Cranial Content Changes in Craniosynostotic Rabbits

Wendy Kay Fellows-Mayle

PhD Thesis 2004

Cranial base and vault deformities in individuals with craniosynostosis are thought to be related, in part, to changes in intracranial pressure (ICP). However, this relationship remains unclear due to patient heterogeneity and variable surgical intervention techniques and timing. A longitudinal study of ICP changes in a homogenous rabbit model of familial coronal suture synostosis has been performed. Results from this study have shown a significant increase in ICP at 25 days of age, which drops to control levels by 42 days of age without surgical intervention in a large sample of affected rabbits. This decrease in ICP suggests that compensatory changes are occurring within the cranium of rabbits with coronal suture synostosis.

The present study was designed to quantitatively investigate compensatory changes in intracranial contents in rabbits with coronal suture synostosis and compare these changes with those incurred during normal brain growth in non affected rabbits. There are three groups in the study: wild-type rabbits (n=6); rabbits with delayed-onset synostosis of the coronal sutures (n=6). MRI of the intracranial contents was performed in three anatomic planes at or near 10, 25, and 42 days of age. Spin echo magnetic resonance images were acquired at 1mm intervals.

The images were used to calculate the size and intracranial indices of the brain parenchyma, the volume of brain parenchyma and cerebrospinal fluid spaces, and the area of the venous sinuses. Cranial base length measurements, cranial base angles, and skull thickness near the coronal suture were obtained as well. Immediately following MRI, ICP measurements were obtained from four rabbits per group. ICP was obtained for a total 20 minutes. Measurement of volumes, areas, lengths, and angles was performed using Image J software. The use of MRI enabled the visualization of brain morphology that had not previously been investigated in craniosynostotic rabbits.

Results of the present study have demonstrated several factors craniosynostotic rabbit brain morphology which were previously unknown. These include the enlargement of the lateral ventricles and the possible progressive obstruction of the venous sinuses. Volumetric changes in brain parenchyma and cerebrospinal fluid pathways, changes in cranial base length and skull thickness near the coronal suture were compared among groups and correlated to changes in ICP using Path Analysis. Path analysis was performed on the three groups studied to analyze the three most prevalent theories regarding the primary source of craniosynostosis. The three models proposed were the Hyperostosis Model, the Cranial Base Model, and the Brain Parenchyma Model.

Based on the results of path analysis in the present study, premature fusion of the coronal sutures seems to be the primary locus of changes in craniosynostotic rabbits. This premature fusion was most closely related to a decrease in the length of the cranial base. These two factors combined probably result in brain morphology changes seen in the present study. These changes include an overall decrease in the size of the brain, an increase in the size of cerbrospinal fluid pathways, and an increase in intracranial pressure. The results of the present study suggest that there are several mechanisms at work in the cranium of craniosynostotic rabbits and had given possible insight into the causal pathway of craniosynostosis.