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Title: Inflammation and delayed cerebral ischaemia induced byaneurysmal subarachnoid haemorrhage
Author: McMahon, Catherine Jane
ISNI:       0000 0001 3625 7623
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2008
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Stroke is a sudden, unpredictable, often devastating neurological event. The commonest cause of morbidity and mortality associated with subarachnoid haemorrhage (SAH) is delayed cerebral ischaemia (DCI). Ischaemic and haemorrhagic strokes are recognised to induce a significant peripheral and central inflammatory response. These responses may be important in the exacerbation of ischaemic damage and in the development and exacerbation of DCI after SAH. A number of studies have examined the potential contribution of pro-inflammatory cytokines, such as interleukin-l (IL-l) and interleukin-6 (IL-6), to damage caused by experimental ischaemia. Intracerebroventricular (ICV) injection of interleukin-lP(IL-l P) causes a marked exacerbation of ischaemic damage in experimental paradigms of cerebral ischaemia. Conversely, administration of the cytokine anatgonist, interleukin-l receptor antagonist (ILlRA), or other inhibitors of IL-l release and action confer neuroprotection; The aim of this work was to test two primary hypotheses, namely (1) circulating markers of inflammation, (specifically, C-reactive protein (CRP), IL-6 and IL-lRA) predict the development of DCI after SAH, and (2) that there is a direct relationship between peripheral and central inflammation. Clinicai predictors of any cerebrovascular event, and outcome after SAH, were also determined. In a prospective study of 179 aneurysmal SAH patients between January 2004 and August 2007, plasma samples (and in 25 patients CSF samples) were obtained over a period of 15 days after SAH. Levels of inflammatory markers and presence· or absence of DCI was determined. In case-control analysis of 159 patients, only rate of change of IL-6 (OR 2.3, CI 1.1 to 5, pO.03) was predictive of DCI. In a secondary analysis of Erythrocyte sedimentation rate (ESR) and WCC, initial ESR (OR 2.4, CI 1.3 to 4.6, pO.006) average ESR (OR 2.3, CI 1.3 to 4.2, pO.006), peak ESR (OR 2.1, CI 1.1 to 3.9, pO.02) and final ESR (OR 2.0, CI 1.2 to 3.3, pO.009) in addition to final WCC (OR 1.2, CI 1 to 1.3, pO.Ol) and rate of change of WCC (OR 1.3, CI 1 to 1.6, pO.OS) were significantly associated with the development of DCI. A direct relationship was not demonstrated between peripheral and central inflammation. In unifactorial analysis of the 179 patient cohort, female sex (HR 1.8, CI 1 to 3.1, pO.04) hypertension (HI3-Z-,_CL1)_J.Q__~:;?,. pO.OOS), statin use (HR 2, CI 1 to 3.8, pO.04), infection peri-study (HR 1.9, CI 1.2 to 3.0, pO.007), increasing WFNS grade (II & III, HR 2.5, CI 1.5 to 4.2, pO.OOO; IV & V, HR 3.8, CI 2to 7.3, p
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available