Background: Lennox-Gastaut syndrome (LGS) is a drug-resistant epileptic encephalopathy that typically begins in infancy or childhood but often persists into adulthood, becoming a lifelong condition. Typical electroencephalographic (EEG) findings include generalized paroxysms of 2.5 Hz slow spike-wave and bursts of generalized paroxysmal fast activity and anterior predominant slow spike-wave during sleep. For adult patients with LGS, corpus callosotomy (CC) has proven to be an effective surgical intervention for seizure management, yet its effects on clinical and EEG outcomes in this population have been scarce. This study aims to address this gap by evaluating the long-term seizure outcomes and EEG changes of patients with LGS who underwent either radiosurgical or open anterior CC.

Methods: A retrospective study was conducted at a referral center to evaluate seizure and EEG outcomes in adult patients with LGS who underwent anterior CC using either an open surgical or radiosurgical approach with no additional interventions, except in two cases where a VNS device had been previously implanted but the battery had expired. Outcomes were assessed over a 24-month follow-up period through univariate analysis.

Results: A total of 38 patients with LGS who underwent CC were included, with 29 undergoing open surgery and nine radiosurgical approach. Overall seizure frequency revealed a significant reduction following CC; 27 (71.05 %) had a 90 % reduction of seizure frequency, 5 (13.16 %) had 50-90 % seizure reduction, and 6 (15.79 %) had a < 50 % seizure frequency reduction. All seizure types per month mean number were 184.18 ± SD 216.25 before CC and 52.18 ± SD 65.23 (p = 0.001) after CC. Prior to CC, patients used a mean of 3.34 ± SD 1.36 ASMs with no differences between surgical approaches. During follow-up, the mean number of ASMs was 2.93 ± SD 1.035. (p = 0.725). EEG findings demonstrated a statistically significant improvement post-CC. Diffuse/bilateral slowing and diffuse/bilateral epileptiform discharges were observed to become more focal. Notably, EEG normalization was achieved in 4 (10.52 %) patients. Disconnection syndrome presented in 31.6 %. Complications were observed in 12 (31.6 %) following CC, including surgical site infections (10.5 %), frontal lobe edema (7.9 %), status epilepticus (7.9 %), hemorrhage (2.6 %), and pneumocephalus (5.3 %).

Conclusions: Anterior corpus callosotomy, either open or radiosurgical, effectively reduced atonic, tonic, and generalized tonic-clonic seizures in adults with drug-resistant LGS. EEG changes post-CC suggest a network reorganization, guiding potential additional therapies. Also, anterior CC had a low rate of complications in the adult population with LGS. Further research is needed to explore the relationship between seizure reduction and neuropsychological outcomes.