Magnetic Resonance Imaging in patients with craniosynostosis.

Currently the focus of clinicians treating craniosynostosis is shifting from
only the skull to the skull and the brain. The old hypotheses stated that
elevated intracranial pressure (ICP) was caused by a too small intracranial
volume due to the synostosis of the cranial sutures and that the elevated ICP
induced the neurocognitive development impairment. Our ongoing research on this
topic has proven this theory wrong: patients have a normal brain volume and a
normal or enlarged intracranial volume! The first studies we performed on brain
anomalies were done in 6 to 12 year old patients with syndromic
craniosynostosis. Their MRI findings suggest that the observed brain anomalies
are a direct result of the causative genetic mutation. Our current hypothesis
is that elevated ICP is mainly is caused by venous hypertension and local
perfusion disturbances of the brain. Additional factors that have a detrimental
effect on ICP are increased cerebrospinal fluid volume and obstructive sleep
apnea, but these are only of significance for patients with syndromic
craniosynostosis.
To prove this hypothesis, this study focuses on the brain malformations by
performing magnetic resonance (MR) scans (1.5 TESLA) with diffusion tensor
imaging (DTI) and arterial spin labelling (ASL) as part of the standard MR scan
protocol to visualize disturbances in the white matter of the brain and
cerebral blood flow. Additionally, this study aims to find the correlation
between brain imaging and brain function by combining the MRI data with the
outcome of standardized neurodevelopmental tests performed according to
standard treatment protocol.
By assessing these data at a young age in a broad group of craniosynostosis
patients, before and after surgery, a better understanding of the condition
will be achieved, which will optimize its treatment.

1. To assess whether microarchitectural alterations in the brain of different
types of craniosynostosis patients are indeed primary.
2. To assess local cerebral perfusion in craniosynostosis patients and its
change after surgery.
3. To understand the relation between local brain perfusion and the occurrence
of elevated ICP.

This will be an observational study: a prospective cohort study with a (nested)
case-control study.

First of all, patients need to visit the hospital to receive their MR scans;
this will take time and costs. While performing the MR scan patients will
receive general anaesthesia. Given the experience of our anaesthesiologists in
the childrens hospital and the safe environment in which this procedure will be
performed risks remain low. However, adverse events that can occur are seen
more frequently in children below one year of age than in older children,
mostly concerning respiratory events or ventilation problems.
Benefits
By performing MR scans in a broad selection of craniosynostosis patients a
better understanding of the underlying pathophysiology, particularly of the
elevated intracranial pressure and blood flow disturbances, will be achieved.
It could well be that detectable changes in blood flow precede the occurrence
of papilledema which is a late sign of elevated ICP. If this is the case, an
important change of the screening method during follow-up may be advised.
DTI focuses on the quality of white matter tracts in the brain and anomalies
were demonstrated in our syndromic craniosynostosis patients at age 6 to 12;
studying white matter quality in very young craniosynostosis patients will
reveal whether or not these changes are truly inborn. By linking MRI findings
with cognitive, language and motor development a better understanding of this
pathophysiology is acquired and would contribute to an optimal treatment of
these patients regarding counselling, type of surgery, timing of surgery and
even cognitive, language and/or motor function intervention.