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

Huntington disease (HD) is characterized by severe abnormalities in neurotr ansmitter concentrations and neuroreceptor density. Quantitative changes in dopa mine D-2 receptors occur in the early stages of HD and may be detecta ble with functional neuroimaging techniques. The aim of this study was to d etermine whether dopamine D-2 receptor imaging with single-photon emission tomography (SPET) identifies preclinical abnormalities in HD. The study pop ulation comprised 32 subjects from families affected by HD: II were genetic ally 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 S PET imaging 120 min following intravenous injection of iodine-123 epideprid e. Ratios of target (striatal) to nontarget (occipital or whole-brain) upta ke were calculated from the reconstructed image data. Striatum to occiput a nd 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 t he moderate-advanced subjects but was still normal for the asymptomatic and early symptomatic stages. It is concluded that reductions in striatal dopa mine D-2 receptor density can be detected with I-123 epidepride at moderate or advanced stages of HD. In contrast to other reports, we could not ident ify abnormalities in clinically unaffected or early stages of HD.