Peri-operative anti-inflammatory drug use and seizure recurrence after resective epilepsy surgery: Target trials emulation
Assessing the effect of different antiinflammatory drugs taken during brain surgery (focal resections) on long-term recurrence of epileptic seizures.
We conducted a retrospective observational study to examine whether anti-inflammatory medications prescribed peri-operatively of resective brain surgery can reduce long-term seizure recurrence for individuals with drug-resistant focal epilepsy. We used insurance-claims data from across the United States to screen medications prescribed to 1,993 individuals undergoing epilepsy. We then validated the results in a well-characterized cohort of 671 epilepsy patients from a major surgical center. Twelve medications met the screening criteria and were evaluated, identifying dexamethasone and zonisamide as potentially beneficial. Dexamethasone reduced seizure recurrence by 42% over 9 years of follow-up (hazard-ratio = 0.742; 95% CI = 0.662, 0.831), and zonisamide reduced recurrence by 33% (HR = 0.782; 95% CI = 0.667, 0.917). While dexamethasone could not be validated, analysis of zonisamide in the clinical cohort corroborated the beneficial effect (HR = 0.828; 95% CI = 0.706, 0.971). If prospectively validated, this study suggests surgeons could improve long-term outcomes of epilepsy surgery by medically reducing neuro-inflammation in the surgical bed.
Citation
@article{szlak2025peri,
title={Peri-operative anti-inflammatory drug use and seizure recurrence after resective epilepsy surgery: Target trials emulation},
author={Szlak, Liran and Shen, Jingdi and Zohar, Eden and Karavani, Ehud and Rotroff, Daniel and Vegh, Deborah and Punia, Vineet and Rosen-Zvi, Michal and Shimoni, Yishai and Jehi, Lara},
journal={iScience},
volume={28},
number={4},
year={2025},
publisher={Elsevier}
}