Predicting the development of levodopa-induced dyskinesias: a presynaptic mechanism?

After chronic levodopa use, many patients with Parkinson disease (PD) develop involuntary movements. Whether disabling or minor, levodopa-induced dyskinesia (LID) constitutes an undesirable outcome calling for better treatment strategies. Options for managing LID include delaying its onset by combining a dopaminergic agonist with levodopa from the start(1) or symptomatic control using amantadine. However, fundamental questions about LID remain: by what mechanisms does it develop, and why don't all patients go on to experience LID after sustained levodopa exposure?