Quick viewing(Text Mode)

Importance of Rapid Eye Movement Sleep Behavior Disorder to the Primary Care Physician

Importance of Rapid Eye Movement Sleep Behavior Disorder to the Primary Care Physician

CONCISE REVIEW FOR CLINICIANS

Importance of Rapid Movement Behavior Disorder to the Primary Care Physician

Stuart J. McCarter, BA, and Michael J. Howell, MD

From the University of Min- nesota Medical School, Min- CME Activity neapolis (S.J.M.); Department fi of Neurology, University of Target Audience: The target audience for Mayo Clinic Proceedings is primar- ensure balance, independence, objectivity, and scienti c rigor in its educa- ily internal medicine physicians and other clinicians who wish to advance tional activities. Course Director(s), Planning Committee members, Faculty, Minnesota Medical Center, their current knowledge of clinical medicine and who wish to stay abreast and all others who are in a position to control the content of this educational Minneapolis (M.J.H.); and of advances in medical research. activity are required to disclose all relevant financial relationships with any Minnesota Regional Sleep Statement of Need: General internists and primary care physicians must maintain commercial interest related to the subject matter of the educational activity. Disorders Center, Hennepin an extensive knowledge base on a wide variety of topics covering all body systems as Safeguards against commercial bias have been put in place. Faculty also will County Medical Center, Min- well as common and uncommon disorders. Mayo Clinic Proceedings aims to leverage disclose any off-label and/or investigational use of pharmaceuticals or instru- neapolis (M.J.H.). the expertise of its authors to help physicians understand best practices in diagnosis ments discussed in their presentation. Disclosure of this information will be and management of conditions encountered in the clinical setting. published in course materials so that those participants in the activity may Accreditation: Mayo Clinic College of Medicine is accredited by the Accred- formulate their own judgments regarding the presentation. itation Council for Continuing Medical Education to provide continuing med- In their editorial and administrative roles, William L. Lanier, Jr, MD, Terry L. ical education for physicians. Jopke, Kimberly D. Sankey, and Nicki M. Smith, MPA, have control of the Credit Statement: Mayo Clinic College of Medicine designates this journal- content of this program but have no relevant financial relationship(s) with based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s). industry. Dr Howell is a consultant to the Sleep and Performance Institute. Physicians should claim only the credit commensurate with the extent of Method of Participation: In order to claim credit, participants must com- their participation in the activity. plete the following: Credit Statement: Successful completion of this CME activity, which includes 1. Read the activity. participation in the evaluation component, enables the participant to earn up to 2. Complete the online CME Test and Evaluation. Participants must achieve 1 MOC points in the American Board of Internal Medicine’s (ABIM) Mainte- a score of 80% on the CME Test. One retake is allowed. nance of Certification (MOC) program. Participants will earn MOC points Visit www.mayoclinicproceedings.org, select CME, and then select CME arti- equivalent to the amount of CME credits claimed for the activity. It is the cles to locate this article online to access the online process. On successful CME activity provider’s responsibility to submit participant completion infor- completion of the online test and evaluation, you can instantly download and mation to ACCME for the purpose of granting ABIM MOC credit. print your certificate of credit. Learning Objectives: On completion of this article, you should be able to Estimated Time: The estimated time to complete each article is approxi- (1) recognize the clinical manifestations of rapid sleep mately 1 hour. behavior disorder, (2) describe the importance of early diagnosis and treat- Hardware/Software: PC or MAC with Internet access. ment of this disorder, and (3) identify which factors are associated with an Date of Release: 10/1/2016 increased rate of progression from rapid eye movement sleep behavior dis- Expiration Date: 9/30/2018 (Credit can no longer be offered after it has order to clinically overt neurodegenerative disease. passed the expiration date.) Disclosures: As a provider accredited by ACCME, Mayo Clinic College of Privacy Policy: http://www.mayoclinic.org/global/privacy.html Medicine (Mayo School of Continuous Professional Development) must Questions? Contact [email protected].

Abstract

Sleep disorders and neurodegenerative diseases are commonly encountered in primary care. A common, but underdiagnosed , rapid eye movement sleep behavior disorder (RBD), is highly associated with Parkinson disease and related disorders. Rapid eye movement sleep behavior disorder is common. It is esti- mated to affect 0.5% of the general population and more than 7% of individuals older than 60 years; however, most cases go unrecognized. Rapid eye movement sleep behavior disorder presents as enactment, often with patients thrashing, punching, and kicking while they are sleeping. Physicians can quickly assess for the presence of RBD with high sensitivity and specificity by asking patients the question “Have you ever been told that you act out your , for example by punching or flailing your arms in the air or screaming and shouting in your sleep?” Patients with RBD exhibit subtle signs of neurodegenerative disease, such as mild motor slowing, constipation, or changes in sense of smell. These signs and symptoms may predict develop- ment of a neurodegenerative disease within 3 years. Ultimately, most patients with RBD develop a neurode- generative disease, highlighting the importance of serial neurological examinations to assess for the presence of parkinsonism and/or cognitive impairment and prognostic counseling for these patients. Rapid eye movement sleep behavior disorder is treatable with (3-6 mg before ) or clonazepam (0.5-1 mg before bed) and may be the most common, reversible cause of sleep-related injury. Thus, it is important to identify patients at risk of RBD in a primary care setting so that safety can be addressed and treatment may be initiated. ª 2016 Mayo Foundation for Medical Education and Research n Mayo Clin Proc. 2016;91(10):1460-1466

1460 Mayo Clin Proc. n October 2016;91(10):1460-1466 n http://dx.doi.org/10.1016/j.mayocp.2016.07.019 www.mayoclinicproceedings.org n ª 2016 Mayo Foundation for Medical Education and Research RAPID EYE MOVEMENT SLEEP BEHAVIOR DISORDER

leep disorders are common in the setting of autoimmune conditions.6,7 Further- general population and can lead to a more, women have less violent and, therefore, marked impairment in daytime func- less injurious DEB and thus are less likely to S 7 tioning and quality of life; however, they are receive medical attention. Another contrib- often underdiagnosed.1 Obstructive sleep uting factor to this discrepancy is likely due apnea (OSA), , restless legs to the sex difference in life expectancy; elderly syndrome, and excessive daytime sleepiness women are less likely to have bed partners are among the most commonly encountered than elderly men, leading to unwitnessed par- sleep problems in the primary care setting.2 asomnia behaviors. Rapid eye movement Furthermore, primary care physicians are sleep behavior disorder typically presents in often tasked with the challenge of unraveling either the sixth or the seventh decade; howev- the complexities of abnormal motor behaviors er, when questioned specifically, many pa- during sleep, ranging from to tients will report a long-standing history nocturnal seizures and confusional arousals. suggestive of DEB.8 Population-based However, an underdiagnosed sleep disorder, studies9,10 estimate that 0.5% of the general rapid eye movement (REM) sleep behavior population and 7.7% of individuals older disorder (RBD), is a potentially injurious para- than 60 years have probable RBD. However, somnia that should be considered in older pa- most individuals with RBD go unrecognized tients presenting to the primary care physician or underreported. Patients and bed partners complaining of abnormal activity during sleep. are often unsure how to broach the frequently Sleep is divided broadly into nonerapid taboo subject of out-of-control activities in eye movement (NREM) sleep and REM sleep, the bedroom. Furthermore, physicians often with unique nocturnal behaviors arising from interpret the behaviors as symptoms of an un- NREM and REM sleep, respectively. Under derlying or conflict between normal physiological conditions, REM sleep spouses rather than a primary sleep is typified by active mentation (dreams) and disturbance. . Rapid eye movement Despite the seemingly disruptive nature sleep skeletal muscle atonia is critical to pre- of punching, flailing, and screaming during vent dream enactment and promote a period sleep, up to 44% of patients with RBD are of quiescence for REM sleeperelated unaware of their DEB. In addition, it is not consolidation. Rapid eye movement sleep uncommon to identify a history of RBD as behavior disorder is characterized by dream a secondary symptom when evaluating a pa- enactment behavior (DEB) that emerges result- tient for other sleep problems such as OSA ing from the loss of REM sleep without atonia. or insomnia.3 Dream enactment behaviors Although RBD was initially thought to be sim- can range from violent and complex behav- ply an intriguing nocturnal phenomenon, lon- iors, such as thrashing in bed, punching gitudinal studies of patients with RBD revealed and kicking bed partners, and jumping out high potential for injuries to patients with RBD of windows, to simple activities of daily and their bed partners as well as a concerning living such as playing the piano or washing connection to parkinsonian neurodegenerative dishes.11 In fact, it is likely that the minority diseases that make this disorder important to of patients with RBD involve impressive and be recognized by primary care physicians. obvious DEB whereas most DEB may be un- obtrusive movements limited to the hands, EPIDEMIOLOGY AND PHENOMENOLOGY OF otherwise known as hand babbling.Thevio- RBD lent nature of RBD can often result in injury, Spontaneous RBD is traditionally considered with 55% to 96% of patients and/or bed to be a disorder of older adults, with large partners reporting injury, highlighting the published case series reporting approximately importance for timely recognition and treat- an 80% male prevalence with the onset of dis- ment of this disorder.12,13 Injuries range ease most commonly in the fifth to sixth from bruises and scratches to the more se- decade of life.3-5 However, there is evidence vere: fractures of the cervical vertebrae and to suggest that RBD in women is underrecog- basilar skull, shoulder dislocations, or nized, particularly in the young and in the hematomas.12

Mayo Clin Proc. n October 2016;91(10):1460-1466 n http://dx.doi.org/10.1016/j.mayocp.2016.07.019 1461 www.mayoclinicproceedings.org MAYO CLINIC PROCEEDINGS

SCREENING FOR RBD patients are often confused after arousal with Fortunately, it is easy to screen for RBD. Poly- little recollection.15 somnography (PSG) is the standard for a diag- As in RBD, patients with nosis of RBD; however, given the time- and such as and sleep terrors will resource-intensive nature of PSG, primary often vocalize during sleep. However, patients care clinicians can use survey methods to with nightmares do not have associated mo- identify those with likely RBD.14 The observa- tor activity and night terrors occur without tions of a bed partner or someone who has dream recall and typically occur in young witnessed the patient’s sleep are invaluable, children, a population in which RBD is as the patients themselves, as noted above, incredibly rare. Nocturnal frontal lobe are often unaware of their behaviors. In pa- epilepsy can be confused with RBD; however, tients without a bed partner, clues suggesting patients are often younger, present with possible RBD include vivid or terrifying stereotyped behaviors, and often have epilep- dreams, falling out of bed, or unexplained tiform activity on the electroencephalogram nocturnal bruising. Rapid eye movement sleep (Table 1).15 behavior disorder can be accurately identified with the following screening question: “Have RAPID EYE MOVEMENT SLEEP BEHAVIOR you ever been told that you act out your DISORDER AND ITS ASSOCIATION WITH dreams (eg, punching or flailing arms in the PSYCHIATRIC DISEASE air of screaming and shouting in your Rapid eye movement sleep behavior disorder sleep?).”14,p1 The Mayo Sleep Questionnaire14 cases among women are more likely to be has been validated in a community sample younger (age, <50 years) and often occur in with a sensitivity and specificity of 100% the setting of autoimmune disease or by using and 95%, respectively, and uses input from .5,6,16,17 Patients with a psychi- the patient’s bed partner, which is important atric disease history have a 10-fold increased given the limited insight of patients into their risk of developing RBD, whereas sleep habits. use increases the likelihood of RBD diagnosis 5-fold.18 Depression is the most common psychiatric disorder associated with RBD; DIFFERENTIAL DIAGNOSIS however, patients with posttraumatic stress dis- Not all nocturnal motor activity is RBD, and order may also evolve DEB and increased REM primary care physicians are often tasked with sleep muscle tone after exposure to trauma.16 initially trying to distinguish between different Rapid eye movement sleep behavior dis- parasomnias. Nonerapid eye movement para- order has been reported to evolve in patients somnias include confusional arousals, sleep- after the initiation of antidepressants, espe- walking, and sleep terrors, whereas REM cially selective reuptake inhibitors parasomnias mainly include RBD and night- (SSRIs). In addition, neurophysiological mares. Although history may distinguish these studies have shown abnormally increased disorders from RBD, PSG is often required for muscle tone during REM sleep definitive diagnosis. Nonerapid eye move- (without the development of dream enact- ment parasomnias tend to present in youth, ment) in patients taking antidepressants as often during childhood, as compared with compared with healthy controls and RBD. In addition, RBD episodes typically last psychiatric patients not taking antidepres- less than 60 seconds and occur during the sec- sants.16 Although the pathogenesis of ond half of the night with patients reporting antidepressant-induced RBD remains un- vivid dream recall. Nonerapid eye movement clear, it is not thought that antidepressants parasomnias tend to emanate from the first directly cause RBD and parkinsonism (see half of the night and generally last about 5 section Rapid Eye Movement Sleep Behavior to 10 minutes (longer if associated with seda- Disorder as a Prodromal Neurodegenerative tive medication). Furthermore, patients with Disease).16,17 Fortunately, antidepressant- RBD are often alert and oriented and immedi- induced RBD may decrease in severity with ately recall vivid dream mentation as cessation of the medication or decrease in compared with NREM parasomnias, in which the dose. Bupropion may be less likely

1462 Mayo Clin Proc. n October 2016;91(10):1460-1466 n http://dx.doi.org/10.1016/j.mayocp.2016.07.019 www.mayoclinicproceedings.org RAPID EYE MOVEMENT SLEEP BEHAVIOR DISORDER

than SSRIs to cause RBD and may be trialed in patients with RBD who require mood dis- order treatment. not present; þ /

RAPID EYE MOVEMENT SLEEP BEHAVIOR ¼

DISORDER AS A PRODROMAL NEURODE- lobe epilepsy Nocturnal frontal

GENERATIVE DISEASE at Antiepileptic medications Longitudinal studies of patients with RBD have Throughout the night revealed a strong association with the future strongly present; development of neurodegenerative disease, especially Parkinson disease (PD) and other þþ ¼ related conditions such as dementia with Lewy bodies (DLB) and multiple system atro- phy.4,5,8 Rapid eye movement sleep behavior sleep disorder disorder has traditionally been separated into sleep period Correct underlying

2 categories: idiopathic (RBD without signs of restless legs syndrome; ¼ neurodegenerative disease) or symptomatic/ secondary (RBD associated with known neuro- degenerative disease, , or medica- tion). Nearly all patients with idiopathic a RBD (81%-91%) will go on to develop - 0-10 min 5-20 min 3-5 min e synuclein mediated disorders such as PD or overlap disorder Sleep terrors rapid eye movement; RLS disorder, clonazepam ¼ AntidepressantsCorrect underlying sleep , OSA Daytime epilepsy DLB, especially if symptoms emerge after the Throughout the night First half of the age of 60 years, suggesting that idiopathic RBD is likely an early manifestation of a pro- gressive neurodegenerative disorder.19,20 How- ever, the risk of neurodegenerative disease in þþ young patients with RBD (ie, patients with / RBD younger than 50 years), women with associated with sedative medication) deprivation, sedative medication sleep disorder RBD, and those with antidepressant-induced sleep period RLS, OSA, sleep Correct underlying RBD remains to be elucidated. First half of the Although most patients with idiopathic RBD eventually progress to neurodegenerative disease, the prevalence of RBD varies among a e rapid eye movement sleep behavior disorder; REM

-synuclein mediated disorders: up to 50% ¼ in PD, up to 80% in DLB, and 80% to 95% in multiple system atrophy, suggesting that sedative medication sleep disorder idiopathic RBD may be a unique form of dis- sleep period OSA, sleep deprivation, First half of the ease.4,5 Rapid eye movement sleep behavior disorder may also worsen the prognosis of PD, as patients with PD with RBD appear to rapid eye movement; RBD have a more aggressive form of disease, with e increased cognitive impairment, visual halluci- non ¼ þþþþ þ nations, orthostatic hypotension, and more rapid motor decline as compared with patients may or may not be present. and related disorders 4 sleep period ¼ Parkinson disease with PD without RBD. Furthermore, patients / with PD with RBD are more likely to develop þ DLB or PD dementia than do patients with PD alone.21 Most importantly, for primary care physi- obstructive ; NREM Variable RBD Confusional arousals Sleep walking ¼ cians, patients with idiopathic RBD often sometimes present; manifest nonmotor signs of neurological conditions Sleep-related injury Dream recall DurationComorbid 0-60 s 5-10 min 5-10 min (longer if Treatment Melatonin, clonazepam Correct underlying Typical age rangeSleep stageTime of behaviors Middle aged, elderly Second half of the REM Childhood, young adult Childhood, young adult Young adult NREM Preadolescence NREM Childhood, young adult NREM/REM NREM/REM NREM TABLE 1. Differential Diagnosis of RBD OSA þ¼ dysfunction, such as orthostatic hypotension,

Mayo Clin Proc. n October 2016;91(10):1460-1466 n http://dx.doi.org/10.1016/j.mayocp.2016.07.019 1463 www.mayoclinicproceedings.org MAYO CLINIC PROCEEDINGS

constipation, hyposmia, and cognitive impair- bed. Medications known to cause RBD, such ment, especially in the domains of attention as antidepressants (especially SSRIs), should and executive function, as compared with be discontinued, if possible. As noted above, healthy controls.4,5,9,22,23 In fact, these fea- bupropion has not been strongly associated tures may be present 10 to 20 years before with the evolution of RBD and may be trialed the onset of clinically overt features of PD or in patients requiring treatment for depression. DLB.23 Patients with antidepressant-induced In addition, all patients with dream enactment RBD also manifest these prodromal symptoms history should be screened for OSA, which of neurodegenerative disease but have a longer can mimic RBD. Patients often report a duration from manifestation of RBD symp- decrease in DEB frequency after treatment of toms to clinically evident PD or DLB as their OSA.24 compared with patients with RBD who were Some patients have mild RBD symptoms not taking antidepressants.17 These findings and, therefore, prefer not to be treated. can be used to predict which patients with Because the frequency of DEB does not appear RBD are more likely to develop PD in the to be predictive of injury, it could be argued near future. In particular, if a patient with that treatment, or at a minimum bedroom RBD is older at the age of dream enactment safety measures, should be initiated as soon onset; has difficulty with smell, color vision, as the RBD diagnosis is made.12 The most constipation; and is not taking an antidepres- commonly used medications for RBD are clo- sant, they are highly likely to progress onto nazepam and/or melatonin. In addition to a PD or a related condition in the next 3 years small clinical trial4 for melatonin, there has (Table 2).22 been a paucity of placebo-controlled studies of RBD, and the consensus on management TREATMENT OF RBD is based on a case series and this small clinical Rapid eye movement sleep behavior disorder trial. Low doses of clonazepam (0.5-1 mg) at is a readily treatable condition. The most bedtime have been reported to be effective in important initial management strategies are reducing DEBs in up to 90% of cases; how- environmental to protect the patient and the ever, clonazepam may cause sedation and worsen underlying cognitive impairment, bed partner: removing objects that could 3,4,12 pose a danger, especially firearms, but also sleep apnea, and gait impairment. nightstands, lamps, or sleeping separately until Melatonin has also been reported to be DEB are under control.4 Sleeping bags can effective in reducing RBD symptoms and injury occurrence with a median effective help prevent a patient from leaving the bed. 3,25 Patients may place their on the floor dose of 6 mg at bedtime. A recent retro- next to the bed to prevent from falling out of spective analysis comparing clonazepam and melatonin reported that they were equally effective in reducing falls and injury in patients TABLE 2. Assessing Risk of Neurodegeneration in with RBD, with melatonin having considerably RBDa,b fewer adverse effects. In addition, melatonin Low risk High risk was better tolerated in patients with comorbid (>3y)of (<3y)of neurodegenerative disease.25 Other medica- developing developing tions such as dopaminergic agonists (prami- Variable PD/DLB PD/DLB pexole) and acetylcholinesterase inhibitors Age at diagnosis (y) <65 >65 (rivastigmine) have been trialed with variable Smell Normal Abnormal success in patients with RBD and may be Color vision Normal Abnormal considered in treatment-refractory patients.26 Antidepressant use Yes No Constipation Absent Present WHEN TO REFER PATIENTS WITH RBD TO Orthostasis Absent Present Motor slowing Absent Present SPECIALTY CARE As mentioned above, the frequency of DEB a ¼ ¼ DLB dementia with Lewy bodies; PD Parkinson disease. often decreases dramatically with a relatively bCombining risk factors results in significantly higher risk compared to patients with single risk factor. low dose of melatonin or clonazepam. How- ever, patients with persistent DEB requiring

1464 Mayo Clin Proc. n October 2016;91(10):1460-1466 n http://dx.doi.org/10.1016/j.mayocp.2016.07.019 www.mayoclinicproceedings.org RAPID EYE MOVEMENT SLEEP BEHAVIOR DISORDER

polytherapy or high doses of clonazepam or patients screening positive for RBD be ques- melatonin may benefit from referral to a sleep tioned about antidepressant use, changes in specialist for further management and PSG to sense of smell or bowel function, as well as rule out RBD mimics (confusional arousals be evaluated with serial neurological examina- and nocturnal seizures) or conditions that tions and receive prognostic counseling and may worsen dream enactment (OSA). In addi- consideration for enrollment in future clinical tion, patients with an unclear history may trials of neuroprotective therapies. benefit from referral to sleep specialist for PSG to rule out other parasomnias. Abbreviations and Acronyms: DEB = dream enactment Patients with RBD with concern for motor behavior; DLB = dementia with Lewy bodies; NREM = dysfunction (slowing, tremor, shuffling gait, nonerapid eye movement; OSA = ; and postural instability) should be referred to PD = Parkinson disease; PSG = ; RBD = rapid eye movement sleep behavior disorder; REM = rapid a movement disorder specialist for a detailed eye movement; SSRI = selective serotonin reuptake neurological evaluation. Similarly, patients inhibitor with concern for cognitive impairment may benefit from a behavioral neurology consult Potential Competing Interests: Dr Howell is a consultant to the Sleep and Performance Institute. and neuropsychiatric evaluation. Neurology referral is important not only for symptomatic Correspondence: Address to Stuart J. McCarter, BA, MS4, management (ie, levodopa for parkinsonism University of Minnesota Medical School, 420 Delaware St, and acetylcholinesterase inhibitors for cogni- SE, Minneapolis, MN 55455 ([email protected]). tive impairment) but also for enrollment in clinical trials of neuroprotective therapies and REFERENCES prognostic counseling for patients with RBD 1. Ohayon MM. Prevalence and comorbidity of sleep disorders in on risk of developing neurodegenerative general population [in French]. Rev Prat. 2007;57(14): disease. 1521-1528. 2. Alattar M, Harrington JJ, Mitchell CM, Sloane P. Sleep problems in primary care: a North Carolina Family Practice Research CONCLUSION Network (NC-FP-RN) study. J Am Board Fam Med. 2007; Rapid eye movement sleep behavior disorder 20(4):365-374. is a common and potentially injurious sleep 3. Fernández-Arcos A, Iranzo A, Serradell M, Gaig C, Santamaria J. The clinical phenotype of idiopathic rapid eye movement sleep disorder affecting primarily older adults and behavior disorder at presentation: a study of 203 consecutive is likely underrecognized in the primary care patients. Sleep. 2016;39(1):121-132. setting. Primary care physicians can quickly 4. Howell MJ, Schenck CH. Rapid eye movement sleep behavior disorder and neurodegenerative disease. JAMA Neurol. 2015; and accurately screen for RBD during clinical 72(6):707-712. interview by asking the question “Have you 5. McCarter SJ, St Louis EK, Boeve BF. REM sleep behavior disor- ever been told that you act out your dreams?” der and REM sleep without atonia as an early manifestation of degenerative neurological disease [published correction ap- or by using a questionnaire (such as the Mayo pears in Curr Neurol Neurosci Rep. 2012;12(2):226]. Curr Neurol Sleep Questionnaire) that the patient can com- Neurosci Rep. 2012;12(2):182-192. plete during triage. Rapid eye movement sleep 6. Ju YE. Rapid eye movement sleep behavior disorder in adults younger than 50 years of age. Sleep Med. 2013;14(8): behavior disorder may be treated with clonaz- 768-774. epam (0.5-1 mg) or melatonin (3-6 mg) at 7. Zhou J, Zhang J, Li Y, et al. Gender differences in REM sleep bedtime to help reduce risk of injury to the pa- behavior disorder: a clinical and polysomnographic study in China. Sleep Med. 2015;16(3):414-418. tients and their bed partners, although mela- 8. Claassen DO, Josephs KA, Ahlskog JE, Silber MH, Tippmann- tonin may be preferable given its similar Peikert M, Boeve BF. REM sleep behavior disorder preceding efficacy and more favorable adverse-effect pro- other aspects of by up to half a century. file as compared with clonazepam. Rapid eye Neurology. 2010;75(6):494-499. 9. Mahlknecht P, Seppi K, Frauscher B, et al. Probable RBD and movement sleep behavior disorder can evolve association with neurodegenerative disease markers: a after the initiation of antidepressants, espe- population-based study. Mov Disord. 2015;30(10):1417- cially SSRIs, and may remit with cessation of 1421. 10. Boot BP, Boeve BF, Roberts RO, et al. Probable rapid eye the medication or by using an alternative anti- movement sleep behavior disorder increases risk for mild depressant such as bupropion. More impor- cognitive impairment and Parkinson disease: a population- tantly, given the emerging evidence that RBD based study. Ann Neurol. 2012;71(1):49-56. 11. Oudiette D, De Cock VC, Lavault S, Leu S, Vidailhet M, Arnulf I. is part of a spectrum of progressive neurode- Nonviolent elaborate behaviors may also occur in REM sleep generative diseases, it is important that behavior disorder. Neurology. 2009;72(6):551-557.

Mayo Clin Proc. n October 2016;91(10):1460-1466 n http://dx.doi.org/10.1016/j.mayocp.2016.07.019 1465 www.mayoclinicproceedings.org MAYO CLINIC PROCEEDINGS

12. McCarter SJ, St Louis EK, Boswell CL, et al. Factors associated initially diagnosed with idiopathic rapid eye movement sleep with injury in REM sleep behavior disorder. Sleep Med. 2014; behavior disorder: a 16-year update on a previously reported 15(11):1332-1338. series. Sleep Med. 2013;14(8):744-748. 13. Olson EJ, Boeve BF, Silber MH. Rapid eye movement sleep 21. McCarter SJ, St Louis EK, Boeve BF. Is rapid eye movement behaviour disorder: demographic, clinical and laboratory find- sleep behavior disorder in Parkinson disease a specific disease ings in 93 cases. . 2000;123(pt 2):331-339. subtype? Sleep Med. 2013;14(10):931-933. 14. Boeve BF, Molano JR, Ferman TJ, et al. Validation of the Mayo 22. Postuma RB, Gagnon JF, Bertrand JA, Génier Marchand D, Sleep Questionnaire to screen for REM sleep behavior disorder Montplaisir JY. Parkinson risk in idiopathic REM sleep behavior in a community-based sample. J Clin Sleep Med. 2013;9(5): disorder: preparing for neuroprotective trials. Neurology. 2015; 475-480. 84(11):1104-1113. 15. Howell MJ. Parasomnias: an updated review. Neurotherapeutics. 23. Postuma RB, Gagnon JF, Pelletier A, Montplaisir J. Prodromal 2012;9(4):753-775. autonomic symptoms and signs in Parkinson’s disease and de- 16. McCarter SJ, St Louis EK, Sandness DJ, et al. Antidepressants in- mentia with Lewy bodies. Mov Disord. 2013;28(5):597-604. crease REM sleep muscle tone in patients with and without 24. McCarter SJ, St Louis EK, Duwell EJ, et al. Diagnostic thresholds REM sleep behavior disorder. Sleep. 2015;38(6):907-917. for quantitative REM sleep phasic burst duration, phasic and 17. Postuma RB, Gagnon JF, Tuineaig M, et al. Antidepressants and tonic muscle activity, and REM atonia index in REM sleep REM sleep behavior disorder: isolated side effect or neurode- behavior disorder with and without comorbid obstructive sleep generative signal? Sleep. 2013;36(11):1579-1585. apnea. Sleep. 2014;37(10):1649-1662. 18. Teman PT, Tippmann-Peikert M, Silber MH, Slocumb NL, 25. McCarter SJ, Boswell CL, St Louis EK, et al. Treatment out- Auger RR. Idiopathic rapid-eye-movement sleep disorder: asso- comes in REM sleep behavior disorder. Sleep Med. 2013; ciations with antidepressants, psychiatric diagnoses, and other 14(3):237-242. factors, in relation to age of onset. Sleep Med. 2009;10(1):60-65. 26. Aurora RN, Zak RS, Maganti RK, et al; Standards of Practice 19. Iranzo A, Fernández-Arcos A, Tolosa E, et al. Neurodegenera- Committee; American Academy of . Best prac- tive disorder risk in idiopathic REM sleep behavior disorder: tice guide for the treatment of REM sleep behavior disorder study in 174 patients. PLoS One. 2014;9(2):e89741. (RBD) [published correction appears in J Clin Sleep Med. 20. Schenck CH, Boeve BF, Mahowald MW. Delayed emergence 2010;6(2):table of contents]. J Clin Sleep Med. 2010;6(1): of a parkinsonian disorder or dementia in 81% of older men 85-95.

1466 Mayo Clin Proc. n October 2016;91(10):1460-1466 n http://dx.doi.org/10.1016/j.mayocp.2016.07.019 www.mayoclinicproceedings.org

Top View