Deep brain stimulation in pediatric drug-resistant epilepsy: Implications for the developing connectome

Abstract

Epilepsy is increasingly recognized as a disorder of brain networks, and intracranial neuromodulation has emerged as a therapeutic strategy for individuals with drug-resistant epilepsy (DRE). In pediatric populations, however, ongoing brain development raises important questions regarding safety, efficacy, and long-term consequences of chronic neuromodulation. In this review, we examine the emerging role of deep brain stimulation (DBS) in the treatment of DRE in children and adolescents. We synthesize current evidence supporting the neurobiological rationale for DBS in pediatric epilepsy, with particular attention to thalamic and limbic targets and their associated networks. Available clinical data are critically reviewed, including findings from emerging prospective studies, with emphasis on seizure outcomes, quality of life, neurodevelopmental trajectories, and safety. We also discuss surgical, clinical, and ethical considerations unique to the application of chronic intracranial stimulation in the developing brain. Finally, we outline future directions for the field, including network-informed target selection, comparisons to responsive stimulation paradigms, and the need for developmentally relevant, longitudinal outcome measures. Although pediatric DBS remains largely off-label and supported by limited high-quality evidence, it is increasingly incorporated into specialized epilepsy care. Continued progress will depend on coordinated multicenter efforts that prioritize both seizure control and long-term neurodevelopmental and psychosocial outcomes.