124 - Multimodal Approach to Examine Neuropathophysiological Mechanisms Underlying Neurocognitive Differences in Congenital Hyperinsulinism

Poster Number: 124
Publication Number: 124.169

Background: Congenital hyperinsulinism (HI) is the leading cause of persistent hypoglycemia in infants and children. Adverse neurocognitive outcomes remain one of the most concerning sequalae of HI. Efforts to improve these outcomes have been hampered by limited understanding of the underlying pathophysiologic mechanisms.

Objective: Advance understanding of how hyperinsulinism affects brain development and function.

Design/Methods: Cross-sectional study of adolescents and adults with HI. Participants completed electroencephalogram (EEG), magnetic resonance imaging (MRI), and neurocognitive assessments including validated self (≥18y), or caregiver ( < 18y)-reported instruments for adaptive function (Adaptive Behavior Assessment System – Third Edition [ABAS-3]), social, emotional, and behavioral function (Child Behavior Checklist [CBCL, < 18y]/Adult Self Report [ASR, ≥18y]), and executive function (Behavior Rating Inventory of Executive Function [BRIEF]– Second Edition [ < 18y]/Adult Version [≥18y]). Formal testing was performed using NIH Toolbox® Cognition Battery (NIHTB-CB) with age-corrected standard score on the Fluid Cognition Composite (mean 100, SD 15) as the primary outcome measure. One-sample, one-sided z-tests of proportions were used to compare the observed proportion of participants with scores >1 and >2 SD from the mean with the expected proportion in a normal distribution. Scores >1 SD below the mean for ABAS-3 and NIHTB-CB, and scores >1 SD above the mean for BRIEF and CBCL/ASR measures, are considered indicative of clinical concern. Relationships between neurocognitive test scores, EEG, and MRI measures were explored.

Results: Seventeen participants, median age 24 (IQR: 18-30) years, 71% female, completed study procedures. The proportion of participants with score >1 SD below the mean was significantly greater than that expected on the Fluid Cognition Composite, primary outcome, but did not differ from expected on the report-based measures (Table 1). Seven participants (41%) had abnormalities on EEG. Fluid Cognition Composite score was significantly lower among those with EEG abnormalities (82.6 ± 12.2 vs. 100.8 ± 14.8, p=0.02, two-tailed t-test). Analysis of MRI data is ongoing.

Conclusion(s): Clinically significant differences in neurocognitive function are highly prevalent among adolescents and adults with HI. Attention and inhibitory control, episodic memory, and processing speed appear particularly affected.