Abstracts

Rationale: Anti-seizure medications (ASMs) are the primary treatment for epilepsy, suppressing seizures completely in about 2/3^rd of patients. In the remaining 1/3^rd drug-resistant population, ASMs are still shown to reducing seizure frequency and severity. In this population, each patient is usually on a combination of ASMs, but the effects of ASM dosage on seizure severity are not fully understood.


Methods: Long-term intracranial EEG recordings (icEEG) conducted in preparation for resective surgery in drug-resistant patients sometimes perform ASM tapering to provoke seizures. This set up offers a controlled environment to study the effects of a short-term reduction in ASM dosage on seizure severity. We examined icEEG recordings in 37 individuals with drug resistant focal epilepsy during long-term monitoring with reported concurrent ASM tapering. ASM plasma levels were estimated using known pharmaco-kinetics. In each patient, we obtained classifications and descriptions for each seizure, including over 300 seizures across the cohort. We also derived a range of quantitative EEG severity measures for each seizure.


Results: We found an increased seizure frequency and a higher proportion of focal to subclinical seizures during reduced ASM periods. Seizure duration shows a dose-dependent negative correlation, as lower ASM levels were associated with longer seizures for both subclinical and focal seizures. Postictal EEG suppression was primarily seen in focal seizures, and appear more suppressed with more reduction in ASMs. Seizure spread on the EEG shows a combination of dose-dependent and type-specific effect: focal seizures spread across larger brain tissue volumes with more reduced ASM, whereas subclinical seizures spread less in general and did not show any dose-dependent effect. Lastly, a reduction in ASM levels correlated with a decrease in peak band power across all canonical frequency bands in subclinical seizures, while in focal seizures, this effect was observed most strongly in the beta band.


Conclusions: The observed effects of ASM tapering on seizure frequency, duration and postictal suppression are consistent with previous studies. However, the combination of dose-dependent and type-specific effects observed on seizure spread and band power suggests that ASM modulation may influence distinct neural mechanisms. Understanding these changes can assist in optimizing treatment plans and improving surgical outcomes. Further research should explore the underlying mechanisms, ideally with a larger sample size and considering epilepsy type, specific ASMs and affected brain regions.


Funding: This study was supported by UKRI Future Leaders Fellowships (MR/T04294X/1, MR/V026569/1).