M.Sc.(Med.), Faculty of Health Sciences, University of the Witwatersrand, 2008 / Introduction It is widely recognised that stroke is a multi-factorial disorder in which platelets play a crucial role in thrombus formation resulting in ischaemic stroke. Platelet adhesion and aggregation are initiated by the interaction of various platelet glycoproteins (GP’s) such as GPIbα, which binds to von Willebrand Factor and GPIIb/IIIa a fibrinogen receptor. Recent studies have shown that the GP’s are polymorphic and the polymorphisms described within GPIbα such as Kozak- 5T/C, the variable number of tandem repeats (VNTR) and the Human Platelet antigen 2 (HPA2), have been implicated in the development of stroke, while the PIA polymorphism of GPIIb/IIIa was found to contribute to “aspirin resistance”. Therefore, these polymorphisms may be potentially important for early detection and early intervention and thus setting the need to provide for a high volume genotype testing at health care centres. One of the most used techniques to determine platelet function is platelet aggregometry. However, the major disadvantages of platelet aggregation is that it is influenced by a number of environmental factors and its access is limited to tertiary health centres. Platelet aggregation measures the functional expression of platelets, which is known to deteriorate over time. It is for this reason that new methods at molecular level such as polymerase chain reaction (PCR) are needed to explore the role of genotypic expressions, which are not influenced by environmental factors. Currently, conventional PCR is used to detect platelet polymorphisms in the research settings and has limitations as a routine diagnostic test. Furthermore, it is time consuming and is prone to contamination. With the recent advances in real-time PCR it is possible to genotype large sample batches rapidly without compromising on the quality, accuracy and precision of results. This study aims to adapt conventional PCR methodology onto a real-time platform for detecting platelet polymorphisms that have been implicated in both stroke and aspirin resistance. Materials and methods A total of 60 caucasian patients classified as having ischaemic stroke by virtue of MRI and Doppler analysis from the Stroke Clinic at the Johannesburg Hospital were enrolled for this study. Healthy caucasian individuals (38), age and gender matched were enrolled as controls. DNA samples were extracted from all the subjects and the prevalence of the Kozak –5T/C, HPA-2, VNTR and GPIIIa PIA polymorphisms were determined first by using conventional PCR and then the real-time LightCycler TM PCR method. Results The frequency of the unfavourable alleles ( the PIA2 allele for the GPIIIa PIA polymorphism, the T allele for the Kozak –5T/C polymorphism, the B allele for the HPA-2 polymorphism and the C allele for the VNTR polymorphism) of the different GP’s were higher in the stroke patients when compared to the control subjects but did not reach statistical significance. There was complete statistical agreement between the results obtained for the conventional PCR as compared to the results obtained for real-time PCR except for the VNTR polymorphism, due to the difficulty in designing and the unavailability of probes for the real-time PCR assay. However, it is important to note that adapting the real-time PCR as a new methodology would greatly benefit both the patients and the clinicians by providing early detection and the possibility of early therapeutic intervention. Conclusion Therefore in conclusion, it is possible to perform not only conventional PCR for platelet polymorphism but also real-time PCR on a large scale without compromising on the quality, accuracy and precision on platelet polymorphisms that play a significant role in stroke and aspirin resistance. However, a larger population based study needs to be performed to confirm the findings.

Short Report submitted to the Faculty of Health Sciences, University of the Witwatersrand, in fulfillment of the requirements for the degree of Master of Science in Occupational Therapy Johannesburg 2017 / This research project described the outcomes for upper limb motor function (ULMF) and personal management (PM) for patients attending occupational therapy at Chris Hani Baragwanath Academic Hospital post-stroke. A quantitative, descriptive correlation design was used. A purposive sample of adult patients who met the inclusion criteria was selected. The researcher completed initial assessments of ULMF using the Fugl–Meyer assessment and the South African Data for Functional Measurements: Beta Scale to assess independence in PM. Research participants received rehabilitation as usual. The same measurements were administered on discharge and during out-patient follow up appointments at one, two and three months. Data was analysed using descriptive statistics. Results indicated that recovery of ULMF was influenced by the site of lesion. Gender and age did not influence recovery of ULMF. Severe motor disability, which resulted in poor recovery of UL and LL, yielded poor independence in PM. / MT2017

"Magnetic resonance imaging (MRI) has emerged as the imaging modality of choice in a wide variety experimental and clinical applications. In this dissertation, I will describe novel MRI techniques for the characterization of neural and pulmonary vascular function in preclinical models of disease. In the first part of this dissertation, experimental results will be presented comparing the identification of ischemic lesions in experimental stroke using dynamic susceptibility contrast (DSC) and a well validated arterial spin labeling (ASL). We show that DSC measurements of an index of cerebral blood flow are sensitive to ischemia, treatment, and stroke subregions. Further, we derived a threshold of cerebral blood flow for ischemia as measured by DSC. Finally, we show that ischemic lesion volumes as defined by DSC are comparable to those defined by ASL. In the second part of this dissertation, a methodology of visualizing clots in experimental animal models of stroke is presented. Clots were rendered visible by MRI through the addition of a gadolinium based contrast agent during formation. Modified clots were used to induce an experimental embolic middle cerebral artery occlusion. Clots in the cerebral vasculature were visualized in vivo using MRI. Further, the efficacy of recombinant tissue plasminogen activator (r-tPA) and the combination of r-tPA and recombinant annexin-2 (rA2) was characterized by clot visualization during lysis. In the third part of this dissertation, we present results of the application of hyperpolarized helium (HP-He) in the characterization of new model of experimental pulmonary ischemia. The longitudinal relaxation time of HP-He is sensitive to the presence of paramagnetic oxygen. During ischemia, oxygen exchange from the airspaces of the lungs to the capillaries is hindered resulting in increased alveolar oxygen content which resulted in the shortening of the HP-He longitudinal relaxation time. Results of measurements of the HP-He relaxation time in both normal and ischemic animals are presented. In the final part of this dissertation, I will present results of a new method to measure pulmonary blood volume (PBV) using proton based MRI. A T1 weighted, inversion recovery spin echo sequence with cardiac and respiratory gating was developed to measure the changes in signal intensity of lung parenchyma before and after the injection of a long acting intravascular contrast agent. PBV is related to the signal change in the lung parenchyma and blood before and after contrast agent. We validate our method using a model of hypoxic pulmonary vasoconstriction in rats."

BACKGROUND: Moyamoya disease (MMD) is a chronic, occlusive cerebrovascular disease characterized by progressive stenosis of intracranial arteries, specifically the internal carotid arteries, and the compensatory formation of an abnormal vascular network at the base of the brain. The exact cause of MMD is still not well understood. Many factors including genetic, environmental, and immunologic have been associated with the disease. RNF213 is considered the main susceptibility gene, especially in Eastern Asian patients. The founder mutation, p.R4810K, has been associated strongly with MMD, especially in Japan and Korea but has been shown to have low penetrance and has never been described in non-Eastern Asian MMD cases. RNF213 encodes for an E3 ubiquitin-protein ligase with ATPase activity. It has described to regulate angiogenesis giving rise to the possibility that variants in RNF213 may play a role in cerebrovascular diseases other than MMD. OBJECTIVES: The aims of this study were to determine if variation in the RNF213 gene contributes to MMD in a cohort of 15 unrelated patients with MMD of predominantly European descent, to investigate other potential genes implicated in MMD in these 15 patients, and to investigate if RNF213 also influences more common vascular phenotypes. METHODS: Patient history, detailed family history and a blood sample were collected from 15 patients with well-characterized MMD. DNA was extracted from a peripheral venous blood sample, assessed for quality, and DNA concentration quantified by PicoGreen®. The extracted DNA was sent for whole exome sequencing. Genome_GPS_2.0 was used to carry out secondary analysis of sequencing data and all data were stored in Oracle TRC. The files were aligned using Novoalign, variants analyzed using GATK, visualized using IGV and annotated using BioR-Web. Variants of interest were determined using Ingenuity® Variant Analysis™. To determine if RNF213 also influences more common vascular phenotypes, previously collected and whole exome sequenced samples from the Mayo Clinic Florida Familial Cerebrovascular Diseases Registry were analyzed. Variants in RNF213 were determined using the same approach as for MMD. RESULTS: Likely pathogenic variants in RNF213 were found in 13% (2/15) of patients. The p.R4810K variant has been previously published as the founder mutation for MMD in Eastern Asian populations. The affected patient was also of Eastern Asian origin. The other variant, p.R4019C, was found in a European descent case and has been described as a candidate pathogenic variant. Eight variants in five other genes previously associated with MMD were found. Of these, one previously reported variant, p.D455H in RPTN, was found in two patients. The other seven have not previously been described in MMD. In the analysis of the potential role for RNF213 in other cerebrovascular diseases, 54% (22/41) of African American patients had a non-synonymous, exonic variant in RNF213 with a MAF of less than 3%. A novel RNF213 variant was also found in a Caucasian patient who had a subarachnoid hemorrhage. CONCLUSION: The p.R4810K variant in RNF213 was confirmed to only be associated with MMD in Eastern Asians and not found in other ethnicities. However, a variant in RNF213 was found in a Caucasian patient suggesting RNF213 may indeed be disease causing in patients of diverse origin. RNF213 may also be implicated in other cerebrovascular diseases suggesting a common pathogenesis while other genes also appear to be involved in the pathogenesis of MMD.

Stroke is one of the leading causes of death and disability worldwide with 20% of ischemic strokes attributed to carotid atherosclerosis. In recent years, morphological characteristics of atherosclerotic plaque such as a thin fibrous cap, large lipid-rich necrotic core, intraplaque haemorrhage and ulceration have shown correlations with subsequent clinical events. High resolution, multi-contrast magnetic resonance imaging (MRI) can qualitatively identify these features and monitor disease progression. Compared to traditional contrast weighted imaging, quantitative MRI could provide an objective assessment of disease. Therefore, the general hypothesis investigated in this thesis is: Quantitative MRI methods can be used to acquire objective biomarkers of carotid vessel wall and atherosclerotic plaque, with high accuracy and good repeatability. The research presented in this thesis describes the use of multiple quantitative MRI methods to evaluate the carotid vessel wall. These include dynamic contrast-enhanced (DCE) MRI analysis for the assessment of plaque inflammation/neovascularization and the development of black-blood quantitative T2/T2* mapping sequences for plaque component characterisation. The acceleration of the sequences was also investigated using a combination of compressed sensing (CS) and parallel imaging (PI). Chapter 3 investigated the hypothesis that plaque functional characteristics and surface morphology can be evaluated using a high temporal and spatial resolution 4D contrast-enhanced MRI/MR angiography (MRA) sequence. Chapter 4 tested the hypothesis that magnetisation prepared 3D fast-spin-echo (FSE) is the best sequence for in vivo T2 mapping. Four different black-blood T2 mapping sequences were developed and compared in phantom and volunteers. Chapter 5 tested the hypothesis that the optimised iMSDE 3D FSE T2 mapping sequence can be combined with CS and PI to further reduce the acquisition time without significantly affecting image quality and the measured T2 relaxation times. Chapter 6 investigated the hypothesis that compressed sensing can be used to reduce the overall examination time of a comprehensive multi-contrast MRI protocol, comprising black-blood T1 weighted, T2 weighted and proton density weighted sequences. Finally, Chapter 7 investigated the hypothesis that accurate 3D vessel wall R2* mapping can be achieved through black-blood preparation. In summary, this thesis investigated the use of multiple quantitative MRI methods in evaluating the carotid vessel wall and atherosclerotic plaque. The results demonstrate that quantitative MRI is an accurate and reproducible method for the carotid plaque characterization.

大动脉闭塞性疾病是脑卒中常见病因，包括颅内外狭窄性血管病变。本研究旨在分析卒中患者颅内外大动脉狭窄斑块的血管造影特征以及相关治疗方案。进一步了解颅内斑块的形态学变化，以及颅外大动脉狭窄的血管造影特征和侧枝循环状态，对于研究其发病机制及临床治疗有指导意义。 / 研究目的 / 研究1：通过前瞻性纵向研究，利用三维旋转血管造影（3D-RA），探讨颅内斑块形态学变化。 / 研究2：通过病例对照研究分析症状性放射性闭塞性血管病变(ORV)的血管造影特征及侧枝循环状态。 / 研究3：通过病例对照研究分析放射性血管病变（RIV）患者进行颈动脉支架治疗（CAS）后血管造影特征及临床预后。 / 研究方法 / 研究1：24例颅内重度狭窄(>70%)的急性缺血性卒中患者，严格控制其危险因素，应用3D-RA研究其发病时及12个月后颅内斑块的形态学变化。 / 研究2：分析96例ORV以及115例非放疗所致严重颈动脉狭窄（>70%）的缺血性卒中患者血管造影特点，比较其病变分布，形态学改变及侧枝循环状态。 / 研究3：比较63例ORV以及87例动脉粥样硬化性颈动脉狭窄的卒中患者的血管造影及预后。主要终点事件包括短暂性脑缺血发作，卒中和死亡。次要终点事件为24个月时支架内再狭窄。 / 结果 / 研究1：颅内动脉粥样硬化性斑块的厚长比不能预测其稳定性。12个月的血管造影提示：13例（50%)斑块逆转；10例（38.5%)斑块无明显变化；3例（11.5%)斑块进展。 / 研究2：ORV更多累及颈总动脉，多见双侧颈动脉受累（54% vs 22%)或出现闭塞（30% vs 9%），常见椎动脉受累(28% vs 14%)（均P<0.05）。ORV常见代偿性软脑膜动脉、前后交通动脉开放，及逆向眼动脉血流。 / 研究3：两组间围手术期并发症，长期生存率和卒中复发率无统计学差异。 / 结论 / 研究1：3D-RA可评价颅内斑块形态学变化；颅内光滑斑块亦可为易损斑块。严格控制危险因素可能逆转斑块。 / 研究2： ORV患者更多见颈动脉及椎基底动脉狭窄-闭塞性病变，并伴随侧枝循环开放。侧枝循环代偿功能减退可能诱导ORV患者发生卒中。 / 研究3：RIV患者与对照组相比，CAS的耐受性和临床预后无明显差异。 / Large artery occlusive disease, encompassing stenosis in intracranial and extracranial vasculature, is the most common stroke subtype worldwide. In this thesis, we aimed to investigate angiographic plaque morphology and treatments in stroke patients attributed to intracranial and/or extracranial stenosis. A better understanding of intracranial plaque morphology, angiographic characteristics and collateral circulations of extracranial occlusive vasculopathy may help clarify pathogenesis and formulate treatment. / Objectives / Study 1: In this prospective longitudinal study, we investigated the intracranial plaque morphology of acute stroke patients by three-dimensional rotational angiography (3D-RA). / Study 2: We aimed to delineate the angiographic attributes and collateral circulations in symptomatic occlusive radiation vasculopathy (ORV) patients by a case-controlled study. / Study 3: We investigated the angiographic and clinical outcome of carotid artery stenting (CAS) in stroke patients attributed to ORV. / Methods / Study 1: Twenty-four patients with acute strokes attributed to a >70% intracranial stenosis were recruited to undergo 3D-RA at baseline and in 12 months after an intensive control of atherosclerotic risks. We described the degree of stenosis and morphology that might be associated with plaque vulnerability. / Study 2: We performed digital subtraction angiograms (DSA) in 96 patients who had first-ever ischemic strokes attributed to ORV, and 115 referent patients who had no radiotherapy (RT) but symptomatic high-grade (>70%) atherosclerotic carotid stenoses. We compared the lesions’ distribution, morphology, and the resultant alteration of collateral flows in both patient groups. / Study 3: We compared the angiographic and clinical outcome of CAS in 63 symtomatic ORV patients and 87 patients with spontaneous atheromatous carotid stenoses. Primary end-points were transient ischemic attack, stroke and death of all causes. Secondary end-point was instent restenosis in 24 months. / Results / Study 1: Inracranial atherosclerotic plaque is a dynamic lesion.Thickness-to-length ratio may not indicate plaque vulnerability. In 12-month angiogram, 13 patients (50%) had plaque regression, 10 (38.5%) had static plaque, and 3 (11.5%) had plaque progression. / Study 2: Compared with spontaneous atheromatous carotid disease, ORV lesions diffusely involved common carotid artery, and were more frequently bilateral (54% vs 22%), associated with complete occlusion in one or both carotid arteries (30% vs 9%), vertebral artery steno-occlusions (27% vs 14%) (all p<0.05). ORV patients showed more established collateral circulations through leptomeningeal arteries, anterior communicating artery, posterior communicating artery and retrograde flow in ophthalmic artery. / Study 3: We found no significant differences in the frequency of periprocedural complications, the rates of patient survival and stroke recurrence between ORV and control groups. / Conclusions / Study 1: Evaluation of intracranial plaque morphology is feasible with 3D-RA. Smooth plaques might also be vulnerable in intracranial vasculature. Intensive risk factor control may halt progression of intracranial plaques. / Study 2: ORV patients had more steno-occlusions over carotid and vertebral arteries amid mature collateral circulations at initial stroke presentation. Decompensation of collateral flows may precipitate stroke in ORV. / Study 3: The durability and clinical outcome of CAS in ORV patients were comparable to those in patients with spontaneous atherosclerotic carotid stenosis. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Zou, Xinying. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 101-119). / Abstract also in Chinese. / ABSTRACT --- p.i / 摘要 --- p.vi / DECLARATION OF ORIGINALITY --- p.ix / ACKNOWLEDGEMENTS --- p.x / PUBLICATIONS AND PRESENTATIONS --- p.xii / LIST OF ABBREVIATIONS --- p.xiv / LIST OF TABLES --- p.xvii / LIST OF FIGURES --- p.xviii / TABLE OF CONTENTS --- p.xx / Chapter CHAPTER 1 --- INTRODUCTION AND LITERATURE REVIEW --- p.1 / Chapter 1.1 --- An overview of large artery occlusive disease in ischemic stroke --- p.1 / Chapter 1.2 --- Vulnerable plaque and plaque morphology in ischemic stroke --- p.3 / Chapter 1.2.1 --- Definition of vulnerable plaque and plaque morphology --- p.4 / Chapter 1.2.2 --- Imaging of vulnerable plaques --- p.5 / Chapter 1.2.3 --- Factors affecting plaque stability or arterial luminal narrowing --- p.7 / Chapter 1.2.3.1 --- Stenosis severity --- p.7 / Chapter 1.2.3.2 --- Thickness and length of plaque --- p.8 / Chapter 1.2.3.3 --- Mechanical stress, shear stress and hemodynamics on plaque stability --- p.9 / Chapter 1.2.3.4 --- Plaque eccentricity --- p.10 / Chapter 1.2.3.5 --- Plaque surface morphology --- p.11 / Chapter 1.2.4 --- Morphological characteristics of symptomatic plaque --- p.11 / Chapter 1.2.4.1 --- Carotid plaque morphology --- p.11 / Chapter 1.2.4.2 --- Intracranial plaque morphology --- p.12 / Chapter 1.2.5 --- Treatment of vulnerable intracranial stenosis --- p.12 / Chapter 1.3 --- Occlusive radiation vasculopathy (ORV) --- p.13 / Chapter 1.3.1 --- Epidemiology of ORV --- p.13 / Chapter 1.3.2 --- Pathogenesis and Pathophysiology of ORV --- p.14 / Chapter 1.3.3 --- Imaging and angiographic characteristics of ORV --- p.16 / Chapter 1.3.4 --- Collateralization in ORV --- p.18 / Chapter 1.3.5 --- Angioplasty and stenting for ORV --- p.19 / Chapter CHAPTER 2 --- OBJECTIVES --- p.22 / Chapter CHAPTER 3 --- RECRUITMENT OF STUDY PARTICIPANTS --- p.24 / Chapter CHAPTER 4 --- REGRESSION OF SYMPTOMATIC INTRACRANIAL PLAQUE BY INTENSIVE RISK FACTOR CONTROL: A LONGITUDIANL STUDY ON PLAQUE MORPHOLOGY BY 3D-ROTATIONAL ANGIOGRAPHY --- p.28 / Chapter 4.1. --- Background and objectives --- p.28 / Chapter 4.2 --- Methods --- p.32 / Chapter 4.2.1 --- Participants --- p.32 / Chapter 4.2.2 --- Risk factors and intensive control --- p.33 / Chapter 4.2.3 --- Evaluation of intracranial stenosis --- p.33 / Chapter 4.2.3.1 --- DSA and 3D-RA protocol --- p.33 / Chapter 4.2.3.2 --- Severity of stenosis --- p.34 / Chapter 4.2.3.3 --- Analysis of morphological characteristics on 3D-RA --- p.34 / Chapter 4.2.3.4 --- Plaque regression --- p.35 / Chapter 4.2.4 --- Statistical analysis --- p.36 / Chapter 4.3 --- Results --- p.36 / Chapter 4.4 --- Discussion --- p.54 / Chapter CHAPTER 5 --- ANGIOGRAPHY DISTINCTIONS AND COLLATERALIZATION IN SYMPTOMATIC CRANIO-CERVICAL OCCLUSIVE RADIATION VASCULOPATHY: A CASE-REFERENT STUDY --- p.58 / Chapter 5.1 --- Background and objectives --- p.58 / Chapter 5.2 --- Methods --- p.59 / Chapter 5.2.1 --- ORV and referent patients --- p.60 / Chapter 5.2.2 --- Evaluation of vascular lesions and collateral status --- p.61 / Chapter 5.2.3 --- Statistical analysis --- p.64 / Chapter 5.3 --- Results --- p.64 / Chapter 5.4 --- Discussion --- p.81 / Chapter CHAPTER 6 --- SAFETY AND CLINICAL OUTCOME OF CAROTID ARTERY STENTING IN STROKE PATIENTS WITH OCCLUSIVE RADIATION VASCULOPATHY --- p.86 / Chapter 6.1. --- Background and objectives --- p.86 / Chapter 6.2 --- Methods --- p.87 / Chapter 6.2.1 --- Participants --- p.87 / Chapter 6.2.2 --- Baseline clinical assessment --- p.87 / Chapter 6.2.3 --- Carotid artery stenting (CAS) --- p.88 / Chapter 6.2.4 --- Follow-up and end-points --- p.89 / Chapter 6.2.5 --- Statistical analysis --- p.89 / Chapter 6.3. --- Results --- p.90 / Chapter 6.4. --- Discussion --- p.96 / Chapter CHAPTER 7 --- CONCLUSIONS --- p.98 / REFERENCES --- p.101

Introduktion: Stroke är en av våra vanligaste folksjukdomar. Karaktäristiskt vid hemipares till följd av en stroke är ett asymmetriskt gångmönster och en nedsatt gånghastighet jämfört med friska individer. Tidigare studier har visat att gångträning på löpband med body weight support (BWS) som utförs genom en progressiv ökning av hastigheten bidrar till ett förbättrat gångmönster. Gångträning på löpband med BWS på en snabb hastighet har även visat sig förbättra gånghastigheten hos strokedrabbade. Forcerad gångträning innebär en hastighet över individens självvalda bekväma gånghastighet. I nuläget finns det ingen litteraturöversikt som specifikt undersöker detta samt vilka effekter det har på gångmönster och gånghastighet. Syftet var att göra en litteraturöversikt om effekten av forcerad gångträning på löpband för personer med hemipares till följd av en stroke, i den subakuta respektive kroniska fasen. Metod: För att hitta artiklarna användes databaserna; PubMed, AMED och CINAHL. För sökningen användes MeSH-termer; stroke, hemiplegia, walking och gait, samt sökordet treadmill för att precisera sökningen. Kvalitetsgranskning av artiklarna gjordes utifrån en egen modifierad version av Fribergs granskningsmodell. Först lästes artiklarnas titlar och abstrakt, därefter lästes relevanta artiklar i fulltext. Totalt sex artiklar inkluderades. Resultat: Forcerad gångträning bidrar till en ökad gånghastighet men inte till ett mer symmetriskt gångmönster. Konklusion: När gånghastigheten är målet med rehabiliteringen så är forcerad gångträning på löpband en fördelaktig träningsmetod för individer med hemipares till följd av en stroke. Dessa slutsatser är utifrån sex studier och för att helt klarställa klinisk relevans krävs mer forskning inom området.

Stroke is a significant contributor to the global burden of disease in adults. With the risk of recurrent stroke high, preventative medicines aimed at risk factor reduction are the method of choice for addressing the challenge of increased morbidity and mortality and improving patient outcomes. Research in stroke has shown that adherence to medication is problematic and survivors face considerable practical and physical barriers to taking prescribed medicines. Understanding these challenges can inform the development of strategies to improve medication taking behaviour through delivery of interventions in the primary care setting. This thesis aims to identify potential strategies to inform interventions to improve medication taking in stroke. The research: identified key barriers and facilitators of medication adherence for the secondary prevention of stroke - firstly from within the primary care setting and then from the perspective of an online stroke forum; explored the appropriateness of the online forum as a method of data collection for conducting qualitative research compared with a traditional qualitative interview approach; investigated medication taking among community stroke survivors to characterise patients who receive help with medicines and estimate the proportion who have unmet needs and miss medicines; and examined attitudes from across the stroke spectrum towards a novel approach to medication taking for secondary prevention (i.e. fixed-dose combination polypill). Findings showed that survivors face considerable barriers to medicine taking, but that facilitators, particularly the caregiver role, can encourage good medication taking practice. The online forum has potential as a source of data to understand stroke survivors' behaviour, and a novel strategy to taking stroke medicines has promise. These findings enhance current thinking around medicine taking behaviour in stroke and can inform the development of effective interventions to improve medication taking practices and address nonadherence among stroke survivors. Implications for clinical practice are discussed, and recommendations are provided for future research.

Background: Conversation is the archetypal mode of communication. As a process it draws on numerous skills, and predispositions, adapting to dynamic contexts and coordinated in highly sophisticated ways for successful interaction. The combination of these abilities with contextual variables coalesces uniquely to represent what this research proposes to be conversational intelligence. It is argued here that high levels of conversational intelligence rest to a large degree on executive functions (EF) which are steadily becoming more widely acknowledged and researched within the communication domain. The impairment of EF in neurologically injured individuals has significant, though as yet undisclosed, repercussions for recovery, response to therapy and ability to integrate communication skills in every day interactions to support conversational success. This study incorporates some new approaches to the study of communication disorders following stroke, including conversation, executive functions and the possibility of pharmacological intervention. Aims: The aims of this study were to describe in detail the language, executive function and conversational characteristics of ten individuals who had experienced strokes and to examine the relationships among these three areas of functioning. In addition, this research investigated the response of these ten participants to pharmacological therapy on a one month trial of Leviteracetam (LEV). Methods and Procedures: Ten individuals who had suffered single incident strokes were recruited from local community and rehabilitation facility referrals. All ten participated in a four stage randomised, double blind investigation including baseline, active, placebo and withdrawal phases. At each stage participants underwent testing on an EF battery and were recorded having conversations with familiar interlocutors. In addition, significant others completed a rating scale assessing affective features and behaviours and language testing was conducted at the baseline phase using the WAB. The language and EF data were scored and the conversations subjected to Conversation Analysis. For each participant, profiles were created and assessed for interrelationships between the executive characteristics and conversational features representative of each executive construct. Repeated measures analysis of variance was conducted on EF data for the four phases of the study to determine significant pharmacological effects. Outcomes and Results: The majority of the sample presented with significant EF deficits across most areas assessed. Two participants presented with essentially intact profiles which were not explained in terms of types of aphasia or site of lesion. Language results proved to be inconsistently associated with EF deficits, but conversational features reflected underlying executive strengths or deficits with greater consistency. Two participants experienced amelioration (though not statistically significant) of interference control during the active phase, with observable improvements in conversational skill. One participant demonstrated improved conversation without a change in EF scores. The response to LEV is evaluated with reference to potential alternatives. Conclusions: The existence of EF deficits in individuals with stroke is demonstrated. Furthermore, the impact of these impairments is considerable and observable during naturally occurring conversations, suggesting the centrality of the EF contribution to conversational intelligence. The lack of association between formal language test scores and EF impairments argues for the inclusion of more authentic assessment approaches for stroke patients. The data is explored in terms of specific consequences of different lesion sites on EF and communication and briefly addresses bilingualism as a potential variable in explaining some of the variations in the data. Pharmacotherapy is addressed as an important focus of future research protocols. Implications for assessment and treatment are discussed as well as proposals for future study.

Stroke is the fifth leading cause of death and primary cause of long-term disability in the United States. Public awareness of stroke symptoms and ability to activate the emergency medical system (EMS) quickly are essential for early treatment. At a large Joint Commission-certified Comprehensive Stroke Center with over 6,000 employees, a stroke champion program that included both clinical and nonclinical volunteers was initiated to determine whether stroke champion volunteers could learn and disseminate information about stroke symptoms and the importance of activating EMS within their community. Roger's diffusion-of- innovation framework was used to design and evaluate the outcome of the project. A survey of 46 stroke champion hospital clinical and nonclinical employee volunteers was conducted using a secured web-based survey that employed a Likert scale to evaluate the effectiveness of the program. The survey collected information on whether the stroke champion needed a license to perform their job at the hospital and evaluated the content of the program, the setting of the meeting, presenter's effectiveness, instructional method, and learners achievement of the programs objectives. Over 90% of respondents agreed or strongly agreed that the program achieved the objectives set forth in each category of the survey. A stroke champion program that incorporates all employees, not just nurses, could bring about positive social change by increasing health literacy through the dissemination of stroke information to all community members.