Association of daytime sleepiness with nigrostriatal dopaminergic degeneration in early Parkinson's disease

Abstract Introduction Many patients with Parkinson's disease (PD) report daytime sleepiness. Its etiology, however, is still not fully understood. The aim of this study was to examine if the amount of nigrostriatal dopaminergic degeneration is associated with subjective daytime sleepiness in patients with PD. Patients and methods We investigated 21 patients with PD clinically and by means of [¹²³I] FP-CIT-SPECT (DaTSCAN^R). Each patient filled in the Epworth sleepiness scale (ESS), the Parkinson's Disease Sleep Scale (PDSS), and the self-rating depression scale according to Zung (SDS) to assess sleepiness, sleep quality, and depressive symptoms. Results The mean specific dopamine transporter binding in the 21 PD patients (60.8 ± 10.4 years, nine females, median Hoehn and Yahr stage 2.0) was decreased. Nine patients were in Hoehn and Yahr stage 1 (58.7 ± 6.6 years, four females; ESS score 7.4 ± 4.5; PDSS score 105.1 ± 30.9), the other 12 patients were in Hoehn and Yahr stage 2 (62.4 ± 12.6 years, five females; ESS score 6.7 ± 4.7, PDSS score 97.1 ± 25.6). Age, gender, ESS, and PDSS scores were not significantly different in both groups. However, ESS scores showed an inverse correlation with mean DAT binding in the striatum (r = -0.627, p = 0.03), the caudate nucleus (r = -0.708, p = 0.01), and the putamen (r = -0.599, p = 0.04) in patients with Hoehn and Yahr stage 2. There was no correlation of the ESS score with age, disease duration, UPDRS motor score, PDSS score, or depression score. Conclusion Subjective daytime sleepiness seems to be associated with dopaminergic nigrostriatal degeneration in early PD.     

Clinical usefulness of the Parkinson's disease sleep scale

OBJECTIVE: To test the usefulness of the Parkinson's disease sleep scale (PDSS) in identifying sleep disorders in the clinical practice setting. METHODS: Sixty-two PD patients were evaluated with the PDSS and the Epworth sleepiness scale (ESS). A cut-off of less than five for each PDSS item as an indicator of substantial sleep disturbance was chosen. If the ESS was equal to or greater than eight, patients were referred to a sleep disorder specialist and possible polysomnography. RESULTS: The mean total PDSS score was 104.7+/-21.5,which correlated with the mean Hoehn and Yahr score (1.9+/-0.9) as well as the mean ESS score (9.7+/-4.7). A significant correlation was also found between the ESS score and several items of the PDSS. CONCLUSIONS: The PDSS was useful in identifying sleep disturbances which were not previously diagnosed, such as sleep maintenance insomnia and excessive daytime sleepiness. Problems with the PDSS include ambiguities of some questions, lack of quantification and an inability to identify specific sleep disturbances such as sleep apnea.     

The frequency and nature of sleep disorders in a community-based population of patients with Parkinson's disease

Sleep disturbances in Parkinson's disease (PD) are a common problem. The aim of this study was to detail the frequency and nature of sleep disorders in a representative population of PD patients. A recently identified prevalent population, consisting of 161 PD patients were used as a representative population. Twenty-seven of 122 (22%) patients were identified as having marked sleep disorders, with sleep fragmentation and nocturia being the most commonly reported problems. Sleep scores worsened with higher Hoehn and Yahr stages. Sleep disturbances are a relatively common complication of PD and worsen with increasing Hoehn and Yahr stage.     

Sleep disorders in Parkinson's disease.

We sought to estimate the frequency and nature of sleep disturbances in Indian Parkinson's disease (PD) patients. One hundred forty nine consecutive PD patients attending the Movement Disorders Clinic of the All India Institute of Medical Sciences, New Delhi, India and 115 age-matched healthy controls participated. After clinical evaluation, sleep assessment was done using a 23-question, validated sleep questionnaire. Mean age of PD patients and the duration of illness were 58.37 (S.D. 10.45) years and 5.7 (S.D. 3.85) years, respectively. The mean age of the controls was 56.50 (S.D. 11.45) years (P > 0.05). Sleep problems were seen in 63 (42%) PD patients compared to 12% of controls. These were: insomnia in 32%, nightmares in 32%, and excessive day time sleepiness in 15% of PD patients as compared with 5%, 5% and 6%, respectively, in controls (P < 0.025). Presence of nightmares was significantly associated with higher Hoehn and Yahr score (P < 0.002), high unified Parkinson's disease rating scale (UPDRS) Part I score (P < 0.000) and levodopa dose (P < 0.025). Excessive daytime sleepiness correlated with higher Hoehn and Yahr stage (P < 0.004), and levodopa dose (P < 0.040). The sleep latency was longer in PD patients as compared to controls (P < 0.000). Multiple logistic regression analysis showed association of sleep disturbances with UPDRS Part III, Schwab and England score, levodopa dose, rigidity score, and bradykinesia score. Sleep problems are much more common in PD patients compared to controls (P < 0.001), and correlate with increased severity of disease.     

Observational study of sleep-related disorders in Italian patients with Parkinson’s disease: usefulness of the Italian version of Parkinson’s disease sleep scale

Sleep disturbances are common in patients with Parkinson's disease (PD). We aimed to evaluate prevalence and severity of nighttime sleep disturbances in Italian PD patients and to validate the Italian version of the Parkinson's disease sleep scale. A total of 221 PD patients and 57 healthy controls participated in a cross-sectional study with retest. PDSS, Epworth Sleepiness Scale (ESS), Hamilton Depression Rating Scale, Unified Parkinson's Disease Rating Scale (UPDRS), and Hoehn and Yahr staging were applied. PDSS total and individual items scores from patients were significantly lower than those in controls. Internal consistency of PDSS scale was satisfactory and intraclass correlation coefficient for test-retest reliability was 0.96 for total PDSS score. A significant negative correlation was found between total PDSS and ESS scores, and between total PDSS and HDRS scores. PDSS scores were also related to UPDRS sections II, III and IV, and H&Y stage. PDSS and ESS scores were not related to levodopa equivalent dose. Daytime sleepiness, depressive symptoms and disease severity correlate with sleep disturbances in Italian PD patients. The PDSS is a valid and reliable tool to evaluate sleep disturbances in Italian patients.     

SCOPA‐sleep and PDSS: Two scales for assessment of sleep disorder in Parkinson's disease

This study evaluated the comparative validity and usefulness of the Parkinson's Disease Sleep Scale (PDSS) and the Scales for Outcomes in PD‐Sleep Scale (SCOPA‐S), two disease‐specific rating scales for assessing sleep disorders in Parkinson's disease (PD). Hoehn and Yahr staging (HY), SCOPA‐Motor, Mini‐Mental State Examination, Clinical Impression of Severity Index for PD, Hospital Anxiety and Depression Scale, EuroQoL, and SCOPA‐Psychosocial, in addition to PDSS and SCOPA‐S (night‐time sleep (NS) and daytime sleepiness (DS) subscales), were applied to 187 consecutive PD patients. PDSS and SCOPA‐S proved similar in acceptability, scaling assumptions, precision, and internal consistency (Cronbach's α = 0.82–0.84). Factor analysis revealed five separate factors for PDSS (67% of the variance) and one factor for each SCOPA‐S subscale (60% of the variance for NS and 57% for DS). Correlation coefficient between PDSS and SCOPA‐S NS was ?0.60. Sleep scales correlated moderately with mood, low‐to‐moderate with HRQoL, and low with the rest of measures. PDSS and SCOPA‐S DS discriminated between patients grouped by HY severity levels and disease duration. Cutoff points of 82/83 for PDSS and 6/7 for SCOPA‐S NS were drawn to identify PD patients with sleep problems. Depression/anxiety scores explained 26% for PDSS and 22% for SCOPA‐S NS scores. Both scales provide valid, reliable, and useful means to evaluate sleep disorders in PD. PDSS may be used to obtain a profile about potential causes of “bad sleep,” but is barely useful to assess DS, whereas SCOPA‐S assesses nocturnal sleep disorders and daytime somnolence at a similar extent, without exploring the potential causes. © 2008 Movement Disorder Society     

Case-control study of restless legs syndrome and quality of sleep in Parkinson's disease

In a case-control study involving 400 study subjects, we found a higher prevalence of restless legs syndrome (RLS) in our Parkinson's disease (PD) patients compared to controls (3.0% vs 0.5%) (odds ratio 6.2) (p=0.07). Polysomnographic studies confirmed that study subjects with RLS had grossly elevated PLMS index, PLMS arousal index and reduced sleep efficiency. None of these PD patients reported a family history of PD or RLS. The average age of onset of RLS was 61.7+/-10.8 years old. The mean global Pittsburgh Sleep Quality Index (PSQI) score of PD patients was significantly higher than the controls (9.1+/-4.5 vs 4.3+/-2.8, p<0.0001). All the seven components of PSQI in PD patients were significantly different from controls (p<0.0001). Multivariate analysis revealed that only Hoehn and Yahr staging correlated with the global PSQI score (p<0.0001). Similar results were obtained when we compared the PSQI score between PD patients without RLS with controls. Our case-control study demonstrated a weak association between RLS and PD. PD patients have significant poor quality of sleep, and this correlated with the severity of PD. RLS did not play an important role in sleep dysfunction in our PD cohort. A high index of suspicion for sleep problems in advanced PD patients is important as early management could improve their quality of life.     

Correlation between depressive symptoms and nocturnal disturbances in Japanese patients with Parkinson's disease

Depression and nocturnal disturbances are frequent in patients with Parkinson's disease (PD). The aim of this study was to determine the correlation between depressive symptoms and nocturnal disturbances in patients with PD in Japan. The subjects of this multi-center cross-sectional study were 188 patients with PD and 144 age-matched controls who were assessed for nocturnal disturbances by the Parkinson's disease sleep scale (PDSS) and for depressive symptoms by Zung Self-Rating Depression Scale (SDS). Depressive symptoms (SDS score of > or =40) were identified in 122 patients (64.9%). The SDS was significantly higher in PD patients than control subjects. The stepwise regression model identified PDSS (p<0.001) and Unified Parkinson's Disease Rating Scale I (mental state) (p=0.002) as significant determinants of SDS. Stepwise regression analysis identified item 15 (daytime sleepiness) (p=0.002), item 13 (early morning tremor) (p=0.008), item 12 (nocturnal dystonia) (p=0.015), and item 3 (sleep maintenance insomnia) (p=0.026) as significant predictors of SDS. Our results indicated that depressive symptoms in PD correlate significantly with nocturnal disturbances, and that daytime sleepiness, dystonia, tremor and sleep fragmentation are the most common nocturnal disturbances in depressed patients with PD.     

广州地区帕金森病患者睡眠障碍情况调查

目的 调查广州地区帕金森病(Parkinson's disease,PD)患者睡眠质量,分析睡眠障碍特点及影响因素.方法 由中国医学科学院北京协和医院张振馨教授设计,采用PD非运动症状调查问卷中PD睡眠量表(PDSS)及Epworth嗜睡评分量表(ESS)对2007年4-6月在广州6家医院门诊或住院部的PD患者共107例进行睡眠情况调查,用统一PD评分量表(UPDRS)及Hoehn-Yahr(HY)分级进行运动功能的评定,了解睡眠与运动功能之间的关系.结果 107例PD患者中20.6%(22/107)的患者存在睡眠障碍,18.7%(20/107)的患者可能存在睡眠障碍.PD患者睡眠障碍的特点主要为夜尿增多、白天睡眠增多、睡眠浅.PD患者睡眠障碍与病程、H-Y分级、UPDRS及ESS评分相关(rs=-0.322、-0.259、-0.231、-0.198,均P＜0.05).UPDRS得分越高、H-Y分级越大以及病程越长则睡眠情况越差.左旋多巴类药物用量在有或无睡眠障碍患者中差异无统计学意义.结论 睡眠障碍在广州地区PD患者中较常见,主要表现为夜尿增多、睡眠浅及白天睡眠增多,PD的严重程度可能影响患者睡眠质量.     

Sleep complaints and their relation with drug treatment in patients suffering from Parkinson's disease.

The aim of this research was to quantify sleep problems in patients suffering from Parkinson's disease by means of the new Parkinson's Disease Sleep Scale (PDSS) and to correlate such problems with the possible influence of current drug treatment. A total of 70 patients (36 men and 34 women) with a diagnosis of Parkinson's disease were enrolled. Their mean age was 69.7 +/- 8.2 years, and duration of disease was 7.4 +/- 4.8 years. All patients completed the PDSS and the Unified Parkinson's Disease Rating Scale (UPDRS Parts I-IV). Drug consumption and doses were registered. The mean score on the PDSS scale was 109.23 +/- 19.75 and on the UPDRS III scale was 25.24 +/- 11.35. The lowest scores were obtained in Item 3 (sleep fragmentation): 5.53 (2.46); and in Item 8 (nocturia): 5.75 (2.91). There was a weak correlation between the PDSS and UPDRS III (cc = -0.355, P = 0.003), PDSS and UPDRS I (cc = -0.272, P = 0.02), and PDSS and UPDRS IV (cc = -0.416, P < 0.001). Motor conditions, mental state, and drug complications influence sleep quality. Although this effect was significant, it was not of a great magnitude. Dopaminergic drugs did not increase daytime sleepiness. As a whole, sleep quality in patients who took dopaminergic agonists did not differ from that of patients who took levodopa in monotherapy.     

Increased alpha activity in REM sleep in de novo patients with Parkinson's disease.

We compared the sleep structure including a quantitative electroencephalographic (EEG) analysis and the frequency of periodic limb movements (PLM) in 17 patients with Parkinson's disease (PD; 10 men, seven women, mean age 65.9 years, mean Hoehn and Yahr stage 1.8) who had never been treated with dopaminergic agents (de novo), and 10 healthy controls (six men, four women, mean age 64.5 years). The REM sleep EEG of the PD patients was characterized by a sustained increase in the high-theta/alpha (7.8-10.5 Hz) frequency range during the first one-third (i.e., 11.00 p.m. to 01.40 a.m.) of the night. There was no significant difference in the sleep continuity and sleep architecture as well as in the PLM index between both groups. The analysis of the temporal dynamics of the observed changes suggests a dysregulation of the REM sleep homeostasis in the patients with PD.     

Sleep and sleepiness in patients with Parkinson''s disease before and after dopaminergic treatment

Sleep disturbances and daytime sleepiness are well-known phenomena in Parkinson's disease (PD). Fifteen previously untreated PD patients underwent clinical evaluation, subjective sleep evaluation and polysomnographic evaluation (PSG) before and after a treatment period of mean 8+/-3.1 months with dopaminergic drugs. Both mean Unified Parkinson's Disease Rating Scale (UPDRS) total score and mean subset III of the UPDRS were significantly improved with dopaminergic treatment. PSG revealed that administration of dopaminergic drugs resulted in significant increase in mean percentage of stages 1 and 2. The mean Epworth Sleepiness Scale (ESS) score was significantly increased and mean Multiple Sleep Latency Test (MSLT) score was significantly decreased after dopaminergic treatment indicating subjective and objective daytime sleepiness. The differences in MSLT scores were best explained by a higher dose of L-dopa, whereas other variables such as disease duration, treatment duration, Hoehn and Yahr stage, sleep efficiency index or dopamine agonists did not increase the significance. In contrast, any of the variables appeared to explain ESS score variability. This study demonstrates that daytime sleepiness is not present in untreated patients but emerges later during dopaminergic treatment. Total daily L-dopa dose is predictive of objective daytime sleepiness. Furthermore, subjective assessment of sleepiness may cause underestimation of the severity of daytime sleepiness.     

Sleep disturbances in Japanese patients with Parkinson's disease--comparing with patients in the UK

Sleep disorders are common in the general population and occur more frequently with advancing age. However, patients with Parkinson's disease (PD) have been known to have various sleep disturbances beyond those to be expected from the effect of aging alone. We tried to quantify the various aspects of nocturnal sleep problems in PD using the PD sleep scale (PDSS). 64 patients with PD and 60 age- and sex-matched controls completed the PDSS. After neurological examinations, we assessed the degree of sleep disorder by the PDSS. We evaluated the severity of PD by the Hoehn and Yahr Scale and the unified PD rating scale (UPDRS). To compare the various aspects of nocturnal sleep problems in PD between in Japan and in the United Kingdom (UK), we referenced and compared our results with those by Chaudhui et al. The PDSS scores in PD group were significantly different from those in controls. Individual items of the scale showed good discriminatory power between PD and controls. Overall tendencies were the same in Japan and in the UK, but there were some different points, especially absence of refreshing quality of sleep in Japan. We believe that the PDSS provides an objective method for targeted therapeutic approaches for the treatment of disturbed sleep in PD even among countries with different cultures, such as Japan and the UK.     

Variable expression of Parkinson's disease: a base-line analysis of the DATATOP cohort. The Parkinson Study Group

The DATATOP database, which includes clinical information on 800 patients with early untreated Parkinson's disease (PD), is well suited to explore clinical heterogeneity in PD. Patients with early-onset PD (less than or equal to 40 years, N = 33) reached the same level of disability as the late-onset PD (greater than or equal to 70 years, N = 85) group at a significantly slower rate (2.9 vs. 1.7 years). Early-onset PD patients functioned cognitively better than late-onset PD patients. Bradykinesia, and postural instability and gait difficulty (PIGD), were more common at onset in patients with a rapid rate of disease progression ("malignant PD"; duration of symptoms less than 1 year and Hoehn/Yahr stage of 2.5, N = 11) as compared with those with a relatively slow rate of progression ("benign PD"; duration of symptoms greater than 4 years, N = 65). Comparisons of tremor-dominant PD (mean tremor score/mean PIGD score less than or equal to 1.5, N = 441) with the PIGD-dominant type (mean tremor score/mean PIGD score greater than or equal to 1.0, N = 233) provided support for the existence of clinical subtypes. The PIGD group reported significantly greater subjective intellectual, motor, and occupational impairment than the tremor group. Stage II patients had higher depression scores than stage I patients. Among the patients participating in the DATATOP, older age at onset with bradykinesia, or with the PIGD form of PD, is associated with more functional disability than when the symptoms are dominated by tremor or begin at a younger age.     

Characteristics of sleep disturbances in Japanese patients with Parkinson's disease. A study using Parkinson's disease sleep scale

The present multicenter cross‐sectional study was performed using semistructured questionnaires to determine the contributing factors of sleep disturbances in Japanese patients with Parkinson's disease (PD). We used the Parkinson's disease sleep scale (PDSS, Japanese version). All data were obtained by means of interviewed questionnaire and physical examination by neurologists. The study was carried out between April 2005 and December 2005 at eight university hospitals and affiliated facilities in the Kanto area of Japan. A total of 188 (85 men and 103 women) PD patients and 144 controls (64 men and 80 women) were included. Stepwise regression analysis identified complications of treatment, depression, age, and disease duration as significant risk factors of sleep disturbances in PD. Significant differences in total PDSS score were observed between Hoehn & Yahr (H&Y) Stages 1 and 4, between H&Y Stages 2 and 4, and between H&Y stages 3 and 4 (Bonferroni test). The results of this survey suggested that complications due to treatment (dyskinesia, wearing off, on–off), depressive state, and disease stage are significant determinants of sleep disorders in Japanese patients with PD. We speculate that the reduction of neurotransmitters involved in the sleep–wakefulness mechanism and degeneration of neurons progress together in parallel with deterioration of motor function. © 2006 Movement Disorder Society     

Sleep disorders in Chinese patients with Parkinson's disease: validation study of a Chinese version of Parkinson's disease sleep scale

To evaluate the Chinese version of the Parkinson's disease sleep scale (PDSS) as an instrument for measuring sleep disorders in Chinese patients with Parkinson's disease (PD). The objective of the present study was to carry out a metric analysis of a Chinese version of PDSS using a cross-sectional study of 126 patients with PD who participated in the study. Usual measures for PD patients including the Pittsburgh sleep quality index (PSQI), the Epworth sleepiness scale (ESS), the Geriatric Depression Scale (GDS), and the Hamilton Anxiety Scale (HAMA) were applied by neurologists. The intra-class correlation coefficient was 0.880, and test-retest reliability for total PDSS score was 0.914. The Mean total PDSS score was 118.38+/-26.07. There was a significant correlation between the PDSS and PSQI, between the PDSS and ESS, between the PDSS and GDS, between the PDSS and HAMA, between the PDSS and the disease durations, and between the PDSS and the LDE, respectively. The Chinese version of PDSS met some basic standards required for sleep disorders measures. It could lead to better understanding the sleep disorders of PD of China in future studies.     

Excessive daytime sleepiness in Parkinson's disease as assessed by Epworth Sleepiness Scale (ESS)

OBJECTIVE: To assess daytime sleepiness in patients with Parkinson's disease (PD) using the Epworth Sleepiness Scale (ESS). MATERIAL AND METHODS: One hundred and forty-nine patients with PD (126 men, 23 women) and 115 age matched controls recruited from relatives of medical staff or spouses and other family members accompanying patients to the Movement Disorder Clinic of the All India Institute of Medical Sciences in New Delhi were included in the study. An ESS score of > or =8 was considered abnormal. Data obtained were analyzed using Chi square test for categorical variables and Student's t-test for continuous variables. RESULTS: The mean age of patients with PD was 58.37 (S.D.=10.45) years, and that of controls 56.50 (S.D.=11.45) years, with a mean duration of disease of 5.68 (S.D.=3.85) years. The mean ESS score was 4.9 (S.D.=3.63) and 2.17 (S.D.=2.54) in PD patients and controls, respectively (P<0.05). Thirty-two patients with PD (21%) had an ESS score of >8 whereas only 3% of controls scored > or =8 on the ESS (P<0.05). Higher ESS scores were associated with a higher Hoehn and Yahr (H&Y) stage of disease and higher Unified Parkinson's Disease Rating Scale (UPDRS) (part I, III and total) scores (P<0.019, P<0.013 and P<0.011, respectively). CONCLUSION: Excessive daytime sleepiness was more common in PD patients as compared to controls. Higher ESS scores correlated significantly with higher H&Y stage and higher UPDRS (part I, III and total) scores.     

Colour discrimination impairment is not a reliable early marker of Parkinson's disease

Disturbances of colour visual discrimination have been shown to occur frequently in Parkinson's disease (PD). To verify the potential utility of reduced colour sensitivity as a diagnostic marker of early PD, we examined 14 PD patients, mean age 55.4 years, disease duration 2.3 years, in Hoehn and Yahr stages 1, 1.5, or 2, previously untreated with levodopa. Colour discrimination was measured with the Farnsworth-Munsell 100-hue test in patients who were compared with age-matched controls. The examinations were performed under standard conditions in a room illuminated by a daylight lamp Biolux Osram 6500 K. The mean total error score (MTES) and partial error scores (green-yellow and red-green axis) were calculated for every person examined. No significant differences were found between PD patients (MTES 49.1 ± SD 37) and controls (MTES 37.9 ± SD 25). Similarly, the mean partial scores were not significantly elevated in PD patients. We found an elevation of error scores exceeding the upper limit of normality (control mean + 2SD) only in three patients. We conclude that colour visual discrimination is not consistently impaired in early stages of PD and does not appear as a reliable early marker of Parkinson's disease. Received: 26 September 2000, Received in revised form: 20 March 2001, Accepted: 28 March 2001     

Improvement of sleep quality in patients with advanced Parkinson's disease treated with deep brain stimulation of the subthalamic nucleus.

Most Parkinson's patients complain about sleep problems. The subjective effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on nocturnal disabilities and sleep quality was elucidated by the recently established Parkinson's disease sleep scale (PDSS). The DBS-treated group obtained significant improvement of motor function assessed by the Unified Parkinson's Disease Rating Scale. The mean total PDSS improved significantly after surgery whereas no change was found for the control group. Significant improvements of individual questions were obtained for overall sleep quality and motor symptoms whereas nocturia and daytime sleepiness did not change despite significant reduction of parkinsonian medication.