Chen Fan, He Xinghui, Luan Guoming, Li Tianfu
Beijing Key Laboratory of Epilepsy Research, Department of Neurology, Beijing Institute for Brain Disorders, Sanbo Brain Hospital, Capital Medical University, Beijing, China.
Beijing Key Laboratory of Epilepsy Research, Department of Neurosurgery, Beijing Institute for Brain Disorders, Sanbo Brain Hospital, Capital Medical University, Beijing, China.
Front Neurol. 2019 Feb 26;10:119. doi: 10.3389/fneur.2019.00119. eCollection 2019.
Epilepsy is a neurological disorder characterized by a long term propensity to produce unprovoked seizures and by the associated comorbidities including neurological, cognitive, psychiatric, and impairment the quality of life. Despite the clinic availability of several novel antiepileptic drugs (AEDs) with different mechanisms of action, more than one-third of patients with epilepsy suffer with pharmacoresistant epilepsy. Until now, no AEDs have been proven to confer the efficacy in alteration of disease progression or inhibition of the development of epilepsy. The ketogenic diet, the high-fat, low-carbohydrate composition is an alternative metabolic therapy for epilepsy, especially for children with drug-resistant epilepsy. Recently clinical and experimental results demonstrate its efficacy in ameliorating both seizures and comorbidities associated with epilepsy, such as cognitive/psychiatric concerns for the patients with refractory epilepsy. Of importance, ketogenic diet demonstrates to be a promising disease-modifying or partial antiepileptogenesis therapy for epilepsy. The mechanisms of action of ketogenic diet in epilepsy have been revealed recently, such as epigenetic mechanism for increase the adenosine level in the brain and inhibition of DNA methylation. In the present review, we will focus on the mechanisms of ketogenic diet therapies underlying adenosine system in the prevention of epileptogenesis and disease modification. In addition, we will review the role of ketogenic diet therapy in comorbidities associated epilepsy and the underlying mechanisms of adenosine.
癫痫是一种神经系统疾病，其特征是长期有产生无端发作的倾向以及伴有包括神经、认知、精神方面的合并症，且生活质量受损。尽管临床上有几种作用机制不同的新型抗癫痫药物（AEDs），但超过三分之一的癫痫患者患有药物难治性癫痫。到目前为止，尚无AEDs被证明能有效改变疾病进程或抑制癫痫的发展。生酮饮食，即高脂肪、低碳水化合物的组成，是癫痫的一种替代代谢疗法，尤其适用于耐药性癫痫患儿。最近的临床和实验结果表明其在改善癫痫发作及与癫痫相关的合并症方面具有疗效，比如对于难治性癫痫患者的认知/精神方面问题。重要的是，生酮饮食被证明是一种有前景的用于癫痫的疾病修饰或部分抗癫痫发生疗法。生酮饮食在癫痫中的作用机制最近已被揭示，例如通过表观遗传机制提高大脑中的腺苷水平并抑制DNA甲基化。在本综述中，我们将聚焦于生酮饮食疗法在预防癫痫发生和疾病修饰中腺苷系统的潜在机制。此外，我们将综述生酮饮食疗法在癫痫相关合并症中的作用以及腺苷的潜在机制。
