Levodopa-induced dyskinesias

Authors

  • Giovanni Fabbrini MD,

    Corresponding author
    1. Department of Neurological Sciences University of Rome “La Sapienza”, Rome, Italy
    • Department of Neurological Sciences, University “La Sapienza”, Viale dell'Università 30, 00185 Rome, Italy
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    • This manuscript is an adaptation of a syllabus contribution to the Movement Disorder Society's annual congress, 2006. All authors received an honorarium from the MDS for participation in the program related to the syllabus material. Other disclosures include: Dr. Fabbrini: None; Dr. Brotchie: Consultancy fees from Akuta Ltd; Dr. Grandas: Consultancy fees from Schwarz Pharma; Dr. Nomoto: None; Dr. Goetz: Honoraria received from Merck KaGA for serving on the Publication Committee for Sarizotan Programs.

  • Jonathan M. Brotchie PhD,

    1. Toronto Western Research Institute, Toronto Western Hospital, Toronto, Canada
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    • This manuscript is an adaptation of a syllabus contribution to the Movement Disorder Society's annual congress, 2006. All authors received an honorarium from the MDS for participation in the program related to the syllabus material. Other disclosures include: Dr. Fabbrini: None; Dr. Brotchie: Consultancy fees from Akuta Ltd; Dr. Grandas: Consultancy fees from Schwarz Pharma; Dr. Nomoto: None; Dr. Goetz: Honoraria received from Merck KaGA for serving on the Publication Committee for Sarizotan Programs.

  • Francisco Grandas MD, PhD,

    1. Department of Neurology, Hospital General Universitario “Gregorio Marañón”, Madrid, Spain
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    • This manuscript is an adaptation of a syllabus contribution to the Movement Disorder Society's annual congress, 2006. All authors received an honorarium from the MDS for participation in the program related to the syllabus material. Other disclosures include: Dr. Fabbrini: None; Dr. Brotchie: Consultancy fees from Akuta Ltd; Dr. Grandas: Consultancy fees from Schwarz Pharma; Dr. Nomoto: None; Dr. Goetz: Honoraria received from Merck KaGA for serving on the Publication Committee for Sarizotan Programs.

  • Masahiro Nomoto MD, PhD,

    1. Department of Therapeutic Medicine, Faculty of Medicine, Ehime University Hospital, Ehime, Japan
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    • This manuscript is an adaptation of a syllabus contribution to the Movement Disorder Society's annual congress, 2006. All authors received an honorarium from the MDS for participation in the program related to the syllabus material. Other disclosures include: Dr. Fabbrini: None; Dr. Brotchie: Consultancy fees from Akuta Ltd; Dr. Grandas: Consultancy fees from Schwarz Pharma; Dr. Nomoto: None; Dr. Goetz: Honoraria received from Merck KaGA for serving on the Publication Committee for Sarizotan Programs.

  • Christopher G. Goetz MD

    1. Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA
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    • This manuscript is an adaptation of a syllabus contribution to the Movement Disorder Society's annual congress, 2006. All authors received an honorarium from the MDS for participation in the program related to the syllabus material. Other disclosures include: Dr. Fabbrini: None; Dr. Brotchie: Consultancy fees from Akuta Ltd; Dr. Grandas: Consultancy fees from Schwarz Pharma; Dr. Nomoto: None; Dr. Goetz: Honoraria received from Merck KaGA for serving on the Publication Committee for Sarizotan Programs.


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, 5HT2A), 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. © 2007 Movement Disorder Society

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