Neurochemical alterations in spinocerebellar ataxia type 1 and their correlations with clinical status |
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| Authors: | Gülin Öz PhD Diane Hutter RN Ivan Tkáč PhD H Brent Clark MD PhD Myron D Gross PhD Hong Jiang MD PhD Lynn E Eberly PhD Khalaf O Bushara MD Christopher M Gomez MD PhD |
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| Institution: | 1. Center for MR Research, Department of Radiology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA;2. In memory of Vural ?z.;3. Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA;4. Department of Neurology, University of Chicago, Chicago, Illinois, USA;5. Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA;6. Department of Neurology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA |
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| Abstract: | Robust biomarkers of neurodegeneration are critical for testing of neuroprotective therapies. The clinical applicability of such biomarkers requires sufficient sensitivity to detect disease in individuals. Here we tested the sensitivity of high field (4 tesla) proton magnetic resonance spectroscopy (1H MRS) to neurochemical alterations in the cerebellum and brainstem in spinocerebellar ataxia type 1 (SCA1). We measured neurochemical profiles that consisted of 10 to 15 metabolite concentrations in the vermis, cerebellar hemispheres and pons of patients with SCA1 (N = 9) and healthy controls (N = 15). Total NAA (N‐acetylaspartate + N‐acetylaspartylglutamate, tNAA) and glutamate were lower and glutamine, myo‐inositol and total creatine (creatine + phosphocreatine, tCr) were higher in patients relative to controls, consistent with neuronal dysfunction/loss, gliotic activity, and alterations in glutamate–glutamine cycling and energy metabolism. Changes in tNAA, tCr, myo‐inositol, and glutamate levels were discernible in individual spectra and the tNAA/myo‐inositol ratio in the cerebellar hemipheres and pons differentiated the patients from controls with 100% specificity and sensitivity. In addition, tNAA, myo‐inositol, and glutamate levels in the cerebellar hemispheres and the tNAA and myo‐inositol levels in the pons correlated with ataxia scores (Scale for the Assessment and Rating of Ataxia, SARA). Two other biomarkers measured in the cerebrospinal fluid (CSF) of a subset of the volunteers (F2‐isoprostanes asa marker of oxidative stress and glial fibrillary acidic protein (GFAP) as a marker of gliosis) were not different between patients and controls. These data demonstrate that 1H MRS biomarkers can be utilized to noninvasively assess neuronal and glial status in individual ataxia patients. © 2010 Movement Disorder Society |
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| Keywords: | SCA1 MRS ataxia cerebellum neurochemical profile |
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