Inter-ictal spike rates are not modulated by anti-seizure medication taper in the epilepsy monitoring unit: a tale of two confounders^*

<i>Objective.</i>New implantable and wearable devices hold great promise to help patients manage their seizure disorders. One proposed application is measuring the rate of interictal epileptiform discharges as a biomarker of medication levels and seizure risk. This study aims to determine whether interictal epileptiform spike rates (spikes) are independently associated with anti-seizure medication (ASM) levels and evaluate whether spike rates are a reliable biomarker for ASM levels.<i>Approach.</i>We conducted a retrospective analysis of 69 patients with drug resistant epilepsy undergoing intracranial EEG monitoring during ASM taper in the epilepsy monitoring unit. An automated spike detection algorithm, validated seizure annotations, and a model of ASM load were used to assess the relationship between spike rates, ASM level, state of consciousness, and seizure timing using linear mixed effects models. Event related analysis and seasonal autoregressive models were applied to evaluate both short-term and longer-term effects of ASMs on spike rates, respectively.<i>Main Results.</i>Spike rates were found to increase following seizures, during sleep, and in patients experiencing early seizures, with no significant association between ASM load and spike rates after controlling for these confounders. Initial models without controls showed a positive association between ASM load and spike rates. However, this relationship disappeared when the effects of sleep and seizures were accounted for. Medication-specific analysis revealed that only levetiracetam showed a significant impact on spike rates during taper.<i>Significance.</i>This study demonstrates that interictal spike rates are more strongly influenced by seizure activity and sleep than by ASM levels, suggesting limited utility of spike rates as a biomarker for ASM load. However, spikes may still serve as important markers for seizure control and disease severity.