title: 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 D(2) 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 D(2) 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 D(2) receptor density can be detected with (123)I 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.
authors.affiliation: University of Manitoba, Winnipeg, Canada.
authors.forename: W D
authors.initials: WD
authors.lastname: Leslie
authors.forename: C R
authors.initials: CR
authors.lastname: Greenberg
authors.forename: D N
authors.initials: DN
authors.lastname: Abrams
authors.forename: D
authors.initials: D
authors.lastname: Hobson
mesh_terms: D000328:Adult; D001549:Benzamides; D001921:Brain / Q000000981:diagnostic imaging; D016022:Case-Control Studies; D003287:Contrast Media; D003342:Corpus Striatum / Q000000981:diagnostic imaging*; D006801:Humans; D006816:Huntington Disease / Q000000981:diagnostic imaging* / Q000235:genetics; D007091:Image Processing, Computer-Assisted; D007457:Iodine Radioisotopes; D008875:Middle Aged; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2 / Q000032:analysis; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D001549:Benzamides; D003287:Contrast Media; D007457:Iodine Radioisotopes; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; C063525:epidepride