title: Axonal dysfunction in the deep white matter in Machado-Joseph disease.
abstract: We evaluated spectroscopy findings at the deep white matter in Machado-Joseph disease (MJD). We obtained brain MRI and single-voxel proton MR spectroscopy (MRS) over the superior-posterior region of the left hemisphere at the level of the corpus callosum in 40 patients (44.6 +/- 2.3 years-old) and 27 controls (31.4 +/- 3.6 years). Four patients were excluded due to poor quality spectra. We observed a decrease in signal intensity of N-acetylaspartate relative to creatine-phosphocreatine signal (NAA/Cr) in MJD compared to control [1.63 +/- 0.41 (1.15-2.76) versus 1.97 +/- .51 (1.50-2.92); U test = 219.0; P < .001]. No statistical difference was observed in choline-containing compounds relative to creatine (Cho/Cr). There was no significant correlation between NAA/Cr and clinical and genetic variables. Due to the younger age of the control group, we performed a secondary analysis in a subgroup of 15 MJD patients matched by age to 15 controls. Matching was performed blindly to MRS results and subject identification, except for age and sex. A statistically significant difference was observed in NAA/Cr ratios (U test = 44.0; P= .004), as well as Cho/Cr levels (U test = 53.0; P= .014). We conclude that the metabolic abnormalities observed in the deep white matter in MJD suggest extensive neuronal and axonal dysfunction in these patients.
authors.affiliation: Neuroimaging Laboratory, Universidade Estadual de Campinas-UNICAMP, Campinas São Paulo, Brazil.
authors.forename: Anelyssa
authors.initials: A
authors.lastname: D'Abreu
authors.forename: Marcondes
authors.initials: M
authors.lastname: França
authors.forename: Simone
authors.initials: S
authors.lastname: Appenzeller
authors.forename: Iscia
authors.initials: I
authors.lastname: Lopes-Cendes
authors.forename: Fernando
authors.initials: F
authors.lastname: Cendes
mesh_terms: D000328:Adult; D000368:Aged; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D016022:Case-Control Studies; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D005260:Female; D006801:Humans; D017827:Machado-Joseph Disease / Q000378:metabolism* / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism
chemical_list: D010725:Phosphocreatine; D001224:Aspartic Acid; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline