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Levodopa-induced dyskinesia is a form of dyskinesia associated with levodopa used to treat Parkinson's disease. It often involves hyperkinetic movements, including chorea, dystonia, and athetosis. In the context of Parkinson's disease (PD), dyskinesia is often the result of chronic L-DOPA (levodopa) therapy. These motor fluctuations occur in more than half of PD patients after 5–10 years of L-DOPA treatment, with the percentage of affected patients increasing over time.〔Obeso JA, et al. The evolution and origin of motor complications in Parkinson's disease. ''Neurology''. 2000;55 (suppl 4):S13-S20.〕 Based on the relationship with levodopa dosing, dyskinesia most commonly occurs at the time of peak L-DOPA plasma concentrations and is thus referred to as peak-dose dyskinesia (PDD). As patients advance, they may evidence diphasic dyskinesia (DD), which occur when the drug concentration rises or falls. If dyskinesia becomes too severe or impairs the patient's quality of life, a reduction in L-Dopa might be necessary, however this may be accompanied by a worsening of motor performance. Therefore, once established, LID is difficult to treat.〔 Amongst pharmacological treatment, N-methyl-D-aspartate (NMDA) antagonist, (a glutamate receptor), amantadine, has been proven to be clinically effective in a small number of placebo controlled randomized controlled trials, while many others have only shown promise in animal models. Attempts to moderate dyskinesia by the use of other treatments such as bromocriptine (Parlodel), a dopamine agonist, appears to be ineffective.〔van Hilten J, Ramaker C, Stowe R, Ives Nj., 2007. Bromocriptine/levodopa combined versus levodopa alone for early Parkinson's disease. Cochrane Database Syst Rev. 17 October 2007;(4):CD003634.〕 In order to avoid dyskinesia, patients with the young-onset form of the disease or ''young-onset Parkinson's disease'' (YOPD) are often hesitant to commence L-DOPA therapy until absolutely necessary for fear of suffering severe dyskinesia later on. Alternatives include the use of DA agonists (i.e. ropinirole or pramipexole) in lieu of early L-DOPA use which delays the use of L-DOPA. Additionally, a review (Stocchi, F., Clin Neuropharmacol, 2010, 33, 198) shows that highly soluble L-DOPA prodrugs may be effective in avoiding the in vivo blood concentration swings that potentially lead to motor fluctuations and dyskinesia. ==Mechanism== Levodopa-induced dyskinesia (LID) have long been thought to arise through pathological alterations in pre-synaptic and post-synaptic signal transduction in the nigrostriatal pathway (dorsal striatum). It is thought that the stage of illness, the higher the dose and the frequency of L-Dopa treatment, and the younger the age of the patient at onset of symptoms, are considered to underlie the movements In experiments employing real time electrophysiological recordings in awake and behaving animals, LIDs have recently been shown to be strongly associated with cortical gamma-oscillations with accompanying Δc-fos overexpression proposedly due to a dysregulation of dopamine signaling in the cortico-basal ganglia circuitry, concluded partially from reduced TH staining in cortex and the fact that a dopamine receptor 1 antagonist delivered exclusively to the cortex relieved the dyskinesias at the time point of peak-dyskinesias. ΔFosB overexpression in the dorsal striatum (nigrostriatal dopamine pathway) via viral vectors induces levodopa-induced dyskinesias in animal models of Parkinson's disease. Dorsal striatal ΔFosB is overexpressed in rodents and primates with dyskinesias;〔 moreover, postmordem studies of individuals with Parkinson's disease that were treated with levodopa have also observed similar dorsal striatal ΔFosB overexpression.〔 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Levodopa-induced dyskinesia」の詳細全文を読む スポンサード リンク
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