Essential tremor (ET) and Parkinson disease (PD) are common

SCIENTIFIC INVESTIGATIONS pii: jc-00399-14 http://dx.doi.org/10.5664/jcsm.4778 Sleep Disturbances in Essential Tremor and Parkinson Disease: A Polysomnographic Study Banu Ozen Barut, MD 1 ; Nida Tascilar, MD 1,2 ; Armagan Varo, MD 1 1 Department of Neurology, Bülent Ecevit University, Zonguldak, Turkey; 2 Sleep Disorders Center, Bülent Ecevit University, Zonguldak, Turkey Objective: Sleep problems are a common non-motor complication of Parkinson disease (PD), and patients with essential tremor (ET) share a number of motor and non-motor features of PD. To clarify the relationship between these disorders, we evaluated the sleep problems in patients with ET and PD using assessment scales and objective polysomnographic (PSG) testing. Method: Twenty-one consecutive patients with PD, 16 with ET, and 14 healthy subjects participated in this study and were compared in terms of sleep related complaints, final sleep related diagnosis, and polysomnographic features. Results: The results of our study have shown that patients with PD were more likely than were those with ET to have a history of REM sleep behavior disorders (RBD) (p = 0.001) and excessive daytime sleepiness (p 0.05). Additionally, PSG data revealed that ET patients had lower mean SpO 2 values (p 0.05) and REM without atonia (RWA) (p = 0.032) than did patients with PD. Conclusion: This is the first study to use PSG to evaluate sleep problems both in ET and PD patients. The results point out different sleep problems in these two common movement disorders which should be investigated in further studies. Keywords: essential tremor, Parkinson disease, sleep, REM behavior disorder (RBD), REM without atonia (RWA) Citation: Barut BO, Tascilar N, Varo A. Sleep disturbances in essential tremor and Parkinson disease: a polysomnographic study. J Clin Sleep Med 2015;11(6):655 662. Essential tremor (ET) and Parkinson disease (PD) are common movement disorders in the geriatric population. 1,2 In addition to motor symptoms, such as tremor, rigidity, and bradykinesia, non-motor symptoms pose major problems for PD patients and affect their quality of life. 3 There is also growing evidence to suggest that non-motor symptoms also accompany postural tremors in patients with ET. 4 Cognitive difficulties, depression, anxiety, olfactory problems, and sleep disorders are all non-motor symptoms that have been reported in both ET and PD patients. 3,4 Impaired sleep is one of the most common non-motor symptoms of PD. Dopamine, which is the major neurotransmitter that is dysregulated in PD, plays an important role in the regulation of sleep and circadian homeostasis. As a result, sleep problems related to either the disease itself or the medication prescribed are frequently seen in PD patients. 5 Several studies have investigated the sleep problems of PD patients, but only three such studies have been carried out in ET populations. 6 8 A study conducted by Chandran et al. concluded that patients with ET have poor nocturnal sleep quality but not excessive daytime sleepiness, 8 whereas Adler et al. showed that the prevalence of RBD was similar in patients with ET and control group. 7 In contrast, Gerbin et al. observed that sleep scores in ET patients were intermediate between those of patients with PD and controls, suggesting a mild form of sleep disruption. 6 However, none of these studies used objective sleep assessment tools such as polysomnography and instead relied on subjective methods, such as self-report questionnaires, which BRIEF SUMMARY Current Knowledge/Study Rationale: Sleep problems in ET and PD patients had been investigated in few studies by using subjective assessment tools like self-report questionnaires previously. This study was conducted to evaluate and to compare sleep problems in these two common movement disorders by using PSG which is an objective assessment tool. Study Impact: This study will improve the knowledge about sleep problems in ET and PD patients. Furthermore this is the first study comparing sleep problems in ET and PD patients using PSG. are prone to error. Importantly, the study performed by Gerbin recommended a combination of sleep diaries and polysomnography be used in future studies to investigate sleep problems in patients with ET. 6 The aim of our study was to evaluate sleep disturbances and sleep-related events in patients with ET, PD, and controls, using both self-assessment tools and polysomnographic readings. METHODS Study Sample The ethics committee of Bülent Ecevit University approved this prospective study, and informed consent was obtained from all participants. Between 2010 and 2012, 21 patients with PD who fulfilled the Parkinson Disease Society Bank criteria, 9 and 16 patients with ET who fulfilled Movement Disorders 655 Journal of Clinical Sleep Medicine, Vol. 11, No. 6, 2015

BO Barut, N Taşçılar and A Varo Society Tremor Investigation Group criteria 10 were recruited from our movement disorders outpatient clinic, along with 14 healthy controls with no sleep disorder. The control group was examined to exclude any Parkinson-like symptoms or postural or kinetic tremors before they were enrolled in the study. All patients were examined by two neurologists one specializing in movement disorders and the other in sleep disorders. All the participants were assessed with the Geriatric Depression Scale to exclude major depression. 11 Patients with secondary parkinsonism or postural or kinetic tremors secondary to other diseases were excluded, as were patients with severe PD (Hoehn and Yahr score 4). The disease severity of PD and ET patients was assessed using the United Parkinson s Disease Rating Scale (UPDRS) motor subscale 12 and the Fahn-Tolosa- Marin tremor assessment scale (FTM TAS), 13 respectively. Study Design All eligible patients were examined in our accredited sleep disorder center. Sleep-related complaints were evaluated in patients with PD, ET, and controls in face-to-face interviews, including a formal routine sleep questionnaire. After this interview, in the same session, the Epworth Sleepiness Scale (ESS), 14 the Turkish version of the Pittsburgh Sleep Quality Index (PSQI), 15 and the Fatigue Severity Scale (FSS), 16 were used to determine excessive daytime sleepiness (EDS), subjective sleep quality, and fatigue, respectively. REM sleep behavior disorder (RBD) occurs in up to 50% of patients with PD and is often considered to be a primary manifestation of the disease. 17 It was therefore investigated first in face-to-face interviews with two neurologists in separate sessions; patients were then assessed using an RBD screening questionnaire and polysomnography. Patients and/or their bed partners and caregivers were asked about any dream-enacting, violent, or injurious behavior during sleep to establish a clinical history of RBD for each participant. 18 The PSG results of ET and PD patients were then compared based on the presence of a clinical history of RBD (RBD-H), PSG evidence of RBD or subclinical RBD (RBD-P), and an actual diagnosis of RBD (RBD-D). Subclinical RBD, defined as REM without atonia (RWA), contains polysomnographic features of RBD. 19 For this reason, subclinical RBD, RWA, and PSG features of RBD were used interchangeably. Sleep-related diagnoses, including obstructive sleep apnea syndrome (OSAS), periodic limb movements in sleep (PLMS), and RBD-D, were made based on the results of PSG according to the International Classification of Sleep Disorders (ICSD-2). 19 As the use of antidepressants by patients with PD is common, due to ethical concerns, we did not request that patients stop taking antidepressant medication. Instead, we compared the results of patients who were and were not being treated for depression. Polysomnography Polysomnographic recordings were taken of all subjects using ALICE Sleepware 5 (Philips Respironics, Murrysville, PA, USA) in our sleep disorder clinic, which was accredited by the Turkish Sleep Medicine Society in 2008. PSG included 6 electroencephalogram channels (F4, M1-C4, M1-O2, M1- F3, M2-C3, M2-O1, and M2) based on the 10-20 international electrode placement system, right and left electrooculogram channels, a chin electromyogram, and electrocardiography channels. Airflow was monitored by nasal cannula and thermistors, and respiratory movements were assessed by thoracic and abdominal strain gauges. Snoring was monitored using a microphone placed above the larynx, and sleep saturation was measured continuously using a finger oximeter. The body position of each subject was recorded, and leg movements were assessed using left and right tibial electromyogram channels, as described by Coleman et al. 20 PSG recordings were based on the American Academy of Sleep Medicine (AASM) manual for the scoring of sleep and associated events. 21 The apnea-hypopnea index (AHI), respiratory disturbance index (RDI), arousals (total arousal index [TAI], spontaneous arousal index [SAI], respiratory arousal index [RAI], and leg movement arousal index [LAI]), periodic leg movement index (PLMI), and RWA/RBD-P were scored according to the AASM manual. 21 All sleep and respiratory events were manually scored at 30-s intervals. The following PSG parameters were evaluated: time in bed (TIB), total sleep time (TST), wake time after sleep onset (WASO), sleep efficiency index (SEI; percent of TST TIB), sleep continuity index (SCI; percent of TST SPT), percentage of time spent in each sleep stage (AHI, RDI, TAI, SAI, and RAI), and percentage of minimum and mean oxygen saturation during sleep and PLMI. Statistical Analysis Descriptive statistics of data were computed as Mean ± SE, count, and percent. Kolmogorov-Smirnov test for numerical variables (Tables 3 6) was used for normality assumption; and all numerical variables according to this test had a normal distribution. Likelihood ratio χ 2 test was used for relation between group and categorical variables. To understand the necessity of adjustments according to age and BMI, groups were compared with one-way ANOVA in terms of age and BMI. This analysis showed that BMI did not differ significantly among the groups, but groups were significantly different according to age. Before correction, age groups were compared by one-way ANOVA (Tables 3 and 6). Following that, covariance analysis followed by Tukey multiple comparison test was used for differences among the groups with regard to numerical variables. Only age was included in this analysis as a covariate (results in Tables 4 and 6). Type I error was accepted as 0.05 (significant result, p 0.05), and PASW (ver. 18) program was used in all statistical analysis. RESULTS The PD group consisted of 21 patients (13 male and 8 female) with a mean age of 61.9 ± 1.97 years; they had been suffering from PD for 2 to 13 years, with mean disease duration of 5.57 ± 0.75 years. The mean UPDRS motor subscale score of this group was 19.23 ± 1.97. When medications were analyzed, 13 patients with PD were using a combination of levodopa and a dopamine agonist (DA), 4 were using only a DA, 3 patients were taking levodopa alone, and one was not taking any medication. Eight patients in the PD group were taking medication for depression. The levodopa equivalency dose was 571.00 ± 192.09 mg among PD patients. Journal of Clinical Sleep Medicine, Vol. 11, No. 6, 2015 656

Essential Tremor and Parkinson Disease Table 1 Demographic features. PD (n = 21) ET (n = 16) Control (n = 14) p Age 61.9 ± 1.97 66.12 ± 2.12 50.57 ± 2.30 0.0001 * Gender (F/M) 8/13 5/11 5/9 0.110 ** BMI 27.01 ± 0.79 29.32 ± 1.01 27.57 ± 1.40 0.254 * Antidepressant usage (+/ ) 8/13 4/12 0.396 ** Disease severity PD (FTM TAS Score) 25.56 ± 3.53 Disease severity ET (UPDRS Score ) 19.23 ± 1.97 PD Treatment # LD + DA 13 LD 3 DA 4 ET Treatment ## P+B 4 P 7 B 3 Levodopa dose equivalency (mg) 571.00 ± 192.09 PD Duration (year) 5.57 ± 0.75 ET Duration (year) 12 ± 2.42 # LD+DA, number of patients using both levodopa and dopamine agonists; LD, number of patients using only levodopa; DA, number of patients using only dopamine agonist. ## P+B, number of patients using both primidone and β-blockers; P, number of patients using only primidone; B, number of patients using only β-blockers. * One-way ANOVA analysis was used. ** Likelihood ratio χ 2 test was used. BMI; body mass index; PD, Parkinson disease; ET, essential tremor. The ET group consisted of 16 patients (5 female and 11 male) with a mean of age 66.12 ± 2.12 years; they had been suffering from ET for 3 to 35 years, with mean disease duration of 12 ± 2 years. Disease severity was assessed using the FTM TAS; mean score of this group was 25.56 ± 3.53. Two patients were not taking any medication; 7 were taking primidone; 3 were taking β-blockers; and 4 were taking a combination of primidone and β-blockers. Additionally, 4 patients with ET were taking serotonergic antidepressant medication. We found no significant differences in the antidepressant use of the PD and ET groups (p = 0.396). The control group consisted of volunteers who were either patient relatives or hospital personnel and who had no sleep problems. Fourteen control subjects (9 male and 5 female) with a mean of age of 50.57 ± 2.30 years participated in the study. Participants in the control group were significantly younger than members of both the PD and ET groups (p = 0.0001). Accordingly, the mean data acquired were therefore adjusted by age, and the results were re-analyzed. Demographic features are summarized in Table 1 Sleep Complaints Based on Face-to-Face Interviews and Sleep-Related Questionnaires Sleep-related complaints, including insomnia and RBD-H, were assessed during face-to-face interviews, and the ESS, PSQI, and FSS scores were calculated for all participants. We found no statistically significant differences in sleep insomnia between PD and ET groups (p = 0.132), but the RBD-H was higher in the PD than the ET group (p = 0.001; Table 2). Initial results suggested that the control group scored significantly higher on the PSQI and ESS than did the PD group (p = 0.003 and p = 0.041, respectively; Table 3). However, because of the age difference between the groups, statistical analyses were repeated after age adjustment. After re-analysis, the PD group had higher PSQI and FSS scores than the control group (p = 0.011 and p 0.05, respectively) and higher ESS scores than the ET group (p 0.05; Table 4). Polysomnography and Sleep Disorders When the polysomnographic parameters were analyzed, PD patients spent a longer time in stage 1 sleep and were more likely to report WASO than the control group (p = 0.029 and p = 0.05, respectively), although these changes were no longer statistically significant after adjustment for age. The mean SpO 2 was significantly lower in the ET than the PD group (p = 0.017), and this remained significant after adjustment for age. Patients were diagnosed as suffering from RBD-D, OSAS, PLMS, or RBD-P (RWA) according to the AASM manual. 21 The incidence of RBD-H, RBD-P, and RBD-D were significantly higher in the PD group than the ET group (p = 0.001, p = 0.032, and p = 0.012, respectively, Table 2). Because the use of antidepressants has been linked with RBD and RWA, 22 analyses were repeated excluding patients taking medication for depression. Although RBD-H and RWA were still more common in patients with PD than in those with ET (p = 0.015 and p = 0.048, respectively), the difference in RBD-D was no longer statistically significant (p = 0.096; Table 2). DISCUSSION It can be challenging to distinguish between ET and PD due to the existence of Parkinson-like symptoms (e.g., bradykinesia, rest tremors) in patients with ET and postural tremors in patients with PD. 23 As a result, Jain et al. reported that 657 Journal of Clinical Sleep Medicine, Vol. 11, No. 6, 2015

BO Barut, N Taşçılar and A Varo approximately one-third of patients with ET are misdiagnosed, and some actually suffer from PD. 24 Specific clinical parameters, such as features of the tremor (frequency, amplitude, pattern, and distribution) and associated neurological findings can be beneficial in differentiating between these conditions. Additionally, laboratory tests, such as accelerometry, surface Table 2 Comparison of sleep related problems and final diagnoses of patients with PD and ET. Patients without Antidepressant All Patients, n (%) Medication, n (%) PD ET p PD ET p Insomnia 0.132 0.305 + 7 (33.3) 2 (12.5) 3 (23.1) 1 (8.3) 14 (66.7) 14 (87.5) 10 (76.9) 11 (91.7) RBD-H 0.001 0.015 + 8 (38.1) 0 (0) 4 (30.8) 0 (0) 13 (61.9) 16 (100.0) 9 (69.2) 12 (100.0) RBD-D 0.012 0.096 + 5 (23.8) 0 (0) 2 (15.4) 0 (0.0) 16 (76.2) 16 (100.0) 11 (84.6) 12 (100.0) OSAS 0.234 0.070 + 9 (42.9) 10 (62.5) 4 (30.8) 8 (66.7) 12 (57.1) 6 (37.5) 9 (69.2) 4 (33.3) PLMS 0.893 0.568 + 7 (33.3) 5 (31.3) 3 (23.1) 4 (33.3) 14 (66.7) 11 (68.8) 10 (76.9) 8 (66.7) RBD-P/RWA 0.032 0.048 + 11 (52.4) 3 (18.8) 7 (53.8) 2 (16.7) 10 (47.6) 13 (81.3) 6 (46.2) 10 (83.3) Table 3 Polysomnographic and sleep screening tool results. Sleep Measure PD (n = 21) ET (n = 16) Control (n = 14) p Time in bed 458.73 ± 13.56 465.81 ± 7.86 451.35 ± 14.44 0.751 Total sleep time 321.65 ± 18.54 339.84 ± 19.89 358.25 ± 14.021 0.375 Wake before sleep 11.60 ± 2.27 20.40 ± 5.70 12.21 ± 1.99 0.178 Wake after sleep onset 139.78 ± 18.37 105.53 ± 18.07 80.30 ± 8.37 0.050 Sleep efficiency index 69.49 ± 3.74 73.33 ± 4.39 79.61 ± 1.70 0.166 Sleep continuity index 73.98 ± 3.73 77.89 ± 4.24 83.96 ± 1.90 0.165 REM sleep % 10.54 ± 1.99 10.90 ± 1.45 13.99 ± 1.81 0.391 Stage I sleep % 46.10 ± 4.81 40.90 ± 4.77 27.79 ± 3.97 0.029 Stage II sleep % 37.26 ± 3.36 37.91 ± 4.26 46.10 ± 3.24 0.208 Stage III sleep % 6.09 ± 1.53 10.23 ± 2.78 10.49 ± 2.38 0.257 Central apnea (#/h) 1.06 ± 0.86 0.25 ± 0.21 0.05 ± 0.02 0.469 Apnea-hypopnea index 10.95 ± 4.17 8.30 ± 2.16 1.87 ± 0.49 0.148 Respiratory disturbance index 12.51 ± 4.21 14.18 ± 4.98 2.55 ± 0.50 0.133 Total arousal index 27.07 ± 2.71 23.88 ± 2.29 18.57 ± 2.09 0.069 Respiratory arousal index 5.35 ± 2.03 4.68 ± 1.33 1.40 ± 0.26 0.222 Leg movement arousal index 5.12 ± 0.78 6.05 ± 1.01 5.80 ± 0.81 0.726 Spontaneous arousal index 16.07 ± 1.99 12.85 ± 1.88 11.22 ± 1.65 0.191 SpO 2 mean 93.50 ± 0.60 91.13 ± 0.58 93.14 ± 0.58 0.017 Periodic leg movement index 14.95 ± 5.36 14.06 ± 4.69 4.98 ± 2.37 0.291 Pittsburgh Sleep Quality Index 8.85 ± 1.10 5.87 ± 1.03 3.78 ± 0.66 0.030 Epworth Sleep Scale score 9.19 ± 1.63 5.25 ± 1.18 4.57 ± 0.88 0.041 Fatigue Severity Scale score 35.19 ± 4.23 32.26 ± 5.36 22.76 ± 4.39 0.182 Journal of Clinical Sleep Medicine, Vol. 11, No. 6, 2015 658

Essential Tremor and Parkinson Disease Table 4 Polysomnographic and sleep screening tool results (after age adjustment). Sleep Measure PD (n = 21) ET (n = 16) Control (n = 14) p Time in bed 456.75 ± 11.38 459.15 ± 13.9 461.93 ± 16.03 0.965 Total sleep time 321.05 ± 17.14 338.44 ± 20.25 360.70 ± 24.00 0.420 Wake before sleep 12.14 ± 3.38 21.82 ± 4.01 9.81 ± 4.69 0.117 Wake after sleep onset 138.50 ± 15.59 99.42 ± 18.33 89.70 ± 21.69 0.108 Sleep efficiency index 69.49 ± 3.37 73.32 ± 4.12 79.61 ± 4.75 0.242 Sleep continuity index 74.04 ± 3.37 78.09 ± 4.03 83.65 ± 4.62 0.258 REM sleep % 10.88 ± 1.65 12.02 ± 2.02 12.21 ± 2.33 0.851 Stage I sleep % 45.00 ± 4.14 37.21 ± 5.06 33.66 ± 5.83 0.225 Stage II sleep % 37.84 ± 3.31 39.84 ± 4.04 43.03 ± 4.66 0.671 Stage III sleep % 6.32 ± 1.98 11.01 ± 2.42 9.26 ± 2.79 0.287 Central apnea (#/h) 0.94 ± 0.56 0.16 ± 0.69 0.70 ± 0.79 0.453 Apnea-hypopnea index 9.68 ± 2.61 4.03 ± 3.19 8.67 ± 3.68 0.377 Respiratory disturbance index 11.21 ± 3.44 9.80 ± 4.20 9.51 ± 4.85 0.944 Total arousal index 26.85 ± 2.29 23.14 ± 2.80 19.73 ± 3.23 0.192 Respiratory arousal index 4.87 ± 1.40 3.07 ± 1.71 3.96 ± 1.97 0.700 Leg movement arousal index 5.07 ± 0.80 5.87 ± 0.98 6.08 ± 1.13 0.699 Spontaneous arousal index 16.38 ± 16.38 13.88 ± 2.11 9.58 ± 2.44 0.093 SpO 2 mean 93.66 ± 0.52 91.81 ± 0.66 92.18 ± 0.73 0.050 Periodic leg movement index 13.64 ± 4.09 9.44 ± 4.89 12.13 ± 5.61 0.291 Pittsburgh Sleep Quality Index 8.78 ± 0.93 5.62 ± 1.13 4.17 ± 1.31 0.011 Epworth Sleep Scale score 8.98 ± 1.26 4.54 ± 1.54 5.69 ± 1.78 0.050 Fatigue Severity Scale score 34.23 ± 4.08 29.16 ± 5.09 27.89 ± 5.88 0.050 Table 5 Polysomnographic and sleep screening tool results in patients with PD and ET (excluding patients using serotonergic antidepressants). Sleep Measure PD (n = 13) ET (n = 12) Control (n = 14) p Time in bed 465.57 ± 20.84 459.50 ± 8.76 451.35 ± 14.44 0.809 Total sleep time 324.96 ± 23.37 356.12 ± 13.03 358.25 ± 14.02 0.331 Wake before sleep 11.20 ± 2.93 16.83 ± 5.22 12.21 ± 1.99 0.513 Wake after sleep onset 146.86 ± 25.46 86.54 ± 12.34 80.30 ± 8.37 0.013 Sleep efficiency index 70.38 ± 4.98 77.63 ± 2.79 79.61 ± 1.70 0.141 Sleep continuity index 74.90 ± 4.87 81.95 ± 2.50 83.96 ± 1.90 0.132 REM sleep % 9.43 ± 2.18 12.15 ± 1.45 13.99 ± 1.81 0.222 Stage I sleep % 48.38 ± 6.82 39.94 ± 5.44 27.79 ± 3.97 0.034 Stage II sleep % 36.23 ± 4.64 37.49 ± 4.57 46.10 ± 3.24 0.189 Stage III Sleep % 5.96 ± 1.68 10.38 ± 3.60 10.49 ± 2.38 0.385 Central apnea (#/h) 1.56 ± 1.40 0.30 ± 0.29 0.05 ± 0.02 0.383 Apnea-hypopnea index 7.43 ± 3.09 7.06 ± 2.15 1.87 ± 0.49 0.128 Respiratory disturbance index 8.76 ± 3.11 14.46 ± 6.46 2.55 ± 0.50 0.110 Total arousal index 26.94 ± 2.84 24.17 ± 2.75 18.57 ± 2.09 0.680 Respiratory arousal index 2.93 ± 0.81 4.08 ± 1.39 1.40 ± 0.26 0.116 Leg movement arousal index 4.64 ± 0.69 5.93 ± 1.09 5.80 ± 0.81 0.525 Spontaneous arousal index 18.70 ± 2.57 14.05 ± 2.32 11.22 ± 1.65 0.060 SpO 2 mean 93.83 ± 0.68 91.54 ± 0.75 93.14 ± 0.58 0.070 Periodic leg movement index 6.35 ± 1.63 8.97 ± 3.13 4.98 ± 2.37 0.510 Pittsburgh Sleep Quality Index 7.61 ± 1.14 5.58 ± 0.78 3.78 ± 0.66 0.013 Epworth Sleep Scale score 7.23 ± 2.00 4.83 ± 1.05 4.57 ± 0.88 0.340 Fatigue Severity Scale score 29.00 ± 5.19 27.27 ± 5.31 22.76 ± 4.39 0.680 659 Journal of Clinical Sleep Medicine, Vol. 11, No. 6, 2015

BO Barut, N Taşçılar and A Varo Table 6 Polysomnographic and sleep screening tool results in patients with PD and ET (after age adjustment and exclusion of patients using serotonergic antidepressants). Sleep Measure PD (n = 13) ET (n = 12) Control (n = 14) p Time in bed 463.06 ± 16.48 455.68 ± 17.83 456.96 ± 18.17 0.943 Total sleep time 326.51 ± 18.39 358.48 ± 19.89 354.79 ± 20.28 0.406 Wake before sleep 13.35 ± 3.69 19.36 ± 3.77 8.20 ± 3.93 0.176 Wake after sleep onset 140.65 ± 16.67 74.55 ± 17.03 96.63 ± 17.65 0.020 Sleep efficiency index 71.02 ± 3.56 78.60 ± 3.85 78.19 ± 3.93 0.249 Sleep continuity index 75.61 ± 3.45 83.06 ± 3.61 82.40 ± 3.64 0.239 REM sleep % 10.88 ± 1.65 12.02 ± 2.02 12.21 ± 2.33 0.851 Stage I sleep % 45.00 ± 4.14 37.21 ± 5.06 33.66 ± 5.83 0.225 Stage II sleep % 37.84 ± 3.31 39.84 ± 4.04 43.03 ± 4.66 0.671 Stage III sleep % 6.32 ± 1.98 11.01 ± 2.42 9.26 ± 2.79 0.287 Central apnea (#/h) 0.94 ± 0.56 0.16 ± 0.69 0.70 ± 0.79 0.453 Apnea-hypopnea index 9.68 ± 2.61 4.03 ± 3.19 8.67 ± 3.68 0.377 Respiratory disturbance index 11.21 ± 3.44 9.80 ± 4.20 9.51 ± 4.85 0.944 Total arousal index 26.85 ± 2.29 23.14 ± 2.80 19.73 ± 3.23 0.192 Respiratory arousal index 4.87 ± 1.40 3.07 ± 1.71 3.96 ± 1.97 0.700 Leg movement arousal index 5.07 ± 0.80 5.87 ± 0.98 6.08 ± 1.13 0.699 Spontaneous arousal index 16.38 ± 1.73 13.88 ± 2.11 9.58 ± 2.44 0.093 SpO 2 mean 93.66 ± 0.52 91.81 ± 0.66 92.18 ± 0.73 0.050 Periodic leg movement index 13.64 ± 4.09 9.44 ± 4.89 12.13 ± 5.61 0.797 Pittsburgh Sleep Quality Index 8.78 ± 0.93 5.62 ± 1.13 4.17 ± 1.31 0.011 Epworth Sleep Scale score 8.98 ± 1.26 4.54 ± 1.54 5.69 ± 1.78 0.050 Fatigue Severity Scale score 34.23 ± 4.08 29.16 ± 5.09 27.89 ± 5.88 0.050 EMG, spiral analysis, dopamine transporter imaging, and olfactory assessments, have also been used to distinguish between ET and PD. In several prospective studies it has been suggested that at least four common non-motor symptoms of PD occur before motor deficits: RBD, constipation, loss of olfactory function, and depression. 3 It is therefore reasonable to study these parameters to try to distinguish between ET and PD, even during the early stages of disease. A study comparing RBD in patients with ET and PD found that probable RBD is more frequent in those with PD than in those with ET. 7 This is consistent with our observations that RBD-H was more prevalent in the PD group than the ET group. To confirm data obtained from the subjective analysis and questionnaires, we assessed the patients using PSG. Overnight polysomnography is an objective method of measuring the parameters of sleep architecture and pathophysiological events during sleep. 25 To our knowledge, although several studies have been conducted with PD patients using PSG, 26 sleep disorders in ET patients have not previously been investigated using this technology. In our study, we found no differences among PD, ET, and control groups in terms of TST, WBS, SEI, SCI, CA, AHI, RDI, arousal indices, or PLMI. These results might be interpreted as surprising since sleep problems in PD patients are common in clinical practice. However when the polysomnographic studies in PD patients are analyzed, the results are conflicting, as discussed in a review written by Peeraully et al. 26 This review concluded that the majority of studies using polysomnography have shown no increase in arousals in PD patients; but some have shown that awakenings may be increased in PD patients but are influenced by dopaminergic treatment. Additionally, no differences between patients and controls in terms of sleep stages were reported. Although the PLMI was increased in two studies, it was unchanged in five. No obvious association was found between OSAS and PD. On the contrary three of five studies suggested that the control group had increased OSAS compared with the PD group. 26 We also found five previous studies analyzing RBD in patients with PD. The RBD diagnostic criteria were modified in 2005, requiring RWA to be demonstrated by EMG in submental and limb muscles and the existence of a clear history of dream-enacting behaviors, suggesting that PSG is essential for establishing an accurate diagnosis of RBD. We therefore only analyzed studies that met the modified 2005 criteria. In two of the five case-control studies, RBD-D was not elevated in PD patients, 27,28 although an additional two studies revealed that RBD-D and RWA were higher in those with PD. 29,30 WASO and sleep 1 stage were significantly longer in the PD compared with the control group in the initial analysis of our study, but these data were not statistically significant after age adjustment. This suggests that the difference observed initially may have been related to age. However, this was not confirmed in patients with ET (who were comparable in age to those with PD), who were more likely to have insomnia. In the Perully review, there were conflicting data regarding TST, sleep efficiency, and REM sleep in PD patients. 26 The reason for these conflicting results might be related Journal of Clinical Sleep Medicine, Vol. 11, No. 6, 2015 660

Essential Tremor and Parkinson Disease to dopaminergic medication, disease stage, age, genetics, and psychosocial situation of the patients. We also observed significantly elevated mean SpO 2 in patients with PD compared with those with ET. In previous studies conducted by Cochen de Cock and Diederich et al., the mean and minimal oxygen saturations were higher in PD patients than in controls. 31,32 Additionally, OSAS was significantly more prevalent in the control compared with the PD group. However, our study found no difference between the prevalence of OSAS in the ET and PD groups. This phenomenon has been investigated in more detail in clinical studies. Valko et al. compared PD patients with OSAS, PD patients without OSAS, and a control group with OSAS. PD patients with OSAS had a higher minimal SpO 2 and shorter duration of apnea. The investigators concluded that the sympathetic response in PD patients with OSAS was blunted, whereas they also had disturbed apnea-induced sympathetic activation, 33 which could be attributed to the autonomic dysfunction in PD. In our study, the SpO 2 values were significantly different between ET and PD patients, but not between the control and PD groups. The reason for this discrepancy may be that we excluded patients with OSAS from the control but not the ET group. Another sleep-related problem confirmed by our study using PSG is RWA, which was elevated in patients with PD compared with those with ET. Data were re-analyzed after excluding patients taking antidepressant medication, and the results supported the same conclusion. As RWA may correlate with the onset of PD, 34 it may even be useful in the early stages of disease. Although RBD-P/RWA and RBD-H were more prevalent in patients with PD than in those with ET, RBD-D was not; thus, our data did not fulfill ICSD-2 criteria. This suggests that some of the RBD-like events described by PD patients may be due to other disorders, such as nightmares, sleepwalking, sleep terrors, nocturnal seizures, OSA with atypical arousals from REM sleep, posttraumatic stress disorder, nocturnal panic disorder, psychogenic dissociative states, and delirium. 34 Although we found that RWA was significantly higher in PD patients than those with ET, it is difficult to say if RWA could be used in the differential diagnosis of ET and PD since three of the ET patients had also RWA in their polysomnographic investigation. As we did not find any study showing RWA in ET patients, those ET patients with RWA might be patients with early onset PD or another α-synucleinopathy, and diagnosis will be made during continued follow-up. A previous study suggested that RBD-H is only approximately 33% sensitive for diagnosing RBD, as sleep apnea produces similar symptoms. 19 The RBD history of each patient should therefore be combined with PSG data before diagnosis and treatment. For example, previous studies have revealed that RBD patients exhibit normal atonia and lack of phasic activity on mentalis recordings but have increased phasic activity in the upper limbs. 35 As we did not record data from the upper extremities, we were not able to capture this phasic activity. In future studies, detailed EMG recordings could be used in patients with suspected RBD. Different types of sleep problems have been reported in patients with ET. Excessive daytime sleep, assessed by ESS, was increased significantly in PD compared with ET patients. 7 In a study conducted by Gerbin et al., ET and PD patients were compared using the ESS and PSQI, and individuals with ET obtained scores that were in an intermediate position between those obtained by normal individuals and those obtained by individuals with PD. 6 In another study comparing non-motor symptoms, such as sleep, depression, sleep quality, anxiety, and fatigue in ET and normal populations, sleep quality (assessed with the PSQI) was significantly inferior in patients with ET. 8 In our study, we found that PSQI and ESS scores were significantly higher in the PD group than the control group. In the age-adjusted analysis, PSQI scores were unchanged, but FSS (instead of ESS) scores were also increased in the PD compared with the control group. The PSQI and FSS scores of ET patients were intermediate between those of the PD and control groups; this is consistent with previous observations. 7 Additionally, the ESS scores of PD patients were significantly higher than those of ET patients, suggesting that excessive daytime sleep is a problem more commonly seen in PD. Although EDS has been linked to dopaminergic treatment, there are studies suggesting that it may be a primary feature of PD, 19 and, as such, that it might be used to differentiate ET from PD in the early stages of the diseases. Our study has several limitations. First, our study population was small, and our results need to be confirmed in a follow-up study with a larger sample. Second, we had to perform age-adjusted analyses because of the age difference between the PD and ET groups on the one hand, and the control group on the other. We also evaluated PSG for only one night, and the results might have been influenced by a first-night effect or by variations in daily sleep disturbances. Finally, we used routine PSG recordings, with EMG channels only in the lower extremities and chin. Thus we did not capture upper extremity EMG data, as is now recommended in possible RBD patients. 35 Despite these limitations, the results may be helpful in designing further studies to differentiate sleep problems in ET and PD. Our study also has several strengths. First, two independent neurologists (one a specialist in movement disorders and the other in sleep medicine) assessed the clinical history of RBD in all participants. Next, all patients in the PD, ET, and control groups underwent polysomnography. Finally, all data were reanalyzed to compare data from patients taking and not taking medication for depression. In conclusion, this is the first study to compare the sleep architecture of ET and PD patients using PSG. We found that RWA was elevated significantly in PD compared with ET patients. Additionally, EDS was a more common sleep disorder in PD patients, who also had increased SpO 2 compared with ET patients, suggesting an autonomic dysfunction in PD. ABBREVIATIONS BMI, body mass index DA, dopamine agonist EDS, excessive daytime sleepiness ESS, Epworth Sleepiness Scale ET, essential tremor FSS, Fatigue Severity Scale LAI, leg movement arousal index PD, Parkinson disease PLMI, periodic leg movement index 661 Journal of Clinical Sleep Medicine, Vol. 11, No. 6, 2015

BO Barut, N Taşçılar and A Varo PSG, polysomnogram PSQI, Pittsburgh Sleep Quality Index RAI, respiratory arousal index RBD, REM sleep behavior disorders RBD-D, actual diagnosis of RBD RBD-P, PSG evidence of RBD or subclinical RBD REM, rapid eye movement RWA, REM without atonia SAI, spontaneous arousal index SCI, sleep continuity index SEI, sleep efficiency index TAI, total arousal index TIB, time in bed TST, total sleep time UPDRS, United Parkinson Disease Rating Scale WASO, wake time after sleep onset REFERENCES 1. Moghal S, Rajput AH, D Arcy C, Rajput R. Prevalence of movement disorders in elderly community residents. Neuroepidemiology 1994;13:175 8. 2. De Lau LM, Breteler MM. Epidemiology of Parkinson s disease. Lancet Neurol 2006;5:525 35. 3. Chaudhuri KR, Odin P, Antonini A, Martinez-Martin P. Parkinson s disease: the non-motor issues. Parkinsonism Relat Disord 2011;10:717 23. 4. Chandran V, Pal PK. Essential tremor: beyond the motor features. 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