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Motor and nonmotor complications in Parkinson’s disease: an argument for continuous drug delivery?

The complications of long-term levodopa therapy for Parkinson’s disease (PD) include motor fluctuations, dyskinesias, and also nonmotor fluctuations—at least equally common, but less well appreciated—in autonomic, cognitive/psychiatric, and sensory symptoms. In seeking the pathophysiologic mechanism...

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Autores principales: Chaudhuri, K. Ray, Rizos, Alexandra, Sethi, Kapil D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Vienna 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3751411/
https://www.ncbi.nlm.nih.gov/pubmed/23456290
http://dx.doi.org/10.1007/s00702-013-0981-5
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author Chaudhuri, K. Ray
Rizos, Alexandra
Sethi, Kapil D.
author_facet Chaudhuri, K. Ray
Rizos, Alexandra
Sethi, Kapil D.
author_sort Chaudhuri, K. Ray
collection PubMed
description The complications of long-term levodopa therapy for Parkinson’s disease (PD) include motor fluctuations, dyskinesias, and also nonmotor fluctuations—at least equally common, but less well appreciated—in autonomic, cognitive/psychiatric, and sensory symptoms. In seeking the pathophysiologic mechanisms, the leading hypothesis is that in the parkinsonian brain, intermittent, nonphysiological stimulation of striatal dopamine receptors destabilizes an already unstable system. Accordingly, a major goal of PD treatment in recent years has been the attainment of continuous dopaminergic stimulation (CDS)—or, less theoretically (and more clinically verifiable), continuous drug delivery (CDD). Improvements in the steadiness of the plasma profiles of various dopaminergic therapies may be a signal of progress. However, improvements in plasma profile do not necessarily translate into CDS, or even into CDD to the brain. Still, it is reassuring that clinical studies of approaches to CDD have generally been positive. Head-to-head comparative trials have often failed to uncover evidence favoring such approaches over an intermittent therapy. Nevertheless, the findings among recipients of subcutaneous apomorphine infusion or intrajejunal levodopa/carbidopa intestinal gel suggest that nonmotor PD symptoms or complications may improve in tandem with motor improvement. In vivo receptor binding studies may help to determine the degree of CDS that a dopaminergic therapy can confer. This may be a necessary first step toward establishing whether CDS is, in fact, an important determinant of clinical efficacy. Certainly, the complexities of optimal PD management, and the rationale for an underlying strategy such as CDS or CDD, have not yet been thoroughly elucidated.
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spelling pubmed-37514112013-08-27 Motor and nonmotor complications in Parkinson’s disease: an argument for continuous drug delivery? Chaudhuri, K. Ray Rizos, Alexandra Sethi, Kapil D. J Neural Transm (Vienna) Neurology and Preclinical Neurological Studies - Review Article The complications of long-term levodopa therapy for Parkinson’s disease (PD) include motor fluctuations, dyskinesias, and also nonmotor fluctuations—at least equally common, but less well appreciated—in autonomic, cognitive/psychiatric, and sensory symptoms. In seeking the pathophysiologic mechanisms, the leading hypothesis is that in the parkinsonian brain, intermittent, nonphysiological stimulation of striatal dopamine receptors destabilizes an already unstable system. Accordingly, a major goal of PD treatment in recent years has been the attainment of continuous dopaminergic stimulation (CDS)—or, less theoretically (and more clinically verifiable), continuous drug delivery (CDD). Improvements in the steadiness of the plasma profiles of various dopaminergic therapies may be a signal of progress. However, improvements in plasma profile do not necessarily translate into CDS, or even into CDD to the brain. Still, it is reassuring that clinical studies of approaches to CDD have generally been positive. Head-to-head comparative trials have often failed to uncover evidence favoring such approaches over an intermittent therapy. Nevertheless, the findings among recipients of subcutaneous apomorphine infusion or intrajejunal levodopa/carbidopa intestinal gel suggest that nonmotor PD symptoms or complications may improve in tandem with motor improvement. In vivo receptor binding studies may help to determine the degree of CDS that a dopaminergic therapy can confer. This may be a necessary first step toward establishing whether CDS is, in fact, an important determinant of clinical efficacy. Certainly, the complexities of optimal PD management, and the rationale for an underlying strategy such as CDS or CDD, have not yet been thoroughly elucidated. Springer Vienna 2013-03-02 2013 /pmc/articles/PMC3751411/ /pubmed/23456290 http://dx.doi.org/10.1007/s00702-013-0981-5 Text en © The Author(s) 2013 https://creativecommons.org/licenses/by/2.0/ Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Neurology and Preclinical Neurological Studies - Review Article
Chaudhuri, K. Ray
Rizos, Alexandra
Sethi, Kapil D.
Motor and nonmotor complications in Parkinson’s disease: an argument for continuous drug delivery?
title Motor and nonmotor complications in Parkinson’s disease: an argument for continuous drug delivery?
title_full Motor and nonmotor complications in Parkinson’s disease: an argument for continuous drug delivery?
title_fullStr Motor and nonmotor complications in Parkinson’s disease: an argument for continuous drug delivery?
title_full_unstemmed Motor and nonmotor complications in Parkinson’s disease: an argument for continuous drug delivery?
title_short Motor and nonmotor complications in Parkinson’s disease: an argument for continuous drug delivery?
title_sort motor and nonmotor complications in parkinson’s disease: an argument for continuous drug delivery?
topic Neurology and Preclinical Neurological Studies - Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3751411/
https://www.ncbi.nlm.nih.gov/pubmed/23456290
http://dx.doi.org/10.1007/s00702-013-0981-5
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