Child Neurology Section, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States.
Neuropediatrics. 2020 Apr;51(2):135-145. doi: 10.1055/s-0040-1701694. Epub 2020 Feb 20.
Dravet syndrome (DS), previously known as severe myoclonic epilepsy of infancy, is a severe developmental and epileptic encephalopathy caused by loss-of-function mutations in one copy of (haploinsufficiency), located on chromosome 2q24, with decreased function of Nav1.1 sodium channels in GABAergic inhibitory interneurons. Pharmacoresistant seizures in DS start in the infancy in the form of hemiclonic febrile status epilepticus. Later, other intractable seizure types develop including myoclonic seizures. Early normal development in infancy evolves into moderate to severe intellectual impairment, motor impairment, behavioral abnormalities, and later a characteristic crouching gait. Clobazam, valproate, levetiracetam, topiramate, zonisamide, ketogenic diet, and vagus nerve stimulation had been shown to be effective, but even with polytherapy, only 10% of patients get adequate seizure control. The author provides a narrative review of the current treatment paradigm as well as recent advances in the management of DS based on a comprehensive literature review (MEDLINE using PubMed and OvidSP vendors with appropriate keywords to incorporate recent evidence), personal practice, and experience. In recent years, the treatment paradigm of DS is changing with the approval of pharmaceutical-grade cannabidiol oil and stiripentol. Another novel antiepileptic drug (AED), fenfluramine, had also shown excellent efficacy in phase 3 studies of DS. However, these AEDs primarily control seizures without addressing the underlying pathogenesis and other important common comorbidities such as cognitive impairment, autistic behavior, neuropsychiatric abnormalities, and motor impairment including crouching gait. Several agents targeted for DS are in the developmental stage: TAK935, lorcaserin, clemizole, huperzine analog, ataluren, selective sodium channel modulators and activators, antisense oligonucleotide therapy, and adenoviral vector therapy. As DS is associated with a high risk of sudden unexpected death in epilepsy, seizure detection devices can be used in this population for testing and clinical validation of these devices.
德拉维雷综合征（DS），以前称为婴儿严重肌阵挛性癫痫，是一种严重的发育性和癫痫性脑病，由 1 号染色体上 （杂合子不足）的功能丧失突变引起，GABA 能抑制性中间神经元中的 Nav1.1 钠通道功能降低。DS 的耐药性癫痫发作始于婴儿期，表现为热性局灶性癫痫持续状态。后来，还会出现其他难治性癫痫发作类型，包括肌阵挛发作。婴儿期的早期正常发育会发展为中度至重度智力障碍、运动障碍、行为异常，以及后来特有的蹲伏步态。氯巴占、丙戊酸、左乙拉西坦、托吡酯、唑尼沙胺、生酮饮食和迷走神经刺激已被证明有效，但即使采用多药治疗，也只有 10%的患者能获得足够的癫痫控制。作者基于全面的文献回顾（使用 MEDLINE 及 PubMed 和 OvidSP 供应商的适当关键字纳入最新证据）、个人实践和经验，提供了对当前治疗模式以及 DS 管理方面最新进展的叙述性综述。近年来，随着医药级大麻二酚油和 stiripentol 的批准，DS 的治疗模式正在发生变化。另一种新型抗癫痫药物（AED）芬氟拉明在 DS 的 3 期研究中也显示出了极好的疗效。然而，这些 AED 主要控制癫痫发作，而不能解决潜在的发病机制和其他重要的常见合并症，如认知障碍、自闭症行为、神经精神异常以及包括蹲伏步态在内的运动障碍。几种针对 DS 的药物正在研发阶段：TAK935、lorcaserin、clemizole、石杉碱甲类似物、ataluren、选择性钠通道调节剂和激活剂、反义寡核苷酸治疗和腺相关病毒载体治疗。由于 DS 与癫痫猝死风险增加有关，因此可以在该人群中使用癫痫发作检测设备来测试和验证这些设备的临床效果。
