The Optimal Target and Connectivity for Deep Brain Stimulation in Lennox–Gastaut Syndrome

Abstract

Objective Deep brain stimulation (DBS) can reduce seizures in Lennox–Gastaut syndrome (LGS). However, little is known about the optimal target and whether efficacy depends on connectivity of the stimulation site. Using outcome data from the ESTEL trial, we aimed to determine the optimal target and connectivity for DBS in LGS. Methods A total of 20 patients underwent bilateral DBS of the thalamic centromedian nucleus (CM). Outcome was percentage seizure reduction from baseline after 3 months of DBS, defined using three measures (monthly seizure diaries, 24‐hour scalp electroencephalography [EEG], and a novel diary‐EEG composite). Probabilistic stimulation mapping identified thalamic locations associated with higher/lower efficacy. Two substitute diffusion MRI datasets (a normative dataset from healthy subjects and a “disease‐matched” dataset from a separate group of LGS patients) were used to calculate structural connectivity between DBS sites and a map of areas known to express epileptic activity in LGS, derived from our previous EEG‐fMRI research. Results Results were similar across the three outcome measures. Stimulation was most efficacious in the anterior and inferolateral “parvocellular” CM border, extending into the ventral lateral nucleus (posterior subdivision). There was a positive association between diary‐EEG composite seizure reduction and connectivity to areas of a priori EEG‐fMRI activation, including premotor and prefrontal cortex, putamen, and pontine brainstem. In contrast, outcomes were not associated with baseline clinical variables. Interpretation Efficacious CM‐DBS for LGS is linked to stimulation of the parvocellular CM and the adjacent ventral lateral nucleus, and is associated with connectivity to, and thus likely modulation of, the “secondary epileptic network” underlying the shared electroclinical manifestations of LGS. ANN NEUROL 2022;92:61–74

Management of Lennox-Gastaut syndrome with deep brain stimulation: A systematic literature review

“… 11 - 13 In our study, 17 out of 50 had normal brain anatomy and 20 had underlying pathological diseases, and genetic mutations. 11 - 13 …”

“… 11 - 13 It was also reported that seizure reduction was achieved after stimulation of anterior, inferior, and lateral borders of the CMN. 13 In the study that was done in Australia, seizure outcomes after 3 months were measured using diaries (52% reduction), EEG (57% reduction), and diary-EEG (44% reduction), EEG and diary EEG were only reported in 17 out of 20 patients because 2 patients mandated lock-down due to COVID-19, while the other 2 studies reported long term follow up data only. 11 - 13 …”

“…Preoperative functional MRI (fMRI) and intraoperative EEG were used to locate the region of interest (ROI). 11 - 13 The thalamic regions showed positive connectivity for LGS Targeting the CMN in 50 patients. Seizure reduction was achieved in more than 50% in all patients among whom 2 patients were seizure free.…”

“…Electroencephalography (EEG) findings from all studies reported slow spike waves (SSWs) in 70% of all patients (35/50), generalized epileptiform discharges (GEDS) accounts for 28% (24/50), 26% (13/50) were not reported. 11 - 13 …”

“… 11 - 13 Seizure type was reported to be 62% (31/50) Generalized tonic-clonic, 40% (20/50) tonic, 36% 18/50) atonic, 34% (17/50) atypical absence, 42% (21/50) others including focal impaired awareness seizures, myoclonic seizures, generalized tonic seizures, spasms, 26% (13/50) were not known. 11 - 13 …”