| Non-motor dopamine withdrawal syndrome after surgery for Parkinson's disease: predictors and underlying mesolimbic denervation. | |
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MedLine Citation:
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PMID: 20237128 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Apathy has been reported to occur after subthalamic nucleus stimulation, a treatment of motor complications in advanced Parkinson's disease. We carried out a prospective study of the occurrence of apathy and associated symptoms, predictors and mechanisms in the year following subthalamic stimulation. Dopamine agonist drugs were discontinued immediately after surgery and levodopa was markedly reduced within 2 weeks. Apathy and depression were assessed monthly, using the Starkstein apathy scale and the Beck Depression Inventory. Dopamine agonists were re-introduced if patients developed apathy or depression. Preoperative non-motor fluctuations were evaluated using the Ardouin Scale. Depression, apathy and anxiety were evaluated both on and off levodopa. Analysis of predictors of apathy was performed using a Cox proportional hazard model. Twelve patients who developed apathy and a control group of 13 patients who did not underwent [11C]-raclopride positron emission tomography scanning before and after oral intake of methylphenidate. In 63 patients with Parkinson's disease treated with subthalamic stimulation, dopaminergic treatment was decreased by 82% after surgery. Apathy occurred after a mean of 4.7 (3.3-8.2) months in 34 patients and was reversible in half of these by the 12-month follow-up. Seventeen patients developed transient depression after 5.7 (4.7-9.3) months and these fell into the apathy group with one single exception. At baseline, fluctuations in depression, apathy and anxiety scores were greater in the group with apathy. Fluctuations in apathy, depression and anxiety ratings during a baseline levodopa challenge were also significant predictors of postoperative apathy in univariate analysis, but not motor and cognitive states or the level of reduction of dopaminergic medication. The multivariate model identified non-motor fluctuations in everyday life and anxiety score during the baseline levodopa challenge as two independent significant predictors of postoperative apathy. Without methylphenidate, [11C]-raclopride binding potential values were greater in apathetic patients bilaterally in the orbitofrontal, dorsolateral prefrontal, posterior cingulate and temporal cortices, left striatum and right amygdala, reflecting greater dopamine D2/D3 receptor density and/or reduced synaptic dopamine level in these areas. The variations of [11C]-raclopride binding potential values induced by methylphenidate were greater in non-apathetic patients in the left orbitofrontal cortex, dorsolateral prefrontal cortex, thalamus and internal globus pallidus and bilaterally in the anterior and posterior cingulate cortices, consistent with a more important capacity to release dopamine. Non-motor fluctuations are related to mesolimbic dopaminergic denervation. Apathy, depression and anxiety can occur after surgery as a delayed dopamine withdrawal syndrome. A varying extent of mesolimbic dopaminergic denervation and differences in dopaminergic treatment largely determine mood, anxiety and motivation in patients with Parkinson's disease, contributing to different non-motor phenotypes. |
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Authors:
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Stéphane Thobois; Claire Ardouin; Eugénie Lhommée; Hélène Klinger; Christelle Lagrange; Jing Xie; Valérie Fraix; Maria Clara Coelho Braga; Rachid Hassani; Andrea Kistner; Alexandra Juphard; Eric Seigneuret; Stephan Chabardes; Patrick Mertens; Gustavo Polo; Anthonin Reilhac; Nicolas Costes; Didier LeBars; Marc Savasta; Léon Tremblay; Jean-Louis Quesada; Jean-Luc Bosson; Alim-Louis Benabid; Emmanuel Broussolle; Pierre Pollak; Paul Krack |
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Publication Detail:
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Type: Clinical Trial; Comparative Study; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't Date: 2010-03-17 |
Journal Detail:
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Title: Brain : a journal of neurology Volume: 133 ISSN: 1460-2156 ISO Abbreviation: Brain Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-04-08 Completed Date: 2010-04-27 Revised Date: 2010-11-03 |
Medline Journal Info:
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Nlm Unique ID: 0372537 Medline TA: Brain Country: England |
Other Details:
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Languages: eng Pagination: 1111-27 Citation Subset: AIM; IM |
Affiliation:
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Universitée Lyon I, Hospices Civils de Lyon, Hôpital Neurologique Pierre Wertheimer, Service de Neurologie C, Lyon, France. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Deep Brain Stimulation / adverse effects Denervation / psychology Depression / etiology, psychology Dopamine Agonists / adverse effects* Double-Blind Method Female Follow-Up Studies Humans Limbic System / surgery* Male Middle Aged Parkinson Disease / drug therapy, psychology*, surgery* Postoperative Complications / chemically induced, etiology, psychology Predictive Value of Tests Prospective Studies Substance Withdrawal Syndrome / etiology, psychology* |
| Chemical | |
Reg. No./Substance:
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0/Dopamine Agonists |
| Comments/Corrections | |
Comment In:
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Brain. 2010 Nov;133(11):e155; author reply e156
[PMID:
20659959
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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