Axonal Dysfunction in the Deep White Matter in Machado-Joseph Disease

Authors

  • Anelyssa D'Abreu MD,

    1. From the Neuroimaging Laboratory (AD, SA, FC); Neurology Department (MF, FC); and Department of Medical Genetics-Universidade Estadual de Campinas-UNICAMP, Campinas São Paulo, Brazil (IL-C).
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  • Marcondes França Jr MD,

    1. From the Neuroimaging Laboratory (AD, SA, FC); Neurology Department (MF, FC); and Department of Medical Genetics-Universidade Estadual de Campinas-UNICAMP, Campinas São Paulo, Brazil (IL-C).
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  • Simone Appenzeller MD,

    1. From the Neuroimaging Laboratory (AD, SA, FC); Neurology Department (MF, FC); and Department of Medical Genetics-Universidade Estadual de Campinas-UNICAMP, Campinas São Paulo, Brazil (IL-C).
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  • Iscia Lopes-Cendes MD, PhD,

    1. From the Neuroimaging Laboratory (AD, SA, FC); Neurology Department (MF, FC); and Department of Medical Genetics-Universidade Estadual de Campinas-UNICAMP, Campinas São Paulo, Brazil (IL-C).
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  • Fernando Cendes MD, PhD

    1. From the Neuroimaging Laboratory (AD, SA, FC); Neurology Department (MF, FC); and Department of Medical Genetics-Universidade Estadual de Campinas-UNICAMP, Campinas São Paulo, Brazil (IL-C).
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  • Disclosure: The authors have reported no conflicts of interest.

Correspondence: Address correspondence to Dr. Fernando Cendes, MD, PhD, Rua Tessália Vieira de Camargo, 126; FCM 11, Cidade Universitária Zeferino Vaz; Campinas-SP, 13083-970 Brazil. E-mail: fcendes@unicamp.br

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.

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