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Section A is a review of the literature on psychological adjustment following stroke. Empirical research is critically reviewed with reference to two research questions: (1) What do we understand about adjustment following survival of stroke? (2) What psychosocial interventions have been used to support adjustment post-stroke and what are the outcomes? Theoretical models for adjustment to stroke are drawn upon to illuminate the findings. Gaps within the literature are discussed and future directions for research are suggested. Section B describes a study using mixed methods. The purpose of the study was to evaluate whether narrative group therapy could facilitate psychosocial adjustment in survivors of stroke, and to explore the impact of stroke on survivors’’ lives through their shared narratives. Methods: Ten participants took part in a six-week narrative group therapy intervention for stroke survivors. Quality of life, use of coping strategies and illness representations were measured pre- and post-intervention, and thematic analysis was conducted on the content of the intervention sessions. Results: There was no statistically significant change on the outcome measures post-intervention. However the inductive thematic analysis resulted in the identification of four master themes: ‘using the group’, ‘negative talk’, ‘positive talk’ and ‘relationships’. These themes, respectively, revealed that the social aspects of the group allowed comparing experiences and exchanging information; participants were able to discuss the perceived negative aspects of surviving a stroke; with support, participants could identify the adaptations and achievements made since the stroke; and how the stroke impacted on relationships between the survivor and the systems around them. Conclusion: The findings indicate that narrative therapy requires further evaluation in terms of facilitation of adjustment. However, the thematic analysis supports the utility of group discussions and the provision of information to stroke survivors and their carers, thus indicating potential development of psychoeducation group programmes, provisionally as part of a stepped care model.

Stroke is a leading cause of disability in the UK and has a range of psychological sequelae including apathy, depression and fatigue. Psychological consequences of stroke have been associated with poor rehabilitation outcomes. Apathy, depression and fatigue are often considered to overlap and the research indicates that they may occur both independently and in unison after stroke. Sixty-three people aged over 55 years who had a stroke and lived in the community were included in this study. They were assessed using the Apathy Evaluation Scale, Geriatric Depression Scale, the Fatigue Severity Scale and the Barthel index. Socio-demographic data were also collected along with information about their stroke. 60.3% of participants reached cut-off levels for apathy, 58.6% for depression and 58.7% for fatigue. While there was an overlap in terms of these psychological disorders, they also occurred independently. Physical functioning was the only factor which was related to apathy, depression and fatigue. Apathy was a mediator in the relationship between physical functioning and depression; and depression was a mediator in the relationship between apathy and fatigue. Based on these findings, a significant structural equation model accounting for the relationships between apathy, fatigue, physical functioning and depression was developed. The study concluded that apathy, depression and fatigue are common post-stroke. The inter-relationships between these post-stroke sequelae are also related to the person’s physical functioning and not to age, side of weakness or time since stroke. Results have implications in terms of the clinical assessment and management of post-stroke psychological sequelae.

Post-stroke sexual difficulties are common but sexuality is an area frequently neglected within stroke rehabilitation. This study aimed to explore the process by which healthcare professionals approach and work with the topic of sexuality within stroke rehabilitation. This was hoped to improve understanding of why current guidelines around addressing post-stroke sexual issues are not followed, and what would support professionals to meet patients’ needs. Ten healthcare professionals working within stroke rehabilitation were interviewed, covering a range of disciplines and settings. The data was analysed using grounded theory methodology. Fourteen major categories were co-constructed from participants’ data and a theoretical model was developed. Although the majority of participants rarely engaged with sexual issues, they adopted both direct and indirect strategies for engaging with the sexual concerns of their patients. Concerns were usually addressed through the provision of information and supportive conversation with a professional. Professionals’ own personal level of comfort with the topic of sexuality interacted with a series of barriers to limit opportunities for engaging with sexual concerns. These barriers included environmental factors relating to the context of stroke rehabilitation, professionals’ perception of lacking abilities and unhelpful attitudes towards patients and sexuality. Positive and inclusive attitudes towards sexuality and professional roles and building a strong therapeutic relationship facilitated professionals taking action. The findings are considered in relation to existing guidelines and research, and the clinical implications for rehabilitation and staff training are discussed.

Stroke is a major cause of premature death and disability throughout the world and atrial fibrillation (AF) is one of the most common preventable causes of stroke. AF affects about 10% of individuals aged ≥80 years, but warfarin is substantially under-used in this age group despite being effective in preventing AF-related thromboembolic events. AF-related ischaemic strokes tend to be severe and incur high care costs, and non-cerebral systemic embolism secondary to AF is also a major clinical burden. Despite that, there are few population-based studies on AF-related ischaemic stroke, and no recent study of the burden of AF-related thromboembolism and the population impact of under-treatment. I have used data from the Oxford Vascular Study (OXVASC), a prospective, population-based incidence study of vascular disease in all territories, which was started in April 2002 and is on-going. The study population comprises of 92,728 individuals registered with 100 family physicians in nine general practices and uses multiple overlapping methods of “hot” and “cold” pursuit to achieve near-complete ascertainment of all patients with acute vascular events. There are several findings described by the research in this thesis which have important implications for public health and can be utilised to improve secondary prevention in stroke. First, I have shown that one-third of all incident embolic events were related to AF and 60% of AF-related embolic events occurred at ≥80 years. Second, I have shown that only 9% of patients aged ≥80 years with incident embolic event related to known prior AF were on premorbid warfarin, and consequently three quarters of those previously independent were dead or disabled six months post event. Third, I have shown that there has been no reduction in age-specific incidence of AF-related ischaemic stroke in Oxfordshire over the last 25 years. Fourth, I have shown that assuming age-specific incidence does not continue to rise, if prevention is not improved, the number of embolic events at age ≥80 years would be expected to treble by 2050 (72,975 AF-related embolic events), with 84% of events at all ages occurring at age ≥80. Fifth, I have shown through a meta-analysis that one in five incident strokes had a history of prior AF of which only 19% were on premorbid warfarin, and AF was related to one in three incident ischaemic strokes. Sixth, I have shown that 1 in 5 stroke patients with known prior AF subsequently became institutionalised and incurred high acute and long-term care costs. Seventh, I have shown that one in five patients with undetermined cerebral ischaemic event subsequently had AF-related late recurrent stroke. Eighth, I have shown that even though TIA or ischaemic stroke patients who subsequently turned out to have new AF at follow-up had significantly higher baseline NT-proBNP compared to non-AF group, its utility is limited by low sensitivity and specificity. Ninth, I have shown in another meta-analysis that the duration of cardiac monitoring after cerebral ischaemic events was the main determinant of the observed rate of pAF, and that 5-7 days of monitoring may be adequate in unselected patient populations. Finally, I have shown that using 5-day event loop recording in clinic patients with TIA and minor ischaemic stroke could detect 12% new AF and the delay in monitoring did not reduce the sensitivity of pAF detection.

Cerebral blood flow dynamics is an essential component for preserving cerebral integrity. Cerebral blood flow abnormalities are often seen in patients with central nervous system pathologies such as epilepsy, migraine, Alzheimer's Disease, vascular dementia, stroke, and even HIV/AIDS. There is increasing clinical and experimental evidence implicating cerebral hypoperfusion during ageing. The determination of cerebral perfusion has therefore become an important objective in physiological, pathological, pharmacological, and clinical investigations. The knowledge of regional cerebral blood flow further provides useful diagnostic information and/or data for a better understanding of the complex clinical presentations in patients with neurological and psychiatric disorders. Several cerebrovasoactive drugs have found application in the clinical setting of cerebrovascular diseases such as migraine and dementia. Due to the similarities between humans and non-human primates with respect to their brains, both structurally and behaviourally, numerous studies have been conducted and several non-human primate models have been developed for physiological, pathological, pharmacological, and clinical studies, amongst others in Parkinson's disease and diabetes. The relatively large size of the Cape baboon Papio Ursinus with a weight of 27-30 kg for a large male, makes this primate especially suitable for in vivo brain studies using radiotracers and Single Photon Emission Computed Tomography (SPECT). The main aim of the current study was therefore to develop a suitable radiotracer (99m Tc-hexamethylpropylene amine oxime (HMPAO) or 99m Tc_ethyl_cysteinatedimer (ECD) or 123l-iodoamphetamine (IMP)) for adapted in vivo cerebral blood flow measurements in a non-human primate (Papio ursinus) as an investigative model. The model was to be validated and applied in various drug studies for the evaluation of pharmacological interventions. The study design made use of split-dose methodology, whereby the radiopharmaceutical (radiotracer) was administered twice during each study. The first administration was injected soon after the induction of the anaesthesia, and was followed by the first SPECT data acquisition. The second administration of the radioligand, a double dose of radioactivity with respect to the first radioligand injection, was done at a specific time during the study, which took into account the pharmacodynamics of the drug. A second SPECT data acquisition followed subsequently. The drugs that were included in the study were acetazolamide, a carbonic acid anhydrase inhibitor (often used in nuclear medicine to determine cerebral reserve); sumaptriptan, a 5-HT (serotonin) agonist used for treatment of migraine; sodium valproate (an anti-epileptic drug); nimodipine, a calcium channel blocker and nitro-glycerine, a vasodilator used for angina. Arterial blood pressures were recorded from a catheter in the femoral artery and heart rates were concurrently monitored. The split-dose method was successfully applied to develop a non-human primate cerebral blood flow model under anaesthesia. The model showed differences in cerebral perfusion of the different anaesthesia regimes. These anaesthesia data sets were suitable as control/baseline results for drug intervention studies. Acetazolamide evaluation through the split-dose method in the baboon confirmed the sensitivity of the model by presenting comparable perfusion. This result compared to those already familiar prompted the model to be applied in pharmacological intervention studies. Subsequent results of these investigations showed increases in perfusion for single drug nimodipine treatment (25%). However, nimodipine attenuated the increases in perfusion when administered in combination with acetazolamide. Sumatriptan was able to decrease and normalise the increased perfusion after long duration anaesthesia. Decreased cerebral blood flow was observed for combinations of nimodipine with sodium valproate suggesting drug-drug interaction with important clinical implications. Similar decreases were found also for sumatriptan and nitro-glycerine when administered in combination with nimodipine. Studies with the various tracers (99m Tc_HMPAO or 99m Tc_ECD or 123l_IMP) showed clear differences in the perfusion data, confirming variation in the biochemical performance of the tracers. These differences, if not taken into consideration, caution for inappropriate clinical conclusions and subsequent erroneous therapeutic decisions. Improvement of radiotracer efficacy was subsequently attempted through application of the cyclodextrine complexation approach. Although cyciodextrine technology did not markedly improve the brain disposition of the 99m Tc-ECD, protection of the tracer against degradation was demonstrated. This study encouraged further exploration of this method for protection of the tracer against chemical and metabolic degradation. The current study was aimed to develop and effectively apply a non-human primate model with nuclear medicine technology for cerebral blood flow determinations after pharmacological interventions. This was achieved through the split-dose method and dedicated computer programming, which yielded a successful model with the non-human primate under anaesthesia. The model was validated with the application of acetazolamide to confirm familiar cerebrovascular reserve results, indicating that the model is sensitive to CBF changes. The model was also effectively applied in several pharmacological intervention studies, whereby cerebropharmacodynamics of selected drugs were investigated and established. This unique model of a non-human primate, Papio ursinus for cerebral blood flow determinations has served pharmacological research successfully during the past 12 years and could do so in the future, with scope to investigate new frontiers with improved technologies. / Thesis (Ph.D. (Pharmacology))--North-West University, Potchefstroom Campus, 2004.

CONTENT 1. INTRODUCTION 7 2. PATIENTS AND METHODS 8 2.1. Patients 8 2.2. Control Group 8 2.3. Study Methods 9 2.4. Treatment of Patients 9 2.5. Outcome State 10 2.6. Statistical Data Analysis 10 3. RESULTS 10 3.1. Clinical Manifestations of Cerebral Arteriovenous Malformations 10 3.2. Consciousness according to Glasgow Coma Scale 10 3.3. Distribution of Patients According to Spetzler-Martin Classification 11 3.4. Localization of Cerebral Arteriovenous Malformations 11 3.5. The Localization of Intracranial Haemorrhages after the Rupture of Cerebral Arteriovenous Malformations 11 3.6. Distribution of Patients with Intracerebral Haemorrhages after the Ruptures of Cerebral Arteriovenous Malformations and without Haemorrhages according to Spetzler-Martin classification 12 3.7. The Relationships between Haemorrhagic Manifestation and Size of Cerebral Arteriovenous Malformations 13 3.8. Transcranial Doppler Sonography Sensitivity and Specificity in Patients with Cerebral Arteriovenous Malformations 13 3.9. Cerebral Haemodynamics in Patients with Cerebral Arteriovenous Malformations and Healthy Controls 15 3.10. Cerebral Haemodynamics Changes in Patients with Cerebral Arteriovenous Malformations before and after the Surgery 16 3.11. Transcranial Doppler evaluation of Different Localizations Cerebral Arteriovenous Malformations 18 3.12. Cerebral Haemodynamics in Patients with Intracerebral Haematomas after Ruptures of Cerebral Arteriovenous Malformations 19 3.13. Cerebral... [to full text]

Cerebral blood flow dynamics is an essential component for preserving cerebral integrity. Cerebral blood flow abnormalities are often seen in patients with central nervous system pathologies such as epilepsy, migraine, Alzheimer's Disease, vascular dementia, stroke, and even HIV/AIDS. There is increasing clinical and experimental evidence implicating cerebral hypoperfusion during ageing. The determination of cerebral perfusion has therefore become an important objective in physiological, pathological, pharmacological, and clinical investigations. The knowledge of regional cerebral blood flow further provides useful diagnostic information and/or data for a better understanding of the complex clinical presentations in patients with neurological and psychiatric disorders. Several cerebrovasoactive drugs have found application in the clinical setting of cerebrovascular diseases such as migraine and dementia. Due to the similarities between humans and non-human primates with respect to their brains, both structurally and behaviourally, numerous studies have been conducted and several non-human primate models have been developed for physiological, pathological, pharmacological, and clinical studies, amongst others in Parkinson's disease and diabetes. The relatively large size of the Cape baboon Papio Ursinus with a weight of 27-30 kg for a large male, makes this primate especially suitable for in vivo brain studies using radiotracers and Single Photon Emission Computed Tomography (SPECT). The main aim of the current study was therefore to develop a suitable radiotracer (99m Tc-hexamethylpropylene amine oxime (HMPAO) or 99m Tc_ethyl_cysteinatedimer (ECD) or 123l-iodoamphetamine (IMP)) for adapted in vivo cerebral blood flow measurements in a non-human primate (Papio ursinus) as an investigative model. The model was to be validated and applied in various drug studies for the evaluation of pharmacological interventions. The study design made use of split-dose methodology, whereby the radiopharmaceutical (radiotracer) was administered twice during each study. The first administration was injected soon after the induction of the anaesthesia, and was followed by the first SPECT data acquisition. The second administration of the radioligand, a double dose of radioactivity with respect to the first radioligand injection, was done at a specific time during the study, which took into account the pharmacodynamics of the drug. A second SPECT data acquisition followed subsequently. The drugs that were included in the study were acetazolamide, a carbonic acid anhydrase inhibitor (often used in nuclear medicine to determine cerebral reserve); sumaptriptan, a 5-HT (serotonin) agonist used for treatment of migraine; sodium valproate (an anti-epileptic drug); nimodipine, a calcium channel blocker and nitro-glycerine, a vasodilator used for angina. Arterial blood pressures were recorded from a catheter in the femoral artery and heart rates were concurrently monitored. The split-dose method was successfully applied to develop a non-human primate cerebral blood flow model under anaesthesia. The model showed differences in cerebral perfusion of the different anaesthesia regimes. These anaesthesia data sets were suitable as control/baseline results for drug intervention studies. Acetazolamide evaluation through the split-dose method in the baboon confirmed the sensitivity of the model by presenting comparable perfusion. This result compared to those already familiar prompted the model to be applied in pharmacological intervention studies. Subsequent results of these investigations showed increases in perfusion for single drug nimodipine treatment (25%). However, nimodipine attenuated the increases in perfusion when administered in combination with acetazolamide. Sumatriptan was able to decrease and normalise the increased perfusion after long duration anaesthesia. Decreased cerebral blood flow was observed for combinations of nimodipine with sodium valproate suggesting drug-drug interaction with important clinical implications. Similar decreases were found also for sumatriptan and nitro-glycerine when administered in combination with nimodipine. Studies with the various tracers (99m Tc_HMPAO or 99m Tc_ECD or 123l_IMP) showed clear differences in the perfusion data, confirming variation in the biochemical performance of the tracers. These differences, if not taken into consideration, caution for inappropriate clinical conclusions and subsequent erroneous therapeutic decisions. Improvement of radiotracer efficacy was subsequently attempted through application of the cyclodextrine complexation approach. Although cyciodextrine technology did not markedly improve the brain disposition of the 99m Tc-ECD, protection of the tracer against degradation was demonstrated. This study encouraged further exploration of this method for protection of the tracer against chemical and metabolic degradation. The current study was aimed to develop and effectively apply a non-human primate model with nuclear medicine technology for cerebral blood flow determinations after pharmacological interventions. This was achieved through the split-dose method and dedicated computer programming, which yielded a successful model with the non-human primate under anaesthesia. The model was validated with the application of acetazolamide to confirm familiar cerebrovascular reserve results, indicating that the model is sensitive to CBF changes. The model was also effectively applied in several pharmacological intervention studies, whereby cerebropharmacodynamics of selected drugs were investigated and established. This unique model of a non-human primate, Papio ursinus for cerebral blood flow determinations has served pharmacological research successfully during the past 12 years and could do so in the future, with scope to investigate new frontiers with improved technologies. / Thesis (Ph.D. (Pharmacology))--North-West University, Potchefstroom Campus, 2004.

O Acidente Vascular Encefálico (AVE) em crianças possui particularidades em relação à faixa etária acometida, apresentação clínica inicial, fatores de risco, etiologias e evolução diferente dos achados de AVE em adultos. O objetivo do presente trabalho é elaborar um protocolo para o registro de Acidente Vascular Encefálico em crianças, adapatado da versão para adultos (REAVER)desenvolvida pelo Professor Octávio Marques Pontes Neto e colaboradores, do Departamento de Neurociências da FMRP-USP,que, consiste em um registro clínico prospectivo de base hospitalar para doenças cerebrovasculares, cada um dos itens foi analisado e adequado à faixa pediátrica sendo fundamentadopor uma revisão bibliográfica de AVE na criança e de um levantamento de casos de AVE tipo isquêmico (AVEi) em crianças e jovens, excetuando a faixa etárianeonatal, atendidos em hospital de nível terciário. Um estudo observacional retrospetivo, secional foi procedido pela revisão de registros médicos de pacientes com menos de 18 anos exceto a idade de neonatal (entre 2 meses e 18 anos), de 1996 a 2014, assistidos no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (HCFMRP-USP). Foram incluídas na amostra 89 crianças com um tempo mínimo de acompanhamento de 12 meses e extraídas informações abrangentes quanto à apresentação clínica e fatores associados. Do total de pacientes, 40 (44.94%) pertenciam ao sexo masculino e 49 (55.05%) ao feminino. A média de idade do diagnóstico de AVEi foi de 3,57 ± 0,26 anos. Detectamos 49.43% dos pacientes no período de lactente, 23.59% no período pré-escolar, 17.97% no escolar, e 8.98% dos pacientes no período pré-púbere, não houve nenhum paciente nos grupos púbere e pós púbere. Destes, 77 pacientes (86.51%) eram da raça branca, 11 negros e 1 oriental. Dos pacientes analisados, 24 (26.96%) apresentavam doenças relacionadas ao AVEi, diagnosticadas previamente ao evento. A principal doença previamente diagnosticada foi a cardiopatia complexa ou malformação cardíaca diagnosticadas no período neonatal em 7 (7.86%) pacientes e valvopatia congênita identificada no período de lactente em 1. Em 44 (49,43 %) pacientes houve relato de associação a fatores ambientais, sendo mais prevalente a síndrome febril/infeciosa, precedendo o início dos sintomas do AVEi em até 8 semanas, totalizando 40 (44,94%) casos, com a infecção de vias aéreas superiores mais prevalente, responsável por 27 casos. Na fase aguda, o déficit focal motor esteve presente isoladamente em 28 (31.46%) crianças, crise convulsiva sem outros sinais em 25 (28,08%), e, se contabilizarmos os casos com mais de um sinal clínico (exemplo: crise convulsiva associada a déficit focal) a crise convulsiva foi a principal apresentação clínica, presente em 41 (46.06%) casos. Entre os 56 (62,92%) com etiologia confirmada, relação direta com causas infeciosas foi a mais prevalente totalizando 16 pacientes. Apesar da extensa investigação realizada em 72 (80,89%) pacientes, os quais realizaram protocolo de investigação do AVEi em jovens, 33 (37,07%) permaneceram com etiologia indeterminada. O tempo médio de acompanhamento dos pacientes foi de 5,76 ± 0,37 anos. Vinte (22,47%) pacientes foram a óbito no período de estudo, ocorrendo principalmente dentro do primeiro ano de acompanhamento, ocorrendo em 14 crianças. Embora relativamente raro, comparado com muitas outras doenças de infância, o AVE pediátrico carrega com ele uma morbidez desproporcionalmente alta e o preço pessoal e social de longo prazo. / The brain stroke in children has special features regarding age distribution, initial clinical presentation, risk factors, etiology and evolution different from adult stroke. The objective of this study is to develop a protocol for stroke registration in children, anadaptation of adult version (REAVER) developed by Professor Octavio Marques Pontes Neto and colleagues from the Department of Neurosciences of the FMRP-USP consisting of a prospective clinical registry, hospital-based, on cerebrovascular disease. Each item was analyzed and suitable for pediatric patients, with particular focus on environmental factors, comorbidities and the diseases associated with stroke in children.It is grounded bya review of the literature and a survey of cases of ischemic stroke in children and young people, attended at a tertiary care level hospital. A retrospective, cross-sectional observational study was proceded by review of medical records ofpatients aged less than 18 years except for the neonatal age (less than 2 months old), attended at teaching hospital of School of Medicine of Ribeirão Preto, São Paulo University (HCFMRP-USP). Eighty-ninechildren were included with a minimum of 12 months follow-up. Of all patients, 40 (44.94%) were male and 49 (55.05%) female. The mean age of diagnosis of ischemic stroke was 3.57 ± 0.26 years. We detected 44 (49.43%) patients in the infant period, 21 (23:59%) in the preschool period, 16 (17.97%) in the school, and 8 patients (8.98%) in pre-pubertal period, there were no patients in groups pubescent and postpubescent. 77 patients (86.51%) were white, 11 (12:35%) black and 1 (1.12%) eastern patient. Of the patients analyzed 24 (26.96%) were previously diagnosed with a disease known to be related to ischemic stroke. The main previously diagnosed disease was complex heart disease or heart malformation, with 7 (7.86%) patients diagnosed in the neonatal period and 1 (1.12%) Congenital valve disease identified in the infant period. 44 (49.43%) patientshad environmental factorspreceding the stroke. The most prevalent were febrile / infectious syndromes (44.94%), that preceded the stroke up to eight weeks. Among them, upper airway infection, accounted for 27 (30.33%) cases.In the acute phase, the motor focal deficit alone was present in 28 (31.46%) children, seizures without other signs in 25 (28.08%) cases, and if we add cases with more than one clinical signs (example: any focal deficits withseizure) the seizure was the main clinical presentation, present in 41 ( 46.06%) cases. Among the 56 (62.92%) with confirmed etiology, 16 patients had infectious causes directly related tostroke.Despite extensive researchthat has been carried out in 72 (80.89%) patients, 33 (37.07%)remained with undetermined etiology. The mean follow-up of patients was 5.76 ± 0.37 years. Twenty (22.47%) patients died during the study period, occurring mainly within the first year of follow-up, occurring in 14 (15.73%) childrenAlthough relatively uncommon, compared with many other childhood diseases, pediatric stroke carries with it a disproportionately high morbidity and long-term personal and societal cost.