Objective: To study the level of dysfunction in the peripheral and central nervous system in idiopathic REM sleep behaviour disorder (iRBD) patients.

Background: α-synuclein (α-syn) aggregates, the characteristic pathology of Parkinson’s disease (PD), have been shown to display prion-like cellular transmission. It has been hypothesized that the initial aggregates may arise in peripheral autonomic nerve terminals years prior to motor symptom onset and subsequently spread to the spinal cord and brainstem. If so, patients with iRBD, a prodromal phenotype of PD and dementia with Lewy bodies (DLB), could display a gradient of pathology with associated dysfunction from the periphery to the nigrostriatal dopamine system.

Methods: Twenty-two iRBD subjects were recruited in this prospective study. 123I-MIBG scintigraphy was performed to measure function of cardiac sympathetic innervation, 11C-donepezil PET/CT to measure cholinergic (in-cluding parasympathetic) functional integrity of the gut, neuromelanin-sensitive MRI to detect loss of pigmented neurons of the LC, 11C-MeNER PET to measure noradrenergic nerve terminal function originat-ing from the LC, and 18F-DOPA PET to assess nigrostriatal dopamine storage capacity. For each modality, data were compared to reference groups of healthy controls and PD patients.

Results: Dysfunction of the sympathetic and parasympathetic nervous system, comparable to that seen in PD, was found in iRBD along with loss of LC pigmented cells. Noradrenergic thalamic nerve terminals were also dysfunctional, but putaminal dopaminergic storage capacity was normal in 71% of the iRBD cases.

Conclusions: The iRBD subjects displayed severe dysfunction of the autonomic nervous system but milder cell loss and dysfunction in their upper brainstem and thalamus. This supports the hypothesis that α-syn pathology initially targets the peripheral autonomic nerves in prodromal PD and DLB with RBD and, therefore, that disease in these cases may begin in the intestine.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/in-vivo-staging-of-pathology-in-rem-sleep-behaviour-disorder/