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1.  Characterizing sleep disorders of adults with tuberous sclerosis complex: A questionnaire-based study and review 
Epilepsy & behavior : E&B  2010;20(1):68-74.
An adult cohort with tuberous sclerosis complex was investigated for the prevalence of sleep disturbances and the relationship with seizure variables, medication, and psychological functioning. Information on 35 adults was gathered using four questionnaires: Epworth Sleepiness Scale (ESS), Sleep and Epilepsy Questionnaire (SEQ), Sleep Diagnosis List (SDL), and Adult Self-Report Scale (ASR). In addition, clinical, genetic and electrophysiological data were collected. Of 35 respondents, 25 had a history of epilepsy. A subjective sleep disorder was found in 31% of the cohort. Insomnia scores showed a significant positive correlation with obstructive sleep apnea syndrome and restless legs syndrome scores. Significant correlations were found between daytime sleepiness and scores on depression, antisocial behavior, and use of mental health medication. A subgroup using antiepileptic medication showed high correlations between daytime sleepiness, attention deficits, and anxiety scores.
doi:10.1016/j.yebeh.2010.10.023
PMCID: PMC3439194  PMID: 21130696
Epilepsy; Sleep; Tuberous sclerosis complex; Behavior
2.  Probable rapid eye movement sleep behavior disorder, nocturnal disturbances and quality of life in patients with Parkinson’s disease: a case-controlled study using the rapid eye movement sleep behavior disorder screening questionnaire 
BMC Neurology  2013;13:18.
Background
Increasing evidence provides a clear association between rapid eye movement sleep behavior disorders (RBD) and Parkinson’s disease (PD), but the clinical features that determine the co-morbidity of RBD and PD are not yet fully understood.
Methods
We evaluated the characteristics of nocturnal disturbances and other motor and non-motor features related to RBD in patients with PD and the impact of RBD on their quality of life. Probable RBD (pRBD) was evaluated using the Japanese version of the RBD screening questionnaire (RBDSQ-J).
Results
A significantly higher frequency of pRBD was observed in PD patients than in the controls (RBDSQ-J ≥ 5 or ≥ 6: 29.0% vs. 8.6%; 17.2% vs. 2.2%, respectively). After excluding restless legs syndrome and snorers in the PD patients, the pRBD group (RBDSQ-J≥5) showed higher scores compared with the non-pRBD group on the Parkinson’s disease sleep scale-2 (PDSS-2) total and three-domain scores. Early morning dystonia was more frequent in the pRBD group. The Parkinson’s Disease Questionnaire (PDQ-39) domain scores for cognition and emotional well-being were higher in the patients with pRBD than in the patients without pRBD. There were no differences between these two groups with respect to the clinical subtype, disease severity or motor function. When using a cut-off of RBDSQ-J = 6, a similar trend was observed for the PDSS-2 and PDQ-39 scores. Patients with PD and pRBD had frequent sleep onset insomnia, distressing dreams and hallucinations. The stepwise linear regression analysis showed that the PDSS-2 domain “motor symptoms at night”, particularly the PDSS sub-item 6 “distressing dreams”, was the only predictor of RBDSQ-J in PD.
Conclusion
Our results indicate a significant impact of RBD co-morbidity on night-time disturbances and quality of life in PD, particularly on cognition and emotional well-being. RBDSQ may be a useful tool for not only screening RBD in PD patients but also predicting diffuse and complex clinical PD phenotypes associated with RBD, cognitive impairment and hallucinations.
doi:10.1186/1471-2377-13-18
PMCID: PMC3575252  PMID: 23394437
Parkinson’s disease; Rapid eye movement sleep behavior disorder; Cognition; Quality of life; Nocturnal problems
3.  Probable REM Sleep Behavior Disorder Increases Risk for Mild Cognitive Impairment and Parkinson’s Disease: A Population-Based Study 
Annals of Neurology  2012;71(1):49-56.
Objective
REM sleep behavior disorder (RBD) is associated with neurodegenerative disease and particularly with the synucleinopathies. Convenience samples involving subjects with idiopathic RBD have suggested an increased risk of incident mild cognitive impairment (MCI), dementia (usually dementia with Lewy bodies) or Parkinson’s disease (PD). There is no data on such risk in a population-based sample.
Methods
Cognitively normal subjects aged 70–89 in a population-based study of aging who screened positive for probable RBD using the Mayo Sleep Questionnaire were followed at 15 month intervals. In a Cox Proportional Hazards Model, we measured the risk of developing MCI, dementia, PD among the exposed (pRBD+) and unexposed (pRBD−) cohorts.
Results
Forty-four subjects with pRBD+ at enrollment (median duration of pRBD features was 7.5 years), and 607 pRBD− subjects, were followed prospectively for a median of 3.8 years. Fourteen of the pRBD+ subjects developed MCI and one developed PD (15/44=34% developed MCI / PD); none developed dementia. After adjustment for age, sex, education, and medical comorbidity, pRBD+ subjects were at increased risk of MCI / PD [Hazard Ratio (HR) 2.2, 95% Confidence Interval (95%CI) 1.3 – 3.9; p=0.005]. Inclusion of subjects who withdrew from the study produced similar results, as did exclusion of subjects with medication-associated RBD. Duration of pRBD symptoms did not predict the development of MCI / PD (HR 1.05 per 10 years, 95%CI 0.84 – 1.3; p=0.68).
Interpretation
In this population-based cohort study, we observed that pRBD confers a 2.2-fold increased risk of developing MCI / PD over four years.
doi:10.1002/ana.22655
PMCID: PMC3270692  PMID: 22275251
sleep disorders; parasomnias; dementia; Alzheimer’s disease; dementia with Lewy bodies; parkinsonism; synuclein
4.  Correlation between Nocturia and Sleep: A Questionnaire Based Analysis 
Korean Journal of Urology  2010;51(11):757-762.
Purpose
This study evaluated the effectiveness and quality of sleep (QoS) in adult patients with nocturnal lower urinary tract symptoms (LUTS) including nocturia and nocturnal polyuria.
Materials and Methods
A total of 102 patients with nocturia and daytime LUTS were enrolled in this study. All patients completed a questionnaire that included the International Prostate Symptom Score (IPSS), quality of life score (QoL), overactive bladder questionnaire (OABq), and a sleepiness index. The sleepiness index was measured with the Korean Beck Depression Inventory (K-BDI), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), Berlin Questionnaire (BQ), and the International Restless Legs Syndrome Study Group (IRLSSG). Statistical analyses included the Student's t-test and chi-square test. Differences were considered significant at a p-value of less than 0.05.
Results
Nocturia during sleep was experienced by 68 (66.7%) out of 102 patients. There was no significant association between the nocturia- and the sleep-related scales, but with multiple regression analysis for sex and age, the K-BDI score (p=0.05), IPSS score (p=0.05), and OABq (p=0.02) were significantly higher in patients who woke up to void during sleep. A total of 57 (55.9%) patients diagnosed with overactive bladder with nocturia had severe daytime sleepiness on the ESS questionnaire (p=0.019) and more urgency symptoms on the IPSS questionnaire (p=0.007).
Conclusions
Patients with nocturia had a greater risk of being depressive and felt sleepier during the daytime. LUTS including nocturia and sleep quality closely affected each other. Therefore, clinicians should consider patients' LUTS and sleep problems or QoS as well to provide more satisfying outcomes.
doi:10.4111/kju.2010.51.11.757
PMCID: PMC2991572  PMID: 21165195
Nocturia; Quality of life; Sleep disorders
5.  Parkinson's Disease and Sleep/Wake Disturbances 
Parkinson's Disease  2012;2012:205471.
Parkinson's disease (PD) has traditionally been characterized by its cardinal motor symptoms of bradykinesia, rigidity, resting tremor, and postural instability. However, PD is increasingly being recognized as a multidimensional disease associated with myriad nonmotor symptoms including autonomic dysfunction, mood disorders, cognitive impairment, pain, gastrointestinal disturbance, impaired olfaction, psychosis, and sleep disorders. Sleep disturbances, which include sleep fragmentation, daytime somnolence, sleep-disordered breathing, restless legs syndrome (RLS), nightmares, and rapid eye movement (REM) sleep behavior disorder (RBD), are estimated to occur in 60% to 98% of patients with PD. For years nonmotor symptoms received little attention from clinicians and researchers, but now these symptoms are known to be significant predictors of morbidity in determining quality of life, costs of disease, and rates of institutionalization. A discussion of the clinical aspects, pathophysiology, evaluation techniques, and treatment options for the sleep disorders that are encountered with PD is presented.
doi:10.1155/2012/205471
PMCID: PMC3544335  PMID: 23326757
6.  Improved Sleep Efficiency after Anti-Tumor Necrosis Factor α Therapy in Rheumatoid Arthritis Patients 
Background:
Poor sleep health is increasingly recognized as contributing to decreased quality of life, increased morbidity/mortality and heightened pain perception. Our purpose in this study was to observe the effect on sleep parameters, specifically sleep efficiency, in rheumatoid arthritis (RA) patients treated with anti-tumor necrosis factor alpha (anti-TNF-α) therapy.
Methods:
This was a prospective observational study of RA patients with hypersomnolence/poor sleep quality as defined by the Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI). Study patients underwent overnight polysomnograms and completed questionnaire instruments assessing sleep prior to starting anti-TNF-α therapy and again after being established on therapy. The questionnaire included the ESS, PSQI, the Berlin instrument for assessment of obstructive sleep apnea (OSA) risk, restless legs syndrome (RLS) diagnostic criteria, and measures of disease activity/impact.
Results:
A total of 12 RA patients met inclusion criteria, of which 10 initiated anti-TNF-α therapy and underwent repeat polysomnograms and questionnaire studies approximately 2 months later. Polysomnographic criteria for OSA were met by 60% of patients. Following anti-TNF-α therapy initiation, significant improvements were observed by polysomnography (PSG) for sleep efficiency, increasing from 73.9% (SD 13.5) to 85.4% (SD 9.6) (p = 0.031), and ‘awakening after sleep onset' time, decreasing from 84.1 minutes (SD 43.2) to 50.7 minutes (SD 36.5) (p = 0.048). Questionnaire instrument improvements were apparent in pain, fatigue, modified Health Assessment Questionnaire (mHAQ), and Rheumatoid Arthritis Disease Activity Index (RADAI) scores.
Conclusions:
Improved sleep efficiency and ‘awakening after sleep onset’ time were observed in RA patients treated with anti-TNF-α therapy.
doi:10.1177/1759720X11416862
PMCID: PMC3383532  PMID: 22870481
anti-TNF; obstructive sleep apnea; polysomnogram; restless legs syndrome; rheumatoid arthritis; sleep
7.  Daytime sleepiness in Japanese patients with multiple system atrophy: prevalence and determinants 
BMC Neurology  2012;12:130.
Background
The recent SLEEMSA study that evaluated excessive daytime sleepiness (EDS) in Caucasian patients with multiple system atrophy (MSA) demonstrated that EDS was more frequent in patients (28%) than in healthy subjects (2%). However, the prevalence and determinants of EDS in other ethnic populations have not been reported to date.
Methods
We performed a single-hospital prospective study on patients with probable MSA. To ascertain the prevalence and determinants of EDS in Japanese MSA patients, we assessed the patients’ degree of daytime sleepiness by using the Japanese version of the Epworth Sleepiness Scale (ESS). In addition, we investigated the effects of sleep-disordered breathing (SDB) and abnormal periodic leg movements in sleep (PLMS), which were measured by polysomnography, on the patients’ ESS scores.
Results
A total of 25 patients with probable MSA (21 patients with cerebellar MSA and 4 patients with parkinsonian MSA) were included in this study. All patients underwent standard polysomnography. The mean ESS score was 6.2 ± 0.9, and EDS was identified in 24% of the patients. SDB and abnormal PLMS were identified in 24 (96%) and 11 (44%) patients, respectively. The prevalences of EDS in patients with SDB and abnormal PLMS were 25% and 18%, respectively. No correlations were observed between ESS scores and the parameters of SDB or abnormal PLMS.
Conclusions
The frequency of EDS in Japanese patients with MSA was similar to that in Caucasian MSA patients. SDB and abnormal PLMS were frequently observed in MSA patients, although the severities of these factors were not correlated with EDS. Further investigations using objective sleep tests need to be performed.
doi:10.1186/1471-2377-12-130
PMCID: PMC3517378  PMID: 23116490
Multiple system atrophy; Excessive daytime sleepiness; Epworth Sleepiness Scale; Sleep-disordered breathing; Abnormal periodic leg movements in sleep
8.  Prevalence of high Epworth Sleepiness Scale scores in a rural population 
BACKGROUND:
Increased daytime sleepiness is an important symptom of obstructive sleep apnea (OSA). OSA is frequently underdiagnosed, and the Epworth Sleepiness Scale (ESS) can be a useful tool in alerting physicians to a potential problem involving OSA.
OBJECTIVE:
To measure the prevalence and determinants of daytime sleepiness measured using the ESS in a rural community population.
METHODS:
A community survey was conducted to examine the risk factors associated with ESS in a rural population in 154 households comprising 283 adults. Questionnaire information was obtained regarding physical factors, social factors, general medical history, family medical history, ESS score, and self-reported height and weight. Multivariable binary logistic regression analysis based on the generalized estimating equations approach to account for clustering within households was used to predict the relationship between a binary ESS score outcome (normal or abnormal) and a set of explanatory variables.
RESULTS:
The population included 140 men (49.5%) and 143 women (50.5%) with an age range of 18 to 97 years (mean [± SD] 52.0±14.9 years). The data showed that 79.2% of the study participants had an ESS score in the normal range (0 to 10) and 20.8% had an ESS score >10, which is considered to be abnormal or high sleepiness. Multivariable regression analysis revealed that obesity was significantly associated with an abnormal or high sleepiness score on the ESS (OR 3.40 [95% CI 1.31 to 8.80).
CONCLUSION:
High levels of sleepiness in this population were common. Obesity was an important risk factor for high ESS score.
PMCID: PMC3373290  PMID: 22536583
Epworth Sleepiness Scale; Obesity; Rural; Snoring
9.  Fatigue, reduced sleep quality and restless legs syndrome in Charcot-Marie-Tooth disease: a web-based survey 
Journal of Neurology  2009;257(4):646-652.
To investigate the prevalence of fatigue, daytime sleepiness, reduced sleep quality, and restless legs syndrome (RLS) in a large cohort of patients with Charcot-Marie-Tooth disease (CMT) and their impact on health-related quality of life (HRQoL). Participants of a web-based survey answered the Epworth Sleepiness Scale, the Pittsburgh Sleep Quality Index, the Multidimensional Fatigue Inventory, and, if the diagnostic criteria of RLS were met, the International RLS Severity Scale. Diagnosis of RLS was affirmed in screen-positive patients by means of a standardized telephone interview. HRQoL was assessed by using the SF-36 questionnaire. Age- and sex-matched control subjects were recruited from waiting relatives of surgical outpatients. 227 adult self-reported CMT patients answered the above questionnaires, 42.9% were male, and 57.1% were female. Age ranged from 18 to 78 years. Compared to controls (n = 234), CMT patients reported significantly higher fatigue, a higher extent and prevalence of daytime sleepiness and worse sleep quality. Prevalence of RLS was 18.1% in CMT patients and 5.6% in controls (p = 0.001). RLS severity was correlated with worse sleep quality and reduced HRQoL. Women with CMT were affected more often and more severely by RLS than male patients. With regard to fatigue, sleep quality, daytime sleepiness, RLS prevalence, RLS severity, and HRQoL, we did not find significant differences between genetically distinct subtypes of CMT. HRQoL is reduced in CMT patients which may be due to fatigue, sleep-related symptoms, and RLS in particular. Since causative treatment for CMT is not available, sleep-related symptoms should be recognized and treated in order to improve quality of life.
Electronic supplementary material
The online version of this article (doi:10.1007/s00415-009-5390-1) contains supplementary material, which is available to authorized users.
doi:10.1007/s00415-009-5390-1
PMCID: PMC3128702  PMID: 19937049
Charcot-Marie-Tooth disease; Fatigue; Restless legs syndrome; Quality of life
10.  Subjective and Objective Appraisal of Activity in Adults with Obstructive Sleep Apnea 
Journal of Aging Research  2011;2011:751819.
Objective. This study examined the association between obstructive sleep apnea (OSA), daytime sleepiness, functional activity, and objective physical activity. Setting. Subjects (N = 37) being evaluated for OSA were recruited from a sleep clinic. Participants. The sample was balanced by gender (53% male), middle-aged, primarily White, and overweight or obese with a mean BMI of 33.98 (SD = 7.35; median BMI = 32.30). Over 40% reported subjective sleepiness (Epworth Sleepiness Scale (ESS) ≥10) and had OSA (78% with apnea + hypopnea index (AHI) ≥5/hr). Measurements. Evaluation included questionnaires to evaluate subjective sleepiness (Epworth Sleepiness Scale (ESS)) and functional outcomes (Functional Outcomes of Sleep Questionnaire (FOSQ)), an activity monitor, and an overnight sleep study to determine OSA severity. Results. Increased subjective sleepiness was significantly associated with lower scores on the FOSQ but not with average number of steps walked per day. A multiple regression analysis showed that higher AHI values were significantly associated with lower average number of steps walked per day after controlling patient's age, sex, and ESS. Conclusion. Subjective sleepiness was associated with perceived difficulty in activity but not with objectively measured activity. However, OSA severity was associated with decreased objective physical activity in aging adults.
doi:10.4061/2011/751819
PMCID: PMC3022211  PMID: 21253491
11.  AB 5. Sleep quality, quality of life, and sleep disorders in patients with end-stage renal disease undergoing long-term haemodialysis 
Journal of Thoracic Disease  2012;4(Suppl 1):AB5.
Background
Sleep disturbances are commonly reported by patients with end- stage renal disease undergoing dialysis. The aim of this study was to assess sleep quality and quality of life and to examine the prevalence of sleep disorders in a group of uremic patients on maintenance dialysis.
Patients and methods
Enrolled were 92 patients on maintenance dialysis, to whom 5 different questionnaires were distributed, examining sleep characteristics and quality of life [Athens Insomnia Scale (AIS), Epworth Sleepiness Scale (ESS), Pittsburg Sleep Quality Index (PSQI), IRLS-Study group questionnaire, WHO-5 Well Being Index].
Results
Low sleep quality was reported by 42 patients (45.7%), and insomnia by 28.3% (n=26). Additionally, Restless Legs Syndrome was reported by 42.4% (n=39). On the contrary, only one patient had an ESS score, indicative of excessive daytime sleepiness. Finally, 32 patients (34.8%) had a score indicative of low quality of life in WHO-5 questionnaire.
Conclusions
A significant presence of sleep disorders among haemodialysis patients was recorded. Still, further studies using polysomnographic records are necessary to confirm these results.
doi:10.3978/j.issn.2072-1439.2012.s109
PMCID: PMC3537421
12.  Evaluation of an auto-CPAP device for treatment of obstructive sleep apnoea 
Thorax  1998;53(8):643-648.
BACKGROUND—Auto-CPAP machines used in the treatment of obstructive sleep apnoea (OSA) are designed to vary the treatment pressure automatically in order always to apply the actually needed pressure. Consequently they should be able to achieve at least identical therapeutic effects as conventional constant pressure CPAP with a lower mean treatment pressure. The present study was designed to evaluate the therapeutic efficacy and the treatment pressure of an auto-CPAP machine (REM+auto®, SEFAM) in comparison with a conventional CPAP device.
METHODS—Following CPAP titration, 16 patients with OSA were allocated to receive conventional CPAP and auto-CPAP treatment under polysomnographic control in a randomised order. After each treatment the patients were asked to assess the therapy using a questionnaire; a vigilance test was also carried out and subjective daytime sleepiness was evaluated using the Epworth Sleepiness Scale (ESS).
RESULTS—The mean (SD) apnoea/hypopnoea index (AHI) during auto-CPAP treatment was comparable with that during conventional CPAP treatment (4.2 (5.1) versus 3.6 (4.0)). Neither an analysis of sleep architecture nor the arousal index (7.4 (4.1) versus 7.0 (4.3)) revealed any significant differences. Daytime sleepiness measured with the ESS was also comparable (5.3 (3.4) versus 6.5 (4.2)). The vigilance test showed normal values after both treatments in all patients with no significant differences. The mean pressure during auto-CPAP treatment (8.1 (2.9) mbar), however, was significantly higher than that employed in conventional CPAP treatment (7.6 (2.7) mbar; mean difference 0.5 mbar; 95% CI 0.1 to 0.9 mbar; p<0.05).
CONCLUSIONS—Auto-CPAP was equally as effective as conventional CPAP with respect to therapeutic efficacy. The aim of reducing the treatment pressure with auto-CPAP, however, was not achieved.


PMCID: PMC1745298  PMID: 9828849
13.  REM sleep behavior disorder preceding other aspects of synucleinopathies by up to half a century(e–Pub ahead of print)(CME) 
Neurology  2010;75(6):494-499.
Background:
Idiopathic REM sleep behavior disorder (RBD) may be the initial manifestation of synucleinopathies (Parkinson disease [PD], multiple system atrophy [MSA], or dementia with Lewy bodies [DLB]).
Methods:
We used the Mayo medical records linkage system to identify cases presenting from 2002 to 2006 meeting the criteria of idiopathic RBD at onset, plus at least 15 years between RBD and development of other neurodegenerative symptoms. All patients underwent evaluations by specialists in sleep medicine to confirm RBD, and behavioral neurology or movement disorders to confirm the subsequent neurodegenerative syndrome.
Results:
Clinical criteria were met by 27 patients who experienced isolated RBD for at least 15 years before evolving into PD, PD dementia (PDD), DLB, or MSA. The interval between RBD and subsequent neurologic syndrome ranged up to 50 years, with the median interval 25 years. At initial presentation, primary motor symptoms occurred in 13 patients: 9 with PD, 3 with PD and mild cognitive impairment (MCI), and 1 with PDD. Primary cognitive symptoms occurred in 13 patients: 10 with probable DLB and 3 with MCI. One patient presented with primary autonomic symptoms, diagnosed as MSA. At most recent follow-up, 63% of patients progressed to develop dementia (PDD or DLB). Concomitant autonomic dysfunction was confirmed in 74% of all patients.
Conclusions:
These cases illustrate that the α-synuclein pathogenic process may start decades before the first symptoms of PD, DLB, or MSA. A long-duration preclinical phase has important implications for epidemiologic studies and future interventions designed to slow or halt the neurodegenerative process.
GLOSSARY
= dementia with Lewy bodies;
= mild cognitive impairment;
= multiple system atrophy;
= Parkinson disease;
= PD with associated mild cognitive impairment;
= Parkinson disease dementia;
= polysomnogram;
= REM sleep behavior disorder.
doi:10.1212/WNL.0b013e3181ec7fac
PMCID: PMC2918473  PMID: 20668263
14.  Increased Corticomuscular Coherence in Idiopathic REM Sleep Behavior Disorder 
The authors hypothesized that if locomotor drive increases along with rapid eye movement (REM) sleep without atonia in idiopathic REM sleep behavior disorder (RBD), then RBD patients would have greater corticomuscular coherence (CMC) values during REM sleep than at other sleep stages and than in healthy control subjects during REM sleep. To explore this hypothesis, we analyzed beta frequency range CMC between sensorimotor cortex electroencephalography (EEG) and chin/limb muscle EMG in idiopathic RBD patients. Eleven drug naive idiopathic RBD patients and 11 age-matched healthy control subjects were included in the present study. All participants completed subjective sleep questionnaires and underwent polysomnography for one night. The CMC value between EEGs recorded at central electrodes and EMGs acquired at leg and chin muscles were computed and compared by repeated measures analysis of variance (ANOVA). Sleep stages and muscle (i.e., chin vs. leg) served as within-subject factors, and group served as the between-subject factor. Repeated measures ANOVA revealed no significant main effect of group (F1,20 = 0.571, p = 0.458) or muscle (F1,20 = 1.283, p = 0.271). However, sleep stage was found to have a significant main effect (F2.067,41.332 = 20.912, p < 0.001). The interaction between group and sleep stage was significant (F2.067,41.332 = 3.438, p = 0.040). RBD patients had a significantly higher CMC value than controls during REM sleep (0.047 ± 0.00 vs. 0.052 ± 0.00, respectively, p = 0.007). This study reveals increased CMC during REM sleep in patients with RBD, which indicates increased cortical locomotor drive. Furthermore, this study supports the hypothesis that sufficient locomotor drive plays a role in the pathophysiology of RBD in addition to REM sleep without atonia.
doi:10.3389/fneur.2012.00060
PMCID: PMC3332227  PMID: 22536195
REM sleep behavior disorder; pathophysiology; corticomuscular coherence; REM sleep without atonia
15.  Pupillometric Assessment of Sleepiness in Narcolepsy 
Purpose: Excessive daytime sleepiness is highly prevalent in the general population, is the hallmark of narcolepsy, and is linked to significant morbidity. Clinical assessment of sleepiness remains challenging and the common objective multiple sleep latency test (MSLT) and subjective Epworth sleepiness scale (ESS) methods correlate poorly. We examined the relative utility of pupillary unrest index (PUI) as an objective measure of sleepiness in a group of unmedicated narcoleptics and healthy controls in a prospective, observational pilot study. Methods: Narcolepsy (n = 20; untreated for >2 weeks) and control (n = 56) participants were tested under the same experimental conditions; overnight polysomnography was performed on all participants, followed by a daytime testing protocol including: MSLT, PUI, sleepiness visual analog scale (VAS), ESS, and the psychomotor vigilance test (PVT). Results: The narcolepsy and control groups differed significantly on psychomotor performance and each measure of objective and subjective sleepiness, including PUI. Across the entire sample, PUI correlated significantly with objective (mean sleep latency, SL) and subjective (ESS and VAS) sleepiness, but none of the sleepiness measures correlated with performance (PVT). Among narcoleptics, VAS correlated with PVT measures. Within the control group, mean PUI was the only objective sleepiness measure that correlated with subjective sleepiness. Finally, in an ANCOVA model, SL and ESS were significantly predictive of PUI as measure of sleepiness. Conclusion: The role of PUI in quantifying and distinguishing sleepiness of narcolepsy from sleep-satiated healthy controls merits further investigation as it is a portable, brief, and objective test.
doi:10.3389/fpsyt.2011.00035
PMCID: PMC3113169  PMID: 21713070
pupillary unrest index; narcolepsy; daytime sleepiness; vigilance-performance
16.  Modification of the Epworth Sleepiness Scale in Central China 
Quality of Life Research  2011;20(10):1721-1726.
Purpose
The well-known excessive daytime sleepiness (EDS) assessment, Epworth Sleepiness Scale (ESS), is not consistently qualified for patients with diverse living habits. This study is aimed to build a modified ESS (mESS) and then to verify its feasibility in the assessment of EDS for patients with suspected sleep-disordered breathing (SDB) in central China.
Methods
A Ten-item Sleepiness Questionnaire (10-ISQ) was built by adding two backup items to the original ESS. Then the 10-ISQ was administered to 122 patients in central China with suspected SDB [among them, 119 cases met the minimal diagnostic criteria for obstructive sleep apnea by sleep study, e.g., apnea and hypopnea index (AHI) ≥ 5 h−1] and 117 healthy central Chinese volunteers without SDB. Multivariate exploratory techniques were used for item validation. The unreliable item in the original ESS was replaced by the eligible backup item, thus a modified ESS (mESS) was built, and then verified.
Results
Item 8 proved to be the only unreliable item in central Chinese patients, with the least factor loading on the main factor and the lowest item-total correlation both in the 10-ISQ and in the original ESS, deletion of it would increase the Cronbach’s alpha (from 0.86 to 0.87 in the 10-ISQ; from 0.83 to 0.85 in the original ESS). The mESS was subsequently built by replacing item 8 in the original ESS with item 10 in the 10-ISQ. Verification with patients’ responses revealed that the mESS was a single-factor questionnaire with good internal consistency (Cronbach’s alpha = 0.86). The sum score of the mESS not only correlated with AHI (P < 0.01) but was also able to discriminate the severity of obstructive apnea (P < 0.01). Nasal CPAP treatment for severe OSA reduced the score significantly (P < 0.001). The performance of the mESS was poor in evaluating normal subjects.
Conclusion
The mESS improves the validity of ESS for our patients. Therefore, it is justified to use it instead of the original one in assessment of EDS for patients with SDB in central China.
doi:10.1007/s11136-011-9898-3
PMCID: PMC3220816  PMID: 21484529
Epworth Sleepiness Scale; Excessive daytime sleepiness; Sleep-disordered breathing
17.  Excessive daytime sleepiness assessed by the Epworth Sleepiness Scale and its association with health related quality of life: a population-based study in China 
BMC Public Health  2012;12:849.
Background
Excessive daytime sleepiness (EDS) is a common condition worldwide that has many negative effects on people who were afflicted with it, especially on their health-related quality of life (HRQOL). The Epworth Sleepiness Scale (ESS) is a commonly used method for evaluating EDS in English-speaking countries. This paper reported the prevalence of subjective EDS in China as assessed by the Mandarin version of the ESS; tested the scale’s response rate, reliability and validity; and investigated the relationship between ESS scores and HRQOL.
Methods
A population-based sample of 3600 residents was selected randomly in five cities in China. The demographic information was collected, subjective EDS was assessed by the Mandarin version of the ESS (ESS scores >10), and HRQOL was evaluated by the Mandarin version of the 36-item Short Form Health Survey (SF-36).
Results
The Mandarin version of ESS had very few missing responses, and the average response rate of its eight items was 97.92%. The split-half reliability coefficient and Cronbach’s α coefficient were 0.81 and 0.80, respectively. One factor was identified by factor analysis with an eigenvalue of 2.78. The ESS scores showed positive skewness in the selected sample, with a median (Q1, Q3) of 6 (3, 0). 644 (22.16%) respondents reported subjective EDS, and all of the scores of the eight dimensions of the SF-36 were negatively correlated with ESS scores.
Conclusions
The Mandarin version of ESS is an acceptable, reliable, and valid tool for measuring EDS. In addition, subjective EDS is common in China, based on the ESS results, and impairs HRQOL.
doi:10.1186/1471-2458-12-849
PMCID: PMC3524046  PMID: 23039935
Excessive daytime sleepiness; Mandarin; Epworth Sleepiness Scale; Health-related quality of life
18.  Periodic Limbic Movement Disorder during Sleep as Diabetes-Related Syndrome? A Polysomnographic Study 
ISRN Endocrinology  2011;2011:246157.
Introduction. Periodic limb movements during sleep (PLMs) is common in the elderly. When quality-of-life drops due to sleep disturbances, we speak about periodic limb movement disorder during sleep (PLMD). Another similar disorder, restless legs syndrome (RLS), is considered to be related to diabetes; RLS and PLMDs are genetically related. Our aim was to detect PLMDs in a population of diabetic patients and identify them as possible hallmarks of these autonomic disorders. Material and Methods. We selected 41 type-2 diabetics with no sleep comorbidity, and compared them with 38 healthy matched volunteers. All participants underwent the Epworth Sleepiness Scale (ESS) and polysomnography (PSG). A periodic limb movement (PLM) index >5, that is, the higher number of PLMs/sleep hour for the entire night, was considered as abnormal. Results. Diabetics showed lower sleep efficiency than controls on the ESS, lower proportions of REM and non-REM sleep, and higher arousal and PLM indexes, as assessed through PSG. PLMDs were diagnosed in 13 of 41 diabetic patients (31%); the latter showed lower sleep efficiency, lower non-REM slow-wave sleep, and increased arousal and PLM indexes. Conclusion. The relationship between PLMs-related sleep fragmentation and endocrine carbohydrate metabolism regulation might be casual or genetically determined. This deserves further investigations.
doi:10.5402/2011/246157
PMCID: PMC3262626  PMID: 22363869
19.  Snoring and obstructive sleep apnoea syndrome among hypertensive Nigerians: Prevalence and clinical correlates 
Background
Obstructive sleep apnoea (OSA) syndrome is a common disorder in the community. Association between hypertension and sleep apnoea and /or snoring has been described. The Berlin questionnaire is a validated instrument that is used to identify individuals who are at risk for OSA. The study aim to describe the prevalence of snoring and OSA among hypertensive subjects in South Western, Nigeria.
Methods
This was a descriptive study conducted at the Cardiology clinic of Ladoke Akintola University of Technology LAUTECH Teaching Hospital, Osogbo, South West Nigeria. One hundred consecutive hypertensive patients were recruited from the clinic. The Berlin questionnaire and the Epworth sleepiness scale (ESS) were used to determine excessive daytime sleepiness and the risk of having OSA. Statistical analysis was done using SPSS 16.0. Data were summarized as means ± S.D and percentages.
Results
The study participants consisted of 40 males (40.0%). The demographic data were similar between both genders except that females had higher mean body mass index than males. The prevalence of snoring was 50.0%. 52% were categorized as being at high risk of having OSA. Snorers were more likely to be older, males and to have a higher fasting blood sugar than non-snorers.96% of snorers reported excessive daytime somnolence as predicted by the ESS score compared to 4% of non snorers. Prevalence of snoring was also higher among overweight and obese hypertensive subjects than normal body mass index hypertensive subjects.
Conclusion
Snoring is common among hypertensive subjects in South Western Nigeria. Clinically suspected OSA was similarly high in prevalence among them. Early identification and management may reduce the cardiovascular risk of hypertensive subjects.
PMCID: PMC3361213  PMID: 22655109
Snoring; sleep apnoea; hypertension; prevalence; clinical correlates; Nigeria
20.  Associations between sleep disturbance and primary headaches: the third Nord-Trøndelag Health Study 
The Journal of Headache and Pain  2010;11(3):197-206.
The aim of the study was to evaluate the association between sleep disturbance and headache type and frequency, in a random sample of participants in the third Nord-Trøndelag Health Survey. The headache diagnoses were set by neurologists using the ICHD-2 criteria performing a semi structured face-to-face interview. Sleep problems were measured by the two validated instruments Karolinska Sleep Questionnaire (KSQ) and Epworth Sleepiness Scale (ESS). Among 297 participants, 77 subjects were headache-free, whereas 135 were diagnosed with tension-type headache (TTH), 51 with migraine, and 34 with other headache diagnoses. In the multivariate analyses, using logistic regression, excessive daytime sleepiness, defined as ESS ≥ 10, was three times more likely among migraineurs compared with headache-free individuals (OR = 3.3, 95% CI 1.0–10.2). Severe sleep disturbances, defined as KSQ score in the upper quartile, was five times more likely among migraineurs (OR = 5.4, 95% CI 2.0–15.5), and three times more likely for subjects with TTH (OR = 3.3, 1.4–7.3) compared with headache-free individuals. Subjects with chronic headache were 17 times more likely to have severe sleep disturbances (OR = 17.4, 95% CI 5.1–59.8), and the association was somewhat stronger for chronic migraine (OR = 38.9, 95% CI 3.1–485.3) than for chronic TTH (OR = 18.3, 95% CI 3.6–93.0). In conclusion, there was a significant association between severe sleep disturbances and primary headache disorders, most pronounced for those with chronic headache. Even though one cannot address causality in the present study design, the results indicate an increased awareness of sleep problems among patients with headache.
doi:10.1007/s10194-010-0201-8
PMCID: PMC3451918  PMID: 20224943
Chronic headache; Migraine; Tension-type headache; Karolinska Sleep Questionnaire; Daytime sleepiness
21.  Validation of the Mayo Sleep Questionnaire to Screen for REM Sleep Behavior Disorder in an Aging and Dementia Cohort 
Sleep medicine  2011;12(5):445-453.
Objective
To validate a questionnaire focused on REM sleep behavior disorder (RBD) among participants in an aging and dementia cohort.
Background
RBD is a parasomnia that can develop in otherwise neurologically-normal adults as well as in those with a neurodegenerative disease. Confirmation of RBD requires polysomnography (PSG). A simple screening measure for RBD would be desirable for clinical and research purposes.
Methods
We had previously developed the Mayo Sleep Questionnaire (MSQ), a 16 item measure, to screen for the presence of RBD and other sleep disorders. We assessed the validity of the MSQ by comparing the responses of patients’ bed partners with the findings on PSG. All subjects recruited in the Mayo Alzheimer’s Disease Research Center at Mayo Clinic Rochester and Mayo Clinic Jacksonville from 1/00 to 7/08 who had also undergone a PSG were the focus of this analysis.
Results
The study sample was comprised of 176 subjects [150 male; median age 71 years (range 39–90)], with the following clinical diagnoses: normal (n=8), mild cognitive impairment (n=44), Alzheimer’s disease (n=23), dementia with Lewy bodies (n=74), as well as other dementia and/or parkinsonian syndromes (n=27). The core question on recurrent dream enactment behavior yielded a sensitivity (SN) of 98% and specificity (SP) of 74% for the diagnosis of RBD. The profile of responses on four additional subquestions on RBD and one on obstructive sleep apnea improved specificity.
Conclusions
These data suggest that among aged subjects with cognitive impairment and/or parkinsonism, the MSQ has adequate SN and SP for the diagnosis of RBD. The utility of this scale in other patient populations will require further study.
doi:10.1016/j.sleep.2010.12.009
PMCID: PMC3083495  PMID: 21349763
sleep disorders; parasomnias; dementia; Alzheimer’s disease; dementia with Lewy bodies; parkinsonism
22.  Daytime sleepiness in elderly Parkinson’s disease patients and treatment with the psychostimulant modafinil: A preliminary study 
Background:
Patients with Parkinson’s disease (PD) or Parkinsonian syndromes often report excessive daytime sleepiness (EDS). The aim of this study was to evaluate the effects of the psychostimulant modafinil on elderly, institutionalized, severely impaired PD patients with EDS.
Method:
A three-week open study on ten institutionalized PD patients scoring >10 points on the Epworth Sleepiness Scale (ESS) with modafinil eventually on 100 mg twice a day. Patients were assessed at the start, week 1, and week 3 with ESS, Clinical Global Impression (CGI) scale severity of PD and appetite.
Results:
Reduction of ESS score and PD severity over time were found as well as a significant increase in appetite and reduction in CGI score.
Conclusion:
Modafinil 100 mg twice a day was safe and modestly effective for the treatment of EDS in elderly, institutionalized PD patients. Sustaining wakefulness throughout all stages of PD is crucial for participating in life, maintaining social life, and improving quality of life.
PMCID: PMC2854085  PMID: 20396641
Parkinson’s disease; daytime sleepiness; Epworth sleepiness scale; psychostimulant
23.  Validation of the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale in Older Black and White Women 
Sleep medicine  2011;13(1):36-42.
Objectives
Despite routine use with older adults, the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) have not been adequately validated in older samples, particularly those from diverse racial backgrounds. The objective of this study was to determine the reliability and validity of and to provide normative data for these questionnaires in community-dwelling older women.
Methods
Participants were 306 black and 2,662 white women aged ≥70 from the Study of Osteoporotic Fractures. Participants completed the PSQI and ESS, and provided self-reported assessments of mood, cognition, and functioning, and underwent wrist actigraphy for sleep-wake estimation.
Results
Good internal consistency in both black and white women was demonstrated for the PSQI and ESS. Two PSQI subscales, however, were found to have inadequate reliability (Medications, Daytime Dysfunction). Both the PSQI and ESS were associated with theoretically similar measures in the expected directions. The PSQI also differentiated participants with no reported sleep disorder from those reporting at least one sleep disturbance, such as insomnia, sleep apnea, and restless legs. The ESS only differentiated women reporting no sleep disorder from those reporting insomnia.
Conclusions
In general, findings suggest that the PSQI and ESS are internally consistent, valid measures of self-reported sleep conditions problems in older women. Additional research is required to evaluate the impact of removing the Medications and Daytime Dysfunction PSQI subscales on this measure's internal consistency in older women.
doi:10.1016/j.sleep.2011.04.005
PMCID: PMC3586742  PMID: 22033120
sleep; geriatric assessment; actigraphy; oldest old; women; aged
24.  Self assessment of daytime sleepiness: patient versus partner. 
Thorax  1995;50(9):994-995.
BACKGROUND--Patients with the sleep apnoea/hypopnoea syndrome (SAHS) and their spouses often differ in their assessment of the patient's sleepiness. A study was therefore undertaken to investigate whether either the patient's or partner's rating on the Epworth sleepiness scale (ESS) was better related to illness severity. METHODS--Nocturnal variables (apnoeas+hypopnoeas/hour (AHI) and arousals/hour) and patient and partner ESS scores were compared in 103 new patients attending the sleep clinic. RESULTS--Mean patient and partner ESS scores were not different. In the whole population neither patient nor partner ESS variables correlated with AHI or arousal frequency. In the patients with SAHS (AHI > or = 15), partner ESS correlated weakly with AHI, but patient ESS did not. CONCLUSIONS--This study suggests that neither patient nor partner ESS ratings are strong predictors of SAHS severity.
PMCID: PMC1021317  PMID: 8539684
25.  Hallucinations, dreaming and frequent dozing in Parkinson’s disease: Impact of right-hemisphere neural networks 
Objective
To relate sleep disturbances in Parkinson’s disease (PD) to hemispheric asymmetry of initial presentation.
Background
Sleep disturbances are common in PD arising from the neurodegenerative process underlying the disease, which is usually lateralized at onset. Patients with left-side onset (LPD: right hemisphere dysfunction) exhibit reduced vigilance relative to those with right-side onset (RPD: left hemisphere dysfunction), leading us to hypothesize that sleep-related disturbances, particularly excessive daytime sleepiness, would be more severe for LPD than for RPD.
Methods
Thirty-one non-demented participants with PD (17 RPD and 14 LPD) and 17 age-matched control participants with chronic health conditions (CO) were administered the Parkinson’s Disease Sleep Scale and polysomnography was performed on a subset of the PD participants.
Results
Both PD subgroups exhibited more nighttime motor symptoms than the CO group, but only LPD endorsed more nocturnal hallucinations and daytime dozing. Controlling for mood additionally revealed more vivid dreaming in LPD than RPD. There were no significant differences between LPD and RPD on measures of sleep architecture.
Conclusions
Increased dreaming, hallucinations, and daytime somnolescence in LPD may be related to changes in right-hemisphere neural networks implicated in the generation and control of visual images, arousal and vigilance. Our results underscore the need to consider side of onset in regard to sleep disturbances in PD.
doi:10.1097/WNN.0b013e318185e698
PMCID: PMC2630478  PMID: 18797256
Parkinson’s disease; hemiparkinsonism; sleep disturbances; hypersomnia

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