Samanta Debopam
Division of Child Neurology, Department of Pediatrics, University of Arkansas for Medical Sciences, 1 Children's Way, Little Rock, AR 72202, USA.
J Clin Med. 2025 Sep 6;14(17):6302. doi: 10.3390/jcm14176302.
Lennox-Gastaut syndrome (LGS) is a severe childhood-onset developmental and epileptic encephalopathy characterized by treatment-resistant seizures and significant morbidity. Despite multiple approved anti-seizure medications (ASMs), optimal seizure control remains elusive. This has led to ongoing interest in newer ASMs, including those not specifically approved for LGS. This review evaluates the emerging evidence on the use of these agents in LGS management. We conducted a comprehensive literature search of PubMed, Web of Science, and Embase to identify studies examining perampanel, brivaracetam, cenobamate, ganaxolone, and stiripentol in LGS populations. Both randomized controlled trials and observational studies were included. Perampanel was studied in approximately 300 patients across one Phase 3 trial and seven observational studies, showing responder rates of 26-69% with particular efficacy for generalized tonic-clonic and myoclonic seizures, though behavioral side effects (irritability, aggression) were dose-related concerns. Brivaracetam demonstrated inconsistent efficacy in 59 patients across six studies (0-61.5% responder rates) but offered better behavioral tolerability than levetiracetam. Cenobamate showed exceptional promise in 223 patients across seven studies with 50-85% responder rates and significant polypharmacy reduction, though requiring careful titration. Ganaxolone demonstrated efficacy in LGS-like CDKL5 deficiency phenotypes with 28.2% drop seizure reduction versus placebo. Stiripentol showed potential benefit for generalized seizures in limited LGS data. Several newer ASMs show therapeutic promise in LGS. Perampanel offers the most extensive evidence base, cenobamate demonstrates exceptional efficacy potential, while brivaracetam provides an alternative for levetiracetam-intolerant patients. Further controlled studies are needed to define optimal treatment algorithms.
伦诺克斯 - 加斯托综合征（LGS）是一种严重的儿童期起病的发育性和癫痫性脑病，其特征为耐药性癫痫发作和严重的发病情况。尽管有多种已获批的抗癫痫药物（ASMs），但最佳的癫痫发作控制仍然难以实现。这使得人们对新型ASMs持续保持兴趣，包括那些未专门获批用于LGS的药物。本综述评估了这些药物在LGS治疗中应用的新证据。我们对PubMed、科学网和Embase进行了全面的文献检索，以确定在LGS人群中研究吡仑帕奈、布瓦西坦、司替戊醇、加奈索酮和塞诺巴胺的研究。随机对照试验和观察性研究均被纳入。在一项3期试验和七项观察性研究中，约300名患者接受了吡仑帕奈研究，其有效率为26% - 69%，对全身强直 - 阵挛性发作和肌阵挛性发作有特别疗效，不过行为副作用（易怒、攻击行为）与剂量相关，是需要关注的问题。在六项研究中的59名患者中，布瓦西坦的疗效不一致（有效率为0 - 61.5%），但其行为耐受性优于左乙拉西坦。在七项研究中的223名患者中，塞诺巴胺显示出巨大潜力，有效率为50% - 85%，且显著减少了联合用药，不过需要仔细滴定。加奈索酮在类似LGS的CDKL5缺乏表型中显示出疗效，与安慰剂相比，癫痫发作减少了28.2%。在有限的LGS数据中，司替戊醇对全身性发作显示出潜在益处。几种新型ASMs在LGS中显示出治疗潜力。吡仑帕奈拥有最广泛的证据基础，塞诺巴胺显示出卓越的疗效潜力，而布瓦西坦为不耐受左乙拉西坦的患者提供了一种替代选择。需要进一步的对照研究来确定最佳治疗方案。
