MRI FINDINGS INFORM NEURODEVELOPMENTAL OUTCOMES IN INDIVIDUALS WITH AGENESIS OF THE CORPUS CALLOSUM (ACC): ANALYSIS OF A PROSPECTIVE COHORT

Objectives: The phenotypic spectrum of ACC patients is quite broad, ranging from mild symptoms to severe neurodevelopmental impairment and intractable epilepsy. This variability limits the ability of clinicians to give accurate family planning advice and delays the design of appropriate therapy interventions. We sought to establish reliable correlations between MRI findings and clinical profiles in individuals with ACC with the goal of informing prognostic discussions and aiding therapeutic decisions.

Methods: Prospectively enrolled participants with MRI confirmed ACC (n=55) were evaluated using several well-established neurodevelopmental assessment tools: (1) Vineland Adaptive Behavior Scales, (2) Functional Independence Measure for Children (WeeFIM), (3) the Pediatric Cerebral Performance Category Scale (PCPC) and (4) a semi-quantitative analysis of seizure activity. MRI scans were evaluated by three individuals in a standardized format, assessing features including other midline commisures, malformations of cortical development and white matter volume loss. Single variable and multivariate analyses were performed to determine correlations between clinical profiles and MRI findings.

Results: We found a number of novel correlations that underscore the utility of this approach. Anterior commisure size correlated highly with the age-adjusted total WeeFIM (p=0.003). This correlation also extended to total Vineland scores. These findings importantly replicate what we observed in our initial analysis of a retrospective ACC cohort. We also found that seizure severity correlated with multiple MRI findings: (1) A decrease in white matter volume (p=0.017), (2) small or dysplastic cerebellar vermis (p=0.0046) and (3) a small brainstem (p=0.007). A trend toward significance was also observed with seizure severity and the anterior commisure size, cortical malformations, and heterotopia.

Conclusion: We have found several statistically and clinically significant links, specifically (1) between seizure scores and the MRI findings of white matter volume, cerebellar vermis and brainstem anomalies and (2) between anterior commissure size and clinical outcomes. If confirmed in another prospective cohort, these findings may help guide decisions made by families.