The epileptic hypothesis: Developmentally related arguments based on animal models

Summary The significant morbidity linked to epileptic encephalopathies of childhood has prompted the need to identify and dissect the factors and mechanisms that contribute to the resultant functional regression. Although experiments specifically assessing language in rodents are difficult to design, a number of studies have shed light on the conditions that contribute to the functional deterioration. In particular, interictal spikes and seizures, especially if prolonged or frequent, may cause acute or long‐lasting effects on brain functioning and development, which may impair performance in a variety of behavioral tests. These effects are further modified by a number of genetic, biological, and epigenetic factors, including age, sex, and underlying pathology, which further diversify outcome. Of special importance is the developmental age when the epileptic disorder manifests, because it may dictate outcome but also may be a deciding factor in selecting appropriate therapies.