Abstract
BACKGROUND: Pure autonomic failure (PAF) is a rare disease characterized clinically by neurogenic orthostatic hypotension (nOH) and biochemically by peripheral noradrenergic deficiency. Clinically diagnosed PAF can evolve ("phenoconvert") to a central Lewy body disease (LBD, e.g., Parkinson's disease (PD) or dementia with Lewy bodies (DLB)) or to the non-LBD synucleinopathy multiple system atrophy (MSA). We examined whether cardiac (18)F-dopamine positron emission tomography (PET) predicts the trajectory of phenoconversion in PAF. Since cardiac (18)F-dopamine-derived radioactivity always is decreased in LBDs with nOH and usually is normal in MSA, we hypothesized that PAF patients with low cardiac (18)F-dopamine-derived radioactivity may phenoconvert to a central LBD but do not phenoconvert to MSA. METHODS: We reviewed data from all the patients seen at the National Institutes of Health Clinical Center from 1994 to 2023 with a clinical diagnosis of PAF and data about serial (18)F-dopamine PET. RESULTS: Twenty patients met the above criteria. Of 15 with low cardiac (18)F-dopamine-derived radioactivity, 6 (40%) phenoconverted to PD or DLB and none to MSA. Of 5 patients with consistently normal (18)F-dopamine PET, 4 phenoconverted to MSA, and the other at autopsy had neither a central LBD nor MSA. CONCLUSION: In this case series, 40% of patients with nOH and low cardiac (18)F-dopamine-derived radioactivity phenoconverted to PD or DLB during follow-up; none phenoconverted to MSA. Cardiac (18)F-DA PET therefore can predict the type of phenoconversion in PAF. This capability could refine eligibility criteria for entry into disease-modification trials aiming to prevent evolution of PAF to symptomatic central LBDs.