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This Article Figures Only Full Text Full Text (PDF) CME: Take the course for this article: Volume 72, Number 14, April 7, 2009 Italian Translation All Versions of this Article: 01.wnl.0000338631.73211.56v1 72/14/1211    most recent Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Troiano, A. R. Articles by Stoessl, A. J. Search for Related Content PubMed PubMed Citation Articles by Troiano, A. R. Articles by Stoessl, A. J. Related Collections PET Parkinson's disease/Parkinsonism Basal ganglia

PET demonstrates reduced dopamine transporter expression in PD with dyskinesias

From the Pacific Parkinson’s Research Centre (A.R.T., R.d.l.F.-F., M.S., E.M., T.J.R., A.J.S.), Department of Physics and Astronomy (V.S.), and TRIUMF (V.S.), UBC, Vancouver, BC, Canada.

Address correspondence and reprint requests to Dr. André R. Troiano. Pacific Parkinson’s Research Centre, 2221 Wesbrook Mall, Purdy Pavillion. Vancouver, BC, Canada V6T 2B5

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 [¹¹C]-d-threo-methylphenidate (MP) and [¹¹C]-(±) 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.

BP = binding potential; COMTi = catechol-O-methyl transferase inhibitors; CR = controlled release; DA = dopamine; DAT = DA transporter; DTBZ = [¹¹C]-(±) dihydrotetrabenazine; DVR = distribution volume; MF = motor fluctuation; MP = [¹¹C]-d-threo-methylphenidate; PD = Parkinson disease; ROI = region of interest; UPDRS = Unified Parkinson’s Disease Rating Scale.

andretroiano{at}gmail.com

Editorial, page 1202

e-Pub ahead of print on November 19, 2008, at www.neurology.org.

Supported by a CIHR Team Grant in Parkinson’s Disease, an operating grant from CIHR, a Research Unit award from the Michael Smith Foundation for Health Research, the National Parkinson Foundation, and the Pacific Parkinson’s Research Institute. V.S. was supported by the Michael Smith Foundation for Health Research, A.J.S. by the Canada Research Chairs, and A.R.T. by the Pacific Parkinson’s Research Institute.

Disclosure: The authors report no disclosures.

Received May 28, 2008. Accepted in final form September 26, 2008.

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