Levodopa-induced dyskinesias.
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.
Fabbrini
Giovanni
G
Department of Neurological Sciences University of Rome "La Sapienza", Rome, Italy.
Brotchie
Jonathan M
JM
Toronto Western Research Institute, Toronto Western Hospital, Toronto, Canada.
Grandas
Francisco
F
Department of Neurology, Hospital General Universitario "Gregorio Marañón", Madrid, Spain.
Nomoto
Masahiro
M
Department of Therapeutic Medicine, Faculty of Medicine, Ehime University Hospital, Ehime, Japan.
Goetz
Christopher G
CG
Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA.
D000978:Antiparkinson Agents / Q000009:adverse effects*; D004409:Dyskinesia, Drug-Induced / Q000453:epidemiology / Q000209:etiology* / Q000523:psychology / Q000628:therapy; D006801:Humans; D007980:Levodopa / Q000009:adverse effects*; D010300:Parkinson Disease / Q000188:drug therapy; D039781:PubMed / Q000706:statistics & numerical data; D011788:Quality of Life; D012196:Review Literature as Topic
D000978:Antiparkinson Agents; D007980:Levodopa