Decreased dopamine transporter binding in Machacio-Joseph disease

The aim of this study was to use Tc-99m-TRODAT-1 brain SPECT for investigation of the binding of dopamine transporter (DAT) in the nigrostriatal dopaminergic pathway of symptomatic Machado-Joseph disease (MJD) and to compare the results with the abnormal cytidylate, adenylate, and guanylate (CAG) expansion in the MJD1 gene and other clinical factors. Methods: Ten symptomatic MJD patients (8 women, 2 men; age range, 20-71 y; mean age +/- SD, 36.4 +/- 10.6 y, mean duration of illness, 9.8 +/- 5.4 y) and 21 healthy volunteers (age range, 24-71 y; mean age, 47.6 +/- 20.1 y) were examined. Brain SPECT images were acquired 4 h after injection. The ratio of specific to nonspecific nigrostriatal Tc-99m-TRODAT-1 binding was measured and compared with the clinical symptoms, duration of illness, and size of abnormal expanded GAG repeats. Results: All nigrostriatal Tc-99m-TRODAT-1 ratios were significantly lower in MJD patients than in healthy Volunteers (P < 0.05). Discriminant function analysis of all MJD patients showed that the decreased binding of Tc-99m-TRODAT-1 in the putamen was not significantly different from that in the caudate nucleus. Eight of 10 MJD patients had significantly decreased Tc-99m-TRODAT-1 uptake. Of these 8, 2 had extrapyramidal signs and 6 had no obvious extrapyramidal signs. The other 2 patients, who had normal Tc-99m-TRODAT-1 uptake, had no obvious extrapyramidal signs. Conclusion: Our findings indicate that Tc-99m-TRODAT-1 brain SPECT is an appropriate method for evaluating damage to the nigrostriatal DAT in symptomatic MJD patients with and without extrapyramidal signs.The decreased binding of (TC)-T-99m-TRODAT-1 in the nigrostriatal dopaminergic pathway in symptomatic MJD patients correlates with the phenotype of extrapyramidal signs but not with the abnormal CAG repeat length ,age at disease onset, or disease duration.