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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.
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.
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.
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).
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.
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.
PMCID: PMC3575252  PMID: 23394437
Parkinson’s disease; Rapid eye movement sleep behavior disorder; Cognition; Quality of life; Nocturnal problems
3.  Restless legs syndrome and daytime sleepiness are prominent in myotonic dystrophy type 2 
Neurology  2013;81(2):157-164.
Although sleep disturbances are common in myotonic dystrophy type 1 (DM1), sleep disturbances in myotonic dystrophy type 2 (DM2) have not been well-characterized. We aimed to determine the frequency of sleep disturbances in DM2.
We conducted a case-control study of 54 genetically confirmed DM2 subjects and 104 medical controls without DM1 or DM2, and surveyed common sleep disturbances, including symptoms of probable restless legs syndrome (RLS), excessive daytime sleepiness (EDS), sleep quality, fatigue, obstructive sleep apnea (OSA), probable REM sleep behavior disorder (pRBD), and pain. Thirty patients with DM2 and 43 controls responded to the survey. Group comparisons with parametric statistical tests and multiple linear and logistic regression analyses were conducted for the dependent variables of EDS and poor sleep quality.
The mean ages of patients with DM2 and controls were 63.8 and 64.5 years, respectively. Significant sleep disturbances in patients with DM2 compared to controls included probable RLS (60.0% vs 14.0%, p < 0.0001), EDS (p < 0.001), sleep quality (p = 0.02), and fatigue (p < 0.0001). EDS and fatigue symptoms were independently associated with DM2 diagnosis (p < 0.01) after controlling for age, sex, RLS, and pain scores. There were no group differences in OSA (p = 0.87) or pRBD (p = 0.12) scores.
RLS, EDS, and fatigue are frequent sleep disturbances in patients with DM2, while OSA and pRBD symptoms are not. EDS was independently associated with DM2 diagnosis, suggesting possible primary CNS hypersomnia mechanisms. Further studies utilizing objective sleep measures are needed to better characterize sleep comorbidities in DM2.
PMCID: PMC3770170  PMID: 23749798
4.  Family history of idiopathic REM behavior disorder 
Neurology  2013;80(24):2233-2235.
To compare the frequency of proxy-reported REM sleep behavior disorder (RBD) among relatives of patients with polysomnogram-diagnosed idiopathic RBD (iRBD) in comparison to controls using a large multicenter clinic-based cohort.
A total of 316 patients with polysomnography-confirmed iRBD were recruited from 12 RBD study group centers, along with 316 controls matched on sex and age group. All subjects completed a self-administered questionnaire that collected proxy-reported information on family history of tremor, gait trouble, balance trouble, Parkinson disease, memory loss, and Alzheimer disease. The questionnaire also included a single question that asked about possible symptoms of RBD among first-degree relatives (siblings, parents, and children).
A positive family history of dream enactment was reported in 13.8% of iRBD cases compared to 4.8% of controls (odds ratio [OR] = 3.9, 95% confidence interval [CI] 2.0–7.7). ORs were increased for both siblings (OR = 6.1, 95% CI 2.1–18.1) and parents (OR = 3.2, 95% CI 1.4–7.8). We found no significant difference in sex, current age (65.3 ± 10.2 vs 66.9 ± 10.2 years), or age at self-reported RBD onset (55.2 ± 11.7 vs 56.6 ± 15.1 years) in possible familial vs sporadic iRBD. No differences were found in family history of tremor, walking and balance troubles, Parkinson disease, memory loss, or Alzheimer disease.
We found increased odds of proxy-reported family history of presumed RBD among individuals with confirmed iRBD. This suggests the possibility of a genetic contribution to RBD.
PMCID: PMC3721098  PMID: 23658378
5.  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.
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.
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.
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).
In this population-based cohort study, we observed that pRBD confers a 2.2-fold increased risk of developing MCI / PD over four years.
PMCID: PMC3270692  PMID: 22275251
sleep disorders; parasomnias; dementia; Alzheimer’s disease; dementia with Lewy bodies; parkinsonism; synuclein
6.  Correlation between Nocturia and Sleep: A Questionnaire Based Analysis 
Korean Journal of Urology  2010;51(11):757-762.
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.
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).
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.
PMCID: PMC2991572  PMID: 21165195
Nocturia; Quality of life; Sleep disorders
7.  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.
PMCID: PMC3544335  PMID: 23326757
8.  Improved Sleep Efficiency after Anti-Tumor Necrosis Factor α Therapy in Rheumatoid Arthritis Patients 
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.
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.
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.
Improved sleep efficiency and ‘awakening after sleep onset’ time were observed in RA patients treated with anti-TNF-α therapy.
PMCID: PMC3383532  PMID: 22870481
anti-TNF; obstructive sleep apnea; polysomnogram; restless legs syndrome; rheumatoid arthritis; sleep
9.  Daytime sleepiness in Japanese patients with multiple system atrophy: prevalence and determinants 
BMC Neurology  2012;12:130.
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.
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.
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.
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.
PMCID: PMC3517378  PMID: 23116490
Multiple system atrophy; Excessive daytime sleepiness; Epworth Sleepiness Scale; Sleep-disordered breathing; Abnormal periodic leg movements in sleep
10.  Prevalence of high Epworth Sleepiness Scale scores in a rural population 
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.
To measure the prevalence and determinants of daytime sleepiness measured using the ESS in a rural community population.
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.
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).
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
11.  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.
PMCID: PMC3128702  PMID: 19937049
Charcot-Marie-Tooth disease; Fatigue; Restless legs syndrome; Quality of life
12.  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.
PMCID: PMC3022211  PMID: 21253491
13.  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.
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].
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.
A significant presence of sleep disorders among haemodialysis patients was recorded. Still, further studies using polysomnographic records are necessary to confirm these results.
PMCID: PMC3537421
14.  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
15.  Daytime Sleepiness, Circadian Preference, Caffeine Consumption and Khat Use among College Students in Ethiopia 
Journal of sleep disorders-- treatment & care  2013;3(1):10.4172/2325-9639.1000130.
To estimate the prevalence of daytime sleepiness and circadian preferences, and to examine the extent to which caffeine consumption and Khat (a herbal stimulant) use are associated with daytime sleepiness and evening chronotype among Ethiopian college students.
A cross-sectional study was conducted among 2,410 college students. A self-administered questionnaire was used to collect information about sleep, behavioral risk factors such as caffeinated beverages, tobacco, alcohol, and Khat consumption. Daytime sleepiness and chronotype were assessed using the Epworth Sleepiness Scale (ESS) and the Horne & Ostberg Morningness /Eveningness Questionnaire (MEQ), respectively. Linear and logistic regression models were used to evaluate associations.
Daytime sleepiness (ESS≥10) was present in 26% of the students (95% CI: 24.4–27.8%) with 25.9% in males and 25.5% in females. A total of 30 (0.8%) students were classified as evening chronotypes (0.7% in females and 0.9% in males). Overall, Overall, Khat consumption, excessive alcohol use and cigarette smoking status were associated with evening chronotype. Use of any caffeinated beverages (OR=2.18; 95%CI: 0.82–5.77) and Khat consumption (OR=7.43; 95%CI: 3.28–16.98) increased the odds of evening chronotype.
The prevalence of daytime sleepiness among our study population was high while few were classified as evening chronotypes. We also found increased odds of evening chronotype with caffeine consumption and Khat use amongst Ethiopian college students. Prospective cohort studies that examine the effects of caffeinated beverages and Khat use on sleep disorders among young adults are needed.
PMCID: PMC4015623  PMID: 24818170
16.  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.
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]).
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.
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.
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.
= 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.
PMCID: PMC2918473  PMID: 20668263
17.  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.
PMCID: PMC3332227  PMID: 22536195
REM sleep behavior disorder; pathophysiology; corticomuscular coherence; REM sleep without atonia
18.  Prevalence of Sleep Disturbances in Mild Cognitive Impairment and Dementing Disorders: A Multicenter Italian Clinical Cross-Sectional Study on 431 Patients 
Sleep disturbances are common in the elderly and in persons with cognitive decline. The aim of this study was to describe frequency and characteristics of insomnia, excessive daytime sleepiness, sleep-disordered breathing, REM behavior disorder and restless legs syndrome in a large cohort of persons with mild cognitive impairment or dementia.
431 consecutive patients were enrolled in 10 Italian neurological centers: 204 had Alzheimer's disease, 138 mild cognitive impairment, 43 vascular dementia, 25 frontotemporal dementia and 21 Lewy body dementia or Parkinson's disease dementia. Sleep disorders were investigated with a battery of standardized questions and questionnaires.
Over 60% of persons had one or more sleep disturbances almost invariably associated one to another without any evident and specific pattern of co-occurrence. Persons with Alzheimer's disease and those with mild cognitive impairment had the same frequency of any sleep disorder. Sleep-disordered breathing was more frequent in vascular dementia. REM behavior disorder was more represented in Lewy body or Parkinson's disease dementia.
A careful clinical evaluation of sleep disorders should be performed routinely in the clinical setting of persons with cognitive decline. Instrumental supports should be used only in selected patients.
PMCID: PMC3696366  PMID: 22415141
Sleep disorders; Excessive daytime sleepiness; Mild cognitive impairment; Alzheimer's disease; Frontotemporal dementia; Lewy body dementia; Parkinson's disease dementia; Vascular dementia
19.  Sleep disturbances in patients with multiple sclerosis 
Neurological Sciences  2012;34:1291-1296.
Sleep disturbances constitute one of the important yet underestimated aspects of functioning of patients with multiple sclerosis (MS). The objective of this study was to evaluate sleep disturbances in patients with MS, with regard to demographic factors, disease-related variables, co-existing conditions and fatigue. In 100 MS patients, Epworth Sleepiness Scale (ESS) and a questionnaire about sleep disturbances (SlD) were implemented. ESS and SlD results were analyzed with regard to age, gender, duration of MS, type of its course, degree of disability in Expanded Disability Status Scale (EDSS), MS therapies, coexisting diseases, results of Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS). ESS score indicated increased daytime sleepiness in 19 patients. In SlD, 49 subjects reported sleep disturbances and 35 more than one of their kind (most commonly terminal and middle insomnia). No relationships were found between ESS and SlD scores and age, gender, MS duration, type of its course, EDSS or coexisting diseases. In 36 patients, somatic complaints interfered with sleep. The patients with depression had significantly lower ESS result and those currently treated with immunomodulation had significantly lower SlD score. SlD score correlated positively with FSS and MFIS. Sleep disturbances in MS patients may occur independently from demographic and disease-related variables, but they are often influenced by the symptoms of MS and therapies used. Sleep disturbances may contribute to fatigue in the course of MS.
PMCID: PMC3747317  PMID: 23109097
Multiple sclerosis; Sleep disturbances; Fatigue
20.  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.
PMCID: PMC3113169  PMID: 21713070
pupillary unrest index; narcolepsy; daytime sleepiness; vigilance-performance
21.  Daytime Sleepiness in Parkinson's Disease: Perception, Influence of Drugs, and Mood Disorder 
Sleep Disorders  2014;2014:939713.
Parkinson's disease (PD) is associated with sleep complaints as excessive daytime sleepiness (EDS) and several factors have been implicated in the genesis of these complaints. Objective. To correlate the subjective perception of EDS with variables as the severity of the motor symptoms, medications, and the presence of depressive symptoms. Materials and Methods. A cross-sectional study, using specific scales as Epworth sleepiness scale (ESS), Beck depression inventory (iBeck) and Hoehn and Yahr (HY), in 42 patients with PD. Results. The patients had a mean age of 61.2 ± 11.3 years and mean disease duration of 4.96 ± 3.3 years. The mean ESS was 7.5 ± 4.7 and 28.6% of patients reached a score of abnormally high value (>10). There was no association with gender, disease duration, and dopamine agonists. Patients with EDS used larger amounts of levodopa (366.7 ± 228.0 versus 460.4 ± 332.25 mg, P = 0.038), but those who had an iBeck >20 reached lower values of ESS than the others (5.9 ± 4.1 versus 9.3 ± 4.8, P = 0.03). Conclusions. EDS was common in PD patients, being related to levodopa intake. Presence of depressed mood may influence the final results of self-assessment scales for sleep disorders.
PMCID: PMC3920819  PMID: 24587912
22.  REM sleep behaviour disorder is associated with worse quality of life and other non-motor features in early Parkinson's disease 
Concomitant REM sleep behaviour disorder (RBD) is commonly observed in patients with Parkinson's disease (PD). Although the brainstem structures responsible for the symptoms of RBD correspond to the premotor stages of PD, the association of RBD with motor and non-motor features in early PD remains unclear.
The study evaluated 475 patients with PD within 3.5 years of diagnosis for the presence of probable RBD (pRBD) using the REM Sleep Behaviour Disorder Screening Questionnaire (RBDSQ). A neurologist and a trained research nurse carried out evaluation of each participant blinded to the results of the RBDSQ. Standardised rating scales for motor and non-motor features of PD, as well as health-related quality of life measures, were assessed. Multiple linear and logistic regression analyses were used to determine the relationship between pRBD and a variety of outcomes, controlling for confounding factors.
The overall frequency of pRBD was 47.2% (95% CI 42.7% to 51.9%). None of the patients had a previous diagnosis of RBD. Patients with PD and concomitant pRBD did not differ on motor phenotype and scored comparably on the objective motor scales, but reported problems with motor aspects of daily living more frequently. Adjusted for age, sex, disease duration and smoking history, pRBD was associated with greater sleepiness (p=0.001), depression (p=0.001) and cognitive impairment (p=0.006).
pRBD is common and under-recognised in early PD. It is associated with increased severity and frequency of non-motor features, poorer subjective motor performance and a greater impact on health-related quality of life.
PMCID: PMC3995329  PMID: 24187013
23.  Effect of Poor Sleep Quality and Excessive Daytime Sleepiness on Factors Associated with Diabetes Self-Management 
The Diabetes educator  2012;39(1):74-82.
The purpose of this study is to investigate the association of impaired sleep quality and daytime sleepiness on self-reported diabetes control and psychological and social factors that impact diabetes self-management.
Participants were 107 adults with type 2 diabetes (T2DM) with self-reported daytime sleepiness. Subjective sleepiness was assessed using the Epworth Sleepiness Scale (ESS); sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI) Global score and its 3 factors of Perceived Sleep Quality, Sleep Efficiency, and Daily Disturbances. The Diabetes Care Profile (DCP) scales (Control Problems, Social and Personal Factors, Positive Attitude, Negative Attitude, Self-Care Adherence, and Diet Adherence) were used to measure difficulty in maintaining glycemic control and factors important for diabetes control.
Poor sleep quality was associated with significantly worse scores on the DCP scales, with lower diabetes control, negative attitude, decreased positive attitude, lower self-care adherence, and decreased adherence to dietary adherence. Hierarchal linear regression modeling revealed no significant associations between diabetes control problems and age, education, gender and daytime sleepiness. Being married or partnered significantly decreased glycemic control problems, while poor sleep quality increased diabetes control problems. Further examination of PSQI factors (perceived sleep quality, sleep efficiency, and daily disturbances) found being married or partnered significantly decreased diabetes control problems while of the 3 factors of the PSQI, only the Daily Disturbances factor was significantly associated with increased diabetes control problems.
Impaired sleep quality and daytime sleepiness are associated with decreased diabetes self-management in adults with T2DM.
PMCID: PMC3677551  PMID: 23192600
24.  Psychometric Evaluation of the Epworth Sleepiness Scale in an Obstetric Population 
Sleep medicine  2012;14(1):116-121.
The Epworth Sleepiness Scale (ESS) was initially developed to measure daytime sleep propensity in patients affected by a variety of sleep disorders. Obstetrical research has measured sleepiness in pregnant women with the ESS, although a psychometric analysis and dimensionality evaluations have never been conducted with this population.
to perform a psychometric evaluation of the ESS in an obstetric population.
secondary data analysis of subjects enrolled in the Prenatal Exposures and Preeclampsia Prevention III (PEPP) study.
subjects who received prenatal care at Magee-Women’s Hospital UPMC in Pittsburgh, Pennsylvania.
337 pregnant women in their first trimester who completed the ESS.
principal components analysis and confirmatory factor analysis were performed using SPSS and M-Plus. Additionally, reliability was assessed and construct validity was measured using the Life Orientation Test (LOT). Lastly, a relationship between daytime sleepiness and snoring was investigated using Item 5e from the Pittsburgh Sleep Quality Index (PSQI).
PCA with varimax rotation yielded two factors that explained approximately 50% of the variance. CFA results verified the two-factor solution. An overall Cronbach’s alpha (0.751) revealed moderate reliability (Factor 1α = .754 ; Factor 2α = .524 ). Both convergent and discriminant validity were established.
The ESS is appropriate for use in an obstetric population to measure daytime sleepiness. Future work should include additional evaluations of the ESS in a diverse group of pregnant women.
PMCID: PMC3693185  PMID: 23218535
Epworth Sleepiness Scale; pregnancy; psychometrics; sleepiness; sleep; Confirmatory Factor Analysis; Exploratory Factor Analysis
25.  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.
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.
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).
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.
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.
PMCID: PMC3524046  PMID: 23039935
Excessive daytime sleepiness; Mandarin; Epworth Sleepiness Scale; Health-related quality of life

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