Neuroscience Unit, UCL Great Ormond Street Institute of Child Health, London, UK; Department of Clinical Neurophysiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
Department Paediatric Neurology, University Hospitals, Leuven, Belgium.
Neuropharmacology. 2020 Jun 15;170:107854. doi: 10.1016/j.neuropharm.2019.107854. Epub 2019 Nov 18.
In contrast to epilepsy in adolescents and adults, neonatal seizures and early onset epilepsy poses unique challenges with significant repercussion for treatment choices. Most importantly, high seizure burden and epileptic encephalopathy are associated with developmental, behavioural and cognitive problems. The causes are multifactorial and include etiology, seizure burden, epileptic encephalopathy, but also antiseizure medication. In contrast to adults and older children only very few drugs have been licenced for infants and neonates, and after a long delay. Very recently, extrapolation of adult data has become possible as a path to speed up drug development for younger children but this is not necessarily possible for infants and neonates. With the advances in understanding the molecular basis of many epilepsies, targeted therapies become available, for example for KCNQ2 mutation related epilepsies, Dravet syndrome or tuberous sclerosis complex. Drug trials in neonates are particularly challenging because of their inconspicuous clinical presentation, the need for continuous EEG monitoring, high co-morbidity, and poor response to antiepileptic drugs. There is an urgent need for development of new drugs, evaluation of safety and efficacy of current antiseizure drugs, as well as for national policies and guidelines for the management of seizures and epilepsy in neonates and infants. This article is part of the special issue entitled 'New Epilepsy Therapies for the 21st Century - From Antiseizure Drugs to Prevention, Modification and Cure of Epilepsy'.
与青少年和成人癫痫相比,新生儿癫痫和早发性癫痫具有独特的挑战,对治疗选择有重大影响。最重要的是,高发作负担和癫痫性脑病与发育、行为和认知问题有关。病因是多因素的,包括病因、发作负担、癫痫性脑病,还包括抗癫痫药物。与成人和年龄较大的儿童不同,只有极少数药物被许可用于婴儿和新生儿,而且是在很长时间的延迟之后。最近,由于为年龄较小的儿童加速药物开发成为可能,从成人数据外推成为一种途径,但这对于婴儿和新生儿来说不一定可行。随着对许多癫痫分子基础理解的进步,靶向治疗成为可能,例如针对 KCNQ2 突变相关癫痫、Dravet 综合征或结节性硬化症。新生儿药物试验特别具有挑战性,因为它们的临床表现不明显,需要持续进行脑电图监测,合并症高,以及对抗癫痫药物的反应不佳。迫切需要开发新药,评估现有抗癫痫药物的安全性和疗效,以及制定国家政策和指南,以管理新生儿和婴儿的癫痫发作和癫痫。本文是特刊“21 世纪的新型癫痫治疗方法-从抗癫痫药物到癫痫的预防、改善和治愈”的一部分。