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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Summary: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
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ISSN:0364-5134
1531-8249
1531-8249
DOI:10.1002/ana.25364