The dopamine transporter is decreased in the striatum of subjects with restless legs syndrome

Abstract

Study objectives: Prior studies, all using SPECT techniques, failed to find any differences for dopamine transporter (DAT) in restless legs syndrome (RLS) subjects. The distinct pharmacokinetic properties associated with SPECT-determined DAT along with rapid biodynamic changes in DAT may, however, have missed membrane-bound DAT differences. The current studies assessed real-time DAT binding potentials (BP) in striatum of RLS patients using (11)C-methylphenidate and PET techniques.

Design: RLS medications were stopped at least 11 days prior to the PET study. Clinical severity of RLS was also assessed. PET scans were performed at 2 different times of day (starting at 08:30 and 19:30) in separate groups of subjects. The primary outcome measure was total striatal DAT BP.

Participants: Thirty-six patients with primary RLS and 34 age- and gender-matched controls.

Results: RLS subjects had significantly lower DAT binding in the striatum compared to controls on both the Day and the Night scans. DAT was decreased in putamen and caudate but not the ventral striatum of RLS subjects. There were no diurnal differences in DAT for the total group or for control and RLS separately. DAT BP did not correlate with any clinical measures of RLS.

Conclusion: The current study found a significant decrease in DAT BP in two independent studies. These results when viewed along with prior RLS SPECT and autopsy studies of DAT, and cell culture studies with iron deficiency and DAT, suggest that membrane-bound striatal DAT, but not total cellular DAT, may be decreased in RLS.

Keywords: Restless leg syndrome; dopamine transporter; positron emission tomography; striatum.

Figures

Figure 1

DAT binding potential in the striatum from the Day and the Night studies for all control, all RLS and dopaminergic-drug naive (No DA) RLS subjects. Individual data points are presented as smallest dots, two overlapping data are presented as medium dots and three overlapping data are presented as the largest dot.

Figure 2

Representative example of [11C]methylphenidate binding potential in the striatum of a RLS and Control subject.