The rapid-eye-movement sleep behavior disorder in Chinese-Taiwanese patients

Authors

  • Feng-Cheng Lin md ,

    1. Department of Neurology, Kaohsiung Medical University Hospital and
    2. Department of Neurology, Pingtung Hospital, Pingtung, Taiwan
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  • Chiou-Lian Lai md, phd,

    1. Department of Neurology, Kaohsiung Medical University Hospital and
    2. Department of Master's Program in Neurology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung and
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  • Poyin Huang md ,

    1. Department of Neurology, Kaohsiung Medical University Hospital and
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  • Ching-Kuan Liu md, phd,

    1. Department of Neurology, Kaohsiung Medical University Hospital and
    2. Department of Master's Program in Neurology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung and
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  • Chung-Yao Hsu md, phd

    Corresponding author
    1. Department of Neurology, Kaohsiung Medical University Hospital and
    2. Department of Master's Program in Neurology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung and
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  • Disclosure Statement: No significant financial interest/other relationship to disclose.

*Chung-Yao Hsu, MD, PhD, Department of Neurology, Kaohsiung Medical University Hospital, No.100, Tzyou 1st Road, Kaohsiung City 80754, Taiwan. Email: cyhsu@kmu.edu.tw

Abstract

Aims:  While the features of rapid-eye-movement sleep behavior disorder (RBD) have been reported in Caucasian patients, the characteristics of Chinese-Taiwanese patients with RBD have never been examined.

Methods:  Subjects were retrospectively recruited between April 2005 and February 2008 from the neurological clinic and sleep laboratory in the Department of Neurology of Kaohsiung Medical University Hospital. A total of 70 consecutive subjects fulfilling the criteria for RBD were recruited.

Results:  The records of standard overnight polysomnography in patients with RBD were analyzed retrospectively. Twenty-five (35.7%) of the patients were female; the mean age of diagnosis was 67 years and the mean age of symptom onset was 60 years. Among patients with idiopathic RBD, there were 28 men (61%) and 18 women (39%). Nocturnal wandering in the bedroom was reported in 11 cases and out of the bedroom in seven cases. Nineteen patients (27.1%) had accidental falling from bed and 27 patients (38.6%) had sleep-related injury that resulted in ecchymosis and laceration of the head, face or limbs.

Conclusions:  We found that some features in Chinese-Taiwanese patients with RBD were different from Caucasian patients, such as a greater female ratio, lower injury episodes during sleep and more sleep wandering.

RAPID EYE MOVEMENT (REM) sleep behavior disorder (RBD) in humans, which was formally identified in 1986,1 is a parasomnia characterized by loss of normal voluntary muscle tone during REM sleep, usually associated with vivid dreams. 2–4 RBD is either idiopathic or symptomatic. Symptomatic RBD is usually associated with neurodegenerative diseases 5,6, including Parkinson's disease (PD),7,8 dementia with Lewy bodies (DLB),9–11 spinocerebellar ataxia and multiple system atrophy.12,13 Other causes of symptomatic RBD include narcolepsy, cerebrovascular disease, brain tumor, demyelinating disease, alcoholism and drugs.14

The major characteristics of Caucasian subjects with RBD are old age, male predominance, high prevalence of sleep-related injury, and periodic limb movements during sleep (PLMS).4,15 However, there have only been two original papers dealing with RBD in Chinese patients.16,17 Here we present the demographic, clinical features and polysomnographic study of RBD in Chinese-Taiwanese patients.

METHODS

Subjects

Subjects were retrospectively recruited between April 2005 and February 2008 from the neurological clinic and sleep laboratory in the Department of Neurology of Kaohsiung Medical University Hospital, which is the largest university-affiliated teaching hospital in Southern Taiwan. During this period 1343 patients (male to female ratio was 1.29) were referred to receive polysomnography (PSG). Patients with abnormal movement at sleep were interviewed by neurologists in clinics. They were also encouraged to fill in sleep questionnaires, including the Epworth Sleepiness Scale (ESS), and the Pittsburgh Sleep Quality Index (PSQI). It was arranged for subjects who were suspected of having nocturnal seizure to receive routine electroencephalography (EEG) or video-EEG monitoring and for those who were suspected of having stroke, space-occupying lesions or neurodegenerative diseases to receive brain imaging study (computerized tomography [CT] or magnetic resonance imaging [MRI]).

Overnight polysomnography

Overnight PSG consists of standard EEG (C3-A1, C4-A2), electrooculography (EOG), submental surface electromyography (EMG), right and left anterior tibialis surface EMG, electrocardiography (ECG), nasal thermometer, thoracic and abdominal respiratory movements, and pulse oximetry. Sleep stages were scored according to the standard criteria.18

Diagnosis of RBD and other sleep disorders

Patients were diagnosed with RBD according to the International Classification of Sleep Disorders (ICSD-II, 2005) criteria.19 REM sleep without muscle atonia (RWA) was defined as: (i) sustained muscle activity (tonic activity) in REM sleep (an epoch of REM sleep with at least 50% of the duration of the epoch having a chin EMG amplitude greater than the minimum amplitude than in non-REM sleep); or (ii) excessive transient muscle activity (phasic phase) in REM sleep: an epoch of REM sleep divided into 10 sequential 3-s mini-epochs (at least five [50%]) of the mini-epochs contain bursts of transient muscle activity with 0.1–5.0 s in duration and at least 4 times as high in amplitude as the background EMG activity). The percentage of RWA was also scored and the RWA was observed in all RBD cases.

The medical records of patients with suspicion of RBD were clearly reviewed. Symptomatic RBD was defined as occurrence of RBD that was attributed to certain neurological disorders, or medications. The periodic limb movement index (PLMI) was defined as the number of periodic leg movements per hour of sleep. PLMS was defined as PLMI greater than 15 per hour. The apnea–hypopnea index (AHI) was defined as the number of apneas and hypopneas per hour of sleep. Sleep apnea was defined as AHI greater than 10. Obstructive sleep apnea (OSA) was diagnosed when more than 85% of respiratory events were obstructive. To exclude pseudo-RBD caused by sleep apnea, PSG of patients with sleep apnea was examined to reassure the presence of augmented EMG activity or dream-enacting behavior during REM sleep was not exclusively the result of a respiratory event.

RESULTS

In total, 70 consecutive subjects (45 men and 25 women) fulfilling the criteria for RBD were recruited. Their demographic and clinical characteristics are presented in Table 1. Twenty-five (35.7%) of them were female. The mean age of diagnosis was 66 years and the mean age of symptom onset was 60 years. Patients with RBD were divided to two groups: idiopathic (46 cases) and symptomatic RBD (24 cases). There were 28 men (61%) and 18 women (39%) in patients with idiopathic RBD and 17 men (70.8%) and seven women (29.2%) with symptomatic RBD. The etiology of symptomatic RBD included Parkinson's diseases (11 cases), dementia with Lewy bodies (one case), small vessel disease with vascular parkinsonism (one case), medication-related (four cases), old cerebrovascular disease (five cases), narcolepsy (one case) and viral encephalitis (one case). Among the patients who had undergone brain imaging (36 cases), 24 cases were diagnosed as symptomatic RBD.

Table 1.  Demographic details and numbers or percentages of patients showing various clinical features of rapid-eye-movement sleep behavior disorder (RBD)
Gender (n = 70)45 (64.3%) male; 25 (35.7%) female
  1. EDS, excessive daytime sleepiness; ESS, Epworth Sleepiness Scale; OSA, obstructive sleep apnea; PLMI, periodic limb movement index; PLMS, periodic limb movements during sleep; PSQI, Pittsburgh Sleep Quality Index; RDI, Respiratory Distress Index.

Mean age at onset (years) (n = 42)60 (range 20–75)
Mean age at diagnosis (years) (n = 70)66 (range 36–84)
Injury during sleep (n = 70)27 (38.6%)
Violent behavior during sleep (n = 70)20 (28.5%)
Sleep talking/shouting (n = 70)30 (42.9%)
Falling from the bed during sleep (n = 70)19 (27.1%)
Nocturnal wandering (n = 70)11 (15.7%)
Wandering out of the bedroom (n = 70)7 (10%)
EDS (ESS > 10) (n = 43)16 (37.2%)
Poor sleep quality (PSQI > 5) (n = 21)17 (80.9%)
PLMS (PLMI > 15/h) (n = 70)40 (57.1%)
OSA (RDI > 10/h) (n = 70)17 (24.3%)
Mixed type sleep apnea (n = 70)5 (7.1%)
Symptomatic RBD (n = 24) 
Parkinsonism13 (54.2%)
 Parkinson's disease11
 Diffuse Lewy body disease1
 Vascular parkinsonism1
Old cerebrovascular disease5 (20.8%)
Medication-related4 (16.7%)
Narcolepsy1 (4.2%)
Prior encephalitis1 (4.2%)

The most common nocturnal behaviors were waving arms and kicking legs (47.1%). The behavior was not confined to bed in 29 patients (41.4%). Among them, wandering in the bedroom was reported in 11 cases and out of the bedroom in seven cases. Nineteen patients (27.1%) had accidental falling from bed and 27 patients (38.6%) had sleep-related injury that resulted in ecchymosis and laceration of the head, face or limbs. One case suffered from clavicle fracture during an episode of RBD. Patients had concomitant sleep disorders in terms of PLMS in 40 (57.1%), OSA in 17 (24.2%), and mixed-type sleep apnea in five (7.1%).

The polysomnographic and imaging findings are presented in Table 2. The mean sleep latency was 12.7 min and the mean REM latency was 114.8 min. The mean percentage of REM sleep was 15.8% and the mean percentage of slow-wave sleep was 14.6%. Among patients older than 58 years, 17 patients (32%) had increased slow-wave sleep (>15%). Comparing PSG findings in idiopathic and symptomatic RBD, there is no significant difference in sleep latency, REM latency, sleep efficiency, stage 2, 3, 4 and REM sleep. Brain imaging obtained in 36 patients (CT in 28 cases and MRI in eight cases) resulted in non-significant findings including brain atrophy (24 cases), lacunar infarcts in the lentiform nucleus (four cases), and frontoparietal subdural hygromas (two cases). EEG obtained in 30 cases including 11 patients who had extraordinary behavior of nocturnal wandering did not show any epileptiform discharge. Forty-four patients without sleep apnea (48 cases) were treated by clonazepam with a dosage of 0.5 to 2 mg per day. Their nocturnal behaviors were either partially or completely controlled except three cases that were refractory to clonazepam therapy. One patient was successfully treated by quetiapine 25 mg per day.

Table 2.  Laboratory findings of all patients (n = 70)
Polysomnography 
  1. REM, rapid eye movement; RWA, REM sleep without muscle atonia.

Mean Sleep latency12.7 ± 14.5 min
Mean of REM latency114.8 ± 82.8 min
Mean Sleep efficiency77.5 ± 14.8%
Mean % of Stage I23.5 ± 15.4%
Mean % of Stage II45.7 ± 13.5%
Mean % of Stage III9.8 ± 8.3%
Mean % of Stage IV4.6 ± 6.6%
Mean % of REM sleep15.8 ± 8.7%
Mean % of RWA40.7 ± 25.5%
Patients older than 58 years old with >15% slow wave sleep (n = 53)17 (32.0%) cases
Brain imaging (n = 36)Number of patients
Normal imaging10
Non-specific cortical atrophy14
Frontal cortical atrophy2
Parietal cortical atrophy1
Bilateral frontoparietal subdural hygromas2
Lacunar infarction6
Inflammation over bilateral medial temporal lobe1

DISCUSSION

Our study is the first large-scaled polysomnographic study focused on RBD in Chinese-Taiwanese patients. An epidemiological study in Hong Kong reported sleep-related injury in the elderly.16 The authors interviewed the elderly aged 70 years or above and estimated that the prevalence of RBD was about 0.38% in the Chinese population. Of the 1034 elderly subjects, 0.77% (eight cases) reported a history of sleep-related injury and four of them were confirmed to have RBD by PSG. Another case series study in China had similar findings, although the case number was small (six cases with RBD).17

Generally RBD is thought to be male predominant. Schenck et al. reported that 87.5% of 96 patients with RBD were male, and Olsen et al. reported that 87% of 93 patients with RBD were male.4,15 In our study, 25 (35.7%) of the total cases of RBD and 18 (39.1%) cases of idiopathic RBD were female. Compared with Caucasian patients, Chinese-Taiwanese patients with RBD have a higher female to male ratio (35.7% vs 12–13%). Our findings may support previous studies of Chinese patients with RBD that found that one in four subjects was female (25%) in Hong Kong and two in six subjects were female in China (33%), although their sample sizes were too small to make a conclusion.16,17 The gender difference between Caucasian and Chinese patients with RBD may be due to cultural and genetic factors. One possible reason related to cultural factors is that traditionally older women usually live with family in Taiwan. Even if the symptoms of RBD are mild, the patient's family can notice the abnormal nocturnal behavior and seek medical assistance. This is supported by our finding that there was less sleep-related injury in our patients (38.6%) than that in previous reports (66–79%).

Another reason of gender difference may be related to genetic factor. In Caucasian patients with RBD reported by Schenck et al.,20 25 men underwent human leukocyte antigen (HLA) class II antigen typing and 84% of them (n = 21) were DQwl positive. DQB1*0501 (n = 9) and DQB1*0602 (n = 7) were the most common phenotypes. The DQwl positive rate (84%) in men with RBD was significantly higher (P = 0.015) than that (56%) found in a local white comparison group (n = 66). This finding suggests that HLA DQB1*05 and DQB1*06 are associated with RBD. Therefore further genetic study is worth performing in Chinese-Taiwanese patients with RBD.

Nocturnal wandering is another interesting feature in RBD. Silber et al. showed that 10 of 93 patients (11%) with RBD exhibited nocturnal wandering but there was no information about how far they went.4 In our report, there were 11 (15.7%) patients with nocturnal wandering. The prevalence is similar to that in Caucasian patients. However, seven of our 11 patients presented with wandering out of their bedroom: one danced in the kitchen; one went to her son's room; one went to the elevator; one went to the refrigerator. None of the RBD patients with nocturnal wandering had a history of sleep walking or epilepsy and their EEG did not show any epileptiform discharge to support nocturnal seizure. Their PSG showed increased EMG activity over tibialis during REM sleep, which is different to other parasomnias, such as sleep walking. This is an interesting point that Chinese-Taiwanese patients with RBD could have more complicated behaviors that have not been reported in Caucasian RBD patients. Further dream content analysis in Chinese-Taiwanese patients with RBD will help to understand whether these behaviors are related to the Chinese tradition that the elderly are still living with their children and dealing with house affairs.

Another typical feature of RBD is sleep-related injury. Nocturnal motor behaviors, such as screaming, punching, grasping and kicking, are potentially harmful to themselves or bed partners and can even result in subdural hematomas.21 One epidemiological study revealed that RBD accounted for 36% of sleep-related injury.22 Sleep-related injury was reported frequently in RBD according to previous studies, raging from 66–79%.4,15 The prevalence of sleep-related injury in our study was 38.6% (27 of 70) which is about half of that in Caucasian patients. Early detection of RBD in the family and more female patients who may have less aggressive behavior are two possible reasons for less sleep-related injury in Chinese-Taiwanese patients.

Patients with severe OSA may have nocturnal behavior mimicking RBD.23 Iranzo presented 16 subjects with severe OSA who reported dream-enacting behaviors resembling RBD, but those patients had no increased REM sleep tonic and phasic submental and bilateral anterior tibialis EMG activity. The mean AHI of these patients was 67.5 ± 18.7 (range, 41–105) with a mean AHI during REM sleep of 59.6 ± 18.0 (range, 32–98). PSG demonstrated OSA-induced abnormal motor and vocal behaviors. Therefore they suggested that in subjects with OSA, ‘pseudo-RBD’ is only seen in subjects with high AHI and severe oxyhemoglobin desaturations. However, in our patients, only three patients with obstructive sleep apnea had AHI over 30 (one for 73.11, one for 40.43, and the other for 31.7). The PSG of our patients with concomitant RBD and sleep apnea showed augmentation of EMG activity during REM sleep which was not induced by sleep apnea. Thus OSA should not be the cause of RBD in these patients.

PLMS is common in RBD, being reported in about 50–70% of patients.4,15,24 The prevalence of PLMS in our patients with RBD was 57.1% (40/70), which was similar to that in previous reports. An increased percentage of slow-wave sleep (SWS) and delta power during non-REM sleep in idiopathic RBD patients, compared with control subjects, has been observed in several studies. In Silber's series, 33% of patients >58 years had >15% slow-wave sleep.4 In Schenck's series, 80% of patients >58 years had >15% slow wave sleep.15 Our study shows that 32% (17) of patients >58 years had >15% slow-wave sleep. The mean percentage of slow-wave sleep in these 17 cases was 29.7% (range 16.2–54%). Nigrostriatal dopaminergic impairment in RBD patients may be the underlying mechanism of increased SWS and may be associated with neurodegenerative disorders.25

In conclusion, our study shows that the demographic, clinical and laboratory features in Chinese-Taiwanese patients with RBD are similar to those in Caucasian patients but there are some different points which need to be high-lighted, such as a higher female to male ratio, a lower rate of sleep-related injury, and a higher rate of nocturnal wandering out of the bedroom. Cultural or genetic difference may play a role and further studies are necessary to clarify these issues.

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