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[Preprint]. 2023 Jul 17:rs.3.rs-3157807.
doi: 10.21203/rs.3.rs-3157807/v1.

Cardiac 18F-Dopamine Positron Emission Tomography Predicts the Type of Phenoconversion of Pure Autonomic Failure

Abhishek Lenka  1 , Risa Isonaka  2 , Courtney Holmes  2 , David S Goldstein  2
Affiliations

Cardiac 18F-Dopamine Positron Emission Tomography Predicts the Type of Phenoconversion of Pure Autonomic Failure

Abhishek Lenka et al. Res Sq. .

Update in

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 18F-dopamine positron emission tomography (PET) predicts the trajectory of phenoconversion in PAF. Since cardiac 18F-dopamine-derived radioactivity always is decreased in LBDs with nOH and usually is normal in MSA, we hypothesized that PAF patients with low cardiac 18F-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 18F-dopamine PET.

Results: Twenty patients met the above criteria. Of 15 with low cardiac 18F-dopamine-derived radioactivity, 6 (40%) phenoconverted to PD or DLB and none to MSA. Of 5 patients with consistently normal 18F-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 18F-dopamine-derived radioactivity phenoconverted to PD or DLB during follow-up; none phenoconverted to MSA. Cardiac 18F-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.

Keywords: Parkinson’s disease; Pure autonomic failure; dementia with Lewy bodies; fluorodopamine; multiple system atrophy.

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Conflict of interest statement

Conflicts of interest: The authors have no conflicts of interest.

Figures

Figure 1
Figure 1. Flow diagram of patients
Abbreviations: 18F-DA=18F-dopamine-derived radioactivity; DLB=dementia with Lewy bodies; LBD=Lewy body disease; MSA=multiple system atrophy; PAF=pure autonomic failure; PD+OH=Parkinson’s disease with orthostatic hypotension; PET=positron emission tomography.
Figure 2
Figure 2. Clinical and imaging timelines of patients with pure autonomic failure (PAF) evolving to central Lewy body diseases
Insets show 13N-ammonia and 18F-dopamine positron emission tomographic images, with matched spectral scales (in (A) minimum radioactivity black, maximum red; (B) minimum radioactivity black, maximum white). Abbreviations: 18F-DA=18F-dopamine-derived radioactivity; Dx=diagnosis; GBA=glucocerebrosidase gene; MoCA=Montreal Cognitive Assessment; NE=norepinephrine; 13NH3=13N-ammonia; OH=orthostatic hypotension; PD=Parkinson’s disease; PUT/OCC=putamen/occipital cortex ratio of 18F-DOPA-derived radioactivity; TH=tyrosine hydroxylase; UPDRS=Unified Parkinson Disease Rating Scale.
Figure 3
Figure 3. Clinical and imaging timelines of patients with pure autonomic failure (PAF) evolving to central Lewy body diseases
Insets show 13N-ammonia and 18F-dopamine positron emission tomographic images, with matched spectral scales (in (A) minimum radioactivity black, maximum red; in (B) minimum radioactivity black, maximum white). Abbreviations: 18F-DA=18F-dopamine-derived radioactivity; DLB=dementia with Lewy bodies; Dx=diagnosis; ED=erectile dysfunction; Ejac. Failure=ejaculatory failure; MoCA=Montreal Cognitive Assessment; NE=norepinephrine; 13NH3=13N-ammonia; OH=orthostatic hypotension; PAF=pure autonomic failure; PD=Parkinson’s disease; PGP=protein gene product; PUT/OCC=putamen/occipital cortex ratio of 18F-DOPA-derived radioactivity; TH=tyrosine hydroxylase; UPDRS=Unified Parkinson Disease Rating Scale; UPSIT=University of Pennsylvania Smell Identification Test
Figure 4
Figure 4. Clinical and imaging timelines of patients with pure autonomic failure (PAF) who evolved to (A) Parkinson’s disease with orthostatic hypotension (PD+OH) or (B) dementia with Lewy bodies (DLB).
Insets show 13N-ammonia and 18F-dopamine positron emission tomographic images, with matched spectral scales (minimum radioactivity black, maximum white or red). Abbreviations: AFib=atrial fibrillation; A.Pili=arrector pili muscle; DLB=dementia with Lewy bodies; Dx=diagnosis; 18F-DA=18F-dopamine-derived radioactivity; MoCA=Montreal Cognitive Assessment; 13NH3=13N-ammonia; OH=orthostatic hypotension; PD=Parkinson’s disease; PUT/OCC=putamen/occipital cortex ratio of 18F-DOPA-derived radioactivity; RUE=right upper extremity; RBD=rapid eye movement behavior disorder; TH=tyrosine hydroxylase; UPDRS=Unified Parkinson Disease Rating Scale; UPSIT=University of Pennsylvania Smell Identification Test; y.o.=years old
Figure 5
Figure 5. Clinical and imaging timelines of a patient with pure autonomic failure (PAF) who evolved to the parkinsonian form of multiple system atrophy (MSA).
Insets show 13N-ammonia and 18F-dopamine positron emission tomographic images, with matched spectral scales (minimum radioactivity black, maximum red). Abbreviations: 18F-DA=18F-dopamine-derived radioactivity; Dx=diagnosis; MoCA=Montreal Cognitive Assessment; 13NH3=13N-ammonia; OH=orthostatic hypotension; PD=Parkinson’s disease; PUT/OCC=putamen/occipital cortex ratio of 18F-DOPA-derived radioactivity; RBD=rapid eye movement behavior disorder; UPDRS=Unified Parkinson Disease Rating Scale; UPSIT=University of Pennsylvania Smell Identification Test. Note persistently normal UPSIT scores and 18F-DA-derived radioactivity.
See this image and copyright information in PMC

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