Biochemical variations in the synaptic level of dopamine precede motor fluctuations in Parkinson's disease: PET evidence of increased dopamine turnover
Identifieur interne : 003257 ( Main/Exploration ); précédent : 003256; suivant : 003258Biochemical variations in the synaptic level of dopamine precede motor fluctuations in Parkinson's disease: PET evidence of increased dopamine turnover
Auteurs : Raúl De La Fuente-Fernández [Canada] ; Jian-Qiang Lu [Canada] ; Vesna Sossi [Canada] ; Salma Jivan [Canada] ; Michael Schulzer [Canada] ; James E. Holden [États-Unis] ; Chong S. Lee [Canada] ; Thomas J. Ruth [Canada] ; Donald B. Calne [Canada] ; A. Jon Stoessl [Canada]Source :
- 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
Affiliations:
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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><affiliations><list><country><li>Canada</li><li>États-Unis</li></country><region><li>Wisconsin</li></region></list><tree><country name="Canada"><noRegion><name sortKey="De La Fuente Ernandez, Raul" sort="De La Fuente Ernandez, Raul" uniqKey="De La Fuente Ernandez R" first="Raúl" last="De La Fuente-Fernández">Raúl De La Fuente-Fernández</name></noRegion><name sortKey="Calne, Donald B" sort="Calne, Donald B" uniqKey="Calne D" first="Donald B." last="Calne">Donald B. Calne</name><name sortKey="Jivan, Salma" sort="Jivan, Salma" uniqKey="Jivan S" first="Salma" last="Jivan">Salma Jivan</name><name sortKey="Lee, Chong S" sort="Lee, Chong S" uniqKey="Lee C" first="Chong S." last="Lee">Chong S. Lee</name><name sortKey="Lu, Jian Iang" sort="Lu, Jian Iang" uniqKey="Lu J" first="Jian-Qiang" last="Lu">Jian-Qiang Lu</name><name sortKey="Ruth, Thomas J" sort="Ruth, Thomas J" uniqKey="Ruth T" first="Thomas J." last="Ruth">Thomas J. Ruth</name><name sortKey="Schulzer, Michael" sort="Schulzer, Michael" uniqKey="Schulzer M" first="Michael" last="Schulzer">Michael Schulzer</name><name sortKey="Sossi, Vesna" sort="Sossi, Vesna" uniqKey="Sossi V" first="Vesna" last="Sossi">Vesna Sossi</name><name sortKey="Stoessl, A Jon" sort="Stoessl, A Jon" uniqKey="Stoessl A" first="A. Jon" last="Stoessl">A. Jon Stoessl</name><name sortKey="Stoessl, A Jon" sort="Stoessl, A Jon" uniqKey="Stoessl A" first="A. Jon" last="Stoessl">A. Jon Stoessl</name></country><country name="États-Unis"><region name="Wisconsin"><name sortKey="Holden, James E" sort="Holden, James E" uniqKey="Holden J" first="James E." last="Holden">James E. Holden</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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