Pathophysiology of levodopa-induced dyskinesias in Parkinson's disease: problems with the current model

The anatomical and physiological basis of levodopa-induced dyskinesias (LIDs) in patients with Parkinson's disease (PD) is reviewed in the light of the current model for the organization of the basal ganglia. This model, which was developed in the late 1980s, works relatively well in explaining the motor features of PD but, for example, it does not account for why tremor, rigidity, bradykinesia, gait dysfunction and postural instability present to differing degrees in different patients, and may respond differently to levodopa treatment or surgical procedures. Recent information suggests that LIDs develop as a consequence of pulsatile stimulation of dopamine receptors, with consequent dysregulation of genes and proteins in downstream neurons resulting in changes in neuronal firing patterns. A modified model of the basal ganglia in PD patients with LID is proposed, which incorporates more recent clinical and experimental data.