Increased serotonin-to-dopamine transporter ratios in Parkinson disease dyskinesias: a longitudinal study
File(s)
Author(s)
Type
Conference Paper
Abstract
Background and aims
Serotonergic terminals play an important role in levodopa-induced dyskinesias (LIDs) in patients with Parkinson’s disease (PD). An increased SERT-over-DAT terminal ratio in the putamen has been proposed to be a risk factor for the appearance of LIDs. We investigated the temporal relationship between serotonergic terminal changes and dopaminergic loss in the putamen and the appearance of LIDs.
Methods
Twelve PD patients underwent PET with 11C-DASB and 11C-PE2I; which are specific in vivo markers of serotonin (SERT) and dopamine transporters (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.
Results
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, the mean 11C-PE2I BP was (1.39±0.41) reduced by 14.52% from baseline (p<0.001); the 11C-DASB BP had only reduced by 4.32% (1.23±0.19)(p>0.10). Percentage changes in 11C-PE2I BP at follow-up were significantly greater than percentage changes in 11C-DASB BP (p<0.05). The SERT-to-DAT ratios significantly increased by 12.76% (p<0.01) over this time. Three PD patients became dyskinetic;their SERT-to-DAT ratios were 0.978, 0.878, and 1.282.
Conclusion
The imbalance in the rate of SERT and DAT decline reflects the increase of the SERT–to–DAT ratio over time. Our findings suggest that there may be a threshold of SERT-over-DAT availability in the putamen, above which PD patients are likely to become dyskinetic.
Serotonergic terminals play an important role in levodopa-induced dyskinesias (LIDs) in patients with Parkinson’s disease (PD). An increased SERT-over-DAT terminal ratio in the putamen has been proposed to be a risk factor for the appearance of LIDs. We investigated the temporal relationship between serotonergic terminal changes and dopaminergic loss in the putamen and the appearance of LIDs.
Methods
Twelve PD patients underwent PET with 11C-DASB and 11C-PE2I; which are specific in vivo markers of serotonin (SERT) and dopamine transporters (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.
Results
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, the mean 11C-PE2I BP was (1.39±0.41) reduced by 14.52% from baseline (p<0.001); the 11C-DASB BP had only reduced by 4.32% (1.23±0.19)(p>0.10). Percentage changes in 11C-PE2I BP at follow-up were significantly greater than percentage changes in 11C-DASB BP (p<0.05). The SERT-to-DAT ratios significantly increased by 12.76% (p<0.01) over this time. Three PD patients became dyskinetic;their SERT-to-DAT ratios were 0.978, 0.878, and 1.282.
Conclusion
The imbalance in the rate of SERT and DAT decline reflects the increase of the SERT–to–DAT ratio over time. Our findings suggest that there may be a threshold of SERT-over-DAT availability in the putamen, above which PD patients are likely to become dyskinetic.
Date Issued
2016-06-23
Date Acceptance
2016-03-03
Citation
European Journal of Neurology, 2016, 23 (Suppl 2), pp.105-105
ISSN
1468-1331
Publisher
Wiley
Start Page
105
End Page
105
Journal / Book Title
European Journal of Neurology
Volume
23
Issue
Suppl 2
Copyright Statement
© 2016 EAN.
Sponsor
Michael J Fox Foundation
Imperial College Healthcare NHS Trust- BRC Funding
Grant Number
N/A
RDC04 79560
Source
2nd Congress of the European Academy of Neurology
Subjects
Neurology & Neurosurgery
Clinical Sciences
Neurosciences
Publication Status
Published
Start Date
2016-05-28
Finish Date
2016-05-31
Coverage Spatial
Copenhagen, DENMARK