Preliminary studies of differential impairments of the dopaminergic system in subtypes of progressive supranuclear palsy

Backbround: Richardson's syndrome (RS) and progressive supranuclear palsy-parkinsonism (PSP-P) are the most common subtypes of PSP syndrome. The clinical features, responses to levodopa, and progression are relatively different but overlap. Determining whether combined molecular imaging studies of dopamine transporter and D2 receptor are helpful for further differentiation of these two subtypes is important. Methods: Ten patients with PSP (six suffering from RS and four from PSP-P) were studied. We also enrolled 10 patients with Parkinson's disease (PD) as disease control and seven healthy individuals as normal controls. Each individual underwent two sets of single photon emission computer tomography imaging, [2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8- azabicyclo[3,2,1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino] ethanethiolato(3-)-N2,N2′2,S2,S2′2]oxo[1R-(exo-exo)])-[ ^99mTc] Technetium (^99mTc-TRODAT-1) dopamine transporter (DAT) and ¹²³I-iodobenzamide D2 receptor. The specific uptake ratio was calculated as (basal ganglia counts-occipital cortex counts)/occipital cortex counts. Results: In DAT scan, the mean striatal uptake was reduced in the RS group compared with that in the PSP-P group, although it did not reach statistical significance. The putamen-to-caudate nucleus ratios were significantly different between PD and all PSP patients (P<0.001), but no difference in putamen-to-caudate ratios was found between the RS and PSP-P groups. In the I iodobenzamide scan, striatal uptake was significantly reduced in the RS group (-22.62%, P=0.022); on the contrary, it was mildly increased in the PSP-P group. Conclusion: The studies showed different alterations of DAT and D2 receptor function between the RS and PSP-P groups. Different DAT imaging might be helpful to distinguish PSP-P from PD in the early stage.