Idiopathic rapid eye movement sleep behaviour disorder: diagnosis, management, and the need for neuroprotective interventions

Idiopathic rapid eye movement (REM) sleep behaviour disorder (IRBD) manifests as unpleasant dreams and vigorous behaviours during REM sleep that can result in injuries. Patients with IRBD have no known neurological diseases or motor or cognitive complaints; however, this sleep disorder is not harmless. In most cases, IRBD is the prelude of the synucleinopathies Parkinson's disease, dementia with Lewy bodies, or, less frequently, multiple system atrophy. Patients can show abnormalities that are characteristic of the synucleinopathies, and longitudinal follow-up shows that most patients develop parkinsonism and cognitive impairments with time. Thus, diagnosis of IRBD needs to be accurate and involves informing the patient of the risk of developing a neurodegenerative disease. It is extraordinary for a sleep disorder to precede the full expression of a neurodegenerative disease, which renders IRBD of particular interest in studies of the prodromal stage of the synucleinopathies, and in the development of neuroprotective interventions to stop or slow neurodegenerative deterioration before motor and cognitive symptomatology emerges. Such therapeutics do not currently exist, and thus represent an unmet need in IRBD.

[1]  A. Lang,et al.  Potential early markers of Parkinson disease in idiopathic REM sleep behavior disorder , 2006, Neurology.

[2]  E. Tolosa,et al.  Assessment of α-synuclein in submandibular glands of patients with idiopathic rapid-eye-movement sleep behaviour disorder: a case-control study , 2016, The Lancet Neurology.

[3]  C. Schenck,et al.  A novel therapy for REM sleep behavior disorder (RBD). , 2011, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[4]  E. Tolosa,et al.  Characteristics of idiopathic REM sleep behavior disorder and that associated with MSA and PD , 2005, Neurology.

[5]  R. Postuma,et al.  REM Sleep Behavior Disorder and Prodromal Neurodegeneration – Where Are We Headed? , 2013, Tremor and other hyperkinetic movements.

[6]  C. Schenck,et al.  Rapid eye movement sleep behavior disorder in women: relevance to general and specialty medical practice. , 2009, Journal of women's health.

[7]  R. Postuma,et al.  Parkinson risk in idiopathic REM sleep behavior disorder , 2015, Neurology.

[8]  Geert Mayer,et al.  The REM sleep behavior disorder screening questionnaire—A new diagnostic instrument , 2007, Movement disorders : official journal of the Movement Disorder Society.

[9]  Zhao Ying Physiological Basis of Sleep , 2010 .

[10]  J. Santamaria,et al.  Changes in dreaming induced by CPAP in severe obstructive sleep apnea syndrome patients , 2006, Journal of sleep research.

[11]  Yo-El S. Ju,et al.  Rapid eye movement sleep behavior disorder in adults younger than 50 years of age. , 2013, Sleep medicine.

[12]  Dong Zhou,et al.  Gender differences in REM sleep behavior disorder: a clinical and polysomnographic study in China. , 2015, Sleep medicine.

[13]  C. M. Lum,et al.  Sleep-related injury in the elderly--an epidemiological study in Hong Kong. , 2000, Sleep.

[14]  V. Mok,et al.  Prospective outcome of rapid eye movement sleep behaviour disorder: psychiatric disorders as a potential early marker of Parkinson's disease , 2012, Journal of Neurology, Neurosurgery & Psychiatry.

[15]  R. Riha,et al.  Diagnostic delay in REM sleep behavior disorder (RBD). , 2012, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[16]  D. Oudiette,et al.  Dreamlike mentations during sleepwalking and sleep terrors in adults. , 2009, Sleep.

[17]  E. Tolosa,et al.  Longitudinal assessment of olfactory function in idiopathic REM sleep behavior disorder. , 2013, Parkinsonism & related disorders.

[18]  E. Tolosa,et al.  Quantification of electromyographic activity during REM sleep in multiple muscles in REM sleep behavior disorder. , 2008, Sleep.

[19]  K. Walters,et al.  Prediagnostic presentations of Parkinson's disease in primary care: a case-control study , 2015, The Lancet Neurology.

[20]  Ronald C Petersen,et al.  Validation of the Mayo Sleep Questionnaire to screen for REM sleep behavior disorder in an aging and dementia cohort. , 2011, Sleep medicine.

[21]  G. Uguccioni,et al.  Fight or flight? Dream content during sleepwalking/sleep terrors vs. rapid eye movement sleep behavior disorder. , 2013, Sleep medicine.

[22]  Y. Wing,et al.  REM sleep behaviour disorder in Hong Kong Chinese: clinical outcome and gender comparison , 2008, Journal of Neurology, Neurosurgery, and Psychiatry.

[23]  R. Postuma,et al.  Markers of neurodegeneration in idiopathic rapid eye movement sleep behaviour disorder and Parkinson's disease. , 2009, Brain : a journal of neurology.

[24]  S D Ross,et al.  Systematic review and meta-analysis of the literature regarding the diagnosis of sleep apnea. , 2000, Sleep.

[25]  Francesco Rundo,et al.  Comparison between an automatic and a visual scoring method of the chin muscle tone during rapid eye movement sleep. , 2014, Sleep medicine.

[26]  J. Montplaisir,et al.  Breakdown in REM sleep circuitry underlies REM sleep behavior disorder , 2014, Trends in Neurosciences.

[27]  E. Tolosa,et al.  Progress in defining the premotor phase of Parkinson's disease , 2011, Journal of the Neurological Sciences.

[28]  M. Silber,et al.  REM sleep behavior disorder preceding other aspects of synucleinopathies by up to half a century , 2010, Neurology.

[29]  Ki Woong Kim,et al.  Progression of cognitive impairments in idiopathic REM sleep behaviour disorder , 2015, Journal of Neurology, Neurosurgery & Psychiatry.

[30]  B. Mollenhauer,et al.  Associated factors for REM sleep behavior disorder in Parkinson disease , 2011, Neurology.

[31]  R. Postuma,et al.  Olfaction and color vision identify impending neurodegeneration in rapid eye movement sleep behavior disorder , 2011, Annals of neurology.

[32]  Kevin F. Bieniek,et al.  Validation of the Mayo Sleep Questionnaire to screen for REM sleep behavior disorder in a community-based sample. , 2013, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[33]  E. Tolosa,et al.  Brainstem raphe and substantia nigra echogenicity in idiopathic REM sleep behavior disorder with comorbid depression , 2015, Journal of Neurology.

[34]  M. Vidailhet,et al.  Nonviolent elaborate behaviors may also occur in REM sleep behavior disorder , 2009, Neurology.

[35]  G. E. Smith,et al.  REM sleep behavior disorder and degenerative dementia , 1998, Neurology.

[36]  B. Boeve,et al.  Rapid eye movement sleep behavior disorder and subtypes in autopsy‐confirmed dementia with Lewy bodies , 2012, Movement disorders : official journal of the Movement Disorder Society.

[37]  W. Oertel,et al.  Comorbidity and medication in REM sleep behavior disorder , 2014, Neurology.

[38]  E. Tolosa,et al.  Usefulness of the SINBAR electromyographic montage to detect the motor and vocal manifestations occurring in REM sleep behavior disorder. , 2011, Sleep medicine.

[39]  M. Thorpy,et al.  International classification of sleep disorders , 2017 .

[40]  M. Mahowald,et al.  Potentially Lethal Behaviors Associated With Rapid Eye Movement Sleep Behavior Disorder: Review of the Literature and Forensic Implications , 2009, Journal of forensic sciences.

[41]  Carlos H Schenck,et al.  Violent behavior during sleep: prevalence, comorbidity and consequences. , 2010, Sleep medicine.

[42]  R. Postuma,et al.  Olfactory deficit in idiopathic rapid eye movements sleep behavior disorder , 2006, Brain Research Bulletin.

[43]  K. Hirata,et al.  Reduced cardiac 123I-MIBG scintigraphy in idiopathic REM sleep behavior disorder , 2006, Neurology.

[44]  B. Boeve Idiopathic REM sleep behaviour disorder in the development of Parkinson's disease , 2013, The Lancet Neurology.

[45]  E. Tolosa,et al.  Prevalence and timeline of nonmotor symptoms in idiopathic rapid eye movement sleep behavior disorder , 2015, Journal of Neurology.

[46]  B. Högl,et al.  Defining muscle activities for assessment of rapid eye movement sleep behavior disorder: from a qualitative to a quantitative diagnostic level. , 2013, Sleep medicine.

[47]  J. Molinuevo,et al.  Decreased striatal dopamine transporter uptake and substantia nigra hyperechogenicity as risk markers of synucleinopathy in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study , 2010, The Lancet Neurology.

[48]  R. Postuma,et al.  Antidepressants and REM sleep behavior disorder: isolated side effect or neurodegenerative signal? , 2013, Sleep.

[49]  C. Derry,et al.  The Sleep Manifestations of Frontal Lobe Epilepsy , 2011, Current neurology and neuroscience reports.

[50]  A. Lang,et al.  How does parkinsonism start? Prodromal parkinsonism motor changes in idiopathic REM sleep behaviour disorder. , 2012, Brain : a journal of neurology.

[51]  Yves Dauvilliers,et al.  Polysomnographic diagnosis of idiopathic REM sleep behavior disorder , 2010, Movement disorders : official journal of the Movement Disorder Society.

[52]  T. Nielsen,et al.  Dream-enacting behaviors in a normal population. , 2009, Sleep.

[53]  D. Kunz,et al.  A two‐part, double‐blind, placebo‐controlled trial of exogenous melatonin in REM sleep behaviour disorder , 2010, Journal of sleep research.

[54]  W. Oertel,et al.  Risk factors for neurodegeneration in idiopathic rapid eye movement sleep behavior disorder: A multicenter study , 2015, Annals of neurology.

[55]  I. Arnulf REM sleep behavior disorder: Motor manifestations and pathophysiology , 2012, Movement disorders : official journal of the Movement Disorder Society.

[56]  G. Greenough,et al.  Ethical considerations in REM sleep behavior disorder. , 2013, Continuum.

[57]  V. Mok,et al.  Validation of a new REM sleep behavior disorder questionnaire (RBDQ-HK). , 2010, Sleep medicine.

[58]  J. Molinuevo,et al.  Five‐year follow‐up of substantia nigra echogenicity in idiopathic REM sleep behavior disorder , 2014, Movement disorders : official journal of the Movement Disorder Society.

[59]  Carlos H Schenck,et al.  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. , 2013, Sleep medicine.

[60]  Jacques Montplaisir,et al.  Polysomnographic features of REM sleep behavior disorder , 1992, Neurology.

[61]  J. Santamaria,et al.  Severe obstructive sleep apnea/hypopnea mimicking REM sleep behavior disorder. , 2005, Sleep.

[62]  Margarete Delazer,et al.  Validation of the Innsbruck REM sleep behavior disorder inventory , 2012, Movement disorders : official journal of the Movement Disorder Society.

[63]  B. Boeve REM sleep behavior disorder , 2010, Annals of the New York Academy of Sciences.

[64]  S. Cappa,et al.  Neuropsychological assessment in idiopathic REM sleep behavior disorder (RBD) , 2004, Neurology.

[65]  E. Dietrichs,et al.  REM sleep behavior disorder in Parkinson's disease--is there a gender difference? , 2013, Parkinsonism & related disorders.

[66]  Michael C. Chen,et al.  Rapid eye movement sleep behavior disorder , 2013, Current Opinion in Neurobiology.

[67]  J. Molinuevo,et al.  Neuropathology of prodromal Lewy body disease , 2014, Movement disorders : official journal of the Movement Disorder Society.

[68]  Raffaele Manni,et al.  Motor-behavioral episodes in REM sleep behavior disorder and phasic events during REM sleep. , 2009, Sleep.

[69]  V. Pankratz,et al.  Probable rapid eye movement sleep behavior disorder increases risk for mild cognitive impairment and Parkinson disease: A population‐based study , 2012, Annals of neurology.

[70]  J. Carrier,et al.  REM sleep behavior disorder and REM sleep without atonia in Parkinson’s disease , 2002, Neurology.

[71]  M. Uchiyama,et al.  Incidental Lewy body disease in a patient with REM sleep behavior disorder , 1995, Neurology.

[72]  Joan Santamaria,et al.  Normative EMG values during REM sleep for the diagnosis of REM sleep behavior disorder. , 2012, Sleep.

[73]  J. O'Brien,et al.  Prodromal dementia with Lewy bodies , 2014, Psychological Medicine.

[74]  J. Molinuevo,et al.  Serial dopamine transporter imaging of nigrostriatal function in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study , 2011, The Lancet Neurology.

[75]  Y. Wing,et al.  Development of scales for assessment of rapid eye movement sleep behavior disorder (RBD). , 2013, Sleep medicine.

[76]  M. Mahowald,et al.  REM sleep behavior disorder: clinical, developmental, and neuroscience perspectives 16 years after its formal identification in SLEEP. , 2002, Sleep.

[77]  Poul Jennum,et al.  A single‐question screen for rapid eye movement sleep behavior disorder: A multicenter validation study , 2012, Movement disorders : official journal of the Movement Disorder Society.

[78]  E. Sinforiani,et al.  Cognitive performances and mild cognitive impairment in idiopathic rapid eye movement sleep behavior disorder: results of a longitudinal follow-up study. , 2013, Sleep.

[79]  Mark W. Mahowald,et al.  Delayed emergence of a parkinsonian disorder in 38% of 29 older men initially diagnosed with idiopathic rapid eye movement sleep behavior disorder , 1996, Neurology.

[80]  J. Santamaria,et al.  The Clinical Phenotype of Idiopathic Rapid Eye Movement Sleep Behavior Disorder at Presentation: A Study in 203 Consecutive Patients. , 2016, Sleep.

[81]  E. Tolosa,et al.  Pathological description of a non-motor variant of multiple system atrophy , 2008, Journal of Neurology, Neurosurgery, and Psychiatry.

[82]  C Trenkwalder,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. , 2013, Sleep medicine.

[83]  Klaus Seppi,et al.  Probable RBD and association with neurodegenerative disease markers: A population‐based study , 2015, Movement disorders : official journal of the Movement Disorder Society.

[84]  D. Mechanic The contributions of sociology to psychiatry , 1973, Psychological Medicine.

[85]  T. Kim,et al.  REM sleep behavior disorder in the Korean elderly population: prevalence and clinical characteristics. , 2013, Sleep.

[86]  D. Kunz Melatonin in rapid eye movement sleep behavior disorder: why does it work? , 2013, Sleep medicine.

[87]  J. Molinuevo,et al.  Neurodegenerative Disorder Risk in Idiopathic REM Sleep Behavior Disorder: Study in 174 Patients , 2014, PloS one.

[88]  M. Vendette,et al.  Quantifying the risk of neurodegenerative disease in idiopathic REM sleep behavior disorder , 2009, Neurology.

[89]  J. Santamaria,et al.  Absence of alterations in serum sex hormone levels in idiopathic REM sleep behavior disorder. , 2007, Sleep.

[90]  José Luis Molinuevo,et al.  Rapid-eye-movement sleep behaviour disorder as an early marker for a neurodegenerative disorder: a descriptive study , 2006, The Lancet Neurology.

[91]  S. Auerbach,et al.  Best practice guide for the treatment of REM sleep behavior disorder (RBD). , 2010, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[92]  Friederike Sixel-Döring,et al.  REM sleep behavior disorder in Parkinson’s disease , 2014, Journal of Neural Transmission.

[93]  G. Plazzi,et al.  A quantitative statistical analysis of the submentalis muscle EMG amplitude during sleep in normal controls and patients with REM sleep behavior disorder , 2008, Journal of sleep research.

[94]  Physiological basis of sleep , 2004 .

[95]  Ji Eun Kim Diagnosis of REM sleep behavior disorder , 2009 .

[96]  B. Boeve,et al.  Melatonin therapy for REM sleep behavior disorder: a critical review of evidence. , 2015, Sleep medicine.

[97]  Michael Schocke,et al.  White and gray matter abnormalities in idiopathic rapid eye movement sleep behavior disorder: A diffusion‐tensor imaging and voxel‐based morphometry study , 2011, Annals of neurology.

[98]  B. Boeve,et al.  Insights into REM sleep behavior disorder pathophysiology in brainstem-predominant Lewy body disease. , 2007, Sleep medicine.

[99]  L. Ferini-Strambi,et al.  Aggressive dream content without daytime aggressiveness in REM sleep behavior disorder , 2005, Neurology.

[100]  W. Poewe,et al.  Trial designs used to study neuroprotective therapy in Parkinson's disease , 2013, Movement disorders : official journal of the Movement Disorder Society.

[101]  E. Tolosa,et al.  Enteric nervous system α-synuclein immunoreactivity in idiopathic REM sleep behavior disorder , 2015, Neurology.

[102]  E. Bézard,et al.  Slowing of neurodegeneration in Parkinson's disease and Huntington's disease: future therapeutic perspectives , 2014, The Lancet.

[103]  C. Adler,et al.  Clinicopathologic correlations in 172 cases of rapid eye movement sleep behavior disorder with or without a coexisting neurologic disorder. , 2013, Sleep medicine.

[104]  J. Molinuevo,et al.  Neurodegenerative disease status and post-mortem pathology in idiopathic rapid-eye-movement sleep behaviour disorder: an observational cohort study , 2013, The Lancet Neurology.