PET demonstrates reduced dopamine transporter expression in PD with dyskinesias.
OBJECTIVE
Dyskinesias are common in Parkinson disease (PD). Prior investigations suggest that dopamine (DA) terminals compensate for abnormal DA transmission. We verified whether similar adaptations could be related to the development of treatment-related complications.


METHODS
Thirty-six patients with PD with motor fluctuations were assessed with PET using [(11)C]-d-threo-methylphenidate (MP) and [(11)C]-(+/-) dihydrotetrabenazine (DTBZ). The expression of DA transporter relative to DA nerve terminal density was estimated by determining the MP/DTBZ ratio. Age, treatment, and disease severity were also taken into account in the evaluation of our data.


RESULTS
Twenty-seven of the 36 patients had dyskinesias. Nine individuals had motor fluctuations without dyskinesia. The two patient groups were comparable in terms of age, disease duration and severity, medication, and striatal MP and DTBZ binding potentials. The MP/DTBZ ratio in the caudate was not different between groups (nondyskinesia 1.54 +/- 0.36, dyskinesia 1.39 +/- 0.28; mean +/- SD, p = 0.23). Putaminal MP/DTBZ was decreased in individuals with dyskinesia (1.18 +/- 0.24), compared to those who had motor fluctuations without dyskinesia (1.52 +/- 0.24, p = 0.019). The relationship between putaminal MP/DTBZ ratio and the presence of dyskinesias was not altered after correcting for age, treatment, and measures of disease severity.


CONCLUSIONS
This investigation supports the role of presynaptic alterations in the appearance of dyskinesias. Dopamine (DA) transporter downregulation may minimize symptoms by contributing to increased synaptic DA levels in early Parkinson disease, but at the expense of leading to increased extracellular DA catabolism and oscillating levels of DA. Such oscillations might ultimately facilitate the appearance of dyskinesias.
Troiano
A R
AR
Pacific Parkinson's Research Centre, Vancouver, BC, Canada. andretroiano@gmail.com
de la Fuente-Fernandez
R
R
Sossi
V
V
Schulzer
M
M
Mak
E
E
Ruth
T J
TJ
Stoessl
A J
AJ
D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000096:biosynthesis* / Q000235:genetics; D020820:Dyskinesias / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008774:Methylphenidate; D008875:Middle Aged; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011699:Putamen / Q000000981:diagnostic imaging / Q000378:metabolism; D019275:Radiopharmaceuticals; D013747:Tetrabenazine / Q000031:analogs & derivatives
D050483:Dopamine Plasma Membrane Transport Proteins; D019275:Radiopharmaceuticals; D008774:Methylphenidate; C032811:dihydrotetrabenazine; D013747:Tetrabenazine