173 General Discussion Assessing CBF and microstructural white matter properties in older trigonocephaly patients in relation with neurocognitive data would improve our ability to make longitudinal inferences at each stage of development. A study of both neurocognitive data and brain properties of 5-6 years old operated trigonocephaly patients compared with non-operated trigonocephaly patients, will learn us more about the added value of surgery. In syndromic patients studying the effect of CBF and genetic profile on microstructural properties will give us more information on the pathophysiology and consequently the indication to treat these patients. In the future, it is important to design studies per syndrome and include patients in larger cohorts. In syndromic craniosynostosis patients we aim to treat/prevent ICH. It would be important to further expand the research on the course of ventriculomegaly and tonsillar herniation. What would be the best severity threshold for FOHR? What role does time of increase and duration of ventriculomegaly have on neurocognitive functioning? Further studies may identify whether stable ventriculomegaly is as harmful as progressive ventriculomegaly, and if so, at what age, duration or cut-off point this should be treated. Knowing these answers, treatment could be aligned with these factors preventing loss of cognitive function. Which degree of tonsillar herniation will cause symptoms and/or become progressive? In children with syndromic craniosynostosis and involvement of lambdoid sutures, the order of events and causes remain unclear. Is it crowding of the posterior fossa which causes functional stenosis of the aqueduct, with subsequent hydrocephalus and tonsillar herniation? Or is it tonsillar herniation that restricts the outflow of the 4th ventricle what subsequently causes progressive hydrocephalus? What is the role of venous obstruction? Does it generate engorgement thereby adding to posterior fossa crowding? A predictive tool on development of progressive ventriculomegaly for children at their first hospital visit would be of value. This would require a good understanding of the causes and potential interactions. Also, the potential interaction of ventriculomegaly treatment by ventriculoperitoneal shunt (VPS) on the course of tonsillar herniation needs further study. CSF overdrainage and restricted skull growth as a result of the VPS, are associated with the occurrence of tonsillar herniation in non-synostosis patients and it is likely that the same phenomenon occurs in craniosynostosis patients. This mechanism may add to the finding that while ventricular size decreases over time the incidence of TH increases over time in craniosynostosis patients. Furthermore, we would like to answer the question: How does ICH impact white matter development in the craniosynostosis brain? As we learned from this thesis, 10
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