Clinical deficits in Huntington disease correlate with reduced striatal uptake on iodine-123 epidepride single-photon emission tomography

Abstract.

Huntington disease (HD) is characterized by severe abnormalities in neurotransmitter concentrations and neuroreceptor density. Quantitative changes in dopamine D₂ receptors occur in the early stages of HD and may be detectable with functional neuroimaging techniques. The aim of this study was to determine whether dopamine D₂ receptor imaging with single-photon emission tomography (SPET) identifies preclinical abnormalities in HD.The study population comprised 32 subjects from families affected by HD: 11 were genetically normal while 21 were genetically positive for HD (seven asymptomatic, six early, three moderate and five advanced findings). Disease severity was determined using a standardized quantitative neurological examination (QNE) and the mini-mental status examination (MMSE). Subjects underwent brain SPET imaging 120 min following intravenous injection of iodine-123 epidepride. Ratios of target (striatal) to nontarget (occipital or whole-brain) uptake were calculated from the reconstructed image data. Striatum to occiput and striatum to whole-brain count ratios correlated negatively with disease stage (P=0.002 and P=0.0002) and QNE (P<0.002 and P=0.0002), and positively with the MMSE (P=0.001 and P<0.001). Uptake was significantly reduced in the moderate-advanced subjects but was still normal for the asymptomatic and early symptomatic stages. It is concluded that reductions in striatal dopamine D₂ receptor density can be detected with ¹²³I epidepride at moderate or advanced stages of HD. In contrast to other reports, we could not identify abnormalities in clinically unaffected or early stages of HD.