dysplasia had extratemporal polyspikes.
Discussion: Noninvasively recorded regional polyspikes suggest cortical dysplasias as etiology of predominantly extratemporal epilepsies.     

Reversal of vision metamorphopsia: a manifestation of focal seizure due to cortical dysplasia

Upside-down reversal of vision has rarely been reported in the literature. The reported causes are diverse, including posterior circulation stroke, tumors, trauma, and multiple sclerosis. The term seizure has been used in only two cases in the literature, the cause of which was stroke. To our knowledge, this is the first reported case of cortical dysplasia in the posterior parietal cortex as the cause of complex partial seizures beginning with upside-down reversal of vision. As the pathophysiological characteristics of this phenomenon remain unclear, this case implies that the posterior parietal cortex is a possible anatomical localization of the central integrator of visual extra-personal orientation.     

Pathogenetic mechanisms of focal cortical dysplasia

Focal cortical dysplasias (FCDs) constitute a prevalent cause of intractable epilepsy in children, and is one of the leading conditions requiring epilepsy surgery. Despite recent advances in the cellular and molecular biology of these conditions, the pathogenetic mechanisms of FCDs remain largely unknown. The purpose if this work is to review the molecular underpinnings of FCDs and to highlight potential therapeutic targets. A systematic review of the literature regarding the histologic, molecular, and electrophysiologic aspects of FCDs was conducted. Disruption of the mammalian target of rapamycin (mTOR) signaling comprises a common pathway underlying the structural and electrical disturbances of some FCDs. Other mechanisms such as viral infections, prematurity, head trauma, and brain tumors are also posited. mTOR inhibitors (i.e., rapamycin) have shown positive results on seizure management in animal models and in a small cohort of patients with FCD. Encouraging progress has been achieved on the molecular and electrophysiologic basis of constitutive cells in the dysplastic tissue. Despite the promising results of mTOR inhibitors, large‐scale randomized trials are in need to evaluate their efficacy and side effects, along with additional mechanistic studies for the development of novel, molecular‐based diagnostic and therapeutic approaches. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here .     

Surgical management of focal cortical dysplasia

Focal cortical dysplasia is a malformation caused by abnormalities of cortical development. It is characterized by no dysmorphic or ballon cells (type I), dysmorphic neurons witout or with ballon cells (type II). It is the main cause of pharmacoresistant epilepsy. The combination of clinical and neurophysiological findings provided by VEEG and MRI had lead to an improvement in the diagnosis and outcome of FCD. This paper describes our experience in the form of a retrospective study conducted on the patients affected by FCD who were treated in the Clinical Neurophysiology Service at University Hospital of Lille in France.