Nine de Planque

167 General Discussion technical variables, such as the type of MRI scanner and the scanner settings. This makes comparing our studies with other studies challenging. Part I. To what extent do primary brain abnormalities exist in non-operated isolated and syndromic craniosynostosis, looking at intracerebral blood flow and brain microstructures? We investigated CBF and white matter integrity in non-operated children with isolated metopic suture synostosis and the white matter integrity in non-operated children with syndromic craniosynostosis. Isolated metopic suture synostosis In trigonocephaly patients the functional indication for surgery is debated. Whether premature closure of the metopic suture restricts brain development mechanically, and whether craniofacial surgery has a positive effect on development has never been proven. Previous studies show that operated patients with trigonocephaly are still at risk of developing mental deficiencies, behavioral problems, and delays in speech and language.5, 6 This suggests surgery is not preventing impairment of cognitive development. However, we do not know what these outcomes will be without surgery. Literature describes that ICH is negligible in trigonocephaly patients (<2%) and that non-operated trigonocephaly patients have a normal intracranial volume compared to controls. 7 8 Also, studies have shown that some genetic mutations found in patients with trigonocephaly overlap with patients with developmental delay disorders, suggesting that the brain could be affected intrinsically.9-11 First, we investigated CBF of the frontal lobe in unoperated trigonocephaly patients by ASL. We found similar values in non-operated trigonocephaly patients compared to controls. This implies that metopic synostosis is not related to impaired perfusion in the frontal lobes up to the age of 18 months. In a second study, using DTI, microstructural parameters of white matter tracts of the frontal lobe of trigonocephaly patients were compared to those of controls aged 0-3 years. FA or MD of frontal lobe white matter microstructure in trigonocephaly were similar to controls. Findings from these two studies imply that both local CBF as well as white matter integrity are neither affected by compression of the metopic suture synostosis nor by a genetic cause at this age. However, at this young age the potential differences may have been too subtle or were not yet measurable with ASL or DTI due to the following reasons. First, from 0-2 years the brain is in the main phase of myelination. The timing of myelination is different per brain region and different per individual, which makes it difficult to interpret subtle diffusivity differences between patients and controls. Secondly, including healthy controls for this cohort was challenging because of the young age, what made exact age-matched controls impossible. Thirdly, we investigated whole tracts instead of zooming in to a voxel-based brain matter. Insight in more peripheral, localized, focal 10

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