Decrease of D2 receptors indicated by ¹²³I‐iodobenzamide single‐photon emission computed tomography relates to neurological deficit in treated Wilson's disease

Abstract

Single-photon emission computed tomography with 123I-iodobenzamide, a dopamine D2 receptor antagonist, was employed to study dopamine D2 receptor densities in 17 patients with biochemically proved Wilson's disease and stable neurological status with therapy and in 5 age-matched control subjects. Of the 17 patients with Wilson's disease, 5 were neurologically asymptomatic, 3 had cerebellar signs, 1 exhibited a mild parkinsonian syndrome, 7 showed a parkinsonian syndrome and cerebellar signs, and 1 had generalized dystonia and a parkinsonian syndrome. In 5 age-matched control subjects specific isotope binding as calculated by the basal ganglia to frontal cortex ratio was 1.57 +/- 0.04 (mean +/- standard deviation). The ratio in patients with Wilson's disease ranged from 1.56 +/- 0.05 (n = 5, asymptomatic patients) to 1.17 +/- 0.02 (n = 4, marked neurological impairment). We observed an almost linear correlation between the reduction of 123I-iodobenzamide (IBZM) binding and the severity of neurological signs at the time of IBZM-SPECT (correlation coefficient, -0.84; p < 0.01). We suggest that the reduction of postsynaptic striatal dopamine D2 receptors as detected by IBZM-SPECT reflects striatal neuronal damage in Wilson's disease.

Is increased D2 receptor availability associated with response to stimulant medication in ADHD

“…The frontal cortex is used to determine the unspecific binding because the D2 receptor density is only very low in this cortical area (Camps et al 1989). In this study, the specific binding ratios of our young patients with ADHD at baseline were relatively higher (20 to 60%) than those obtained in other studies using healthy young adults (Brücke et al 1991, Oertel et al 1992, Costa et al 1993, Oder et al 1996, Ichise et al 1998) and were reduced significantly within a range of 0 to 30% after 3 months of methylphenidate therapy. These findings must be interpreted with caution, however, due to the lack of data from a directly age-matched healthy control group acquired under identical conditions.…”

“…Thus, the in vivo approximation of specific binding (Bmax/Kd) in each individual was obtained by the ratio index -mean basal ganglia:frontal cortex (BG:FC) ratio over 120 to 180 minutes after injection. This method has been shown to provide accurate and reliable data and to be sensitive to changes in dopaminergic function (Goyette et al 1978, Brücke et al 1991, Oertel et al 1992, Costa et al 1993, Oder et al 1996, Ichise et al 1998). Furthermore, subregional D2 receptor availability was also measured by drawing anatomical regions of interest on four brain areas rich in dopamine (head of the caudate and putamen on the right and left side) and again the in vivo approximation of regional specific binding in each participant was obtained by the ratio index.…”

“…In order to assess the significance of baseline D2 levels, one sample t-test was performed (two tailed, 95% confidence interval) with a hypothetical specific D2 level of 1.80 derived from previously published data obtained from healthy young adults (Goyette et al 1978, Oertel et al 1992, Costa et al 1993, Oder et al 1996, Ichise et al 1998. Correlation between specific binding and symptoms were performed initially with the Pearson product moment correlation and subsequently by simple linear regression.…”

“…It readily passes the blood-brain barrier (Kung et al 1990), has a moderate but adequate affinity to the D2 receptor (Kessler et al 1991), and a relative high specificity (Kung et al 1989). SPECT imaging with 123I IBZM allows semiquantitative assessment of D2 receptor binding capacity by relating striatal activity to that of the frontal cortex (Brücke et al 1991, Oertel et al 1992, Costa et al 1993, Oder et al 1996, Ichise et al 1998. The frontal cortex is used to determine the unspecific binding because the D2 receptor density is only very low in this cortical area (Camps et al 1989).…”

Psychopathology and personality traits in patients with treated Wilson disease grouped according to gene mutations

“…Neuroimaging findings in WD suggest a complex pathogenesis involving both afferent nigrostriatal dopaminergic projections [50], loss of a dopamine transporter [51] and efferent nigrostriatal dopamin ergic projections (loss of D2 receptors in striatum) [27,52] as well as an alteration of presynaptic serotonergic transporters (SERT) availability [49]. Eggers et al found that the degree of depression symptoms as determined by means of the Hamilton rating scale for depression correlated negatively with the density of presynaptic SERT in 23 patients with WD [53].…”