Electrical Stimulation for the Induction of Seizures is Safe, Well-tolerated and High-Yield in Children with Drug-Resistant Epilepsy

Introduction One third of children with epilepsy develop drug-resistant epilepsy (DRE). Epilepsy surgery is the treatment for DRE, and selecting the surgical target typically requires recording spontaneous seizures during intracranial monitoring with stereoelectroencephalography (sEEG). In adults, induced seizures have been shown to help define surgical targets and are associated with superior surgical outcomes. No published studies focus on the safety, tolerability, and yield of electrical stimulation for the induction of seizures (ESIS) in children.

Stimulation at 1 Hz and 50 Hz was performed prospectively and comprehensively (all gray matter channels) during sEEG in children and young adults with DRE. Induced seizures were categorized into four groups: electroclinical habitual, clinical habitual (aura), subclinical and non-habitual. Primary safety outcome was use of rescue medication. Patient and caregiver tolerability were assessed by questionnaire. Yield was measured as induced seizure rate.

Sixty-seven patients (n=30 female) were included, ages 1-21 years (mean ± SD, 11.1 ± 5.7). Three patients participated twice, yielding 70 patient admissions. n=10,135 stimulation trials were performed, requiring 175 ± 61 minutes per patient. Only one seizure required acute rescue medication. Patient and caregiver tolerability ratings were overall favorable and improved from pre- to post-session. At least one induced seizure was obtained in 62/70 (89%) patients, representing 283/10,135 trials (2.8%). Combined, habitual seizures and habitual auras accounted for most induced seizures (58%); non-habitual seizures were uncommon (12%). Of those with induced seizures, multiple seizure types occurred in 28/62 (45%). Seizures were induced at both 1 Hz and 50 Hz in 22/67 patients (33%). Significance Comprehensive seizure stimulation during sEEG is safe, well-tolerated, and high-yield in children. Both 1 Hz and 50 Hz stimulation induce seizures. These findings motivate a more systematic utilization of ESIS in pediatric EMUs. Competing Interest Statement The authors have declared no competing interest. Clinical Trial NCT05469373 Funding Statement This research was supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under award number K12NS098482. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Cincinnati Childrens Hospital Medical Center (CCHMC) Institutional Review Board (IRB) gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability All data produced in the present study will be made available upon reasonable request to the authors, pending the completion of ongoing additional analyses including outcomes data. These ongoing analyses are expected to be completed by 2027.