Efficacy of perampanel in epilepsy patients with autism spectrum disorder

Abstract Aim The aim of this study was to assess the usefulness of perampanel (PER), and to identify the relationship between behavioral impairments and electroencephalogram (EEG) findings in epilepsy patients with autism spectrum disorder (ASD). Methods Participants were ASD patients with epilepsy recruited between June 1, 2016 and June 30, 2018. Inclusion criteria were: seizures refractory to two appropriate antiseizure medications (ASMs); presence of neuropsychological impairments; and ≥12 months of monitoring. PER was administered once daily, starting at a dose of 2 mg/day, increased to 12 mg/day. Seizure/EEG responders were identified as participants showing a >50 % reduction in seizure/interictal epileptiform discharge (IED) frequency (indicated as complete disappearance and response). Behavioral responders were identified as participants with a ≥50 % reduction in scores of the Japanese manuals for the Aberrant Behavior Checklist (ABC-J). Results Eleven (64.7 %) of 17 patients were considered to be both seizure and EEG responders. Five (45.5 %) of these 11 patients with seizure/EEG response were considered as behavioral responders. Mean ABC-J scores were significantly decreased at 12 months after PER administration (p = 0.0002). A correlation between decreased IED frequency and ABC-J score was evident in frontal IEDs, but not in non-frontal IEDs. Participants presenting with frontal IEDs showed a significantly higher correlation between seizures/EEG and behavioral improvements (p = 0.023). Moreover, 2 of 6 patients without seizure/EEG improvement were considered as behavioral responders. No patients discontinued PER. Conclusions The results from this study suggest the utility of PER treatment in reducing clinical seizures and IEDs for ASD patients with intractable epilepsy, at least in some patients. Moreover, the present results also indicate the usefulness of PER in improving neuropsychiatric impairments, including behavioral disturbances in ASD related to improvement of clinical seizures/frontal IEDs, but also unrelated to seizure/EEG improvement in at least some ASD patients.