Objective: Using multi-modal imaging this study aimed to characterize the deterioration of the parasympathetic and sympathetic nervous system in pure autonomic failure (PAF) in comparison to patients with isolated REM sleep behaviour disorder (iRBD).

Background: PAF is often a rare α-synucleinopathy characterized by severe symptoms from the autonomic nervous system including profound orthostatic hypotension, urinary dysfunction and constipation. With time some PAF patients develop RBD and some progress on to Parkinson’s disease, dementia with Lewy bodies, or multiple system atrophy. Progression from PAF to overt CNS involvement is proposed to follow the body-first trajectory as described in the α-Synuclein Origin and Connectome (SOC) model[1].

Method: To measure parasympathetic deterioration, we quantified colonic binding of 11C-Donepezil using positron emission tomography (PET) and measured colonic transit time using radiopaque markers. 123I-MIBG was used to quantify the sympathetic innervation of the myocardium. Also, video-polysomnography (v-PSG) was carried out to diagnose co-morbid RBD. These methods were also used in a previously published study of a cohort of 22 patients with isolated RBD[2].

Results: Until now, 19 patients with PAF have been recruited, hereof 5 patients with comorbid RBD. All patients with PAF had severe orthostatic hypotension with a median systolic drop of -81 mmHg (IQR = -107, -66). Colonic transit time was significantly prolonged in PAF compared to iRBD (4.5 days vs. 2.5 days, p < 0.001) and colonic volume was enlarged to a similar degree in both disorders (p = 0.73). No differences in MIBG heart-mediastinum or Sniffin’ Sticks were detectable with the current sample size when comparing PAF to iRBD, yet better olfaction was seen in PAF without RBD compared to iRBD (p = 0.014). Results of colonic 11C-Donepezil-PET will be presented at MDS 2024 along with additional imaging measures and findings from an autonomic test battery.

Conclusion: Here, our preliminary results demonstrate that the degree of sympathetic and parasympathetic deterioration in PAF is similar to or worse than that seen in iRBD. Notably, while colonic transit is severely prolonged in PAF compared to iRBD, olfaction seems to be relatively unaffected in PAF without RBD. Final conclusions will be presented at the MDS 2024.

References: [1] Borghammer, P. The alpha-Synuclein Origin and Connectome Model (SOC Model) of Parkinson’s Disease: Explaining Motor Asymmetry, Non-Motor Phenotypes, and Cognitive Decline. J Parkinsons Dis 11, 455-474, doi:10.3233/JPD-202481 (2021).
[2] Knudsen, K. et al. In-vivo staging of pathology in REM sleep behaviour disorder: a multimodality imaging case-control study. The Lancet. Neurology 17, 618-628, doi:10.1016/S1474-4422(18)30162-5 (2018).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/pure-autonomic-failure-as-a-severe-body-first-subtype-of-lewy-body-disease-a-multimodal-imaging-study-of-the-autonomic-nervous-system/