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Levodopa-induced dyskinesias.
Mov Disord. 2007 Jul 30; 22(10):1379-1389.MD

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, alpha2 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.

Authors+Show Affiliations

Department of Neurological Sciences University of Rome "La Sapienza", Rome, Italy.Toronto Western Research Institute, Toronto Western Hospital, Toronto, Canada.Department of Neurology, Hospital General Universitario "Gregorio Marañón", Madrid, Spain.Department of Therapeutic Medicine, Faculty of Medicine, Ehime University Hospital, Ehime, Japan.Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

17427940

Citation

Fabbrini, Giovanni, et al. "Levodopa-induced Dyskinesias." Movement Disorders : Official Journal of the Movement Disorder Society, vol. 22, no. 10, 2007, pp. 1379-1389.
Fabbrini G, Brotchie JM, Grandas F, et al. Levodopa-induced dyskinesias. Mov Disord. 2007;22(10):1379-1389.
Fabbrini, G., Brotchie, J. M., Grandas, F., Nomoto, M., & Goetz, C. G. (2007). Levodopa-induced dyskinesias. Movement Disorders : Official Journal of the Movement Disorder Society, 22(10), 1379-1389. https://doi.org/10.1002/mds.21475
Fabbrini G, et al. Levodopa-induced Dyskinesias. Mov Disord. 2007 Jul 30;22(10):1379-1389. PubMed PMID: 17427940.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Levodopa-induced dyskinesias. AU - Fabbrini,Giovanni, AU - Brotchie,Jonathan M, AU - Grandas,Francisco, AU - Nomoto,Masahiro, AU - Goetz,Christopher G, PY - 2007/4/13/pubmed PY - 2007/10/4/medline PY - 2007/4/13/entrez SP - 1379 EP - 1389 JF - Movement disorders : official journal of the Movement Disorder Society JO - Mov Disord VL - 22 IS - 10 N2 - 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, alpha2 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. SN - 0885-3185 UR - https://www.unboundmedicine.com/medline/citation/17427940/Levodopa_induced_dyskinesias_ L2 - https://doi.org/10.1002/mds.21475 DB - PRIME DP - Unbound Medicine ER -