Levetiracetam Versus Levetiracetam Plus Sodium Channel Blockers for Postoperative Epileptic Seizure Prevention in Brain Tumor Patients.

Abstract

BackgroundBrain tumor patients tend to develop postoperative epileptic seizures, which can lead to an unfavorable outcome. Although the incidence of postoperative epileptic seizures and adverse events are improved with the advent of levetiracetam (LEV), postoperative epilepsy occurs at a frequency of 4.6% or higher. In brain tumor patients, the addition of sodium channel blockers (SCBs) to LEV significantly reduces seizures, though confirmed in a non-postoperative study. Thus, the combination of SCBs with LEV might be promising.ObjectiveIn this prospective randomized controlled trial we investigated the safety, evaluated by adverse events during one and two weeks after surgery, and the efficacy, evaluated by the incidence of early epilepsy, including non-convulsive status epilepticus (NCSE), of using LEV alone or SCBs added to LEV in patients who underwent craniotomy or biopsy for brain tumors or brain mass lesions.MethodsPatients with brain tumors or brain mass lesions undergoing surgical interventions, excluding endoscopic endonasal surgery (EES), with a diagnosis of epilepsy were eligible for this study. Patients are randomized into either Group A or B (B1 or B2) after the informed consents are taken; LEV alone in Group A patients, while LEV and SCBs in Group B patients (GroupB1, intravenous fosphenytoin plus oral lacosamide (LCM) and GroupB2, intravenous LCM plus oral LCM) were administered postoperatively. Fifty-three patients were enrolled during the first two and a half years of the study and four of them were excluded, resulting in the accumulation of 49 patients’ data.ResultsPostoperative epileptic seizures occurred only in three out of 49 patients during the first week (6.1%) and in seven patients within two weeks after surgery (14.3%, including the three patients during the first week). In Group A, epileptic seizures occurred in two out of 26 patients during the first week (7.7%) and in five patients within two weeks (19.2%) after surgery. In Group B, epileptic seizures occurred in one out of 23 patients during the first week (4.3%) and in two patients during the first two weeks (8.7%). Low complication grade of epileptic seizures was observed in Group B rather than in Group A, however, without significant difference (p=0.256). There was no difference in the frequency of adverse effects in each group.ConclusionAlthough not statistically significant, the incidence of epileptic seizures within one week after surgery was lesser in LEV+SCBs groups than in LEV alone. No hepatic damage or renal function worsening occurred with the addition of LCM, suggesting the safety of LEV+SCBs therapy.