Besag Frank M C, Vasey Michael J, Chin Richard F M
East London NHS Foundation Trust, Bedford, UK.
School of Pharmacy, University College London, London, UK.
Expert Opin Pharmacother. 2023 May-Aug;24(11):1249-1268. doi: 10.1080/14656566.2023.2215924. Epub 2023 Jun 5.
Lennox-Gastaut syndrome (LGS) is a severe childhood-onset epileptic encephalopathy, characterized by multiple seizure types, generalized slow spike-and-wave complexes in the EEG, and cognitive impairment. Seizures in LGS are typically resistant to treatment with antiseizure medications (ASMs). Tonic/atonic ('drop') seizures are of particular concern, due to their liability to cause physical injury.
We summarize evidence for current and emerging ASMs for the treatment of seizures in LGS. The review focuses on findings from randomized, double-blind, placebo-controlled trials (RDBCTs). For ASMs for which no double-blind trials were identified, lower quality evidence was considered. Novel pharmacological agents currently undergoing investigation for the treatment of LGS are also briefly discussed.
Evidence from RDBCTs supports the use of cannabidiol, clobazam, felbamate, fenfluramine, lamotrigine, rufinamide, and topiramate as adjunct treatments for drop seizures. Percentage decreases in drop seizure frequency ranged from 68.3% with high-dose clobazam to 14.8% with topiramate. Valproate continues to be considered the first-line treatment, despite the absence of RDBCTs specifically in LGS. Most individuals with LGS will require treatment with multiple ASMs. Treatment decisions should be individualized and take into account adverse effects, comorbidities, general quality of life, and drug interactions, as well as individual efficacy.
伦诺克斯 - 加斯托综合征（LGS）是一种严重的儿童期起病的癫痫性脑病，其特征为多种发作类型、脑电图显示广泛性慢棘慢复合波以及认知障碍。LGS的癫痫发作通常对抗癫痫药物（ASMs）治疗耐药。强直/失张力（“跌倒”）发作尤其令人担忧，因为它们容易导致身体受伤。
我们总结了用于治疗LGS癫痫发作的现有和新兴ASM的证据。该综述重点关注随机、双盲、安慰剂对照试验（RDBCTs）的结果。对于未找到双盲试验的ASM，则考虑质量较低的证据。还简要讨论了目前正在研究用于治疗LGS的新型药物。
RDBCTs的证据支持使用大麻二酚、氯巴占、非氨酯、芬氟拉明、拉莫三嗪、鲁非酰胺和托吡酯作为跌倒发作的辅助治疗。跌倒发作频率的百分比下降范围从高剂量氯巴占的68.3%到托吡酯的14.8%。尽管缺乏专门针对LGS的RDBCTs，但丙戊酸盐仍被视为一线治疗药物。大多数LGS患者需要多种ASM联合治疗。治疗决策应个体化，并考虑不良反应、合并症、总体生活质量、药物相互作用以及个体疗效。
