Biochemical variations in the synaptic level of dopamine precede motor fluctuations in Parkinson's disease: PET evidence of increased dopamine turnover
Identifieur interne : 000C37 ( Istex/Corpus ); précédent : 000C36; suivant : 000C38Biochemical variations in the synaptic level of dopamine precede motor fluctuations in Parkinson's disease: PET evidence of increased dopamine turnover
Auteurs : Raúl De ; Jian Lu ; Vesna Sossi ; Salma Jivan ; Michael Schulzer ; James Holden ; Chong Lee ; Thomas Ruth ; Donald Calne ; A StoesslSource :
- Annals of Neurology [ 0364-5134 ] ; 2001-03-01.
Abstract
Motor fluctuations are a major disabling complication in the treatment of Parkinson's disease. To investigate whether such oscillations in mobility can be attributed to changes in the synaptic levels of dopamine, we studied prospectively patients in the early stages of Parkinson's disease with a follow‐up after at least 3 years of levodopa treatment. At baseline, 3 positron emission tomography (PET) scans using [11C]raclopride before and after (1 hour and 4 hours) orally administered levodopa were performed on the same day for each patient. Patients who developed “wearing‐off” fluctuations during the follow‐up period had a different pattern of levodopa‐induced changes in [11C]raclopride binding potential (BP) from that observed in patients who were still stable by the end of the follow‐up. Thus, 1 hour post‐levodopa the estimated increase in the synaptic level of dopamine was 3 times higher in fluctuators than in stable responders. By contrast, only stable responders maintained increased levels of synaptic dopamine in the PET scan performed after 4 hours. These results indicate that fluctuations in the synaptic concentration of dopamine precede clinically apparent “wearing‐off” phenomena. The rapid increase in synaptic levels of dopamine observed in fluctuators suggests that increased dopamine turnover might play a relevant role in levodopa‐related motor complications. Ann Neurol 2001;49:298–303
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DOI: 10.1002/ana.65
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To investigate whether such oscillations in mobility can be attributed to changes in the synaptic levels of dopamine, we studied prospectively patients in the early stages of Parkinson's disease with a follow‐up after at least 3 years of levodopa treatment. At baseline, 3 positron emission tomography (PET) scans using [11C]raclopride before and after (1 hour and 4 hours) orally administered levodopa were performed on the same day for each patient. Patients who developed “wearing‐off” fluctuations during the follow‐up period had a different pattern of levodopa‐induced changes in [11C]raclopride binding potential (BP) from that observed in patients who were still stable by the end of the follow‐up. Thus, 1 hour post‐levodopa the estimated increase in the synaptic level of dopamine was 3 times higher in fluctuators than in stable responders. By contrast, only stable responders maintained increased levels of synaptic dopamine in the PET scan performed after 4 hours. These results indicate that fluctuations in the synaptic concentration of dopamine precede clinically apparent “wearing‐off” phenomena. The rapid increase in synaptic levels of dopamine observed in fluctuators suggests that increased dopamine turnover might play a relevant role in levodopa‐related motor complications. Ann Neurol 2001;49:298–303</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Raúl De La Fuente‐Fernández MD</name><affiliations><json:string>Neurodegenerative Disorders Centre, Vancouver Hospital and Health Sciences Centre, Vancouver, BC, Canada</json:string></affiliations></json:item><json:item><name>Jian‐Qiang Lu MD, PhD</name><affiliations><json:string>Neurodegenerative Disorders Centre, Vancouver Hospital and Health Sciences Centre, Vancouver, BC, Canada</json:string></affiliations></json:item><json:item><name>Vesna Sossi PhD</name><affiliations><json:string>TRIUMF, University of British Columbia, Vancouver, BC, Canada</json:string></affiliations></json:item><json:item><name>Salma Jivan BSc</name><affiliations><json:string>TRIUMF, University of British Columbia, Vancouver, BC, Canada</json:string></affiliations></json:item><json:item><name>Michael Schulzer MD, PhD</name><affiliations><json:string>Neurodegenerative Disorders Centre, Vancouver Hospital and Health Sciences Centre, Vancouver, BC, Canada</json:string></affiliations></json:item><json:item><name>James E. Holden PhD</name><affiliations><json:string>University of Wisconsin, Madison, WI</json:string></affiliations></json:item><json:item><name>Chong S. Lee MD, FRCPC</name><affiliations><json:string>Neurodegenerative Disorders Centre, Vancouver Hospital and Health Sciences Centre, Vancouver, BC, Canada</json:string></affiliations></json:item><json:item><name>Thomas J. Ruth PhD</name><affiliations><json:string>TRIUMF, University of British Columbia, Vancouver, BC, Canada</json:string></affiliations></json:item><json:item><name>Donald B. Calne DM, FRCPC</name><affiliations><json:string>Neurodegenerative Disorders Centre, Vancouver Hospital and Health Sciences Centre, Vancouver, BC, Canada</json:string></affiliations></json:item><json:item><name>A. 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Patients who developed “wearing‐off” fluctuations during the follow‐up period had a different pattern of levodopa‐induced changes in [11C]raclopride binding potential (BP) from that observed in patients who were still stable by the end of the follow‐up. Thus, 1 hour post‐levodopa the estimated increase in the synaptic level of dopamine was 3 times higher in fluctuators than in stable responders. By contrast, only stable responders maintained increased levels of synaptic dopamine in the PET scan performed after 4 hours. These results indicate that fluctuations in the synaptic concentration of dopamine precede clinically apparent “wearing‐off” phenomena. The rapid increase in synaptic levels of dopamine observed in fluctuators suggests that increased dopamine turnover might play a relevant role in levodopa‐related motor complications. 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Jon</forename><surname>Stoessl</surname></persName><roleName type="degree">MD, FRCPC</roleName><note type="correspondence"><p>Correspondence: Neurodegenerative Disorders Centre, Vancouver Hospital and Health Sciences Centre, Purdy Pavilion, 2221 Wesbrook Mall, V6T 2B5 Vancouver, BC, Canada</p></note><affiliation>Neurodegenerative Disorders Centre, Vancouver Hospital and Health Sciences Centre, Vancouver, BC, Canada</affiliation></author></analytic><monogr><title level="j">Annals of Neurology</title><title level="j" type="abbrev">Ann Neurol.</title><idno type="pISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><idno type="DOI">10.1002/(ISSN)1531-8249</idno><imprint><publisher>John Wiley & Sons, Inc.</publisher><pubPlace>New York</pubPlace><date type="published" when="2001-03-01"></date><biblScope unit="volume">49</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="298">298</biblScope><biblScope unit="page" to="303">303</biblScope></imprint></monogr><idno type="istex">6A00A035AF114E61BA5FAA15558B9138D300A770</idno><idno type="DOI">10.1002/ana.65</idno><idno type="ArticleID">ANA65</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2001</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Motor fluctuations are a major disabling complication in the treatment of Parkinson's disease. To investigate whether such oscillations in mobility can be attributed to changes in the synaptic levels of dopamine, we studied prospectively patients in the early stages of Parkinson's disease with a follow‐up after at least 3 years of levodopa treatment. At baseline, 3 positron emission tomography (PET) scans using [11C]raclopride before and after (1 hour and 4 hours) orally administered levodopa were performed on the same day for each patient. Patients who developed “wearing‐off” fluctuations during the follow‐up period had a different pattern of levodopa‐induced changes in [11C]raclopride binding potential (BP) from that observed in patients who were still stable by the end of the follow‐up. Thus, 1 hour post‐levodopa the estimated increase in the synaptic level of dopamine was 3 times higher in fluctuators than in stable responders. By contrast, only stable responders maintained increased levels of synaptic dopamine in the PET scan performed after 4 hours. These results indicate that fluctuations in the synaptic concentration of dopamine precede clinically apparent “wearing‐off” phenomena. The rapid increase in synaptic levels of dopamine observed in fluctuators suggests that increased dopamine turnover might play a relevant role in levodopa‐related motor complications. 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E.</givenNames><familyName>Holden</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au7" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Chong S.</givenNames><familyName>Lee</familyName><degrees>MD, FRCPC</degrees></personName></creator><creator xml:id="au8" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Thomas J.</givenNames><familyName>Ruth</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au9" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Donald B.</givenNames><familyName>Calne</familyName><degrees>DM, FRCPC</degrees></personName></creator><creator xml:id="au10" creatorRole="author" affiliationRef="#af1" corresponding="yes"><personName><givenNames>A. Jon</givenNames><familyName>Stoessl</familyName><degrees>MD, FRCPC</degrees></personName><contactDetails><email>jstoessl@interchange.ubc.ca</email></contactDetails></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="CA" type="organization"><unparsedAffiliation>Neurodegenerative Disorders Centre, Vancouver Hospital and Health Sciences Centre, Vancouver, BC, Canada</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="CA" type="organization"><unparsedAffiliation>TRIUMF, University of British Columbia, Vancouver, BC, Canada</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="US" type="organization"><unparsedAffiliation>University of Wisconsin, Madison, WI</unparsedAffiliation></affiliation></affiliationGroup><fundingInfo><fundingAgency>Canadian Institutes for Health Research</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Pacific Parkinson's Research Institute (Vancouver, Canada)</fundingAgency></fundingInfo><fundingInfo><fundingAgency>British Columbia Health Research Foundation</fundingAgency></fundingInfo><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>Motor fluctuations are a major disabling complication in the treatment of Parkinson's disease. To investigate whether such oscillations in mobility can be attributed to changes in the synaptic levels of dopamine, we studied prospectively patients in the early stages of Parkinson's disease with a follow‐up after at least 3 years of levodopa treatment. At baseline, 3 positron emission tomography (PET) scans using [<sup>11</sup>C]raclopride before and after (1 hour and 4 hours) orally administered levodopa were performed on the same day for each patient. Patients who developed “wearing‐off” fluctuations during the follow‐up period had a different pattern of levodopa‐induced changes in [<sup>11</sup>C]raclopride binding potential (BP) from that observed in patients who were still stable by the end of the follow‐up. Thus, 1 hour post‐levodopa the estimated increase in the synaptic level of dopamine was 3 times higher in fluctuators than in stable responders. By contrast, only stable responders maintained increased levels of synaptic dopamine in the PET scan performed after 4 hours. These results indicate that fluctuations in the synaptic concentration of dopamine precede clinically apparent “wearing‐off” phenomena. The rapid increase in synaptic levels of dopamine observed in fluctuators suggests that increased dopamine turnover might play a relevant role in levodopa‐related motor complications. Ann Neurol 2001;49:298–303</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Biochemical variations in the synaptic level of dopamine precede motor fluctuations in Parkinson's disease: PET evidence of increased dopamine turnover</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Dopamine Turnover and Motor Fluctuations</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Biochemical variations in the synaptic level of dopamine precede motor fluctuations in Parkinson's disease: PET evidence of increased dopamine turnover</title></titleInfo><name type="personal"><namePart type="given">Raúl</namePart><namePart type="family">De La Fuente‐Fernández</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Neurodegenerative Disorders Centre, Vancouver Hospital and Health Sciences Centre, Vancouver, BC, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jian‐Qiang</namePart><namePart type="family">Lu</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Neurodegenerative Disorders Centre, Vancouver Hospital and Health Sciences Centre, Vancouver, BC, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Vesna</namePart><namePart type="family">Sossi</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>TRIUMF, University of British Columbia, Vancouver, BC, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Salma</namePart><namePart type="family">Jivan</namePart><namePart type="termsOfAddress">BSc</namePart><affiliation>TRIUMF, University of British Columbia, Vancouver, BC, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Michael</namePart><namePart type="family">Schulzer</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>Neurodegenerative Disorders Centre, Vancouver Hospital and Health Sciences Centre, Vancouver, BC, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">James E.</namePart><namePart type="family">Holden</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>University of Wisconsin, Madison, WI</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Chong S.</namePart><namePart type="family">Lee</namePart><namePart type="termsOfAddress">MD, FRCPC</namePart><affiliation>Neurodegenerative Disorders Centre, Vancouver Hospital and Health Sciences Centre, Vancouver, BC, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Thomas J.</namePart><namePart type="family">Ruth</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>TRIUMF, University of British Columbia, Vancouver, BC, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Donald B.</namePart><namePart type="family">Calne</namePart><namePart type="termsOfAddress">DM, FRCPC</namePart><affiliation>Neurodegenerative Disorders Centre, Vancouver Hospital and Health Sciences Centre, Vancouver, BC, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">A. Jon</namePart><namePart type="family">Stoessl</namePart><namePart type="termsOfAddress">MD, FRCPC</namePart><affiliation>Neurodegenerative Disorders Centre, Vancouver Hospital and Health Sciences Centre, Vancouver, BC, Canada</affiliation><description>Correspondence: Neurodegenerative Disorders Centre, Vancouver Hospital and Health Sciences Centre, Purdy Pavilion, 2221 Wesbrook Mall, V6T 2B5 Vancouver, BC, Canada</description><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article">article</genre><originInfo><publisher>John Wiley & Sons, Inc.</publisher><place><placeTerm type="text">New York</placeTerm></place><dateIssued encoding="w3cdtf">2001-03-01</dateIssued><dateCaptured encoding="w3cdtf">2000-07-18</dateCaptured><dateValid encoding="w3cdtf">2000-10-19</dateValid><copyrightDate encoding="w3cdtf">2001</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">3</extent><extent unit="tables">2</extent><extent unit="references">35</extent><extent unit="words">4588</extent></physicalDescription><abstract lang="en">Motor fluctuations are a major disabling complication in the treatment of Parkinson's disease. To investigate whether such oscillations in mobility can be attributed to changes in the synaptic levels of dopamine, we studied prospectively patients in the early stages of Parkinson's disease with a follow‐up after at least 3 years of levodopa treatment. At baseline, 3 positron emission tomography (PET) scans using [11C]raclopride before and after (1 hour and 4 hours) orally administered levodopa were performed on the same day for each patient. Patients who developed “wearing‐off” fluctuations during the follow‐up period had a different pattern of levodopa‐induced changes in [11C]raclopride binding potential (BP) from that observed in patients who were still stable by the end of the follow‐up. Thus, 1 hour post‐levodopa the estimated increase in the synaptic level of dopamine was 3 times higher in fluctuators than in stable responders. By contrast, only stable responders maintained increased levels of synaptic dopamine in the PET scan performed after 4 hours. These results indicate that fluctuations in the synaptic concentration of dopamine precede clinically apparent “wearing‐off” phenomena. The rapid increase in synaptic levels of dopamine observed in fluctuators suggests that increased dopamine turnover might play a relevant role in levodopa‐related motor complications. Ann Neurol 2001;49:298–303</abstract><note type="funding">Canadian Institutes for Health Research</note><note type="funding">Pacific Parkinson's Research Institute (Vancouver, Canada)</note><note type="funding">British Columbia Health Research Foundation</note><relatedItem type="host"><titleInfo><title>Annals of Neurology</title></titleInfo><titleInfo type="abbreviated"><title>Ann Neurol.</title></titleInfo><subject><genre>article category</genre><topic>Original Article</topic></subject><identifier type="ISSN">0364-5134</identifier><identifier type="eISSN">1531-8249</identifier><identifier type="DOI">10.1002/(ISSN)1531-8249</identifier><identifier type="PublisherID">ANA</identifier><part><date>2001</date><detail type="volume"><caption>vol.</caption><number>49</number></detail><detail type="issue"><caption>no.</caption><number>3</number></detail><extent unit="pages"><start>298</start><end>303</end><total>6</total></extent></part></relatedItem><identifier type="istex">6A00A035AF114E61BA5FAA15558B9138D300A770</identifier><identifier type="DOI">10.1002/ana.65</identifier><identifier type="ArticleID">ANA65</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2001 Wiley‐Liss, Inc.</accessCondition><recordInfo><recordOrigin>John Wiley & Sons, Inc.</recordOrigin><recordContentSource>WILEY</recordContentSource></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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