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Intracranial pressure (ICP) is an important component of the fluid dynamic environment of the brain and plays a central role with regards to the maintenance of normal cerebral blood flow and neuronal function. However, many regulatory mechanisms controlling the ICP are still poorly understood. One major gap in knowledge in this regard is the mechanism behind the postural/gravitational control of ICP. This is partly due to the fact that most ICP investigations are performed with the patients in a supine or recumbent position. Since most people spend 16 hours a day in an upright position, understanding these mechanics is highly motivated. Also spurring research on this topic is the increasing number of reports of the spaceflight-associated neuro-ocular syndrome (SANS) found in astronauts after prolonged exposure to weightlessness (i.e. microgravity), where evidence suggests that a disrupted balance between ICP and intraocular pressure (IOP) may be an underlying cause. Understanding how ICP is regulated with respect to posture could therefore provide important insight into the alterations introduced by microgravity, where postural effects are removed, and how to improve the safety of astronauts who are susceptible to this syndrome. Here on earth, disturbances in the ICP or cerebrospinal fluid (CSF) dynamics are associated with the development of chronic neurological diseases. One particular disease of interest is communicating hydrocephalus, where the cerebral ventricles are enlarged despite the absence of macroscopic CSF flow obstructions. A common finding in these patients is that of altered pulsatile flow in the CSF. The overall aim of this thesis was to utilize fluid dynamic principles to describe and validate potential regulatory mechanisms behind postural changes in ICP and causes of ventriculomegaly. The thesis is based on four scientific papers (paper I—IV).

A postural dependency of the IOP-ICP pressure difference was verified by simultaneous measurements of ICP (assessed through lumbar puncture) and IOP (measured with an Applanation Resonance Tonometer) (paper I). Based on these measurements, a 24-hour average of the IOP-ICP pressure difference at the level of the eye was estimated for the state of microgravity, predicting a reduced pressure difference in space compared with that on earth.

A hypothesis where postural changes in ICP are described by hydrostatic effects in the venous system, and where these effects are altered by the collapse of the internal jugular veins (IJVs) in more upright positions, was evaluated (paper II and III). Using ultrasound data, it was shown that the venous hydrostatic pressure gradient was balanced by viscous pressure losses in the collapsed IJVs to uphold a near atmospheric pressure at the level of the neck in the upright posture (paper II). A full evaluation of the hypothesis was then performed, based on simultaneous assessment of ICP, central venous pressure (through a PICC-line) and venous collapse in 7 postures of upper-body tilt in healthy volunteers (paper III).The proposed description could accurately predict the general changes seen in the measured ICP for all investigated postures (mean difference: -0.03±2.7 mmHg or -4.0±360 Pa).

Pulsatile CSF flow-induced pressure differences between the ventricles and subarachnoid space were evaluated as a source for ventriculomegaly in communicating hydrocephalus (paper IV). The pressure distributions resulting from the pulsatile CSF flow were calculated using computational fluid dynamics based on MRI data. The estimated pressures revealed a net pressure difference (mean: 0.001±0.003 mmHg or 0.2±0.4 Pa, p=0.03) between the ventricles and the subarachnoid space, over the cardiac cycle, with higher pressure in the third and lateral ventricles.

In conclusion, the results of this thesis support venous hydrostatics and jugular venous collapse as key governing factors in the postural/gravitational control of ICP. Furthermore, a postural dependency of the IOP-ICP pressure difference was demonstrated, providing a potential explanation for how an imbalance between the pressure of the eye and brain can be introduced in microgravity. Computational fluid dynamic analysis revealed that the altered pulsations in communicating hydrocephalus generate a pressure gradient within the CSF system. However, the gradient was small and additional effects are probably needed to explain the ventriculomegaly in these patients.