Relief of parkinsonism and dyskinesia

Dyskinesia is a common adverse outcome intruding upon all the good that levodopa can do for Parkinson disease (PD). Though investigated in scores of studies for almost 30 years, the pathogenesis of these involuntary movements remains an enigma. Levodopa, a durable veteran of PD therapeutics and still the most widely used medication for this disorder, is unlikely to be replaced by better treatments. Hence, levodopa's propensity to induce dyskinesia remains an ongoing challenge for clinicians and neuroscientists.

Levodopa-induced dyskinesia (LID) can arise within months to years after the start of levodopa therapy. To illustrate the changing relationship between plasma levodopa concentration and clinical effects like LID, a schematic graph purporting to explain these phenomena has appeared countless times before neurology audiences. This diagram implies that, over time, dopaminergic stimulation thresholds for antiparkinsonian effect and for dyskinesia change differentially. A model with an uncomplicated explanation for the origin of LID is desirable, but, as Nutt et al.¹ point out in the current issue of Neurology®, this pictoralization is more myth than reality. Their report argues for an alternative conceptualization (figure 1B in their article) that better fits what is known. A shrinking therapeutic window over time, which has been a prevailing notion about the changing levodopa response profile, does not figure into their current understanding of LID.

The data behind this report come from retrospective analysis of extensive clinical investigations by Nutt …