History of Lennox-Gastaut Syndrome: Sixty Years of Advancements in Therapeutic Practices

Lennox-Gastaut Syndrome (LGS) is a severe, lifelong form of epileptic encephalopathy that presents significant treatment challenges. The management of LGS remains primarily symptomatic. Historically, the effectiveness of traditional antiseizure medications (ASMs) has been limited, prompting practitioners to explore off-label treatments and anecdotal drugs, including medications not originally intended for epilepsy. Although some controlled clinical trials have been conducted, LGS management often remains empirical and largely dependent on clinical experience. Recent advances in ASMs and adjunctive therapies have enhanced patient outcomes, yet LGS remains one of the most treatment-resistant forms of epilepsy, with complete seizure control rarely being achieved. Beyond ASMs, interventions such as a ketogenic diet, vagus nerve stimulation, and callosotomy may be considered based on individual patient needs. Recent developments in deep brain stimulation have also presented promising new therapeutic options. This article aims to provide a comprehensive overview of both pharmacological and non-pharmacological treatment strategies for LGS, tracing progress from the syndrome's first description in 1966 to the current management approaches.