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A Neurologist's Guide to REM Sleep Behavior Disorder Roguski, A. , Rayment, D., Whone, A., Jones, M., & Rolinski, M. (2020). A Neurologist's Guide to REM Sleep Behavior Disorder. Frontiers in Neurology, 11, [610]. https://doi.org/10.3389/fneur.2020.00610 Publisher's PDF, also known as Version of record License (if available): CC BY Link to published version (if available): 10.3389/fneur.2020.00610 Link to publication record in Explore Bristol Research PDF-document This is the final published version of the article (version of record). It first appeared online via Frontiers Media at https://doi.org/10.3389/fneur.2020.00610. Please refer to any applicable terms of use of the publisher. University of Bristol - Explore Bristol Research General rights This document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/red/research-policy/pure/user-guides/ebr-terms/ REVIEW published: 08 July 2020 doi: 10.3389/fneur.2020.00610 A Neurologist’s Guide to REM Sleep Behavior Disorder Amber Roguski 1, Dane Rayment 2, Alan L. Whone 3,4, Matt W. Jones 1 and Michal Rolinski 3,4* 1 School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, United Kingdom, 2 Rosa Burden Centre, Southmead Hospital, Bristol, United Kingdom, 3 Department of Neurology, Southmead Hospital, Bristol, United Kingdom, 4 Translational Health Sciences, University of Bristol, Bristol, United Kingdom REM Sleep Behavior Disorder (RBD) is a chronic sleep condition characterized by dream enactment and loss of REM atonia. Individuals often present to clinic with complaints of injury to themselves or their bed-partner due to violent movements during sleep. RBD patients have a high risk of developing one of the neurodegenerative α- synucleinopathy diseases: over 70% will develop parkinsonism or dementia within 12 years of their diagnosis. RBD patients also exhibit accelerated disease progression and a more severe phenotype than α-synucleinopathy sufferers without RBD. The disease’s low prevalence and the relatively limited awareness of the condition amongst medical professionals makes the diagnosis and treatment of RBD challenging. Uncertainty in patient management is further exacerbated by a lack of clinical guidelines for RBD patient care. There are no binary prognostic markers for RBD disease course and there are Edited by: K. Ray Chaudhuri, no clinical guidelines for neurodegeneration scaling or tracking in these patients. Both King’s College London, clinicians and patients are therefore forced to deal with uncertain outcomes. In this review, United Kingdom we summarize RBD pathology and differential diagnoses, diagnostic, and treatment Reviewed by: Camila Aquino, guidelines as well as prognostic recommendations with a look to current research in McMaster University, Canada the scientific field. We aim to raise awareness and develop a framework for best practice Chiara Prosperetti, for RBD patient management. Neurocenter of Southern Switzerland, Switzerland Keywords: REMsleep behavior disorder (RBD), Parkinson’s disease, prodromal Parkinson’s disease, sleep *Correspondence: disorders, neurology, neuroscience, sleep Michal Rolinski [email protected] SYMPTOMS AND DIAGNOSTIC CONSIDERATIONS Specialty section: This article was submitted to Rapid Eye Movement (REM) Sleep Behavior Disorder (RBD) is a non-familial sleep disorder, Movement Disorders, characterized by the loss of the inherent muscle atonia observed during normal REM sleep. a section of the journal This phenomenon is often referred to as REM Sleep without Atonia (RSWA). Whilst isolated Frontiers in Neurology RSWA is frequently an incidental finding in sleep studies, it forms the substrate of the dream Received: 14 January 2020 enactment behavior which defines RBD. Here, individuals experience vivid dreams which they act Accepted: 25 May 2020 out during sleep. Published: 08 July 2020 It is important to remember that dream enactment and limb movements during sleep can Citation: occur in the healthy population, often in the context of heightened emotional states (1–3). Roguski A, Rayment D, Whone AL, The same symptoms may also be experienced during withdrawal from sedatives or alcohol. In Jones MW and Rolinski M (2020) A Neurologist’s Guide to REM Sleep non-pathological dream enactment, individuals typically respond to dream content during the Behavior Disorder. transition from REM sleep to the awake state and while maintaining REM atonia during much of Front. Neurol. 11:610. the REM period. In contrast, RBD individuals will maintain REM sleep during and immediately doi: 10.3389/fneur.2020.00610 after most of their dream enactments. As acute dream enactment is generally self-limiting, the Frontiers in Neurology | www.frontiersin.org 1 July 2020 | Volume 11 | Article 610 Roguski et al. A Neurologist’s Guide to RBD chronicity of symptoms (>6 months) is a key distinguishing RBD is characterized not just by an increase in small sleep factor, and forms part of the diagnostic criteria for RBD (4). twitches but also complex movements and dream enactment, it is Anecdotally, dreams are often reported by patients with RBD likely that abnormal disinhibition occurs in the pyramidal motor as violent or aggressive, resulting in violent motor behaviors tract during REM sleep, leading to execution of the complex which may pose a threat to them or their bedpartner (5). movements “imagined” by the motor cortex. Imaging studies Whilst accounts of individuals kicking, punching, biting, or even have shown that RBD can also be accompanied by changes in strangling their bedpartners during sleep paint an emotive image multiple neurotransmitter systems, including the cholinergic, of the condition and often capture public interest, they are noradrenergic, and dopaminergic circuits (15). Thus, one of the prone to recall bias. More systematic studies have revealed that key challenges in treating RBD derives from the uncertainty violent dreams and behaviors only make up a small percentage surrounding its causative pathology and the extent of dysfunction of all events (6–8). When a dream enactment is occurring, throughout the brain. the individual’s eyes will remain closed as they engage with RBD may present on its own, often referred to as idiopathic the dream environment and their movements are generally RBD (iRBD), or may exist as a secondary entity in the context contained to their immediate surroundings, thus differentiating another condition. Regardless of cause, all RBD subtypes are these episodes from NREM parasomnias such as sleepwalking likely to reflect dysfunction at some point in the complex, (4). Upon awakening from a large motor event, the RBD interconnected REM atonia circuits. individual will be alert and orientated to their surroundings (4). The frequency of motor events may vary greatly between “Idiopathic” RBD RBD individuals; ranging from multiple episodes per night, to These patients usually present to sleep clinics with a history one episode per month (9). In any one patient, the severity and of dream enacting behaviors and a present complaint of recent frequency of the behaviors may also vary from night to night, and sleep-related injury to themselves or their bedpartner, despite over the course of their condition (10). The mechanisms behind no other health complaints or recent medication changes. this fluctuation remains unknown. Whilst previously considered an idiopathic phenomenon, the Etiology unquestionable link with alpha-synucleinopathies has challenged this view. The behavioral states of wake and sleep are initiated and Approximately 10 years after the first description of RBD in maintained by complex interplay between multiple brainstem the scientific literature, Schenck et al. reported the development and diencephalic nuclei. Dysregulation, disease or degeneration of parkinsonism in ∼40% iRBD individuals (16). Since then, of these nuclei can result in sleep disorders, such as narcolepsy, RBD has emerged as one of the most specific predictors of and subtle changes to sleep-wake patterns. In the case of RBD, the synuclein-mediated neurodegenerative diseases: Parkinson’s the primary pathology appears to be an excitation/inhibition disease (PD), Multiple System Atrophy (MSA) and Dementia imbalance in the brainstem nuclei controlling REM muscle tone. with Lewy Bodies (DLB). It is now estimated that up to 90% Movement during REM sleep is controlled by two systems: of patients with “iRBD” will eventually develop one of the α- one controls the input to spinal cord motoneurons to generate synucleinopathies (17). muscle atonia (extrapyramidal), and the other controls motor Given that RBD is found to occur, on average, 8 years cortex activation to suppress locomotor activity (pyramidal). before the presentation of the core motor or cognitive symptoms The main generator of REM-sleep is the predominantly- required for the clinically diagnosis of PD or DLB (18), there glutamatergic Subcoeruleus/Pre-Locus Coeruleus complex is increasing evidence to suggest that in most cases RBD is [SubC/PC- analogous to the rat/mouse sublaterodorsal the early manifestation, or prodrome, of a clinically-defined nucleus (SLD)], which is anatomically situated just below neurodegenerative disease. Indeed, detailed assessments often the noradrenergic locus coeruleus in the pons (11). As well as reveal subtle features of these conditions, such as hyposmia, projecting to many subcortical brain regions to promote and constipation, or a slight tremor
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