MRI measurement of intracranial MPAs (minor physical anomalies) in autism

Abstract

BACKGROUND: Autism is a neurodevelopmental disorder in which MPAs (minor physical anomalies, particularly of the face) are thought to occur more frequently. MPAs form during the same time window as brain developmental abnormalities are thought to begin i.e. in the first trimester of fetal life. MPAs may therefore represent a convenient biomarker for neurodevelopmental anomaly. Traditionally, measurement of MPAs has depended on direct observation of the subject which is bias-laden. Using MRI brain scan, observer bias can be avoided, multi-centre data collection facilitated, and early diagnosis is a realistic goal. OBJECTIVES: In this study we aimed to establish an MRI measurement protocol of intracranial MPAs in autism and determine the extent to which there are significant differences in intracranial landmarks in autism. Specific preliminary objectives were to measure optical and aural MPAs in children with autism who are age- and gender-matched to healthy children, ‘blinded’ to subject identity. Longer-term, the objective is to identify a reliable endophenotypic marker is to assist early diagnosis, facilitate early treatment, and enhance future outcome in autism. METHODS: We conducted a pilot study of MPAs in a sample of children aged 7- 14 with autism (n=25), compared with their age and gender matched controls (n=46). MPA measurements were performed using MRI and blind to group membership. Intra-class coefficient ICC was 0.95. RESULTS: We noted the following preliminary results in this sample : (1) Eye-ear distance : Significant effect of group between autism and control in Left Ear Height (Autism mean: 108; Control mean: 103) (p<.0005) and a near-to-significant difference in Interorbital (Autism mean: 23.36; Control mean: 22.14) (p<.053). (2) Inter-lens/interorbital distance : Significant positive correlations between Interlens/Interorbital distance and age in controls but not in patient group. (3) Inter-optic distance: Larger inter-orbital nerve angle in controls (mean: 66 degrees) than autism (mean: 62 degrees) (p<.18) but only the autism group showed significant negative correlation between the inter-optic angle and age (r=-.617, p<.001). CONCLUSIONS: Measurement of intracranial MPAs using MRI scan is feasible and straightforward. Significant differences between children with autism and typically developing controls can be identified. Smaller inter-optic angle in the autism group is compatible with early developmental changes in brain because the inter-optic angle reduces from wide angle during embryological life to become fixed at around 68 degrees by age 3.