Clinical and video-polysomnographic characterization of restless sleep disorder in adult patients

Abstract

Adults with restless sleep disorder (RSD) have never been studied clinically and polysomnographically. This study aimed to describe the clinical manifestation, duration, and distribution of sleep-related movements in adult patients with restless sleep disorder. Patients who had performed VPSG from Jan 2021 to Jan 2022 and met the diagnosis criteria of RSD were enrolled in the study. Patients’ bed partners were also interviewed or telephoned in identifying this disorder. Scoring of movements during sleep was according to the diagnosis criteria of RSD and scoring of large muscle group movements during sleep proposed by the International RLS Study Group in 2020 and 2021, respectively. The clinical manifestation, the distribution of sleep stage as well as the types and duration of the movements were carefully recorded and analyzed. We included ten patients in the study with a mean age of 27.6 years (range 22–38). There was a male prevalence in adults with RSD. The study highlighted the findings from video-polysomnography, which indicated frequent sleep-related movements occurring throughout the Night. These movements were most prominent during N1 and N2 sleep stage, followed by REM sleep, while fewer movements were observed during N3 sleep. Adults with RSD experienced significant daytime functioning impairments, including non-refreshing sleep, daytime fatigue/sleepiness, and mood disturbance. Two of the patients in the study were diagnosed with anxiety and depression, further underscoring the impact of RSD on mental health. Adult patients also suffer from severe RSD, and the RSD that originates in childhood tends to persist into adulthood. In these cases, longer duration of the disease and poor sleep quality may be associated with an increased risk of developing psychiatric comorbidities. Our cases represent an objectively documented type of RSD in younger adult patients.

Supplementary Information

The online version contains supplementary material available at 10.1007/s41105-024-00524-1.

Introduction

In recent years, restless sleep disorder (RSD) has been proposed as a new diagnostic category for children who have sleep complaints that do not meet the criteria for any other sleep disorder [1]. The diagnostic criteria for RSD include eight essentials, and it is known to cause significant functional impairment [1]. In recent years, we have evaluated some adult patients with the main complaint of restless sleep, which presented as sleep-related movements persisted throughout the night that meets the criteria for RSD. However, the existence and characteristics of RSD in adult patients have been rarely reported, and it is unknown whether RSD that begins in childhood persists into adulthood. To the best of our knowledge, assessing the clinical and VPSG characterizations of RSD in adult patients has never been reported. For these reasons, the present study aimed to characterize the clinical manifestations of RSD in adult patients by utilizing video-polysomnography (VPSG).

Methods

Participants

We retrospectively reviewed the VPSG of 868 patients who visited our sleep center for sleep problems from Jan 2021 to Jan 2022, and 194 patients were presented with a movements index > 5. Among them, 184 were excluded from the study according to the ICSD-3, with 94 patients presented with typical periodic limb movements during sleep, 8 with restless legs syndrome, 42 with obstructive sleep apnea, 24 with narcolepsy, 1 with propriospinal myoclonus, 15 with neurodegenerative disease. Ten patients met the diagnostic criteria for RSD (Fig 1). The comprehensive past medical history and sleep condition were recorded and analyzed.

Fig. 1.

Flowchart of the study

VPSG recordings

Full-night VPSG data were collected using the Natus SleepWorks system, which included electroencephalography (F3, F4, C3, C4, O1, and O2), electrooculography, and electromyography of the mentalis, bilateral anterior tibialis, trapezius, and sternocleidomastoid muscles. Thoracic and abdominal movements, oxyhemoglobin saturation, oral and nasal airflow, and electrocardiography were recorded. Scoring of sleep stages, respiratory events, arousals, and limb movements was done by a registered polysomnographic technologist and validated by a board-certified sleep physician to ensure consensus. Scoring was according to the scoring rules of the American Academy of Sleep Medicine (AASM) guidelines. (AASM Manual for the Scoring of Sleep and Associated Events, Version 2.5) [2]. We obtained sleep stages (including N1, N2, N3, and REM sleep), sleep latency, wakefulness after sleep onset, limb movement counts and index, apnea–hypopnea index, and arousal counts and index via VPSG.

Movement measures

Scoring of movements during sleep was according to consensus diagnostic criteria of RSD [1]. Movements were defined as (1) begin during sleep; (2) visible on video; (3) last for at least 1 s; (4) involve the whole body, arms, legs, or head; and (5) are NOT associated with respiratory events or seizure activity, or meet the criteria for periodic limb movements of sleep (PLMS), sleep-related rhythmic movements, hypnagogic foot tremor, alternating leg muscle activation (ALMA), motor tics during sleep, or REM sleep behavior disorder. Scoring of large muscle movements was according to the most recent scoring rules: scoring of large muscle group movements during sleep proposed by the International RLS Study Group in 2021 [3]. The recommendation for large muscle movement duration was 3–45 s for adults. Movement duration shorter than 1 s did not score to avoid twitch or brief muscle spasms.

Data analysis/statistics

We used descriptive statistics to quantify movement counts, type, duration, and time of the movements. The total movement index indicates the sum of the type of movements divided by total sleep time. We analyzed the duration of movements according to the video recordings of PSG. We plotted the distributions of movements using the Origin 2021 software (MicroCal, America).

Ethical permission has been given by the Xijing Hospital Research Ethics Committee. All the participants provided written informed consent before enrollment.

Results

Demographic information and clinical characteristics

We diagnosed ten patients with RSD, and all of them presented with abnormal sleep-related motor behavior persisting at intervals through the night that severely disrupted their sleep as well as their bed partner’s sleep. Adults with RSD have pronounced daytime impairment, and two of ten patients were diagnosed with anxiety and depression. Table 1 details the main clinical characteristics of this case series. There was a male prevalence in adults with RSD. All of them were young patients with a mean age of 27.6 years (range 22–38). For all the subjects, the median disease duration of RSD was 12.3 years (range 1–25). Four patients identified their onset age from childhood as told to them by their parents. The other six patients only vaguely remembered the beginning of the abnormal sleep behaviors from adolescence or adulthood. The abnormal behaviors manifested as various limb movements which occurred almost every night, some of them were vigorous movements, such as body rocking, scratching, kicking and punching, and occasionally associated with vocalizations (talking or shouting). Neuroimaging was negative, and neurological examination was normal for all cases. On admission, patient 2 was already taking oxazepam for having anxiety (45 mg/daily). No family history of other sleep disorders such as parasomnias, RLS, OSA, and RBD was identified in these patients.

Table 1.

Clinical features of the ten adult patients with restless sleep disorders

Patient	Gender/age	Disease durations	Main complaint and significant daytime impairment	Clinical manifestation of sleep-related limb movements	Disruption of bed partner's sleep
1	M/22	12	Sleep-related abnormal movements and vocalization; social function	Two feet rubbing vigorously; wiggling hips associated with limb movements	Yes
2	M/30	4	Sleep-related abnormal movements and vocalization; daytime sleepiness; non-refreshing sleep; anxiety	Various limb movements involving body and head	Yes
3	M/24	2	Sleep-related abnormal movements and vocalization; daytime fatigue/sleepiness; social function	Vigorous lower limb movements (resembling kicking)	Yes
4	M/23	1	Sleep-related abnormal movements; non-refreshing sleep; social function	Jerky upper limb movements followed with motor behaviors	Yes
5	M/24	23	Sleep-related abnormal movements; daytime fatigue/sleepiness; non-refreshing sleep; mood disturbance; occupational and educational function	Complex motor behaviors (arching/scratching)	Yes
6	M/32	14	Sleep-related abnormal movements; daytime sleepiness; non-refreshing sleep	Complex motor movements involving upper and lower limbs	Yes
7	F/28	18	Sleep-related abnormal movements; non-refreshing sleep; daytime fatigue; depression	Limb movements with complex motor behaviors	Yes
8	F/34	4	Sleep-related abnormal movements; frequent wakefulness during sleep; daytime sleepiness; non-refreshing sleep; dizziness	Complex lower limb movements	Yes
9	M/34	25	Sleep-related abnormal movements and vocalization; insomnia; daytime fatigue/sleepiness	Large and vigorous body movements	Yes
10	M/25	20	Headache; daytime fatigue; non-refreshing sleep; mood disturbance	Various limb movements	Yes

Video-PSG findings

VPSG revealed various motor behaviors during sleep in the10 cases, associated with frequent awakenings/arousals after sleep onset, more N1 sleep, and more frequent shifts to N1 sleep or waking from deeper stages of sleep. Table 2 shows the results of the visual analysis of movements, including the duration of wakefulness after sleep onset, the total sleep-related movement counts and index, as well as the larger muscle movements (LMM), the mean index of movements related arousals, N1 sleep percentage, REM latency, N3 sleep percentage and sleep efficiency. None of them presented with REM sleep without atonia. Significant obstructive sleep apnea was absent except for patients 2 and 6, in whom the results showed occasional obstructive sleep apnea with AHI of 0.5 and 3.8, respectively.

Table 2.

PSG features of RSD-related sleep movements in the ten Patients

Num	Sex/age	Sleep-related movements			ADM (s)	Arousal (counts/index)	Awaking times after sleep (counts/index)	WASO (min)	N1 sleep percentage (%)	REM latency (min)	N3 sleep percentage (%)	Sleep efficiency (%)
		Total	LMM	Index
1	M/22	261	175 (67%)	31.8	5.7	241/33.4	19/2.6	28.5	33.30	86.5	9.60	84.60
2	M/30	227	55 (24%)	27.7	2.3	225/26.0	18/2.2	53.2	14.20	80.5	27.60	93.10
3	M/24	115	44 (38%)	17.4	2	122/14.1	16/1.9	24.5	10.90	67	28.30	93.00
4	M/23	239	186 (78%)	32.5	6	139/17.8	23/3.0	78.3	18.00	144.5	16.20	84.90
5	M/24	384	364 (95%)	52.9	15.1	380/51.1	45/6.2	63.1	54.40	5.5	0.40	88.70
6	M/32	268	212 (79%)	35	6.4	237/30.1	63/8.0	105	39.50	3	18.10	81.60
7	F/28	345	123 (36%)	59.7	3.3	235/35.1	85/12.7	134.5	43.30	470	2.50	70.90
8	F/34	398	288 (72%)	67.8	6.2	370/59.0	55/8.8	132	32.00	228	14.40	73.80
9	M/34	243	111 (46%)	37.1	4.1	132/20.2	22/3.4	149	31.30	126	0.00	71.00
10	M/25	306	276 (90%)	43.7	9.9	263/29.9	17/1.9	39.5	19.20	98	8.30	92.00

PSG: polysomnography; RSD: restless sleep disorder; LMM: larger muscle movement; ADM: average duration of movements; WASO: wakefulness after sleep onset

Movements’ manifestations

Three patients (Patients 1, 6 and 8) rubbed their feet vigorously and rhythmically while wiggling their hips. These movements lasted with a mean duration of 6 s (video 1). Five patients (Patients 2, 3, 7, 9, and 10) showed vigorous limb movements resembling kicking and rocking with a mean duration lasting 2–9.9 s (video 2 and 3) which also induced arousal. Patient4 exhibited two different types of LMM. The first was brief, stereotyped and vigorous upper limbs jerking followed by arousal behavior. The second type consisted of rubbing of the feet, and then followed by lower limbs moving and stretching. Both occurred predominantly in NREM sleep. Patient 5 arched his back and scratched four limbs which frequently induced arousal and awakenings (video 4).

Stage distribution

The total sleep-related movements of the ten cases were most prominent during N1 and N2 sleep stage, followed by REM sleep, while fewer movements were observed during N3 sleep. Specifically, in patients 1, 2, 6 and 9, the abnormal motor behavior occurred at intervals through the night with predominant in N1, N2 and REM sleep, but not N3 (Fig 2A). In patients 3, movements were more in REM sleep than in NREM (Fig 2B). In patients 4 and 5, movements were predominantly in NREM, and seldom in REM sleep (Fig.2C). In patients 7 and 8, movements occurred through the night regardless of NREM or REM sleep (Fig 2D). Stage hypnograms unveiled fragmented sleep with frequent sleep stage transitions, especially in patients with a higher arousal index (> 50) or waking index (> 5). For example, in patient 5 and 9, the N3 sleep was entirely absent, and REM sleep was less due to the frequent stage shift toward N1 sleep and wake. Inpatient 7, the N3 and REM sleep duration lasted around 10 min. The disturbed night sleep resulted in excessive daytime sleepiness and fatigue.

Fig. 2.

Stage hypnogram showing patients has frequent transitions from any sleep stage sleep to wake and N1sleep, and the stage distribution of LMM was highest in N1 and N2, and then REM sleep, while N3 held few of movements

Duration of movements and counts of movement-related arousal or awaking

Movement durations varied in each patient, and LMM among them ranged from 24 to 95%.

Patient 3 had the minimum movement duration lasting for 1 s. The maximum duration lasting for 30 s occurred in patient 5. The minimum and maximum mean duration last for 2 s and 15 s occurred in patients 3 and 5, respectively. Figure 3 shows the duration of the movements. All ten patients with higher movement index over 15 times per hour. Three even presented with a higher index over 50 times per hour.

Fig. 3.

The duration of sleep-related movements in all cases.

The arousal index was higher in our patients ranging from 14 to 59.1 times/hours, and the average percentage of movement-related arousals was 82.1% (range 46.8–95.6%). Some motor behaviors entailed the transitions from sleep to wakefulness. The highest number of waking times following the movement was 85 times in patient 7, who also presented with a longer duration of wakefulness with 134 mines after sleep.

Discussion

Our study has identified a significant number of sleep-related movements in adults with RSD and analyzed the type, length, and night distribution of movements throughout the night. We have demonstrated that adults with RSD frequently experience arousals or awaking during sleep, leading to significant daytime impairment.

We also observed a higher prevalence of RSD in males among our adult patients. This gender ratio is consistent with findings from previous studies involving children [4]. The median disease duration of our patients was approximately 12.3 years (ranging from 1 to 23 years). However, only four patients had precise information about the onset of RSD during childhood, as reported by their parents. The remaining six patients vaguely recollected the onset of abnormal sleep behaviors occurring during adolescence or adulthood. It is possible that these six patients may have also experienced sleep-related movements since childhood, and it is also plausible that RSD can onset in adulthood. Therefore, there may be some inherent bias in the reported disease durations.

The available data using VPSG to evaluate RSD in adults are limited. In our study, we observed a lower prevalence of RSD in adults, with only 10 out of 868 participants (1.15%) exhibiting the disorder. It has been reported that the prevalence of RSD in a clinical sample is approximately 7–8%in children [5]. There are three main reasons that could explain the lower prevalence of RSD in adults in our study. First, our study was conducted at an adult sleep center, where adults often present with sleep difficulties such as OSA, propriospinal myoclonus, and neurodegenerative disease. These conditions may lower the prevalence of RSD at our center. Second, the lack of awareness about RSD among physicians and patients may lead to under-referral of individuals with this disorder to our sleep center. Third, our study also demonstrates that these abnormal sleep motor behaviors seriously interfere with bed partners’ sleep. Although VPSG recording revealed excessive abnormal motor movements, three of our patients were unaware of their behaviors. They came to see the doctor because their bed partner's sleep was disturbed by them. Therefore, restless sleep might underreport in adults. The physician should interview the patient and bed partner for a detailed history of the newly suspected RSD patients.

Furthermore, we observed that adults with RSD had a significantly higher percentage of sleep stage N1 compared to normal young adults. Some patients also exhibited more N1 sleep and less N3 sleep. Frequent and vigorous movements characteristic of RSD often trigger arousal and cause shifts in sleep stages, particularly to N1 or wakefulness. This leads to fragmented sleep and daytime fatigue.

Previous studies reported sleep stage N1 tends to have the highest occurrence of movements, followed by REM, N2, and N3 [6]. Similarly, in our study, we found that RSD-related limb movements were most prevalent during N1 and N2 sleep, and then REM sleep, and least in N3 sleep. This suggests that the motor control associated with RSD varies across different sleep stages.

It is noteworthy that the RSD-related sleep motor behaviors should not be classified as known sleep disorders such as RLS [7], PLMD [2], narcolepsy [8], RBD [9], and nocturnal seizures [10]. RSD-related movements should be differentiated with typical PLMD, which are stereotyped repetitive episodes consisting in extension of the great toe and ankle, and sometimes accompanied by flexion of the knee and hip. PLMD are strongly associated with RLS, which is characterized by the presence of unpleasant or uncomfortable urge to move the legs that occurs during periods of inactivity and is transiently relieved by movement. Our cases denied the presence of unpleasant or uncomfortable feeling in the lower limbs. RSD-related sleep motor behaviors usually involve more muscles, which occur beyond the lower limbs and extend to the upper limbs, head, and torso. In video 3, the movements in the patient presented as vigorously shaking legs and sometimes involving the whole body, mainly occurring in REM sleep, rarely in NREM sleep. This scenario is different from typical PLMD, which commonly occurs in N1 and N2 and rarely in REM. However, not all PLMD are associated by RLS, and some involve muscles other than lower limbs, accompanied by flexion of the knee and hip. Our patients with RSD involving large muscle groups of the whole body might be a severe form of PLMD. Larger sample studies are needed to find out whether there are symptoms overlapping between severe form of PLMD and RSD.

Differentiating RSD from nocturnal seizures is also important. Nocturnal seizures, which are a subset of epilepsy, can sometimes be misidentified as RSD due to the presence of movements during sleep. However, there are several key differences between the two. Nocturnal seizures occur less frequently and typically last 1–3 min, whereas RSD movements are more frequent and shorter lasting, lasting only several seconds. Additionally, the seizure semiology in nocturnal seizures is often more complex and stereotyped, and EEG recordings may show epileptic discharges or ictal rhythms. In RSD, the EEG recorded during movements typically only shows artifacts without any epileptic activity.

Furthermore, it is important to differentiate RSD from idiopathic RBD, which can be an early manifestation of neurodegenerative diseases [11]. REM sleep without atonia (RWA) is the hallmark of isolated REM sleep behavior disorder that has idiopathic and symptomatic forms (including neurodegenerative, autoimmune, infectious or other brainstem lesions) [12]. RBD is characterized by the absence of muscle atonia during REM sleep, leading to the acting out of dreams. RBD is more frequent in the elderly, but younger forms occur as well [13]. In view of the abundant movements during REM sleep, RBD could have been raised. However, RSD can be distinguished from RBD by the persistence of movements throughout the entire night in RSD.

The patients in this study did not receive an appropriate treatment plan due to this lack of guidance. It is noteworthy that two of the patients in the study were diagnosed with anxiety and depression, respectively. The importance of sleep for mental health is emphasized; as poor sleep quality has been linked to higher rates of depression and anxiety [14]. From the findings of our study, it can be speculated that RSD patients with longer disease duration and poor sleep may be at an increased risk of developing psychiatric comorbidities.

However, it is important to acknowledge the limitations of the study. This study is conducted in a single-center study with a small sample size, which may limit the generalizability of the results. The accuracy of disease duration based on patients’ and caregivers’ memory is also questionable, as it may not accurately reflect the actual disease course. To gain a more comprehensive understanding of RSD in adults, larger studies are needed to assess the prevalence and underlying mechanisms of the condition. Furthermore, a more thorough analysis of psychiatric symptoms and quality of life impairments would contribute to our overall knowledge of RSD. Lastly, with a better understanding of the disorder, further research into treatment options is necessary.

Conclusion

Adult patients also suffer from RSD, and the RSD that originates in childhood tends to persist into adulthood. RSD-related sleep movements are accompanied by changes in sleep stage, arousals, and awakenings which can significantly disrupt the quality of patients’ sleep, and lead to significant daytime impairment. Furthermore, RSD also interfere with the sleep of patients’ bed partner. Our findings also emphasize the advantages of Video-PSG in classifying the polymorphic nature of RSD-related sleep movements and distinguishing between various sleep disorders. Further studies involving multiple centers and larger numbers of patients are needed to investigate the prevalence, pathophysiology, and treatment of RSD.

Supplementary Information

Below is the link to the electronic supplementary material.

Abbreviations

RSD

Restless sleep disorder

VPSG

Video-polysomnography

RLS

Restless leg syndrome

OSA

Obstructive sleep apnea

EMG

Electromyogram

RERA

Respiratory effort-related arousal

REM

Rapid eye movement

NREM

Non-rapid eye movement

LMM

Larger muscle movements

AHI

Apnea Hypopnea Index

RBD

Rapid eye movement sleep behavior disorder

PLMD

Periodic leg movement disorder

IRLSSG

International Restless Legs Syndrome Study Group

ICSD-3

International Classification of Sleep Disorders edition 3

AASM

American Academy of Sleep Medicine

Author contributions

XW and YP: study concept and design data collection and analysis, drafting and revision of the manuscript for content. LM: drafting and revision of the manuscript for content. NY: major role in the acquisition and analysis of data. YL: drafting and revision of the manuscript for content, study concept and design. All authors contributed to the article and approved the submitted version.

Declarations

Conflict of interest

The other authors report no financial disclosure and no conflict of interest statement.

Ethical approval

All authors have seen and approved of this manuscript. The study was approved by Xijing Hospital Research Ethics Committee, all authors reported that they have conformed to the principles of ethics in publishing and ethical guidelines for journal publication, and written informed consent was obtained from the parents regarding publication of this report. None of the authors has any conflict of interest to disclose.