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180 Chapter 11 SUMMARY Craniosynostosis patients are at risk for developing emotional, behavioral and cognitive disabilities. While the most important aim of surgical treatment is to strive for reducing the risk of developing intracranial hypertension (ICH), it remains unknown what the added value of surgery is with respect to neurocognitive outcome. Is brain development in craniosynostosis mainly affected by intrinsic brain abnormalities or by the potential effect of ICH through compression and subsequent reduced perfusion? This chapter will summarize the most important findings and the clinical implications following from this thesis. Our first aim was to assess cerebral blood flow in children with craniosynostosis. The ongoing myelination in newborns and infants gives a low gray-white matter contrast on structural brain MRI images, which makes measuring cerebral blood flow in young craniosynostosis patients complicated. In Chapter 2 we perform the first step of a new technical set up using the arterial spin labeling (ASL) cerebral blood flow (CBF) image as a contrast for spatial normalization instead of the structural image. Validating this new approach for the pediatric setting, ASL CBF contrast shows to be a viable alternative for use in spatial normalization when structural images have poor contrast. After validating this approach, we further explore cerebral blood perfusion of the frontal lobe in non-operated trigonocephaly patients compared to controls, in Chapter 3. Our findings suggest that the frontal lobes of trigonocephaly patients aged under 18 months old have a normal CBF before surgery. In addition to the previously reported very low prevalence of papilledema or impaired skull growth, this finding further supports our hypothesis that craniofacial surgery for trigonocephaly is rarely indicated for signs of raised intracranial pressure or restricted perfusion for patients younger than 18 months. In Chapter 4 we respond to a letter to the editor regarding this article. We go into detail about the concern that objective criteria are missing for wat constitutes true trigonocephaly or benign metopic ridge and we elaborate on the potential effect of sevoflurane. With Chapter 5 microstructural characteristics of the frontal lobe in non-operated trigonocephaly patients aged 0 to 3 years are analyzed. In this study we do not identify significant differences of microstructural parameters of the white matter frontal lobe between trigonocephaly patients and controls. This suggests both the absence of mechanical restriction of the synostosed metopic suture as well as the absence of intrinsically affected white matter. However, at this age, differences could be too subtle to measure with DTI or ASL.

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