The Measurement and Interpretation of Intracranial Pressure

Abstract

The intracranial pressure (ICP) is the most commonly monitored brain parameter in neurocritical care. Its rise, which may be benign, acute or chronic, is a common yet serious problem. ICP can rise because of a number of critical medical conditions such as hydrocephalus, traumatic brain injury, intracranial mass lesions, brain swelling, disturbances in CSP circulation and/or its production and reabsorption cycle, choroid plexuses tumours, idiopathic intracranial hypertension, and more diffused intracranial pathological processes. Monitoring and treatment of raised ICP in patients currently focuses on curtailing the mean ICP below a pressure threshold(s) of 15-20 mmHg depending on the cause of ICP rise. However, there is growing evidence that understanding ICP signal dynamics may provide additional information to assist with diagnostic and treatment decisions. In early 1900's Harvey Cushing provided evidence of the 'Cushing's response' where large increases in mean ICP (>50 mmHg) produced matching increases in blood pressure, such that cerebral perfusion pressure remained almost constant. This implied that within a rigid cranium, the cerebral circulation is limited in its ability to expand and accommodate an increase in blood volume. Thus, making blood supply pressure or cerebral perfusion pressure (CPP) to the brain a key determinant of brain blood flow. In addition, an emerging new hypothesis in cardiovascular control proposes that the brain puts utmost priority on maintaining its own blood supply, even at the expense of high blood pressure to the rest of the body. Furthermore, the increased sympathetic tone is associated with many cardiovascular diseases, but its origins are not clearly understood. Therefore, finding a causative link between ICP dynamics and arterial pressure (AP, i.e. AP-ICP=CPP) may depend upon understanding how changes in cerebral perfusion pressure affect the sympathetic nervous system. We know that the regulation of ICP and CPP is fundamental for normal brain functioning. However, the interactions between AP and ICP under normal physiological conditions (i.e. healthy condition) are not well understood, but we postulate they may be sympathetically driven. In humans, our understanding of normal ICP dynamics, its regulation, and relationship with physiological signals such as AP and sympathetic nerve activity are extremely limited. There have been no reported recordings of ICP in healthy individuals uncomplicated by trauma or chronic illness. Thus, an animal model permitting the chronic measurement and controlled manipulation of ICP and blood pressure would lend itself to a range of applications and improve our understanding of the healthy ICP dynamics, its regulation and relationship with other physiological signals. I am addressing the gaps (as mentioned above) in the understanding of healthy and unhealthy ICP dynamics, their relationship with AP and the sympathetic mediation in such relationships, in this thesis. Using signal processing and analysis techniques on chronic ICP, AP, and renal sympathetic nerve activity signals collected from healthy and unhealthy conscious animals. Such chronic recordings enable the dynamic and steady-state analysis of interactions amongst these signals during disease development and under healthy conditions within the same animal, and minimises the variability in physiological parameters and make the analysis meaningful and robust. The overall objective is to use the knowledge thus obtained to advance the understanding of ICP dynamics and contribute to improving the treatment and management of patients with high ICP in neuro-critical care due to hydrocephalus. To investigate ICP dynamics and its relationships with AP under normal and Kaolin induced hydrocephalic (high ICP) conditions in conscious rats, the chronic recordings of ICP and AP signals were analysed in time and frequency domains. To explore the AP- ICP relationship under control and hydrocephalic conditions, the signal transmission gain (for the AP-ICP system) was calculated at physiologically significant frequency bands. The analysis revealed that increased mean ICP decreased cranial compliance and allowed previously filtered (under healthy conditions) higher frequency cardiac oscillations from AP to be transmitted into ICP. In addition, similar results indicating a decreased cranial compliance with increased mean ICP were found in our experiments in conscious (saline infused hydrocephalic) sheep, based on the time and frequency analysis of their ICP and AP signals. Another objective of this research was to continue the development of ICP system analysis methods to incorporate physiological signals like renal sympathetic nerve activity to advance our understanding of ICP waveform and explore its connection with them. During this project, I evaluated the possibility of AP control by ICP via renal sympathetic nerve activity at physiological mean ICP levels in conscious sheep and verified the existence of ICP-AP closed loop feedback system to enhance our understanding of the endogenous regulation of AP and the ICP related pressor response. More specifically, increased mean ICP within physiological levels produced linearly matched increase AP (in conscious sheep), and not just at pathological elevated ICP levels as conventionally thought. Overall, this thesis has resulted in better understanding of ICP waveform dynamics, the novel discovery of its pressor response at physiological levels and the verification of sympathetic mechanism mediating such pressor response in healthy conscious sheep. I hope that such advances will contribute towards the improvement of treatment of patients with high/disturbed ICP.