Structural signature of SCA3: From presymptomatic to late disease stages

Autor(es)

Ribeiro Rezende, Thiago Junqueira ^[1] ; Ribeiro de Paiva, Jean Levi ^[1] ; Muro Martinez, Alberto Rolim ^[1] ; Lopes-Cendes, Iscia ^[2] ; Pedroso, Jose Luiz ^[3] ; Povoas Barsottini, Orlando Graziani ^[3] ; Cendes, Fernando ^[1] ; Franca, Jr., Marcondes C. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Sch Med Sci, Dept Neurol, Campinas, SP - Brazil

^[2] Univ Estadual Campinas, Sch Med Sci, Dept Med Genet, Campinas, SP - Brazil

^[3] Fed Univ Sao Paulo UNIFESP, Dept Neurol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: ANNALS OF NEUROLOGY; v. 84, n. 3, p. 401-408, SEP 2018.
• Citações Web of Science: 2

Resumo

ObjectiveMachado-Joseph disease (SCA3/MJD) is the most frequent spinocerebellar ataxia worldwide and characterized by brainstem, basal ganglia, and cerebellar damage. However, little is known about the natural history of the disease. This motivated us to determine the extension and progression of central nervous system involvement in SCA3/MJD using multimodal magnetic resonance imaging (MRI)-based analyses in a large cohort of patients (n=79) and presymptomatic subjects (n=12). MethodsAll subjects underwent MRI in a 3T device to assess gray and white matter. To evaluate the cerebral and cerebellar cortices, we used measures from FreeSurfer and SUIT. T1-multiatlas assessed deep gray matter. Diffusion tensor imaging multiatlas was used to investigate cerebral white matter (WM) and SpineSeg to assess the cervical spinal cord. ResultsThere was widespread WM and cerebellar damage, in contrast to the restricted motor cortex involvement when all patients are compared to age- and sex-matched controls. Presymtomatic patients showed WM microstructural abnormalities mainly in the cerebellar and cerebral peduncles and volumetric reduction of midbrain, spinal cord, and substantia nigra. To assess the disease progression, we divided patients into four subgroups defined by time from ataxia onset. There was a clear pattern of evolving structural compromise, starting in infratentorial structures and progressing up to the cerebral cortex. ConclusionStructural damage in SCA3/MJD begins in the spinal cord, cerebellar peduncles, as well as substantia nigra and progresses to cerebral areas in the long term. These structural differences reveal some insights into the pathogenesis of SCA3/MJD and suggest a staging scheme to map the progression of the disease. Ann Neurol 2018;84:401-408 (AU)

• Processo FAPESP: 13/07559-3 - Instituto Brasileiro de Neurociência e Neurotecnologia - BRAINN
• Beneficiário: Fernando Cendes
• Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 13/01766-7 - Contribuição ao diagnóstico, à fisiopatologia e à terapêutica das neuronopatias sensitivas
• Beneficiário: Marcondes Cavalcante Franca Junior
• Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores
• Processo FAPESP: 17/13102-7 - Caraterização e comparação dos métodos de segmentação cerebelar e cerebral
• Beneficiário: Thiago Junqueira Ribeiro de Rezende
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 14/19786-7 - Cálculo automatizado dos tempos de relaxação transversal: identificação de depósitos de ferro no cérebro
• Beneficiário: Thiago Junqueira Ribeiro de Rezende
• Linha de fomento: Bolsas no Brasil - Doutorado