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Neurochemical alterations in spinocerebellar ataxia type 1 and their correlations with clinical status
Author(s) -
Öz Gülin,
Hutter Diane,
Tkáč Ivan,
Clark H. Brent,
Gross Myron D.,
Jiang Hong,
Eberly Lynn E.,
Bushara Khalaf O.,
Gomez Christopher M.
Publication year - 2010
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.23067
Subject(s) - neurochemical , ataxia , spinocerebellar ataxia , medicine , phosphocreatine , endocrinology , glutamate receptor , creatine , gliosis , neuroscience , pathology , biology , receptor , energy metabolism
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 ( 1 H 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 (F 2 ‐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 1 H MRS biomarkers can be utilized to noninvasively assess neuronal and glial status in individual ataxia patients. © 2010 Movement Disorder Society

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