Concordant pre- and postsynaptic deficits of dopaminergic neurotransmission in neurologic Wilson disease

Abstract

Background and purpose: 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).

Conclusion: 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.

Fig 1.

Typical examples of [¹²³I]β-CIT (top row) and [¹²³I]IBZM (bottom row) SPECT images in a subject from the control group (left), a non-neurologic WD patient (middle), and a neurologic WD patient (right). Transverse sections at the level of maximal diameter of the striatum are shown. No differences were noted between the control subject and the non-neurologic WD patient. In contrast, specific binding is reduced for both radiotracers in the striata of the neurologic WD patient.

Fig 2.

Box plots show the striatal [¹²³I]β-CIT and [¹²³I]IBZM binding ratios in non-neurologic and neurologic WD patients, given in percentages, as related to those in the control group. No differences were noted in the non-neurologic WD patients, but a highly significant deficit was observed in neurologic WD patients. *** indicates P < .001.

Fig 3.

Scatter plot shows the positive correlation between the [¹²³I]β-CIT and [¹²³I]IBZM binding ratios in the striatum of non-neurologic WD patients (solid dots) and neurologic WD patients (open dots). The correlation was proved to be linear and highly significant.