Peri-operative anti-inflammatory drug use and seizure recurrence after resective epilepsy surgery: Target trials emulation

causal inference
healthcare

Assessing the effect of different antiinflammatory drugs taken during brain surgery (focal resections) on long-term recurrence of epileptic seizures.

Authors
Affiliations

Liran Szlak

IBM Research

Jingdi Shen

Cleveland Clinic

Eden Zohar

IBM Research

Ehud Karavani

IBM Research

Daniel Rotroff

Cleveland Clinic

Deborah Vegh

Cleveland Clinic

Vineet Punia

Cleveland Clinic

Michal Rosen-Zvi

IBM Research

Yishai Shimoni

IBM Research

Lara Jehi

Cleveland Clinic

Published

April 18, 2025

Doi
Abstract

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}
}