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Title: The Optimal Target and Connectivity for Deep Brain Stimulation in Lennox-Gastaut Syndrome.
Austin Authors: Warren, Aaron E L;Dalic, Linda J ;Bulluss, Kristian J ;Roten, Annie ;Thevathasan, Wesley;Archer, John S 
Affiliation: Medicine (University of Melbourne)
Bionics Institute, East Melbourne, Vic, Australia..
Murdoch Children's Research Institute, Parkville, Vic, Australia..
The Florey Institute of Neuroscience and Mental Health
Department of Surgery, University of Melbourne, Parkville, Vic, Australia..
Issue Date: Jul-2022 2022
Publication information: Annals of Neurology 2022; 92(1): 61-74
Abstract: 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. 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 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. 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.
DOI: 10.1002/ana.26368
Journal: Annals of neurology
PubMed URL: 35429045
PubMed URL:
Type: Journal Article
Appears in Collections:Journal articles

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