Vascular Investigation and Management of Ischaemic Stroke

Overell, James Richard (2002) Vascular Investigation and Management of Ischaemic Stroke. MD thesis, University of Glasgow.

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A variety of aetiological factors serve as targets for both treatment and prevention in ischaemic stroke. Research has shifted towards acute therapy and improving the risk / benefit ratio in secondary prevention. Current evidence based practice in ischaemic stroke is discussed in chapter one, and the background to subsequent chapters is introduced. The thesis is then divided into two broad areas that examine mechanisms by which vascular disease may cause ischaemic stroke, and the manner in which vascular risk may be modulated. Chapters two to four highlight controversies in investigation and management. Chapter two addresses a clinical dilemma - essentially whether a carotid lesion ipsilateral to a lacunar stroke should be considered symptomatic. Observational data comparing incidence of lacunar disease contralateral (group 1) or ipsilateral (group 2) to carotid artery disease, and stroke recurrence in patients in whom co-existent lacunar and carotid disease had been identified, were analysed. 32 patients had carotid disease contralateral to their lacunar stroke, compared to 61 patients with ipsilateral lacunar disease. Chi-squared testing indicated a positive association between unilateral lacunar stroke and ipsilateral carotid disease (p=0.003), and a just significant trend towards more severe carotid disease in group 2 (p=0.049). Recurrent ischaemic stroke occurred more commonly in group 2 than group 1, although this difference just failed to reach statistical significance (p=0.059). A positive association therefore exists between lacunar stroke and ipsilateral carotid disease that confers a poor prognosis. Cryptogenic stroke accounts for approximately 30% of ischaemic stroke. Inter-atrial septal abnormalities (patent foramen ovale (PFO) and atrial septal aneurysm) have been proposed as a cause of stroke. Chapter three details a meta-analysis of data examining the relationship between inter-atrial septal abnormalities and stroke. Comparing ischaemic stroke to controls, the odds ratio (OR) associated with PFO for all ages was 1.83 (95% C.I.=1.25-2.66). For atrial septal aneurysm it was 2.35 (1.46-3.77), and for both lesions in conjunction it was 4.96 (2.37-10.39). Homogeneous results were found within the group 55 years (1.27 (0.80-2.01), 3.43 (1.89-6.22) and 5.09 (1.25-20.74) respectively). Comparing cryptogenic stroke patients to patients with known stroke cause, heterogeneous results derived from total group examination (PFO 3.16 (2.30-4.35), atrial septal aneurysm 3.65 (1.34- 9.97), PFO and atrial septal aneurysm 23.26 (5.24-103.20)). In those <55, for PFO the OR was 6.00 (3.72-9.68) with only one study examining atrial septal aneurysm or combined lesions. In those >55, 3 studies produced heterogeneous results for PFO (2.26 (0.96-5.31)), while no data were available on atrial septal aneurysm prevalence. Meta-analysis therefore demonstrates significant association between both PFO and atrial septal aneurysm and ischaemic stroke in patients <55 years. Further studies are needed to firmly establish whether an association exists between PFO and ischaemic stroke in those >55 years. The climate of uncertainty that surrounds the subject of 'PFO-associated stroke' has led to a wide spectrum of practice amongst specialists, which is examined in chapter four, using a questionnaire. 17% of respondents would investigate for PFO in all cryptogenic stroke patients, while 60% investigate only in those <55 years. 23% would not investigate for PFO at all. Antiplatelet therapy alone was chosen as an initial strategy by 47% of respondents for those >55 years, and by 33% of respondents for those <55 years (p<0.01 for comparison of proportions). In a patient of any age with recurrent events, less than 5% of respondents would continue to use antiplatelet therapy alone. 45% would use warfarin, and 42% would refer the patient for a corrective procedure. For a patient with a large PFO, 57% (55 years) would refer (p=0.01), and for a patient with concomitant atrial septal aneurysm, 62% (55 years) would refer (p<0.01). A large PFO was felt to be the most important factor in decisions regarding lesion correction. Investigation practice varied considerably amongst specialists. Randomised trial design should reflect management practice in this area. The second part of the thesis reports clinical trials designed to examine the manner in which agents aimed at the modification of vascular risk may act in the acute and subacute phase of ischaemic stroke. The cholesterol- independent effects of statins may explain their efficacy in patients at high vascular risk. (Abstract shortened by ProQuest.).

Item Type: Thesis (MD)
Qualification Level: Doctoral
Additional Information: Adviser: Iain Sim
Keywords: Medicine
Date of Award: 2002
Depositing User: Enlighten Team
Unique ID: glathesis:2002-75764
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 19 Nov 2019 18:14
Last Modified: 19 Nov 2019 18:14

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