DBS of thalamic centromedian nucleus for Lennox-Gastaut syndrome (ESTEL trial).

Abstract

Prior uncontrolled studies have reported seizure reductions following Deep Brain Stimulation (DBS) in patients with Lennox-Gastaut syndrome (LGS), but evidence from randomized controlled studies is lacking. We aimed to formally assess the efficacy and safety of DBS to the centromedian thalamic nucleus (CM) for treatment of LGS. Prospective, double-blind, randomized study of continuous, cycling stimulation of CM-DBS, in patients with LGS. Following pre- and post-implantation periods, half received three-months stimulation (blinded phase), then all received three-months stimulation (unblinded phase). The primary outcome was the proportion of participants with ≥50% reduction in diary-recorded seizures in stimulated versus control participants, measured at the end of the blinded phase. A secondary outcome was the proportion of participants with a ≥ 50% reduction in electrographic seizures on 24-hour ambulatory EEG at the end of blinded phase. Between November 2017-December 2019, 20 young adults with LGS (17-37 years;13 females) underwent bilateral CM-DBS at a single centre in Australia, with 19 randomized (treatment, n = 10; control, n = 9). 50% of the stimulation group achieved ≥50% seizure reduction, compared with 22% of controls (OR3.1; 95%CI 0.44-21.45; p = 0.25). For electrographic seizures, 59% of the stimulation group had ≥50% reduction at the end of the blinded phase, compared with none of the controls (OR23.25; 95%CI 1.0-538.4; p = 0.05). Across all patients, median seizure reduction (baseline vs study exit) was 46.7% (IQR 28-67%) for diary-recorded seizures and 53.8% (IQR 27-73%) for electrographic seizures. CM-DBS in patients with LGS reduced electrographic rather than diary-recorded seizures, after three-months of stimulation. 50% of all participants had diary-recorded seizures reduced by half at study exit, providing supporting evidence of treatment effect. This article is protected by copyright. All rights reserved.