Pre- and post-synaptic dopaminergic dysfunction in multiple system atrophy: Combined [18F]FP-CIT and [18F]FDG-PET study

Abstract

Objective: To investigate the integrity of presynaptic nigral and postsynaptic striatal dopaminergic systems in MSA patients, especially in relation to the presence of parkinsonism Methods: We studied 26 patients who were diagnosed with probable or possible MSA based on the second consensus statement on the diagnosis of MSA and underwent both [ 18 F]FP-CIT PET and [ 18 F]FDG PET. The PET images were analyzed with 12 striatial subregional volume-of-interest templates (bilateral ventral striatum, anterior and posterior caudate, anterior, posterior and ventral putamen). The PET results of study subjects were compared with the results of age-matched normal controls. Results: Of 26 MSA patients, eight patients had no parkinsonism. Between MSA patients with parkinsonism and those without parkinsonism, there were no significant differences in age at onset, age at study, sex, disease duration, and global disability scale. Seven (87.5%) MSA patients without parkinsonism, and all MSA patients with parkinsonism revealed decreased striatal binding value in the [ 18 F]FP-CIT PET. In five (62.5%) MSA patients without parkinsonism and 14 (77.8%) MSA patients with parkinsonism showed decreased striatal glucose metabolism in [ 18 F]FDG PET. The dissociation between [ 18 F]FP-CIT PET and [ 18 F]FDG PET were considered in 11 MSA patients with parkinsonism and 6 MSA patients without parkinsonism. In quantitative analyses, the binding values of [ 18 F]FP-CIT PET and [ 18 F]FDG PET are correlated in the caudate region (r = 0.504, p = 0.009), but not correlated in the putamen region. Conclusions: High prevalence of subclinical dopaminergic denervation in MSA without parkinsonism could suggest that the evaluation of dopaminergic system using PET scans might be useful in differential diagnosis of cerebellar ataxia. The dissociation between presynaptic and postsynaptic dopaminergic denervation in MSA patients suggest the presence of presynatic type parkinsonism in MSA. Further research is needed to find out levodopa responsiveness according to the dissociation of presynaptic and postsynaptic dopaminergic denervation.