Samanta Debopam
Division of Child Neurology, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Epilepsy Behav. 2025 Mar;164:110272. doi: 10.1016/j.yebeh.2025.110272. Epub 2025 Jan 23.
Lennox-Gastaut syndrome (LGS) is a severe developmental and epileptic encephalopathy marked by drug-resistant seizures and profound cognitive and behavioral impairments, with nearly 95% of individuals affected by moderate to severe intellectual disability. This review comprehensively explores the cognitive and behavioral impacts of current treatment options for LGS, including antiseizure medications (ASMs), neuromodulation strategies, the ketogenic diet, and surgical interventions. Given the limited availability of LGS-specific data for several ASMs, the evidence base is supplemented with findings from general epilepsy populations and individuals with epilepsy and intellectual disabilities. The evidence reveals that ASMs exert varied cognitive and behavioral effects in LGS. Medications such as valproate, lamotrigine, cannabidiol, fenfluramine, levetiracetam, brivaracetam, felbamate, and rufinamide generally support cognitive stability, while topiramate and zonisamide are associated with cognitive challenges. Behavioral outcomes also vary: stability is observed with valproate, lamotrigine, rufinamide, cannabidiol, and fenfluramine, whereas medications like levetiracetam, perampanel, brivaracetam, clobazam, and zonisamide can increase aggression or irritability. Nonpharmacological therapies, particularly when they reduce seizure frequency, typically provide greater cognitive and behavioral stability, with some offering improvement. Early intervention-especially through surgical options-appears most beneficial for preserving cognitive function. Additionally, therapies such as the ketogenic diet and neuromodulation may provide independent cognitive benefits beyond seizure control. This review emphasizes the importance of personalized treatment strategies, integrating cognitive and behavioral evaluations in therapy selection. Key components include baseline cognitive and behavioral assessments, followed by regular follow-up evaluations, particularly after therapy changes. Consideration of minimizing ASM polytherapy, careful evaluation of drug-drug interactions, pharmacogenomic implications, and the need for therapeutic drug monitoring in cases of cognitive adverse effects is essential. Future research should focus on developing assessment tools tailored to the unique needs of individuals with LGS, utilizing connectivity measures to assess intervention impacts, and advancing precision therapeutics to improve cognitive and behavioral outcomes.
伦诺克斯 - 加斯托综合征（LGS）是一种严重的发育性和癫痫性脑病，其特征为耐药性癫痫发作以及严重的认知和行为障碍，近95%的患者患有中度至重度智力残疾。本综述全面探讨了LGS当前治疗方案对认知和行为的影响，包括抗癫痫药物（ASMs）、神经调节策略、生酮饮食和手术干预。鉴于几种ASMs针对LGS的特定数据有限，证据基础通过一般癫痫人群以及患有癫痫和智力残疾个体的研究结果进行补充。证据表明，ASMs在LGS中产生不同的认知和行为影响。丙戊酸盐、拉莫三嗪、大麻二酚、芬氟拉明、左乙拉西坦、布瓦西坦、非氨酯和卢非酰胺等药物通常有助于认知稳定性，而托吡酯和唑尼沙胺则与认知挑战相关。行为结果也各不相同：丙戊酸盐、拉莫三嗪、卢非酰胺、大麻二酚和芬氟拉明可观察到行为稳定性，而左乙拉西坦、吡仑帕奈、布瓦西坦、氯巴占和唑尼沙胺等药物可能会增加攻击性或易怒性。非药物疗法，特别是当它们降低癫痫发作频率时，通常能提供更大的认知和行为稳定性，有些还能带来改善。早期干预——尤其是通过手术选择——似乎对保护认知功能最为有益。此外，生酮饮食和神经调节等疗法可能在控制癫痫发作之外提供独立的认知益处。本综述强调个性化治疗策略的重要性，在治疗选择中纳入认知和行为评估。关键组成部分包括基线认知和行为评估，随后进行定期随访评估，尤其是在治疗方案改变后。考虑尽量减少ASM联合治疗、仔细评估药物相互作用、药物基因组学影响以及在出现认知不良反应时进行治疗药物监测的必要性至关重要。未来的研究应专注于开发针对LGS患者独特需求的评估工具，利用连接性测量来评估干预效果，并推进精准治疗以改善认知和行为结果。
