Cognitive and behavioral clinical outcome assessments in children with developmental and epileptic encephalopathies: Issues and instruments

Children with developmental and epileptic encephalopathies (DEEs) face cognitive and behavioral challenges that may have a greater impact than seizures on their quality of life (QoL). The need to assess these nonseizure outcomes for evaluating treatments is increasingly recognized. Advances in genomic technologies have transformed the diagnostic landscape of rare genetic epilepsies, including DEEs, opening new opportunities for precision medicine. There is also growing interest in drug repurposing, identifying well-tolerated medications for other indications for use in DEEs. Innovative trial designs and the systematic collection of prospective natural history data are essential, given the rarity and heterogeneity of DEEs. The selection of reliable, valid, and meaningful outcome measures of cognition and behavior is crucial for clinical trials and natural history studies. Commonly used tools for assessing cognition and adaptive behavior often exhibit floor effects and may fail to capture subtle, yet clinically significant, changes in functioning that are meaningful for children and their families. There is thus a need to explore a fuller range of clinical outcome assessments (COAs) and scoring methods that could be sensitive to change and suitable for use in rare disease populations. Assessing behavioral and emotional outcomes in children with DEEs is additionally challenging, as many assessment instruments have been developed and validated for use in children without intellectual disability. To fully realize the potential of precision medicine in the DEEs, a robust framework for outcomes assessment is required, one that incorporates sensitive, reliable, and meaningful COAs tailored to this population. Coordinated efforts to identify and adapt existing measures or develop new outcome tools will be crucial for advancing therapeutic strategies that genuinely improve QoL for children with DEEs. This article summarizes the issues faced when selecting outcome measures for DEE trials and reviews commonly used instruments for assessing cognition and behavior in children with DEEs.