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      Young children with multidrug-resistant epilepsy and vagus nerve stimulation responding to perampanel: A case report

      case-report

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          Abstract

          BACKGROUND

          Perampanel (PER), a third-generation antiepileptic drug, is a selective and noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, and has been approved for the treatment of adults and adolescents with focal epilepsy. However, there are only a few studies about the efficacy and tolerability of PER in young children with multidrug-resistant epilepsy. In this case, we aimed to share our clinical experience in this group.

          CASE SUMMARY

          A 4-year-old boy without perinatal asphyxia and familial history of epilepsy began to have ictal seizures from age 14 mo, with jerky movement of four limbs and head nodding. Abnormal multifocal discharge and background activity were recorded through electroencephalography, and no pathogenic mutation was found in the whole exome sequencing for the patient and his parents. He had received valproate, levetiracetam, topiramate, oxcarbazepine, clonazepam and lacosamide sequentially at different times, but he still had frequent seizures even after vagus nerve stimulation (VNS) implantation. He was diagnosed with idiopathic multidrug-resistant epilepsy. However, his seizure frequency was significantly reduced after PER administration in a dose-dependent manner, and better cognitive behavior was observed. In addition, the adverse reactions of anger and aggression also appeared.

          CONCLUSION

          PER is effective as add-on therapy for young children with multidrug-resistant epilepsy who have previously undergone VNS implantation.

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          Most cited references16

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          Evidence-based guideline update: vagus nerve stimulation for the treatment of epilepsy: report of the Guideline Development Subcommittee of the American Academy of Neurology.

          To evaluate the evidence since the 1999 assessment regarding efficacy and safety of vagus nerve stimulation (VNS) for epilepsy, currently approved as adjunctive therapy for partial-onset seizures in patients >12 years. We reviewed the literature and identified relevant published studies. We classified these studies according to the American Academy of Neurology evidence-based methodology. VNS is associated with a >50% seizure reduction in 55% (95% confidence interval [CI] 50%-59%) of 470 children with partial or generalized epilepsy (13 Class III studies). VNS is associated with a >50% seizure reduction in 55% (95% CI 46%-64%) of 113 patients with Lennox-Gastaut syndrome (LGS) (4 Class III studies). VNS is associated with an increase in ≥ 50% seizure frequency reduction rates of ≈ 7% from 1 to 5 years postimplantation (2 Class III studies). VNS is associated with a significant improvement in standard mood scales in 31 adults with epilepsy (2 Class III studies). Infection risk at the VNS implantation site in children is increased relative to that in adults (odds ratio 3.4, 95% CI 1.0-11.2). VNS is possibly effective for seizures (both partial and generalized) in children, for LGS-associated seizures, and for mood problems in adults with epilepsy. VNS may have improved efficacy over time. VNS may be considered for seizures in children, for LGS-associated seizures, and for improving mood in adults with epilepsy (Level C). VNS may be considered to have improved efficacy over time (Level C). Children should be carefully monitored for site infection after VNS implantation.
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            Ionotropic Glutamate Receptors in Epilepsy: A Review Focusing on AMPA and NMDA Receptors

            It is widely accepted that glutamate-mediated neuronal hyperexcitation plays a causative role in eliciting seizures. Among glutamate receptors, the roles of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors in physiological and pathological conditions represent major clinical research targets. It is well known that agonists of NMDA or AMPA receptors can elicit seizures in animal or human subjects, while antagonists have been shown to inhibit seizures in animal models, suggesting a potential role for NMDA and AMPA receptor antagonists in anti-seizure drug development. Several such drugs have been evaluated in clinical studies; however, the majority, mainly NMDA-receptor antagonists, failed to demonstrate adequate efficacy and safety for therapeutic use, and only an AMPA-receptor antagonist, perampanel, has been approved for the treatment of some forms of epilepsy. These results suggest that a misunderstanding of the role of each glutamate receptor in the ictogenic process may underlie the failure of these drugs to demonstrate clinical efficacy and safety. Accumulating knowledge of both NMDA and AMPA receptors, including pathological gene mutations, roles in autoimmune epilepsy, and evidence from drug-discovery research and pharmacological studies, may provide valuable information enabling the roles of both receptors in ictogenesis to be reconsidered. This review aimed to integrate information from several studies in order to further elucidate the specific roles of NMDA and AMPA receptors in epilepsy.
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              Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs II: Treatment-resistant epilepsy

              To update the 2004 American Academy of Neurology guideline for managing treatment-resistant (TR) epilepsy with second- and third-generation antiepileptic drugs (AEDs).
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                Author and article information

                Contributors
                Journal
                World J Clin Cases
                WJCC
                World Journal of Clinical Cases
                Baishideng Publishing Group Inc
                2307-8960
                16 April 2022
                16 April 2022
                : 10
                : 11
                : 3511-3517
                Affiliations
                Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
                Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China. yudan540@ 123456163.com
                Author notes

                Author contributions: Yang H wrote the manuscript; Yang H and Yu D collected the data and participated in patient care; Yu D reviewed and edited the manuscript.

                Corresponding author: Dan Yu, MD, Doctor, Professor, Department of Pediatrics, West China Second University Hospital, Sichuan University, No. 20, Section 3, South Renmin Road, Chengdu 610041, Sichuan Province, China. yudan540@ 123456163.com

                Article
                jWJCC.v10.i11.pg3511
                10.12998/wjcc.v10.i11.3511
                9048547
                b489ce4c-4dcc-48be-9615-9bc427f6a43e
                ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.

                This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

                History
                : 9 August 2021
                : 23 November 2021
                : 27 February 2022
                Categories
                Case Report

                perampanel,young children,drug-resistant epilepsy,vagus nerve stimula-tion,case report

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