Estudo tractográfico dos indivíduos com mutação para doença de Huntington nas fases sintomática e pré-sintomática
Data
2015-10-28
Autores
Pinto, Roberta Arb Saba Rodrigues 
Orientadores
Ferraz, Henrique Ballalai
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Introdução: a doença de Huntington (DH) é decorrente de uma mutação com penetrância completa no gene da proteína huntingtina. Ainda não há um tratamento neuroprotetor efetivo para os indivíduos portadores da mutação, mas há testes em andamento com novas drogas. Uma das limitações para os ensaios clínicos de fase pré-sintomática da doença é a ausência de um marcador biológico confiável para se avaliar a progressão do processo neurodegenerativo. Na DH ocorre perda progressiva do volume da substância branca (SB) e de sua integridade. A técnica de imagem por tensor de difusão (DTI - Diffusion Tensor Imaging) para avaliar a anisotropia fracionada (FA - Fractionalanisotropy) é capaz de estudar os tractos da SB. Objetivo: identificar o envolvimento dos tractos da substância branca na DH, através desta técnica e assim avaliá-la como um possível biomarcador para a doença. Métodos: Foram selecionados 34 sujeitos e divididos em três grupos: 11 pacientes com doença de Huntington, 12 indivíduos pré-sintomáticos (teste molecular positivo para DH, porém sem sintomas clínicos, fase pré-sintomática) e 11 indivíduos controles (com teste molecular negativo para DH). Os pacientes foram submetidos à avaliação clínica, das funções motora, cognitiva e comportamental. Os sujeitos de pesquisa realizaram exame de ressonância magnética de encéfalo com tractografia da substância branca utilizando o DTI, com mensuração da FA. Resultados: observou-se uma diminuição estatisticamente significante da FA da SB dos tractos córtico espinhal; coroa radiada; joelho, corpo e esplênio do corpo caloso; cápsula externa; radiações talâmicas; fascículo longitudinal superior e inferior e fascículo fronto-occiptal inferior, quando comparados os grupos DH aos controles e pré-sintomáticos, o que denota diminuição da congruência/orientação das fibras nestas estruturas, demonstrando processo degenerativo e perda axonal nos pacientes com DH sintomática. Não houve diferença estatisticamente significante entre o grupo pré-sintomático e controle. A SB é acometida de maneira generalizada e vários são os tractos envolvidos, demonstrando que a SB parece ter um papel importante na fisiopatologia da DH. Conclusão: a tractografia nos parece uma técnica interessante para se aplicar aos pacientes com DH, mas outros estudos com amostras maiores devem ser realizados para se avaliar o possível papel na progressão do processo neurodegenerativo.
Intorduction:Huntington's disease (HD) is caused by a mutation with complete penetrance in the huntingtin protein gene. There is still no effective neuroprotective treatment for individuals with the mutation, but there are ongoing trials with new drugs. One of the limitations of clinical trials during presymptomatic stage of the disease is the lack of a reliable biological marker for assessing the progression of neurodegeneration. HD occurs in progressive loss of white matter (WM) volume and its integrity. The imaging technique through diffusion tensor imaging (DTI - Diffusion Tensor Imaging) to evaluate the fractional anisotropy (FA - Fractional anisotropy), is able to study the tracts of WM. Objective: to identify the involvement of white matter tracts in HD, using this technique and, thus, evaluate it as a potential biomarker for the disease. Methods: 34 subjects were selected and divided into three groups: 11 patients with Huntington's disease, 12 presymptomatic individuals (positive HD molecular test, without clinical symptoms, presymptomatic phase), and 11 control subjects (negative HD molecular test). Patients underwent clinical assessment of motor, cognitive and behavioral functions. Study subjects performed Magnetic Resonance Imaging (MRI) of the brain with tractography of white matter using DTI, with measurement of FA. Results: there was a statistically significant decrease of FA in the cortical spinal tracts; corona radiata; knee, body and splenium of the corpus callosum; external capsule, thalamic radiations; superior and inferior longitudinal fasciculus and inferior frontal-occipital fasciculus WM, when compared DH group to the control and presymptomatic groups. This shows decreased congruence / orientation of the fibers in these structures, demonstrating degenerative process and axonal loss in patients with symptomatic HD. There was no statistically significant difference between the presymptomatic group and control group. WM is affected in a generalized form and various tracts are involved, demonstrating that the WM appears to have an important role in the pathophysiology of HD. Conclusion: the tractography seems to be an interesting technique to be applied to patients with DH, but other studies with larger sample are required to assess the possible role in the progression of the neurodegenerative process.
Intorduction:Huntington's disease (HD) is caused by a mutation with complete penetrance in the huntingtin protein gene. There is still no effective neuroprotective treatment for individuals with the mutation, but there are ongoing trials with new drugs. One of the limitations of clinical trials during presymptomatic stage of the disease is the lack of a reliable biological marker for assessing the progression of neurodegeneration. HD occurs in progressive loss of white matter (WM) volume and its integrity. The imaging technique through diffusion tensor imaging (DTI - Diffusion Tensor Imaging) to evaluate the fractional anisotropy (FA - Fractional anisotropy), is able to study the tracts of WM. Objective: to identify the involvement of white matter tracts in HD, using this technique and, thus, evaluate it as a potential biomarker for the disease. Methods: 34 subjects were selected and divided into three groups: 11 patients with Huntington's disease, 12 presymptomatic individuals (positive HD molecular test, without clinical symptoms, presymptomatic phase), and 11 control subjects (negative HD molecular test). Patients underwent clinical assessment of motor, cognitive and behavioral functions. Study subjects performed Magnetic Resonance Imaging (MRI) of the brain with tractography of white matter using DTI, with measurement of FA. Results: there was a statistically significant decrease of FA in the cortical spinal tracts; corona radiata; knee, body and splenium of the corpus callosum; external capsule, thalamic radiations; superior and inferior longitudinal fasciculus and inferior frontal-occipital fasciculus WM, when compared DH group to the control and presymptomatic groups. This shows decreased congruence / orientation of the fibers in these structures, demonstrating degenerative process and axonal loss in patients with symptomatic HD. There was no statistically significant difference between the presymptomatic group and control group. WM is affected in a generalized form and various tracts are involved, demonstrating that the WM appears to have an important role in the pathophysiology of HD. Conclusion: the tractography seems to be an interesting technique to be applied to patients with DH, but other studies with larger sample are required to assess the possible role in the progression of the neurodegenerative process.
Descrição
Citação
PINTO, Roberta Arb Saba Rodrigues. Estudo tractográfico dos indivíduos com mutação para doença de Huntington nas fases sintomática e pré-sintomática. 2015. 83 f. Tese (Doutorado em Neurologia - Neurociências) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, 2015.