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Title: The pathophysiology of chronic subdural haematoma and the role of the dexamethasone
Author: Edlmann, Ellie
ISNI:       0000 0004 8500 9484
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2019
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Chronic subdural haematoma (CSDH) is an encapsulated collection of blood and fluid overlying the surface of the brain, which is often treated with surgical drainage to prevent cerebral compression. Despite treatment it can recur, requiring further surgery and causing significant morbidity. Historically CSDH formation was considered to occur due to the ageing and expansion of acute bleeding following head trauma. However, within this thesis the natural progression of CSDH was assessed with serial imaging following trauma and highlighted the novel process of CSDH formation from a normal CT. This was hypothesised to occur through injury initiating inflammation within the subdural space which drives formation of a hypervascular membrane responsible for fluid and blood accumulation over time. This theory was investigated by examining 68 CSDH samples for the presence of selected inflammatory markers and haemoglobin concentration. All pro-inflammatory markers were significantly elevated in CSDH fluid compared to venous blood, particularly vascular endothelial growth factor (VEGF). Haemoglobin degradation products were quantified with UV-Vis spectroscopy and more recent haemorrhage indicated an increased CSDH recurrence risk. This work was performed alongside the Dex-CSDH trial, a randomised, placebo-controlled trial of the potent anti-inflammatory dexamethasone. Blinded interim results of the trial are discussed, but the main focus are the scientific, mechanistic sub-studies. A method for detecting dexamethasone in CSDH and blood was developed using high performance liquid chromatography (HPLC), and suggested there is no accumulation of the drug within the CSDH space. However, many of the inflammatory markers were reduced post-operatively following dexamethasone treatment. Volumetric and density analysis of pre-operative and post-operative imaging was also performed and may aid prediction of which patients are more likely to have a poor outcome or recurrence. This could help identify patients in the future who would benefit most from adjuvant therapies such as dexamethasone.
Supervisor: Hutchinson, Peter ; Carpenter, Keri ; Whitfield, Peter Sponsor: Royal college of Surgeons of England ; Rosetrees Trust ; National Institute of Health Research (NIHR)
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
Keywords: Head injury ; trauma ; subdural ; elderly ; dexamethasone ; inflammation ; neurosurgery ; surgery ; imaging