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Perampanel for amyotrophic lateral sclerosis: A systematic review and meta-analysis

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Abstract

Background

Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disease. There is still no established cost-effective treatment that can improve functional status and survival of ALS patients. Perampanel, by inhibiting neuronal calcium ion influx and preventing dyslocalization of nuclear proteins, has the potential to ameliorate ALS neurodegeneration.

Objectives

This study aims to determine the efficacy and safety of perampanel among ALS patients in terms of improvement in functional status using a review of relevant studies.

Methods

MedLine, Cochrane Central Register for Controlled Trials, Scopus, Embase, Literatura Latino-Americana e do Caribe em Ciências da Saúde, ClinicalTrials.gov website, and HERDIN databases were searched from inception to August 2021 for relevant studies.

Results

The search yielded 132 articles; 3 studies were included in the analysis. Pooled evidence shows that perampanel compared to placebo significantly improves cortical motor hyperexcitability but not the ALS functional rating scale-revised score. Perampanel is associated with adverse events such as aggression, somnolence, anger, and dysarthria.

Conclusion

There is no sufficient evidence to support the role of perampanel in improving functional status of ALS patients. Although it can ameliorate motor cortical hyperexcitability, its clinical benefit has not yet been elucidated. Perampanel is not well tolerated among ALS patients as it is associated with adverse events such as aggression, somnolence, anger, and dysarthria. Further studies investigating the role of perampanel early in the ALS disease course, excluding ALS patients with frontotemporal lobe degeneration features and C9ORF72 repeat expansion, and using gradual drug titration schedule are needed to evaluate the potential benefit of perampanel in ALS.

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Authors and Affiliations

  1. Division of Adult Neurology, Department of Neurosciences, Philippine General Hospital, College of Medicine and Philippine General Hospital, University of the Philippines Manila, Taft Avenue, Ermita, 1000, Manila, Philippines

    Christian Wilson R. Turalde, Kevin Michael C. Moalong & Mario B. Prado Jr.

  2. Department of Clinical Epidemiology, College of Medicine, University of the Philippines Manila, Manila, Philippines

    Adrian I. Espiritu

  3. Division of Neurology, Department of Medicine, University of Toronto, Toronto, Canada

    Adrian I. Espiritu

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  1. Christian Wilson R. Turalde
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Correspondence to Christian Wilson R. Turalde.

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Turalde, C.W.R., Moalong, K.M.C., Espiritu, A.I. et al. Perampanel for amyotrophic lateral sclerosis: A systematic review and meta-analysis. Neurol Sci 43, 889–897 (2022). https://doi.org/10.1007/s10072-022-05867-6

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  • DOI: https://doi.org/10.1007/s10072-022-05867-6

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