Levodopa‐induced dyskinesia in Parkinson disease: Current and evolving concepts

Levodopa‐induced dyskinesia is a common complication in Parkinson disease. Pathogenic mechanisms include phasic stimulation of dopamine receptors, nonphysiological levodopa‐to‐dopamine conversion in serotonergic neurons, hyperactivity of corticostriatal glutamatergic transmission, and overstimulatio...

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Published inAnnals of neurology Vol. 84; no. 6; pp. 797 - 811
Main Authors Espay, Alberto J., Morgante, Francesca, Merola, Aristide, Fasano, Alfonso, Marsili, Luca, Fox, Susan H., Bezard, Erwan, Picconi, Barbara, Calabresi, Paolo, Lang, Anthony E.
Format Journal Article
LanguageEnglish
Published United States Wiley Subscription Services, Inc 01.12.2018
Subjects
Acetylcholine receptors (nicotinic)
Axons
Cortex
Dopamine
Dopamine receptors
Dyskinesia
Glutamatergic transmission
Hyperactivity
Levodopa
Movement disorders
Neurodegenerative diseases
Parkinson's disease
Receptors
Serotonin
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Abstract Levodopa‐induced dyskinesia is a common complication in Parkinson disease. Pathogenic mechanisms include phasic stimulation of dopamine receptors, nonphysiological levodopa‐to‐dopamine conversion in serotonergic neurons, hyperactivity of corticostriatal glutamatergic transmission, and overstimulation of nicotinic acetylcholine receptors on dopamine‐releasing axons. Delay in initiating levodopa is no longer recommended, as dyskinesia development is a function of disease duration rather than cumulative levodopa exposure. We review current and in‐development treatments for peak‐dose dyskinesia but suggest that improvements in levodopa delivery alone may reduce its future prevalence. Ann Neurol 2018;84:797–811
AbstractList Levodopa‐induced dyskinesia is a common complication in Parkinson disease. Pathogenic mechanisms include phasic stimulation of dopamine receptors, nonphysiological levodopa‐to‐dopamine conversion in serotonergic neurons, hyperactivity of corticostriatal glutamatergic transmission, and overstimulation of nicotinic acetylcholine receptors on dopamine‐releasing axons. Delay in initiating levodopa is no longer recommended, as dyskinesia development is a function of disease duration rather than cumulative levodopa exposure. We review current and in‐development treatments for peak‐dose dyskinesia but suggest that improvements in levodopa delivery alone may reduce its future prevalence. Ann Neurol 2018;84:797–811
Levodopa-induced dyskinesia is a common complication in Parkinson disease. Pathogenic mechanisms include phasic stimulation of dopamine receptors, nonphysiological levodopa-to-dopamine conversion in serotonergic neurons, hyperactivity of corticostriatal glutamatergic transmission, and overstimulation of nicotinic acetylcholine receptors on dopamine-releasing axons. Delay in initiating levodopa is no longer recommended, as dyskinesia development is a function of disease duration rather than cumulative levodopa exposure. We review current and in-development treatments for peak-dose dyskinesia but suggest that improvements in levodopa delivery alone may reduce its future prevalence. Ann Neurol 2018;84:797-811.
Levodopa-induced dyskinesia is a common complication in Parkinson disease. Pathogenic mechanisms include phasic stimulation of dopamine receptors, nonphysiological levodopa-to-dopamine conversion in serotonergic neurons, hyperactivity of corticostriatal glutamatergic transmission, and overstimulation of nicotinic acetylcholine receptors on dopamine-releasing axons. Delay in initiating levodopa is no longer recommended, as dyskinesia development is a function of disease duration rather than cumulative levodopa exposure. We review current and in-development treatments for peak-dose dyskinesia but suggest that improvements in levodopa delivery alone may reduce its future prevalence. Ann Neurol 2018;84:797-811.Levodopa-induced dyskinesia is a common complication in Parkinson disease. Pathogenic mechanisms include phasic stimulation of dopamine receptors, nonphysiological levodopa-to-dopamine conversion in serotonergic neurons, hyperactivity of corticostriatal glutamatergic transmission, and overstimulation of nicotinic acetylcholine receptors on dopamine-releasing axons. Delay in initiating levodopa is no longer recommended, as dyskinesia development is a function of disease duration rather than cumulative levodopa exposure. We review current and in-development treatments for peak-dose dyskinesia but suggest that improvements in levodopa delivery alone may reduce its future prevalence. Ann Neurol 2018;84:797-811.
Author Calabresi, Paolo
Picconi, Barbara
Fasano, Alfonso
Lang, Anthony E.
Morgante, Francesca
Marsili, Luca
Fox, Susan H.
Merola, Aristide
Bezard, Erwan
Espay, Alberto J.
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  surname: Espay
  fullname: Espay, Alberto J.
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  organization: University of Cincinnati
– sequence: 2
  givenname: Francesca
  surname: Morgante
  fullname: Morgante, Francesca
  organization: St George's University of London
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  surname: Merola
  fullname: Merola, Aristide
  organization: University of Cincinnati
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  fullname: Fasano, Alfonso
  organization: Krembil Brain Institute
– sequence: 5
  givenname: Luca
  surname: Marsili
  fullname: Marsili, Luca
  organization: University of Cincinnati
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  givenname: Susan H.
  surname: Fox
  fullname: Fox, Susan H.
  organization: Krembil Brain Institute
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  givenname: Erwan
  surname: Bezard
  fullname: Bezard, Erwan
  organization: National Center for Scientific Research, Institute of Neurodegenerative Diseases
– sequence: 8
  givenname: Barbara
  surname: Picconi
  fullname: Picconi, Barbara
  organization: IRCCS San Raffaele Pisana, University San Raffaele
– sequence: 9
  givenname: Paolo
  surname: Calabresi
  fullname: Calabresi, Paolo
  organization: University of Perugia, Santa Maria della Misericordia Hospital
– sequence: 10
  givenname: Anthony E.
  surname: Lang
  fullname: Lang, Anthony E.
  organization: Krembil Brain Institute
BackLink https://www.ncbi.nlm.nih.gov/pubmed/30357892$$D View this record in MEDLINE/PubMed
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Snippet Levodopa‐induced dyskinesia is a common complication in Parkinson disease. Pathogenic mechanisms include phasic stimulation of dopamine receptors,...
Levodopa-induced dyskinesia is a common complication in Parkinson disease. Pathogenic mechanisms include phasic stimulation of dopamine receptors,...
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SubjectTerms Acetylcholine receptors (nicotinic)
Axons
Cortex
Dopamine
Dopamine receptors
Dyskinesia
Glutamatergic transmission
Hyperactivity
Levodopa
Movement disorders
Neurodegenerative diseases
Parkinson's disease
Receptors
Serotonin
Title Levodopa‐induced dyskinesia in Parkinson disease: Current and evolving concepts
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fana.25364
https://www.ncbi.nlm.nih.gov/pubmed/30357892
https://www.proquest.com/docview/2159553163
https://www.proquest.com/docview/2125299398
Volume 84
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