NEUROCHEMICAL ALTERATIONS IN SPINOCEREBELLAR ATAXIA TYPE 1 AND THEIR CORRELATIONS WITH CLINICAL STATUS
Identifieur interne : 002B27 ( Ncbi/Checkpoint ); précédent : 002B26; suivant : 002B28NEUROCHEMICAL 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] ; Lynn E. Eberly [États-Unis] ; Khalaf O. Bushara [États-Unis] ; Christopher M. Gomez [États-Unis]Source :
- Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 2010.
English descriptors
- KwdEn :
- Analysis of Variance, Aspartic Acid (analogs & derivatives), Brain Chemistry, Case-Control Studies, Female, Functional Laterality, Glial Fibrillary Acidic Protein (cerebrospinal fluid), Humans, Inositol, Isoprostanes (cerebrospinal fluid), Magnetic Resonance Imaging (methods), Magnetic Resonance Spectroscopy (methods), Male, Middle Aged, Phosphocreatine, Protons (diagnostic use), Severity of Illness Index, Spinocerebellar Ataxias (metabolism), Spinocerebellar Ataxias (physiopathology), Statistics as Topic.
- 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 10–15 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,
Url:
DOI: 10.1002/mds.23067
PubMed: 20310029
PubMed Central: 2916651
Affiliations:
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PMC:2916651Le document en format XML
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<series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title>
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<term>Aspartic Acid (analogs & derivatives)</term>
<term>Brain Chemistry</term>
<term>Case-Control Studies</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>
<term>Magnetic Resonance Imaging (methods)</term>
<term>Magnetic Resonance Spectroscopy (methods)</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Phosphocreatine</term>
<term>Protons (diagnostic use)</term>
<term>Severity of Illness Index</term>
<term>Spinocerebellar Ataxias (metabolism)</term>
<term>Spinocerebellar Ataxias (physiopathology)</term>
<term>Statistics as Topic</term>
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<keywords scheme="MESH" type="chemical" qualifier="cerebrospinal fluid" xml:lang="en"><term>Glial Fibrillary Acidic Protein</term>
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<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Spinocerebellar Ataxias</term>
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<term>Magnetic Resonance Spectroscopy</term>
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<term>Functional Laterality</term>
<term>Humans</term>
<term>Inositol</term>
<term>Male</term>
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<front><div type="abstract" xml:lang="en"><p id="P2">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 (<sup>1</sup>
H MRS) to neurochemical alterations in the cerebellum and brainstem in spinocerebellar ataxia type 1 (SCA1). We measured neurochemical profiles that consisted of 10–15 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, <italic>myo</italic>
-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, <italic>myo</italic>
-inositol and glutamate levels were discernible in individual spectra and the tNAA/<italic>myo</italic>
-inositol ratio in the cerebellar hemipheres and pons differentiated the patients from controls with 100% specificity and sensitivity. In addition, tNAA, <italic>myo</italic>
-inositol and glutamate levels in the cerebellar hemispheres and the tNAA and <italic>myo</italic>
-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<sub>2</sub>
-isoprostanes as a 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 <sup>1</sup>
H MRS biomarkers can be utilized to non-invasively assess neuronal and glial status in individual ataxia patients.</p>
</div>
</front>
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<name sortKey="Bushara, Khalaf O" sort="Bushara, Khalaf O" uniqKey="Bushara K" first="Khalaf O." last="Bushara">Khalaf O. Bushara</name>
<name sortKey="Clark, H Brent" sort="Clark, H Brent" uniqKey="Clark H" first="H. Brent" last="Clark">H. Brent Clark</name>
<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>
<name sortKey="Hutter, Diane" sort="Hutter, Diane" uniqKey="Hutter D" first="Diane" last="Hutter">Diane Hutter</name>
<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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