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PubMed2025

Steroid hormone biosynthesis and dietary related metabolites associated with excessive daytime sleepiness.

BACKGROUND: Excessive daytime sleepiness (EDS) is a complex sleep problem that affects approximately 33% of the United States population. Although EDS usually occurs in conjunction with insufficient sleep and other sleep and circadian disorders, recent studies have shown unique genetic markers and metabolic pathways underlying EDS. Here, we aimed to further elucidate the biological profile of EDS using large-scale single- and pathway-level metabolomics analyses. METHODS: Metabolomics data were available for 877 metabolites in 6071 individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). EDS was assessed using the Epworth Sleepiness Scale (ESS) questionnaire. We performed linear regression for each metabolite on the continuous ESS score, adjusting for demographic, lifestyle, and physiological confounders, and in sex specific groups. Subsequently, gaussian graphical modelling was performed coupled with pathway and enrichment analyses to generate a holistic interactive network of the metabolomic profile of EDS associations. FINDINGS: We identified seven metabolites belonging to steroids, sphingomyelin, and long-chain fatty acids sub-pathways in the primary model associated with EDS, and an additional three metabolites in the male-specific analysis. INTERPRETATION: Our findings indicate that an EDS metabolomic profile is characterised by endogenous and dietary metabolites within the steroid hormone biosynthesis pathway, with some pathways that differ by sex. These pathways may be useful for understanding the causes or consequences of EDS and related sleep disorders. FUNDING: Details regarding funding supporting this work and all studies involved are provided in the acknowledgements section.

Humans↗

PubMedDate not supplied

235 cases of excessive daytime sleepiness. Diagnosis and tentative classification.

A series of 235 consecutive patients refferred to the Stanford University Sleep Disorders Clinic with the complaint of excessive daytime sleepiness (EDS) were investigated extensively. A satisfactory final diagnosis involving a consistent syndrome or pathogenic process was made in all but 7 patients. In the course of this work a variety of tests, including prolonged polygraphic monitoring of multiple variables and CSF measurements before and after probenecid ingestion, were utilized. Different syndromes were confirmed (harmonious hypersomnia, subwakefulness syndrome); the definitions of others were clarified and extended (narcolepsy, drug dependency, periodic hypersomnia associated with menstruation, upper airway sleep apnea in children). Two new entities were tentatively identified (narcolepsy with sleep apnea, the neutral state syndrome). Narcolepsy and upper airway sleep apnea accounted for the majority of the cases (199). A strategic schema utilizing specific categories and frequency of occurrence in the case series is presented to improve the diagnosis of the complaint of excessive daytime sleepiness by the practicing physician. This case series was analysed in order to develop tentatively a meaningful nosology.

Adolescent↗

PubMed1978

Excessive daytime sleepiness in man: multiple sleep latency measurement in narcoleptic and control subjects.

Excessive daytime sleepiness is a complaint characterizing many disorders of the wakefulness--sleep cycle. This paper addresses the complaint of sleepiness objectively by an attempt to differentiate a group of control subjects from a group of patients with unambiguous narcolepsy. Fourteen control and 27 narcoleptic subjects were evaluated by one of three protocols involving nocturnal recordings, detailed interviews, and 5 or more 20-min opportunities to sleep offered at 2-h intervals beginning at 10.00 o'clock, +/- 30 min. Each 20-min opportunity to sleep was given to subjects lying in a darkened quiet room and asked to try to fall asleep. Polysomnographic variables were monitored and sleep was scored in 30-sec epochs by standard criteria. The interval from the start of each test to the first epoch of NREM (including stage 1 sleep) or REM sleep was called sleep latency. In two of the protocols, the subjects were awakened immediately after sleep onset. In the third protocol, the subjects were awakened after 10 min of sleep. Narcoleptics consistently fell asleep much more readily than did control subjects. We conclude that the Multiple Sleep latency test, in addition to providing opportunities to clinically document sleep onset REM sleep periods, can demonstrate pathological sleepiness. Based on these data, we suggest that an average sleep latency less than 5 min be set as the minimum cutoff point for pathological sleepiness.

Adult↗

PubMed2026

Blue light therapy delivered through light glasses improves sleep quality and daytime sleepiness in Parkinson's disease: A randomized trial.

BackgroundSleep disturbances, including excessive daytime sleepiness (EDS) and fragmented nocturnal sleep, are common in Parkinson's disease (PD) and significantly reduce quality of life. This pilot study evaluated the efficacy of a novel approach using blue light, delivered via dedicated glasses with integrated LED lights, to improve sleep and non-motor symptoms.MethodsRandomised, placebo-controlled, single-blind pilot study with a 2-week light intervention. Participants were assessed at baseline, two weeks, and five weeks. The study was designed to evaluate between- and within-group changes. Participants were randomly allocated to receive blue light therapy (n = 15) or red light placebo (n = 15), delivered via LED-integrated glasses for one hour, twice daily, given for a 2-week period. Primary outcome was improvement in sleep quality, assessed via the Pittsburgh Sleep Quality Index. Secondary outcomes included diary-based sleep outcomes, excessive daytime sleepiness, mood, anxiety, and motor symptoms.ResultsThere was a significant group × time effect with blue light therapy leading to better Pittsburgh Sleep Quality Index scores (p = 0.021). Between-group analyses showed that at two weeks a trend toward significance was observed (p = 0.065), while sleep quality significantly improved at five weeks compared to placebo (p = 0.029) with a large effect size (0.896). Excessive sleepiness improved in the blue light group (p < 0.001), with a reduction in clinically relevant sleepiness from 50.0% to 6.7% (p = 0.005).ConclusionsBlue light therapy delivered through dedicated glasses appeared to show an improvement in sleep quality and daytime sleepiness in individuals with PD. Blue light therapy offers a promising alternative to traditional light therapy utilising lower light intensities and eliminating the need for light boxes.

Aged↗

PubMed2026

HYPNOSA: Study protocol for a prospective observational cohort of patients with obstructive sleep apnea.

BACKGROUND: Obstructive Sleep Apnea (OSA) is a common chronic disease that affects more than 20% of the adult population. One of the most frequent and characteristic symptoms of OSA is excessive daytime sleepiness (EDS). This symptom is typically treated in patients with OSA with the application of continuous positive airway pressure (CPAP), the gold-standard treatment for this disease. In some patients who are adequately treated with CPAP, residual excessive daytime sleepiness (REDS) persists. The prevalence, associations, and outcomes associated with REDS remain poorly understood. METHODS: Multicenter, prospective, observational cohort study including 1000 patients. Participants will undergo a sleep study for the diagnosis of obstructive sleep apnea (OSA), 24-h ambulatory blood pressure monitoring, clinical assessment, quality-of-life questionnaires, Epworth Sleepiness Scale, and collection of biochemical variables and biological samples. Patients with OSA will receive standard care, and those prescribed continuous positive airway pressure (CPAP) will be monitored for treatment adherence. OSA patients will be assessed at baseline and at 6, 12, and 24 months. DISSCUSION: We aim to establish a prospective observational cohort of patients with obstructive sleep apnea (OSA) treated with CPAP, with and without REDS. The HYPNOSA project will create the largest available registry of patients with OSA and REDS using real-world data, providing accurate prevalence estimates and long-term outcomes. Biological samples will be analyzed to assess the role of specific biomarkers. TRIAL REGISTRATION: Registered at ClinicalTrials.gov. Identifer: NCT06514482.

Adult↗

PubMed1976

The pathophysiology of sleep disorders in pediatrics. Part II. Sleep disorders in children.

In this part of the chapter we have used new terminology and developed a new system for classification of sleep disorders in children. We suggest that excessive daytime sleepiness should be investigated by clinicians before troubles at school necessitate referral. The narcolepsy-hypersomnia syndrome generally has not been recognized in the pediatric age group. Symptoms of excessive fear of falling asleep need to be viewed in this context. Sleep apnea-hypersomnia has received insufficient attention in the American literature. It is a syndrome that affects both adults and children with potentially disastrous cardiovascular and pulmonary complications. The relationship of the sleep apnea-hypersomnia syndrome to the sudded infant death syndrome remains speculative, although preliminary results from our longitudinal study have indicated a possible link. Both the narcolepsy-hypersomnia and the sleep apnea-hypersomnia syndromes are reviewed in detail. In contrast, we review briefly the NREM dyssomnias, including night terrors, sleepwalking, sleep talking and enuresis. All are well known to clinicians dealing with children, and we have related them to findings emanating from the sleep laboratory. We suggest that they are physiologically rather than psychogenically based and frequently represent immaturities of the central nervous system. Finally, the insomnias of childhood are presented. We emphasize that they are rare, and after ruling out organic conditions and drug-dependency syndromes, cultural styles or family stresses generally account for the majority of complaints.

Apnea↗

PubMed1977

Retrognathia and sleep apnea. A life-threatening condition masquerading as narcolepsy.

The association of sleep apnea with daytime hypersomnolence without obesity, and its potentially lethal cardiopulmonary sequelae, make it crucial that this condition be distinguished from narcolepsy. A patient with retrognathia who had been diagnosed as a narcoleptic for 15 years had the primary complaint of excessive daytime sleepiness. Sleep laboratory evaluation showed severe hypoxemia and a mean of 366 upper airway obstructions per night. The patient was treated with a tracheotomy; this resulted in relief of the sleep-related upper airway obstructions, hypoxemia, and hypersomnolence.

Airway Obstruction↗

PubMed2026

Genetic Association Between Sleep Traits and Vertigo Risk: A Two-sample Bidirectional Mendelian Randomization Study.

BACKGROUND: Observational studies suggest the potential association between sleep traits and vertigo; however, causal evidence remains limited. OBJECTIVE: This study aimed to explore the relationship between genetically predicted sleep traits and vertigo with the Mendelian randomization (MR) method. METHODS: Instrumental variables for sleep traits (snoring, sleep duration, insomnia, daytime sleepiness, daytime napping, and chronotype) were adopted from genomewide association studies (GWAS) data of European ancestry from UK Biobank. The summary-level datasets of vertigo were retrieved from the GWAS of FinnGen. Inversevariance weighted (IVW) method was adopted as the main analysis. RESULTS: IVW analysis revealed a significant association between genetically predicted daytime napping (OR = 1.51, 95% CI =1.08-2.12, P = 0.016) and chronotype (OR = 1.13, 95% CI =1.01-1.26, P = 0.033), both of which were associated with an increased risk of vertigo. However, we did not find evidence for a causal effect of snoring, overall sleep duration, long sleep duration, short sleep duration, insomnia, and excessive daytime sleepiness on vertigo. No reverse causality was detected. CONCLUSION: Our findings suggest that abnormal sleep patterns may serve as risk factors for vertigo disorders and offer opportunities for the prevention and management of vertigo disorders.

Humans↗

PubMed2026

Treatment of OSA using mandibular advancement versus CPAP in improving cardiovascular health.

BACKGROUND: Obstructive sleep apnea is a significant risk factor for hypertension. We assessed the relative effectiveness of mandibular advancement device (MAD) versus continuous positive airway pressure (CPAP) in reducing 24 h ambulatory blood pressure (BP) and other health-related outcomes over 12 months. METHODS: In a randomized, non-inferiority trial, 321 participants with hypertension and increased cardiovascular risk were recruited for polysomnography. Of these, 220 with moderate-to-severe OSA (apnea-hypopnea index (AHI) ≥15 events/hour) were randomized to MAD or CPAP (1:1). We report the final outcomes at the 12-month follow-up. RESULTS: A total of 180 participants (MAD: 89; CPAP: 91) completed the 12-month follow-up. Median usage for MAD and CPAP was 5.5 and 4.9 h per night, respectively. Compared to baseline, the 24 h mean arterial BP at 12 months decreased by 2.3 mmHg (P = 0.200) in the MAD group and by 1.0 mmHg (P = 0.999) in the CPAP group. The difference between-groups was -0.6 mmHg (95% confidence interval: -2.53 to 1.39, non-inferiority P < 0.019). The MAD group demonstrated a larger reduction in asleep BP compared to the CPAP group. The prevalence of excessive daytime sleepiness in the MAD group decreased from 30.3% at baseline to 10.1% at 12-month follow-up (P = 0.001), and from 38.5% to 7.7% in the CPAP group (P < 0.001). The between-group difference was 10.6% (P = 0.097). No significant within-group or between-group differences were observed in the prevalence of arrhythmias and plasma levels of cardiac biomarkers. CONCLUSION: At 12-month, MAD is non-inferior to CPAP for reducing 24 h mean arterial BP in participants with hypertension and increased cardiovascular risk. TRIAL REGISTRATION: NCT04119999.

Humans↗

PubMed2026

Safety, tolerability, and efficacy of alixorexton, a selective orexin 2 receptor agonist for narcolepsy type 1 (Vibrance-1): a randomised, double-blind, placebo-controlled, phase 2 trial.

BACKGROUND: The clinical potential of orexin 2 receptor (OX2R) agonism for improving measures of wakefulness and cataplexy in patients with narcolepsy type 1 has been described in a phase 2 study. Here, we aimed to evaluate the safety, tolerability, and efficacy of alixorexton, another oral OX2R agonist, in narcolepsy type 1. METHODS: In this randomised, double-blind, placebo-controlled, phase 2 trial, adult participants (aged 18-70 years) with narcolepsy type 1 were recruited from 46 hospitals and private research centres across the USA, Europe, and Australia. Participants were centrally randomly assigned (1:1:1:1) in blocks of four via an interactive response technology system stratified by region and baseline weekly cataplexy rate (WCR) to receive 4 mg, 6 mg, or 8 mg tablets of alixorexton or placebo once daily for 6 weeks, followed by an optional 7-week open-label extension. Participants had narcolepsy type 1, diagnosed per the International Classification of Sleep Disorders, Third Edition, and confirmed by overnight polysomnography and the Multiple Sleep Latency Test or cerebrospinal hypocretin-1 concentrations. The sponsor, assessors, investigators, and participants were masked during the randomised double-blind treatment period. Efficacy and safety assessments were conducted in participants who received at least one dose of study drug. The primary endpoint was change from baseline to week 6 in mean sleep latency (MSL) on the Maintenance of Wakefulness Test (MWT). Safety endpoints included treatment-emergent adverse events. This trial was registered with ClinicalTrials.gov (NCT06358950) and is completed. FINDINGS: Between May 24, 2024, and May 5, 2025, 153 individuals were screened and 92 participants were randomly assigned to receive alixorexton 4 mg (n=23), 6 mg (n=22), 8 mg (n=24), or placebo (n=23). Mean age was 33·5 years (SD 12·1), 57 (62%) were women, and 35 (38%) were men. At week 6, the observed MSL on the MWT was 2·3 min (SD 2·7) for placebo, 24·0 min (8·7) for alixorexton 4 mg, 25·9 min (9·4) for 6 mg, and 28·2 min (11·4) for 8 mg. Alixorexton improved MSL on the MWT, with a least-squares mean placebo-corrected change from baseline of 22·2 min (95% CI 17·2-27·2) for alixorexton 4 mg, 24·1 min (19·0-29·1) for 6 mg, and 26·0 min (21·0-31·0) for 8 mg (adjusted p=0·0099 for 4 mg, adjusted p<0·0001 for 6 mg and 8 mg). Treatment-emergent adverse events occurring in at least 5% of participants given alixorexton and more frequently than those given placebo up to week 6 were pollakiuria (38 [55%]), insomnia (19 [28%]), salivary hypersecretion (17 [25%]), micturition urgency (ten [14%]), blurred vision (ten [14%]), and hyperhidrosis (five [7%]). INTERPRETATION: In this phase 2 trial, once-daily oral alixorexton provided clinically meaningful improvements at 6 weeks for participants with narcolepsy type 1, including in wakefulness, excessive daytime sleepiness, and cataplexy. The treatment was generally well tolerated, with adverse events consistent with the known on-target effects of OX2R agonists. Together, these findings support the further phase 3 evaluation of alixorexton as a potential therapeutic option for people with narcolepsy type 1. FUNDING: Alkermes.

Humans↗

PubMed2026

Clinical insights into catathrenia: A real-world analysis from a tertiary sleep center.

INTRODUCTION: Catathrenia is a rare sleep-related breathing disorder marked by groaning during prolonged expiration, often underrecognized or misdiagnosed as obstructive or central sleep apnoea (OSA or CSA) or parasomnia. Understanding its clinical and polysomnographic features is essential for accurate diagnosis and management. MATERIALS AND METHODS: We performed a retrospective observational study of adult patients diagnosed with catathrenia at Serviço de Medicina do Sono de Coimbra. Diagnosis was established by attended overnight polysomnography (PSG) with synchronised audio-video recording. Demographic data, symptoms, comorbidities, PSG variables, treatment modalities, and outcomes were reviewed. Catathrenia events were defined as deep inhalation followed by prolonged exhalation with monotonous groaning. RESULTS: Ten patients were included. Median age was 46 years (range 27-78), mostly female (70%). Common comorbidities included obesity (n = 4), depression (n = 2), Parkinson's disease (n = 1), and restless legs syndrome (n = 1). Six patients (60%) had concomitant obstructive sleep apnoea (OSA). Seven patients had excessive daytime sleepiness (Epworth Sleepiness Scale > 10). All catathrenia episodes occurred exclusively during REM sleep. Continuous positive airway pressure (CPAP) therapy was the most frequently used treatment and was associated with objective or subjective improvement in most patients. Two patients experienced spontaneous remission. CONCLUSION: Catathrenia remains underdiagnosed and can mimic other sleep disorders. Recognition of its REM-sleep predominance and PSG pattern is essential. Individualised treatment, often involving PAP therapy, may improve symptoms and patient outcomes.

Humans↗

PubMed1978

Respiratory and hemodynamic study during wakefulness and sleep in myotonic dystrophy.

Six young male patients with grade I (mild) myotonic dystrophy and a complaint of excessive daytime sleepiness were studied during wakefulness and sleep. Pulmonary function tests during wakefulness showed evidence of mild abnormality related to respiratory muscle weakness. During sleep, some patients developed a sleep apnea syndrome with high sleep Apnea Indices. There was no relation between hypoxic and hypercapnic ventilatory responses during wakefulness and sleep Apnea Indices. But hypoxemia and hypercapnia worsened considerably during REM sleep. Myotonic dystrophy patients with sleep apnea presented increased pulmonary and systemic arterial pressures during sleep. It was also during sleep that arrhythmias were observed.

Adult↗

PubMed1979

Narcolepsy and automatic behavior: a case report.

Narcolepsy is characterized by excessive daytime sleepiness and cataplexy, which may be accompanied by hypnogogic or hypnopompic hallucinations and sleep paralysis. Automatic behavior is a relatively newly recognized symptom of the narcolepsy syndrome. This case report describes a particularly troublesome sort of automatic behavior--shoplifting--in a narcoleptic patient. It illustrates how a sleep-laboratory evaluation was used to confirm the diagnosis of narcolepsy and considers aspects of the treatment of the problem.

Automatism↗

PubMed1976

Sleep apnea in eight children.

Eight children, 5 to 14 years of age, were diagnosed by means of nocturnal polygraphic monitoring with a sleep apnea syndrome similar to that seen in adults. Excessive daytime sleepiness, decrease in school performance, abnormal daytime behavior, recent enuresis, morning headache, abnormal weight, and progressive development of hypertension should suggest the possibility of a sleep apnea syndrome when any of these symptoms is associated with loud snoring interrupted by pauses during sleep. Surgery may eliminate the clinical symptomatology.

Adenoidectomy↗

PubMed1975

Altered states of consciousness in disorders of daytime sleepiness.

Patients with daytime sleepiness present altered states of consciousness. The occurrence of these states impairs their professional, social and familial activities and may threaten life itself. The automatic behavior syndrome is characterized by continuation of mechanical activity and complete amnesia. Episodes lasting from a few seconds to several hours are correlated with repetitive micro-sleep periods. During cataplectic attacks, patients may have a meshing of reality with hallucinatory dream contents. Sleep-induced apnea may lead to abnormal movement and abnormal ambulation during sleep as well as hallucinations in the early morning. These altered states of consciousness must be considered as diagnostic indexes in differentiating epileptic syndromes from syndromes of daytime sleepiness.

Adult↗

PubMed1978

Hypersomnia-sleep apnea due to micrognathia. Reversal by tracheoplasty.

A 67-year-old woman with acquired micrognathia developed severe daytime hypersomnia, loud snoring, nocturnal enuresis, encopresis, and hypertension. A polysomnogram demonstrated 564 sleep apneas, primarily obstructive, recurrent hypoxia, a bradytachycardia, and absent stages III, IV, and REM sleep. Endoscopy during sleep revealed recurrent active closure of the upper pharynx associated with loud snoring. A tracheoplasty was done because of severity of symptoms and failure of conservative therapy. Dramatic improvement in sleepiness and hypertension occurred within 48 hours. On postoperative night 15 a repeated polysomnogram showed only 23 apneas, no hypoxia or bradytachycardia, and long periods of stage II, IV, and REM sleep. Patients with the hypersomnia-sleep apnea syndrome should be provided with a tracheal opening during sleep when severe daytime somnolence, cardiac arrhythmias, and hypertension are present.

Aged↗