Abstracts

Previous research has recognized the frequent association of epilepsy and autism (7%-42%; Tuchman, 2000). Debate has ensued whether a causal relationship exists between EEG epileptiform abnormalities and autistic regression in the absence of clinical seizures. AED use with autistic children has suggested benefits in areas of hyperactivity, impulsivity, aggression, and affective instability associated with autism (Hollander, 2001; Rugino, 2002). The purpose of this study was to investigate whether autistic children with EEG epileptiform abnormalities treated with levetiracetam would show improvement in certain core features of autism., Participants were 9 boys and 2 girls, ages 3 to 11 years ([italic]M[/italic] = 6.43) with a diagnosis of autism spectrum disorder and with epileptiform discharges on EEG. Multiple baseline and outcomes measures evaluating core features in autism were employed, including daily behavioral diaries assessing social interaction, emotional response, awareness, expressive language, receptive language, play/imagination, body movement, rigid/habitual behaviors, and other behaviors. Study design was a 24-week, open label, non-forced titration of levetiracetam with initial daily dose of 10mg/kg/d and target dose of 60 mg/kg/d. Baseline concommitant medications were not considered reason for exclusion., Ten (91%) children had a formal diagnosis of autism; one of Aspergers. Incidence of regressive sybtype was overrepresented (64%) compared to expected (30-39%). Early termination occured in 6 of 11, primarily due to aggression and emotionality seen at higher doses. Curvilinear analysis suggested the maximum benefit was at lower doses (5-10/mg/kg) in 7 of 11 children. No serious adverse events were observed and all side effects reversed with discontinuance of medication.
Preliminary results from daily behavioral diaries indicate positive trends in awareness (10 of 11). Differential results for regressive subtype suggest benefit in the domain of play/imagination (6 of 7). Participants with EEG patterns of left focal epileptiform discharges and bifrontal sharps evidenced positive trends in the area of expressive language (5 of 6, and 2 of 2, respectively). Children with right focal discharges experienced negative effects in expressive language (3 of 3)., Preliminary results suggest levetiracetam is safe in children with ASD and EEG epileptiform abnormalities, and that certain behavioral domains of autism may benefit from low doses. Increasing dose did not correspond to increased performance, and resulted in a higher incidence of early termination from the study. Epileptiform discharges involving the dominant hemisphere may predict benefit in the domain of expressive language. These results warrant further investigation targeting concepts of EEG abnormaility and language effects with levetiracetam., (Supported by UCB Pharma, Inc.)