Levetiracetam-induced seizure aggravation-case series and literature review

Abstract

Purpose: Levetiracetam (LEV) is often a first-line epilepsy treatment due to its broad efficacy and favorable side effect profile. While LEV-induced seizure aggravation (LISA) has been reported in up to 18 % of LEV users in certain patient populations, the risk factors for LISA have not been well delineated. This study aims to provide a comprehensive assessment of seizure aggravation associated with LEV.

Methods: We conducted a comprehensive literature review of LISA case reports and case series. Additionally, we report a case series of seven patients treated at Hadassah Medical Center from 2015 to 2025 who experienced LISA.

Results: Our literature review identified 26 papers comprising 143 patient descriptions of LISA. Patients were 9 months to 80 years old, and seizure aggravation manifested as increased seizure frequency, status epilepticus, and the appearance of non-habitual seizures. Patients had both focal and generalized epilepsy, secondary to a variety of underlying lesion, and genetic mutation. LEV dosing ranged from 500 to 4500 mg per day. All patients in our case series experienced increased seizure frequency during LEV treatment, with two patients developing epilepsia partialis continua. Reducing or stopping LEV decreased seizures, sometimes leading to seizure freedom.

Conclusion: We found that LISA can occur across different age groups, epilepsy types and underlying etiologies. Clinicians should consider LISA in the differential diagnosis of seizure exacerbation following LEV treatment and evaluate the potential benefits of LEV discontinuation. Further studies are needed to determine the occurrence and risk factors of LISA to optimize ASM treatment.

Keywords: ASM; Drug discontinuation; Drug resistant epilepsy; Epilepsia parcialis continua; Paradoxical response.