Samanta Debopam, Naik Sunil
Division of Child Neurology, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Department of Pediatrics and Neurology, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA.
Epilepsy Behav. 2025 Sep;170:110472. doi: 10.1016/j.yebeh.2025.110472. Epub 2025 May 22.
Lennox-Gastaut Syndrome (LGS) is a severe developmental and epileptic encephalopathy characterized by multiple drug-resistant seizure types, presenting significant challenges for treatment. This comprehensive review examines seizure-type-specific response patterns to various therapeutic interventions in LGS. We conducted an extensive literature review of randomized controlled trials, observational studies, and real-world evidence, covering research up to February 2025. Our analysis shows that atonic seizures respond particularly well to corpus callosotomy (CC) and Vagus Nerve Stimulation (VNS), with CC demonstrating superior efficacy. Generalized tonic-clonic seizures (GTCS) show favorable responses to antiseizure medications (ASMs) such as felbamate, lamotrigine, topiramate, fenfluramine, lacosamide, and perampanel. Myoclonic seizures tend to respond better to clonazepam, topiramate, zonisamide, brivaracetam, and perampanel, but may show limited responsiveness to neuromodulation and CC. Atypical absence seizures may respond to valproate, topiramate, and rufinamide, but show poor responses to brivaracetam and perampanel. The ketogenic diet and resective epilepsy surgery demonstrate broad efficacy across seizure types, although specific data for each type remain limited. VNS is most effective for atonic and tonic seizures, with less consistent responses in GTCS and focal seizures. Emerging neuromodulation techniques, including deep brain stimulation (DBS) and responsive neurostimulation (RNS), show promise, particularly for tonic and GTCS, but further investigation is needed. This review underscores the importance of tailoring treatment to predominant seizure types and calls for more rigorous, seizure-type-specific outcome reporting in future clinical trials, along with the need for long-term studies. The findings advocate for a precision, network-based approach to treatment, where therapeutic decisions are guided by individual seizure patterns and supported by evidence-based, seizure-type-specific efficacy data.
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，其特征为多种耐药性癫痫发作类型，给治疗带来了重大挑战。本综述全面考察了LGS中针对不同治疗干预措施的癫痫发作类型特异性反应模式。我们对随机对照试验、观察性研究和真实世界证据进行了广泛的文献综述，涵盖截至2025年2月的研究。我们的分析表明，失张力发作对胼胝体切开术（CC）和迷走神经刺激（VNS）反应特别良好，CC显示出更高的疗效。全身强直 - 阵挛发作（GTCS）对抗癫痫药物（ASMs）如非氨酯、拉莫三嗪、托吡酯、芬氟拉明、拉科酰胺和吡仑帕奈反应良好。肌阵挛发作对氯硝西泮、托吡酯、唑尼沙胺、布瓦西坦和吡仑帕奈反应往往更好，但对神经调节和CC的反应可能有限。非典型失神发作可能对丙戊酸盐、托吡酯和卢非酰胺有反应，但对布瓦西坦和吡仑帕奈反应不佳。生酮饮食和切除性癫痫手术对各种癫痫发作类型均显示出广泛疗效，尽管每种类型的具体数据仍然有限。VNS对失张力和强直发作最有效，对GTCS和局灶性发作的反应则不太一致。新兴的神经调节技术，包括深部脑刺激（DBS）和反应性神经刺激（RNS），显示出前景，特别是对于强直和GTCS，但仍需要进一步研究。本综述强调了根据主要癫痫发作类型定制治疗的重要性，并呼吁在未来的临床试验中进行更严格的、癫痫发作类型特异性的结果报告，同时需要进行长期研究。研究结果提倡采用精确的、基于网络的治疗方法，其中治疗决策以个体癫痫发作模式为指导，并以基于证据的、癫痫发作类型特异性疗效数据为支持。
