Familial progressive supranuclear palsy - Detection of subclinical cases using F-18-dopa and (18)fluorodeoxyglucose positron emission tomography

Background: Progressive supranuclear palsy (PSP) is generally considered to be a sporadic disease; however, occasional cases of familial PSP have been described. The rarity of reports of familial PSP may be attributed in part to an inability to detect subclinical disease in affected relatives who su bsequently die before symptoms clinically develop. Objective: To study regional cerebral dopaminergic function and glucose met abolism in members of 2 large kindreds with familial PSP to identify subcli nical cases. Methods: Three clinically affected members from the 2 PSP kindreds were sca nned with both F-18-dopa and (18)fluorodeoxyglucose ((18)FDG) positron emis sion tomography (PET). Fifteen asymptomatic first-degree relatives were sca nned with F-18-dopa PET; 10 of them also underwent a second PET study with (18)FDG. Results: All 3 clinically affected PSP patients showed a significant reduct ion in caudate and putamen F-18-dopa uptake along with a significant reduct ion in striatal, lateral, and medial premotor area and dorsal prefrontal co rtex glucose metabolism. In 4 of the 15 asymptomatic relatives, caudate and putamen F-18-dopa uptake was 2.5 SDs lower than the normal mean. These 4 s ubjects and a fifth asymptomatic relative with normal F-18-dopa uptake show ed a significant reduction of cortical and striatal glucose metabolism in a pattern similar to that of their affected relatives. Conclusion: F-18-dopa and (18)FDG PET allowed us to identify 5 cases with s ubclinical. metabolic dysfunction among 15 subjects (33%) at risk for PSP, suggesting that this approach is useful for characterizing the pattern of a ggregation in PSP kindreds.