ORIGINAL RESEARCH article
Front. Neurol.
Sec. Neurotrauma
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1665997
This article is part of the Research TopicIntegrative Approaches to Acute Brain Injury: Vascular, Electrical, and Metabolic InteractionsView all 9 articles
Acute Symptomatic Seizure Prevention with Perampanel in moderate and severe Traumatic Brain Injury: A Retrospective Comparison with Levetiracetam
Provisionally accepted
Junzo Nakao*
Hideki KashiwagiKohie Yoshimura
Akihiro KambaraRyusuke KoderaKotaro Honda
Yu AmemiyaJunji HatakeyamaKen Sakakibara
Kazuma Yamakawa
Shinji Kawabata
Masahiko WanibuchiAkira Takasu- Osaka Medical and Pharmaceutical University, Takatsuki, Japan
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Background: Acute symptomatic seizures (ASS) occurring within 7 days after traumatic brain injury (TBI) may exacerbate secondary brain injury via excitotoxicity and elevated intracranial pressure. They are also risk factors for post-traumatic epilepsy (PTE). However, the optimal anti-seizure medication for preventing ASS remains unclear. This study aimed to compare the effectiveness of perampanel (PER) versus levetiracetam (LEV) for ASS prevention in patients with moderate to severe TBI. Methods: We conducted a retrospective cohort study including 32 patients with moderate to severe TBI who received either LEV (n = 19) or PER (n = 13) as prophylactic anti-seizure therapy. The primary outcome was the incidence of ASS within 7 days post-injury. Secondary outcomes included PTE development, psychiatric adverse events (PAEs), and functional outcomes assessed by the Glasgow Outcome Scale–Extended (GOS-E) at 3 months. Incidence rates were compared between groups using appropriate statistical tests. Results: The incidence of ASS was significantly lower in the PER group (7.7%) compared to the LEV group (42.1%) (OR 0.115, p = 0.050), despite a higher prevalence of cerebral contusions in the PER group. There were no significant differences in the incidence of PTE (23.1% vs. 26.3%, OR 0.84, p > 0.99), PAEs (23.1% vs. 26.3%, p > 0.99), or favorable GOS-E scores (38.5% vs. 26.3%, p = 0.707) between the PER and LEV groups. Conclusion: PER demonstrated a significant advantage over LEV in preventing ASS following moderate to severe TBI. Given its comparable psychiatric safety profile and functional outcomes, PER may be a promising therapeutic option for acute seizure prophylaxis in this population. However, further prospective studies with larger sample sizes are warranted to validate these findings.
Keywords: AMPA receptor blockade, Neuroprotection, head trauma, Secondary brain injury, seizure prophylaxis
Received: 14 Jul 2025; Accepted: 25 Sep 2025.
Copyright: © 2025 Nakao, Kashiwagi, Yoshimura, Kambara, Kodera, Honda, Amemiya, Hatakeyama, Sakakibara, Yamakawa, Kawabata, Wanibuchi and Takasu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Junzo Nakao, junzo.nakao@ompu.ac.jp
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