STRIATAL GLUCOSE-METABOLISM AND DOPAMINE D-2 RECEPTOR-BINDING IN ASYMPTOMATIC GENE CARRIERS AND PATIENTS WITH HUNTINGTONS-DISEASE

We used PET scans with the tracers [F-18]fluorodeoxyglucose (FDG) and [C-11]raclopride (RACLO) to study glucose metabolism and dopamine D-2 receptor binding in the caudate nucleus and putamen of 18 carriers of the Huntington's disease gene mutation (10 asymptomatic subjects and e ight untreated symptomatic Huntington's disease patients in an early d isease stage). We also performed MRI scans and measured the bicaudate ratio (BCR) in the same subjects. Data were compared with those from n ine mutation-negative members of Huntington's disease families and sep arate groups of age matched controls. The PET scans were repeated 1.5- 3 years later in six of the asymptomatic gene carriers. Symptomatic Hu ntington's disease patients showed a marked reduction of FDG and RACLO uptake in the caudate nucleus and putamen and a significant increase of BCR. Asymptomatic mutation carriers revealed significant hypometabo lism in the caudate nucleus and putamen. The RACLO binding was signifi cantly decreased in the putamen. Decrements of caudate nucleus tracer uptake, particularly RACLO, correlated significantly with BCR increase s in both symptomatic and asymptomatic gene carriers. In asymptomatic carriers, metabolic and receptor binding decreases were also significa ntly associated with the CAG repeat number but not with the individual 's age. Discriminant function analysis correctly classified clinical a nd genetic status in 24 of 27 subjects on the basis of their striatal PET values (83% sensitivity and 100% specificity). Three asymptomatic mutation carriers were classified/grouped together with mutation-negat ive subjects, indicating that these individuals had normal striatal RA CLO and FDG uptake. Follow-up PET data from gene-positive subjects sho wed a significant reduction in the mean striatal RACLO binding of 6.3% per year Striatal glucose metabolism revealed an overall non signific ant 2.3% decrease per year These data indicate that asymptomatic Hunti ngton's disease mutation carriers may show normal neuronal function fo r a long period of life. These findings also suggest that it may be po ssible to predict when an asymptomatic gene carrier will develop clini cal symptoms from serial PET measurements of striatal function.