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Effects of New-Generation Antiepileptic Drug Prophylaxis on Delayed Neurovascular Events After Aneurysmal Subarachnoid Hemorrhage

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Abstract

Neuroelectric disruptions such as seizures and cortical spreading depolarization may contribute to the development of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH). However, effects of antiepileptic drug prophylaxis on outcomes remain controversial in SAH. The authors investigated if prophylactic administration of new-generation antiepileptic drugs levetiracetam and perampanel was beneficial against delayed neurovascular events after SAH. This was a retrospective single-center cohort study of 121 consecutive SAH patients including 56 patients of admission World Federation of Neurological Surgeons grades IV − V who underwent aneurysmal obliteration within 72 h post-SAH from 2013 to 2021. Prophylactic antiepileptic drugs differed depending on the study terms: none (2013 − 2015), levetiracetam for patients at high risks of seizures (2016 − 2019), and perampanel for all patients (2020 − 2021). The 3rd term had the lowest occurrence of delayed cerebral microinfarction on diffusion-weighted magnetic resonance imaging, which was related to less development of DCI. Other outcome measures were similar among the 3 terms including incidences of angiographic vasospasm, computed tomography-detectable delayed cerebral infarction, seizures, and 3-month good outcomes (modified Rankin Scale 0 − 2). The present study suggests that prophylactic administration of levetiracetam and perampanel was not associated with worse outcomes and that perampanel may have the potential to reduce DCI by preventing microcirculatory disturbances after SAH. Further studies are warranted to investigate anti-DCI effects of a selective α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor antagonist perampanel in SAH patients in a large-scale prospective study.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank Ms. Chiduru Nakamura (Department of Neurosurgery, Mie University Graduate School of Medicine) for her administrative assistance.

Funding

This work was funded by Taiju Life Social Welfare Foundation (grant number, N/A) to Dr. Suzuki, Japan Society for the Promotion of Science KAKENHI grant number JP21K09097 to Dr. Miura, JP19K18423 to Dr. Nishikawa, JP20K17963 and Sanikai Foundation (grant number, N/A) to Dr. Kawakita, and Okasan-Kato Foundation (grant number, N/A) to Dr. Fujimoto.

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Authors and Affiliations

  1. Department of Neurosurgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan

    Hidenori Suzuki, Ryuta Yasuda, Tetsushi Yago, Hisashi Mizutani, Tomonori Ichikawa, Takahiro Miyazaki, Yotaro Kitano, Hirofumi Nishikawa, Fumihiro Kawakita, Masashi Fujimoto & Naoki Toma

  2. Center for Vessels and Heart, Mie University Hospital, Tsu, Japan

    Yoichi Miura

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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Hidenori Suzuki and Masashi Fujimoto. The first draft of the manuscript was written by Hidenori Suzuki, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Hidenori Suzuki.

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Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the ethical committee of Mie University Hospital (Ethics approval number: 2544 and H2018-031).

This article does not contain any studies with animals performed by any of the authors.

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The ethical committee waived the need for informed consent with opt-out.

Conflict of Interests

Dr. Suzuki is one of the Editorial Board Members in this journal, reported personal fees from Eisai and Kowa, and a research fund from Japan Blood Products Organization outside the submitted work. The other authors declare that they have no conflict of interest.

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Suzuki, H., Miura, Y., Yasuda, R. et al. Effects of New-Generation Antiepileptic Drug Prophylaxis on Delayed Neurovascular Events After Aneurysmal Subarachnoid Hemorrhage. Transl. Stroke Res. 14, 899–909 (2023). https://doi.org/10.1007/s12975-022-01101-9

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