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Semin Neurol 2017; 37(04): 461-470
DOI: 10.1055/s-0037-1605595
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Clinical Overview of REM Sleep Behavior Disorder

Verna R. Porter
1   Mary S. Easton Alzheimer's Disease Research Center, Department of Neurology, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California
,
Alon Y. Avidan
2   UCLA Sleep Disorders Center, Department of Neurology, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California
› Author Affiliations
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Publication History

Publication Date:
24 August 2017 (online)

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Abstract

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by loss of muscle atonia during REM sleep that allows motor responses to dream content. Patients display patterns of unusual, complex, and even violent motor activities. There is a high risk for harm to the patients or their bedpartners. REM sleep behavior disorder is more likely to occur in synucleinopathies such as Parkinson's disease, Lewy body dementia, and multiple system atrophy and may precede clinical manifestations by decades. In secondary RBD, brainstem centers involved in muscle atonia during REM are disrupted. These conditions include multiple sclerosis, cerebral vascular accidents, and brainstem tumors. The acute onset of RBD may associate with the use of antidepressants and acute withdrawal from alcohol. The diagnosis of RBD should be confirmed by polysomnography utilizing multiple-limb electromyography and synchronized digital video monitoring and demonstrate elevation of muscle tone during REM sleep along with dream enactment behavior. The differential diagnosis includes sleepwalking, nocturnal seizures, sleep apnea, and periodic limb movement disorder. Management focuses on maximizing safety, use of clonazepam/melatonin, and discussion of prognosis with patients.

Keywords

sleep - rapid eye movement sleep - REM sleep without atonia - REM sleep behavior disorder - dream enactment behavior - parasomnia - Parkinson's disorders - synucleinopathy - neurodegenerative disease
 

  • References

  • 1 Schenck CH, Bundlie SR, Ettinger MG, Mahowald MW. Chronic behavioral disorders of human REM sleep: a new category of parasomnia. Sleep 1986; 9 (02) 293-308
    CrossrefPubMedSearch in Google Scholar
  • 2 Schenck CH, Mahowald MW. REM sleep behavior disorder: clinical, developmental, and neuroscience perspectives 16 years after its formal identification in SLEEP. Sleep 2002; 25 (02) 120-138
    CrossrefPubMedSearch in Google Scholar
  • 3 American Academy of Sleep Medicine. The International Classification of Sleep Disorders, Revised: Diagnostic and Coding Manual. 3rd ed. Darien, IL: American Academy of Sleep Medicine; 2014
    Search in Google Scholar
  • 4 Krenzer M, Lu J, Mayer G, Oertel W. From bench to bed: putative animal models of REM sleep behavior disorder (RBD). J Neural Transm (Vienna) 2013; 120 (04) 683-688
    CrossrefPubMedSearch in Google Scholar
  • 5 Jiang H, Huang J, Shen Y. , et al. RBD and neurodegenerative diseases. Mol Neurobiol 2017; 54 (04) 2997-3006
    CrossrefPubMedSearch in Google Scholar
  • 6 Claassen DO, Josephs KA, Ahlskog JE, Silber MH, Tippmann-Peikert M, Boeve BF. REM sleep behavior disorder preceding other aspects of synucleinopathies by up to half a century. Neurology 2010; 75 (06) 494-499
    CrossrefPubMedSearch in Google Scholar
  • 7 Iranzo A, Graus F, Clover L. , et al. Rapid eye movement sleep behavior disorder and potassium channel antibody-associated limbic encephalitis. Ann Neurol 2006; 59 (01) 178-181
    CrossrefPubMedSearch in Google Scholar
  • 8 Postuma RB, Gagnon JF, Vendette M, Fantini ML, Massicotte-Marquez J, Montplaisir J. Quantifying the risk of neurodegenerative disease in idiopathic REM sleep behavior disorder. Neurology 2009; 72 (15) 1296-1300
    CrossrefPubMedSearch in Google Scholar
  • 9 Schenck CH, Bundlie SR, Mahowald MW. Delayed emergence of a parkinsonian disorder in 38% of 29 older men initially diagnosed with idiopathic rapid eye movement sleep behaviour disorder. Neurology 1996; 46 (02) 388-393
    CrossrefPubMedSearch in Google Scholar
  • 10 Boeve BF. REM sleep behavior disorder: updated review of the core features, the REM sleep behavior disorder-neurodegenerative disease association, evolving concepts, controversies, and future directions. Ann N Y Acad Sci 2010; 1184: 15-54
    CrossrefPubMedSearch in Google Scholar
  • 11 Boeve BF, Silber MH, Saper CB. , et al. Pathophysiology of REM sleep behaviour disorder and relevance to neurodegenerative disease. Brain 2007; 130 (Pt 11): 2770-2788
    CrossrefPubMedSearch in Google Scholar
  • 12 Uchiyama M, Isse K, Tanaka K. , et al. Incidental Lewy body disease in a patient with REM sleep behavior disorder. Neurology 1995; 45 (04) 709-712
    CrossrefPubMedSearch in Google Scholar
  • 13 Aurora RN, Zak RS, Maganti RK. , et al; Standards of Practice Committee; American Academy of Sleep Medicine. Best practice guide for the treatment of REM sleep behavior disorder (RBD). J Clin Sleep Med 2010; 6 (01) 85-95
    PubMedSearch in Google Scholar
  • 14 Bonakis A, Howard RS, Ebrahim IO, Merritt S, Williams A. REM sleep behaviour disorder (RBD) and its associations in young patients. Sleep Med 2009; 10 (06) 641-645
    CrossrefPubMedSearch in Google Scholar
  • 15 Ju YE, Larson-Prior L, Duntley S. RBD and antidepressants. Sleep Med 2012; 13 (02) 211-212
    PubMedSearch in Google Scholar
  • 16 Teman PT, Tippmann-Peikert M, Silber MH, Slocumb NL, Auger RR. Idiopathic rapid-eye-movement sleep disorder: associations with antidepressants, psychiatric diagnoses, and other factors, in relation to age of onset. Sleep Med 2009; 10 (01) 60-65
    CrossrefPubMedSearch in Google Scholar
  • 17 Chiu HF, Wing YK, Chung DW, Ho CK. REM sleep behaviour disorder in the elderly. Int J Geriatr Psychiatry 1997; 12 (09) 888-891
    CrossrefPubMedSearch in Google Scholar
  • 18 Tang JBB, Tippmann-Peikert M, Silber M. Gender effect in patients with REM sleep behavior disorder associated with multiple system atrophy compared with Parkinson's disease and dementia with Lewy bodies. Neurology 2009; 72: A325
    PubMedSearch in Google Scholar
  • 19 Arnulf I. REM sleep behavior disorder: motor manifestations and pathophysiology. Mov Disord 2012; 27 (06) 677-689
    CrossrefPubMedSearch in Google Scholar
  • 20 Iranzo A, Santamaría J. Severe obstructive sleep apnea/hypopnea mimicking REM sleep behavior disorder. Sleep 2005; 28 (02) 203-206
    CrossrefPubMedSearch in Google Scholar
  • 21 Wetter TC, Pollmächer T. Restless legs and periodic leg movements in sleep syndromes. J Neurol 1997; 244 (04) (Suppl. 01) S37-S45
    CrossrefPubMedSearch in Google Scholar
  • 22 Nightingale S, Orgill JC, Ebrahim IO, de Lacy SF, Agrawal S, Williams AJ. The association between narcolepsy and REM behavior disorder (RBD). Sleep Med 2005; 6 (03) 253-258
    CrossrefPubMedSearch in Google Scholar
  • 23 Jennum P, Christensen JA, Zoetmulder M. Neurophysiological basis of rapid eye movement sleep behavior disorder: informing future drug development. Nat Sci Sleep 2016; 8: 107-120
    PubMedSearch in Google Scholar
  • 24 Comella CL, Nardine TM, Diederich NJ, Stebbins GT. Sleep-related violence, injury, and REM sleep behavior disorder in Parkinson's disease. Neurology 1998; 51 (02) 526-529
    CrossrefPubMedSearch in Google Scholar
  • 25 Boeve BF, Silber MH, Ferman TJ. , et al. REM sleep behavior disorder and degenerative dementia: an association likely reflecting Lewy body disease. Neurology 1998; 51 (02) 363-370
    CrossrefPubMedSearch in Google Scholar
  • 26 American Academy of Sleep Medicine. International Classification of Sleep Disorders. 3rd ed. Darien, IL: American Academy of Sleep Medicine; 2014
    Search in Google Scholar
  • 27 Lam SP, Li SX, Zhang J, Wing YK. Development of scales for assessment of rapid eye movement sleep behavior disorder (RBD). Sleep Med 2013; 14 (08) 734-738
    CrossrefPubMedSearch in Google Scholar
  • 28 Boeve BF, Molano JR, Ferman TJ. , et al. Validation of the Mayo Sleep Questionnaire to screen for REM sleep behavior disorder in a community-based sample. J Clin Sleep Med 2013; 9 (05) 475-480
    CrossrefPubMedSearch in Google Scholar
  • 29 Iranzo A, Molinuevo JL, Santamaría J. , et al. Rapid-eye-movement sleep behaviour disorder as an early marker for a neurodegenerative disorder: a descriptive study. Lancet Neurol 2006; 5 (07) 572-577
    CrossrefPubMedSearch in Google Scholar
  • 30 Molano J, Boeve B, Ferman T. , et al. Mild cognitive impairment associated with limbic and neocortical Lewy body disease: a clinicopathological study. Brain 2010; 133 (Pt 2): 540-556
    CrossrefPubMedSearch in Google Scholar
  • 31 McKeith IG, Dickson DW, Lowe J. , et al; Consortium on DLB. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 2005; 65 (12) 1863-1872
    CrossrefPubMedSearch in Google Scholar
  • 32 Boeve BF, Silber MH, Ferman TJ, Lucas JA, Parisi JE. Association of REM sleep behavior disorder and neurodegenerative disease may reflect an underlying synucleinopathy. Mov Disord 2001; 16 (04) 622-630
    CrossrefPubMedSearch in Google Scholar
  • 33 Gjerstad MD, Boeve B, Wentzel-Larsen T, Aarsland D, Larsen JP. Occurrence and clinical correlates of REM sleep behaviour disorder in patients with Parkinson's disease over time. J Neurol Neurosurg Psychiatry 2008; 79 (04) 387-391
    CrossrefPubMedSearch in Google Scholar
  • 34 Gagnon JF, Bédard MA, Fantini ML. , et al. REM sleep behavior disorder and REM sleep without atonia in Parkinson's disease. Neurology 2002; 59 (04) 585-589
    CrossrefPubMedSearch in Google Scholar
  • 35 Kumru H, Santamaria J, Tolosa E. , et al. Rapid eye movement sleep behavior disorder in parkinsonism with parkin mutations. Ann Neurol 2004; 56 (04) 599-603
    CrossrefPubMedSearch in Google Scholar
  • 36 Pramstaller PP, Schlossmacher MG, Jacques TS. , et al. Lewy body Parkinson's disease in a large pedigree with 77 Parkin mutation carriers. Ann Neurol 2005; 58 (03) 411-422
    CrossrefPubMedSearch in Google Scholar
  • 37 Gagnon JF, Petit D, Fantini ML. , et al. REM sleep behavior disorder and REM sleep without atonia in probable Alzheimer disease. Sleep 2006; 29 (10) 1321-1325
    CrossrefPubMedSearch in Google Scholar
  • 38 Schenck CH, Garcia-Rill E, Skinner RD, Anderson ML, Mahowald MW. A case of REM sleep behavior disorder with autopsy-confirmed Alzheimer's disease: postmortem brain stem histochemical analyses. Biol Psychiatry 1996; 40 (05) 422-425
    CrossrefPubMedSearch in Google Scholar
  • 39 Ferman TJ, Boeve BF, Smith GE. , et al. Dementia with Lewy bodies may present as dementia and REM sleep behavior disorder without parkinsonism or hallucinations. J Int Neuropsychol Soc 2002; 8 (07) 907-914
    PubMedSearch in Google Scholar
  • 40 Schenck CH, Lee SA, Bornemann MA, Mahowald MW. Potentially lethal behaviors associated with rapid eye movement sleep behavior disorder: review of the literature and forensic implications. J Forensic Sci 2009; 54 (06) 1475-1484
    CrossrefPubMedSearch in Google Scholar
  • 41 Iranzo A, Fernández-Arcos A, Tolosa E. , et al. Neurodegenerative disorder risk in idiopathic REM sleep behavior disorder: study in 174 patients. PLoS One 2014; 9 (02) e89741
    CrossrefPubMedSearch in Google Scholar
  • 42 Schenck CH, Boeve BF, Mahowald MW. Delayed emergence of a parkinsonian disorder or dementia in 81% of older men initially diagnosed with idiopathic rapid eye movement sleep behavior disorder: a 16-year update on a previously reported series. Sleep Med 2013; 14 (08) 744-748
    CrossrefPubMedSearch in Google Scholar
  • 43 Schenck CH, Montplaisir JY, Frauscher B. , et al. Rapid eye movement sleep behavior disorder: devising controlled active treatment studies for symptomatic and neuroprotective therapy--a consensus statement from the International Rapid Eye Movement Sleep Behavior Disorder Study Group. Sleep Med 2013; 14 (08) 795-806
    CrossrefPubMedSearch in Google Scholar
  • 44 Lu J, Sherman D, Devor M, Saper CB. A putative flip-flop switch for control of REM sleep. Nature 2006; 441 (7093): 589-594
    CrossrefPubMedSearch in Google Scholar
  • 45 Dyken ME, Afifi AK, Lin-Dyken DC. Sleep-related problems in neurologic diseases. Chest 2012; 141 (02) 528-544
    CrossrefPubMedSearch in Google Scholar
  • 46 Saper CB, Fuller PM, Pedersen NP, Lu J, Scammell TE. Sleep state switching. Neuron 2010; 68 (06) 1023-1042
    CrossrefPubMedSearch in Google Scholar
  • 47 Siegel JM. The stuff dreams are made of: anatomical substrates of REM sleep. Nat Neurosci 2006; 9 (06) 721-722
    CrossrefPubMedSearch in Google Scholar
  • 48 Attarian HP, Schenck CH, Mahowald MW. Presumed REM sleep behavior disorder arising from cataplexy and wakeful dreaming. Sleep Med 2000; 1 (02) 131-133
    CrossrefPubMedSearch in Google Scholar
  • 49 Mahowald MW, Cramer Bornemann MA, Schenck CH. The early and accurate objective diagnosis of RBD--why should we care?. Mov Disord 2010; 25 (13) 2003-2005
    CrossrefPubMedSearch in Google Scholar
  • 50 Hendricks JC, Morrison AR, Mann GL. Different behaviors during paradoxical sleep without atonia depend on pontine lesion site. Brain Res 1982; 239 (01) 81-105
    CrossrefPubMedSearch in Google Scholar
  • 51 Rye DB. Contributions of the pedunculopontine region to normal and altered REM sleep. Sleep 1997; 20 (09) 757-788
    CrossrefPubMedSearch in Google Scholar
  • 52 Boeve BF, Lin SC, Strongosky A, Dickson DW, Wszolek ZK. Absence of rapid eye movement sleep behavior disorder in 11 members of the pallidopontonigral degeneration kindred. Arch Neurol 2006; 63 (02) 268-272
    CrossrefPubMedSearch in Google Scholar
  • 53 Boissard R, Fort P, Gervasoni D, Barbagli B, Luppi PH. Localization of the GABAergic and non-GABAergic neurons projecting to the sublaterodorsal nucleus and potentially gating paradoxical sleep onset. Eur J Neurosci 2003; 18 (06) 1627-1639
    CrossrefPubMedSearch in Google Scholar
  • 54 Boissard R, Gervasoni D, Schmidt MH, Barbagli B, Fort P, Luppi PH. The rat ponto-medullary network responsible for paradoxical sleep onset and maintenance: a combined microinjection and functional neuroanatomical study. Eur J Neurosci 2002; 16 (10) 1959-1973
    CrossrefPubMedSearch in Google Scholar
  • 55 Culebras A, Moore JT. Magnetic resonance findings in REM sleep behavior disorder. Neurology 1989; 39 (11) 1519-1523
    CrossrefPubMedSearch in Google Scholar
  • 56 Panossian LA, Avidan AY. Review of sleep disorders. Med Clin North Am 2009; 93 (02) 407-425 , ix
    CrossrefPubMedSearch in Google Scholar
  • 57 Knudsen S, Gammeltoft S, Jennum PJ. Rapid eye movement sleep behaviour disorder in patients with narcolepsy is associated with hypocretin-1 deficiency. Brain 2010; 133 (Pt 2): 568-579
    CrossrefPubMedSearch in Google Scholar
  • 58 Lessig S, Ubhi K, Galasko D. , et al. Reduced hypocretin (orexin) levels in dementia with Lewy bodies. Neuroreport 2010; 21 (11) 756-760
    CrossrefPubMedSearch in Google Scholar
  • 59 Fronczek R, Overeem S, Lee SY. , et al. Hypocretin (orexin) loss in Parkinson's disease. Brain 2007; 130 (Pt 6): 1577-1585
    CrossrefPubMedSearch in Google Scholar
  • 60 Thannickal TC, Lai YY, Siegel JM. Hypocretin (orexin) cell loss in Parkinson's disease. Brain 2007; 130 (Pt 6): 1586-1595
    CrossrefPubMedSearch in Google Scholar
  • 61 Devnani P, Fernandes R. Management of REM sleep behavior disorder: an evidence based review. Ann Indian Acad Neurol 2015; 18 (01) 1-5
    CrossrefPubMedSearch in Google Scholar
  • 62 Postuma RB, Gagnon JF, Tuineaig M. , et al. Antidepressants and REM sleep behavior disorder: isolated side effect or neurodegenerative signal?. Sleep 2013; 36 (11) 1579-1585
    CrossrefPubMedSearch in Google Scholar
  • 63 McGrane IR, Leung JG, St Louis EK, Boeve BF. Melatonin therapy for REM sleep behavior disorder: a critical review of evidence. Sleep Med 2015; 16 (01) 19-26
    CrossrefPubMedSearch in Google Scholar
  • 64 Boeve BF, Silber MH, Ferman TJ. Melatonin for treatment of REM sleep behavior disorder in neurologic disorders: results in 14 patients. Sleep Med 2003; 4 (04) 281-284
    CrossrefPubMedSearch in Google Scholar
  • 65 Kunz D, Bes F. Melatonin effects in a patient with severe REM sleep behavior disorder: case report and theoretical considerations. Neuropsychobiology 1997; 36 (04) 211-214
    CrossrefPubMedSearch in Google Scholar
  • 66 Kunz D, Bes F. Melatonin as a therapy in REM sleep behavior disorder patients: an open-labeled pilot study on the possible influence of melatonin on REM-sleep regulation. Mov Disord 1999; 14 (03) 507-511
    CrossrefPubMedSearch in Google Scholar
  • 67 Takeuchi N, Uchimura N, Hashizume Y. , et al. Melatonin therapy for REM sleep behavior disorder. Psychiatry Clin Neurosci 2001; 55 (03) 267-269
    CrossrefPubMedSearch in Google Scholar
  • 68 Di Giacopo R, Fasano A, Quaranta D, Della Marca G, Bove F, Bentivoglio AR. Rivastigmine as alternative treatment for refractory REM behavior disorder in Parkinson's disease. Mov Disord 2012; 27 (04) 559-561
    CrossrefPubMedSearch in Google Scholar
  • 69 Kashihara K, Nomura T, Maeda T. , et al. Beneficial effects of ramelteon on rapid eye movement sleep behavior disorder associated with Parkinson's disease—results of a multicenter open trial. Intern Med 2016; 55 (03) 231-236
    CrossrefPubMedSearch in Google Scholar
  • 70 Nomura T, Kawase S, Watanabe Y, Nakashima K. Use of ramelteon for the treatment of secondary REM sleep behavior disorder. Intern Med 2013; 52 (18) 2123-2126
    CrossrefPubMedSearch in Google Scholar