Abstracts

Rationale: Determining meaningful change is important to understand the natural history of any developmental disorder. While there is no gold standard, growth scale values (GSVs) are one option when available. GSVs are transformed from raw scores using a Rasch analysis and are therefore an equal interval scale. The purpose of this study is to determine the frequency of statistically significant change using GSVs across each domain of the Bayley Scales of Toddler and Infant Development – Fourth Edition (Bayley-4) in children with STXBP1 – related epilepsy. The STXBP1-related disorders are rare, developmental epileptic encephalopathies.

Methods: Forty-two children enrolled in the multi-site STARR Natural History Study (STXBP1 Clinical Trial Readiness) who had completed more than one serial assessment approximately 6-months apart were included (mean combined age=9.2 (5.5) years; 43% female; 2% Asian, 5% Black/African American, 67% White, 2% multiple races, 24% other; 14% Hispanic or Latino). We employed use of the cutoffs provided in the Bayley manual for statistically significant GSV change.

Results: See Table 1. Frequency of statistically significant change over 6-month assessments varied by domain but ranged between 24% (fine motor) and 54% (expressive language). Some children had more than one change across repeated evaluations. The domain with the most frequent gains was expressive language (31%), followed by cognitive (29%). Though overall frequency of change was less common in other domains, about equal proportions of children displayed changes in receptive language and fine motor skills. Most children displayed gains in gross motor skills. Overall frequency of statistically significant change was most common in the youngest cohort (ages 6-months to 4-years, 11-months, more gains in all domains except for receptive language), though gains were also made in the middle cohort (ages 5 to 11-years 11-months). See Table 2.

Conclusions: While developed for neurotypical children, GSV scores are sensitive to change in individuals with STXBP1-related epilepsy. Significant changes are most evident in expressive language and cognitive skills, with most changes explained by gains, though there was also expressive language loss. Gains in cognition, expressive language, and gross motor skills are consistent with anticipated developmental trajectory; losses in expressive language are also commonly reported by caregivers. Individuals may require more than 6-months to show gains in fine motor skills. More frequent change in younger individuals is consistent with developmental expectations; however, individuals with STXBP1-related epilepsy continue to reach certain early developmental milestones up to at least age 12-years. Recruitment for older individuals should be increased. Along with other metrics, further analysis of GSVs will continue to contribute to understanding the natural history of change in STXBP1-related epilepsy. Future work will determine cutoffs for statistically significant change over and above both testing session characteristics and natural history expectations.

Funding: This work was supported by the STXBP1 Foundation and the Center for Epilepsy and Neurodevelopmental Disorders (ENDD).