Neurochemical alterations in spinocerebellar ataxia type 1 and their correlations with clinical status
Identifieur interne : 001B60 ( Main/Exploration ); précédent : 001B59; suivant : 001B61Neurochemical alterations in spinocerebellar ataxia type 1 and their correlations with clinical status
Auteurs : Gülin Öz [États-Unis] ; Diane Hutter [États-Unis] ; Ivan Tká [États-Unis] ; H. Brent Clark [États-Unis] ; Myron D. Gross [États-Unis] ; Hong Jiang [États-Unis, République populaire de Chine] ; Lynn E. Eberly [États-Unis] ; Khalaf O. Bushara [États-Unis] ; Christopher M. Gomez [États-Unis]Source :
- Movement Disorders [ 0885-3185 ] ; 2010-07-15.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
- Analysis of Variance, Aspartic Acid (analogs & derivatives), Brain Chemistry, Case-Control Studies, Cerebellum, Female, Functional Laterality, Glial Fibrillary Acidic Protein (cerebrospinal fluid), Humans, Inositol, Isoprostanes (cerebrospinal fluid), MRS, Magnetic Resonance Imaging (methods), Magnetic Resonance Spectroscopy (methods), Male, Middle Aged, Nervous system diseases, Phosphocreatine, Protons (diagnostic use), SCA1, Severity of Illness Index, Spinocerebellar Ataxias (metabolism), Spinocerebellar Ataxias (physiopathology), Spinocerebellar ataxia, Statistics as Topic, ataxia, cerebellum, neurochemical profile.
- MESH :
- chemical , analogs & derivatives : Aspartic Acid.
- chemical , cerebrospinal fluid : Glial Fibrillary Acidic Protein, Isoprostanes.
- chemical , diagnostic use : Protons.
- metabolism : Spinocerebellar Ataxias.
- methods : Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy.
- physiopathology : Spinocerebellar Ataxias.
- Analysis of Variance, Brain Chemistry, Case-Control Studies, Female, Functional Laterality, Humans, Inositol, Male, Middle Aged, Phosphocreatine, Severity of Illness Index, Statistics as Topic.
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
Url:
- https://api.istex.fr/document/0DD77DE275F2F6700E5396735C2BAAFA018D828B/fulltext/pdf
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2916651
DOI: 10.1002/mds.23067
Affiliations:
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<term>Aspartic Acid (analogs & derivatives)</term>
<term>Brain Chemistry</term>
<term>Case-Control Studies</term>
<term>Cerebellum</term>
<term>Female</term>
<term>Functional Laterality</term>
<term>Glial Fibrillary Acidic Protein (cerebrospinal fluid)</term>
<term>Humans</term>
<term>Inositol</term>
<term>Isoprostanes (cerebrospinal fluid)</term>
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<term>Magnetic Resonance Imaging (methods)</term>
<term>Magnetic Resonance Spectroscopy (methods)</term>
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<term>Nervous system diseases</term>
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<term>Spinocerebellar Ataxias (physiopathology)</term>
<term>Spinocerebellar ataxia</term>
<term>Statistics as Topic</term>
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<term>Functional Laterality</term>
<term>Humans</term>
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<front><div type="abstract" xml:lang="en">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</div>
</front>
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<name sortKey="Eberly, Lynn E" sort="Eberly, Lynn E" uniqKey="Eberly L" first="Lynn E." last="Eberly">Lynn E. Eberly</name>
<name sortKey="Gomez, Christopher M" sort="Gomez, Christopher M" uniqKey="Gomez C" first="Christopher M." last="Gomez">Christopher M. Gomez</name>
<name sortKey="Gross, Myron D" sort="Gross, Myron D" uniqKey="Gross M" first="Myron D." last="Gross">Myron D. Gross</name>
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<name sortKey="Jiang, Hong" sort="Jiang, Hong" uniqKey="Jiang H" first="Hong" last="Jiang">Hong Jiang</name>
<name sortKey="Tka, Ivan" sort="Tka, Ivan" uniqKey="Tka I" first="Ivan" last="Tká">Ivan Tká</name>
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<country name="République populaire de Chine"><noRegion><name sortKey="Jiang, Hong" sort="Jiang, Hong" uniqKey="Jiang H" first="Hong" last="Jiang">Hong Jiang</name>
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