Genetics and epigenetics of rare hypersomnia.

Herein we focus on connections between genetics and some central disorders of hypersomnolence - narcolepsy types 1 and 2 (NT1, NT2), idiopathic hypersomnia (IH), and Kleine-Levin syndrome (KLS) - for a better understanding of their etiopathogenetic mechanisms and a better diagnostic and therapeutic definition. Gene pleiotropism influences neurological and sleep disorders such as hypersomnia; therefore, genetics allows us to uncover common pathways to different pathologies, with potential new therapeutic perspectives. An important body of evidence has accumulated on NT1 and IH, allowing a better understanding of etiopathogenesis, disease biomarkers, and possible new therapeutic approaches. Further studies are needed in the field of epigenetics, which has a potential role in the modulation of biological specific hypersomnia pathways.

Study of the different sleep disturbances during the prodromal phase of depression and mania in bipolar disorders.

BACKGROUND: One of the challenges in bipolar disorder (BD) lies in early detection of the illness and its recurrences, to improve prognosis. Sleep disturbances (SD) have been proposed as reliable predictive markers of conversion. While preliminary studies have explored the relationship between SD and the onset of mood episodes, the results remain heterogeneous and a few have specifically examined patients' perception of prodromal symptoms and their progression until the episode occurs. Identifying prodromes represents a crucial clinical challenge, as it enables early intervention, thereby reducing the severity of BD. Therefore, the objective of this study is to better characterize and evaluate the progressive nature of SD as prodromal symptoms of mood episodes, and patients' perception of it. METHODS: Patients diagnosed with BD, either hospitalized or seeking treatment for a (hypo)manic or depressive episode benefited from standardized questionnaires, structured interviews, and self-report questionnaires to evaluate SD prior to the current episode, as well as sociodemographic and clinical information. RESULTS: Out of the 41 patients included, 59% spontaneously reported SD prior to the episode, appearing 90 days before depression and 35 days before mania (pre-indexed/spontaneous reports: 51.22% insomnia complaints, 4.88% hypersomnolence complaints, 7.32% parasomnias, 2.44% sleep movements). After inquiry about specific SD, the percentage of patients reporting prodromal SD increased significantly to 83%, appearing 210 days before depression and 112.5 days before mania (post-indexed reports: 75.61% presented with insomnia complaints appearing 150 days before depression and 20 days before mania, 46.34% had hypersomnolence complaints appearing 60 days before depression, 43.9% had parasomnias appearing 210 days before depression and 22.5 days before mania, 36.59% had sleep movements appearing 120 days before depression and 150 days before mania). Of note, bruxism appeared in 35% of patients before mania, and restless legs syndrome in 20% of patients before depression. CONCLUSION: This study highlights the very high prevalence of SD prior to a mood episode in patients with BD with differences between depressive and manic episodes. The more systematic screening of sleep alterations of the prodromal phase improved the recognition and characterization of different symptoms onset by patients. This underscores the need for precise questioning regarding sleep patterns in patients, to better identify the moment of transition toward a mood episode, referred to as "Chronos syndrome". The study emphasizes the importance of educating patients about the disorder and its sleep prodromal symptoms to facilitate early intervention and prevent recurrences.

Idiopathic hypersomnia years after the diagnosis.

Little attention has been paid to the long-term development of idiopathic hypersomnia symptoms and idiopathic hypersomnia comorbidities. The aim of this study was to describe the general health of patients with idiopathic hypersomnia years after the initial diagnosis, focusing on current subjective hypersomnolence and the presence of its other possible causes. Adult patients diagnosed with idiopathic hypersomnia ≥ 3 years ago at sleep centres in Prague and Kosice were invited to participate in this study. A total of 60 patients were examined (age 47.3 ± SD = 13.2 years, 66.7% women). In all participants, their hypersomnolence could not be explained by any other cause but idiopathic hypersomnia at the time of diagnosis. The mean duration of follow-up was 9.8 + 8.0 years. Fifty patients (83%) reported persisting hypersomnolence, but only 33 (55%) had no other disease that could also explain the patient's excessive daytime sleepiness and/or prolonged sleep. In two patients (3%), the diagnosis in the meantime had changed to narcolepsy type 2, and 15 patients (25%) had developed a disease or diseases potentially causing hypersomnolence since the initial diagnosis. Complete hypersomnolence resolution without stimulant treatment lasting longer than 6 months was reported by 10 patients (17%). To conclude, in a longer interval from the diagnosis of idiopathic hypersomnia, hypersomnolence may disappear or may theoretically be explained by another newly developed disease, or the diagnosis may be changed to narcolepsy type 2. Thus, after 9.8 years, only 55% of the examined patients with idiopathic hypersomnia had a typical clinical picture of idiopathic hypersomnia without doubts about the cause of the current hypersomnolence.

Autonomic cardiovascular control is unaffected in children referred for assessment of excessive daytime sleepiness.

There is conflicting evidence for impaired autonomic control of heart rate (HR) in adults with narcolepsy and idiopathic hypersomnolence (IH). Despite these chronic hypersomnia conditions primarily being diagnosed around the age of puberty, there are limited studies in children. The present study investigated cardiovascular control using heart rate variability (HRV) and the extent of nocturnal HR dipping during sleep in children and adolescents with narcolepsy and IH. Children having an overnight polysomnographic study followed by a multiple sleep latency test (MSLT) for investigation of excessive daytime sleepiness (EDS) between May 2010 to December 2023 were included: 28 children diagnosed with narcolepsy, 11 with IH, and 26 subjectively sleepy children who did not meet the diagnostic criteria for either narcolepsy or IH. Each clinically referred child was matched for age and sex with a control. Time domain and frequency domain HRV were calculated from ECG recorded at 512 Hz. There were no differences in either time domain or spectral analysis of HRV between clinical groups or between clinical groups and their control group. The expected sleep state differences in HRV were observed in all groups. There was also no difference in HR nocturnal dipping between groups. Despite evidence for abnormal autonomic function in adults with narcolepsy and IH, our study did not identify any abnormalities in HR, HR control, or nocturnal dipping of HR in children referred for assessment of EDS. This suggests that autonomic dysfunction may be a feature of these conditions that develops in later life.

Hypersomnia in anti-glutamic acid decarboxylase 65 (GAD65) associated neurological syndromes: A pilot study.

BACKGROUND AND PURPOSE: Despite their detrimental impact on the quality of life in autoimmune encephalitis, sleep disorders have not been investigated in anti-glutamic acid decarboxylase (GAD65) associated neurological syndromes. METHODS: Six consecutive adult patients diagnosed with anti-GAD65-associated neurological syndromes (four with limbic encephalitis and two with stiff-person syndrome) and 12 healthy controls were enrolled. Participants underwent sleep interviews and sleep studies including night-time video-polysomnography, followed by five daytime multiple sleep latency tests (MSLTs, to assess propensity to fall asleep) and an 18 h bed rest polysomnography (to assess excessive sleep need). RESULTS: Patients reported the need for daily naps and that their cognition and quality of life were altered by sleepiness, but they had normal scores on the Epworth sleepiness scale. Compared with controls, sleep latencies during the MSLT were shorter in the patient group (median 5.8 min, interquartile range [IQR] 4.5, 6.0 vs. 17.7 min, IQR 16.3, 19.7, p = 0.001), and the arousal index was reduced (2.5/h, IQR 2.3, 3.0 vs. 22.3/h, IQR 13.8, 30.0, p = 0.002), although total sleep time was similar between groups (621 min, IQR 464, 651 vs. 542.5 min, IQR 499, 582, p = 0.51). Remarkably, all six patients had MSLT latencies ≤8 min, indicating severe sleepiness. No parasomnia or sleep-disordered breathing was detected. CONCLUSION: Central hypersomnia is a relevant characteristic of anti-GAD65-associated neurological syndromes.

Elusive hypersomnolence in seasonal affective disorder: actigraphic and self-reported sleep in and out of depressive episodes.

BACKGROUND: Hypersomnolence has been considered a prominent feature of seasonal affective disorder (SAD) despite mixed research findings. In the largest multi-season study conducted to date, we aimed to clarify the nature and extent of hypersomnolence in SAD using multiple measurements during winter depressive episodes and summer remission. METHODS: Sleep measurements assessed in individuals with SAD and nonseasonal, never-depressed controls included actigraphy, daily sleep diaries, retrospective self-report questionnaires, and self-reported hypersomnia assessed via clinical interviews. To characterize hypersomnolence in SAD we (1) compared sleep between diagnostic groups and seasons, (2) examined correlates of self-reported hypersomnia in SAD, and (3) assessed agreement between commonly used measurement modalities. RESULTS: In winter compared to summer, individuals with SAD (n = 64) reported sleeping 72 min longer based on clinical interviews (p < 0.001) and 23 min longer based on actigraphy (p = 0.011). Controls (n = 80) did not differ across seasons. There were no seasonal or group differences on total sleep time when assessed by sleep diaries or retrospective self-reports (p's > 0.05). Endorsement of winter hypersomnia in SAD participants was predicted by greater fatigue, total sleep time, time in bed, naps, and later sleep midpoints (p's < 0.05). CONCLUSION: Despite a winter increase in total sleep time and year-round elevated daytime sleepiness, the average total sleep time (7 h) suggest hypersomnolence is a poor characterization of SAD. Importantly, self-reported hypersomnia captures multiple sleep disruptions, not solely lengthened sleep duration. We recommend using a multimodal assessment of hypersomnolence in mood disorders prior to sleep intervention.

The language of sleepiness in obstructive sleep apnea beyond the Epworth.

PURPOSE: Obstructive sleep apnea (OSA) is underdiagnosed, partially from variable clinical presentations. Emphasis is often placed on Epworth Sleepiness Scale (ESS), a subjective measure of sleepiness, but variable in OSA. We hypothesized that daytime complaints measured with Language of Sleepiness Questionnaire (LOS) in OSA are not being captured by ESS. METHODS: Adults referred to a tertiary sleep clinic undergoing sleep studies completed ESS and LOS questionnaires (20 items with various patient-reported descriptors). LOS was examined in patients who had or did not have OSA without sleepiness based on ESS < 10. Cluster analysis was performed to assess whether or not groups of individuals differed based on classification with or without OSA and with or without ESS-based sleepiness. RESULTS: Approximately half the study population (n = 185 completed) had OSA. ESS score (mean ± SD) was 9.0 ± 5.4. There was no significant difference in ESS between patients with and without OSA (9.0 ± 5.1 vs 9.1 ± 5.7, p = 0.969). In patients with OSA, females, older patients and white patients were significantly less likely to have an ESS ≥ 10 when compared to patients with an ESS < 10. In patients with an ESS < 10, there were no significant differences in descriptors of sleepiness between patients with and without OSA with the most common descriptors selected being "I lack energy," "I wake up sleepy," "I keep waking up," and "I don't sleep enough." CONCLUSIONS: The ESS failed to discriminate patients with OSA from those without OSA. Despite an ESS < 10, both daytime and sleep complaints using the LOS questionnaire were present in patients with OSA. Asymptomatic OSA may be less common than previously reported.

Evaluation of hypersomnolence: From symptoms to diagnosis, a multidimensional approach.

Hypersomnolence is a major public health issue given its high frequency, its impact on academic/occupational functioning and on accidentology, as well as its heavy socio-economic burden. The positive and aetiological diagnosis is crucial, as it determines the therapeutic strategy. It must consider the following aspects: i) hypersomnolence is a complex concept referring to symptoms as varied as excessive daytime sleepiness, excessive need for sleep, sleep inertia, or drowsiness, all of which warrant specific dedicated investigations; ii) the boundary between physiological and abnormal hypersomnolence is blurred, since most symptoms can be encountered in the general population to varying degrees without being considered as pathological, meaning that their severity, frequency, context of occurrence and related impairment need to be carefully assessed; iii) investigation of hypersomnolence relies on scales/questionnaires as well as behavioural and neurophysiological tests, which measure one or more dimensions, keeping in mind the possible discrepancy between objective and subjective assessment; iv) aetiological reasoning is driven by knowledge of the main sleep regulation mechanisms, epidemiology, and associated symptoms. The need to assess hypersomnolence is growing, both for its management, and for assessing the efficacy of treatments. The landscape of tools available for investigating hypersomnolence is constantly evolving, in parallel with research into sleep physiology and technical advances. These investigations face the challenges of reconciling subjective perception and objective data, making tools accessible to as many people as possible and predicting the risk of accidents.

Sleep-disordered breathing in high-risk pregnancies is associated with elevated arterial stiffness and increased risk for preeclampsia.

BACKGROUND: Impaired vascular function is a central feature of pathologic processes preceding the onset of preeclampsia. Arterial stiffness, a composite indicator of vascular health and an important vascular biomarker, has been found to be increased throughout pregnancy in those who develop preeclampsia and at the time of preeclampsia diagnosis. Although sleep-disordered breathing in pregnancy has been associated with increased risk for preeclampsia, it is unknown if sleep-disordered breathing is associated with elevated arterial stiffness in pregnancy. OBJECTIVE: This prospective observational cohort study aimed to evaluate arterial stiffness in pregnant women, with and without sleep-disordered breathing and assess the interaction between arterial stiffness, sleep-disordered breathing, and preeclampsia risk. STUDY DESIGN: Women with high-risk singleton pregnancies were enrolled at 10 to 13 weeks' gestation and completed the Epworth Sleepiness Score, Pittsburgh Sleep Quality Index, and Restless Legs Syndrome questionnaires at each trimester. Sleep-disordered breathing was defined as loud snoring or witnessed apneas (≥3 times per week). Central arterial stiffness (carotid-femoral pulse wave velocity, the gold standard measure of arterial stiffness), peripheral arterial stiffness (carotid-radial pulse wave velocity), wave reflection (augmentation index, time to wave reflection), and hemodynamics (central blood pressures, pulse pressure amplification) were assessed noninvasively using applanation tonometry at recruitment and every 4 weeks from recruitment until delivery. RESULTS: High-risk pregnant women (n=181) were included in the study. Women with sleep-disordered breathing (n=41; 23%) had increased carotid-femoral pulse wave velocity throughout gestation independent of blood pressure and body mass index (P=.042). Differences observed in other vascular measures were not maintained after adjustment for confounders. Excessive daytime sleepiness, defined by Epworth Sleepiness Score >10, was associated with increased carotid-femoral pulse wave velocity only in women with sleep-disordered breathing (Pinteraction=.001). Midgestation (first or second trimester) sleep-disordered breathing was associated with an odds ratio of 3.4 (0.9-12.9) for preeclampsia, which increased to 5.7 (1.1-26.0) in women with sleep-disordered breathing and hypersomnolence, whereas late (third-trimester) sleep-disordered breathing was associated with an odds ratio of 8.2 (1.5-39.5) for preeclampsia. CONCLUSION: High-risk pregnant women with midgestational sleep-disordered breathing had greater arterial stiffness throughout gestation than those without. Sleep-disordered breathing at any time during pregnancy was also associated with increased preeclampsia risk, and this effect was amplified by hypersomnolence.

Comparing objective wakefulness and vigilance tests to on-the-road driving performance in narcolepsy and idiopathic hypersomnia.

Patients with narcolepsy or idiopathic hypersomnia (IH) are at increased risk of driving accidents. Both excessive daytime sleepiness, i.e. unwanted sleep episodes during the day, and disturbed vigilance are core features of these disorders. We tested on-the-road driving performance of patients with narcolepsy or IH coming in for a routine driving fitness evaluation and examined: (1) correlations between driving performance and the Maintenance of Wakefulness Test (MWT), Sustained Attention to Response Task (SART) and Psychomotor Vigilance Test (PVT) as objective tests; (2) the predictive power of the MWT and SART for increased risk of impaired driving; (3) the best set of objective predictors for increased risk of impaired driving. Participants were 44 patients (aged 18-75 years) with narcolepsy type 1 (NT1), type 2 (NT2) or IH. They completed the MWT, SART, PVT, a subjective sleepiness questionnaire, and a standardised on-the-road driving test. The standard deviation of the lateral position (SDLP) was used as outcome measure of driving performance. The MWT had low correlation with the SDLP (ρ = -0.41 to -0.49, p < 0.01). The SART and PVT had low correlations with SDLP (ρ = 0.30 and ρ = 0.39, respectively, both p < 0.05). The predictive power of MWT for an increased risk of impaired driving was significant, but low (area under the curve = 0.273, p = 0.012), and non-significant for SART. We conclude that in our present group, none of the tests had adequate ability to predict impaired driving, questioning their use for clinical driving fitness evaluation in narcolepsy and IH. Real-time monitoring of sleepiness while driving seems more promising in these patients.

Relationship between sleep efficacy endpoints and measures of functional status and health-related quality of life in participants with narcolepsy or obstructive sleep apnea treated for excessive daytime sleepiness.

This study examined the correlation between improvements in excessive daytime sleepiness in participants with obstructive sleep apnea or narcolepsy and changes in functional status, work productivity and health-related quality of life. Data from two 12-week randomized controlled trials of solriamfetol were analyzed. Participants completed the Epworth Sleepiness Scale, 10-item Functional Outcomes of Sleep Questionnaire, Work Productivity and Activity Impairment questionnaire and 36-Item Short Form Health Survey and performed the Maintenance of Wakefulness Test at baseline and weeks 4, 8 and 12. Patient Global Impression of Change was assessed at weeks 4, 8 and 12. Pearson correlations were calculated for change in scores from baseline to week 12. For both studies, changes in the 10-item Functional Outcomes of Sleep Questionnaire were highly correlated (absolute value >0.5) with changes in Epworth Sleepiness Scale scores; changes in multiple domain scores of the 36-Item Short Form Health Survey and Work Productivity and Activity Impairment questionnaire were moderately correlated (0.3-0.5) with changes in Epworth Sleepiness Scale scores in both studies and highly correlated for participants with narcolepsy. Changes in Maintenance of Wakefulness Test scores correlated moderately with changes in Epworth Sleepiness Scale scores in both studies. At week 12, Patient Global Impression of Change ratings correlated highly with Epworth Sleepiness Scale and 10-item Functional Outcomes of Sleep Questionnaire scores for both disorders. Other correlations were low. Self-reported assessments of sleepiness and global improvement appear to be more strongly correlated with measures of functioning and health-related quality of life than objectively assessed sleepiness.

Excessive daytime sleepiness in cancer patients.

PURPOSE: Excessive daytime sleepiness (EDS) is commonly reported in patients with cancer, and it is also a cardinal feature of central disorders of hypersomnolence. Multiple sleep latency testing (MSLT) is used for objective assessment. METHODS: A retrospective review of patients with cancer history who underwent formal sleep evaluation and MSLT from 2006 to 2019 was performed. Clinical characteristics, sleep-related history, and polysomnographic data were reviewed. RESULTS: Of 16 patients with cancer history, 9 were women (56%) and median age was 49. Cancer diagnoses included 4 central nervous system, 3 breast, 1 lymphoma, and 9 other solid malignancies, and 31% were undergoing active treatment. Comorbid conditions included depression, obstructive sleep apnea, and cancer-related fatigue. Daytime fatigue (94%), daily naps (81%), and EDS (69%) were the most common symptoms. Hypnopompic and hypnogogic hallucinations, sleep paralysis, sleep attacks, and cataplexy were present in a few. Epworth Sleepiness Scale scores were consistent with EDS in 88%, and mean sleep latency was less than 8 min in 69%. Only 31% had more than 2 sleep-onset REM periods. MSLT supported diagnoses of central disorders of hypersomnolence in 5 patients (4 narcolepsy, 1 idiopathic hypersomnia); 5 hypersomnia due to a medical disorder, psychiatric condition, or medication; and 6 with normal results. Pharmacotherapy was prescribed in 5 patients. CONCLUSIONS: EDS in patients with cancer may be multifactorial, but persistent symptoms may indicate an underlying disorder of hypersomnolence. Sleep referral and polysomnography to exclude other sleep disorders may be indicated. MSLT can help confirm the diagnosis. In those with normal MSLT, further evaluation for mood disorder should be considered.

Determination of thresholds for minimally important difference and clinically important response on the functional outcomes of sleep questionnaire short version in adults with narcolepsy or obstructive sleep apnea.

PURPOSE: This study estimated thresholds for clinically important responses and minimally important differences for two indicators of improvement for the 10-item version of the functional outcomes of sleep questionnaire (FOSQ-10). METHODS: Participants with excessive daytime sleepiness with narcolepsy or obstructive sleep apnea received 12 weeks of solriamfetol treatment. Participants completed the FOSQ-10 and other patient-reported outcome measures, including the single-item patient global impression of change (PGI-C) assessment. Clinicians completed the single-item clinician global impression of change (CGI-C) for each participant. Data from the two studies were analyzed separately, both without regard to treatment assignment. In total, 690 participants (47% female, mean age 48 years, 77% Caucasian, 91% from North America) were enrolled. Two clinically important changes, defined as a minimally important difference and a clinically important response, were determined using distribution and anchor-based analyses. A receiver operating characteristic analysis was used to determine the optimal FOSQ-10 change threshold. RESULTS: Spearman correlations between change in FOSQ-10 scores and PGI-C and CGI-C were - 0.57 and - 0.49 for participants with narcolepsy and - 0.42 and - 0.37 for participants with obstructive sleep apnea. Receiver operating characteristic analysis suggested minimally important difference and clinically important response estimates of 1.7 and 2.5 and 1.8 and 2.2 points in narcolepsy and obstructive sleep apnea, respectively. CONCLUSIONS: Minimally important difference and clinically important response estimates for the FOSQ-10 for adults with excessive daytime sleepiness in narcolepsy or obstructive sleep apnea will be helpful for interpreting changes over time and defining a clinical responder. CLINICALTRIALS. GOV IDENTIFIERS: NCT02348593 (first submitted January 15, 2015) and NCT02348606 (first submitted January 15, 2015).

A Guide to Management of Sleepiness in ESKD.

Daytime sleepiness, also known as hypersomnolence, is common among patients receiving maintenance dialysis and following successful kidney transplantation. Sleepiness may be secondary to medical comorbid conditions, medication side effect, insufficient sleep syndrome, and sleep-disordered breathing or the result of a primary central disorder of hypersomnolence, such as narcolepsy. Unrecognized and untreated sleep disorders are associated with substantial morbidity and mortality among patients with end-stage kidney disease. Effective management of hypersomnolence can improve quality of life in patients with kidney disease. This review focuses on the principal causes of sleepiness in patients with end-stage kidney disease. Awareness of these disorders by treating nephrologists is crucial. This review provides a systematic approach to guide providers through the recognition, early diagnosis, and treatment of hypersomnolence, which is commonly encountered in this patient population. Areas of future research are also suggested.

The effects of caffeine on drowsiness in patients with narcolepsy: a double-blind randomized controlled pilot study.

PURPOSE: The effects of caffeine on drowsiness and reaction time in patients with narcolepsy are unclear. We aimed to assess the effects of caffeine as add-on therapy in narcolepsy patients. METHODS: A randomized, double-blind, placebo-control clinical pilot trial was conducted with a parallel, two-arm trial allocation ratio of 1:1. Participants attended two study visits 7 days apart. The drug was administered orally in a single opaque capsule containing 200 mg caffeine/placebo daily in the morning for 1 week. Sleepiness was assessed objectively using infrared reflectance oculography to measure the percentage of long eye closure (LEC%) and subjectively using two sleepiness scales, the Stanford Sleepiness Scale (SSS) and Karolinska Sleepiness Scale (KSS). Parameters were measured at baseline (BL) prior to taking the drug, after taking the first dose (FD), and after 1 week (WD) of daily caffeine. RESULTS: Sixteen participants with narcolepsy were included. No significant differences between groups in baseline measurements were observed. LEC% was significantly decreased after the FD and WD compared with baseline levels (BL 1.4 ± 2.1 vs. FD 0.06 ± 0.0.6 and WD 0.03 ± 0.04). Significant improvements in alertness were observed using the KSS when comparing BL with FD and WD (6.3 ± 1.6, 4.9 ± 1.7, and 4.7 ± 1.7, respectively; p = 0.01). No changes in reaction time or SSS scores were noted. CONCLUSION: Our findings suggest that a small dose of caffeine has positive effects on alertness in patients with narcolepsy. However, larger trials are required to confirm these findings. TRIAL REGISTRATION NO: ClinicalTrial.gov NCT02832336.

Comorbid psychiatric disorders among patients with narcolepsy.

PURPOSE: This case-control study assessed the prevalence of psychiatric disorders in Arab (Saudi) patients with narcolepsy using a structured clinical interview. METHODS: The study included 74 adult patients with narcolepsy and 265 controls matched for age and sex. Narcolepsy diagnosis was made according to the International Classification of Sleep Disorders-Third Edition. Psychiatric disorders were diagnosed via using a validated Arabic version of the Mini International Neuropsychiatric Interview DSM-IV (MINI version 6). A multivariate logistic regression model was used to assess the potential influence of narcolepsy on the comorbidity of psychiatric disorders. RESULTS: The mean age of the patients was 29.4 ± 10.2 years, and males accounted for 81% of the study sample. Forty-four patients (60%) were diagnosed with narcolepsy type-1 (NT1) and 30 (40%) with narcolepsy type-2 (NT2). Psychiatric disorders were diagnosed in 45% of patients with narcolepsy compared with 15% of the controls (p < 0.001). The multivariate logistic regression models demonstrated that compared with the controls, patients with narcolepsy were more likely to have major depressive disorders (OR, 4.3 [CI, 2.2-8.2]), and generalized anxiety disorders (OR, 9.5 [CI, 1.8-50.2]). No difference was detected between the prevalence of various psychiatric disorders in patients with NT1 and NT2. CONCLUSION: Comorbid psychiatric disorders are common among Arab (Saudi) patients with narcolepsy compared with the general population. Therefore, clinicians should be aware of the comorbidity of narcolepsy and psychiatric disorders, particularly depression.

Residual excessive daytime sleepiness in patients with obstructive sleep apnea treated with positive airway pressure therapy.

PURPOSE: Patients with obstructive sleep apnea (OSA) commonly report residual excessive daytime sleepiness (EDS) despite treatment with positive airway pressure (PAP). The present study aimed to determine whether patients presenting with subjective sleepiness after treatment with PAP therapy had objective evidence of residual sleepiness. METHODS: We conducted a retrospective analysis of 29 adults with OSA on PAP therapy who underwent a standardized evaluation for EDS. Patients were evaluated with the Epworth Sleepiness Scale (ESS) and attend an in-lab polysomnogram (PSG) with PAP followed by a multiple sleep latency test (MSLT). RESULTS: Our cohort consisted of 23 men (79%) and 6 women (21%) with a mean age of 40.7 years. All patients were subjectively sleepy with an ESS score of > 10 and met minimal PAP usage of 4 h a night for at least 70% of nights with a residual apnea-hypopnea index (AHI) ≤ 10. On MSLT, 31% of patients had an average sleep onset latency (SOL) < 8 min, 35% had a SOL between 8 and 11 min, and 35% had SOL > 11 min. CONCLUSION: After optimizing PAP therapy and sleep in patients with OSA and residual EDS, the majority were found to have objective findings of an abnormally short SOL on MSLT. This is further evidence that there is a distinct OSA phenotype that will have persistent EDS despite appropriate treatment of their sleep-disordered breathing. Objective testing to quantify the degree of sleepiness is recommended for OSA patients with residual EDS.

Ability of the Fitbit Alta HR to quantify and classify sleep in patients with suspected central disorders of hypersomnolence: A comparison against polysomnography.

Measuring sleep duration and early onset rapid eye movement sleep (REMS) is critical in the assessment of suspected central disorders of hypersomnolence (CDH). Current multi-sensor activity trackers that integrate accelerometry and heart rate are purported to accurately quantify sleep time and REMS; however, their utility in suspected CDH has not been established. This investigation aimed to determine the ability of a current, multi-sensor tracker, Fitbit Alta HR (FBA-HR), to quantify and classify sleep in patients with suspected CDH relative to polysomnography (PSG). Forty-nine patients (46 female; mean age, 30.3 ± 9.84 years) underwent ad libitum PSG with concurrent use of the FBA-HR. FBA-HR sleep variable quantification was assessed using Bland-Altman analysis. FBA-HR all sleep (AS), light sleep (LS; PSG N1 + N2), deep sleep (DS; PSG N3) and REMS classification was evaluated using epoch-by-epoch comparisons. FBA-HR-detected sleep-onset rapid eye movement periods (SOREMPs) were compared against PSG SOMREMPs. FBA-HR displayed significant overestimation of total sleep time (11.6 min), sleep efficiency (1.98%) and duration of deep sleep (18.2 min). FBA-HR sensitivity and specificity were as follows: AS, 0.96, 0.58; LS, 0.73, 0.72;DS, 0.67, 0.92; REMS, 0.74, 0.93. The device failed to detect any nocturnal SOREMPs. Device performance did not differ appreciably among diagnostic subgroups. These results suggest FBA-HR cannot replace EEG-based measurements of sleep and wake in the diagnostic assessment of suspected CDH, and that improvements in device performance are required prior to adoption in clinical or research settings.

Chronic pain in narcolepsy type 1 and type 2 - an underestimated reality.

Narcolepsy is a rare sleep disorder classified in types 1 and 2. The co-morbidities of narcolepsy type 1, with hypocretin-1 deficiency, are established. Hypocretin-1 in the central and peripheral nervous systems regulates nociception and pain. However, the patients with narcolepsy type 2 have similar excessive daytime sleepiness and co-morbidities without elucidation. The objective of the study was to determine the frequency and the characteristic of chronic pain according to the type of narcolepsy. We also investigated the effect of the interaction between the nutritional status and the type of narcolepsy. It was a cross-sectional study using self-administered questionnaires. Patients with narcolepsy (33 type 1 and 33 type 2), from Universidade Federal de São Paulo, Brazil, matched by age and gender to 33 control subjects were included. Both types of narcolepsy presented a high frequency of chronic pain (84.84% type 1 versus 75.75% type 2), with indistinct pain characteristics between them. The odds ratio was 20.8 in type 1 and 11.6 in type 2, compared with controls. Obese individuals with narcolepsy type 1 and type 2 did not present a significant difference in pain intensity, compared with obese controls. Patients with narcolepsy type 1 and type 2 were associated with a high frequency of chronic pain. Chronic pain emerged as a co-morbidity never reported before in type 2. Depression possibly influences pain perception in these patients. Obesity might play a role in pain intensity in narcolepsy. The treatment of narcolepsy should take account of chronic pain, depression and obesity management.

The association of sleep disturbances with glycemia and obesity in youth at risk for or with recently diagnosed type 2 diabetes.

OBJECTIVE: Poor sleep may increase obesity and type 2 diabetes (T2D) risk in youth. We explored whether subjective sleep duration, sleep quality, or risk for obstructive sleep apnea (OSA) are associated with glycemia, body mass index (BMI), or blood pressure (BP) in overweight/obese youth. METHODS: Two-hundred and fourteen overweight/obese youth of 10 to 19 years of age at risk for or recently diagnosed with T2D who were screened for the Restoring Insulin Secretion (RISE) Study had a 2-hour oral glucose tolerance test (OGTT) and completed a Cleveland Adolescent Sleepiness questionnaire and a Sleep Disturbances Scale questionnaire. Independent associations between sleep variables and measures of glycemia, BMI, and BP were evaluated with regression models. RESULTS: The multiethnic cohort was 67% female, 14.1 ± 2.1 years, and BMI 35.9 ± 6.5 kg/m2 . Habitual sleep duration <8 hours was reported in 74%. Daytime sleepiness was reported in 51%, poor sleep quality in 26%, and 30% had high obstructive sleep apnea (OSA) risk. Daytime sleepiness was associated with higher HbA1c (0.2%, P = .02) and 2-hour glucose (13.6 mg/dL, P < .05). Sleep duration, sleep quality, and OSA risk were not associated with the evaluated outcomes. Poor sleep quality and OSA risk were associated with higher BMI (2.9 kg/m2 , P = .004 and 2.83 kg/m2 , P < .003, respectively). CONCLUSIONS: In overweight/obese youth with or at risk for T2D, daytime sleepiness was associated with higher HbA1c. In addition, poor sleep quality and OSA risk were associated with higher BMI. These findings support intervention studies aimed at improving sleep quality in obese youth.