Head, Division of Pediatric Neurology Faculty of Medicine, Chulalongkorn University, Thailand
Rationale: Perampanel (PER) is a selective non-competitive AMPA receptor antagonist approved to treat partial and generalised epilepsies as an adjunctive therapy. The United States and Japan FDA has approved PER usage in patients with epilepsy four years or older. Additionally, it is approved in more than 66 countries worldwide. Few or no studies are available evaluating the effectiveness of PER in patients less than four years of age. Here, the results of a retrospective analysis of PER in pediatric patients who were intractable to various antiepileptic drugs (AEDs) and are presented. Methods: Retrospectively review for safety and efficacy of PER in ped. pts with intractable epilepsy from January 2015 – December 2019. Seizure frequency per week were reported by the parents using seizure calendar. All subjects had prior EEG or video EEG monitoring to confirm the seizure type and semiology. PER was titrated up every one week to the maximum dose that each subject could tolerate in the first month. The average seizure frequency in the second and the sixth month at stable dose was then compared to the baseline seizure frequency. The patients also received additional anticonvulsants doses adjustments.Patients whose seizures could not be counted accurately eg with sensory aura only or the parents disagreed to use PER were excluded.PER was discontinued if there is a serious side effect or after two months of administration with no improvement in seizure frequency. Results: PER was administered to 123 patients, 58 were male. Average age was 8.24 year old (1m-18 y) There were 95, 35 and 13 patients age < 12, 4 and 1 year at the time PER were first administered. Average age was 8.24 year old (1 m– 11 y). Average weight was 28.18 kg (4-130 kg). There was 37 patients with unknown etiology. Of the rest, 38 patients had focal cortical dysplasia, 2 patients had schizencephaly, 2 patients had hemimegalencephaly and one patient had holoprosencephaly. Eleven patients had prior brain tumors, including hypothalamic harmatoma, glioma, ganglio-glioma and medulloblastoma. Sixteen patients had genetic epilepsy including SCN1A, mTOR, SCN2A, SCN8A, pyridoxal 5'-phosphate-dependent epilepsy (PNPOD), PIGA , KCNA2 and KCNMA1. Five patients had Lennox-Gastautt Syndromes. Five patients had viral meningo-encephalitis, one had herpetic encephalitis and one had bacterial meningitis. One person each had, SCALP Syndrome, remote stroke, autoimmune encephalitis, near drowning, thalamic haemorrhage, Ohtahara syndrome.Permapanel average initial dose was 2.10 mg (range 0.5-6 mg/day). The average maximum dose of PER was 5.64 mg/day (range 1-12 mg/day).The number of patients remains on PER at 30, 60, 90, 180 days and one year were 123, 121, 117, 115 and 88 patients (100%,98.37%, 95.12%, 93.49% and 71.54%) accordingly. The number of patients with more than 50% reduction of seizure compare to baseline were 65, 85, 86, 88 and 79 patients (52.84 %, 70.24%, 73.50%, 76.52% and 89.77%) accordingly. During the first year of treatment, the number of seizure free patients were 18,18,26, 28 and 7 patients (14.63%, 14.87%, 22.22%, 24.35% and 7.95 %). A pt. with thalamic hemorrhage becomes seizure free and can be weaned off all medications. Several patients whose seizures improved after epilepsy surgery, ketogenic diet and immunotherapy decided to stop PER due to financial concern.Somnolence was the only adverse event reported (22 patients, 17.89%) as many patients were infants or children with mental retardation who could not express dissatisfaction. Conclusions: PER seems to be effective in both pediatric partial and generalized epilepsy. Further, studies on larger patient population can gather more insight on various epileptic syndromes in children. Funding: Please list any funding that was received in support of this abstract.: This study was supported as author initiated study by funding grant FYC-IIS-M065-1082 from Eisai Co. Ltd. and Child Neurology Association (Thailand).
