- Email: [email protected]
The REM sleep behavior disorder screening questionnaire: Validation study of a Japanese version
Sleep Medicine 10 (2009) 1151–1154
Contents lists available at ScienceDirect
Sleep Medicine journal homepage: www.elsevier.com/locate/sleep
Brief Communication
The REM sleep behavior disorder screening questionnaire: Validation study of a Japanese version Tomoyuki Miyamoto a, Masayuki Miyamoto a,*, Masaoki Iwanami a, Mina Kobayashi b, Masaki Nakamura b, Yuichi Inoue b, Chiharu Ando c, Koichi Hirata a a
Department of Neurology, Center of Sleep Medicine, Dokkyo Medical University School of Medicine, Tochigi, Japan Japan Somnology Center, Neuropsychiatry Research Institute, Tokyo, Japan c International Research and Education Center, English, Dokkyo Medical University School of Medicine, Tochigi, Japan b
a r t i c l e
i n f o
Article history: Received 5 March 2009 Received in revised form 8 May 2009 Accepted 18 May 2009 Available online 14 July 2009 Keywords: REM sleep behavior disorder screening questionnaire REM sleep behavior disorder Obstructive sleep apnea syndrome Parkinson’s disease Validation study Japanese version
a b s t r a c t Background: REM sleep behavior disorder (RBD) is a parasomnia characterized by intermittent loss of normal skeletal muscle atonia during REM sleep and elaborate motor activity associated with dream mentation. Idiopathic RBD (iRBD) has a known association with neurodegenerative diseases such as synucleinopathies. Recently, a specific screening scale for assessment of REM sleep behavior disorder (RBDSQ) was validated. Detection of RBD using a Japanese version of the RBDSQ would be useful in the stepwise diagnostic process. We investigated the validity and reliability of a Japanese version of this instrument, the RBDSQ-J. Methods: Subjects were 52 patients with iRBD diagnosed according to criteria in the International Classification of sleep disorders, second edition, 55 obstructive sleep apnea syndrome (OSAS) patients who responded well to CPAP therapy after a diagnosis of RBD was ruled out by history and polysomnography (PSG) and 65 healthy subjects. Results: An RBDSQ-J score cut-off of 5.0 was considered useful for differentiating the iRBD group from the healthy subjects or the OSAS group. Cronbach’s alpha for the entire RBDSQ-J was 0.866. Conclusion: The RBDSQ-J had high sensitivity, specificity, and reliability and would be applicable as a screening method for iRBD in the elderly Japanese population. Ó 2009 Elsevier B.V. All rights reserved.
1. Introduction
2. Methods
REM sleep behavior disorder (RBD) is characterized by dreamenacting behaviors and vivid, action-filled or unpleasant dreams and presents a risk for self-injury and harm to others due to abnormal REM sleep during which control of muscle tonus is lacking [1]. Polysomnography (PSG) is required to establish the diagnosis and represents the diagnostic gold standard for revealing loss of REM-related muscle atonia with excessive amounts of sustained or intermittent elevation of submental EMG tone or excessive phasic submental or limb EMG twitching [1]. Recently, a specific screening scale for assessment of RBD, the RBD screening questionnaire (RBDSQ), was validated [2]. This study aimed to validate the Japanese version of the RBDSQ (RBDSQ-J) in a setting different from that used originally.
The objectives of this study were explained to the patent owner of the original version of the RBDSQ [2], and approval was given to translate the original version into Japanese to establish the first RBDSQ-J. Next, we asked a professional translator, who was not a medical provider, to back-translate the Japanese version into English. Then, we asked the authors of the original RBDSQ to confirm that the back-translated English document was equivalent to the original version in content and obtained approval for its use in this study. The RBDSQ-J constructed in this manner was administered to 52 consecutive patients with PSG-confirmed iRBD (66.4 ± 6.9 years; 36 males, 66.1 ± 7.0 years; 16 females, 67.1 ± 6.8 years) recruited from the Dokkyo Medical University Hospital and Japan Somnology Center, 55 consecutive patients with obstructive sleep apnea syndrome (OSAS) who had responded well to CPAP therapy (63.1 ± 7.0 years; 44 males, 63.6 ± 6.8 years; 11 females, 61.2 ± 8.0 years) recruited from the Dokkyo Medical University Hospital, and 65 healthy subjects (64.6 ± 8.8 years; 37 males, 62.1 ± 8.0 years; 28 females, 68.0 ± 8.7 years) recruited from the Dokkyo Medical University Hospital staff and their relatives and friends. These healthy subjects had no symptoms or history
* Corresponding author. Address: Department of Neurology, Center of Sleep Medicine, Dokkyo Medical University School of Medicine, 880-Kitakobayashi, Mibu, Tochigi 321-0293, Japan. E-mail address: [email protected] (M. Miyamoto). 1389-9457/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.sleep.2009.05.007
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of sleep disorders such as OSAS, no neurological diseases and no psychiatric diseases. We analyzed the age difference among three groups (iRBD, OSAS and healthy subjects) using one-way analysis of variance that was Bonferroni corrected for multiple comparisons and found no differences in age among groups (P > 0.05, respectively). But the female OSAS patients were younger than the female iRBD patients (P = 0.023) and healthy male subjects were younger than male iRBD patients (P = 0.007). IRBD was defined according to the criteria in the International Classification of sleep disorders, second edition [3]. The OSAS group was diagnosed as having OSAS without RBD or REM sleep without atonia by PSG or other primary sleep disorders such as restless legs syndrome (RLS), periodic limb movement disorders, or narcolepsy. In selecting the healthy subjects, we excluded those with findings of medical history based on the ICSD-2. We did not perform a PSG examination in these healthy subjects. To validate test–retest reliability, 16 patients with iRBD were selected at random. They were tested again at a mean interval of 166.8 ± 82.9 days, and two RBDSQ-J total scores were statistically analyzed with the intra-class correlation coefficient (ICC, oneway analysis of variance) [4]; Cohen’s kappa coefficient was calculated for each item [5]. Study procedures were approved by the Ethics Review Committee of Dokkyo Medical University. Each subject provided informed consent. 3. Statistical analysis Sample means of the RBDSQ-J total score in the iRBD, OSAS and healthy groups were compared by the Mann–Whitney U test. Sensitivity and specificity for different cut-off points were calculated and presented by means of a ROC function. The diagnostic value of the RBDSQ-J was calculated by the area under the curve (AUC), which is independent of an arbitrary choice of a cut-off point and tested for statistical significance using the Mann–Whitney U test. As a measure of reliability of the questionnaire, Cronbach’s a-coefficient, ICC (one-way random average measures on SPSS, ICC [1,1]) [4] for repeated RBDSQ-J scores and the Cohen’s kappa coefficient for categorical items were calculated. Kappa values were interpreted according to conventional groups (0.0–0.20 = slight agreement; 0.21–0.40 = fair; 0.41–0.60 = moderate; 0.61–0.80 = substantial; 0.81–1.00 = almost perfect) [5]. Spearman rank correlation test was used to evaluate whether disease duration was correlated with the RBDSQ-J score in the iRBD group. Statistical analyses were performed with the Statistical Package for Social Science Software (Graphpad Prism, San Diego, CA, and SPSS 15.0J for Windows, Tokyo, Japan). 4. Results The mean RBDSQ-J score in the entire iRBD group was 7.5 ± 2.8 (range 1–12) points, with a score of 7.8 ± 2.8 (range 1–12) points
for men and 6.9 ± 2.7 (range 2–12) points for women (P < 0.0001, respectively). This is in comparison with the entire OSAS group, which had a score of 1.9 ± 2.3 (range 0–11) (2.1 ± 2.6 [range 0– 11] points for men and 1.5 ± 1.0 [range 0–3] points for women) (P < 0.0001, respectively). The mean score for the healthy subjects was 1.6 ± 1.2 (range 0–6) points, with a score of 2.1 ± 2.6 (range 0– 5) points for men and 1.7 ± 1.4 (range 0–6) points for women (P < 0.0001, respectively). Next, the optimal cut-off value and sensitivity and specificity of the RBDSQ-J score in the iRBD group were calculated, and the AUC was compared with the minimum possible score of 0.5; the difference was highly significant (P < 0.000) as shown in Table 1 and Fig. 1. Single item analysis revealed the highest specificity for item 5 and the highest sensitivity for item 6.1 for the iRBD group when compared with the OSAS group or healthy subjects (Table 2). Cronbach’s alpha for the entire RBDSQ-J was 0.866. Test–retest reliability for the RBDSQ-J total score was 0.836 (95% CI = 0.601–0.939) for the iRBD. The Cohen’s kappa coefficients of the RBDSQ-J items 1, 2, 5 and 6.1 were evaluated to be substantial (0.61 or greater; Table 2). Mean disease duration of RBD from symptom onset was 4.6 ± 5.0 years, range 0.2–18 years. The RBDSQ-J score had no correlation with the duration of RBD (r = 0.254, n = 50, P = 0.075). 5. Discussion Sensitivity and specificity using a cut-off of 4.5 were high in differentiating the iRBD group from healthy subjects or the OSAS group. Therefore, a cut-off of 5.0 was considered useful for differentiating the iRBD group from healthy subjects or the OSAS group. The original instrument, the RBDSQ, could discriminate RBD patients from healthy controls with a sensitivity of 96% and specificity of 56% at a cut-off level of 5.0 [2]. The mean original RBDSQ score in the RBD group was 9.5 ± 2.8 points [2]. The reason that the total RBDSQ score was higher than the total RBDSQ-J score was that the sensitivities of items 9 and 10 were markedly low for the RBDSQ-J, while concomitant disease, such as sleep and/or neurologic disorders, had a larger impact in the original RBDSQ, increasing the total score. Items 4, 5, 6.2, and 7, which are related to limb movements, were non-specific and this selection bias predisposed these items to positive answers [2]. Marked physical movements during sleep do not always represent a pathogenesis indicating RBD. In particular, untreated OSAS may be associated with physical movements during sleep [6], making it important to first differentiate patients with iRBD from those with OSAS with abnormal sleep behavior. Therefore, we selected patients with this syndrome as control subjects. It is understandable that answers to some items varied or had lower sensitivity. For example, for items 5, 6.2, and 6.3 a bed partner would be needed to provide answers, and situations referred to in items 6.4 and 8 were often obscure. In evaluation of reliability, items that enlarged the kappa coefficient were 1, 2, 5, and 6.1 for
Table 1 Stratified analyses for RBDSQ-J between groups. Compared with iRBD
Cut-off value
Sensitivity %
Specificity %
Positive predictive value %
Negative predictive value %
Likelihood ratio
ROC AUC (95% CI)
Pvalue
Healthy subjects
4.5
88.5
96.9
97.9
91.4
28.5
<0000
OSAS
4.5
88.5
90.9
90.2
89.3
9.72
OSAS (male)*
4.5
88.9
88.6
86.5
90.7
7.79
0.966 (0.933– 0.999) 0.927 (0.873– 0.980) 0.918 (0.853– 0.983)
<0000 <0000
RBDSQ-J, REM sleep behavior disorder screening questionnaire Japanese version; iRBD, idiopathic REM sleep behavior disorder; OSAS: obstructive sleep apnea syndrome; ROC AUC, receiver operating characteristic area under curve. * iRBD (male) versus OSAS (male) patients.
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Fig. 1. (A) Receiver-operator characteristic curves (ROC) from subjects with idiopathic REM sleep behavior disorder (iRBD) versus healthy subjects. Area under the curve (AUC) = 0.966. (B) ROC from iRBD (entire) versus obstructive sleep apnea syndrome (entire). AUC = 0.927. (C) ROC from iRBD (male) versus obstructive sleep apnea syndrome (male). AUC = 0.918.
Table 2 Sensitivity and specificity* and test–retest reliability** of RBDSQ-J item. RBDSQ-J item
1 2 3 4 5 6.1 6.2 6.3 6.4 7 8 9 10
Sensitivity (%)
Specificity (%)
Positive predictive value (%)
Negative predictive value (%)
iRBD (n = 16)**
OSAS
Healthy subjects
OSAS
Healthy subjects
OSAS
Healthy subjects
OSAS
Healthy subjects
ICC (j)
P
80.8 71.2 69.2 67.3 42.3 88.5 59.6 61.5 30.8 75.0 69.2 23.1 11.5
80.8 75.5 69.2 67.3 42.3 88.5 59.6 61.5 30.8 75.0 69.2 23.1 11.5
76.4 92.7 96.4 56.4 96.4 85.5 90.9 94.5 87.3 85.5 67.3 87.3 89.1
52.3 77.9 83.1 61.5 92.3 75.4 90.8 86.2 92.3 64.6 47.7 89.2 96.9
76.4 90.2 94.7 59.3 91.7 85.2 86.1 91.4 69.6 83.0 66.7 63.2 50.0
57.5 71.2 76.6 58.3 81.5 74.2 83.8 78.0 76.2 62.9 51.4 63.2 75.0
80.8 77.3 76.8 64.6 63.9 88.7 70.4 72.2 57.1 78.3 69.8 54.5 51.6
77.3 81.5 77.1 70.2 66.7 89.1 73.8 73.7 62.5 76.4 66.0 59.2 57.8
0.636 0.765 0.213 0.538 0.750 1.000 0.538 0.333 0.347 0.600 0.455 0.347 0.448
P = 0.006 P = 0.002 P = 0.377 P = 0.029 P = 0.002 P < 0.000 P < 0.029 P = 0.146 P = 0.142 P = 0.009 P = 0.064 P = 0.142 P = 0.032
RBDSQ-J, RBD screening questionnaire Japanese version; ICC (j), intraclass correlation coefficients (Cohen’s kappa coefficient); iRBD, idiopathic REM sleep behavior disorder; OSAS, obstructive sleep apnea syndrome. Data were obtained from 55 OSAS patients and 65 healthy subjects. ** Data were obtained from 16 iRBD patients selected at random. *
iRBD. It can be proposed that future evaluations should use weighted scores for RBDSQ-J items, which may improve the accuracy of the questionnaire. The idiopathic form of RBD has a male preponderance and usually emerges after the age of 50. IRBD has not been reported to be associated with any other neurological symptoms except for those characteristic of RBD itself. That being said, recent pathophysiological and neuropsychological studies did reveal the insidious supervention of neurological symptoms on iRBD. IRBD might be a cryptogenetic neurological disease [1]. Men over the age of 50 years who have iRBD have been shown to be at very high risk for future parkinsonism [1]. In clinical practice, the RBDSQ-J may be applied within a stepwise diagnostic process, beginning with the questionnaire, followed by an interview and PSG. Thus, identifying clinical RBD as early as possible would be useful in clinical practice and in clinical trials of a potentially neuroprotective substance in the Japanese elderly population. Early-onset patients (650 years) were reported to have significantly more past and present psychiatric diagnoses and antidepressant usage than
late-onset patients (>50 years) [7]. In the future, it will be useful to validate the RBDSQ-J in early-onset patients. This study has some limitations. First, OSAS patients responding well to CPAP therapy were selected as the PSG-confirmed control group. Second, the male-to-female ratio was not matched between the iRBD and OSAS groups, and few female subjects were included. Third, the lack of spousal input was a potential problem as well as differentiating the severity of RBD within that group. Acknowledgments The authors thank Dr. K. Stiasny-Kolster (Department of Neurology, Center of Nervous diseases, Philips-University, Marburg, Germany) for permission to develop a Japanese version of the instrument and for her helpful comments. The authors thank T. Sairenchi (Department of Public Health, Dokkyo Medical University) for his valuable suggestions concerning statistical analysis.
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Appendix A
References
RBD screening questionnaire (RBDSQ) (Stiasny-Kolster et al. [2]).
[1] Gagnon JF, Postuma RB, Mazza S, Doyon J, Montplaisir J. Rapid-eye-movement sleep behaviour disorder and neurodegenerative diseases. Lancet Neurol 2006;5:424–32. [2] Stiasny-Kolster K, Mayer G, Schäfer S, Möller JC, Heinzel-Gutenbrunner M, Oertel WH. The REM sleep behavior disorder screening questionnaire–a new diagnostic instrument. Mov Disord 2007;22:2386–93. [3] American Academy of Sleep Medicine. Internal classification of sleep disorders, 2nd ed.: diagnosis and cording manual. Am Acad Sleep Med. Westchester Illinois; 2005 [p. 148–152]. [4] Shrout PE. Fleiss JL: intraclass correlations: uses in assessing rater reliability. Phychol Bull 1979;86:420–8. [5] Landis JR, Koch GGT. He measurement of observer agreement for categorical data. Biometrics 1977;33:159–74. [6] Iranzo A, Santamaria J. Severe obstructive sleep apnea/hypopnea mimicking REM sleep behavior disorder. Sleep 2005;28:203–6. [7] Teman PT, Tippmann-Peikert M, Silber MH, Slocumb NL, Robert Auger R. Idiopathic rapid-eye-movement sleep disorder: associations with antidepressants, psychiatric diagnoses, and other factors, in relation to age of onset. Sleep Med 2009;10:60–5.
English
Question
Answer
1 2
I sometimes have very vivid dreams My dreams frequently have aggressive or action-packed contents The dream contents mostly match my nocturnal behavior I know that my arms or legs move when I sleep It happened that I (almost) hurt my bed partner or myself I have or had the following phenomena during my dreams Speaking, shouting, swearing, laughing, loudly Sudden limb movements, ‘‘fights” Gesture, complex movements, that are useless during sleep, e.g., to wave, to salute, to frighten mosquitoes, fall off bed Things that fell down around the bed, e.g., bedside lamp, book, glasses It happens that my movements awaken me After awakening I mostly remember the content of my dreams well My sleep is frequently disturbed I have/had a disease of the nervous system (e.g., stroke, head trauma parkinsonism, RLS, narcolepsy, depression, epilepsy, inflammatory disease of the brain), which?
Yes/no Yes/no
3 4 5 6 6.1 6.2 6.3
6.4 7 8 9 10
Yes/no Yes/no Yes/no
Yes/no Yes/no Yes/no
Yes/no Yes/no Yes/no Yes/no Yes/no
Contents lists available at ScienceDirect
Sleep Medicine journal homepage: www.elsevier.com/locate/sleep
Brief Communication
The REM sleep behavior disorder screening questionnaire: Validation study of a Japanese version Tomoyuki Miyamoto a, Masayuki Miyamoto a,*, Masaoki Iwanami a, Mina Kobayashi b, Masaki Nakamura b, Yuichi Inoue b, Chiharu Ando c, Koichi Hirata a a
Department of Neurology, Center of Sleep Medicine, Dokkyo Medical University School of Medicine, Tochigi, Japan Japan Somnology Center, Neuropsychiatry Research Institute, Tokyo, Japan c International Research and Education Center, English, Dokkyo Medical University School of Medicine, Tochigi, Japan b
a r t i c l e
i n f o
Article history: Received 5 March 2009 Received in revised form 8 May 2009 Accepted 18 May 2009 Available online 14 July 2009 Keywords: REM sleep behavior disorder screening questionnaire REM sleep behavior disorder Obstructive sleep apnea syndrome Parkinson’s disease Validation study Japanese version
a b s t r a c t Background: REM sleep behavior disorder (RBD) is a parasomnia characterized by intermittent loss of normal skeletal muscle atonia during REM sleep and elaborate motor activity associated with dream mentation. Idiopathic RBD (iRBD) has a known association with neurodegenerative diseases such as synucleinopathies. Recently, a specific screening scale for assessment of REM sleep behavior disorder (RBDSQ) was validated. Detection of RBD using a Japanese version of the RBDSQ would be useful in the stepwise diagnostic process. We investigated the validity and reliability of a Japanese version of this instrument, the RBDSQ-J. Methods: Subjects were 52 patients with iRBD diagnosed according to criteria in the International Classification of sleep disorders, second edition, 55 obstructive sleep apnea syndrome (OSAS) patients who responded well to CPAP therapy after a diagnosis of RBD was ruled out by history and polysomnography (PSG) and 65 healthy subjects. Results: An RBDSQ-J score cut-off of 5.0 was considered useful for differentiating the iRBD group from the healthy subjects or the OSAS group. Cronbach’s alpha for the entire RBDSQ-J was 0.866. Conclusion: The RBDSQ-J had high sensitivity, specificity, and reliability and would be applicable as a screening method for iRBD in the elderly Japanese population. Ó 2009 Elsevier B.V. All rights reserved.
1. Introduction
2. Methods
REM sleep behavior disorder (RBD) is characterized by dreamenacting behaviors and vivid, action-filled or unpleasant dreams and presents a risk for self-injury and harm to others due to abnormal REM sleep during which control of muscle tonus is lacking [1]. Polysomnography (PSG) is required to establish the diagnosis and represents the diagnostic gold standard for revealing loss of REM-related muscle atonia with excessive amounts of sustained or intermittent elevation of submental EMG tone or excessive phasic submental or limb EMG twitching [1]. Recently, a specific screening scale for assessment of RBD, the RBD screening questionnaire (RBDSQ), was validated [2]. This study aimed to validate the Japanese version of the RBDSQ (RBDSQ-J) in a setting different from that used originally.
The objectives of this study were explained to the patent owner of the original version of the RBDSQ [2], and approval was given to translate the original version into Japanese to establish the first RBDSQ-J. Next, we asked a professional translator, who was not a medical provider, to back-translate the Japanese version into English. Then, we asked the authors of the original RBDSQ to confirm that the back-translated English document was equivalent to the original version in content and obtained approval for its use in this study. The RBDSQ-J constructed in this manner was administered to 52 consecutive patients with PSG-confirmed iRBD (66.4 ± 6.9 years; 36 males, 66.1 ± 7.0 years; 16 females, 67.1 ± 6.8 years) recruited from the Dokkyo Medical University Hospital and Japan Somnology Center, 55 consecutive patients with obstructive sleep apnea syndrome (OSAS) who had responded well to CPAP therapy (63.1 ± 7.0 years; 44 males, 63.6 ± 6.8 years; 11 females, 61.2 ± 8.0 years) recruited from the Dokkyo Medical University Hospital, and 65 healthy subjects (64.6 ± 8.8 years; 37 males, 62.1 ± 8.0 years; 28 females, 68.0 ± 8.7 years) recruited from the Dokkyo Medical University Hospital staff and their relatives and friends. These healthy subjects had no symptoms or history
* Corresponding author. Address: Department of Neurology, Center of Sleep Medicine, Dokkyo Medical University School of Medicine, 880-Kitakobayashi, Mibu, Tochigi 321-0293, Japan. E-mail address: [email protected] (M. Miyamoto). 1389-9457/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.sleep.2009.05.007
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of sleep disorders such as OSAS, no neurological diseases and no psychiatric diseases. We analyzed the age difference among three groups (iRBD, OSAS and healthy subjects) using one-way analysis of variance that was Bonferroni corrected for multiple comparisons and found no differences in age among groups (P > 0.05, respectively). But the female OSAS patients were younger than the female iRBD patients (P = 0.023) and healthy male subjects were younger than male iRBD patients (P = 0.007). IRBD was defined according to the criteria in the International Classification of sleep disorders, second edition [3]. The OSAS group was diagnosed as having OSAS without RBD or REM sleep without atonia by PSG or other primary sleep disorders such as restless legs syndrome (RLS), periodic limb movement disorders, or narcolepsy. In selecting the healthy subjects, we excluded those with findings of medical history based on the ICSD-2. We did not perform a PSG examination in these healthy subjects. To validate test–retest reliability, 16 patients with iRBD were selected at random. They were tested again at a mean interval of 166.8 ± 82.9 days, and two RBDSQ-J total scores were statistically analyzed with the intra-class correlation coefficient (ICC, oneway analysis of variance) [4]; Cohen’s kappa coefficient was calculated for each item [5]. Study procedures were approved by the Ethics Review Committee of Dokkyo Medical University. Each subject provided informed consent. 3. Statistical analysis Sample means of the RBDSQ-J total score in the iRBD, OSAS and healthy groups were compared by the Mann–Whitney U test. Sensitivity and specificity for different cut-off points were calculated and presented by means of a ROC function. The diagnostic value of the RBDSQ-J was calculated by the area under the curve (AUC), which is independent of an arbitrary choice of a cut-off point and tested for statistical significance using the Mann–Whitney U test. As a measure of reliability of the questionnaire, Cronbach’s a-coefficient, ICC (one-way random average measures on SPSS, ICC [1,1]) [4] for repeated RBDSQ-J scores and the Cohen’s kappa coefficient for categorical items were calculated. Kappa values were interpreted according to conventional groups (0.0–0.20 = slight agreement; 0.21–0.40 = fair; 0.41–0.60 = moderate; 0.61–0.80 = substantial; 0.81–1.00 = almost perfect) [5]. Spearman rank correlation test was used to evaluate whether disease duration was correlated with the RBDSQ-J score in the iRBD group. Statistical analyses were performed with the Statistical Package for Social Science Software (Graphpad Prism, San Diego, CA, and SPSS 15.0J for Windows, Tokyo, Japan). 4. Results The mean RBDSQ-J score in the entire iRBD group was 7.5 ± 2.8 (range 1–12) points, with a score of 7.8 ± 2.8 (range 1–12) points
for men and 6.9 ± 2.7 (range 2–12) points for women (P < 0.0001, respectively). This is in comparison with the entire OSAS group, which had a score of 1.9 ± 2.3 (range 0–11) (2.1 ± 2.6 [range 0– 11] points for men and 1.5 ± 1.0 [range 0–3] points for women) (P < 0.0001, respectively). The mean score for the healthy subjects was 1.6 ± 1.2 (range 0–6) points, with a score of 2.1 ± 2.6 (range 0– 5) points for men and 1.7 ± 1.4 (range 0–6) points for women (P < 0.0001, respectively). Next, the optimal cut-off value and sensitivity and specificity of the RBDSQ-J score in the iRBD group were calculated, and the AUC was compared with the minimum possible score of 0.5; the difference was highly significant (P < 0.000) as shown in Table 1 and Fig. 1. Single item analysis revealed the highest specificity for item 5 and the highest sensitivity for item 6.1 for the iRBD group when compared with the OSAS group or healthy subjects (Table 2). Cronbach’s alpha for the entire RBDSQ-J was 0.866. Test–retest reliability for the RBDSQ-J total score was 0.836 (95% CI = 0.601–0.939) for the iRBD. The Cohen’s kappa coefficients of the RBDSQ-J items 1, 2, 5 and 6.1 were evaluated to be substantial (0.61 or greater; Table 2). Mean disease duration of RBD from symptom onset was 4.6 ± 5.0 years, range 0.2–18 years. The RBDSQ-J score had no correlation with the duration of RBD (r = 0.254, n = 50, P = 0.075). 5. Discussion Sensitivity and specificity using a cut-off of 4.5 were high in differentiating the iRBD group from healthy subjects or the OSAS group. Therefore, a cut-off of 5.0 was considered useful for differentiating the iRBD group from healthy subjects or the OSAS group. The original instrument, the RBDSQ, could discriminate RBD patients from healthy controls with a sensitivity of 96% and specificity of 56% at a cut-off level of 5.0 [2]. The mean original RBDSQ score in the RBD group was 9.5 ± 2.8 points [2]. The reason that the total RBDSQ score was higher than the total RBDSQ-J score was that the sensitivities of items 9 and 10 were markedly low for the RBDSQ-J, while concomitant disease, such as sleep and/or neurologic disorders, had a larger impact in the original RBDSQ, increasing the total score. Items 4, 5, 6.2, and 7, which are related to limb movements, were non-specific and this selection bias predisposed these items to positive answers [2]. Marked physical movements during sleep do not always represent a pathogenesis indicating RBD. In particular, untreated OSAS may be associated with physical movements during sleep [6], making it important to first differentiate patients with iRBD from those with OSAS with abnormal sleep behavior. Therefore, we selected patients with this syndrome as control subjects. It is understandable that answers to some items varied or had lower sensitivity. For example, for items 5, 6.2, and 6.3 a bed partner would be needed to provide answers, and situations referred to in items 6.4 and 8 were often obscure. In evaluation of reliability, items that enlarged the kappa coefficient were 1, 2, 5, and 6.1 for
Table 1 Stratified analyses for RBDSQ-J between groups. Compared with iRBD
Cut-off value
Sensitivity %
Specificity %
Positive predictive value %
Negative predictive value %
Likelihood ratio
ROC AUC (95% CI)
Pvalue
Healthy subjects
4.5
88.5
96.9
97.9
91.4
28.5
<0000
OSAS
4.5
88.5
90.9
90.2
89.3
9.72
OSAS (male)*
4.5
88.9
88.6
86.5
90.7
7.79
0.966 (0.933– 0.999) 0.927 (0.873– 0.980) 0.918 (0.853– 0.983)
<0000 <0000
RBDSQ-J, REM sleep behavior disorder screening questionnaire Japanese version; iRBD, idiopathic REM sleep behavior disorder; OSAS: obstructive sleep apnea syndrome; ROC AUC, receiver operating characteristic area under curve. * iRBD (male) versus OSAS (male) patients.
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Fig. 1. (A) Receiver-operator characteristic curves (ROC) from subjects with idiopathic REM sleep behavior disorder (iRBD) versus healthy subjects. Area under the curve (AUC) = 0.966. (B) ROC from iRBD (entire) versus obstructive sleep apnea syndrome (entire). AUC = 0.927. (C) ROC from iRBD (male) versus obstructive sleep apnea syndrome (male). AUC = 0.918.
Table 2 Sensitivity and specificity* and test–retest reliability** of RBDSQ-J item. RBDSQ-J item
1 2 3 4 5 6.1 6.2 6.3 6.4 7 8 9 10
Sensitivity (%)
Specificity (%)
Positive predictive value (%)
Negative predictive value (%)
iRBD (n = 16)**
OSAS
Healthy subjects
OSAS
Healthy subjects
OSAS
Healthy subjects
OSAS
Healthy subjects
ICC (j)
P
80.8 71.2 69.2 67.3 42.3 88.5 59.6 61.5 30.8 75.0 69.2 23.1 11.5
80.8 75.5 69.2 67.3 42.3 88.5 59.6 61.5 30.8 75.0 69.2 23.1 11.5
76.4 92.7 96.4 56.4 96.4 85.5 90.9 94.5 87.3 85.5 67.3 87.3 89.1
52.3 77.9 83.1 61.5 92.3 75.4 90.8 86.2 92.3 64.6 47.7 89.2 96.9
76.4 90.2 94.7 59.3 91.7 85.2 86.1 91.4 69.6 83.0 66.7 63.2 50.0
57.5 71.2 76.6 58.3 81.5 74.2 83.8 78.0 76.2 62.9 51.4 63.2 75.0
80.8 77.3 76.8 64.6 63.9 88.7 70.4 72.2 57.1 78.3 69.8 54.5 51.6
77.3 81.5 77.1 70.2 66.7 89.1 73.8 73.7 62.5 76.4 66.0 59.2 57.8
0.636 0.765 0.213 0.538 0.750 1.000 0.538 0.333 0.347 0.600 0.455 0.347 0.448
P = 0.006 P = 0.002 P = 0.377 P = 0.029 P = 0.002 P < 0.000 P < 0.029 P = 0.146 P = 0.142 P = 0.009 P = 0.064 P = 0.142 P = 0.032
RBDSQ-J, RBD screening questionnaire Japanese version; ICC (j), intraclass correlation coefficients (Cohen’s kappa coefficient); iRBD, idiopathic REM sleep behavior disorder; OSAS, obstructive sleep apnea syndrome. Data were obtained from 55 OSAS patients and 65 healthy subjects. ** Data were obtained from 16 iRBD patients selected at random. *
iRBD. It can be proposed that future evaluations should use weighted scores for RBDSQ-J items, which may improve the accuracy of the questionnaire. The idiopathic form of RBD has a male preponderance and usually emerges after the age of 50. IRBD has not been reported to be associated with any other neurological symptoms except for those characteristic of RBD itself. That being said, recent pathophysiological and neuropsychological studies did reveal the insidious supervention of neurological symptoms on iRBD. IRBD might be a cryptogenetic neurological disease [1]. Men over the age of 50 years who have iRBD have been shown to be at very high risk for future parkinsonism [1]. In clinical practice, the RBDSQ-J may be applied within a stepwise diagnostic process, beginning with the questionnaire, followed by an interview and PSG. Thus, identifying clinical RBD as early as possible would be useful in clinical practice and in clinical trials of a potentially neuroprotective substance in the Japanese elderly population. Early-onset patients (650 years) were reported to have significantly more past and present psychiatric diagnoses and antidepressant usage than
late-onset patients (>50 years) [7]. In the future, it will be useful to validate the RBDSQ-J in early-onset patients. This study has some limitations. First, OSAS patients responding well to CPAP therapy were selected as the PSG-confirmed control group. Second, the male-to-female ratio was not matched between the iRBD and OSAS groups, and few female subjects were included. Third, the lack of spousal input was a potential problem as well as differentiating the severity of RBD within that group. Acknowledgments The authors thank Dr. K. Stiasny-Kolster (Department of Neurology, Center of Nervous diseases, Philips-University, Marburg, Germany) for permission to develop a Japanese version of the instrument and for her helpful comments. The authors thank T. Sairenchi (Department of Public Health, Dokkyo Medical University) for his valuable suggestions concerning statistical analysis.
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Appendix A
References
RBD screening questionnaire (RBDSQ) (Stiasny-Kolster et al. [2]).
[1] Gagnon JF, Postuma RB, Mazza S, Doyon J, Montplaisir J. Rapid-eye-movement sleep behaviour disorder and neurodegenerative diseases. Lancet Neurol 2006;5:424–32. [2] Stiasny-Kolster K, Mayer G, Schäfer S, Möller JC, Heinzel-Gutenbrunner M, Oertel WH. The REM sleep behavior disorder screening questionnaire–a new diagnostic instrument. Mov Disord 2007;22:2386–93. [3] American Academy of Sleep Medicine. Internal classification of sleep disorders, 2nd ed.: diagnosis and cording manual. Am Acad Sleep Med. Westchester Illinois; 2005 [p. 148–152]. [4] Shrout PE. Fleiss JL: intraclass correlations: uses in assessing rater reliability. Phychol Bull 1979;86:420–8. [5] Landis JR, Koch GGT. He measurement of observer agreement for categorical data. Biometrics 1977;33:159–74. [6] Iranzo A, Santamaria J. Severe obstructive sleep apnea/hypopnea mimicking REM sleep behavior disorder. Sleep 2005;28:203–6. [7] Teman PT, Tippmann-Peikert M, Silber MH, Slocumb NL, Robert Auger R. Idiopathic rapid-eye-movement sleep disorder: associations with antidepressants, psychiatric diagnoses, and other factors, in relation to age of onset. Sleep Med 2009;10:60–5.
English
Question
Answer
1 2
I sometimes have very vivid dreams My dreams frequently have aggressive or action-packed contents The dream contents mostly match my nocturnal behavior I know that my arms or legs move when I sleep It happened that I (almost) hurt my bed partner or myself I have or had the following phenomena during my dreams Speaking, shouting, swearing, laughing, loudly Sudden limb movements, ‘‘fights” Gesture, complex movements, that are useless during sleep, e.g., to wave, to salute, to frighten mosquitoes, fall off bed Things that fell down around the bed, e.g., bedside lamp, book, glasses It happens that my movements awaken me After awakening I mostly remember the content of my dreams well My sleep is frequently disturbed I have/had a disease of the nervous system (e.g., stroke, head trauma parkinsonism, RLS, narcolepsy, depression, epilepsy, inflammatory disease of the brain), which?
Yes/no Yes/no
3 4 5 6 6.1 6.2 6.3
6.4 7 8 9 10
Yes/no Yes/no Yes/no
Yes/no Yes/no Yes/no
Yes/no Yes/no Yes/no Yes/no Yes/no