Nonseizure Outcomes in Dravet Syndrome: Potential Impact of Pharmacotherapy.

Abstract

Dravet syndrome is a severe developmental and epileptic encephalopathy characterized by drug-resistant seizures and multiple nonseizure comorbidities. While disease management has mainly focused on seizure control, there is growing recognition of the importance of nonseizure outcomes in treatment evaluation. This review examines evidence for treatment effects on key nonseizure domains including cognitive functioning, adaptive behavior, speech and language, neurobehavior, sleep, motor outcomes, orthopedic sequelae, nutrition/growth, and quality of life. There is limited evidence following anti-seizure medication trials suggesting improvements in executive function, particularly in preschool-aged children, though findings are inconsistent across studies. Sodium channel blockers are contraindicated, with evidence linking their use to cognitive decline and reduced quality of life. For neurobehavioral symptoms, pharmacological and nonpharmacological treatments show promise in reducing ADHD and behavioral difficulties. Sleep disturbances affect most patients, but evidence for melatonin efficacy is limited. Motor impairments are common, including delayed development, gait abnormalities, and decreased mobility and limited evidence suggests improvements with pharmacological treatment for parkinsonian symptoms. Orthopedic complications include scoliosis, while feeding difficulties may necessitate gastrostomy tube placement. Quality of life measures indicate significant impact from nonseizure symptoms, with evidence of improvement with anti-seizure medication treatment. Overall, findings are limited by small sample sizes, heterogeneous outcome measures, and over-reliance on caregiver reporting. There is a significant knowledge gap regarding disease comorbidities, and future research should investigate nonseizure outcomes alongside seizure control in interventional studies. Dravet syndrome research will benefit from the development of standardized tools validated in the DS population, and establish a core set of outcome measures, prioritized by families, clinicians and researchers to enable meaningful comparison across studies.