Additional Effect of High-output Current and/or High-duty Cycle in Vagus Nerve Stimulation for Adolescent/Adult Intractable Epilepsy

Abstract

A vagus nerve stimulation (VNS) device delivers electrical pulses to the vagus nerve at a rhythm defined by the duty cycle. The standard therapeutic range is advocated for an output current of 1.5-2.25 mA and a duty cycle of 10%. As the optimal settings vary from patient to patient, some patients may benefit from additional seizure reduction when stimulated beyond the standard range. A total of 74 patients (15 children aged <12 years and 59 adolescents/adults) who underwent VNS implantation between 2011 and 2020 and who were followed up for at least 2 years were included in this retrospective study. Stimulation parameters exceeding 2.25 mA of output current, 25% of duty cycle, and 0.5625 (2.25 mA × 25%) of current × duty cycle were defined as high stimulation. The proportion achieved an additional seizure reduction of 20%, and the 50% seizure reduction rate at the last follow-up was compared between adolescents/adults and children. Approximately 40% of patients in adolescents/adults treated with high stimulation experienced an additional acute effect, resulting in a 50% or greater reduction in seizures in almost all patients. Moreover, in adolescents/adults, 22.2%-41.9% of the patients were treated with high stimulation, and the responder rate was 69.5%. Conversely, the responder rate in children was 26.7%, significantly worse than that in adolescents/adults, despite higher stimulation. VNS with high-stimulation settings is effective for adolescent and adult patients with intractable epilepsy. Even high stimulation may not be effective in extremely refractory pediatric epilepsy with a high seizure frequency.

Keywords: drug-resistant epilepsy; high-duty cycle; high-output current; vagus nerve stimulation.

Fig. 1

Examples of dosing. Only the output current or duty cycle was elevated at one time, not at the same time. One step of elevation was defined as an elevation of output current of 0.25 mA and between 5% and 10% duty cycle. Seizure frequency was compared in the setting before and after one or two steps of elevation. If a 20% reduction in seizures was achieved, further elevation was continued unless adverse effects occurred. If the seizure reduction was less than 20% after two consecutive steps of elevation, the parameters were returned to the setting where an apparent seizure reduction was achieved and maintained until the final follow-up. Yes: more than 20% seizure reduction compared to two steps before. No: less than 20% seizure reduction.

Fig. 2

A histogram of the number of patients who became additional responders at each step of the high stimulation. The first row (A, B) shows the output current, the second row (C, D) shows the duty cycle, and the third row (E, F) shows the product of the output current and duty cycle. The left columns (A, C, E) represent the adolescent and adult groups, and the right columns (B, D, F) represent the pediatric group. The numbers in the histogram represent additional responder rates at each step.