Department of Neurology, Stanford University School of Medicine, Stanford, California, USA.
Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Ann Clin Transl Neurol. 2024 Nov;11(11):2818-2835. doi: 10.1002/acn3.52211. Epub 2024 Oct 23.
Lennox-Gastaut syndrome (LGS) is a severe, childhood-onset epilepsy that is typically refractory to treatment. We surveyed the current landscape of LGS treatment, aiming to identify challenges to the development of efficacious therapies, and to articulate corresponding priorities toward clinical trials that improve outcomes.
The LGS Special Interest Group of the Pediatric Epilepsy Research Consortium integrated evidence from the literature and expert opinion, into a narrative review.
We provide an overview of approved and emerging medical, dietary, surgical and neuromodulation approaches for LGS. We note that quality of care could be improved by standardizing LGS treatment based on expert consensus and empirical data. Whereas LGS natural history is incompletely understood, prospective studies and use of large retrospective datasets to understand LGS across the lifespan would enable clinical trials that address these dynamics. Recent discoveries related to LGS pathophysiology should enable development of disease-modifying therapies, which are currently lacking. Finally, clinical trials have focused chiefly on seizures involving "drops," but should incorporate additional patient-centered outcomes, using emerging measures adapted to people with LGS.
Clinicians and researchers should enact these priorities, with the goal of patient-centered clinical trials that are tailored to LGS pathophysiology and natural history.
Lennox-Gastaut 综合征（LGS）是一种严重的儿童期起病的癫痫，通常对治疗有抗性。我们调查了 LGS 治疗的现状，旨在确定开发有效疗法的挑战，并阐明改善治疗效果的临床试验的相应重点。
儿科癫痫研究联合会的 LGS 特别兴趣小组将文献证据和专家意见整合到叙述性综述中。
我们提供了针对 LGS 的已批准和新兴的医学、饮食、手术和神经调节方法的概述。我们注意到，可以通过基于专家共识和经验数据来标准化 LGS 治疗，从而改善护理质量。虽然 LGS 的自然病史尚未完全了解，但开展前瞻性研究并使用大型回顾性数据集来了解整个生命周期的 LGS，将有助于开展解决这些动态变化的临床试验。最近与 LGS 病理生理学相关的发现应能够开发出目前缺乏的疾病修饰疗法。最后，临床试验主要集中在涉及“发作”的癫痫上，但应纳入其他以患者为中心的结局，使用适用于 LGS 患者的新兴措施。
临床医生和研究人员应采取这些重点措施，目标是开展针对 LGS 病理生理学和自然病史的以患者为中心的临床试验。
