Paradoxical effects of levetiracetam in people with epilepsy with rhythmic epileptiform discharges

Objective: To elucidate the incidence and risk factors for paradoxical effects (i.e., increased seizure fre-quency, increased seizure severity, or onset of new seizure types) of levetiracetam (LEV) in people with epilepsy (PWE) and identify the usefulness of electroencephalography (EEG) in predicting these effects. Methods: We examined data for consecutive PWE treated with LEV. All PWE underwent EEG and mag-netic resonance imaging (MRI) before LEV administration. We also evaluated the incidence of paradoxical LEV effects and conducted multivariate logistic regression analyses to identify the associated factors. Results: In total, 210 (66.2%) of 317 PWEs treated in our department had a history of LEV use. The inci-dence of paradoxical LEV effects was 5.2% (n = 11) and was significantly associated with a high LEV dose (p = 0.029), high seizure frequency (p = 0.005), temporal lobe epilepsy (p = 0.004), focal awareness seizure (p = 0.004), focal impaired awareness seizure (p = 0.007), spike (p = 0.015), rhythmic epileptiform discharges (REDs; p = 0.003), and MRI-identified focal cortical dysplasia (FCD; p < 0.0001). Multivariate analyses revealed that REDs (odds ratio [OR] = 5.35, p = 0.048, 95% confidence interval [CI]: 1.01- 28.21) were independently associated with paradoxical LEV effects. Conclusions: Paradoxical LEV effects occurred in PWE, particularly in those with drug-resistant focal epi-lepsy. Furthermore, the occurrence of REDs in EEG was an independent factor associated with the para-doxical effects of LEV in PWE. (c) 2023 Elsevier Inc. All rights reserved.