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OBJECTIVE  This study aimed to evaluate the efficacy of levetiracetam (LEV) combined with perampanel (PER) therapy for intraoperative seizure treatment to determine whether a combination of LEV and PER can aid in the prevention of intraoperative intractable seizures during awake surgery.    METHODS  The authors performed a retrospective cohort study in 78 consecutive patients with glioma who underwent awake surgery using intraoperative direct electrical stimulation mapping. To prevent intraoperative seizures, 50 patients were treated with the antiepileptic drug LEV only (LEV group) from January 2017 to January 2019, while the remaining 28 patients were treated with LEV plus PER (LEV + PER group) between March 2019 and January 2020. LEV (1000–3000 mg) and/or PER (2–4 mg) were administered before the surgery.    RESULTS  Preoperative seizures with International League Against Epilepsy (ILAE) class II–VI occurred in 44% of the patients in the LEV group and in 35.7% of patients in the LEV + PER group, with no significant difference between groups (p = 0.319). Total intraoperative seizures occurred in 18 patients (36.0%) in the LEV therapy group and in 2 patients (7.1%) in the LEV + PER group (p = 0.009). Of these, there were no patients (0%) with intractable seizures in the LEV + PER group. Regarding factors that influence intraoperative seizures in glioma patients during awake brain surgery, multivariate logistic regression models revealed that the occurrence of intraoperative seizures was significantly related to the involvement of motor-related regions (positive vs negative, HR 6.98, 95% CI 1.71–28.56, p = 0.007), preoperative seizure (ILAE class II–VI vs ILAE class I, HR 4.44, 95% CI 1.22–16.11, p = 0.024), and LEV + PER group (positive vs negative, HR 0.07, 95% CI 0.01–0.44, p = 0.005). Treatment-related adverse effects were rare and mild, including sleepiness, tiredness, and dizziness in both treatment groups.    CONCLUSIONS  This study demonstrates that LEV + PER therapy is significantly associated with a lower risk of intraoperative seizures compared with LEV therapy alone in patients with glioma during awake brain mapping. These findings will help neurosurgeons conduct safe and reliable awake surgeries and reduce the rate of intraoperative intractable seizures during such procedures.

Intraoperative seizure outcome of levetiracetam combined with perampanel therapy in patients with glioma undergoing awake brain surgery