Safety of Intracranial Neuromodulation in Drug-Resistant Pediatric and Adult Epilepsy.

Abstract

Intracranial neuromodulation is an established therapy for drug-resistant epilepsy (DRE) in adults. Improving seizure outcomes and expanding its application to pediatric patients remain priorities. Off-label use of 2-lead and 4-lead devices targeting multiple network nodes, combined with varied stimulation parameters, has emerged in pursuit of better outcomes. Although early findings are promising, the safety of these approaches remains underexplored. This study evaluates adverse event (AE) rates associated with different intracranial neuromodulation devices from a single center. This retrospective study from the Mayo Clinic (Rochester, MN) included patients with DRE who underwent intracranial neuromodulation between August 2004 and December 2024. Demographic data, epilepsy characteristics, treatment indications, procedural details, and AEs were extracted from medical records. AEs are undesirable events associated with implantation and use of the device, regardless of causation. Serious AEs were life threatening or resulted in hospitalization, persistent or significant disability, or death. Patients were classified as children (<13 years), adolescents (13-18 years), or adults (≥19 years). A total of 217 patients (108 male patients, 109 female patients; 14 children, 43 adolescents, 160 adults) were analyzed. Devices included 2-lead deep brain stimulation (DBS) (111 patients), 4-lead DBS (51 patients), and responsive neurostimulation (55 patients). Device-related AEs included stimulation-related paresthesia (7.8%), infections (4.1%), asymptomatic intracranial hemorrhage (ICH) (3.7%), bowstring effect (extension wire tethering that limits neck mobility) (3.2%), operation-related focal weakness (2.3%), wound dehiscence (1.8%), device migration (1.8%), lead malposition (1.4%), lead fracture (1.4%), lead migration (0.5%), extensor wire fracture (0.5%), extrusion (0.5%), and symptomatic ICH (0.5%). While no significant difference in overall AE rates was found between sexes, device explantation was significantly higher in female patients than in male patients (11.9% [13/109] vs 1.9% [2/108], <i>p</i> = 0.006). Children and patients with 4-lead DBS had a higher risk of developing bowstringing compared with other age groups and device types. Intracranial neuromodulation demonstrated an acceptable safety profile across sexes and age groups. However, children and patients with 4-lead DBS systems were at increased risk of the bowstring effect. These findings highlight the need for tailored device design and surgical strategies to optimize safety, particularly in pediatric populations.