Abstract: Background: There are few studies on the efficacy and safety of perampanel in children with drug-resistant epilepsy, and the efficacy and safety are not clear. Objective: To investigate the efficacy and safety of perampanel in the treatment of children with drug-resistant epilepsy. Design: Cohort study. Methods: Children aged 0-18 years who were diagnosed with drug-resistant epilepsy and treated with perampanel in Peking University First Hospital from January to December 2020 were included in the cohort study, and the end point was at least 6 months' treatment. Efficacy was the dependent variable, and the gender, etiology, epileptic syndrome, baseline frequency of seizures, age at onset, age at time of dosing, course of disease at dosing, dosage of drugs, number of treatments were independent variables. The univariate and multivariate logistic regression analysis were used to analyze the related factors of efficacy. The adverse reactions of perampanel in the treatment of children with drug-resistant epilepsy were also analyzed. Main outcome measures: The frequency of seizures decreased ≥50% from baseline at the last follow-up (within 1 month) . Results: A total of 50 patients were included (34 males and 16 females)，and all the patients were followed up at least 6 months. The epileptic syndromes included infantile spasms in 6 cases, Lennox-Gastaut syndrome in 2 cases, epileptic encephalopathy with electrical status epilepticus during sleep in 3 cases, and Rasmussen encephalitis in 2 cases. Specific causes of epilepsy were found in 66.0% (33/50) of the patients, including structural causes in 19 cases, genetic causes in 9 cases, immunological causes in 4 cases, and metabolic causes in 1 case. The baseline frequency of seizures ranged form once per 2 weeks to hundreds of times per day. Eighteen percent (9/50) of the patients had seizure less than once a day, 36.0% (18/50) of the patients with seizures of 1-10 times per day, 32.0% (16/50) with seizures of 1-10 times per day, 14.0% (7/50) with seizures of more than 100 times per day. Three types of treatments (range from 1 to 6 types) were used in combination with perampanel, and three types of treatments (range from 0-10 types) were previously used. The age at time of dosing was 64.5 months (4 months to 18 years), and course of disease at dosing was 22.0 months (2 months to 17.3 years). The duration of perampanel at the last follow-up was 8.0 (6.0-14.0) months. At the last follow-up, the maximum daily dose of perampanel was 0.175 (0.06-0.5) mg·kg-1·d-1 and 4 (0.5-2) mg·d-1.The rate of efficacy was 46.0%(23/50). At the last follow-up, 41 patients were treated with perampanel, and the retention rate was 82.0%. Nine patients stopped treatments because of poor efficacy. No correlation was found between the efficacy and gender, etiology, epileptic syndrome, baseline frequency of seizures, age at onset, age at time of dosing, course of disease at dosing, dosage of drugs, or number of treatments. Six patients (12.0%) were observed with irritability and drowsiness during the treatment, and no other serious adverse reactions were observed. Conclusion: The overall rate of efficacy of using perampanel to treat drug-resistant epilepsy was 46%. The safety and tolerability of perampanel in the treatment of children with drug-resistant epilepsy were relatively good, and no related factors with efficacy were found.

Key words: Perampanel, Epilepsy, Children