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Efficacy and safety of perampanel in refractory and super-refractory status epilepticus: cohort study of 81 patients and literature review

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Abstract

Background

The effective dose of perampanel in status epilepticus (SE), refractory SE (RSE), and super-refractory SE (SRSE) in humans is unknown, and the potential of perampanel in treating SE has not been evaluated in a large cohort.

Methods

Data of intensive care patients with RSE and SRSE treated with perampanel were retrospectively reviewed and analyzed.

Results

Eighty-one patients received perampanel, including 39 females with median age 64 [17–91] years, perampanel responders (n = 27), and non-responders (n = 54). The initial perampanel dose was positively associated with treatment response in patients with RSE or SRSE (OR = 1.27, 95% CI 1.03–1.57, p = 0.025), while the maximum dose was negatively associated with treatment response (OR = 0.74, 95% CI 0.58–0.96, p = 0.022). Hypoxia caused seizures in six patients; five died in hospital and one had severe disability. A statistically non-significant tendency toward better response was found in patients with unique SE type and cause, particularly in nonconvulsive status epilepticus (NCSE) without coma (NCSE without coma vs. generalized tonic–clonic seizure: OR = 4.14, 95% CI 0.98–17.47, p = 0.053). In the high-dose (≥ 16 mg/day) groups, although distributions of modified Rankin Scale (mRS) scores were similar between perampanel responders and non-responders at discharge, a greater proportion of perampanel responders had less change in mRS scores from baseline than did perampanel non-responders (median mRS: 0 vs 4, p = 0.064). No cardiorespiratory adverse events or laboratory abnormalities were noted with perampanel treatment.

Conclusions

Perampanel is effective and has a satisfactory safety profile in the emergency treatment of established RSE and SRSE.

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The data used to support the findings of this study are included within the article.

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Acknowledgements

The authors wish to thank the patients, and the team of research assistants and EEG technologists at Linkou Chang Gung Memorial Hospital.

Funding

This work was supported by the Chang Gung Memorial Hospital, Taiwan (Grant Nos. CORPG3J0491 and CORPG3J0461).

Author information

Authors and Affiliations

  1. Section of Epilepsy, Department of Neurology, Chang Gung Memorial Hospital at Linkou Medical Center and Chang Gung University College of Medicine, 5 Fu-Shin Street, Kwei-Shan, Taoyuan, 333, Taiwan

    Siew-Na Lim, Tony Wu, Wei-En Johnny Tseng, Hsing-I Chiang & Mei-Yun Cheng

  2. Department of Neurology, Xiamen Chang Gung Hospital, Xiamen, Fujian, China

    Tony Wu

  3. Biomedical Engineering, Chang Gung University, Taoyuan, Taiwan

    Wei-En Johnny Tseng

  4. Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital at Linkou Medical Center and Chang Gung University College of Medicine, Taoyuan, Taiwan

    Wey-Ran Lin

  5. Department of Laboratory Medicine, Chang Gung Memorial Hospital at Linkou Medical Center, Taoyuan, Taiwan

    Chia-Ni Lin

  6. Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, Taiwan

    Chia-Ni Lin

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  1. Siew-Na Lim
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Contributions

SNL had made substantial contributions to the conception and study design; SNL, TW, WEJT, HIC, and MYC collected the data; SNL, TW, WEJT, WRL, and CNL analyzed the data; SNL prepared the manuscript, and SNL, all authors critically revision of the manuscript, and read also approved the final version for submission.

Corresponding author

Correspondence to Siew-Na Lim.

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The authors declare that they have no competing interests.

Supplementary Information

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415_2021_10506_MOESM1_ESM.tif

Supplementary file1 Supplementary Figure 1. Perampanel dose and plasma perampanel concentrations in 13 measurements in 9 status epilepticus patients. (A) The perampanel dose given. (B) Plasma perampanel concentration were not significantly different between perampanel responders and non-responders. (C) No correlation between perampanel dose and plasma perampanel concentration. (TIF 107 KB)

Supplementary file2 (DOCX 37 KB)

Supplementary file3 (DOCX 43 KB)

Supplementary file4 (DOCX 27 KB)

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Lim, SN., Wu, T., Tseng, WE.J. et al. Efficacy and safety of perampanel in refractory and super-refractory status epilepticus: cohort study of 81 patients and literature review. J Neurol 268, 3744–3757 (2021). https://doi.org/10.1007/s00415-021-10506-9

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  • DOI: https://doi.org/10.1007/s00415-021-10506-9

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