INTRODUCTION
Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by the loss
of atonia during REM sleep, due to excessive motor activity or even dream performance[1 ],[2 ]. The prevalence of RBD among the general population is approximately 1.8%[3 ], whereas it may reach 55.7% in patients with Parkinson disease (PD)[4 ].
A diagnosis of RBD currently requires confirmation with polysomnography (PSG)[2 ],[5 ]. However, PSG may not be sufficiently available, especially in the public health
system[6 ]. In these situations, a clinical diagnostic measure might be useful[7 ],[8 ],[9 ],[10 ],[11 ]. The RBD screening questionnaire (RBDSQ) is a 13-item, self-administered, dichotomous
instrument, which also allows for the input from the patient’s companion. It was originally
published in German and English[7 ] and subsequently validated in Japan[12 ], China[13 ], South Korea[14 ], Turkey[15 ], and Italy[16 ]. Its use has already been validated for patients with PD[17 ],[18 ].
The objective of the present study was to validate the Brazilian Portuguese version
of the RBDSQ (RBDSQ-BR) for patients with PD.
METHOD
The current study had a cross-sectional, observational design. The sample of 82 patients
with PD was selected from a cohort of subjects participating in a follow-up study
in outpatients at the University Hospital of Ribeirão Preto School of Medicine of
Universidade de São Paulo . The following inclusion criteria used were: of Brazilian ethnicity, ≥18 years of
age, diagnosed with PD according to the United Kingdom Brain Bank criteria[19 ] (allowing the presence of family history of PD). They also needed to be available
for PSG and to provide verbal and written consent to participate in the study. The
inclusion periods were from February 2010 to November 2011 and from July to September
2014. The study was approved by the Research Ethics Committee under protocol numbers
2213/2009 and 13410/2009.
Questionnaire translation and cultural adaptation
The original author of the RBDSQ authorized the current study, which was performed
according to previously published protocols[20 ],[21 ]. The English questionnaire was initially translated by three bilingual Brazilian
natives separately (i.e ., one physician experienced in sleep disorders, one physician experienced in movement
disorders, and one engineer). The three versions were then analyzed by a committee
comprising bilingual physicians (three physicians experienced in movement disorders,
one physician experienced in sleep disorders, and one physician experienced in both
disorders, who were informed about the objective of the study, but were not involved
in the translation) who prepared a single version. This version was administered to
10 subjects (patients or their companions) as a pre-test. The committee then conducted
a revision of this version (RBDSQ-BR, see Online resource) toward identifying any
inconsistencies.
Subsequently, independent back-translation was performed by two native English teachers
(school teachers). These versions were reviewed by a committee of three professionals
(one experienced in movement disorders, one experienced in sleep disorders, and one
experienced in both), preparing a single, back-translated version that was sent to
the original author along with its Brazilian version for review and consent.
Clinical evaluation and polysomnography
Of the 82 patients, 69 patients with clinical and PSG data were selected for analysis.
The remaining 13 consecutive patients only had the RBDSQ-BR results available for
analysis.
The evaluation started with patients filling the RBDSQ-BR with the help of their companion,
immediately after the PSG or on the following day. The patient was then subjected
to a detailed sleep evaluation by an experienced physician who used the diagnostic
criteria from the 3rd edition of the International Classification of Sleep Disorders[5 ] and was blinded to the results from the questionnaire and PSG. This detailed evaluation
occurred within 30 days of the PSG. Evaluation of PD was performed by another experienced
physician who was blinded to the questionnaire, sleep evaluation, and PSG results,
using the Unified Parkinson’s disease rating scale[22 ], the Hoehn and Yahr Staging Scale (HY)[23 ], and the Schwab & England Functional Scale (S&E)[24 ]. All evaluations were performed with the patients in the on state .
PSG was performed using a digital polygraph (Biologic Sleepscan VISION PSG, Natus
Bio-logic Systems Inc., San Carlos, CA) using an extended 10–20 system electroencephalogram
(EEG), electro-oculogram, surface electromyogram (chin, masseter muscles, finger extensors,
and tibialis anterior muscle), nasal-cannula pressure transducer, thermocouple nasal/oral
airflow sensor chest and abdominal respiratory inductive plethysmography band transducers,
peripheral oximetry, electrocardiogram (ECG), snore and body position sensors, and
synched audio/video. The analysis was performed by two experienced physicians blinded
to the RBDSQ-BR results. All of the technical parameters used were performed in accordance
with the AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology,
and Technical Specification[25 ].
Statistical analysis
Categorical variables were assessed using Fisher’s exact test, while quantitative
variables were evaluated using Student’s t-tests or Mann-Whitney tests to compare
the groups of patients with PD, with (PD+RBD), and without (PD-RBD) RBD. Normality
assessment was performed using the Shapiro-Wilk test[26 ].
RBDSQ-BR reliability was assessed by determining both the temporal stability (re-test)
and homogeneity (internal consistency) using Spearman’s rank correlation coefficient
(p) for the re-test (21 days of interval) and the intraclass correlation coefficient
(ICC) for the total score (type III, two-factor, mixed analysis of variance [ANOVA])[27 ], and Cohen’s kappa coefficient (K) for each item. Item-test correlation was used
to estimate the coefficient discrimination of the items, accepting values >0.3. Internal
consistency was determined using the Cronbach’s α reliability estimate[27 ],[28 ],[29 ],[30 ].
The validity of the RBDSQ-BR was assessed using receiver operating characteristic
(ROC) curve and area under the ROC curve (AUC) analysis, with confidence intervals
determined using the exact binomial method[31 ]. Fisher’s exact test was used to evaluate each item. Sensitivity, specificity, positive
(PPV) and negative (NPV) predictive values, accuracy, and the likelihood ratios of
positive (LR+) and negative (LR-) results were calculated for each cut-off score and
item. Pre-test probability of RBD was 72.5% (50 PD+RBD subjects/69 total subjects)[32 ],[33 ].
P<0.05 were considered significant, with test power >80%. Microsoft Office Excel®,
IBM SPSS Statistics 19, and R 3.1.0 software were used for statistical analysis.
RESULTS
Clinical data
[Table 1 ] outlines the clinical data of the 69 patients. Only the presence of companions during
evaluation and dose-equivalent levodopa levels, which were higher in the PD+RBD group,
significantly differed between the groups.
Table 1
Sample characteristics.
•All
•n=69
•PD(-)RBD
•n=19
•PD(+)RBD
•n=50
p-valuea
Males, n (%)
39 (56.5)
10 (52.6)
29 (58.0)
0.79
Age (years; mean, SD)
60.4 (12.0)
59.7 (15.1)
60.7 (10.7)
0.79
PD duration (years; mean, SD)
8.6 (5.4)b
7.9 (6.4)b
8.9 (5.1)
0.57
Patient education (years; mean, SD)
6.1 (5.0)b
5.5 (4.1)b
6.3 (5.3)
0.72
Patients with companion, n (%)
54 (79.4)b
11 (61.1)b
43 (86)
0.04*
Companion is a roommate, n (%)
13 (19.1)b
2 (18.2)b
11 (25.6)
0.10
Companion education (years; mean, SD)
8.2 (4.9)
8.5 (4.8)
8.2 (5.0)
0.59
Part III UPDRS (“on”; mean, SD)
16.3 (9.4)
16.0 (7.9)
16.4 (10.0)
0.87
Total UPDRS (“on”; mean, SD)
33.3 (17.5)
30.0 (14.2)
34.5 (18.7)
0.85
HY (“on”; median, variance)
2 (0–3)
2 (1–2)
2 (0–3)
0.17
S&E (“on”; mean, SD)
84.1 (14.2)
86.3 (12.1)
83.2 (15.0)
0.55
Levodopa dose-equivalent (mg; mean, SD)
797.5 (451.2)b
534.7 (367.7)b
892.2 (443.8)
0.003*
Presence of other sleep disorders, n (%)
OSAS
47 (68.1)
15 (78.9)
32 (64.0)
0.26
RLS
7 (10.1)
0 (0.0)
7 (14.0)
0.18
Insomnia
39 (56.5)
12 (63.2)
27 (54.0)
0.59
>1 of the above disorders (with or without RBD)
29 (42.0)
9 (47.4)
20 (40.0)
0.91
HY: Hoehn and Yahr staging scale; OSAS: obstructive sleep apnea syndrome; PD: Parkinson’s
disease; PD(-)RBD: patient with PD and without RBD; PD(+)RBD: patients with PD and
RBD; RBD: REM sleep behavior disorder; REM: rapid eye movement; RLS: restless leg
syndrome; SD: standard deviation; S&E: Schwab and England Functional Scale; UPDRS:
Unified Parkinson’s Disease Rating Scale. a Comparative analysis between the PD(+)RBD and the PD(-)RBD groups. Fisher’s test was
used for categorical variables, while Mann-Whitney test and Student’s t-test was used
for quantitative variables; normality assessment was conducted using the Shapiro-Wilk
test; b missing data for one patient. *Significant (p<0.05).
Questionnaire reliability
RBDSQ-BR showed adequate internal consistency (0.809 overall Cronbach’s α; 95%CI 0.74–0.89;
n=69). Independent withdrawal of each item from the questionnaire caused no significant
changes in that value. The coefficient of discrimination of the item-test correlation
test was adequate for all items, except item 8 (0.26; p=0.03). Item 10 was inconclusive
(p>0.05). Re-test (n=13, after 21 days) showed moderate-to-strong correlation (p=0.764;
95%CI 0.30–0.97; p=0.002; 0.88 test power) and high agreement for total score (ICC=0.863;
95%CI 0.611–0.956; p<0.001). The evaluation of each item separately in the re-test
(n=13) showed complete agreement for items 2 and 3 (K=1.0), and acceptable agreement
(K>0.6) for items 6.2, 6.3, 7, and 8. The agreement of items 1 and 10 could not be
calculated because the test only elicited positive answers. The analysis of combined
items showed complete agreement for 1+2, and acceptable for 2+6.1, 6.1+6.2, 1+2+6.2,
1+6.2, 1+2+6.1, 1+2+6.1+6.2, 2+6.2, 1+6.1+6.2, and 2+6.1+6.2. No conclusive indication
(p>0.05) was assessed for the combined items 1+6.1.
Questionnaire validity
The RBDSQ-BR score was assessed using the ROC curve ([Figure 1 ]), showing discriminatory power between groups (n=69; 0.728 AUC; 95%CI 0.588–0.867;
p=0.004). According to the shortest distance principle, a cut-off score of 4 was optimum
for balancing sensitivity (84.0%; 95%CI 70.9–92.8) and specificity (57.9%; 95%CI 33.5–79.7),
determining 2.0 LR+ (95%CI 1.2–3.4) and 0.3 LR- (95%CI 0.1–0.6). A cut-off score 3
had the highest sensitivity (90.0%, 95% CI: 80.0, 98.0), with the lowest LR- 0.2 (95%
CI: 0.1, 0.6). Cut-off score 7 had 78.9% specificity (95% CI: 57.9, 94.7), with 2.7
LR+ (95% CI: 1.1, 6.6). ([Table 2 ]).
Figure 1 Receiver operating characteristic curve of the RBDSQ-BR (n=69; 0.728 AUC; 95%CI 0.588–0.867;
p=0.004). A cut-off score of 4 showed the shortest distance from the upper left corner,
balancing the sensitivity and specificity values, with confidence intervals avoiding
the main diagonal line (S=84%; 95%CI 74.0–94.0; E=57.9%; 95%CI 36.85–78.9). The confidence
intervals of cut-off scores 3, 5, 6, 7, 8, and 9 also avoided the main diagonal line.
All patients scored at least 1 in the questionnaire, precluding calculating the values
of that cut-off score (AUC: area under the curve; CI: confidence interval; E: specificity;
RBDSQ-BR: REM Sleep Behavior Disorder Screening Questionnaire - Brazilian Portuguese
version; REM: rapid eye movement; S: sensibility).
Table 2
Analysis of Brazilian Portuguese version of the Rapid Eye Movement Sleep Behavior
Disorder Screening Questionnaire cut-off scores, n=69.
Cut-off scores
•S%
•(95%CI)
•E%
•(95%CI)
•PPV%
•(95%CI)a
•NPV%
•(95%CI)a
•Ac%
•(95%CI)a
•LR+
•(95%CI)
•LR-
•(95%CI)
2
94.0 (88.0–100.0)
5.3 (0.0–15.8)
72.3 (59.8–82.7)
25.0 (0.6–80.6)
69.6 (57.3–80.1)
1.0 (0.9–1.1)
1.1 (0.1–10.3)
3b
90.0 (80.0–98.0)
42.1 (21.0–63.2)
80.4 (70.9–92.8)
61.5 (31.6–86.1)
76.8 (65.1–86.1)
1.6 (1.0–2.3)
0.2 (0.1–0.6)*
4b.c
84.0 (74.0–94.0)
57.9 (36.8–78.9)
84.0 (70.9–92.8)
57.9 (33.5–79.7)
76.8 (65.1–86.1)
2.0 (1.2–3.4)
0.3 (0.1–0.6)
5b
68.0 (56.0–80.0)
63.2 (42.1–84.2)
82.9 (67.9–92.8)
42.9 (24.5–62.8)
66.7 (54.3–77.6)
1.8 (1.0–3.4)
0.5 (0.3–0.9)
6b
66.0 (54.0–78.0)
68.4 (47.4–89.5)
84.6 (69.5–94.1)
43.3 (25.5–62.6)
66.7 (54.3–77.6)
2.1 (1.0–4.2)
0.5 (0.3–0.8)
7b
56.0 (43.9–70.0)
78.9 (57.9–94.7)
87.5 (71.0–96.5)
40.5 (24.8–57.9)
62.3 (49.8–73.7)
2.7 (1.1–6.6)**
0.7 (0.4–0.8)
8b
48.0 (34.0–64.0)
84.2 (63.2–100.0)
88.9 (70.8–97.6)
38.1 (23.6–54.4)
58.0 (45.5–69.8)
3.0 (1.0–8.9)
0.6 (0.4–0.9)
9b
40.0 (26.0–54.0)
89.5 (73.7–100.0)
90.9 (70.8–98.9)
36.2 (22.7–51.5)
53.6 (41.2–65.7)
3.8 (1.0–14.7)
0.7 (0.5–0.9)
10
26.0 (14.0–38.0)
89.5 (73.7–100.0)
86.7 (59.5–98.3)
31.5 (19.5–45.6)
43.5 (31.6–56.0)
2.5 (0.6–9.9)
0.8 (0.7–1.0)
11
14.0 (6.0–24.0)
94.7 (84.2–100.0)
87.5 (47.3–99.7)
29.5 (18.5–42.6)
36.2 (25.0–48.7)
2.7 (0.3–20.1)
0.9 (0.8–1.1)
12
10.0 (2.0–18.0)
94.7 (84.2–100.0)
83.3 (35.9–99.6)
28.6 (17.9–41.3)
33.3 (22.4–45.7)
1.9 (0.2–15.2)
0.9 (0.8–1.1)
13
0.0 (0.0–0.0)
94.7 (84.2–100.0)
0 (0–98.7)
26.5 (16.5–38.6)
26.1 (16.3–38.1)
0 (-)
1.1 (0.9–1.2)
Ac: accuracy; CI: confidence interval; E: specificity; LR+: likelihood ration of a
positive result; LR-: likelihood ration of a negative result; NPV: negative predictive
value; PPV: positive predictive value; REM: rapid eye movement; S: sensitivity. a Pre-test probability: 72.5% (50/69=0,725); b cut-off scores whose CI avoid the main diagonal line of the receiver operating characteristic
(ROC) curve; c cut-off score with the shortest distance from the upper left corner. *Lowest LR- value
within the cut-off scores, whose CI avoided the main diagonal line of the ROC curve.
**Highest LR+ value within the cut-off scores, whose CI avoided the main diagonal
line of the ROC curve. The LR+ CI also excluded the value “1.”
The value of each item for RBD diagnosis is outlined in [Table 3 ]. Items 1, 2, 6.1, and 6.2 were the only items with discriminatory power between
groups (p<0.05), separately. Among them, item 1 had the highest sensitivity (86%;
95%CI 73.3–94.2), with the lowest LR- (0.4; 95%CI 0.1–0.9).
Table 3
Analysis of each Brazilian Portuguese version of the Rapid Eye Movement Sleep Behavior
Disorder Screening Questionnaire itema , n=69.
Item
•S%
•(95%CI)
•E%
•(95%CI)
•PPV%
•(95%CI)b
•NPV
•(95%CI)b
•Ac%
•(95%CI)b
•LR+
•(95%CI)
•LR-
•(95%CI)
p-valuec
1
86.0 (73.3–94.2)**
36.8 (16.3–61.6)
78.2 (65.0–88.2)
50.0 (23.0–77.0)
72.5 (60.4–82.5)
1.4 (0.9–1.9)
0.4 (0.1–0.9)**
0.048*
2d
50.0 (35.5–64.5)
84.2 (60.4–96.6)
89.3 (71.8–97.7)
39.0 (24.2–55.5)
59.4 (46.9–71.1)
3.2 (1.1–9.3)***
0.6 (0.4–0.8)
0.013*
3d
50.0 (35.5–64.5)
73.7 (48.8–90.9)
83.3 (65.3–94.4)
35.9 (21.2–52.8)
56.5 (44.0–68.4)
1.9 (0.8–4.2)
0.7 (0.5–1.0)
0.105
4
58.0 (43.2–71.8)
57.9 (33.5–79.7)
78.4 (61.8–90.2)
34.4 (18.6–53.2)
58.0 (45.5–69.8)
1.4 (0.8–2.4)
0.7 (0.4–1.2)
0.286
5
32.0 (19.5–46.7)
84.2 (60.4–96.6)
84.2 (60.4–96.6)
32.0 (19.5–46.7)
46.4 (34.3–58.8)
2.0 (0.7–6.2)
0.8 (0.6–1.1)
0.235
6.1
58.0 (43.2–71.8)
84.2 (60.4–96.6)
90.6 (75.0–98.0)
43.2 (27.1–60.5)
65.2 (52.8–76.3)
3.7 (1.3–10.6)***
0.5 (0.3–0.7)
0.002*
6.2e
50.0 (35.5–64.5)
84.2 (60.4–96.6)
89.3 (71.8–97.7)
39.0 (24.2–55.5)
59.4 (46.9–71.1)
3.2 (1.1–9.3)***
0.6 (0.4–0.8)
0.013*
6.3e
26.0 (14.6–40.3)
94.7 (74.0–99.9)
92.9 (66.1–99.8)
32.7 (20.7–46.7)
44.9 (32.9–57.4)
4.9 (0.7–35.2)
0.8 (0.6–0.9)
0.091
6.4
28.0 (16.2–42.5)
94.7 (74.0–99.9)
93.3 (68.1–99.8)
33.3 (21.1–47.5)
46.4 (34.3–58.8)
5.3 (0.7–37.7)
0.8 (0.6–0.9)
0.052
7e
60.0 (45.2–73.6)
68.4 (43.4–87.4)
83.3 (67.2–93.6)
39.4 (22.9–57.9)
62.3 (49.8–73.7)
1.9 (0.9–3.8)
0.6 (0.4–0.9)
0.058
8e
62.0 (47.2–75.3)
52.6 (28.9–75.6)
77.5 (61.5–89.2)
34.5 (17.9–54.3)
59.4 (46.9–71.1)
1.3 (0.8–2.2)
0.7 (0.4–1.3)
0.290
9
52.0 (37.4–66.3)
73.7 (48.8–90.9)
83.9 (66.3–94.5)
36.8 (21.8–54.0)
58.0 (45.5–69.8)
2.0 (0.9–4.4)
0.6 (0.4–1.0)
0.064
10
88.0 (75.7–95.5)
15.8 (3.4–39.6)
73.3 (60.3–83.9)
33.3 (7.5–70.1)
68.1 (55.8–78.8)
1.0 (0.8–1.3)
0.8 (0.2–2.7)
0.699
Ac: accuracy; 95%CI: 95% confidence interval; E: specificity; LR+: likelihood ration
of a positive result; LR: likelihood ration of a negative result; NPV: negative predictive
value; PPV: positive predictive value; REM: rapid eye movement; S: sensitivity. a Answer “yes” in the item in question; b pre-test probability: 72.5% (50/69=0.725); c Fisher’s exact test; d items with complete agreement (K=1,0) in the re-test (n=13); e items with acceptable agreement (K>0.6) in the re-test (n=13). *Significant (p<0.05).
**Highest S and lowest LR- among the items with discriminatory power. ***Highest LR+
values among the items with discriminatory power.
[Table 4 ] outlines the combined values of positive answers for those items. The combinations
1+2, 1+6.1, 1+2+6.1, 2+6.1, 2+6.2, 6.1+6.2, 1+2+6.2, and 1+6.1+6.2 had discriminatory
power (p<0.05).
Table 4
Analysis of combined Brazilian Portuguese version of the Rapid Eye Movement Sleep
Behavior Disorder Screening Questionnaire itemsa , n=69.
Items
•S%
•(95%CI)
•E%
•(95%CI)
•PPV%
•(95%CI)b
•NPV%
•(95%CI)b
•Ac%
•(95%CI)b
•LR+
•(95%CI)
•LR-
•(95%CI)
p-valuec
1+2
50.0 (35.5–64.5)
84.2 (60.4–96.6)
89.3 (71.8–97.7)
39.0 (24.2–55.5)
59.4 (46.9–71.1)
3.2 (1.1–9.3)
0.6 (0.4–0.8)
0.013*
1+6.1
52.0 (37.4–66.3)
94.7 (74.0–99.9)
96.3 (81.0–99.9)
42.9 (27.7–59.0)
63.8 (51.3–75.0)
9.9 (1.4–67.8)**
0.5 (0.4–0.7)
0.003*
1+6.2
42.0 (28.2–56.8)
84.2 (60.4–96.6)
87.5 (67.6–97.3)
35.6 (21.9–51.2)
53.6 (41.2–65.7)
2.7 (0.9–7.9)
0.7 (0.5–0.9)
0.051
1+2+6.1
40.0 (26.4–54.8)
94.7 (74.0–99.9)
95.2 (76.2–99.9)
37.5 (24.0–52.6)
55.1 (42.6–67.1)
7.6 (1.1–52.8)**
0.6 (0.5–0.8)
0.007*
1+2+6.1+6.2
30.0 (17.9–44.6)
94.7 (74.0–99.9)
93.8 (69.8–99.8)
34.0 (21.5–48.3)
47.8 (35.6–60.2)
5.7 (0.8–40.2)
0.7 (0.6–0.9)
0.052
2+6.1
40.0 (26.4–54.8)
94.7 (74.0–99.9)
95.2 (76.2–99.9)
37.5 (24.0–52.6)
55.1 (42.6–67.1)
7.6 (1.1–52.8)**
0.6 (0.5–0.8)
0.007*
2+6.2
32.0 (19.5–46.7)
94.7 (74.0–99.9)
94.1 (71.3–99.9)
34.6 (22.0–49.1)
49.3 (37.0–61.6)
6.1 (0.9–42.7)
0.7 (0.6–0.9)
0.027*
6.1+6.2
40.0 (26.4–54.8)
94.7 (74.0–99.9)
95.2 (76.2–99.9)
37.5 (24.0–52.6)
55.1 (42.6–67.1)
7.6 (1.1–52.8)**
0.6 (0.5–0.8)
0.007*
1+2+6.2
32.0 (19.5–46.7)
94.7 (74.0–99.9)
94.1 (71.3–99.9)
34.6 (22.0–49.1)
49.3 (37.0–61.6)
6.1 (0.9–42.7)
0.7 (0.6–0.9)
0.027*
1+6.1+6.2
34.0 (21.2–48.8)
94.7 (74.0–99.9)
94.4 (72.7–99.9)
35.3 (22.4–49.9)
50.7 (38.4–63)
6.5 (0.9–45.2)
0.7 (0.6–0.9)
0.015*
2+6.1+6.2
30.0 (17.9–44.6)
94.7 (74.0–99.9)
93.8 (69.8–99.8)
34.0 (21.5–48.3)
47.8 (35.6–60.2)
5.7 (0.8–40.2)
0.7 (0.6–0.9)
0.052
Ac: accuracy; 95%CI: 95% confidence interval; E: specificity; LR+: likelihood ratio
of a positive result; LR-: likelihood ratio of a negative result; NPV: negative predictive
value; PPV: positive predictive value; REM: rapid eye movement; S: sensitivity. a Answer “yes” in the combined items; b pre-test probability: 72.5% (50/69=0.725); c Fisher’s exact test. *Significant (p<0.05). **LR+ whose confidence intervals excluded
the value 1.
The AUC of the ROC curve of each condition was calculated to assess whether other
sleep disorders might be confounders. Only insomnia was significant, albeit with a
smaller AUC than that of RBD (AUC 0.652; 95%CI 0.519–0.785; p=0.031; [Table 5 ]).
Table 5
Other sleep disorders as Brazilian Portuguese version of the Rapid Eye Movement Sleep
Behavior Disorder Screening Questionnaire confounders: comparison between area under
the curve, n=69.
AUC
95%CI
p-value
RBDa
0.728
0.588, 0.867
0.004*
OSAS
0.456
0.317, 0.596
0.562
RLS
0.674
0.522, 0.826
0.133
Insomnia
0.625
0.519, 0.785
0.031*
AUC: area under the curve; 95%CI: 95% confidence interval; OSAS: obstructive sleep
apnea syndrome; RLS: restless leg syndrome. a Highest AUC value for Rapid Eye Movement Sleep Behavior Disorder Screening Questionnaire
use. *Significant (p<0.05).
DISCUSSION
This study determined the diagnostic value of the Brazilian Portuguese version of
the RBDSQ to validate its use for patients with PD. All participants were subjected
to the gold standard of RBD diagnosis (clinical interview+PSG)[5 ]. The original RBDSQ study[7 ] and other studies that have sought to assess the diagnostic value of the questionnaire[12 ],[13 ],[14 ],[15 ],[16 ],[17 ],[18 ] have also used this gold standard to evaluate participants (except healthy controls).
The sample consisted of 50 participants in the PD+RBD group and 19 participants in
the PD-RBD group. As in a previous study conducted by Stiasny-Kolster et al.[18 ], the sample had a slight predominance of elderly men, although they were slightly
younger (i.e ., 68 years versus 60.4±12 years, respectively). Although the disease duration was similar (approximately
8.5 years), PD was less advanced in the current study (i.e ., 2.0 versus 3.0) according to the HY staging.
RBDSQ-BR proved reliable, with adequate internal consistency (overall Cronbach’s α=0.809)[28 ]. The item-test correlation was adequate (>0.3), except for item 8 (0.26), suggesting
the low discriminatory power of this item. Item 10 was inconclusive (p>0.05). The
total score of the instrument showed high agreement (ICC=0.863). Items 2, 3, 6.2,
6.3, 7, and 8 had adequate agreement when assessed separately (K>0.60)[30 ]. The other items were inconclusive in this regard.
The original study by Stiasny-Kolster et al.[7 ] already had adequate internal consistency (0.885 Cronbach’s α), which was also shown
in other validation studies conducted in Japan[12 ], China[13 ], South Korea[14 ], Turkey[15 ], and Italy[16 ]. The first study, which focused on patients with PD in Japan, found an adequate
internal consistency (0.73 Cronbach’s α)[17 ]. The item-test correlation of all items in the original study[7 ] was satisfactory (>0.3); however, the South Korean and Italian studies reported
inadequate item-test correlations for item 10[14 ],[16 ]. Our study showed low discriminatory power for item 8. This item indicates an awakening
while dreaming due to the motor activity reported in item 7 (see Online resource).
If this relationship is not recognized, it can be assumed that item 8 is about remembering
the dreams that occurred the night before. Considering the low schooling ([Table 1 ]), a misinterpretation could explain the low discriminatory power of this item in
our sample.
Agreement analysis of the re-test total score was reported in some studies[12 ],[13 ],[14 ],[15 ] and proved satisfactory, albeit with variable agreement between the instrument items.
Miyamoto et al.[12 ] showed good agreement for items 1, 2, 5, and 6.1 (K>0.60). Conversely, the South
Korean study[14 ] only reported this for items 7 and 10. Thus far, no study had focused on a population
of patients with PD for assessing the RBDSQ agreement of either its total score or
its items.
In our study, a cut-off score of 4 enabled the correct diagnosis of 76.8% subjects
and provided the best balance between sensitivity (84%) and specificity (57.9%), with
2.0 LR+ and 0.3 LR-. A cut-off score of 3 also correctly diagnosed 76.8% individuals
and provided increased sensitivity (90.0%) with 0.2 LR- (an approximately 5-fold reduction
in the probability of having RBD), whereas a cut-off score of 7 provided increased
specificity (78.9%), with a correct diagnosis of 62.3% subjects and 2.7 LR+. Thus,
total scores of <3 in our study might be useful to exclude RBD (LR- from 0.5 to 0.2
may generate small-to-moderate changes in post-test probability)[33 ]. The separate analysis of each item in our study enabled us to increase its specificity.
Both items 2 and 6.2 had a specificity of 84.2%, with 3.2 LR+ (an increase of slightly
more than 3 times the probability) and may be regarded as of little (but not necessarily
unimportant) utility for RBD diagnosis[33 ]. The use of combined items also enabled us to further increase the specificity.
The combination of positive answers in items 1+2+6.2, 2+6.1, and 6.1+6.2 determined
a specificity of 94.7%, rendering more robust LR+ (6.1 up to 7.6, indicating an approximately
6-to-8-fold increase in the probability of having RBD) with acceptable reliability.
The original study by Stiasny-Kolster et al.[7 ] indicated a higher value (cut-off score 5) of the balance between sensitivity and
specificity (96% sensitivity and 56% specificity). The low specificity of the total
score of the instrument was attributed to the presence of comorbidities associated
with excessive motor activity during sleep, including restless leg syndrome (RLS),
obstructive sleep apnea syndrome (OSAS), periodic limb movements, and narcolepsy.
Those comorbidities would render positive answers in items indicating limb movements
(sub-items 4, 5, 6.2, and 7), inflating the resulting score. Another explanation was
the presence of other sleep and neurological disorders, which would have rendered
positive answers in sub-items 9 and 10, increasing the final score. As in the present
study, the analysis of separate items in the Stiasny-Kolster study also allowed an
increase of specificity, with 85.3-91.1% specificity when items 5, 6.3, and 6.4 were
answered positively.
In our study, both the PD+RBD and PD-RBD subgroups included patients with other sleep
disorders (such as RLS, OSAS, and insomnia), at similar ratios between groups. Thus,
the low specificity found in the current study may be explained using the same arguments.
The RBDSQ-BR score, however, showed no potential to select those patients, except
in the case of insomnia. Even in this case, the resulting AUC (0.625) was less than
that related to RBD (0.728), which was the target of the questionnaire.
The RBDSQ versions that were validated in Far East Asia[12 ],[13 ],[14 ],[15 ] confirmed the cut-off score of 5 reported in the original study[7 ], with sensitivity ranging from 88.5 to 100%, albeit with markedly high specificities
(more often >90%). A new validation in Europe (Italy)[16 ] indicated a higher value as the best cut-off score (i.e ., 8), with sensitivity of 84.2% and lower specificity of 78.0%. The validation study
in Japan reported item 5 as the most specific one (92.3-96.4%) when the items were
analyzed separately[12 ]. Tari et al.[15 ] found higher specificities in the Turkish population, not only for item 5 (85.7-97.4%),
but also for items 7 (94.9%) and 10 (93.6%). Curiously, the Italian study[16 ] not only had higher specificities in some items separately (83.2-83.5% for items
5, 6.3, and 6.4), but also higher sensitivities than the cut-off total score (90.8-92.1%
for items 1, 3, and 6.1).
The samples of those studies, however, were different from ours in that they were
sometimes highly heterogeneous. Few studies have included patients with PD[7 ],[15 ], and except for that by Wang et al.[13 ], the number of subjects with PD in these studies was minimal. Further, the method
of selecting participants was not homogeneous between studies. Moreover, although
the RBDSQ allows the companion to help, not all studies included that participation[12 ],[15 ].
The study by Nomura et al.[17 ] from 2011 was the first with the primary objective of evaluating RBDSQ performance
specifically in patients with PD. Using the version validated in Japan[12 ], consecutive patients with PD and patients with RBD alone were evaluated. The ROC
curve of patients with PD showed a value of 6 as the best cut-off score, with a sensitivity
similar to that observed in our study (84.2%), albeit with a considerably higher specificity
(96.2%), which was comparable to other studies conducted in Far East Asia. The increase
of 1 point in the cut-off score was explained by the positivity necessarily present
in item 10 of the instrument. A possible explanation for the high value of specificity
may be the fact that apparently no other sleep disorders were identified in the patients.
Otherwise, they would have tended to score several items of the instrument, as previously
mentioned.
In 2015, Wang et al.[13 ] included a sub-sample of patients with PD, with and without RBD. The cut-off score
of 6 was also the most adequate for those subjects, with a sensitivity and specificity
of 90.9 and 91.9%, respectively, which determined the diagnostic accuracy in 91.52%
of patients. Their results did not show other sleep disorders in those patients, which
might explain the high specificity.
In the same year, Stiasny-Kolster et al.[18 ] evaluated consecutive patients with PD, with no help from the companion, and concluded
that the “learning” effect resulting from a detailed clinical evaluation before filling
in the questionnaire may have significantly affected the diagnostic power of the instrument,
at least in the case of PD.
In our study, the patients filled in the questionnaire before the clinical evaluation,
which may explain why the overall RBDSQ-BR performance was clearly similar to the
poor performance of the group that filled the instrument first in the previous study[18 ]. Nonetheless, the performance of the patients in the current study cohort was relatively
better, which may be explained by the fact that most of our participants were helped
by their companions. However, it should be noted that a possible epidemiological survey
in our setting would most likely include the companion alongside the patient with
PD filling in the questionnaire.
A few limitations in the current study must be noted. First, there was a lack of a
control group of healthy subjects and a group of subjects with RBD and without PD
(RBD alone), which would have improved the evaluation of the questionnaire performance
and increased the generalization of the findings. Second, despite the similarity in
education, either the patients’ or their companions’, between the analysis groups,
its effect on the instrument performance cannot be ruled out. Further, the effect
of companion assistance on instrument accuracy could also not be ruled out. Finally,
the imbalance between the sizes of the groups, i.e ., the small n in the group of patients without RBD, may have affected the determination of a low
cut-off total score compared with the cut-off scores of other studies on patients
with PD.
In conclusion, the results of the current study demonstrated that RBDSQ-BR was a valid
and reliable instrument and that it may be useful for diagnosing RBD in Brazilian
patients with PD. The instrument may also help in improving the selection of cases
for a more detailed clinical evaluation or even polysomnography.
