REM Sleep Behaviour Disorder in Multiple System Atrophy: From Prodromal to Progression of Disease

Abstract

A higher frequency of motor and breathing sleep-related disorders in multiple system atrophy (MSA) populations is reported. REM sleep behaviour disorder (RBD) is one of the most robust markers of an underlying alpha-synucleinopathy. Although a large corpus of literature documented the higher prevalence of RBD in MSA, few studies have systematically investigated the prevalence of RBD as mode of disease onset and its role in disease progression. Moreover, there has been increasing interest in phenoconversion into synucleinopathies of cohorts of patients with isolated RBD (iRBD). Finally, some studies investigated RBD as predictive factor of conversion in isolated autonomic failure, a synucleinopathy presenting with autonomic failure as the sole clinical manifestation that could convert to a manifest central nervous system synucleinopathy. As the field of neurodegenerative disorders moves increasingly towards developing disease-modifying therapies, detecting individuals in the prodromal stage of these synucleinopathies becomes crucial. The aims of this review are to summarise (1) the prevalence of RBD during the course of MSA and as presenting feature of MSA (iRBD), (2) the RBD features in MSA, (3) MSA progression and prognosis in the subgroup of patients with RBD predating disease onset, and (4) the prevalence of MSA conversion in iRBD cohorts. Moreover, we summarise previous results on the role of RBD in the context of isolated autonomic failure as marker of phenoconversion to other synucleinopathies and, in particular, to MSA.

Isolated REM sleep behaviour disorder: current diagnostic procedures and emerging new technologies

“…Secondary RBD is also a known feature of multiple system atrophy (MSA) and can occur in multiple sclerosis (MS) and stroke cases [22][23][24][25]. However, with secondary RBD, it is important to make a distinction between RBD in the context of synucleinopathies (where it is very frequent in 50% of PD, 80% of DLB, and up to 100% of MSA patients [27]) and other neurological diseases (MS and stroke), where it is a rare manifestation [24,25]. These similarities with other conditions and associated factors show how initial suspicion of iRBD can be missed, as investigations into uncommon sleep disorders and referral to specialist services (such as neurology or sleep medicine) are rarely considered in primary care settings [17].…”

Prodromal α-Synucleinopathies

“…Symptoms of autonomic dysfunction may be among the earliest manifestations of α-synucleinopathy, 12 possibly due to early involvement of the vagus nerve and even more peripheral structures (such as the intestines) with α-synuclein pathology 13,14 . Indeed, pure autonomic failure is a rare autonomic nervous system disorder presumed to be due to a peripheral α-synucleinopathy and may progress to involve central structures and manifest with parkinsonism as well 15 …”

Editors' Note: Progression of Nigrostriatal Denervation in Cerebellar Multiple System Atrophy: A Prospective Study

“…Another important clue, not included in the protocol, is the presence of REM sleep behavior disorder (RBD), which is classically a sign suggestive of synucleinopathies, including MSA-C. [2][3][4] The presence of RBD in patients with SLOCA is predictive of the diagnosis of MSA-C because it is rarely found in patients with ILOCA. 5 We believe that the combined use of these clinical data can be a helpful tool in this clinical scenario. Copyright © 2022 American Academy of Neurology…”

“…4 Although we fully agree that incorporation of RBD could improve the specificity of our criteria, the prevalence of RBD in MSA has been shown to be around 75%, reflecting a limited sensitivity. 5 In addition, diagnosing RBD requires a video polysomnography to be performed, which may not be readily available in a routine clinical framework. 2 Because we did not perform video polysomnography in the patients included in our study, we cannot form a definite conclusion on the capacity of RBD, combined with other clinical features, to discriminate ILOCA and MSA-C.…”