title: Cerebral cortex involvement in Machado-Joseph disease.
abstract: OBJECTIVE
  Machado-Joseph disease (MJD/SCA3) is the most frequent spinocerebellar ataxia, characterized by brainstem, basal ganglia and cerebellar damage. Few magnetic resonance imaging based studies have investigated damage in the cerebral cortex. The objective was to determine whether patients with MJD/SCA3 have cerebral cortex atrophy, to identify regions more susceptible to damage and to look for the clinical and neuropsychological correlates of such lesions.
  
  
  METHODS
  Forty-nine patients with MJD/SCA3 (mean age 47.7 ± 13.0 years, 27 men) and 49 matched healthy controls were enrolled. All subjects underwent magnetic resonance imaging scans in a 3 T device, and three-dimensional T1 images were used for volumetric analyses. Measurement of cortical thickness and volume was performed using the FreeSurfer software. Groups were compared using ancova with age, gender and estimated intracranial volume as covariates, and a general linear model was used to assess correlations between atrophy and clinical variables.
  
  
  RESULTS
  Mean CAG expansion, Scale for Assessment and Rating of Ataxia (SARA) score and age at onset were 72.1 ± 4.2, 14.7 ± 7.3 and 37.5 ± 12.5 years, respectively. The main findings were (i) bilateral paracentral cortex atrophy, as well as the caudal middle frontal gyrus, superior and transverse temporal gyri, and lateral occipital cortex in the left hemisphere and supramarginal gyrus in the right hemisphere; (ii) volumetric reduction of basal ganglia and hippocampi; (iii) a significant correlation between SARA and brainstem and precentral gyrus atrophy. Furthermore, some of the affected cortical regions showed significant correlations with neuropsychological data.
  
  
  CONCLUSIONS
  Patients with MJD/SCA3 have widespread cortical and subcortical atrophy. These structural findings correlate with clinical manifestations of the disease, which support the concept that cognitive/motor impairment and cerebral damage are related in disease.
authors.affiliation: Department of Neurology, University of Campinas (UNICAMP), Campinas, Brazil; Department of Cosmic Rays and Chronology, University of Campinas (UNICAMP), Campinas, Brazil.
authors.forename: T J R
authors.initials: TJ
authors.lastname: de Rezende
authors.forename: A
authors.initials: A
authors.lastname: D'Abreu
authors.forename: R P
authors.initials: RP
authors.lastname: Guimarães
authors.forename: T M
authors.initials: TM
authors.lastname: Lopes
authors.forename: I
authors.initials: I
authors.lastname: Lopes-Cendes
authors.forename: F
authors.initials: F
authors.lastname: Cendes
authors.forename: G
authors.initials: G
authors.lastname: Castellano
authors.forename: M C
authors.initials: MC
authors.lastname: França
mesh_terms: D000328:Adult; D001284:Atrophy / Q000473:pathology; D001479:Basal Ganglia / Q000473:pathology*; D001933:Brain Stem / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology*; D005260:Female; D006801:Humans; D017827:Machado-Joseph Disease / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged
keywords: FreeSurfer; Machado−Joseph disease; cerebral cortex; cortical thickness; neuropsychological tests