LEVODOPA-INDUCED DYSKINESIA IN PARKINSON'S: A LONGITUDINAL PET STUDY

Abstract

<h3>Background/Aim</h3> Serotonergic terminals play an important role in levodopa-induced dyskinesias (LIDs) in patients with Parkinson9s disease (PD). In particular the SERT/DAT ratio changes may be critical for the appearance of LIDs. We investigated serotonergic terminal changes and dopaminergic loss in the putamen over time and their relationship to LIDs. <h3>Methods</h3> Twelve PD patients underwent PET with 11C-DASB and 11C-PE2I; which are specific in vivo markers of SERT and DAT respectively. All patients repeated 11C-DASB and 11C-PE2I PET after 17 months (±11 weeks). The simplified reference tissue model was employed using the cerebellum as a reference. 11C-DASB binding potential (BP), 11C-PE2I BP and 11C-DASB-to-11C-PE2I BP ratios were calculated. <h3>Results</h3> At baseline, all PD patients were non-dyskinetic. The mean 11C-DASB BP was 1.28 (±0.14), the mean 11C-PE2I BP was 1.63 (±0.41), and the median of the SERT-to-DAT ratio was 0.779 (±0.19). At follow-up, mean 11C-PE2I BP was reduced by 14.52% from baseline (p&lt;0.001), while the 11C-DASB BP was only reduced by 4.32% (p&gt;0.10).). The SERT-to-DAT ratios significantly increased by 12.76% (p&lt;0.01) over this time. Three PD patients at follow up had developed dyskinesia. <h3>Conclusion</h3> The imbalance in the rate of decline of SERT and DAT is reflected by the increase of the SERT–to–DAT ratio over time. There may be a threshold of SERT-over-DAT availability in the putamen, above which PD patients are likely to become dyskinetic.