Rationale:
Developmental and Epileptic Encephalopathies (DEEs), such as Dravet Syndrome, are characterized by drug-resistant seizures and a wide spectrum of non-seizure comorbidities. Cognitive difficulties are common, including developmental stagnation or regression. As natural history studies and precision medicine trials increasingly emphasize non-seizure outcomes, robust neurodevelopmental assessment has become critical. However, administration of gold-standard developmental tests in individuals with DEEs is often limited by cognitive, sensory, motor, and behavioral difficulties. In this study, we evaluate the feasibility of administering standardized, age-appropriate developmental tests (Bayley-4, WPPSI-IV, WISC-V, WAIS-IV) in individuals with Dravet Syndrome enrolled in the SCN1A Horizons study.
Methods:
We analysed baseline data from participants with Dravet Syndrome within the SCN1A Horizons cohort. This is a multi-centre prospective natural history study. All participants completed a neuropsychological assessment, starting with age-appropriate tests and and adjusting to developmental level when appropriate. Here, we report whether age-appropriate developmental tests were accessed, based on availability of composite standardised scores. Reasons for not accessed tests were recorded by neuropsychology raters using structured codes.
Results:
We analysed baseline data from 65 participants with Dravet Syndrome (male = 33 (50.7%); median age = 7.7; range = 1.3-64 years). Across the cohort, access to age-appropriate standardized developmental assessment varied by test.
The WAIS-IV (for 16 to 90 years old) was attempted in 5 participants, with 1 (20%) completing the assessment and 4 (80%) unable to access it. The WISC-V (6 to 17 years) was attempted in 31 participants, with 11 (35.5%) completing the assessment and 20 (64.5%) unable to access it. The WPPSI-IV (2 years 6 months to 7 years 7 months) was attempted in 19 participants, with 7 (36.8%) completing the assessment and 12 (63.2%) unable to access it. The Bayley-4 (16 days to 42 months) was attempted in 10 participants, with 8 (80%) completing the assessment and 2 (20%) unable to access it.
Key barriers to accessing age-appropriate assessments included cognitive impairment, attention difficulties, behavioral challenges, and low motivation. Notably, 30 (46%) participants needed to be assessed out-of-age-range with the WPPSI-IV (n=12) or the Bayley-4 (n=18).
Conclusions:
These findings highlight significant challenges in administering age-appropriate standardized developmental tests in Dravet Syndrome. The frequent reliance on out-of-age-range assessment underscores the limitations of gold standard tests in this population. There is a need for DEE-specific developmental norms, scoring algorithms and a core outcome set that that allow for comparison across studies. Addressing these limitations is essential to improve the validity of standardized developmental tests in clinical research and to inform standards of care.
Funding:
This work was funded by the SCN1A Horizons study.