Levodopa-induced dyskinesia in Parkinson's disease: sleep matters

OBJECTIVE: The spectrum of clinical symptoms changes during the course of Parkinson's disease. Levodopa therapy, while offering remarkable control of classical motor symptoms, causes abnormal involuntary movements as the disease progresses. These levodopa-induced dyskinesias (LIDs) have been associated with abnormal cortical plasticity. Since slow wave activity (SWA) of nonrapid eye movement (NREM) sleep underlies adjustment of cortical excitability, we sought to elucidate the relationship between this physiological process and LIDs. METHODS: Thirty-six patients at different stages of Parkinson's disease (PD) underwent whole-night video polysomnography-high-density EEG (vPSG-hdEEG), preceded by 1 week of actigraphy. To represent the broad spectrum of the disease, patients were divided into three groups by disease stage, (i) de novo (DNV; n = 9), (ii) advanced (ADV; n = 13), and (iii) dyskinetic (DYS; n = 14) and were compared to an age-matched control group (CTL; n = 12). The SWA-NREM content of the PSG-hdEEG was then temporally divided into 10 equal parts, from T1 to T10, and power and source analyses were performed. T2-T3-T4 were considered early sleep and were compared to T7-T8-T9, representing late sleep. RESULTS: We found that all groups, except the DYS group, manifested a clear-cut SWA decrease between early and late sleep. INTERPRETATION: Our data demonstrate a strong pathophysiological association between sleep and PD. Given that SWA may be a surrogate for synaptic strength, our data suggest that DYS patients do not have adequate synaptic downscaling. Further analysis is needed to determine the effect of drugs that can enhance cortical SWA in LIDs.