103 Microstructures | Syndromic Craniosynostosis in sCS in the corpus callosum genu and the hippocampal segment of the cingulate bundle. In this study 0.1 increase in FOHR gives a significant increase of RD. Higher RD values could indicate less defined tissue organization, axonal pathology, reduced myelination or myelin damage.26, 27 This finding could be related to the mechanical effect of ventriculomegaly. However, it remains unknown if this increase of RD is reversible, if this increase of RD influences cognitive outcome and, if so, which FOHR cut-off point is optimal for performing a third ventriculostomy or shunt insertion to improve the outcome. Limitations Our study has several limitations. To date there are no normal ranges of DTI measurements in children under the age of 2 years in literature. DTI is dependent on many technical variables, such as the type of MRI scanner used and the amount of diffusion encoding directions, which makes it extremely difficult to compare absolute DTI values with other DTI studies. Our diffusion protocol may have been overly sensitive. Our use of a 0.1 threshold made it possible to track all structures in the control group and almost all structures in the craniosynostosis group. However, the 0.1 FA threshold meant that more aberrant tracts were generated and additional AND and NOT ROIs were required to exclude aberrant fibers. Though, equal measurements were made between two groups. Also, the sample size was small and, therefore, we may have failed to identify associations when in fact they do exist, and vice versa. Analysing different syndromes of craniosynostosis as one group, will bias the outcome. The spectrum of FGFR 2 mutations is widely spread, e.g. cognitive functioning of patients with Apert syndrome is significantly different compared to patients with Crouzon syndrome.1 As syndromic craniosynostosis differ substantially from each other, it should preferably be analysed per syndrome. However, we did not have the statistical power to interpret potential differences of individual syndrome in comparison to controls, as undertaken in the supplemental tables. That said, the current report is the largest DTI study, to date, in non-operated craniosynostosis patients. CONCLUSION Before any surgery, microstructural parameters of white matter tracts of syndromic craniosynostosis patients are comparable to those of controls aged 0-2 years. Enlargement of the ventricles plays a significant role on RD in the corpus callosum genu and the hippocampal segment of the cingulate bundle. Conflict of interest disclosure All authors declare no conflict of interests. Acknowledgements We thank Eng. L.H. Boogaart and Eng. S. Hoogstraten for visualizing Figure 1. 6
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