Differential alterations of dopamine transporter in the striatum and midbrain in patients with parkinsonian syndrome.

Abstract

Differential vulnerabilities of subregional dopamine neurons have been suggested in movement disorders such as idiopathic Parkinson disease. In this study, we examined dopamine transporter (DaT) density in the striatum versus midbrain (MB) in patients with nigrostriatal denervation. Brain SPECT was performed in 39 patients with parkinsonian syndrome (age 61 ± 15 years, 18 male patients) 4 hours after IV injection of 3 to 5 mCi 123I ioflupane using SPECT-CT acquisition. Images were reconstructed using OSEM with resolution recovery and correction for scatter and attenuation based on a low-dose CT. Peak pixel counts within the caudate head (CA), mid putamen (PT), and MB localized by sagittal CT, as well as averaged counts around the calcarine fissure as reference, were determined by region-of-interest analysis. Semiquantitative DaT values were expressed as CA, PT, or MB uptake relative to the reference. We then assessed the relationship between the MB measurements and independent clinical evaluation of motor symptoms in these patients. Averaged striatal DaT values for both hemispheres ranged from 1.67 to 6.59 for CA, 1.50 to 5.33 for PT, and 1.08 to 2.24 for MB. Within the high striatal DaT group (mean, 4.76 [SD, 0.55]) and low DaT group (mean, 2.71 [SD, 0.58]; dichotomy defined as a threshold of 4), mean DaT values in MB were 1.68 (SD, 0.32) and 1.53 (SD, 0.29), respectively, indicating nonsignificant 9% decrease (P > 0.15) in comparison to 43% decrease in the averaged striatal uptake. Within the high striatal DaT group, Pearson correlations between DaT values of CA and PT versus MB were highly significant at 0.81 and 0.82 (P ≤ 0.001), respectively, but those correlations were not significant, 0.35 (P > 0.05) and 0.06 (P > 0.75), in the low striatal DaT group. Midbrain uptake measurements did not correlate with motor symptoms (bradykinesia, tremor, rigidity, and postural instability). These findings indicate that reductions in DaT values in the striatum and MB are not necessarily simultaneous with the process of nigrostriatal denervation, and correlation of DaT values among CA/PT and MB becomes weaker as the denervation becomes more severe. Differential regional DaT loss may indicate differential vulnerability of DaT-containing neurons in these structures or could be in part related to tracer binding to non-DaT targets.