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Sleep and Biological Rhythms 2013; 11 (Suppl. 1): 35–39

ORIGINAL ARTICLE

sbr_551

doi:10.1111/j.1479-8425.2012.00551.x

35..39

Phenomenology of rapid eye movement (REM) sleep behavior disorder in Parkinson’s disease: A descriptive study using the REM sleep behavior disorder severity scale (RBDSS) Friederike SIXEL-DÖRING, Ellen TRAUTMANN, Brit MOLLENHAUER and Claudia TRENKWALDER Paracelsus-Elena Klinik, Kassel, Germany

Abstract Using the rapid eye movement (REM) sleep behavior disorder severity scale (RBDSS) as a reliable clinical tool we further assessed the phenomenology of REM sleep behavior disorder (RBD) in 56 Parkinson’s disease patients with RBD. The scale uses phenomenological categories based on the localization of movements in the distal or proximal extremities and/or involving the trunc and on the presence or absence of vocalizations. Inter-rater reliability has been published previously. In the current study we looked into the distribution of motor and vocal phenomena. We identified a small percentage of patients with only vocalizations (4/56), and 8/56 patients with and 10/56 patients without vocalizations and small nonviolent movements of the distal extremities or facial jerks. Ten patients showed more forceful movements of the proximal extremities, 11 patients with movements involving the proximal extremities had additional vocalizations, 5 patients were recorded with axial involvement, and 12 patients with axial movements and vocalizations. These findings underline the clinical variety of RBD manifestation in Parkinson’s disease patients without a certain pattern. However, both extreme variants, the mild one and the violent one, are rare. The RBDSS facilitates the risk estimate for harmful behaviors and may be recommended for comparative studies on RBD and its pharmacotherapy. Key words: clinical scale, Parkinson’s disease, REM sleep behavior disorder, severity.

INTRODUCTION Rapid eye movement (REM) sleep behavior disorder (RBD) is a frequent and clinically relevant nocturnal disturbance in all stages of Parkinson’s disease (PD), contributing to the nighttime problems of PD patients as well as their bed partners and caregivers.1 Various studies have attempted to characterize and quantify RBD, Correspondence: Prof. Dr. Claudia Trenkwalder, Paracelsus-Elena Klinik, Klinikstr. 16, 34128 Kassel, Germany. Email: [email protected] Accepted 17 February 2012.

including electromyographic measurements of tonic and phasic muscle activity during REM sleep,2 differentiation between simple and complex movements,3,4 grading of RBD intensity as mild, moderate, or severe,5 and qualitative descriptions of RBD manifestations in videosupported polysomnography (vPSG).6 Another method requires detailed analysis of the number and types of motor events occurring during REM sleep using a complex and thorough, but time-consuming video classification system.7 While verbally descriptive methods are subject to interpretation influenced by personal and/or cultural aspects, elaborate electromyographic

© 2013 The Authors Sleep and Biological Rhythms © 2013 Japanese Society of Sleep Research

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measurements and detailed video-based movement analysis may yield interesting scientific information about the complex phenomenology of RBD. However, they do not appear feasible for use in clinical practice, for estimating the risk for potentially harmful behaviors, or for comparative studies. We therefore developed the RBD severity scale (RBDSS) as a simple vPSG rating scale for RBD to be used in PD patients. The scale uses phenomenological categories based on the localization and type of movements in the distal or proximal extremities and/or involving the trunc, being simple or complex up to violent behaviors and on the presence or absence of vocalizations. As we could show in a previous study,8 the RBDSS is a reliable and easy-touse tool for assessing motor events during REM sleep on an event-to-event basis while evaluating standard vPSG with good to excellent inter-rater reliability. With the study presented here we sought to describe the phenomenology of RBD in PD using the RBDSS and thus underline the scale’s efficacy in clinical practice.

PATIENTS AND METHODS Patients Inclusion criteria Over a 5-month period all consecutive PD patients suspected of RBD by history of patients or bed partners were included in the study. Diagnosis of PD had to be established according to UK Brain Bank criteria. vPSG was performed as part of a clinical work-up to correctly diagnose and treat their abnormal nocturnal behaviors, reported either by the patients or by the bed partner/ caregiver. All patients gave written informed consent for the evaluation of their clinical data. All patients signed additional consent forms to agree with the use of their nighttime video recordings for scientific and medical educational purposes.

Exclusion criteria Patients with acute psychotic symptoms during wakefulness, patients with severe dementia [Mini Mental State Examination (MMSE) ⱕ 10] as well as patients unable to cooperate in the sleep laboratory had to be excluded from vPSG.

Video-supported polysomnography (vPSG) All patients were studied in the sleep laboratory of the Paracelsus-Elena-Klinik for one night.

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Nighttime sleep recordings started immediately after connecting the patient and calibration with lights off at 22.00 h and ended at 06.00 h the next morning. Cardiorespiratory polysomnography (Xltec: Excel Tech, Oakville, Ontario, Canada) was applied including bilateral monopolar central electroencephalography with two channels, electrooculogram, chin and bilateral tibialis anterior surface electromyography, air flow registration, tracheal sound registration by microphone, thoracic and abdominal belts to measure respiratory movements, electrocardiogram, and oximetry. All patients were documented with an infrared video recording synchronized to the polysomnography. A sleep lab technician monitored each recording. Sleep (including sleep stages), periodic limb movements, and apnoeas were scored visually by a trained technician according to standard criteria. All sleep evaluations were reviewed and supervised by board-certified sleep specialists (FSD and CT). Sleep efficiency was defined as total sleep time/time in bed. Quantitative analysis of sleep stages was calculated as a percentage of total sleep time. RBD was diagnosed by second per second review in time-synchronized video analysis of all REM episodes by experienced raters (FSD & CT) in accordance with electroencephalography, electrooculogram and chin electromyography. RBD was defined as the presence of REM sleep without atonia together with complex movements and/or vocalizations during REM sleep apparently associated with dreaming or dream-enacting behaviors visible in time-synchronized vPSG according to criteria established by Schenck and colleagues9 and the International Classification of Sleep Disorders, second edition.10

REM sleep behavior severity scale (RBDSS) For classifying RBD with the RBDSS motor events in REM were rated on a digital scale from 0 to 3 according to the localization and severity of movements. No visible movement but registration of REM sleep without atonia scored as 0, slight movements restricted to the distal extremities, jerks or facial movements scored as 1, movements involving the proximal extremities, complex and/or violent behaviors scored as 2, and any axial involvement with a possibility of falling out of bed or observed bed falls scored as 3; vocalizations were rated as absent, indicated by “0” or present, indicated by “1” for any sound generated during REM sleep other than respiratory noises. Motor and vocalization scores were

© 2013 The Authors Sleep and Biological Rhythms © 2013 Japanese Society of Sleep Research

RBD severity in Parkinson’s Disease

Table 1 The rapid eye movement (REM) sleep behavior disorder severity scale Motor events 0. = no visible motor activity, REM sleep without atonia (RWA) present Only definition criteria of RWA according to the International Classification of Sleep Disorders are fulfilled, no other phasic muscle activity in the limbs or face is visible or obvious on recording 1. = distal or short movements Isolated, single hand or foot movements or facial jerks visible, restricted to the distal extremities and/or face 2. = proximal movements Single movements or series of movements including proximal extremities, no change of position 3. = axial movements Movements with axial involvement and/or change of body position, falls

Vocalizations .0 = no vocalization Snoring with some sound may be present and should be differentiated from REM-associated vocalization .1 = all sleep-associated sounds other than respiratory noises Talking, shouting, murmuring, laughing, or screaming, either tonic or phasic, are present during at least one REM episode

separated by a full stop. The final RBD severity score was defined by the highest scoring given during second-bysecond video review of all REM epochs during the vPSG night. Table 1 shows the complete RBDSS.

RESULTS During the 5-month period, altogether 75 PD patients were investigated in the sleep laboratory to either confirm or refute the diagnosis of RBD. Patients showed a mean age of 66 ⫾ 9 years, mean disease duration was 7.5 ⫾ 5.3 years, mean Hoehn & Yahr stage was determined at 2.7 ⫾ 1. Sleep parameters are shown in Table 2. Fifty-six PD patients (75%) were identified with RBD in vPSG. Classification of RBD severity with the RBDSS identified four patients with only vocalizations

as “0.1”, eight patients with only small nonviolent movements of the distal extremities or facial jerks as in “1.0”, six patients with minor movements and vocalizations as in “1.1”, 10 patients with more forceful movements of the proximal extremities as in “2.0”, 11 patients with movements involving the proximal extremities with additional vocalizations as in “2.1”, five patients showing axial involvement as in “3.0”, and 12 patients with axial movements and vocalizations as in “3.1”. Table 3 compiles RBDSS scorings of all 56 PD patients identified with RBD during vPSG.

DISCUSSION Using the RBDSS we could demonstrate the clinical variety of RBD in PD patients: 32% of PD patients identified with RBD in this study showed only mild, per se nonviolent, and unspectacular manifestations of dreamenacting behaviors in REM sleep that would probably elude a questionnaire-based analysis. This may account for the previously demonstrated poor sensitivity of clinical interviews for identifying RBD in PD patients.11 Movements involving the trunk and changes of body position, bearing the risk of bed falls and readily fulfilling the criteria of violent, harmful behaviors, were seen in only 30% of our RBD-affected PD patients. Thirtyeight percent of the patients showed proximal limb movements open to interpretation concerning their potential violence and harmfulness. These findings are in contrast to those in idiopathic RBD, where violent behaviors are apparently among those observed most frequently,12 although no epidemiological data are available for mild RBD within this population. However, these observations may well be biased as the complaint of violent behaviors during sleep indicates vPSG in these otherwise healthy individuals. More than half (59%) of the PD patients identified with RBD in this study showed vocalizations. Interestingly, the occurrence of vocalizations increased with RBD severity and was the highest (71%) in the group of patients showing axial involvement in their dream enactment. Only 7% of the PD patients with RBD demonstrated sounds other than respiratory noises as the sole manifestation of dream enactment throughout the night. In accordance to previous findings13 speech was unintelligible most of the time whereas motor control was remarkably restored during the RBD episodes recorded. Whether this points to different sources of motor disinhibition during REM sleep and how dream content possibly influences the manifestations of RBD needs to be clarified by further studies.

© 2013 The Authors Sleep and Biological Rhythms © 2013 Japanese Society of Sleep Research

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Table 2 Sleep parameters of 75 Parkinson’s disease patients clinically suspected of rapid eye movement (REM) sleep behavior disorder (according to interview with patients and/or bedpartner) Sleep efficiency 64 ⫾ 18% TIB

Sleep latency

Sleep stage 1

Sleep stage 2

Sleep stage 3 & 4

Sleep stage REM

Awakenings

PLMS index

RBD

20 ⫾ 18 min

81 ⫾ 38% TST

46 ⫾ 13 % TST

8 ⫾ 9% TST

17 ⫾ 10% TST

29 ⫾ 15

37 ⫾ 55

n = 56 (75%)

PLMS, periodic leg movements in sleep; RBD, rapid eye movement sleep behavior disorder; TIB, time in bed; TST, total sleep time.

Table 3 Rapid eye movement (REM) sleep behavior severity scale (RBDSS) scorings of 56 Parkinson’s disease patients identified with REM sleep behavior disorder in video-supported polysomnography RBDSS 0.1 n=4

RBDSS 1.0

RBDSS 1.1

RBDSS 2.0

RBDSS 2.1

RBDSS 3.0

RBDSS 3.1

n=8

n=6

n = 10

n = 11

n=5

n = 12

The frequency in this relatively small cohort of PD patients was remarkably high with 75%, significantly exceeding the frequency of 46% found in a larger cohort of unspecifically sleep disturbed PD patients.1 This however is determined by a selection bias in this study that primarily aimed at describing the clinical phenomenology of RBD in PD. In this cohort vPSG was indicated by reports of abnormal nocturnal behaviors strongly suggestive of RBD. This may also have influenced the observed level of RBD severity seen here, which may be markedly lower in an unselected group of PD patients. The main limitation to this study is the fact that patients were investigated in the sleep laboratory for only one night. As we have shown in a previous study,8 RBD manifestation and severity shows a considerable intra-individual night-to-night variability. So patients may possibly exhibit a different RBD phenomenology when investigated for several nights. However, we could demonstrate the feasability and applicability of the RBDSS for characterizing RBD in the individual patient. This clinical tool may allow an estimate of potentially violent behaviors and identify those PD patients at risk of harming themselves or their bed partners during the night, calling for sleep hygiene advice and possibly pharmacological treatment. Additionally this scale may facilitate comparative studies on RBD and its pharmacotherapy.

Ellen Trautmann reports no disclosures. Brit Mollenhauer has received lecture fees from Orion Pharma and GlaxoSmithKline, holds or has pending patents re: method of differentially diagnosing dementias; Novel ELISA-based quantification of alpha-synclein proteins in cerebrospinal fluid and peripheral blood products unsing 384-well plates; and Micro RNA expression profilino of cerebrospinal fluid. She serves as consultant for Bayer Schering Pharma AG, and receives research support from TEVA Pharma, Desitin, Boehringer Ingelheim, GE Healthcare, the Michael J. Fox Foundation, the American Parkinson’s Diesease Association and the Stifterverband für die Deutsche Wissenschaft (Dr. Werner Jackstädt Stipendium). Claudia Trenkwalder serves on scientific boards for Boehringer Ingelheim, Cephalon, UCB, Novartis, Munidpharm and Solvay. She has received speaker honoraria from Boehringer Ingelheim, Cephalon, UCB, Novartis, Pfizer and GlaxoSmithKline. She receives research support from TEVA Pharma.

CONFLICT OF INTEREST None of the authors report any conflict of interest with the study presented in this paper.

REFERENCES FINANCIAL DISCLOSURES Friederike Sixel-Döring has received educational lecture fees and honoraria from Boehringer Ingelheim, Cephalon, Medtronic, Orion Pharma, Roche Pharma, Schwarz Pharma. She serves on an advisory board for Orion Pharma.

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1 Sixel-Döring F, Trautmann E, Mollenhauer B, Trenkwalder C. Associated factors for REM sleep behavior disorder in Parkinson disease. Neurology 2011; 77: 1048–54. 2 Consens FB, Chervin RD, Koeppe RA et al. Validation of a polysomnographic score for REM sleep behavior disorder. Sleep 2005; 28: 993–7.

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