This study was performed to determine the diagnostic cutoff value of quantified tonic and phasic rapid eye movement (REM) sleep without atonia (RSWA) automatically calculated from chin and limb muscle electromyograms (EMG) for diagnosis of REM sleep behavior disorder (RBD).
Nocturnal video polysomnographic data of 57 patients diagnosed with RBD and 29 age- and sex-matched controls were reviewed. Tonic activity was measured using submentalis EMG, and phasic activity was measured using submentalis and bilateral anterior tibialis EMG. The proportion of epochs with tonic and phasic activity during the entire REM sleep period was quantified using a self-developed automated algorithm.
The RBD group showed significantly more tonic activity compared with the control group (28.87±36.92% vs. 12.94±31.69%, respectively, p<0.001). The diagnostic cutoff value of quantified submentalis tonic RSWA for RBD showing the best optimal sensitivity and specificity was 0.99% [sensitivity, 77.2%; specificity, 79.3%, area under the receiver operating characteristic curve (AUC), 0.76]. Cutoffs of phasic RSWA were 47.53% when assessed in the submentalis only (sensitivity, 1.8%; specificity, 100%; AUC, 0.46), 0.10% in the anterior tibialis (sensitivity, 66.7%; specificity, 55.2%; AUC, 0.55), and 0.10% in both the submentalis and anterior tibialis (sensitivity, 70.2%; specificity, 51.7%; AUC, 0.53).
This study provided evidence for the diagnosis of RBD using an automated method by assessing RSWA. Tonic activity in the submentalis muscle showed better sensitivity and specificity for diagnosis of RBD than did phasic activity.
Rapid eye movement (REM) sleep behavior disorder (RBD) is a disorder characterized by the loss of muscle atonia that normally appears during REM sleep and the resulting body movements. RBD is associated with alpha-synucleinopathies, such as Parkinson’s disease, Lewy body dementia, and multiple systemic atrophy [
According to the American Academy of Sleep Medicine (AASM) diagnostic criteria, a diagnosis of RBD requires repeated behaviors during REM sleep, and tonic activity in the chin or phasic activity in the chin or limbs during polysomnography (PSG) must be observed [
A number of studies have attempted to quantify RSWA in PSG to diagnose RBD. In 1992, Lapierre and Montplaisir [
Moreover, most previous studies that used automated methods measured RSWA in RBD only in the chin muscles. Previous studies using visual scoring reported that the sensitivity and specificity for the chin muscles were significantly lower than those for the limb muscles in predicting phasic motor activity during sleep [
In this study, we attempted to quantify tonic RSWA and phasic RSWA according to the AASM diagnostic criteria using an automated method, and to obtain the optimal RSWA value that accurately predicts RBD. Tonic RSWA was measured in the chin muscle only, and phasic RSWA was measured in both the chin and limb muscles. RSWA values derived using these methods were compared to determine which method predicts RBD most accurately.
We retrospectively reviewed the medical records of patients >50 years old who underwent nocturnal video PSG (v-PSG) at the Sleep and Chronobiology Center of Seoul National University Hospital between January 1, 2016, and May 31, 2019. The exclusion criteria were 1) current or historical major psychiatric illnesses (schizophrenia, schizoaffective disorder, bipolar disorder, and major depressive disorder) or neurodegenerative diseases, including α-synucleinopathies; 2) current signs or symptoms of parkinsonism; 3) any current or previous serious medical illness, including ischemic heart disease, arrhythmia, or diabetes mellitus; 4) apnea–hypopnea index >15; and 5) periodic limb movement index >15.
Fifty-seven patients (36 males, 21 females) who underwent v-PSG during the study period were diagnosed with RBD at the sleep clinic of the psychiatric department according to clinical evaluation and v-PSG based on International Classification of Sleep Disorders-3 [
This retrospective study was approved by the Institutional Review Board of Seoul National University Hospital (approval no. H-1809-080-97). All procedures were performed in accordance with the ethical standards of the research committee and were implemented in accordance with the 1964 Declaration of Helsinki and subsequent amendments.
At the Center for Sleep and Chronobiology of Seoul National University Hospital, data from overnight v-PSG (Profusion3; Compumedics, Charlotte, NC, USA) consisting of electroencephalograms (electrodes at F3, F4, C3, C4, O1, and O2, using A1 and A2 as reference sites), bilateral electrooculograms, a single-lead electrocardiogram (lead II), submentalis and bilateral anterior tibialis EMG, airflow measurement via a nasal pressure transducer and oronasal thermal sensor, a respiratory inductance plethysmography band to monitor the movements of the chest and abdomen, and a finger pulse oximeter were analyzed. Polysomnographic data were scored by experienced technicians and physicians in accordance with the AASM recommendations [
In principle, the scoring method in this study followed the standard of RBD scoring method based on AASM as possible in a fully automated way. First, EMG signals from the submentalis and bilateral anterior tibialis muscle were digitally band-pass filtered at 10–100 Hz to exclude artifacts. Then, RSWA was quantified as proposed by Lapierre and Montplaisir [
In the present study, when an epoch of REM sleep had an EMG amplitude >10 µV in the submentalis EMG channel during at least 50% of the duration of the epoch, it was defined as an epoch with tonic activity. On the other hand, when determining phasic activity, a 30-s epoch of REM sleep was divided into 10 sequential 3-s mini-epochs. When at least five (50%) of the mini-epochs contained bursts of transient muscle activity with a burst duration >3 s and amplitude >10 µV in the submentalis or anterior tibialis EMG channel, the epoch was defined as having phasic activity. The cutoff amplitude of tonic and phasic activity was set to 10 µV (rather than 2× and 4× the stage R atonia activity, as defined by the AASM) because the background EMG activity of the samples could not always be determined easily [
To summarize the demographic, clinical, and polysomnographic variables, descriptive statistics were used. The Mann–Whitney U-test was used to compare continuous variables and Fisher’s exact test to compare categorical variables to assess the demographic, clinical, and polysomnographic differences between groups.
We used ROC curves to display the true positives and false positives, regarding the diagnosis in medical records according to International Classification of Sleep Disorders-3 as the gold standard. We measured the AUC, which indicates the accuracy of automatically calculated RSWA for diagnosis of RBD. The optimal cutoff value of RSWA that maximizes the sensitivity and specificity of the diagnosis was calculated using Youden’s index [
The demographic and polysomnographic characteristics of the RBD and control groups are shown in
Comparison of RSWA between the RBD and control groups indicated a statistically significant difference only in tonic RSWA (
ROC curves were constructed for tonic and phasic RSWA to determine the cutoff value with the highest sensitivity and specificity to distinguish RBD patients from controls (
The present study was performed to assess the diagnostic accuracies of tonic and phasic RSWA calculated using a fully automated method, with the diagnosis by clinicians according to the conventional visual scoring method used as the gold standard. This is the first study to compare the accuracy of RWSA for detecting RBD by calculating both tonic and phasic RSWA using a fully automated method. It is also the first study to evaluate RSWA in chin muscles as well as limb muscles using a fully automated method in RBD. However, the diagnostic accuracy of RSWA evaluated using AUC values was lower in this study than in previous studies.
Unlike Jeppesen’s semi-automated method [
In addition, in a significant number of controls, tonic or phasic RSWA was detected at a level capable of diagnosing RBD despite the absence of the disease, which led to a further decline in accuracy. In fact, RSWA in controls was observed in previous studies evaluating the diagnostic accuracy of tonic and phasic RSWA measured in the chin muscle [
In this study, tonic RSWA showed higher diagnostic accuracy than did phasic RSWA. In previous studies using visual scoring in patients with Parkinson’s disease, tonic activity showed superior diagnostic accuracy compared with phasic activity [
Tonic RSWA showed relatively good sensitivity and specificity for the diagnosis of RBD, but the cutoff value was lower than those in previous reports using the manual method (0.99–30%) [
Meanwhile, the diagnostic accuracy of the quantified RSWA in this study was even lower than that of previous studies using the fully automated method. This is thought to be because the previous studies minimized the effects of artifacts using the REM atonia index, which might be useful in that the effect of artifacts could be reduced without manual inspection, but could not calculate tonic and phasic activities separately. In our study, we calculated tonic and phasic activity respectively, which could extract quantified RSWA with higher clinical value but might have lead to the increase in the effect of artifacts and decrease in the diagnostic accuracy.
This study had some limitations. First, 57 patients with RBD was an insufficient number to establish a diagnostic method for the disease. However, it is still a relatively large sample size compared to previous studies that attempted to derive diagnostic cutoff through quantified scoring of RBD. This is the highest number except for the Ferri’s study in 2012, which analyzed 74 RBD patients [
In summary, we quantified tonic and phasic RSWA using fully automated techniques in RBD patients and normal controls, thereby evaluating RSWA accuracy for diagnosing RBD. Tonic RSWA showed greater diagnostic accuracy than that of phasic RSWA, which showed better accuracy when measured in limb than chin muscles. To improve the diagnostic accuracy, further prospective studies in more population of various age groups with effective filtering of artifacts are required.
None
The authors have no potential conflicts of interest to disclose.
Conceptualization: Jeong Hun Yang, Yu Jin Lee. Data curation: Jeong Hun Yang, Sang Ho Choi, Mi Hyun Lee, Seong Min Oh. Formal analysis: Jeong Hun Yang, Sang Ho Choi. Investigation: Jeong Hun Yang, Jae-Won Choi. Methodology: Jeong Hun Yang, Kwang Suk Park. Project administration: Jeong Hun Yang, Jee Eun Park. Resources: Jeong Hun Yang, Yu Jin Lee. Software: Jeong Hun Yang, Sang Ho Choi. Supervision: Yu Jin Lee. Validation: Jeong Hun Yang, Mi Hyun Lee. Visualization: Jeong Hun Yang, Seong Min Oh. Writing—original draft: Jeong Hun Yang, Jae-Won Choi. Writing—review & editing: Jee Eun Park, Yu Jin Lee.
ROC curves evaluating the ability of RSWA to diagnose RBD. (A) Tonic RSWA in the submentalis. (B) Phasic RSWA in the submentalis. (C) Phasic RSWA in the anterior tibialis. (D) Phasic RSWA in both the submentalis and anterior tibialis. ROC: receiver operating characteristic, AUC: area under the ROC curve, RSWA: rapid eye movement sleep without atonia, RBD: rapid eye movement sleep behavior disorder.
Comparisons of demographic and polysomnographic characteristics between the RBD patients and control groups
Variable | RBD (n=57) | Control (n=29) | p-value |
---|---|---|---|
Age (yr) | 67.11±6.56 | 67.18±6.08 | 0.87 |
Sex, female | 21 (36.8) | 11 (37.9) | 0.92 |
TIB (min) | 481.99±31.30 | 482.16±25.90 | 0.75 |
TST (min) | 381.61±49.71 | 379.40±59.31 | 0.96 |
Sleep efficiency (%) | 79.57±11.28 | 78.69±11.53 | 0.68 |
WASO (min) | 85.57±57.13 | 90.67±53.02 | 0.54 |
Sleep latency (min) | 19.21±23.44 | 11.60±10.75 | 0.06 |
REM latency (min) | 117.82±64.03 | 102.48±53.84 | 0.31 |
Stage N1 (%) | 23.51±13.14 | 20.39±9.13 | 0.51 |
Stage N2 (%) | 52.02±12.48 | 56.57±7.79 | 0.046 |
Stage N3 (%) | 5.13±7.45 | 3.38±5.32 | 0.33 |
Stage R (%) | 19.35±7.54 | 19.66±6.40 | 0.83 |
AHI | 6.61±4.06 | 5.89±3.89 | 0.31 |
PLMI | 25.73±36.55 | 12.65±18.99 | 0.08 |
Data are presented as numbers (%) or means±standard deviations.
RBD: rapid eye movement sleep behavior disorder, TIB: time in bed, TST: total sleep time, WASO: wake after sleep onset, REM: rapid eye movement, AHI: apnea–hypopnea index, PLMI: periodic limb movement index
Comparisons of tonic and phasic RSWA between the RBD patient and control groups
Variable | RBD (n=57) | Control (n=29) | p-value |
---|---|---|---|
Tonic RSWA (%) | |||
Submentalis | 28.87±36.92 | 12.94±31.69 | <0.001 |
Phasic RSWA (%) | |||
Submentalis | 1.56±10.81 | 0.96±2.90 | 0.35 |
Anterior tibialis | 2.40±4.72 | 5.66±11.88 | 0.45 |
Submentalis+anterior tibialis | 3.96±11.47 | 6.45±12.07 | 0.61 |
Data are presented as means±standard deviations. RBD: rapid eye movement sleep behavior disorder, RSWA: rapid eye movement sleep without atonia