Drug-resistant epilepsy affects approximately one-third of the patients with epilepsy. The pharmacoresistant condition in epilepsy is mainly explained by six hypotheses. In addition, several experimental models have been used to understand the mechanisms involved in pharmacoresistant epilepsy and to identify novel therapies to control this condition. However, the global prevalence of this disease persists without changes. Several factors can explain this situation. First of all, the pharmacoresistant epilepsy is explained by different and independent hypotheses. Each hypothesis indicates specific mechanisms to explain the drug-resistant condition in epilepsy. However, there are different findings suggesting common mechanisms between the different hypotheses. Other important situation is that the experimental models designed for the screening of drugs with potential anticonvulsant effect do not consider factors such as age, gender, type of epilepsy, and comorbid disorders. The present review focuses on indicating the limitations for each hypothesis and the relationships among them. The relevance to consider central and peripheral phenomena associated with the drug-resistant condition in different types of epilepsy is also indicated. The necessity to establish a global hypothesis that integrates all the phenomena associated with the pharmacoresistant epilepsy is proposed. This article is part of the Special Issue "NEWroscience 2018".

中文翻译：

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耐药性癫痫：从多个假设到使用临床前资源的完整解释

耐药性癫痫影响大约三分之一的癫痫患者。癫痫中的药物耐药状况主要由六个假设解释。此外，一些实验模型已被用于了解药物抗性癫痫的机制，并确定控制这种情况的新疗法。然而，这种疾病的全球流行仍然没有改变。有几个因素可以解释这种情况。首先，药物耐药性癫痫由不同且独立的假设解释。每个假设都表明了解释癫痫耐药情况的具体机制。然而，有不同的发现表明不同假设之间的共同机制。另一个重要的情况是，为筛选具有潜在抗惊厥作用的药物而设计的实验模型没有考虑年龄、性别、癫痫类型和共存疾病等因素。本综述重点说明每个假设的局限性以及它们之间的关系。还指出了考虑与不同类型癫痫的耐药情况相关的中枢和外周现象的相关性。提出了建立一个综合所有与耐药性癫痫相关现象的全球假设的必要性。本文是特刊“NEWroscience 2018”的一部分。本综述重点说明每个假设的局限性以及它们之间的关系。还指出了考虑与不同类型癫痫的耐药情况相关的中枢和外周现象的相关性。提出了建立一个综合所有与耐药性癫痫相关现象的全球假设的必要性。本文是特刊“NEWroscience 2018”的一部分。本综述重点说明每个假设的局限性以及它们之间的关系。还指出了考虑与不同类型癫痫的耐药情况相关的中枢和外周现象的相关性。提出了建立一个综合所有与耐药性癫痫相关现象的全球假设的必要性。本文是特刊“NEWroscience 2018”的一部分。