Johannes Dominik Lang ^1,2* Alexander Willno ^1,2 Caroline Reindl ^1,2 Tamara Welte ^1,2 Jenny Stritzelberger ^1,2 Stephanie Gollwitzer ^1,2 Katrin Walther ^1,2 Hajo Hamer ^1,2

• ¹ Epilepsiezentrum, Universitätsklinikum Erlangen, Erlangen, Germany
• ² University Hospital Erlangen, Erlangen, Bavaria, Germany

Background: Interictal epileptiform discharges (IEDs) are an electrographic biomarker of epilepsy. Despite their crucial role in diagnosing epilepsy, heterogeneous findings exist on the mechanisms underlying their occurrence and the effects of anti-seizure medications (ASMs) on IEDs.Methods: We conducted a study to investigate the association between IED frequency and the serum concentration of two commonly used ASMs, levetiracetam (LEV) and lamotrigine (LTG). We included 56 patients undergoing a continuous video EEG monitoring in our centre with tapering of ASM. IED frequency was analyzed using automated and semiautomated methods and serum samples were collected sequentially throughout the stay.Results: The cohort consisted of 41 patients (23 female, 18 male), between 19 and 64 years (mean 37.42 years), most of which were diagnosed with focal epilepsy (93%). IED frequency increased after ASM reduction revealing a negative correlation similarly with LEV and LTG serum concentrations (p = 0.0057 and p = 0.0426, respectively). Discussion: Notably, we observed a significant increase in IED frequency following dose reduction or discontinuation of both medications. This effect was reversed after ASM were re-dosed. This may indicate the suppressive properties of LEV and LTG against epileptic seizures. Furthermore, our study highlights the importance of ASM discontinuation, which may be required for capturing IEDs during diagnostic continuous EEG monitoring, and not be fully explained by circadian or ultradian rhythms alone. Conclusion: Our findings contribute to the understanding of ASM effects on IED frequency dynamics and suggest seizure suppressive properties of LEV and LTG.