Methods of neurodevelopmental assessment in children with neurodegenerative disease: Sanfilippo syndrome

Objectives: (1) Develop a methodology for obtaining reliable cognitive and developmental data in children with neurodegenerative disease and cognitive impairment and in turn monitor disease state and treatment outcomes. (2) Demonstrate validity of age-equivalent scores. Methods: We present guidelines for obtaining accurate test scores in low-functioning and behaviorally disruptive pediatric patients, followed by a method validation study: (1) using disease-specific protocols to assess salient aspects of the known phenotype, (2) selecting appropriate tests, (3) managing behavior, and (4) using age-equivalent scores on standardized tools. We used the Bayley Scales of Infant Development-III or Kaufman Assessment Battery for Children-II with a group of 25 children with mucopolysaccharidosis type IIIA (MPS IIIA or Sanfilippo syndrome type A) with dementia. To demonstrate concurrent validity, we used the Vineland Adaptive Behavior Scales-II, comparing parent-reported age-equivalent scores (AEs) with those of the cognitive measures. Results: We were successful in obtaining cognitive age-equivalents for 25 patients with MPS IIIA including those with severe behavioral disruption and a correlation of 0.95 was obtained comparing scores on the parent measure with cognitive age-equivalents validating the age-equivalent approach. Conclusion: An approach to the assessment of severely impaired children including those with behavioral disruption was implemented and is applicable to children with other severe neurological diseases. This approach will enhance the assessment of disease progression and monitoring of treatment outcome in clinical trials.