Nature and Science of Sleep (May 2023)
Considering REM Sleep Behavior Disorder in the Management of Parkinson’s Disease
Abstract
Michela Figorilli,1 Mario Meloni,2 Giuseppe Lanza,3,4 Elisa Casaglia,1 Rosamaria Lecca,1 Francesca Lea Saibene,2 Patrizia Congiu,1 Monica Puligheddu1 1Sleep Disorder Research Center, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy; 2IRCCS, Fondazione Don Carlo Gnocchi ONLUS, Milan, Italy; 3Department of Surgery and Medical-Surgical Specialties, University of Catania, Catania, Italy; 4Clinical Neurophysiology Research Unit, Oasi Research Institute-IRCCS, Troina, ItalyCorrespondence: Monica Puligheddu, Sleep Disorder Research Center, Department of Medical Sciences and Public Health, SS 554 Km 4500, 09042 Monserrato CA, Cagliari, Italy, 09042, Tel +07051096001, Email [email protected]: Rapid eye movement (REM) sleep behavior disorder (RBD) is the result of the loss of physiological inhibition of muscle tone during REM sleep, characterized by dream-enacting behavior and widely recognized as a prodromal manifestation of alpha-synucleinopathies. Indeed, patients with isolated RBD (iRBD) have an extremely high estimated risk to develop a neurodegenerative disease after a long follow up. Nevertheless, in comparison with PD patients without RBD (PDnoRBD), the occurrence of RBD in the context of PD (PDRBD) seems to identify a unique, more malignant phenotype, characterized by a more severe burden of disease in terms of both motor and non-motor symptoms and increased risk for cognitive decline. However, while some medications (eg, melatonin, clonazepam, etc.) and non-pharmacological options have been found to have some therapeutic benefits on RBD there is no available treatment able to modify the disease course or, at least, slow down the neurodegenerative process underlying phenoconversion. In this scenario, the long prodromal phase may allow an early therapeutic window and, therefore, the identification of multimodal biomarkers of disease onset and progression is becoming increasingly crucial. To date, several clinical (motor, cognitive, olfactory, visual, and autonomic features) neurophysiological, neuroimaging, biological (biofluids or tissue biopsy), and genetic biomarkers have been identified and proposed, also in combination, as possible diagnostic or prognostic markers, along with a potential role for some of them as outcome measures and index of treatment response. In this review, we provide an insight into the present knowledge on both existing and future biomarkers of iRBD and highlight the difference with PDRBD and PDnoRBD, including currently available treatment options.Keywords: Parkinson’s disease, REM sleep behavior disorder, synucleinopathy, biomarkers, neurodegeneration
