Familial progressive supranuclear palsy: detection of subclinical cases using 18F-dopa and 18fluorodeoxyglucose...

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 subsequently die before symptoms clinically develop.

To study regional cerebral dopaminergic function and glucose metabolism in members of 2 large kindreds with familial PSP to identify subclinical cases.

Three clinically affected members from the 2 PSP kindreds were scanned with both (18)F-dopa and (18)fluorodeoxyglucose ((18)FDG) positron emission tomography (PET). Fifteen asymptomatic first-degree relatives were scanned with (18)F-dopa PET; 10 of them also underwent a second PET study with (18)FDG.

All 3 clinically affected PSP patients showed a significant reduction in caudate and putamen (18)F-dopa uptake along with a significant reduction in striatal, lateral, and medial premotor area and dorsal prefrontal cortex glucose metabolism. In 4 of the 15 asymptomatic relatives, caudate and putamen (18)F-dopa uptake was 2.5 SDs lower than the normal mean. These 4 subjects and a fifth asymptomatic relative with normal (18)F-dopa uptake showed a significant reduction of cortical and striatal glucose metabolism in a pattern similar to that of their affected relatives.

(18)F-dopa and (18)FDG PET allowed us to identify 5 cases with subclinical metabolic dysfunction among 15 subjects (33%) at risk for PSP, suggesting that this approach is useful for characterizing the pattern of aggregation in PSP kindreds.