Differential alteration of the nigrostriatal dopaminergic system in Wilson's disease investigated with [I-123]beta-CIT and high-resolution SPET

Wilson's disease (WD) is a copper deposition disorder which can result in a number of extrapyramidal motoric symptoms such as parkinsonism. Therefore, this study was carried out to investigate, for the first time, nigrostriat al dopaminergic function in WD in relation to different courses and severit y of the disease. Using high-resolution single-photon emission tomography ( SPET) after administration of 2 beta -carbomethoxy-3 beta-(4[I-123]iodophen yl)tropane ([I-123]beta -CIT), striatal dopamine transporters (DAT) were im aged in 43 WD patients and a control group of ten subjects. From the SPET i mages, specific [I-123]beta -CIT binding ratios were obtained for the cauda te heads, putamina and entire corpus striatum. In addition, to evaluate a p utative dissociation between the caudate and putaminal [123I]beta -CIT bind ing ratios, the ratio between these binding ratios was calculated (CA/PU ra tio). The SPET data were compared with clinical data on the course of the d isease (CD), the severity of neurological symptoms and the degree of hepati c alteration. Whereas the specific regional [123I]beta -CIT binding ratios in patients with asymptomatic/hepatic CD did not differ from those in the c ontrol group (e.g. striatal ratios: 13.4 +/-3.0 vs 11.7 +/-2.8), in patient s with neurological CD the ratios were significantly reduced for all striat al substructures (P=0.003 after one-factor ANOVA). For the different subgro ups a tendency was detected towards a stepwise decrease in the specific [I- 123]beta -CIT binding ratios from pseudo-sclerosis CD (9.4 +/-2.3), through pseudo-parkinsonian CD (9.1 +/-2.1) to arrhythmic-hyperkinetic CD (8.5 +/- 1.6). However, these group differences reached significance only for the co mparison with asymptomatic/hepatic CD (P=0.02). The CA/PU ratio was signifi cantly higher in WD than in the control group (1.30 +/-0.19 vs 1.11 +/-0.08 ; P=0.003). Severity of neurological symptoms was significantly correlated with all specific regional [I-123]beta -CIT binding ratios (r=-0.49 to -0.5 7). For degree of liver alteration, significant correlations were obtained with the putaminal binding ratio (r=-0.37) and the CA/PU ratio (r=0.44). Fr om these results is concluded that in WD the nigrostriatal dopaminergic fun ction is compromised to varying extents. The degree of this presynaptic alt eration of dopaminergic neurotransmission depends on the clinical course an d severity of this copper deposition brain disorder and also varies in the different striatal substructures.