Autism and epilepsy: historical perspective.

Autism spectrum disorders (ASD) and epilepsy co-occur in approximately 30% of individuals with either ASD or epilepsy. While there is no single unifying ASD-epilepsy phenotype, understanding potential commonalities in subgroups of children with an ASD-epilepsy phenotype will help us disentangle the pathophysiology of both ASD and epilepsy. Throughout this brief historical perspective we selectively review critical trends in ASD-epilepsy research and highlight challenges to clinical and research efforts including terminology, heterogeneity of both ASD and epilepsy, and lack of careful characterization of children affected with both ASD and epilepsy. These complex issues continue to burden research on the diagnosis, neurobiology and management of children with ASD and epilepsy. A key concept that has emerged during the past 40 years is the strong association between intellectual disability and a higher prevalence of epilepsy in individuals with ASD. In addition, the two peaks of seizure onset, one in early childhood and one in adolescence and continuing through adulthood may be unique to individuals with ASD. The overlap of language and autistic regression to epilepsy, EEG epileptiform activity, sleep, and to epileptic encephalopathies such as Landau-Kleffner syndrome continue to be controversial areas of research and of clinical interest. An emerging consensus is that shared developmental genetic, molecular and pathophysiological mechanisms exist and account for the common co-occurrence of ASD and epilepsy.