Chiari malformation type I is a disorder in which the cerebellar tonsils herniate through the foramen magnum. A majority of patients with this condition also develop a fluid filled cavity (syrinx) within the spinal cord. Syrinxes are associated with both sensory and motor disturbances, with extreme cases leading to autonomic dysfunction. The mechanisms that lead to the accumulation of fluid remain unknown. There is no universally accepted treatment and current surgical treatments have variable, but often unsatisfactory, outcomes and side effects are common. There is a need to understand cerebrospinal fluid (CSF) circulation in Chiari malformation to identify the mechanism(s) that cause syrinx formation. This would enable a mechanistically based treatment to be developed.

This thesis presents six interrelated studies investigating CSF circulation and the influence of tonsillar herniation on CSF dynamics, to better understand potential mechanisms for syrinx formation. Methods used include novel real-time magnetic resonance imaging (MRI) of CSF and blood flow, morphological assessments of anatomical MRI, subject-specific computational models of the spinal subarachnoid space, and idealised models of the perivascular space.

The subject-specific models showed that in Chiari patients the peak systolic CSF pressure was increased and occurred earlier in the cardiac cycle, compared with controls. The perivascular space model suggested that these subarachnoid pressure characteristics may cause increased flow into the cord that is favourable for syrinx formation in Chiari patients. Increased overcrowding below the foramen magnum in syrinx free subjects led to an earlier systolic pulse, whereas in syrinx subjects it caused a delay. This difference in behaviour may be related to syrinx patients having a smaller midsagittal cross-sectional area and could explain why not all patients develop a syrinx. Real-time imaging of CSF flow in controls were inconsistent with the currently accepted mechanism for respiratory CSF circulation, suggesting instead that respiratory CSF flow is primarily dependent on the balance of the thoracic and lumbar spinal pressures. Real-time imaging in Chiari patients found coughing and straining produced high velocity cranial flow at the foramen magnum, which may be a marker for Chiari associated headache, but whether this influences syrinx formation requires further investigation.