Nine de Planque

10 Chapter 1 INTRODUCTION This thesis focuses on brain anomalies in children with isolated or syndromic craniosynostosis that arise either as a primary brain development disorder or secondary to disturbed skull growth. Affected children have a higher prevalence of neurocognitive impairment and are at risk to develop intracranial hypertension (ICH), which could further impair cognitive development, cause behavioural issues, and could cause visual loss by damaging the optic nerves.1-3 4 The most important aim of surgical treatment is to strive for best possible neurocognitive outcome by reducing the risk of developing ICH. The pathogenesis of ICH and its interconnected problems, such as hydrocephalus and herniation of the cerebellar tonsils through the foramen magnum, is multifactorial and still ill understood. This thesis seeks to differentiate between primary and secondary brain anomalies in children with craniosynostosis in a search to determine best treatment strategy. Identification of primary, inborn disorders of the brain can prevent overtreatment, as it is unlikely that surgery will be of benefit. On the other hand, the identification of secondary brain disorders and their impact on outcome can guide us to a better screening policy with earlier treatment to prevent these sequelae. Better understanding of the consequences of ICH on brain development will be the scientific basis of treatment protocols, that strive to improve the quality of life of the patients. This thesis will be focusing on answering the following questions: - To what extent do primary brain abnormalities exist in non-operated isolated and syndromic craniosynostosis, looking at intracerebral blood flow and brain microstructures? (Part I) - Are there any secondary effects of ICH and treatment on the brain of operated syndromic craniosynostosis patients, focusing on ventriculomegaly, Chiari and cortical thickness? (Part II) In this introduction, craniosynostosis, intracranial hypertension, cognitive outcome and the used types of imaging are set out, finalized by an outline of each study. Craniosynostosis A newborns’ cranial vault consists of seven bones, which are separated by the metopic, two coronal, the sagittal and two lambdoid sutures.5 These open sutures allow for transient skull distortion during birth and facilitate future growth of the brain. In the first years of life, brain growth is the main incentive of skull growth. Craniosynostosis refers to this premature closure of the skull sutures, which mainly occurs around the 15th-19th week of gestation resulting in an abnormal skull shape.6, 7 The prevalence of

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