Levodopa-induced dyskinesias

Giovanni Fabbrini, Jonathan M. Brotchie, Francisco Grandas, Masahiro Nomoto, Christopher G. Goetz

Research output: Contribution to journalArticlepeer-review

Abstract

Levodopa-induced dyskinesias (LID) are common and difficult to treat. This review focuses on three issues related to LID: clinical features, classification and rating, pathophysiology and pathogenesis, and management. The three primary clinical syndromes are OFF-period dystonia, peak-dose dyskinesia, and diphasic dyskinesia. Several other forms also occur, making the evaluation and choice of treatment complicated. A core component of the pathophysiology of LID is overactivity of the direct striatal output pathway. This pathway provides a direct GABAergic connection by which the striatum inhibits the output regions of the basal ganglia, i.e., the internal globus pallidus and the substantia nigra pars reticulata. Altering dopaminergic dosing and timing can abate dyskinesias, but usually impact the control of parkinsonism. Putative therapies to reduce the problem of dyskinesias could focus on the glutamatergic, GABAergic, α2 adrenergic, serotonergic (5HT1A, 5HT 2A), opioid, histamine H3, adenosine A2A receptors, the monoamine transport or cannabinoid CB1 receptors systems. The only currently available drug with an evidence-based recommendation on efficacy for dyskinesia is amantadine. Therapy goals include the prevention of dyskinesia and treatment of dyskinesias that are troublesome clinically. New rating measures to assess severity and disability related to dyskinesia are in the process of development and clinimetric testing.

Original languageEnglish
Pages (from-to)1379-1389
Number of pages11
JournalMovement Disorders
Volume22
Issue number10
DOIs
Publication statusPublished - Jul 30 2007

Keywords

  • Dyskinesia
  • Levodopa
  • Parkinson

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

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