RESUMO
BACKGROUND AND PURPOSE: MTI is a quantitative MR imaging technique that has recently demonstrated structural integrity differences between controls and patients with HD. Potentially, MTI can be used as a biomarker for monitoring disease progression. To establish the value of MTI as a biomarker, we aimed to examine the change in these measures during the course of HD. MATERIALS AND METHODS: From the Leiden TRACK-HD study, 25 controls, 21 premanifest gene carriers, and 21 patients with manifest HD participated at baseline and during a 2-year follow-up visit. Brain segmentation of the cortical gray matter, white matter, caudate nucleus, putamen, pallidum, thalamus, amygdala, and hippocampus was performed by using the automated tools FAST and FIRST in FSL. Individual MTR values were calculated from these regions, and MTR histograms were constructed. RESULTS: In the premanifest HD group stage "far from disease onset," a significant increase in MTR peak height of the putamen was observed with time. During the manifest HD stage, neither the mean MTR nor the MTR peak height showed a significant change during a 2-year follow-up. CONCLUSIONS: MTI-derived measures are not suitable for monitoring in Huntington disease during a 2-year period because there was no decrease in structural integrity detected in any of the manifest HD groups longitudinally. The finding of increased putaminal MTR peak height in the premanifest far from disease onset group could relate to a predegenerative process, compensatory mechanisms, or aberrant development but should be interpreted with caution until future studies confirm this finding.
Assuntos
Encéfalo/patologia , Doença de Huntington/patologia , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Adulto , Tonsila do Cerebelo/patologia , Gânglios da Base/patologia , Córtex Cerebral/patologia , Progressão da Doença , Seguimentos , Hipocampo/patologia , Humanos , Doença de Huntington/genética , Estudos Longitudinais , Pessoa de Meia-Idade , Tálamo/patologiaAssuntos
Encéfalo/efeitos dos fármacos , Creatina/administração & dosagem , Doença de Huntington/tratamento farmacológico , Administração Oral , Ácido Aspártico/análogos & derivados , Ácido Aspártico/sangue , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Creatina/efeitos adversos , Creatina/sangue , Creatinina/sangue , Relação Dose-Resposta a Droga , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/fisiologia , Humanos , Doença de Huntington/diagnóstico , Doença de Huntington/metabolismo , Espectroscopia de Ressonância Magnética , Testes Neuropsicológicos , Cooperação do Paciente , Fosfocreatina/sangue , Projetos Piloto , Resultado do Tratamento , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologiaAssuntos
Ácido Aspártico/análogos & derivados , Creatina/uso terapêutico , Doença de Huntington/tratamento farmacológico , Trifosfato de Adenosina/metabolismo , Ácido Aspártico/metabolismo , Encéfalo/metabolismo , Colina/metabolismo , Creatina/efeitos adversos , Creatina/metabolismo , Diarreia/induzido quimicamente , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Humanos , Doença de Huntington/diagnóstico , Doença de Huntington/metabolismo , Espectroscopia de Ressonância Magnética , Músculo Esquelético/metabolismo , Náusea/induzido quimicamente , Testes Neuropsicológicos , Fosfocreatina/metabolismo , Projetos Piloto , Valores de Referência , Segurança , Resultado do TratamentoRESUMO
Sporadic inclusion body myositis (s-IBM) is a chronic inflammatory myopathy of unknown pathogenesis. The common findings of ragged red fibres, cytochrome c oxidase-negative fibres and multiple mitochondrial DNA deletions in the muscle of patients with s-IBM have suggested that a deficit of energy metabolism may be of pathogenic relevance. To test this hypothesis we used 31P magnetic resonance spectroscopy to assess in vivo skeletal muscle mitochondrial function in the calf muscles of 12 patients with definite s-IBM. Eleven patients showed multiple mitochondrial DNA deletions in skeletal muscle and 67% showed ragged red fibres and/or cytochrome c oxidase-negative fibres. T1-weighted MR images showed increased signal intensity in the calf muscle of all patients except one. The involvement of calf muscle was confirmed by 31P magnetic resonance spectroscopy of resting muscle, which disclosed abnormalities in metabolite ratios in all patients. However, muscle oxidative metabolism assessed during recovery from exercise was normal in patients with s-IBM, as maximum rates of mitochondrial ATP production and post-exercise ADP recovery rates were within the normal range in all cases. We conclude that muscle mitochondrial abnormalities are a secondary process and unlikely to play a significant role in the pathogenesis of s-IBM.