In May 2012, Brain Pathology published a mini-symposium on “etiology of epilepsy,” to update the neuropathology community on common and difficult to diagnose brain lesions associated with early-onset and drug-resistant focal epilepsy and amenable to epilepsy surgery. At this time, epilepsy surgery became widely accepted as a successful treatment option for a carefully selected group of patients and the number of epilepsy surgery centers had been growing continuously. Under the motto “cause matters,” the authors appraised the rejuvenation of neuropathology in the arena of epileptology and its increasing impact for patient selection and postsurgical management. Articles reviewed (i) the concept of low-grade epilepsy-associated tumors, a terminology still used nowadays in the scientific literature (1); (ii) the 1st international consensus classification system for Focal Cortical Dysplasia (FCD), which was just published in 2011 and became the gold standard for diagnosing FCD in clinical practice and research (2); (iii) anticipating an international classification scheme for Hippocampal Sclerosis, published subsequently in 2013 (3); and (iv) the role of the innate and adaptive immune system in epileptic encephalitis.(4) Over the past 9 years, these topics remained in the center of the scientific interest and fascinating discoveries led to a better understanding of the pathogenesis and potentially druggable targets for pharmacological treatment. We are proud, therefore, to present a follow-up mini-symposium on “Neuropathology and Focal Human Epilepsy” and invited a panel of distinguished and highly recognized authors whom were fundamental to these exciting developments. Five topics were chosen to summarize and discuss most current knowledge in epilepsy-associated brain lesions and the quest for best treatment options in epileptology. The discovery of post-zygous brain somatic mosaicism in cortical malformations and their causal role in the pathogenesis of focal brain lesions as well as epileptogenesis, deciphering also their impact at the single-cell level, will be a focus of our mini-symposium, therefore. Other topics of interest cover new diagnostic entities, new molecular diagnostic platforms, and the impact of a reliable neuropathology diagnosis for the prediction of successful postsurgical outcome.

Drs. Blumcke, Cendes, Miyata, Thom, Aronica, and Najm will start this mini-symposium reflecting not only the success of the FCD classification scheme from 2011 (5), but also highlight its gaps and challenges, which will likely result in a timely first update (currently in preparation). They present a series of three case vignettes, each representing a common, although challenging clinical scenario. We will then better understand the need of a comprehensive integration of diagnostic modalities including high-power neuroimaging, advanced EEG recordings, and the neuropathology phenotype–genotype work up to advance clinical patient management to the next level.

The discovery of somatic brain mutations in the MTOR or GATOR signaling pathway causing distinct subtypes of cortical malformations represented a hallmark of scientific research during the past 5 years. Drs. Kobow, Baulac, von Deimling, and Lee describe the currently known genetic landscape of epileptogenic brain lesions and also introduce novel entities defined by their clinico-pathological and genetic signature (6). Their review will offer an intriguing insight into DNA methylation analysis, which opened the avenue to “Neuropathology 2.0.” Much was learned from brain tumors and the question remains whether this platform can be translated into the arena of epileptology. In fact, electrical activity transmitted by the epileptic seizures may trigger itself an epigenetically encrypted cellular disease memory and DNA methylation shall be successfully used to differentiate the broad spectrum of cortical malformations in epilepsy.

Drs. Khoshkoo, Lal, and Walsh will continue this path to the exciting area of single-cell genomics, which provides a molecular biological basis to better understand the complex issue of epileptogenic neocortical lesions (7). It is the ever challenging question of (i) which gene is mutated, (ii) in which neuroepithelial cell lineage, (iii) in which region, and (iv) at which time point during neocortical development to produce an epileptogenic and anatomo-pathologically complex lesion.

Drs. Coras, Holthausen, and Sarnat address the challenging issue of Focal Cortical Dysplasia ILAE Type 1 (8). They will reflect on the ongoing discussion how to address the clinico-pathological and genetic spectrum of this disease category at the clinical and scientific level. The lack of a specific genetic signature attributed to FCD 1 or its three proposed neuropathology phenotypes, that is, FCD with a vertical, horizontal, or mixed pattern of abnormal cortical neuroanatomy continues to obstruct a reliable disease classification and patient stratification into scientifically sound study groups.

Finally, Drs. Jehi and Braun review postsurgical outcome measures by sharing their experience with large clinical series from Europe and USA (9). It is fair to conclude, that both authors support the concept of early surgery when a lesion can be identified prior to surgery as most successful treatment option until druggable targets will be made available for personalized treatment. However, it is yet to be specified if the histopathology diagnosis and presumptive nature of the lesion also play a role. Our mini-symposium will end with these provocative questions which should alert the international community of neuropathologists to synchronize and foster their efforts toward a comprehensive disease classification integrating histopathology, clinical findings, and genetic studies.

Thus, we wish you a pleasant reading of this mini-symposium with its exciting data collection and provocative theories, which you may find helpful for daily practice, but also to encourage further research and engagement to focal human epilepsies.

2012 年 5 月，Brain Pathology发表了关于“癫痫病因学”的小型研讨会，向神经病理学界更新与早发性和耐药性局灶性癫痫相关的常见和难以诊断的脑部病变，并适合癫痫手术。此时，癫痫手术被广泛接受为精心挑选的一组患者的成功治疗选择，癫痫手术中心的数量不断增长。在“原因很重要”的座右铭下，作者评估了神经病理学在癫痫学领域的复兴及其对患者选择和术后管理的日益增长的影响。文章回顾了 (i) 低级别癫痫相关肿瘤的概念，该术语至今仍在科学文献中使用 ( 1); (ii) 2011年刚刚发布的第一个局灶性皮质发育不良（FCD）国际共识分类系统，成为临床实践和研究中诊断FCD的金标准（2）；(iii) 期待海马硬化症的国际分类方案，随后于 2013 年发布 ( 3 )；(iv) 先天性和适应性免疫系统在癫痫性脑炎中的作用。 ( 4) 在过去的 9 年中，这些主题一直是科学兴趣的中心，而迷人的发现使人们更好地了解了药物治疗的发病机制和潜在的药物靶点。因此，我们很自豪能够举办关于“神经病理学和局灶性人类癫痫”的后续小型研讨会，并邀请了一组杰出且高度认可的作者，他们对这些令人兴奋的发展至关重要。选择了五个主题来总结和讨论与癫痫相关的脑损伤的最新知识以及对癫痫学最佳治疗方案的探索。发现皮质畸形中的后合子脑体细胞嵌合体及其在局灶性脑损伤的发病机制和癫痫发生中的因果作用，还破译了它们在单细胞水平上的影响，因此，这将是我们小型研讨会的重点。其他感兴趣的主题包括新的诊断实体、新的分子诊断平台以及可靠的神经病理学诊断对预测成功的术后结果的影响。

博士。Blumcke、Cendes、Miyata、Thom、Aronica 和 Najm 将启动这个小型研讨会，不仅反映了 FCD 分类方案自 2011 年 ( 5 ) 以来的成功，而且还强调了它的差距和挑战，这可能会导致及时的第一个更新（目前正在准备中）。他们展示了一系列三个案例小插曲，每个小插曲都代表一个常见但具有挑战性的临床场景。然后，我们将更好地了解全面整合诊断方式的需求，包括高功率神经成像、高级脑电图记录和神经病理学表型-基因型工作，以将临床患者管理提升到一个新的水平。

在 MTOR 或 GATOR 信号通路中发现导致不同亚型皮质畸形的体细胞脑突变是过去 5 年科学研究的一个标志。博士。Kobow、Baulac、von Deimling 和 Lee 描述了目前已知的致癫痫性脑损伤的遗传景观，并介绍了由其临床病理学和遗传特征定义的新实体（6）。他们的评论将为 DNA 甲基化分析提供一个有趣的见解，从而为“神经病理学 2.0”开辟了道路。从脑肿瘤中学到了很多东西，问题仍然是这个平台是否可以转化为癫痫学领域。事实上，癫痫发作传递的电活动可能会触发自身的表观遗传加密的细胞疾病记忆，并且 DNA 甲基化应成功用于区分癫痫中广泛的皮质畸形。

博士。Khoshkoo、Lal 和 Walsh 将继续这条通往令人兴奋的单细胞基因组学领域的道路，这为更好地了解致癫痫性新皮质病变的复杂问题提供了分子生物学基础 ( 7 )。这是一个具有挑战性的问题：（i）哪个基因发生突变，（ii）在哪个神经上皮细胞谱系中，（iii）在哪个区域，以及（iv）在新皮质发育过程中的哪个时间点产生致癫痫和解剖病理学复杂的病变。

博士。Coras、Holthausen 和 Sarnat 解决了局灶性皮质发育不良 ILAE 1 型的挑战性问题 ( 8 )。他们将反思正在进行的讨论如何在临床和科学水平上解决该疾病类别的临床病理学和遗传谱。缺乏归因于 FCD 1 或其三种提出的神经病理学表型的特定遗传特征，即具有垂直、水平或混合模式的异常皮质神经解剖学的 FCD 继续阻碍可靠的疾病分类和患者分层到科学合理的研究组.

最后，博士。Jehi 和 Braun 通过分享他们对来自欧洲和美国的大型临床系列的经验来回顾术后结果测量 ( 9 )。可以公平地得出结论，两位作者都支持早期手术的概念，因为可以在手术前将病变识别为最成功的治疗选择，直到可药物靶点可用于个性化治疗。然而，尚不清楚组织病理学诊断和病变的推定性质是否也起作用。我们的小型研讨会将以这些挑衅性的问题结束，这些问题应该提醒国际神经病理学家社区同步和促进他们的努力，以实现整合组织病理学、临​​床发现和遗传研究的综合疾病分类。

因此，我们希望您愉快地阅读本次小型研讨会，其中包含令人兴奋的数据收集和富有启发性的理论，您可能会发现它们对日常实践有所帮助，同时也鼓励进一步研究和参与焦点人类癫痫。