Bruxel Estela M, do Canto Amanda M, Bruno Danielle C F, Geraldis Jaqueline C, Lopes-Cendes Iscia
Departments of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil.
Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, Brazil.
Epilepsia Open. 2022 Aug;7 Suppl 1(Suppl 1):S94-S120. doi: 10.1002/epi4.12536. Epub 2021 Oct 18.
Mesial temporal lobe epilepsy (MTLE) is the most common type of focal epilepsy in adults, and hippocampal sclerosis (HS) is a frequent histopathological feature in patients with MTLE. Pharmacoresistance is present in at least one-third of patients with MTLE with HS (MTLE+HS). Several hypotheses have been proposed to explain the mechanisms of pharmacoresistance in epilepsy, including the effect of genetic and molecular factors. In recent years, the increased knowledge generated by high-throughput omic technologies has significantly improved the power of molecular genetic studies to discover new mechanisms leading to disease and response to treatment. In this review, we present and discuss the contribution of different omic modalities to understand the basic mechanisms determining pharmacoresistance in patients with MTLE+HS. We provide an overview and a critical discussion of the findings, limitations, new approaches, and future directions of these studies to improve the understanding of pharmacoresistance in MTLE+HS. However, it is important to point out that, as with other complex traits, pharmacoresistance to anti-seizure medications is likely a multifactorial condition in which gene-gene and gene-environment interactions play an important role. Thus, studies using multidimensional approaches are more likely to unravel these intricate biological processes.
内侧颞叶癫痫（MTLE）是成人中最常见的局灶性癫痫类型，而海马硬化（HS）是MTLE患者常见的组织病理学特征。至少三分之一的MTLE合并HS（MTLE+HS）患者存在药物抵抗。人们提出了几种假说来解释癫痫药物抵抗的机制，包括遗传和分子因素的影响。近年来，高通量组学技术产生的知识不断增加，显著提高了分子遗传学研究发现导致疾病和治疗反应的新机制的能力。在这篇综述中，我们展示并讨论了不同组学模式对理解MTLE+HS患者药物抵抗基本机制的贡献。我们对这些研究的结果、局限性、新方法和未来方向进行了概述和批判性讨论，以增进对MTLE+HS中药物抵抗的理解。然而，必须指出的是，与其他复杂性状一样，对抗癫痫药物的耐药性可能是一种多因素状况，其中基因-基因和基因-环境相互作用起着重要作用。因此，使用多维方法的研究更有可能揭示这些复杂的生物学过程。
