MIBG uptake in the major salivary glands of patients with rapid eye movement sleep behavior disorder: a case-control pilot study

Background: Rapid eye movement sleep behavior disorder (RBD) is a preclinical stage of α-synucleinopathies such as Parkinson’s disease (PD). Furthermore, pathological and neurological alterations are found in peripheral organs such as the submandibular glands (SMG) and heart in RBD, providing support for the “body-first” model of Lewy body disease. This study aimed to compare ¹²³ I-metaiodobenzylguanidine (MIBG) uptake in the parotid glands (PG) and SMG between patients with RBD, PD patients, and controls, using a novel quantitative semi-automatic analysis method. Methods: Using the mediastinum as a reference, we evaluated MIBG uptake in the early and delayed phases in the PG, SMG, and heart. Subsequently, we compared MIBG uptake among the three groups of participants. We also evaluated the correlations between MIBG uptake and clinical data in patients with RBD. Results: Ten patients with RBD (five polysomnography-confirmed and five probable RBD), 81 PD patients, and 25 controls were included in the present study. MIBG uptake in the PG, SMG, and heart was significantly lower in patients with RBD than in controls, except for the delayed phase in the PG and SMG, although its mean value was lower in RBD than in controls. By contrast, cardiac MIBG uptake was comparable between RBD and PD patients, and was lower in both than in controls. MIBG uptake in the PG and SMG was positively correlated in the early and delayed phases in patients with RBD. Conclusions: The early phase of MIBG uptake in the PG and SMG is reduced in patients with RBD, providing support for peripheral as well as cardiac sympathetic denervation as a preclinical stage of α-synucleinopathies.