Intravenous perampanel for early post-traumatic seizure prophylaxis across a wide range of traumatic brain injury severity: Potential for low incidence and favorable outcomes in a retrospective cohort.

Introduction: Early post-traumatic seizures (EPTS) are a significant complication of traumatic brain injury (TBI) that impairs neurological recovery. Perampanel (PER), a selective AMPA receptor antagonist, is a promising prophylactic agent with neuroprotective potential, but its intravenous use in mixed-severity TBI remains unexplored. Research question: We evaluated EPTS incidence and clinical outcomes in TBI patients of all severities receiving intravenous PER as the sole prophylactic agent within 12 h of injury. Material and methods: This single-center, retrospective study included 75 patients with TBI (GCS 3-15) who received intravenous PER 2 mg within 12 h of injury (May 2024-December 2025). The primary outcome was EPTS incidence within 7 days; secondary outcomes included seizure characteristics, GOS-E, late seizures, mortality, and adverse events. Results: EPTS occurred in five patients (6.7%; 95% CI, 2.88%-14.68%); all seizures were convulsive, with none identified as non-convulsive. EPTS patients had lower GCS scores (median 4 vs. 12; p = 0.03), longer mechanical ventilation (p = 0.024), extended ICU/HCU stays (p = 0.031), and lower GOS-E at discharge and 3 months (favorable: 40% vs. 84.4%; p = 0.043); 81.2% of 69 followed patients achieved favorable GOS-E at 3 months. Late seizures occurred in 4.3%, and one patient (1.3%) had a PER-related adverse event, with no psychiatric events. Discussion and conclusion: Intravenous PER within 12 h of TBI was associated with low EPTS incidence, favorable outcomes, and few adverse events. Given the retrospective, single-arm design and modest sample size, these preliminary, hypothesis-generating findings warrant evaluation in the ongoing PEACE-TBI trial.