As habilidades manuais podem estar prejudicadas na paralisia cerebral (PC), interferindo nas atividades funcionais do cotidiano da criança, como alimentar-se, ir ao banheiro, brincar, o que ocasiona impacto negativo na vida dela e da família. Objetivo: elaborar, aplicar e analisar um protocolo de avaliação da função manual de crianças com PC, de 0 a 7 anos e 11 meses de idade. Método: estudo dividido em 2 etapas - 1) planejamento: definição de objetivo e população alvo, realização de revisão da literatura sobre instrumentos já existentes, tipos de itens e formato de instrumento, 2) construção: construção I -desenvolvimento dos itens, seleção dos instrumentos utilizados como base do protocolo, seleção dos itens relevantes por faixa etária, análise dos itens e adequação do protocolo; projeto piloto - aplicação do protocolo junto a 36 crianças de 0 a 7 anos e 11 meses, sendo 18 com PC e 18 com desenvolvimento típico (DT), análise dos itens e adequação do protocolo; construção II - validação de conteúdo por profissionais/pesquisadores experientes (experts) na área, elaboração e envio do questionário aos juízes especialistas, revisão dos itens (inclusão e exclusão), análise das avaliações dos especialistas e adequação do protocolo. Resultados: foram selecionados 238 itens, sendo 38 itens da Escala Lúdica Pré Escolar de Knox (ELPKR), 126 do Inventário Portage Operacionalizado (IPO), 32 do Teste de Triagem de Desenvolvimento de Denver II (TTDD-R), 38 do Inventário de Avaliação Pediátrica de Incapacidade (PEDI) e 4 do Manual de Avaliação Motora - Escala de Desenvolvimento Motor (MAM-EDM). Todos os itens foram revisados. Realizou-se o agrupamento de 161 itens recorrentes, totalizando 120 itens, os quais foram aplicados em crianças com PC e DT. Após a aplicação, em nova análise do protocolo, foram agrupados 6 itens semelhantes, divididos 2 e excluídos 7, totalizando 109 itens, os quais foram enviados em forma de questionário para os juízes especialistas. Na sequência, as avaliações dos experts foram analisadas e, então, 3 itens foram agrupados, 1 item subdividido e 7 itens excluídos, chegando-se a um protocolo final com 101 itens, divididos em 8 faixas etárias: de 0 a 5 meses, de 6 meses a 11 meses, de 1 ano a 1 ano e 11 meses e, sucessivamente, na sequência anual até de 4 anos a 4 anos e 11 meses; em seguida há uma faixa etária de 5 anos a 6 anos e 11 meses e, após, a faixa etária de 7 anos a 7 anos e 11 meses. O resultado foi então denominado de Avaliação Manual Infantil Geral e Objetiva - AMIGO. Foram observadas 2 crianças de cada grupo em cada faixa etária, sendo que as crianças com DT apresentaram, no geral, melhores pontuações quando comparadas às crianças com PC da mesma faixa etária. Considerações finais: a avaliação AMIGO foi considerada válida e alcançou seu objetivo principal. Ainda está, porém, em processo de construção e, em estudos futuros, passará por mais duas fases de construção, sendo elas a fase III - avaliação quantitativa e a fase IV - validação, para que possa ser considerada totalmente válida e segura a sua utilização na prática clínica e na pesquisa científica. / Manual skills may be affected in cerebral palsy (CP), interfering with functional activities of child\'s daily life, such as eating, toileting, playing, which causes negative impact on child´s life and family. Objective: To develop, implement and analyze an evaluation protocol to assess manual children function with CP, aged between 0-7 years and 11 months old. Method: This study was divided into two stages - 1) planning: setting goals and target population, literature review on existing instruments, types of items and instrument format, 2) Construction: Construction I -development of items, selection of instruments used as basis of the protocol, selection of relevant items by age group, item analysis and protocol adjustment; Pilot Project - protocol application with 36 children 0-7 years, 11 months, 18 CP childerb and 18 children with typical development (TD), item analysis and protocol adjustment; Construction II - Content validation by professional / experienced researchers (experts) in the area, preparation and submission of the questionnaire to expert judges, items review (item inclusion or exclusion), analysis of experts evaluations and suitability of the protocol. Results: We selected 238 items, 38 items Revised Knox Preschool Scale (RKPPS) 126 items from Operationalized Portage Inventory (IPO), 32 from Denver II Developmental Screening Test (DDST-R) 38 from Pediatric Evaluation of Disability Inventory (PEDI) and 4 from Manual of Motor Evaluation - Motor Development Scale (MAM-EDM). All items were reviewed. We grouped 161 recurring items, totalizing 120 items, which we applied both in CP children and with CP and TD children. After the implementation, we performed a new protocol analysis and 6 similar items were grouped, 2 items divided and 7 items excluded, totalizing 109 items, which were sent as questionnaire to the expert judges. Further, experts assessments were analyzed and then 3 items were grouped, 1 item subdivided, and 7 items deleted, coming to a final protocol with 101 items, divided into eight age groups: 0-5 months of 6 months to 11 months, 1 year to 1 year and 11 months and, subsequentially, the annual sequence till 4 years to 4 years and 11 months; then there is an age group between 5 years and 6 years and 11 months, and after the age of 7 years to 7 years and 11 months. The resulting product was then called Children´s Manual Assessment General and Objective - AMIGO. Two children in each group were observed at each age, and children with TD had, overall, better scores compared to children with CP in each age group. The final considerations were that AMIGO has been valid and reached its main goal. But it is still under construction, and in future studies it will go through two more stages of construction, which were phase III - quantitative assessment and phase IV - validation, in order to be considered valid and secure to be uesd in clinical practice and in scientific research.

Orientador: Maria Aparecida Coelho de Arruda Henry / Coorientador: Arthur Oscar Schelp / Coorientador: Roberta Gonçalves da Silva / Banca: Célia Maria Giacheti / Banca: Luiz Roberto Lopes / Resumo: Estudos têm proposto a utilização da Escala Internacional de Acidente Vascular Cerebral do Instituto Nacional de Saúde (NIHSS) como um instrumento de triagem, como preditor clínico da presença de disfagia orofaríngea e indicador de via de alimentação nos indivíduos pós-AVC, mesmo este não pontuando o distúrbio de deglutição. No entanto, a maioria deles preconizou o uso de parâmetros clínicos na avaliação da deglutição, o que dificulta a identificação de alterações específicas que podem direcionar a conduta sobre a via e consistência de alimentação. Sendo assim, este estudo teve como objetivo verificar a correlação entre a pontuação obtida no NIHSS e a presença de penetração laríngea e aspiração laringotraqueal nos indivíduos pós-AVC isquêmico, utilizando o exame de videofluoroscopia da deglutição. Participaram deste estudo 74 indivíduos pós-AVC isquêmico submetidos à avaliação neurológica e aplicação do NIHSS. Os indivíduos foram divididos em quatro grupos conforme a gravidade do AVC na pontuação do NIHSS, sendo G1 (0-4 pontos), G2 (5-10), G3 (11-20) e G4 (≥ 20). Destes indivíduos, dois foram excluídos da avaliação fonoaudiológica da deglutição por apresentarem comprometimento neurológico grave mensurado pelo NIHSS. 72 indivíduos foram submetidos à avaliação fonoaudiológica clinica e ao exame videofluoroscópico da deglutição, realizados no mesmo dia, com o pastoso fino e líquido ralo, observando a presença de penetração laríngea e aspiração laringotraqueal. Foi verificada a ausência de correlação estatisticamente significante entre a pontuação no NIHSS e a presença de penetração laríngea com pastoso fino ... / Abstract: The use of the National Institutes of Health Stroke Scale (NIHSS) have been proposed as a screening tool, as clinical predictors of the presence of oropharyngeal dysphagia and an indicator of the safe way of feeding in individuals after stroke, even these not scoring the swallowing disorder. However, most studies recommend the use of clinical parameters in evaluating of swallowing, which hinder identification of specific alterations that could help to decide the way of feeding and the safe consistency. Therefore, this study aimed to determine the correlation between the NIHSS score and the presence of laryngeal penetration and tracheal aspiration in individuals after ischemic stroke, using videofluoroscopic evaluation of swallowing. Seventy-four after ischemic stroke individuals were evaluated; they had been submitted to neurological and NIHSS evaluation. They were divided into four groups according to the severity of stroke in NIHSS score, G1 (0-4 points), G2 (5-10 points), G3 (11-20 points) and G4 (≥ 20 points). Two of these individuals were excluded from the swallowing clinical assessment because they have severe neurological impairment measured by NIHSS. Seventy two subjects were submitted to swallowing clinical evaluation and videofluoroscopy of swallowing, performed on the same day, using thin pasty e liquid consistencies , observing the presence of laryngeal penetration and tracheal aspiration. The absence of a statistically significant correlation between the NIHSS score and the presence of laryngeal penetration with thin pasty (P = 0.3270) and liquid (P= 0.8138) was verified. Likewise, there was no correction between the NIHSS and the presence of tracheal aspiration with thin pastoso (P = 0.3714) and liquid (P=0.6292). The laryngeal penetration occurred in only 06 (8.33%) individuals with thin pasty, distributed in G1 (66.6%) and G2 (33.3%) of the NIHSS. With liquid, laryngeal penetration ... / Mestre

As habilidades manuais podem estar prejudicadas na paralisia cerebral (PC),interferindo nas atividades funcionais do cotidiano da criança, como alimentar-se, ir ao banheiro, brincar, o que ocasiona impacto negativo na vida dela e da família. Objetivo: elaborar, aplicar e analisar um protocolo de avaliação da função manual de crianças com PC, de 0 a 7 anos e 11 meses de idade. Método: estudo dividido em 2 etapas - 1) planejamento: definição de objetivo e população alvo, realização de revisão da literatura sobre instrumentos já existentes, tipos de itens e formato de instrumento, 2) construção: construção I -desenvolvimento dos itens, seleção dos instrumentos utilizados como base do protocolo, seleção dos itens relevantes por faixa etária, análise dos itens e adequação do protocolo; projeto piloto - aplicação do protocolo junto a 36 crianças de 0 a 7 anos e 11 meses, sendo 18 com PC e 18 com DT, análise dos itens e adequação do protocolo; construção II - validação de conteúdo por profissionais/pesquisadores experientes (experts) na área, elaboração e envio do questionário aos juízes especialistas, revisão dos itens (inclusão e exclusão), análise das avaliações dos especialistas e adequação do protocolo. Resultados: foram selecionados 238 itens, sendo 38 itens da Escala Lúdica Pré Escolar de Knox (ELPK-R), 126 do Inventário Portage Operacionalizado (IPO), 32 do Teste de Triagem de Desenvolvimento de Denver II (TTDDR), 38 do Inventário de Avaliação Pediátrica de Incapacidade (PEDI) e 4 do Manual de Avaliação Motora - Escala de Desenvolvimento Motor (MAM-EDM). Todos os itens foram revisados. Realizou-se o agrupamento de 161 itens recorrentes, totalizando 120 itens, os quais foram aplicados em crianças com PC e DT. Após a aplicação, em nova análise do protocolo, foram agrupados 6 itens semelhantes, divididos 2 e excluídos 7, totalizando 109 itens, os quais foram enviados em forma de questionário para os juízes especialistas. Na sequência, as avaliações dos experts foram analisadas e, então, 3 itens foram agrupados, 1 item subdividido e 7 itens excluídos, chegando-se a um protocolo final com 101 itens, divididos em 8 faixas etárias: de 0 a 5 meses, de 6 meses a 11 meses, de 1 ano a 1 ano e 11 meses e, sucessivamente, na sequência anual até de 4 anos a 4 anos e 11 meses; em seguida há uma faixa etária de 5 anos a 6 anos e 11 meses e, após, a faixa etária de 7 anos a 7 anos e 11 meses. O resultado foi então denominado de Avaliação Manual Infantil Geral e Objetiva - AMIGO. Foram observadas 2 crianças de cada grupo em cada faixa etária, sendo que as crianças com DT apresentaram, no geral, melhores pontuações quando comparadas às crianças com PC da mesma faixa etária. Considerações finais: a avaliação AMIGO foi considerada válida e alcançou seu objetivo principal. Ainda está, porém, em processo de construção e, em estudos futuros, passará por mais duas fases de construção, sendo elas a fase III - avaliação quantitativa e a fase IV - validação, para que possa ser considerada totalmente válida e segura a sua utilização na prática clínica e na pesquisa científica. / Manual skills may be affected in cerebral palsy (CP), interfering with functional activities of child\'s daily life, such as eating, toileting, playing, which causes negative impact on child´s life and family. Objective: To develop, implement and analyze an evaluation protocol to assess manual children function with CP, aged between 0-7 years and 11 months old. Method: This study was divided into two stages - 1) planning: setting goals and target population, literature review on existing instruments, types of items and instrument format, 2) Construction: Construction I -development of items, selection of instruments used as basis of the protocol, selection of relevant items by age group, item analysis and protocol adjustment; Pilot Project - protocol application with 36 children 0-7 years, 11 months, 18 CP childerb and 18 children with typical development (TD), item analysis and protocol adjustment; Construction II - Content validation by professional / experienced researchers (experts) in the area, preparation and submission of the questionnaire to expert judges, items review (item inclusion or exclusion), analysis of experts evaluations and suitability of the protocol. Results: We selected 238 items, 38 items Revised Knox Preschool Scale (RKPPS) 126 items from Operationalized Portage Inventory (IPO), 32 from Denver II Developmental Screening Test (DDST-R) 38 from Pediatric Evaluation of Disability Inventory (PEDI) and 4 from Manual of Motor Evaluation - Motor Development Scale (MAM-EDM). All items were reviewed. We grouped 161 recurring items, totalizing 120 items, which we applied both in CP children and with CP and TD children. After the implementation, we performed a new protocol analysis and 6 similar items were grouped, 2 items divided and 7 items excluded, totalizing 109 items, which were sent as questionnaire to the expert judges. Further, experts assessments were analyzed and then 3 items were grouped, 1 item subdivided, and 7 items deleted, coming to a final protocol with 101 items, divided into eight age groups: 0-5 months of 6 months to 11 months, 1 year to 1 year and 11 months and, subsequentially, the annual sequence till 4 years to 4 years and 11 months; then there is an age group between 5 years and 6 years and 11 months, and after the age of 7 years to 7 years and 11 months. The resulting product was then called Children´s Manual Assessment General and Objective - AMIGO. Two children in each group were observed at each age, and children with TD had, overall, better scores compared to children with CP in each age group. The final considerations were that AMIGO has been valid and reached its main goal. But it is still under construction, and in future studies it will go through two more stages of construction, which were phase III - quantitative assessment and phase IV - validation, in order to be considered valid and secure to be uesd in clinical practice and in scientific research.

Objeto: As relações entre características das malformações arteriovenosas cerebrais (MAV) como o tamanho, localização e a angioarquitetura com o risco subseqüente de hemorragia podem ser úteis para previsão do comportamento das MAV e podem guiar estratégias de tratamento. Métodos: Nós analisamos prospectivamente 390 pacientes com MAV cerebrais no Grupo de Estudo de Malformações Vasculares cerebrais da Universidade de Toronto. A localização, o tamanho, detalhes da angioarquitetura, suprimento sangüíneo e a forma de apresentação clínica foram anotados no início do seguimento. Quarenta e seis pacientes tiveram sangramento devido à MAV em um seguimento de 1205 paciente/anos (média de 3,1 anos/paciente). Na análise ajustada para as múltiplas características da MAV, malformações grandes sangraram mais freqüentemente que lesões pequenas (OR=2,5; 95%CI=1,41 a 4,35; p<0.0001) e MAV profundas tiveram mais sangramentos no seguimento que as superficiais (OR=5,56; 95%CI=2,63 a 12,5; p<0.0001) . Conclusões: As MAV profundas e as grandes foram significativamente mais predispostas a eventos hemorrágicos no seguimento.

The major purpose of this study was to determine whether a relationship exists between cerebral laterality dominance and leadership behavior and traits. An additional purpose was to determine whether a relationship exists between cerebral laterality dominance and gender, ethnicity, and educational position.

Chiu, Wui Man. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 107-128). / Abstracts in English and Chinese. / Abstract --- p.i / 中文摘要 --- p.iv / Acknowledgements --- p.vi / Publications --- p.viii / Table of Contents --- p.ix / List of Tables --- p.xiv / List of Figures --- p.xv / List of Abbreviations --- p.xviii / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Hypoxic-ischemic encephalopathy in human infants --- p.1 / Chapter 1.1.1 --- Incidence --- p.1 / Chapter 1.1.2 --- Biphasic development of HI brain damage --- p.2 / Chapter 1.1.2.1 --- Initiating mechanism: energy failure in immature brain --- p.3 / Chapter 1.1.2.2 --- Biochemical cascades --- p.4 / Chapter 1.1.2.2.1 --- Excitatory amino acid receptor activation by glutamate --- p.4 / Chapter 1.1.2.2.2 --- Intracellular calcium accumulation --- p.4 / Chapter 1.1.2.2.3 --- Formation of free radicals --- p.5 / Chapter 1.1.2.2.3.1 --- Reactive oxygen species (ROS) --- p.5 / Chapter 1.1.2.2.3.2 --- Nitric oxide (NO) --- p.6 / Chapter 1.1.2.3 --- Release of inflammatory mediators --- p.6 / Chapter 1.1.2.4 --- Mitochondrial dysfunction --- p.7 / Chapter 1.1.2.5 --- Final path to death: necrosis or apoptosis --- p.8 / Chapter 1.1.2.6 --- Ways to change: neuronal survival and proliferation signaling --- p.8 / Chapter 1.1.3 --- Interventions for neonatal hypoxia-ischemia --- p.9 / Chapter 1.2 --- Animal models mimicking hypoxia-ischemia brain injury --- p.12 / Chapter 1.2.1 --- Comparisons of animal models of hypoxia-ischemia --- p.12 / Chapter 1.2.2 --- Development of neonatal rat model with hypoxic-ischemic damage --- p.14 / Chapter 1.3 --- Neural stem/progenitor cells --- p.15 / Chapter 1.3.1 --- Effect of hypoxic-ischemia on neural stem/progenitor cells --- p.17 / Chapter 1.4 --- Thrombopoietin --- p.18 / Chapter Chapter 2 --- Objectives --- p.23 / Chapter Chapter 3 --- Materials and Methodology --- p.24 / Chapter 3.1 --- Establishment of neonatal rat model of HI brain damage and effects of TPO on neural protection --- p.24 / Chapter 3.1.1 --- Animal protocols --- p.24 / Chapter 3.1.2 --- Induction of HI brain damage in neonatal rats --- p.24 / Chapter 3.1.3 --- Treatment with TPO --- p.25 / Chapter 3.1.4 --- Sacrifice of rats --- p.25 / Chapter 3.1.5 --- Read-out measurements --- p.26 / Chapter 3.1.5.1 --- Brain weight --- p.26 / Chapter 3.1.5.2 --- Gross injury assessment of the right hemisphere --- p.26 / Chapter 3.1.5.3 --- Histology --- p.27 / Chapter 3.1.5.4 --- Blood cell count --- p.27 / Chapter 3.1.5.6 --- Functional assessments --- p.28 / Chapter 3.1.5.6.1 --- Grip traction test --- p.28 / Chapter 3.1.5.6.2 --- Elevated body swing test --- p.28 / Chapter 3.1.5.7 --- Statistical analysis --- p.28 / Chapter 3.2 --- Establishment of in vitro model of primary mouse NSPs and the effect of TPO on their proliferation --- p.29 / Chapter 3.2.1 --- Mouse embryo dissection for the extraction of NSP --- p.29 / Chapter 3.2.2 --- Culturing of NSP --- p.30 / Chapter 3.2.3 --- Immunofluorescence staining for stem cell markers --- p.31 / Chapter 3.2.4 --- Neurosphere assay with different combinations of mitogens --- p.31 / Chapter 3.2.5 --- Neurosphere assay with different concentrations of TPO --- p.32 / Chapter 3.2.6 --- Neurosphere assay under hypoxia --- p.32 / Chapter 3.2.7 --- Statistical analysis --- p.33 / Chapter Chapter 4 --- Effects of thrombopoietin on neonatal rat models of hypoxia-ischemia brain damage --- p.39 / Chapter 4.1 --- Summary of experimental settings --- p.39 / Chapter 4.2 --- Results --- p.39 / Chapter 4.2.1 --- Mortality --- p.39 / Chapter 4.2.2 --- Effects of TPO on p7 mild damage model 1 week post-surgery --- p.40 / Chapter 4.2.2.1 --- Body and brain weights --- p.40 / Chapter 4.2.2.2 --- Gross injury score --- p.41 / Chapter 4.2.2.3 --- Cortex and hippocampus area --- p.41 / Chapter 4.2.2.4 --- Blood cell counts --- p.42 / Chapter 4.2.3 --- Effects of TPO on p7 severe damage model 1 week post-surgery --- p.43 / Chapter 4.2.3.1 --- Body and brain weights --- p.43 / Chapter 4.2.3.2 --- Gross injury score --- p.43 / Chapter 4.2.3.3 --- Cortex area --- p.44 / Chapter 4.2.3.4 --- Blood cell counts --- p.44 / Chapter 4.2.4 --- Effects of TPO on p7 severe damage model 3 week post-surgery --- p.45 / Chapter 4.2.4.1 --- Body and brain weights --- p.45 / Chapter 4.2.4.2 --- Gross injury score --- p.46 / Chapter 4.2.4.3 --- Blood cell counts --- p.46 / Chapter 4.2.4.4 --- Functional outcomes --- p.46 / Chapter 4.2.5 --- Effects of TPO on pl4 severe damage model 1 week post-surgery --- p.47 / Chapter 4.2.5.1 --- Body and brain weights --- p.47 / Chapter 4.2.5.2 --- Gross injury score --- p.48 / Chapter 4.2.5.3 --- Cortex area --- p.48 / Chapter 4.2.5.4 --- Blood cell counts --- p.49 / Chapter 4.3 --- Discussion --- p.49 / Chapter Chapter 5 --- Effects of thrombopoietin on the proliferation of primary mouse neural stem/ progenitor cells in culture --- p.83 / Chapter 5.1 --- Summary of experimental settings --- p.83 / Chapter 5.2 --- Results --- p.83 / Chapter 5.2.1 --- Effect of EGF or bFGF withdrawal on NSP proliferation --- p.84 / Chapter 5.2.2 --- Dose effect of TPO treatment on NSP proliferation --- p.85 / Chapter 5.2.3 --- Effect of hypoxia --- p.85 / Chapter 5.2.4 --- Effect of TPO treatment in combination with hypoxia --- p.86 / Chapter 5.2.5 --- Detection of neural progenitor cell marker --- p.87 / Chapter 5.3 --- Discussion --- p.88 / Chapter Chapter 6 --- General discussion --- p.101 / Bibliography --- p.106

在亞洲人群包括中國人群中，顱內動脈粥樣硬化（ICAS）發病率很高，是缺血性卒中和短暫性腦缺血發作（TIA）的首要病因。然而，目前ICAS 並未被深入研究。因此我們在一系列研究中通過運用傳統及創新的神經影像學方法，來研究ICAS 的臨床及血流動力學特徵，以期促進其全面評價及危險分層。 / 既往研究發現亞洲人群和西方人群在頭頸部動脈粥樣硬化的發生和發展上存在種族差異。爲了進一步驗證這些種族差異，我們開展了一項社區研究，以探索無癥狀性顱內外動脈粥樣硬化在中國社區成年居民中的發病情況，以及二者之間的相互關係。在該研究中，我們分別採用經顱多普勒（TCD）和頸部血管超聲（CD）來評價顱內和顱外動脈的粥樣硬化。在研究納入的537 例研究對象中，我們發現顱內動脈粥樣硬化的發展優先於頸動脈粥樣硬化，而且不同階段的頸動脈粥樣硬化與顱內動脈粥樣硬化並無獨立相關關係。該結果提示，在中國人群的全身系統性粥樣硬化的過程中，顱內動脈粥樣硬化可能是一個比較早期而且相對獨立的過程，這與西方人群的情況不同。本研究結果進一步支持東西方人群在顱內外動脈粥樣硬化進程上存在的種族差異。 / 根據既往研究結果，病因為癥狀性ICAS的缺血性卒中或TIA患者卒中復發的風險很高。目前，癥狀性ICAS患者的危險分層大多基於其動脈管腔的狹窄程度。然而，管腔的解剖學狹窄程度並不一定與其血流動力學的嚴重程度成比例，而後者也可能影響相關患者的卒中復發風險。因此，我們進行了以下的一系列研究， 以評價癥狀性ICAS的血流動力學特徵，同時初步探索其在相關患者危險分層中的應用價值。 / 我們首先進行了三項研究，採用一種基於磁共振血管成像（MRA）的創新方法來評價癥狀性ICAS的血流動力學嚴重程度。基於時間飛躍法（TOF）MRA的信號對比機制，我們提出了一項名為信號強度比值（SIR）的參數來定量地評價癥狀性ICAS 的血流動力學效應；該參數代表TOF MRA 影像上經過背景信號強度校正后的ICAS 病變后和病變前的信號強度比值。在一項初步研究中，我們確定了該參數的評價和計算方法。在26例癥狀性ICAS病變中，我們發現該參數的計算操作簡便，在臨床上可行，且在同一評價者的兩次評價中具有很高的可重複性。在隨後的一項研究中，我們在102例癥狀性ICAS病變中發現該參數在兩位評價者之間具有顯著的可重複性。在第三項研究中，我們在36例具有癥狀性ICAS的缺血性卒中患者中發現SIR與患者的急性梗死灶體積顯著相關，但我們並未發現該參數與患者1年的卒中復發風險相關，可能由於該研究的樣本量過小。以上三項研究證實，SIR作為一種基於TOF MRA的評價癥狀性ICAS血流動力學嚴重程度的方法，具有可重複性及臨床可行性；而其對於相關患者危險分層的價值需要在前瞻性的較大型研究中進一步驗證。 / 在如下的另外兩項研究中，我們採用計算機流體動力學（CFD）技術對癥狀性ICAS患者的計算機斷層掃描血管成像（CTA）影像進行重建，從而評價其ICAS 病變的血流動力學特徵。首先，在一項初步研究中，我們探索了採用臨床常規CTA影像進行CFD模型重建的可行性。在10例癥狀性ICAS病變中，9例病變的CTA原始圖像成功重建為CFD模型。重建的CFD模型可以定量地反映ICAS病變的各種血流動力學特徵。該初步研究證實了基於臨床常規CTA進行CFD建模從而評價ICAS血流動力學特徵的可行性。在隨後的一項研究中，我們探索了CFD 模型反映的癥狀性ICAS 的血流動力學特徵對於相關患者卒中復發的預測價值。在32例具有70-99%管腔狹窄的癥狀性ICAS病例中，我們發現病變前後血流動力學參數的變化（包括壓力，剪切應變率及血流速度）可能預測患者的卒中復發風險。以上兩項研究證實，基於臨床常規CTA進行CFD模型重建從而定量評價癥狀性ICAS的血流動力學特徵具可行性，同時，這些血流動力學特徵可能對相關患者的卒中復發風險具有預測價值。 / 綜上所述，通過以上研究，我們進一步證實了亞洲人群和西方人群在顱內外動脈粥樣硬化的進程上存在的種族差異。更重要的是，我們的研究證實評價癥狀性ICAS病變的血流動力學特徵具有臨床意義。對於相關患者，採用以上研究中的兩種方法評價癥狀性ICAS的血流動力學特徵，可能對患者的危險分層具有潛在的指導意義。在未來的前瞻性大樣本研究中，上述方法對癥狀性ICAS患者卒中復發風險的預測價值需要進一步證實，以期促進相關的臨床決策，從而在長遠目標上降低相關患者的卒中復發風險。 / Intracranial atherosclerosis (ICAS) is of high prevalence in Asia, which is the leading cause for ischemic stroke and transient ischemic attack (TIA) in Asians, including the Chinese. However, it has not been fully appreciated or adequately investigated in relevant studies. In this thesis, we tried to delineate the hemodynamics and clinical implications of ICAS, by using several traditional and novel neuroimaging methods. / Previous studies had suggested differences in atherogenesis of intra- and extracranial arteries between Asians and Caucasians. To find further evidence, we performed a study to investigate asymptomatic ICAS and carotid atherosclerosis and their correlations in community-dwelling Chinese adults, by using transcranial Doppler and carotid duplex ultrasonography, respectively. For the 537 subjects studied, we found more advanced asymptomatic ICAS than carotid atherosclerosis, and there were no independent correlations between different stages of carotid atherosclerosis and presence of ICAS. The results suggested that atherogenesis of intracranial arteries might be a relatively independent course in systemic atherosclerosis in the Chinese population, which is unlike the case in Caucasians. By combing with previous findings, results of this study further supported the existence of racial differences in cervicocerebral atherogenesis between Asians and Caucasians. / According to previous studies, stroke patients with symptomatic ICAS are at high risk of recurrence. Currently, risk stratification of symptomatic ICAS are usually based on the percentage of luminal stenosis. However, the anatomic severity does not always proportionate to its hemodynamic significance, which may also impact on the risk of stroke recurrence in symptomatic ICAS. Therefore, we performed a series of studies as follows to evaluate the hemodynamics of symptomatic ICAS, and to assess its value in risk stratification of those with such lesions. / We first performed three studies based on time-of-flight (TOF) magnetic resonance angiography (MRA), to gauge the hemodynamic significance of symptomatic ICAS. Based on the signal contrast mechanism of TOF MRA, we developed a novel index, signal intensity ratio (SIR), representing changes of signal intensities (SI) across an ICAS on maximum intensity projections of TOF MRA, to quantify its hemodynamic significance: SIR = (mean post-stenotic SI - mean background SI) / (mean pre-stenotic SI - mean background SI). In a pilot study to establish the methodology of this index, we found it easy to perform, and highly reproducible between repetitive measurements by a same observer in 26 symptomatic ICASs. In a subsequent study, we also found this index to be substantially reproducible between measurements from two observers in 102 symptomatic ICAS lesions. In a third study, we tried to investigate the relationships between SIR of ICAS, other imaging features, and 1 year outcomes of patients with symptomatic ICAS. In the 36 patients enrolled, SIR was found to be significantly, linearly and negatively correlated to acute infarct volume on diffusion-weighted MR images. However, we did not establish a definite correlation between SIR and recurrent ischemic stroke, probably due to the small sample size. These studies suggested that SIR as evaluated on MRA was a feasible and reproducible method to gauge the hemodynamic and functional significance of ICAS. The role of this index in predicting further recurrent risks in those with symptomatic ICAS needs to be verified in future studies. / In another two studies, we applied the computational fluid dynamics (CFD) modeling technique in processing computed tomography angiography (CTA) images, to evaluate the hemodynamic characteristics of ICAS. In a pilot study, we tested the feasibility of CFD modeling of ICAS based on CTA images. Among 10 cases of symptomatic ICAS identified on CTA, the CTA source images of 9 were successfully processed to CFD models, which were able to quantitatively delineate the hemodynamic environment across the lesions. This pilot study demonstrated the feasibility of constructing CFD models of ICAS out of routinely obtained CTA source images. Then in a second study, we preliminarily explored the values of hemodynamics of ICAS revealed by such CFD models, in predicting recurrent risks in patients with symptomatic ICAS of 70-99% luminal stenosis. In the 32 cases evaluated, we found that changes of hemodynamic features across an ICAS lesion, including the changes of pressure, shear strain rate, and blood flow velocity, may be able to predict the recurrent risk in this patient subset. Therefore, it was feasible to model hemodynamics of symptomatic ICAS based on CTA images, and future prospective studies with larger sample sizes are warranted to further validate the role of CFD modeling in risk stratification of affected patients. / In conclusion, in this thesis we found further evidence to support the existence of racial differences in atherogenesis of cervicocerebral arteries between Caucasians and Asians. More importantly, we demonstrated that hemodynamics of symptomatic ICAS could be of clinical significance in characterization of such lesions. In patients with symptomatic ICAS, the two methods to evaluate hemodynamic features of ICAS as used in this thesis, may yield potential values in predicting the recurrent risk of these patients. In the near future, prospective studies enrolling more patients are warranted to further validate findings in this thesis, to embrace more reasonable and comprehensive evaluation of symptomatic ICAS, so as to facilitate decision making in clinical scenarios and patient selection in clinical studies, which in the long run may help reduce the risk of stroke recurrence in affected patients. / 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. / Leng, Xinyi. / Thesis (Ph.D.) Chinese University of Hong Kong, 2014. / Includes bibliographical references (leaves 131-146). / Abstracts also in Chinese.

Objetivo: Analisar e descrever o perfil de expressão das proteínas relacionadas ao mecanismo de apoptose (PARP e AIF), e o perfil de expressão gênica sérica do microRNA-9 relacionado ao mecanismo de apoptose, em ratos submetidos à isquemia cerebral focal por oclusão da ACM por 90 minutos, seguida de reperfusão de 48horas, associado ou não com modelo de alcoolismo crônico. Métodos: Foram utilizados 20 ratos Wistar adultos, subdivididos em 4 grupos experimentais: grupo controle (C): animais submetidos apenas à anestesia; grupo isquêmico (I): animais submetidos à isquemia cerebral focal por 90 minutos seguido por reperfusão de 48 horas; grupo alcoolizado (A): animais que receberam diariamente álcool etílico absoluto diluído a 20% em água durante quatro semanas; e, grupo isquêmico e alcoolizado (IA): animais submetidos ao mesmo tratamento do grupo A e que, após quatro semanas foram submetidos à isquemia cerebral focal durante 90 minutos, seguido por reperfusão de 48 horas. As amostras do encéfalo coletadas foram processadas para a análise imunohistoquímica (para a expressão protéica de PARP-1 e AIF); e o sangue da artéria ventral da cauda foi coletado para a análise da expressão gênica do miRNA-9, relacionada ao mecanismo de apoptose, pela técnica de PCR em tempo real. Resultados: A comparação entre os grupos identificou uma redução da expressão proteica de PARP-1 nos animais do grupo AI quando comparado com os demais. Foi observada marcação positiva nuclear para a proteína AIF somente no grupo IA. Não houve diferença estatisticamente significante da expressão sérica do miRNA-9 entre os grupos. Conclusão: O modelo proposto, pode não ter sido suficiente para promover a ativação de AIF nos grupos C, A e I e desta forma, a apoptose celular por essa via analisada. A expressão proteica de PARP-1 no grupo A, associado com a expressão nula de AIF, indica um efeito neuroprotetor do etanol neste grupo. A redução da expressão proteica de PARP-1 não afetou sua atividade enzimática, proporcionando, mesmo em baixas concentrações, ativação de AIF no grupo IA. A expressão de PARP- 1 no grupo I, associada a expressão nula de AIF indica que o modelo de isquemia possivelmente gerou leves danos no DNA o que estimulou a ativação de PARP-1 somente em níveis suficientes para promover a reparação do DNA e não a ativação do processo de apoptose pela translocação de AIF. A expressão gênica sérica do miRNA- 9 observada indicou que a mesma foi suprimida quando exposta a mecanismos de estresse (alcoolismo, isquemia e a associação dos mesmos). A correlação do miRNA-9 com a expressão proteica de PARP-1 e AIF, indicou um aspecto protetor da baixa regulação do miRNA-9 tanto em animais alcoolizados como em animais isquêmicos. O grupo IA apresentou uma tendência a baixa expressão do miRNA-9, baixa expressão de PARP-1 e alta expressão de AIF, indicando que a associação álcool e isquemia tenha interferido no efeito protetor do miRNA-9 visto nos demais grupos / Aim: To analyze and describe the expression profile of proteins related to apoptosis mechanism (PARP and AIF), and profile of gene expression of miRNA-9 related to apoptosis mechanism in rats submitted to focal cerebral ischemia by occlusion of the CMA for 90 minutes, followed by 48 hours of reperfusion, associated or without associated to chronic alcoholism model. Methods: 20 adult Wistar rats were used, divided into 4 groups: control group (C): animals submitted only to anesthesia; Ischemic group (I): animals subjected to focal cerebral ischemia for 90 minutes followed by 48 hours of reperfusion; alcoholic group (A): animals that received daily solution of 20% of absolute ethyl alcohol diluted in water during four weeks; and ischemic group and alcoholized (IA): Animals subjected to the same treatment group A and after four weeks were subjected to focal cerebral ischemia for 90 minutes followed by 48 hours of reperfusion. The brain samples were collected and processed for immunohistochemical analysis (for protein expression - PARP-1 and AIF); and the blood from ventral artery of tail was collected for the analysis, by PCR in real time, of gene expression of miRNA-9 related to the mechanism of apoptosis. Results: The comparison between the groups identified a decrease in protein expression (PARP-1) in animals from IA group compared to others groups. Nuclear positive staining was observed for the AIF protein only in the IA group. There was no significant difference in serum expression of miRNA-9 between the groups. Conclusion: The proposed model may not have been sufficient to promote the activation of AIF in groups C, A and I, and thus the apoptosis analyzed in this way. Protein expression of PARP-1 in group A associated with a null expression of AIF, indicate a neuroprotective effect of ethanol in this group. The reduction of protein expression PARP-1 did not affect its enzymatic activity, providing even at low concentrations, activation AIF in IA group. The expression of PARP-1 in group I associated with null expression of AIF showed that model of ischemia, possibly, promoted light damage in DNA which stimulated PARP-1 activation just in sufficient levels to promote DNA repair, and without activation of apoptosis by translocation of AIF. The gene expression of miRNA-9 indicated that it was suppressed when exposed to mechanical stress (alcoholism, ischemia and combination thereof). The correlation of miRNA-9 with the protein expression (PARP-1 and AIF), indicated a protective aspect of downregulation of the miRNA-9 in both animals drunk as ischemic animals. IA group showed a trend to low expression of miRNA-9 and PARP- 1, in other hand an overexpression of AIF, indicating that the association between alcohol and ischemia interfered in protective effect of miRNA-9 seen in the other groups

Despite the popularity of home program interventions there is little evidence to demonstrate effectiveness, particularly when an explicit family centred framework is adopted. This single-group pre-post design study evaluates the impact of a standardised occupational therapy home program implemented with a group of 20 children (2-7 years, mean age 3.8)with spastic hemiplegic cerebral palsy. The study measured the effect of the program using: goal attainment scaling(GAS);pediatric evaluation of disability inventory (PEDI); and quality of upper extremity test(QUEST). In addition, parent participation intensity was measured through a home program log. The use of a standardised occupational therapy home program for children with cerebral palsy is recommended as an effective method to achieve therapy goals. Further research using more rigorous designs is required to fully explore treatment efficacy. / Master of Science (Hons.)

Thesis (Ph. D.)--West Virginia University, 2003. / Title from document title page. Document formatted into pages; contains xii, 231 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references.