References for this review were identified by searches of the PubMed database from the 1960 to February 2006, using the terms “REM sleep behavior disorder”, “RBD”, “REM sleep without atonia”, “RSWA”, “sleep in neurodegenerative disorders”, and “sleep in neurological disorders”. Additional references (abstracts) and book chapters that were cited in relevant articles were also used. Most papers used in this review were published in English, although non-English articles with English
ReviewRapid-eye-movement sleep behaviour disorder and neurodegenerative diseases
Section snippets
Clinical description
Rapid-eye-movement (REM) sleep behaviour disorder (RBD) is classified as a parasomnia—ie, a disorder in which undesirable physical events are predominant during sleep.1 RBD is characterised by abnormal and often violent behaviour when dreaming.2 Abnormal behaviour can be classified as simple (laughing, talking, shouting, and excessive jerking of body and limbs) or complex (swearing, gesturing, reaching, grabbing, arm flailing, slapping, punching, kicking, sitting up, leaping from bed, crawling,
Pathophysiology
Animal studies with electrophysiological, lesional, and neuropharmacological models have shown that the occurrence and maintenance of muscle atonia during REM sleep needs the interaction of several neuronal systems in the brainstem. These structures include the magnocellular, gigantocellular and paramedian nuclei, the locus coeruleus-subcoeruleus complex, the raphe nucleus, the pedunculopontine nucleus, and the nigrostriatal system.53, 54, 55 These brainstem structures show reciprocal
Treatment
There are no randomised, double-blind, placebo-controlled studies that have assessed the efficacy of any treatment for RBD. Clonazepam (0·5–2 mg before bedtime), has been reported as highly effective in two large cohorts of patients with RBD and it is well tolerated in most cases.4, 5 This drug suppresses behavioural symptoms and reduces phasic REM muscle activity in patients with RBD but does not restore REM-sleep muscle atonia.74 Side-effects include daytime somnolence, cognitive impairment,
RBD in synucleinopathies
RBD is associated with neurological disorders in 38–75% of cases.4, 5, 11 It is particularly common in neurodegenerative disorders characterised by intraneuronal deposition of α-synuclein (synucleinopathies),84 such as Parkinson's disease, multiple-system atrophy, and dementia with Lewy bodies.
RBD as an early stage in the development of neurodegenerative disorders
RBD commonly precedes, by several years, the first symptoms of neurodegenerative disorders.5, 59, 86, 92, 109 Olson and colleagues5 reported that RBD symptoms preceded those of Parkinson's disease in 13 (52%) of 25 patients by a median of 3 years (range 1–30 years). Schenck and colleagues109 found that a parkinsonian syndrome developed in 11 (38%) of 29 patients initially diagnosed with RBD after 5 years of follow-up. 7 years later, results showed that 19 (65%) patients of the same cohort had
Conclusions
Until recently, RBD had been thought to be a mere sleep disorder. However, findings reviewed here strongly support the hypothesis that RBD, except for pharmacologically induced forms, might be a pathological stage in the development of neurodegenerative disorders. Another important observation is that not all patients with RBD have early markers of neurodegenerative disorders. A longitudinal study of a large cohort of patients with RBD should identify which marker or combination of markers
Search strategy and selection criteria
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Evidence for a role of basal ganglia in the regulation of rapid eye movement sleep by electrical and chemical stimulation for the pedunculopontine tegmental nucleus and the substantia nigra pars reticulata in decerebrate cats
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Severe hypermotility during sleep in treatment of cataplexy with clomipramine
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Effect of antidepressants on human sleep
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Evaluation of short-term and long-term treatment of the narcolepsy syndrome with clomipramine hydrochloride
Acta Neurol Scand
Delirium tremens and dreaming
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Cited by (339)
Synucleinopathies
2023, Handbook of Clinical NeurologyInsomnia and Other Sleep Disorders in Older Adults
2022, Psychiatric Clinics of North AmericaTranslational approaches to influence sleep and arousal
2022, Brain Research BulletinCitation Excerpt :Pioneering pre-clinical work by Shiromani and colleagues suggests that transplantation or gene therapy approaches using viral vectors may represent a potential avenue to treatment (Blanco-Centurion et al., 2013; Liu et al., (2008, 2017). Similar approaches may be valuable to treat the destruction of brainstem muscle atonia neurons which results in RBD (Gagnon et al., 2006; McKenna and Peever, 2017). Gene manipulation techniques are now widely used in basic science research investigating sleep-wake circuitry.