Risk of Seizures Induced by Intracranial Research Stimulation: Analysis of 770 Stimulation Sessions

Background Patients with medically refractory epilepsy often undergo intracranial electroencephalography (iEEG) monitoring to identify a seizure focus and determine their candidacy for surgical intervention. This clinically necessary monitoring period provides an increasingly utilized research opportunity to study human neurophysiology, however, ethical concerns demand a thorough appreciation of the associated risks. Objective We measured the incidence of research stimulation-associated seizures in a large multi-institutional study on brain stimulation’s effect on memory in order to determine if brain stimulation was statistically associated with seizure incidence, and identify potential risk factors for stimulation-associated seizures. Methods 188 subjects undergoing iEEG monitoring across 10 institutions participated in 770 research stimulation sessions over 3.5 years. Seizures within 30 minutes of a stimulation session were included in our retrospective analysis. We analyzed stimulation parameters, seizure incidence, and typical seizure patterns, to assess the likelihood that recorded seizures were stimulation-induced, rather than events that occurred by chance in epilepsy patients prone to seizing. Results In total, 14 seizures were included in our analysis. All events were single seizures, and no adverse events occurred. The mean amplitude of seizure-associated stimulation did not differ significantly from the mean amplitude delivered in sessions without seizures. In order to determine the likelihood that seizures were stimulation induced, we used three sets of analyses: Visual iEEG analysis, statistical frequency, and power analyses. We determined that three of the 14 seizures were likely stimulation-induced, five were possibly stimulation-induced, and six were unlikely stimulation-induced. Overall, we estimate a rate of stimulation-induced seizures between 0.39% and 1.82% of sessions. Conclusions The rarity of stimulation-associated seizures, and that none added morbidity or affected the clinical course of any patient, are important findings for understanding the feasibility and safety of intracranial stimulation for research purposes.