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Levodopa-induced dyskinesias (LID) were first reported by Cotzias et al , the group credited with the first successful use of levodopa in treating Parkinson's disease. 1 Subsequent reports highlighted their high incidence, varied phenomenology, and treatment-limiting effect. Initially thought to be associated only with the peak plasma levels of levodopa, later reports of diphasic dyskinesias and early morning dystonia emphasised a rather complex picture of LID.
EPIDEMIOLOGY AND RISK FACTORS
The reported incidence rates of LID show a wide range, from 9-80%. 2, 3 This is unsurprising as the risk of developing LID depends on age of onset and severity of Parkinson's disease, dose and duration of levodopa therapy, and possibly on some hitherto unknown factors. Moreover, methodological differences in the reporting of LID (for example, relying on patient's history alone versus detection of any dyskinesia by a detailed neurological examination) and lack of a universally agreed assessment scale may account for the differences among studies. The earlier reports of higher rates (81% after 12 months of levodopa therapy) 2 as compared to the significantly lower rates (17% after 12 months) observed in later studies 3 could be explained on the basis of introduction of levodopa at high dosage in relatively advanced stage of Parkinson's disease in the immediate post-levodopa era.
Young-onset Parkinson's disease is associated with a higher incidence of LID. 4 The 5-year risk of LID was 50% in patients with disease onset between 40-59 years of age as compared to 16% in those with disease onset after 70 years. The reason for this propensity is not entirely clear though an interesting suggestion is that there are age-related differences in levodopa dynamics in Parkinson's disease. 5 The presence and extent of nigral denervation (disease severity) are important risk factors. With the dose of levodopa used in clinical practice, LID occur almost exclusively in patients with idiopathic Parkinson's disease, whereas normal people and those with other neurological diseases do not develop LID. 6, 7 In an animal model of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced Parkinson's disease, animals receiving saline plus levodopa did not develop dyskinesias in contrast to the MPTP-treated group that developed significant dyskinesias, implying that nigral damage is required for the production of LID. 8 Patients with post-encephalitis parkinsonism and MPTP-induced parkinsonism develop dyskinesias...