Lennox-Gastaut Syndrome (LGS) is a severe developmental epileptic encephalopathy (DEE) with onset in childhood (under age 18) and is one of the most common epileptic encephalopathies according to the International League Against Epilepsy’s task force.1 LGS is specifically characterized by multiple drug-resistant seizure types, behavioral or cognitive delay, and the characteristic EEG features of slow-spike waves (SSWs) and generalized paroxysmal fast activity (GPFA).2 In addition, seizure types must include tonic seizures and often co-occur with atonic, atypical absence, and tonic-clonic seizures, among others.

Conventional treatments to manage seizures are often ineffective with very few reaching seizure freedom with medications alone. Several surgical techniques have been developed to reduce the frequency of seizures in patients with refractory seizures, including resective and palliative options. There has been a clearly established association between a reduction in seizure frequency including reaching seizure freedom and improved neuro-cognitive outcomes.3 Moreover, epilepsy surgery has been shown to reduce mortality and decrease the risk of sudden unexplained death in epilepsy.4 However, epilepsy surgery remains an undervalued treatment option for patients with developmental epileptic encephalopathies, specifically LGS. Previous research has shown that patients with more complex epilepsy phenotypes are more likely to have prolonged pharmacological management and delayed surgical evaluation, which was further associated with lower rates of seizure freedom.5 The reluctance towards surgical treatments for LGS may be due to the common interpretation of LGS as a “generalized epilepsy,” which often carries a bias towards clinical management over surgery. The "generalized" patterns noted in LGS, particularly bifrontal slow spike and wave (SSW) and generalized paroxysmal fast activity (GPFA), may be a result of an underlying secondary network wherein cerebral networks become unstable and demonstrate generalized epileptiform activity and have been shown to be generated from a single focus.6, 7, 8 Slow-spike and waves are generalized discharges (1.5-2.5 Hz) usually coupled with abnormally slow background and often occur in conjunction with atypical absence seizures, whereas GFPA are bursts of diffuse or bilateral patterns (10-25 Hz) usually recorded during slow wave sleep.9, 10, 11 Both SSW’s and GPFA show distinct but overlapping patterns of blood oxygen level-dependent (BOLD) signal in both cortical and subcortical brain areas, suggesting epileptic onset in LGS may initiate and maintain abnormal network synchrony.12

Fundamentally, when considering epilepsy surgery for LGS, one must first determine the desired outcome and overall goal of treatment. While the majority of LGS patients have intractable seizures, palliative surgery can still provide outcomes that are more efficacious than other therapies in terms of seizure reduction and overall prognosis.13 In fact, surgical treatment for LGS has been associated with increased likelihood of seizure freedom and improved cognitive outcomes with shorter intervals between seizure onset and surgical intervention resulting in improved outcomes.14

Keator (2021)13 previously reviewed and evaluated surgical treatment options, including neuromodulatory and non-neuromodulatory techniques, for patients with LGS. This focused review serves as an update to Keator (2021) and centers on recent advancements in non-neuromodulatory surgical techniques, including resective surgery and corpus callosotomy, over the past five years. These techniques remain viable and effective treatment options for many patients given appropriate pre-surgical evaluation.