Is Cortical Complexity Development Affected By Syndromic Craniosynostosis?

Abstract

INTRODUCTION: In order to fully understand mechanisms of brain development in craniosynostosis, structural relationships must be identified over time. The relationship between cortical surface area and volume allometrically scales with age and is an indicator of neurocognitive ability. The aim of this study was to evaluate cerebral cortical complexity development in syndromic craniosynostosis patients compared with controls. METHODS: Records of all syndromic craniosynostosis patients were reviewed at a single national craniofacial center to include patients with adequate clinical and imaging data for analysis. Age-matched controls with appropriate imaging were also identified. A total of 209 MRIs were included in this study, 171 of which were of syndromic patients (38 Apert, 68 Crouzon, 25 Muenke, 18 Pfeiffer, 22 Saethre-Chotzen) and 38 of which were of controls. All imaging data were processed via FreeSurfer software analysis to determine pial surface area and cortical volumes by lobe. The ratio of surface area to volume was calculated and compared with control data by lobe via linear mixed effect model to account for multiple measurements, syndrome, sex, and age at the time of imaging. Age was observed to vary logarithmically with this ratio and was subsequently log transformed for all analyses. Bonferroni correction was used for multiple comparisons. RESULTS: Average age at the time of magnetic resonance imaging was 8.97 years (SD = 5.26 years) and was significantly associated with an increase in surface area to volume ratio in all lobes (P < 0.001). Mean frontal complexity ratio was 0.29 (SD = 0.02) and did not significantly vary among syndromic status (P = 0.493). Similarly, temporal (0.26; SD = 0.02; P = 0.322) and parietal (0.33; SD = 0.03; P = 0.124) complexity ratios were found to be uninfluenced by syndromic status. Mean complexity ratio for the occipital lobe was 0.38 (SD = 0.05) for all patients but was significantly reduced in Apert syndrome (P = 0.002). Further analysis of isolated cortical volumes demonstrated Apert syndrome patients to have larger volumes in each lobe among all groups (P < 0.001). CONCLUSION: Occipital lobe cortical complexity development is significantly impeded in Apert syndrome, despite adequate gains in brain volume. This is suggestive of cortical folding impairment and may provide an anatomical explanation for neurodevelopmental delay observed in Apert syndrome.