Abstracts

Rationale: The selection of antiepileptic drug (AED) treatment is typically based on seizure type. There is a paucity of evidence for superior effectiveness or potential deterioration of particular AED in specific etiologic subgroups. Several studies have shown that levetiracetam (LEV) may induce aggravation of focal seizures, but none of them detailed the etiology. To address this knowledge gap, we were interested in analyzing if there is any etiological factor associated with increased risk of potential seizure aggravation with LEV. Methods: A retrospective analysis was performed of patients treated with LEV at the University Clinic of Neurology in Skopje, FYR of Macedonia, from 01. 01. 2016 to 06. 30. 2017. Seizure aggravation was defined as 100% or greater increase in seizures frequency, which followed the prescription of LEV with a close time relation after its introduction (1 month), persisted through the treatment period and resolved when the drug was stopped. Patients with paradoxical response to LEV from medical record were invited and interviewed by a member of our group in order to verify and quantify seizure frequency post-LEV treatment. In regard to the etiology, patients were divided into three groups: idiopathic, symptomatic and unknown, with symptomatic ones, further specified as hippocampal sclerosis, post-traumatic, perinatal injury, FCD, post-stroke, post-infectious, neurocutaneous, hydrocephalus, and cavernoma. Results: Among 208 patients who were treated with levetiracetam,  we identified eight patients which fulfilled criteria for drug-induced seizure aggravation. Typically, seizure aggravation appeared immediately after introduction, at low LEV doses (500-1000 mg), although three patients were uptitrated to 2000 i.e. 3000 mg, respectively. In addition to increased frequency and duration, four patients developed new seizure types (including generalized tonic-clonic seizures in one). Withdrawal of LEV resulted in seizure return to background frequency in all patients. In one of the patients,  re-challenge with LEV several months later resulted in reoccurrence of seizure aggravation. Six out of eight patients have distinctive MRI finding of focal cortical dysplasia (FCD). No other factors which might have affected seizure frequency, e.g. concomitant infections, other medical disorders or changes in concomitant AED dosing, were identified. No patients with paradoxical effect of LEV were detected in idiopathic epilepsy group or other types of symptomatic epilepsies. Conclusions: Our results suggest that LEV may possibly induce seizure exacerbation in a subset of patients with FCD-related epilepsy, although large studies are needed to establish the relation. Nevertheless, this report highlights the notion that specific etiologies of epilepsy could impact the treatment choice. The selection of antiepileptic drug which is typically based on seizure type may be at times insufficient because electroclinical semiology might be “final common pathway” of different mechanisms underlying epileptogenesis in diverse etiologies Funding: No funding