Dynamics of cerebral fluids in patients suffering from hydrocephalus and pseudotumour cerebri
University of Cambridge
Doctor of Philosophy (PhD)
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Lalou, D. (2019). Dynamics of cerebral fluids in patients suffering from hydrocephalus and pseudotumour cerebri (Doctoral thesis). https://doi.org/10.17863/CAM.53189
This dissertation is devoted to dynamics of brain liquids in patients with altered CSF circulation and pressure-volume compensation. Since the introduction of intracranial pressure (ICP) monitoring, the studies of CSF dynamics have revealed unique information about the intracranial circulation and opened new opportunities for diagnosis and treatment of hydrocephalus and pseudotumour cerebri. The adaptation of infusion tests in clinical practice over 45 years ago has introduced a practical tool to benefit both patients and research into altered CSF dynamics. Objective testing of intracranial circulation in patients with clinical symptoms constitutes a unique situation, where the discovery of new patterns and reasons for disturbed intracranial circulation can be quantified. Such macroscopic yet practical quantifications can easily be translated to clinically useful information, and back, in real time or alternative past and future synchronicities. The aim of this dissertation is to demonstrate the value of testing CSF dynamics in vivo and how it could provide pathophysiological and clinical insights into hydrocephalus and pseudotumour cerebri syndrome (PTCS). My intention was to describe and reflect the main themes involved in the study of CSF dynamics: a) their role in diagnosis and treatment, b) their use in understanding shunts and shunt malfunction c) the need to optimise our understanding of the contents of ICP, meaning that long-term ICP monitoring or dynamic tests are required in CSF disorders, not snapshot ICP measurements and finally d) the mapping and quantification of the interaction between CSF circulation and cerebral blood flow (CBF). As the above foundations and results of my work lead to the formation of a required, albeit expected, long doctoral treatise, I have structured the later in 9 chapters containing a comprehensive literature review of the Resistance to CSF outflow as well as a systematic literature review of the CBF and autoregulation of the CBF in NPH. I have also dedicated a methods chapter, Chapter 3, into introducing and explaining the variable tested during a CSF infusion test, such as the fundamental amplitude of ICP and the compensatory reserve indices. Following this is the presentation of the data and clinical material used for my original projects. Specifically, my results contain the following: I) Autoregulation of cerebral blood flow in hydrocephalus CSF infusion tests provide a unique setting where both ICP and cerebral blood flow and autoregulation can be measured in ambulatory patients utilising many different methods. Autoregulation has been studied by quantifying the interaction between the CSF and cerebral blood circulation has revealed diagnostic and outcome implications that could perhaps describe the natural course of a CSF disorder, or differentiate between a CSF disorder and a vascular disorder, or the coexistence of the two, opening new chapters to the comprehension of shunt responsive NPH. I have explored the state of global autoregulation in patients undergoing infusion tests, in an attempt to set out a reference for investigations related to NPH, Resistance, autoregulation and their clinical implications. In the 5th chapter, I have: • Described the relationship between Rout, cerebral autoregulation and arterial blood pressure. Rout demonstrates a negative linear relationship with global autoregulation. When I combined these parameters and accounted for the patients’ age, I was able to show a good correlation with outcome, much improved compared to Rout alone. II) CSF dynamics in normal pressure hydrocephalus and pseudotumour cerebri. CSF dynamics in different conditions have shown that parameters such as the Resistance to CSF outflow in NPH and ICP at baseline combined with compensatory reserve indices in PTCS, could provide important diagnostic and management information. This could be a valuable addition of objective evidence to imaging and clinical examination. Using large cohorts of patients, I have explored the Resistance to CSF outflow (Rout) in NPH in the context of different aetiologies of NPH, its relationship with age as well as its overall correlation with outcome after shunting. I have also explored these relationships in relevance to clinical practice. In PTCS, I have described the findings from infusion tests in both adult and paediatric patients and have highlighted the differences with hydrocephalus. In chapter 6, , I have described the following: • Davson’s equation in NPH: The so-called Davson’s equation describes the relationship between ICP, Rout, CSF formation rate and sagittal sinus pressure under physiological circumstances. I have validated the existence of such a linear relationship in NPH. • CSF dynamics in post-traumatic hydrocephalus: Traumatic brain injury, as a cause of secondary NPH, shows some differences in Rout and ICP amplitude compared to idiopathic NPH. I have also described the effect of decompressive craniectomy and of cranioplasty on CSF dynamics. In chapter 7, I have explored the CSF dynamics of PTCS and in particular: • The coupling between CSF pressure and Sagittal sinus pressure (SSp) in PTCS patients at baseline and during infusion tests. I have also shown how this relates to Davson’s equation under an unstable SSp and the possible pathophysiological consequences of this finding. • The CSF dynamics of paediatric patients with PTCS. Those included all patients assessed in Cambridge and classified as definite, probable and not PTCS. III) Shunt testing in vivo. Shunts are currently the mainstay for the management of hydrocephalus, as well as an important part of the management of PTCS. They change CSF dynamic parameters in a way that is easily assessed with shunt infusion tests. The knowledge of the post-shunting CSF circulation contains crucial information on the state of the shunt function, as well as the adequate restoration of the patients’ intracranial circulation. I have described how objective knowledge from shunt testing in vivo impacts clinical practice and patients’ outcomes. In chapter 8, I have presented two studies about testing shunt function in-vivo: • Shunt testing in vivo using infusion tests is important in avoiding unnecessary revisions of patent shunts and allows patients to be managed conservatively, with good outcomes. This also translates to financial benefits for healthcare systems. • In paediatric hydrocephalus, shunt infusion studies are an accurate and useful tool for investigating insidious shunt obstruction. IV) Slow waves of Intracranial Pressure. Reliable, long-term overnight monitoring is the gold standard in monitoring and analysing ICP and its contents. Slow waves, compensatory reserve and relationship with the venous circulation contain reliable information that are again correlated to clinical practice and can be compared and incorporated into the shorter-term infusion test. I have explored the behaviour of slow waves in anaesthetized patients In chapter 9, I have investigated the influence of general anaesthesia on slow waves of ICP in NPH and traumatic brain injury (TBI) patients. Conclusion: Infusion tests are a practical tool for research and possibly diagnosis and treatment in patients with PTCS and NPH. CSF dynamics provide a quantitative description of cerebral pathophysiology in CSF disorders, both for CSF and potentially for cerebral blood flow. After shunting, infusion tests are a reliable and cost-effective tool for identifying or excluding shunt malfunction. Further studies are needed to verify the clinical implications of CSF infusion tests and cerebral blood flow and autoregulation in those patients.
cerebrospinal fluid, neurosciences, cerebral blood flow, cerebral autoregulation, hydrocephalus, normal pressure hydrocephalus, idiopathic intracranial hypertension, pseudotumour cerebri, dementia, intracranial pressure, csf dynamics, csf infusion test
This record's DOI: https://doi.org/10.17863/CAM.53189