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Title: Prediction, detection and suppression of cerebral microemboli associated with carotid disease
Author: Saedon, Mahmud H.
ISNI:       0000 0004 5915 5584
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 2015
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Background Transient cerebral microemboli detected by transcranial Doppler (TCD) have been demonstrated to be a reliable biomarker for short term stroke risk in two clinical settings; patients with carotid artery stenosis and those following carotid endarterectomy. Suppressing cerebral microemboli using TCD-directed antiplatelet treatment reduces risk of recurrent stroke. The association between classical cardiovascular risk factors and cerebral microemboli has not been studied. Furthermore, standard TCD method to detect cerebral microemboli is limited by lack of acoustic temporal bone window which is not available in approximately 1 in 7 patients. TCD is the only real-time imaging modality for detecting microemboli. The demonstration of the kinetic of the microemboli is invaluable in assessing the efficacy of antiplatelet agents. Hypotheses 1. Whether Pocock cardiovascular risk score and ABCD2 risk score are able to predict the presence of cerebral microemboli. 2. The feasibility of using transorbital Doppler as an alternative to transcranial Doppler. 3. The effectiveness of Tirofiban in suppressing cerebral microemboli. Methods 1. Pocock score was assessed for the newly developed Carotid Surgery Registry of 670 patients managed between January 2002 and December 2012. 2. ABCD2 score was determined in 206 patients with hyper-acute symptomatic critical carotid artery stenosis in which 102 of these patients were from Registry. A further 104 consecutive patients were recruited between February 2011 and May 2013 within a new prospective observational study. 3. The feasibility of using transorbital Doppler was assessed based on the Registry data. Further new prospective validation study of transorbital Doppler against standard TCD method involving 100 consecutive patients undergoing elective carotid endarterectomies were undertaken. 4. From the Registry, patients who had microembolic signals acutely following carotid surgery were assessed to evaluate the effectiveness of Tirofiban in suppressing microemboli. Findings 1. A high Pocock score (≥ 0.8%) predicts presence of cerebral microemboli acutely following carotid endarterectomy (Area Under Curve (AUC) 0.582 95% CI 0.507 – 0.658, P = 0.038). It also showed a high sensitivity for the presence of microemboli in patients with hyper-acute symptomatic carotid artery disease. 2. The ABCD2 score did not predict presence of cerebral microemboli ((AUC 0.49 95% CI 0.41 – 0.57, P = 0.860), or carotid disease in over one-quarter of patients with symptomatic critical carotid artery stenosis. 3. Transorbital Doppler imaging appears a valid alternative to transcranial Doppler for detecting microembolic signals in patients with no suitable temporal acoustic window (sensitivity 80 %, specificity 86 %. Bland and Altman analysis revealed no significant bias [bias 0.11 microemboli (95% CI: -0.52 to 0.74), P = 0.81]). 4. Tirofiban has been shown to be more effective in treating microemboli in comparison to other most commonly used antithrombotic agents. The time for complete microemboli resolution (Tirofiban 68 minutes (53-94); dextran 113 (79-146); or in controls 53(49-68); P<0.001, KW) were shorter with tirofiban.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: RC Internal medicine