Introduction
Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia, characterized by skeletal muscle atonia during REM sleep with dream enactment behavior. The prevalence of RBD is estimated to be 0.5%.1 RBD is characterized by idiopathic or secondary to neurodegenerative disease, specifically synucleinopathies such as Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy.2,3 It can also cause by medications use such as fluoxetine, venlafaxine and clomipramine.4,5 The term idiopathic RBD is used for RBD with no accompanying neurological disease, but this may need years of observation to diagnose. The onset of RBD in neurodegenerative patients usually precedes the onset of the motor or cognitive symptoms by several years. This indicates patients diagnosed with idiopathic RBD have risk of developing a neurodegenerative disease.6,7 The description of RBD in relation to neurodegenerative disease has been commonly reported in elderly male patients.6,8,9 However it is now recognized as a disorder of all ages and both sexes. There are only few studies focused on of young age RBD, and association with narcolepsy and medication use have been reported.10 We investigate the differences between young and elderly idiopathic RBD in polysomnography (PSG) findings, and find clinical features of young age RBD.
Methods
Patient selection
This is a retrospective descriptive review study of RBD patients visiting single sleep center from August, 2003 to August, 2014. Patients who visited the sleep center with history of dream enacting behavior; abnormal vocalizations, abnormal motor behavior and altered dream mentation, were recruited. These patients were further evaluated with overnight PSG. Patients were eligible for inclusion in this study if they met the diagnosis criteria for RBD according to the International Classification of the Sleep Disorder-II criteria.11 Medical records were reviewed including use of sedative medication, and major systemic, neurologic, and psychiatric disorders. Patients were grouped by age, and young age RBD was defined as age less than 40 years, and elder RBD as age 40 years or older.
Polysomnography
All subjects were performed overnight PSG. PSG was conducted using a six channel electroencephalogram, a two channel electrooculogram, and minimum of four channel electromyogram (EMG) for chin, intercostals muscles, right and left anterior tibialis, sleep stages, arousals, apneas/hypopneas, and REM sleep without atonia analyzed manually according to the American academy of sleep medicine criteria.12 PSG was conducted by PSG technicians, and reviewed by sleep specialists. For sustained tonic muscle activity in REM sleep was defined as an epoch of REM sleep with at least 50% of the duration of the epoch having chin EMG amplitude greater than the minimum amplitude than in NREM. Excessive transient muscle activity in REM sleep was defined as 50% of an epoch of REM contains bursts of transient muscle activity. Excessive transient muscle activity burst are 0.1–5.0 seconds in duration and at least 4 times as high in amplitude as the background EMG activity.
Statistical analysis
Continuous data are expressed as means (±standard deviations), and categorical data as frequencies and percentages. To test for trends in baseline characteristics, Pearson’s chi-square test was used to analyze categorical variables and the Mann-Whitney test was used for continuous variables. Statistical significance was accepted for two-tailed p values of <0.05. The analysis was performed using Statistical Package for the Social Sciences (SPSS) 21.0 (SPSS Inc., Chicago, IL, USA).
Results
The total of 149 patients (young age RBD: n=22, 14.8%, elderly RBD: n=127, 85.2%) were finally enrolled. Mean age upon diagnosis were 24.10±7.42 years (male: n=17, 77.3%) for young age RBD, and 65.40±8.73 years (male: n=82, 64.6%)for elderly RBD patients.
Polysomnography results reveled young age RBD patients had longer total sleep time [TST (min): 416.16±44.19, 345.73±78.03, p<0.001], higher sleep efficiency [SE (%): 87.60± 6.90, 76.85±14.07, p<0.001], less arousal index [(/hr): 17.85± 20.81, 23.14±12.15, p<0.001]. Sleep architecture reveled less N1 sleep stage [N1 (%): 15.48±16.36, 23.72±12.86, p<0.001], and higher N3 sleep stage [N3 (%): 12.14±10.02, 3.57±6.21, p<0.001]. N2 and REM sleep did not differ between groups (Table 1).
Sleep indicators for respiration were more severe in elderly group; apnea-hypopnea index [AHI (/hr): 8.81±26.69, 12.02± 16.40, p=0.002], respiratory distress index [RDI (/hr): 11.08± 26.90, 15.31±17.09, p=0.003]. And periodic limb movement index (PLMI), and movement arousal index (MAI) were also more remarkable in elderly group [PLMI (/hr): 2.31±6.63, 33.61±49.24, p<0.001, and MAI (/hr): 0.51±0.85, 2.80±4.17, p=0.001].
In young age RBD patients, dream content by history were not differ from previous reports on RBD, which included being chased, protecting oneself, having an argument, and shouting. Five young patients reported prior history of sleep walking and talking, three were also diagnosed with narcolepsy. While one patient was treated with high dose steroid for rheumatologic disorder, none of the patients were on medication, such as serotonin selective reuptake inhibitor.
Discussion
Polysomnography findings indicated young RBD have longer sleep time, have normal sleep latency, normal SE and less arousals indicating sleep better and longer.13 Elderly RBD have mean TST of 5.7 hr, with poor SE and frequent arousals. This in part, can be explained by high AHI, RDI and MAI in elderly patients. And normal aging have decrease in TST and SE.14 Even after excluding age dependent sleep architecture changes, percentage of N1 sleep stage are increased in young and elderly group, N3 sleep stage are decreased in elderly group. Such changes in sleep architecture have been reported in elderly, but N1 sleep stage changes in young RBD have never been reported.13 Aside from increase in N1 sleep stage, PSG findings were not significantly different from normal population.14
Rapid eye movement sleep behavior disorder has been characterized to have major predisposing factors of male sex, age 50 years or older, and an underlying neurological disorder, or medication use.11 Previous studies reported idiopathic RBD patients may eventually be diagnosed with a neurological disorder such as Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. The risk increase to about 40.6–75.7% in ten years and 90.9% in 14 years.15-17 These studies indicate >50% of high conversion rate of neurodegenerative disorders in idiopathic RBD. This implies that RBD as a premotor symptom of neurological disorder may help diagnose and plan for treatment before disability develops. However reported studies have enrolled patients over 50 years of age, and idiopathic RBD in young age is largely unknown.
Rapid eye movement sleep behavior disorder in young age population is extremely rare. Limited data have been published, and there is no reports on whether young age RBD and its risk of developing neurodegenerative disorder as in elderly RBD. It’s relation to neurodevelopmental disorder and use of psychiatric medications has been suggested. There is one study with 15 young age RBD patients who were 3 to 17 years old at diagnosis with mean age at 9.5 years.10 The male predominance was reported as 64.6% (11/15), which correlates well with our study of 77.3% (17/22). High prevalence of RBD (5 of 11) has been reported in autism children.18 And comorbid anxiety, attention deficit hyperactivity disorder, inattentiveness, and developmental delay have been reported.10 Further on narcolepsy in young age RBD have been frequently reported as a case reports, and there were three patients in our study who also had narcolepsy along with RBD.10,19,20 While RBD in young age population have been reported in relation to psychiatric medication, our patients had no history of medication use.10
Further studies need more patient enrollment and long term follow up in young age RBD to determine whether it is related to neurodevelopmental disorder, and a premotor stage of neurodegenerative disorders.