Neurochemical alterations in spinocerebellar ataxia type 1 and their correlations with clinical status
Identifieur interne : 000255 ( Istex/Corpus ); précédent : 000254; suivant : 000256Neurochemical alterations in spinocerebellar ataxia type 1 and their correlations with clinical status
Auteurs : Gülin Öz ; Diane Hutter ; Ivan Tká ; H. Brent Clark ; Myron D. Gross ; Hong Jiang ; Lynn E. Eberly ; Khalaf O. Bushara ; Christopher M. GomezSource :
- Movement Disorders [ 0885-3185 ] ; 2010-07-15.
English descriptors
- KwdEn :
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:
DOI: 10.1002/mds.23067
Links to Exploration step
ISTEX:0DD77DE275F2F6700E5396735C2BAAFA018D828BLe document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Neurochemical alterations in spinocerebellar ataxia type 1 and their correlations with clinical status</title><author><name sortKey="Oz, Gulin" sort="Oz, Gulin" uniqKey="Oz G" first="Gülin" last="Öz">Gülin Öz</name><affiliation><mods:affiliation>Center for MR Research, Department of Radiology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA</mods:affiliation></affiliation></author><author><name sortKey="Hutter, Diane" sort="Hutter, Diane" uniqKey="Hutter D" first="Diane" last="Hutter">Diane Hutter</name><affiliation><mods:affiliation>Center for MR Research, Department of Radiology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA</mods:affiliation></affiliation></author><author><name sortKey="Tka, Ivan" sort="Tka, Ivan" uniqKey="Tka I" first="Ivan" last="Tká">Ivan Tká</name><affiliation><mods:affiliation>Center for MR Research, Department of Radiology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA</mods:affiliation></affiliation></author><author><name sortKey="Clark, H Brent" sort="Clark, H Brent" uniqKey="Clark H" first="H. Brent" last="Clark">H. Brent Clark</name><affiliation><mods:affiliation>Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA</mods:affiliation></affiliation></author><author><name sortKey="Gross, Myron D" sort="Gross, Myron D" uniqKey="Gross M" first="Myron D." last="Gross">Myron D. Gross</name><affiliation><mods:affiliation>Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA</mods:affiliation></affiliation></author><author><name sortKey="Jiang, Hong" sort="Jiang, Hong" uniqKey="Jiang H" first="Hong" last="Jiang">Hong Jiang</name><affiliation><mods:affiliation>Department of Neurology, University of Chicago, Chicago, Illinois, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Current Address: Department of Neurology, Xiangya Hospital Neurodegenerative Disorders Research Center, Central South University, Changsha, Hunan, P.R. China</mods:affiliation></affiliation></author><author><name sortKey="Eberly, Lynn E" sort="Eberly, Lynn E" uniqKey="Eberly L" first="Lynn E." last="Eberly">Lynn E. Eberly</name><affiliation><mods:affiliation>Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA</mods:affiliation></affiliation></author><author><name sortKey="Bushara, Khalaf O" sort="Bushara, Khalaf O" uniqKey="Bushara K" first="Khalaf O." last="Bushara">Khalaf O. Bushara</name><affiliation><mods:affiliation>Department of Neurology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA</mods:affiliation></affiliation></author><author><name sortKey="Gomez, Christopher M" sort="Gomez, Christopher M" uniqKey="Gomez C" first="Christopher M." last="Gomez">Christopher M. Gomez</name><affiliation><mods:affiliation>Department of Neurology, University of Chicago, Chicago, Illinois, USA</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:0DD77DE275F2F6700E5396735C2BAAFA018D828B</idno><date when="2010" year="2010">2010</date><idno type="doi">10.1002/mds.23067</idno><idno type="url">https://api.istex.fr/document/0DD77DE275F2F6700E5396735C2BAAFA018D828B/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">000255</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Neurochemical alterations in spinocerebellar ataxia type 1 and their correlations with clinical status</title><author><name sortKey="Oz, Gulin" sort="Oz, Gulin" uniqKey="Oz G" first="Gülin" last="Öz">Gülin Öz</name><affiliation><mods:affiliation>Center for MR Research, Department of Radiology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA</mods:affiliation></affiliation></author><author><name sortKey="Hutter, Diane" sort="Hutter, Diane" uniqKey="Hutter D" first="Diane" last="Hutter">Diane Hutter</name><affiliation><mods:affiliation>Center for MR Research, Department of Radiology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA</mods:affiliation></affiliation></author><author><name sortKey="Tka, Ivan" sort="Tka, Ivan" uniqKey="Tka I" first="Ivan" last="Tká">Ivan Tká</name><affiliation><mods:affiliation>Center for MR Research, Department of Radiology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA</mods:affiliation></affiliation></author><author><name sortKey="Clark, H Brent" sort="Clark, H Brent" uniqKey="Clark H" first="H. Brent" last="Clark">H. Brent Clark</name><affiliation><mods:affiliation>Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA</mods:affiliation></affiliation></author><author><name sortKey="Gross, Myron D" sort="Gross, Myron D" uniqKey="Gross M" first="Myron D." last="Gross">Myron D. Gross</name><affiliation><mods:affiliation>Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA</mods:affiliation></affiliation></author><author><name sortKey="Jiang, Hong" sort="Jiang, Hong" uniqKey="Jiang H" first="Hong" last="Jiang">Hong Jiang</name><affiliation><mods:affiliation>Department of Neurology, University of Chicago, Chicago, Illinois, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Current Address: Department of Neurology, Xiangya Hospital Neurodegenerative Disorders Research Center, Central South University, Changsha, Hunan, P.R. China</mods:affiliation></affiliation></author><author><name sortKey="Eberly, Lynn E" sort="Eberly, Lynn E" uniqKey="Eberly L" first="Lynn E." last="Eberly">Lynn E. Eberly</name><affiliation><mods:affiliation>Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA</mods:affiliation></affiliation></author><author><name sortKey="Bushara, Khalaf O" sort="Bushara, Khalaf O" uniqKey="Bushara K" first="Khalaf O." last="Bushara">Khalaf O. Bushara</name><affiliation><mods:affiliation>Department of Neurology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA</mods:affiliation></affiliation></author><author><name sortKey="Gomez, Christopher M" sort="Gomez, Christopher M" uniqKey="Gomez C" first="Christopher M." last="Gomez">Christopher M. Gomez</name><affiliation><mods:affiliation>Department of Neurology, University of Chicago, Chicago, Illinois, USA</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Movement Disorders</title><title level="j" type="abbrev">Mov. Disord.</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2010-07-15">2010-07-15</date><biblScope unit="vol">25</biblScope><biblScope unit="issue">9</biblScope><biblScope unit="page" from="1253">1253</biblScope><biblScope unit="page" to="1261">1261</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">0DD77DE275F2F6700E5396735C2BAAFA018D828B</idno><idno type="DOI">10.1002/mds.23067</idno><idno type="ArticleID">MDS23067</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>MRS</term><term>SCA1</term><term>ataxia</term><term>cerebellum</term><term>neurochemical profile</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><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></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Gülin Öz PhD</name><affiliations><json:string>Center for MR Research, Department of Radiology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA</json:string></affiliations></json:item><json:item><name>Diane Hutter RN</name><affiliations><json:string>Center for MR Research, Department of Radiology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA</json:string></affiliations></json:item><json:item><name>Ivan Tkáč PhD</name><affiliations><json:string>Center for MR Research, Department of Radiology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA</json:string></affiliations></json:item><json:item><name>H. Brent Clark MD, PhD</name><affiliations><json:string>Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA</json:string></affiliations></json:item><json:item><name>Myron D. Gross PhD</name><affiliations><json:string>Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA</json:string></affiliations></json:item><json:item><name>Hong Jiang MD, PhD</name><affiliations><json:string>Department of Neurology, University of Chicago, Chicago, Illinois, USA</json:string><json:string>Current Address: Department of Neurology, Xiangya Hospital Neurodegenerative Disorders Research Center, Central South University, Changsha, Hunan, P.R. China</json:string></affiliations></json:item><json:item><name>Lynn E. Eberly PhD</name><affiliations><json:string>Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA</json:string></affiliations></json:item><json:item><name>Khalaf O. Bushara MD</name><affiliations><json:string>Department of Neurology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA</json:string></affiliations></json:item><json:item><name>Christopher M. Gomez MD, PhD</name><affiliations><json:string>Department of Neurology, University of Chicago, Chicago, Illinois, USA</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>SCA1</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>MRS</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>ataxia</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>cerebellum</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>neurochemical profile</value></json:item></subject><language><json:string>eng</json:string></language><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</abstract><qualityIndicators><score>7.93</score><pdfVersion>1.3</pdfVersion><pdfPageSize>612 x 810 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractCharCount>1852</abstractCharCount><pdfWordCount>4930</pdfWordCount><pdfCharCount>31478</pdfCharCount><pdfPageCount>9</pdfPageCount><abstractWordCount>259</abstractWordCount></qualityIndicators><title>Neurochemical alterations in spinocerebellar ataxia type 1 and their correlations with clinical status</title><genre><json:string>Serial article</json:string></genre><host><volume>25</volume><pages><total>9</total><last>1261</last><first>1253</first></pages><issn><json:string>0885-3185</json:string></issn><issue>9</issue><subject><json:item><value>Research Article</value></json:item></subject><genre></genre><language><json:string>unknown</json:string></language><title>Movement Disorders</title><doi><json:string>10.1002/(ISSN)1531-8257</json:string></doi></host><publicationDate>2010</publicationDate><copyrightDate>2010</copyrightDate><doi><json:string>10.1002/mds.23067</json:string></doi><id>0DD77DE275F2F6700E5396735C2BAAFA018D828B</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/0DD77DE275F2F6700E5396735C2BAAFA018D828B/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/0DD77DE275F2F6700E5396735C2BAAFA018D828B/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/0DD77DE275F2F6700E5396735C2BAAFA018D828B/fulltext/tei"><teiHeader type="text"><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Neurochemical alterations in spinocerebellar ataxia type 1 and their correlations with clinical status</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><availability><p>Wiley Subscription Services, Inc., A Wiley Company</p></availability><date>2010</date></publicationStmt><notesStmt><note type="content">*Potential conflict of interest: Nothing to report.</note><note>Bob Allison Ataxia Research Center</note><note>Jay D. Schlueter Ataxia Research Fund</note><note>Minnesota Medical Foundation - No. MMF 3761‐9236‐07;</note><note>National Center for Research Resources (NCRR) biotechnology research resource - No. P41RR008079;</note><note>Neuroscience Center Core Blueprint Award - No. P30NS057091;</note><note>National Center for Research Resources - No. M01 RR00400;</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Neurochemical alterations in spinocerebellar ataxia type 1 and their correlations with clinical status</title><author><persName><forename type="first">Gülin</forename><surname>Öz</surname><roleName type="degree">PhD</roleName></persName><note type="biography">In memory of Vural Öz.</note><affiliation>In memory of Vural Öz.</affiliation><note type="correspondence"><p>Correspondence: Center for MR Research, 2021 6th St., S.E. Minneapolis 55455, MN</p></note><affiliation>Center for MR Research, Department of Radiology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA</affiliation></author><author><persName><forename type="first">Diane</forename><surname>Hutter</surname><roleName type="degree">RN</roleName></persName><affiliation>Center for MR Research, Department of Radiology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA</affiliation></author><author><persName><forename type="first">Ivan</forename><surname>Tkáč</surname><roleName type="degree">PhD</roleName></persName><affiliation>Center for MR Research, Department of Radiology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA</affiliation></author><author><persName><forename type="first">H. Brent</forename><surname>Clark</surname><roleName type="degree">MD, PhD</roleName></persName><affiliation>Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA</affiliation></author><author><persName><forename type="first">Myron D.</forename><surname>Gross</surname><roleName type="degree">PhD</roleName></persName><affiliation>Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA</affiliation></author><author><persName><forename type="first">Hong</forename><surname>Jiang</surname><roleName type="degree">MD, PhD</roleName></persName><affiliation>Department of Neurology, University of Chicago, Chicago, Illinois, USA</affiliation><affiliation>Current Address: Department of Neurology, Xiangya Hospital Neurodegenerative Disorders Research Center, Central South University, Changsha, Hunan, P.R. China</affiliation></author><author><persName><forename type="first">Lynn E.</forename><surname>Eberly</surname><roleName type="degree">PhD</roleName></persName><affiliation>Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA</affiliation></author><author><persName><forename type="first">Khalaf O.</forename><surname>Bushara</surname><roleName type="degree">MD</roleName></persName><affiliation>Department of Neurology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA</affiliation></author><author><persName><forename type="first">Christopher M.</forename><surname>Gomez</surname><roleName type="degree">MD, PhD</roleName></persName><affiliation>Department of Neurology, University of Chicago, Chicago, Illinois, USA</affiliation></author></analytic><monogr><title level="j">Movement Disorders</title><title level="j" type="abbrev">Mov. Disord.</title><idno type="pISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><idno type="DOI">10.1002/(ISSN)1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2010-07-15"></date><biblScope unit="vol">25</biblScope><biblScope unit="issue">9</biblScope><biblScope unit="page" from="1253">1253</biblScope><biblScope unit="page" to="1261">1261</biblScope></imprint></monogr><idno type="istex">0DD77DE275F2F6700E5396735C2BAAFA018D828B</idno><idno type="DOI">10.1002/mds.23067</idno><idno type="ArticleID">MDS23067</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2010</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>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</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>SCA1</term></item><item><term>MRS</term></item><item><term>ataxia</term></item><item><term>cerebellum</term></item><item><term>neurochemical profile</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>Article category</head><item><term>Research Article</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2009-08-25">Received</change><change when="2010-02-05">Registration</change><change when="2010-07-15">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/0DD77DE275F2F6700E5396735C2BAAFA018D828B/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Wiley Subscription Services, Inc., A Wiley Company</publisherName><publisherLoc>Hoboken</publisherLoc></publisherInfo><doi registered="yes">10.1002/(ISSN)1531-8257</doi><issn type="print">0885-3185</issn><issn type="electronic">1531-8257</issn><idGroup><id type="product" value="MDS"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="MOVEMENT DISORDERS">Movement Disorders</title><title type="short">Mov. Disord.</title></titleGroup></publicationMeta><publicationMeta level="part" position="90"><doi origin="wiley" registered="yes">10.1002/mds.v25:9</doi><numberingGroup><numbering type="journalVolume" number="25">25</numbering><numbering type="journalIssue">9</numbering></numberingGroup><coverDate startDate="2010-07-15">15 July 2010</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="210" status="forIssue"><doi origin="wiley" registered="yes">10.1002/mds.23067</doi><idGroup><id type="unit" value="MDS23067"></id></idGroup><countGroup><count type="pageTotal" number="9"></count></countGroup><titleGroup><title type="articleCategory">Research Article</title><title type="tocHeading1">Research Articles</title></titleGroup><copyright ownership="thirdParty">Copyright © 2010 Movement Disorder Society</copyright><eventGroup><event type="manuscriptReceived" date="2009-08-25"></event><event type="manuscriptRevised" date="2009-11-10"></event><event type="manuscriptAccepted" date="2010-02-05"></event><event type="firstOnline" date="2010-03-22"></event><event type="publishedOnlineFinalForm" date="2010-07-19"></event><event type="publishedOnlineAcceptedOrEarlyUnpaginated" date="2010-03-22"></event><event type="xmlConverted" agent="Converter:JWSART34_TO_WML3G version:2.4.8 mode:FullText" date="2011-05-03"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-02-02"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-10-31"></event></eventGroup><numberingGroup><numbering type="pageFirst">1253</numbering><numbering type="pageLast">1261</numbering></numberingGroup><correspondenceTo>Center for MR Research, 2021 6th St., S.E. Minneapolis 55455, MN</correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:MDS.MDS23067.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="4"></count><count type="tableTotal" number="1"></count><count type="referenceTotal" number="41"></count><count type="wordTotal" number="5700"></count></countGroup><titleGroup><title type="main" xml:lang="en">Neurochemical alterations in spinocerebellar ataxia type 1 and their correlations with clinical status<link href="#fn1"></link></title><title type="short" xml:lang="en">MRS Biomarkers of SCA1</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1" corresponding="yes" noteRef="#fn3"><personName><givenNames>Gülin</givenNames><familyName>Öz</familyName><degrees>PhD</degrees></personName><contactDetails><email>gulin@cmrr.umn.edu</email></contactDetails></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Diane</givenNames><familyName>Hutter</familyName><degrees>RN</degrees></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Ivan</givenNames><familyName>Tkáč</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af2"><personName><givenNames>H. Brent</givenNames><familyName>Clark</familyName><degrees>MD, PhD</degrees></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Myron D.</givenNames><familyName>Gross</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au6" creatorRole="author" affiliationRef="#af3" currentRef="#curr1"><personName><givenNames>Hong</givenNames><familyName>Jiang</familyName><degrees>MD, PhD</degrees></personName></creator><creator xml:id="au7" creatorRole="author" affiliationRef="#af4"><personName><givenNames>Lynn E.</givenNames><familyName>Eberly</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au8" creatorRole="author" affiliationRef="#af5"><personName><givenNames>Khalaf O.</givenNames><familyName>Bushara</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au9" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Christopher M.</givenNames><familyName>Gomez</familyName><degrees>MD, PhD</degrees></personName></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="US" type="organization"><unparsedAffiliation>Center for MR Research, Department of Radiology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="US" type="organization"><unparsedAffiliation>Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="US" type="organization"><unparsedAffiliation>Department of Neurology, University of Chicago, Chicago, Illinois, USA</unparsedAffiliation></affiliation><affiliation xml:id="af4" countryCode="US" type="organization"><unparsedAffiliation>Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA</unparsedAffiliation></affiliation><affiliation xml:id="af5" countryCode="US" type="organization"><unparsedAffiliation>Department of Neurology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA</unparsedAffiliation></affiliation><affiliation xml:id="curr1" countryCode="CN"><unparsedAffiliation>Department of Neurology, Xiangya Hospital Neurodegenerative Disorders Research Center, Central South University, Changsha, Hunan, P.R. China</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">SCA1</keyword><keyword xml:id="kwd2">MRS</keyword><keyword xml:id="kwd3">ataxia</keyword><keyword xml:id="kwd4">cerebellum</keyword><keyword xml:id="kwd5">neurochemical profile</keyword></keywordGroup><fundingInfo><fundingAgency>Bob Allison Ataxia Research Center</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Jay D. Schlueter Ataxia Research Fund</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Minnesota Medical Foundation</fundingAgency><fundingNumber>MMF 3761‐9236‐07</fundingNumber></fundingInfo><fundingInfo><fundingAgency>National Center for Research Resources (NCRR) biotechnology research resource</fundingAgency><fundingNumber>P41RR008079</fundingNumber></fundingInfo><fundingInfo><fundingAgency>Neuroscience Center Core Blueprint Award</fundingAgency><fundingNumber>P30NS057091</fundingNumber></fundingInfo><fundingInfo><fundingAgency>National Center for Research Resources</fundingAgency><fundingNumber>M01 RR00400</fundingNumber></fundingInfo><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>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 to 15 metabolite concentrations in the vermis, cerebellar hemispheres and pons of patients with SCA1 (N = 9) and healthy controls (N = 15). Total NAA (<i>N</i>‐acetylaspartate + <i>N</i>‐acetylaspartylglutamate, tNAA) and glutamate were lower and glutamine, <i>myo</i>‐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, <i>myo</i>‐inositol, and glutamate levels were discernible in individual spectra and the tNAA/<i>myo</i>‐inositol ratio in the cerebellar hemipheres and pons differentiated the patients from controls with 100% specificity and sensitivity. In addition, tNAA, <i>myo</i>‐inositol, and glutamate levels in the cerebellar hemispheres and the tNAA and <i>myo</i>‐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 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 <sup>1</sup>H MRS biomarkers can be utilized to noninvasively assess neuronal and glial status in individual ataxia patients. © 2010 Movement Disorder Society</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn1"><p>Potential conflict of interest: Nothing to report.</p></note><note xml:id="fn3"><p>In memory of Vural Öz.</p></note></noteGroup></header></component></istex:document></istex:metadataXml><!--Version 0.6 générée le 4-12-2015--><mods version="3.6"><titleInfo lang="en"><title>Neurochemical alterations in spinocerebellar ataxia type 1 and their correlations with clinical status</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>MRS Biomarkers of SCA1</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Neurochemical alterations in spinocerebellar ataxia type 1 and their correlations with clinical status</title></titleInfo><name type="personal"><namePart type="given">Gülin</namePart><namePart type="family">Öz</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Center for MR Research, Department of Radiology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA</affiliation><description>In memory of Vural Öz.</description><description>Correspondence: Center for MR Research, 2021 6th St., S.E. Minneapolis 55455, MN</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Diane</namePart><namePart type="family">Hutter</namePart><namePart type="termsOfAddress">RN</namePart><affiliation>Center for MR Research, Department of Radiology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ivan</namePart><namePart type="family">Tkáč</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Center for MR Research, Department of Radiology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">H. Brent</namePart><namePart type="family">Clark</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Myron D.</namePart><namePart type="family">Gross</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Hong</namePart><namePart type="family">Jiang</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Neurology, University of Chicago, Chicago, Illinois, USA</affiliation><affiliation>Current Address: Department of Neurology, Xiangya Hospital Neurodegenerative Disorders Research Center, Central South University, Changsha, Hunan, P.R. China</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Lynn E.</namePart><namePart type="family">Eberly</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Khalaf O.</namePart><namePart type="family">Bushara</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Christopher M.</namePart><namePart type="family">Gomez</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Department of Neurology, University of Chicago, Chicago, Illinois, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre authority="originalCategForm">article</genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2010-07-15</dateIssued><dateCaptured encoding="w3cdtf">2009-08-25</dateCaptured><dateValid encoding="w3cdtf">2010-02-05</dateValid><copyrightDate encoding="w3cdtf">2010</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">4</extent><extent unit="tables">1</extent><extent unit="references">41</extent><extent unit="words">5700</extent></physicalDescription><abstract 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</abstract><note type="content">*Potential conflict of interest: Nothing to report.</note><note type="funding">Bob Allison Ataxia Research Center</note><note type="funding">Jay D. Schlueter Ataxia Research Fund</note><note type="funding">Minnesota Medical Foundation - No. MMF 3761‐9236‐07; </note><note type="funding">National Center for Research Resources (NCRR) biotechnology research resource - No. P41RR008079; </note><note type="funding">Neuroscience Center Core Blueprint Award - No. P30NS057091; </note><note type="funding">National Center for Research Resources - No. M01 RR00400; </note><subject lang="en"><genre>Keywords</genre><topic>SCA1</topic><topic>MRS</topic><topic>ataxia</topic><topic>cerebellum</topic><topic>neurochemical profile</topic></subject><relatedItem type="host"><titleInfo><title>Movement Disorders</title></titleInfo><titleInfo type="abbreviated"><title>Mov. Disord.</title></titleInfo><subject><genre>article category</genre><topic>Research Article</topic></subject><identifier type="ISSN">0885-3185</identifier><identifier type="eISSN">1531-8257</identifier><identifier type="DOI">10.1002/(ISSN)1531-8257</identifier><identifier type="PublisherID">MDS</identifier><part><date>2010</date><detail type="volume"><caption>vol.</caption><number>25</number></detail><detail type="issue"><caption>no.</caption><number>9</number></detail><extent unit="pages"><start>1253</start><end>1261</end><total>9</total></extent></part></relatedItem><identifier type="istex">0DD77DE275F2F6700E5396735C2BAAFA018D828B</identifier><identifier type="DOI">10.1002/mds.23067</identifier><identifier type="ArticleID">MDS23067</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2010 Movement Disorder Society</accessCondition><recordInfo><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin><recordContentSource>WILEY</recordContentSource></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Santé/explor/MovDisordV3/Data/Istex/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000255 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Istex/Corpus/biblio.hfd -nk 000255 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Santé
|area= MovDisordV3
|flux= Istex
|étape= Corpus
|type= RBID
|clé= ISTEX:0DD77DE275F2F6700E5396735C2BAAFA018D828B
|texte= Neurochemical alterations in spinocerebellar ataxia type 1 and their correlations with clinical status
}}
| This area was generated with Dilib version V0.6.23. |  |