Anti-seizure medication load is not correlated with early termination of seizure spread

TL;DR

This study investigates whether anti-seizure medication levels influence early seizure termination and finds no correlation, suggesting other mechanisms are responsible for seizure duration control.

Contribution

The paper provides evidence that ASM load does not correlate with early seizure termination, highlighting the need to explore alternative mechanisms affecting seizure duration.

Findings

Seizure duration is longer at lower ASM concentrations.

No significant difference in ASM levels at truncated vs. continuing seizures.

Seizure truncation mechanisms are likely independent of ASM plasma concentration.

Abstract

Objective: Anti-seizure medications (ASMs) are the mainstay of treatment for epilepsy, yet their effect on seizure spread is not fully understood. Higher ASM doses have been associated with shorter and less severe seizures. We aimed to test if this effect was due to limiting seizure spread through early termination of otherwise unchanged seizures. Methods: We retrospectively examined intracranial EEG (iEEG) recordings in 15 subjects who underwent ASM tapering during pre-surgical monitoring. We estimated ASM plasma concentrations based on pharmaco-kinetic modeling. In each subject, we identified seizures that followed the same onset and initial spread patterns, but some seizures terminated early (truncated seizures), and other seizures continued to spread (continuing seizures). We first compared seizure duration to ASM concentration for all seizures and the subset of seizures included in truncated-continuing pairs. Then we compared durations of the matched truncated and continuing seizures. Finally, we compared ASM concentrations at the times of truncated seizures and continuing seizures. Results: Seizure durations were found to be significantly longer at lower ASM concentrations. Continuing seizures were significantly longer in duration than matched truncated seizures. We found no substantial difference between ASM concentrations when truncated vs. continuing seizures occurred. Significance: The lack of difference between ASM concentrations at the time of truncated vs. continuing seizures implies a separate mechanism for shortening the duration of seizures beyond stopping the spread pathways early. Additionally, the mechanism causing seizures to be truncated remains unclear. Further research is needed to understand how ASM may modulate seizure duration and severity.