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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Structural signature of SCA3: From presymptomatic to late disease stages

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Author(s):
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]
Total Authors: 8
Affiliation:
[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
Total Affiliations: 3
Document type: Journal article
Source: ANNALS OF NEUROLOGY; v. 84, n. 3, p. 401-408, SEP 2018.
Web of Science Citations: 7
Abstract

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)

FAPESP's process: 13/07559-3 - BRAINN - The Brazilian Institute of Neuroscience and Neurotechnology
Grantee:Fernando Cendes
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 13/01766-7 - Sensory neuronopathies: investigation of new diagnostic methods, mechanisms of the disease and therapeutic strategies
Grantee:Marcondes Cavalcante Franca Junior
Support type: Research Grants - Young Investigators Grants
FAPESP's process: 17/13102-7 - Characterization and comparison of the segmentation methods for the brain and cerebellum
Grantee:Thiago Junqueira Ribeiro de Rezende
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 14/19786-7 - Automated quantification of transverse relaxation time: identification of iron deposits in the brain
Grantee:Thiago Junqueira Ribeiro de Rezende
Support type: Scholarships in Brazil - Doctorate