Early seizure onset and dysplastic lesion extent independently disrupt cognitive networks

Objective: To determine the most important factors influencing neuropsychological performance in children with intractable epilepsy due to focal cortical dysplasia and the nature of the interaction among significant variables. Methods: Surgical patients with histologically verified focal cortical dysplasia were retrospectively evaluated to determine the impact of histopathology, extent of lobar involvement, hemispheric laterality, age at onset, and duration of epilepsy on cognitive functioning. A composite neuropsychological variable was obtained by transforming data from 5 major cognitive domains using principal components analysis. Multiple regression was used to examine the unique contributions of predictor variables on composite cognition and Full Scale IQ. Data were qualitatively evaluated for nonstatistical trends. Results: Poor cognitive outcomes were associated with early age at onset of epilepsy (AOE) and widespread dysplastic involvement. Extent of dysplasia and AOE together accounted for 35% of Full Scale IQ variance, and 21% of composite cognitive performance. Each factor contributed independently to cognitive dysfunction. Conclusions: Early AOE disrupts critical periods of development and leads to poor cognitive outcome, but children with multilobar dysplasia are likely to have diminished cognitive skills regardless of AOE. Later AOE is not expected to mitigate deficits because of widespread pathology, nor would a localized lesion be likely to mollify the developmental deficits resulting from early AOE.