Axonal Dysfunction In The Deep White Matter In Machado-joseph Disease

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. © 2008 by the American Society of Neuroimaging.191912Rosenberg, R.N., Machado-Joseph disease: An autosomal dominant motor system degeneration (1992) Mov Disord, 7, pp. 193-203D'Abreu, A., Friedman, J., Coskun, J., Non-movement disorder heralds symptoms of Machado-Joseph disease years before ataxia (2005) Mov Disord, 20, pp. 739-741Ishikawa, A., Yamada, M., Makino, K., Aida, I., Idezuka, J., Ikeuchi, T., Soma, Y., Tsuji, S., Dementia and delirium in 4 patients with Machado-Joseph disease (2002) Arch Neurol, 59, pp. 1804-1808Ikeda, K., Kubota, S., Isashiki, Y., Eiraku, N., Osame, M., Nakagawa, M., Machado-Joseph disease with retinal degeneration and dementia (2001) Acta Neurol Scand, 104, pp. 402-405Zawacki, T.M., Grace, J., Friedman, J.H., Sudarsky, L., Executive and emotional dysfunction in Machado-Joseph disease (2002) Mov Disord, 17, pp. 1004-1010Ross, B., Bluml, S., Magnetic resonance spectroscopy of the brain (2001) Anat Rec, 265, pp. 54-84Mascalchi, M., Cosottini, M., Lolli, F., Salvi, F., Tessa, C., Macucci, M., Tosetti, M., Villari, N., Proton MR spectroscopy of the cerebellum and pons in patients with degenerative ataxia (2002) Radiology, 23, pp. 371-378Viau, M., Marchand, L., Bard, C., Boulanger, Y., H magnetic resonance spectroscopy of autosomal ataxias (2005) Brain Res, 1049, pp. 191-202Boesch, S.M., Schocke, M., Bürk, K., Hollosi, P., Fornai, F., Aichner, F.T., Poewe, W., Felber, S., Proton magnetic resonance spectroscopy imaging reveals differences in spinocerebellar ataxia types 2 and 6 (2001) J Magn Reson Imaging, 13, pp. 553-559Guerrini, L., Lolli, F., Ginestroni, A., Belli, G., Della Nave, R., Tessa, C., Foresti, S., Mascalchi, M., Brainstem neurodegeneration correlates with clinical dysfunction in SCA1 but not in SCA2. A quantitative volumetric, diffusion and proton spectroscopy MR study (2004) Brain, 127, pp. 1785-1795Viau, M., Boulanger, Y., Characterization of ataxias with magnetic resonance imaging and spectroscopy (2004) Parkinsonism Relat Disord, 10, pp. 335-351Murata, Y., Kawakami, H., Yamaguchi, S., Nishimura, M., Kohriyama, T., Ishizaki, F., Matsuyama, Z., Nakamura, S., Characteristic magnetic resonance imaging findings in Machado-Joseph disease (1998) Arch Neurol, 55, pp. 33-37Yoshizawa, T., Watanabe, M., Frusho, K., Shoji, S., Magnetic resonance imaging demonstrates differential atrophy of pontine base and tegmentum in Machado-Joseph disease (2003) J Neurol Sci, 215 (1-2), pp. 45-50Tokumaru, A.M., Kamakura, K., Maki, T., Murayama, S., Sakata, I., Kaji, T., Kohyama, S., Hasegawa, S., Magnetic resonance imaging findings of Machado-Joseph disease: Histopathologic correlation (2003) J Comput Assist Tomogr, 27, pp. 241-248Etchebehere, E.C., Cendes, F., Lopes-Cendes, I., Pereira, J.A., Lima, M.C., Sansana, C.R., Silva, C.A., Camargo, E.E., Brain single-photon emission computed tomography and magnetic resonance imaging in Machado-Joseph disease (2001) Arch Neurol, 58, pp. 1257-1263Bottomley, P.A., Spatial localization in NMR spectroscopy in vivo (1987) Ann NY Acad Sci, 508, pp. 333-348Appenzeller, S., Li, L.M., Costallat, L.T., Cendes, F., Evidence of reversible axonal dysfunction in systemic lupus erythematosus: A proton MRS study (2005) Brain, 128, pp. 2933-2940Bürk, K., Globas, C., Bösch, S., Klockgether, T., Zühlke, C., Daum, I., Dichgans, J., Cognitive deficits in spinocerebellar ataxia type 1, 2, and 3 (2003) J Neurol, 250, pp. 207-211Kawai, Y., Takeda, A., Abe, Y., Washimi, Y., Tanaka, F., Sobue, G., Cognitive impairments in Machado-Joseph disease (2004) Arch Neurol, 61, pp. 1757-1760Rudkin, T.M., Douglas, A., Proton magnetic resonance spectroscopy for the diagnosis and management of cerebral disorders (1999) Arch Neurol, 56, pp. 919-926Angelie, E., Bonmartin, A., Boudraa, A., Gonnaud, P.M., Mallet, J.J., Sappey-Marinier, D., Regional differences and metabolic changes in normal aging of the human brain: Proton MR spectroscopic imaging study (2001) AJNR, 22, pp. 119-127Mascalchi, M., Tosetti, M., Plasmati, R., Bianchi, M.C., Tessa, C., Salvi, F., Frontali, M., Tassinari, C.A., Proton magnetic resonance spectroscopy in an Italian family with spinocerebellar ataxia type 1 (1998) Ann Neurol, 43, pp. 244-252Wilkinson, I.D., Hadjivassiliou, M., Dickson, J.M., Wallis, L., Grünewald, R.A., Coley, S.C., Widjaja, E., Griffiths, P.D., Cerebellar abnormalities on proton MR spectroscopy in gluten ataxia (2005) J Neurol Neurosurg Psychiatry, 76, pp. 1011-1013Griffin, J.L., Cemal, C.K., Pook, M.A., Defining a metabolic phenotype in the brain of a transgenic mouse model of spinocerebellar ataxia 3 (2004) Physiol Genomics, 16, pp. 334-34