PURPOSE

Pure autonomic failure (PAF) is a rare disease characterized by neurogenic orthostatic hypotension (nOH), no known secondary cause, and lack of a neurodegenerative movement or cognitive disorder. 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). Since cardiac F-dopamine-derived radioactivity usually is low in LBDs and usually is normal in MSA, we hypothesized that patients with PAF with low cardiac F-dopamine-derived radioactivity would be more likely to phenoconvert to a central LBD than 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 F-dopamine positron emission tomography (PET).

RESULTS

Nineteen patients (15 with low F-dopamine-derived radioactivity, 4 with normal radioactivity) met the above criteria and had follow-up data. Nine (47%) phenoconverted to a central synucleinopathy over a mean of 6.6 years (range 1.5-18.8 years). All 6 patients with low cardiac F-dopamine-derived radioactivity who phenoconverted during follow-up developed a central LBD, whereas none of 4 patients with consistently normal F-dopamine PET phenoconverted to a central LBD (p = 0.0048), 3 evolving to probable MSA and 1 upon autopsy having neither a LBD nor MSA.

CONCLUSION

Cardiac F-dopamine PET can predict the type of phenoconversion of PAF. This capability could refine eligibility criteria for entry into disease-modification trials aimed at preventing evolution of PAF to symptomatic central LBDs.