Samanta Debopam, Bhalla Sonam, Bhatia Sonal, Fine Anthony L, Haridas Babitha, Karakas Cemal, Keator Cynthia Guadalupe, Koh Hyun Yong, Perry M Scott, Stafstrom Carl E, Vidaurre Jorge, Warren Aaron E L
Division of Child Neurology, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Division of Child Neurology, Emory University/Children's Healthcare of Atlanta, USA.
Epilepsy Behav. 2025 Mar;164:110261. doi: 10.1016/j.yebeh.2024.110261. Epub 2025 Jan 23.
Lennox-Gastaut syndrome (LGS) is a severe, childhood-onset developmental and epileptic encephalopathy characterized by multiple drug-resistant seizure types, specific electroencephalogram (EEG) patterns, and significant cognitive and behavioral impairments. To date, eight anti-seizure medications (ASMs) have been specifically approved by the U.S. Food and Drug Administration (FDA) for the treatment of LGS: clonazepam, felbamate, lamotrigine, topiramate, rufinamide, clobazam, cannabidiol, and fenfluramine. Additionally, several other ASMs, including valproate, are frequently used off-label for LGS management. As the therapeutic landscape for LGS expands, clinicians are increasingly faced with complex decisions regarding optimal ASM selection. This narrative review explores evolving treatment strategies, offering a consensus-based treatment algorithm designed by a panel of U.S.- based experts. We analyze both FDA-approved and off-label ASMs, drawing on data from randomized controlled trials, open-label extensions, and real-world studies to assess each drug's efficacy and safety profile. A key challenge in comparing ASMs lies in the heterogeneity of study designs and outcome measures. This review addresses these limitations and considers crucial factors influencing ASM selection, such as seizure outcomes, safety profiles, cognitive and behavioral outcomes, drug-drug interactions, and rational polypharmacy. Barriers to access, including economic and regulatory hurdles, are also discussed. The proposed treatment algorithm emphasizes a personalized approach to LGS management, recommending valproate or clobazam as first-line treatments, followed by individualized combinations based on the specific patient profile and associated comorbidities.
伦诺克斯-加斯东综合征（LGS）是一种严重的、儿童期起病的发育性和癫痫性脑病，其特征为多种耐药性癫痫发作类型、特定的脑电图（EEG）模式以及显著的认知和行为障碍。迄今为止，美国食品药品监督管理局（FDA）已专门批准了八种抗癫痫药物（ASMs）用于治疗LGS：氯硝西泮、非氨酯、拉莫三嗪、托吡酯、卢非酰胺、氯巴占、大麻二酚和芬氟拉明。此外，包括丙戊酸盐在内的其他几种ASMs也经常被用于LGS的非标签治疗。随着LGS治疗领域的不断拓展，临床医生在选择最佳ASMs时面临的决策日益复杂。本叙述性综述探讨了不断演变的治疗策略，提供了一个由一组美国专家设计的基于共识的治疗算法。我们分析了FDA批准的和非标签使用的ASMs，借鉴随机对照试验、开放标签扩展试验和真实世界研究的数据，以评估每种药物的疗效和安全性。比较ASMs的一个关键挑战在于研究设计和结果测量的异质性。本综述解决了这些局限性，并考虑了影响ASM选择的关键因素，如癫痫发作结果、安全性、认知和行为结果、药物相互作用以及合理的联合用药。还讨论了包括经济和监管障碍在内的获取障碍。所提出的治疗算法强调对LGS管理采取个性化方法，推荐丙戊酸盐或氯巴占作为一线治疗药物，随后根据特定患者情况和相关合并症进行个体化联合用药。
