Concordant pre- and postsynaptic deficits of dopaminergic neurotransmission in neurologic Wilson disease.
OBJECTIVE
Although previous brain imaging studies of Wilson disease (WD) focused on the dopaminergic system, correlational data on the integrity of the pre- and postsynaptic compartments are lacking. The present study was initiated to intra-individually determine the integrity of these compartments in patients with WD.


METHODS
A total of 46 patients with WD and 10 matched control subjects underwent [(123)I]2beta-carbomethoxy-3beta-(4[(123)I]iodophenyl)tropane ([(123)I]beta-CIT) and [(123)I]iodobenzamide ([(123)I]IBZM) single photon emission CT (SPECT). For both radiotracers, specific striatal binding ratios (with the cerebellum as the reference region) were calculated after a standardized region-of-interest technique was applied. In addition, the severity of putative neurologic symptoms was evaluated by using a linear scoring system.


RESULTS
In patients without neurologic symptoms, striatal binding ratios of both radiotracers did not differ from those of the control group (13.8 +/- 3.1 vs 12.0 +/- 3.4 and 2.00 +/- 0.19 vs 1.90 +/- 0.27; n.s.). In symptomatic patients, however, striatal binding ratios for both [(123)I]beta-CIT and [(123)I]IBZM were significantly reduced (9.1 +/- 2.3 and 1.64 +/- 0.18; P <.001). In all patients with WD, the [(123)I]beta-CIT and [(123)I]IBZM binding ratios were significantly correlated (r = 0.65, P <.001), as were SPECT parameters and the severity of the neurologic symptoms (r = -0.60 and -0.62; P <.001).


CONCLUSIONS
These findings of a concordant bicompartmental dopaminergic deficit in neurologic WD provide in vivo evidence for assigning WD to the group of secondary Parkinsonian syndromes. These results could be relevant in therapeutic decision making in patients with this copper deposition disorder.
Barthel
Henryk
H
Department of Nuclear Medicine, University of Leipzig, Germany.
Hermann
Wieland
W
Kluge
Regine
R
Hesse
Swen
S
Collingridge
David R
DR
Wagner
Armin
A
Sabri
Osama
O
D000328:Adult; D001549:Benzamides; D001931:Brain Mapping; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000503:physiopathology; D003042:Cocaine / Q000031:analogs & derivatives*; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000503:physiopathology; D004298:Dopamine / Q000502:physiology*; D005260:Female; D006527:Hepatolenticular Degeneration / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007457:Iodine Radioisotopes; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination / Q000706:statistics & numerical data; D010302:Parkinson Disease, Secondary / Q000175:diagnosis / Q000503:physiopathology; D011594:Psychometrics; D011759:Pyrrolidines; D012016:Reference Values; D009435:Synaptic Transmission / Q000502:physiology*; D015899:Tomography, Emission-Computed, Single-Photon
D001549:Benzamides; D007457:Iodine Radioisotopes; D011759:Pyrrolidines; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide; D003042:Cocaine; D004298:Dopamine