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Sleep apnoea syndrome: states of sleep and autonomic dysfunction.

Eleven patients with upper airway apnoea during sleep (one with SHY-Drager syndrome) were monitored polygraphically for wakefulness, sleep, and cardiovascular variables. Systemic hypertension and most of the severe arrhythmias recorded during sleep were secondary to repetitive obstructive apnonea and were mediated through the autonomic nervous system. Sleep related elevations of pulmonary arterial pressure were not influenced by atropine or impaired autonomic functions. Upper airway sleep apnoea is sleep related; the type of sleep (REM or NREM) is critical in the appearance of abnormalities. The distinction between two patient subgroups (total sleep dependent and NREM sleep dependent) has haemodynamic, and possibly long-term, implications. Sleep apnoea syndrome should be looked for in pateints with the Shy-Drager syndrome.

Adult

The importance of dopamine levels and single-nucleotide polymorphism within COMT, DRD1 and DRD2 genes in obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea (OSA) is a prevalent sleep disorder that contributes to serious cardiovascular comorbidities. While the mechanical aspects of OSA are well-studied, its neurobiological underpinnings remain underexplored. In this study, we investigated the role of dopamine and its genetic modulators in OSA pathophysiology. PATIENTS AND METHODS: Serum dopamine levels were assessed in a cohort of 153 participants (96 OSA patients and 57 controls), and single-nucleotide polymorphisms (SNPs) in dopamine-related genes, including COMT, DRD1 and DRD2, were analysed in a cohort of 286 participants (141 OSA patients and 145 controls). RESULTS: Elevated serum dopamine levels were observed in OSA patients (p = 0.01), with dopamine levels correlating independently with OSA and male gender. Genotypic analysis identified the DRD2 rs1800497 T allele as a potential independent predictor of OSA severity (p = 0.011), hypopnea (p = 0.005) and arousals (p = 0.024). CONCLUSIONS: This study advances the understanding of OSA by identifying elevated dopamine levels and genetic variations in DRD2 rs1800497 as potential modulators of its occurrence and severity. These findings pave the way for personalized diagnostic and therapeutic approaches. By integrating neurobiology, genetics, and clinical practice, this research contributes to the evolving framework for precision medicine in sleep disorders.

Humans

Acetazolamide to prevent ventilatory drive withdrawal in REM sleep apnoea: a randomised controlled trial.

BACKGROUND: Obstructive sleep apnoea (OSA) pathogenesis during rapid-eye movement (REM) sleep has been linked to dips in ventilatory drive and downstream genioglossus hypotonia. The carbonic anhydrase inhibitor acetazolamide is known to increase ventilatory drive and improve OSA severity. Therefore, we tested the effect of acetazolamide on REM-predominant OSA severity (apnoea hypopnoea index (AHI) and hypoxic burden, co-primary outcomes) and underlying physiological mechanisms (ventilatory drive, ventilation and pharyngeal muscle activity). METHODS: 11 participants with REM-predominant OSA per baseline polysomnography (REM AHI/non-REM AHI&#x2265;2) were allocated to receiving acetazolamide 500&#x2009;mg for three nights (first night at half dose) or placebo according to a randomised, crossover, double-blind design. Detailed physiological polysomnography with recording of diaphragm and genioglossus electromyography was conducted after each intervention, with a 1-week washout in between. RESULTS: As hypothesised, acetazolamide reduced AHI by 35.5% (95% CI 23.1% to 46.3%) and hypoxic burden by 35.9% (95% CI 21.1% to 48.4%) vs placebo (p<0.001), meeting the primary endpoint. Mechanistic analysis in REM revealed that, unexpectedly, acetazolamide did not mitigate dips in ventilatory drive versus placebo (first decile (+0.1 (-1.0 to 1.3) L/min, p=0.8). Rather, acetazolamide reduced collapsibility (increased ventilation at eupneic drive: +1.4 (1.2 to 1.8) L/min) and raised muscle responsiveness (ventilation vs drive slope: +32 (25 to 41) %ventilation/drive, p<0.001; genioglossus versus drive slope: +0.33 (0.13 to 0.54) %max/(L/min), p=0.001). CONCLUSIONS: Acetazolamide modestly improved REM OSA, with meaningful improvements in upper airway physiology, but failed to mitigate the dips in ventilatory drive responsible for REM OSA. TRIAL REGISTRATION NUMBER: NCT05589792.

Humans

Omics Profiling of Patients with Obstructive Sleep Apnoea Reveals Risks of Diabetes Mellitus and Cardiovascular Diseases.

Obstructive sleep apnoea (OSA) constitutes a multisystemic disorder often associated with cardiovascular and metabolic disorders. Thus, far, the underlying pathophysiological processes are not fully understood. In total, 142 plasma samples were acquired: 50 from controls (CON), 45 from mild/moderate OSA (M-OSA) patients, and 47 from severe OSA (S-OSA) patients. Proteomic and metabolic signatures significantly differed among S-OSA, M-OSA, and CON samples. A novel plasma biomarker panel including two proteins (ACTR2 and ENO1) and three metabolites (2-aminobicyclo[2 2&#xb7;1], heptane-2-carboxylic acid, 1-O-[2r-hydroxy-hexadecyl]-sn-glycerol, and 1-pentadecene) was developed to identify S-OSA (AUC: 1.000) and distinguish severe cases from nonsevere cases (AUC: 0.813). An independent cohort was used to validate the model by distinguishing S-OSA samples from M-OSA (AUC: 0.729) and CON (AUC: 0.990) samples. Glycolysis pathway activation was identified as a characteristic of OSA; it may contribute to diabetes mellitus onset in OSA patients. Dyslipidaemia, foamy macrophage formation, platelet activation, and actin cytoskeleton might collectively play a key role in vascular damage in OSA patients, contributing to the development of atherosclerosis. These findings reveal molecular bases for OSA-related cardiometabolic complications and provide new diagnostic biomarkers for OSA and the identification of severe cases.

Humans

Polygenic scores for obstructive sleep apnoea reveal pathways contributing to cardiovascular disease.

BACKGROUND: Obstructive sleep apnoea (OSA) is a common chronic condition, with obesity its strongest risk factor. Polygenic scores (PGSs) summarise the genetic liability to phenotype and can provide insights into relationships between phenotypes. Recently, large datasets that include genetic data and OSA status became available, providing an opportunity to utilise PGS approaches to study the genetic relationship between OSA and other phenotypes, while differentiating OSA-specific from obesity-specific genetic factors. METHODS: Using race/ethnic diverse samples from over 1.2 million individuals from the Million Veteran Program, FinnGen, TOPMed, All of Us (AoU), Geisinger's MyCode, MGB Biobank, and the Human Phenotype Project, we developed and assessed PGSs for OSA, both without (BMIunadjOSA-PGS) and with adjustment for the genetic contributions of BMI (BMIadjOSA-PGS). FINDINGS: Adjusted odds ratios (ORs) for OSA per 1 standard deviation of the PGSs ranged from 1.38 to 2.75. The associations of BMIadjOSA- and BMIunadjOSA-PGSs with CVD outcomes in AoU shared both common and distinct patterns. Only BMIunadjOSA-PGS was associated with type 2 diabetes, heart failure, and coronary artery disease, while both BMIadjOSA- and BMIunadjOSA-PGSs were associated with hypertension and stroke. Sex stratified analyses revealed that BMIadjOSA-PGS association with hypertension was driven by females (OR = 1.1, p-value = 0.002, OR = 1.01 p-value = 0.2 in males). OSA PGSs were also associated with body fat measures with some sex-specific associations. INTERPRETATION: Distinct components of OSA genetic risk are related and independent of obesity. Sex-specific associations with body fat distribution measures may explain differing OSA risks and associations with cardiometabolic morbidities between sexes. FUNDING: R01AG080598.

Humans

A common pathophysiology for sudden cot death and sleep apnoea. "The vacuum-glossoptosis syndrome".

Several congenital and acquired conditions, characterized by upper airway narrowing, may result in respiratory, cardiac, and sleep disturbances. In all these conditions the leading clinical feature is the occurrence of cyclic obstructive apnoea, mainly during sleep. The common pathogenic mechanism for the airway occlusion seems to be a backward displacement of the tongue and mandible, favoured by the muscle relaxation which occurs during sleep and by gravity in the supine position. A constant factor determining the glossoptosis is the pharyngeal vacuum occurring in these conditions as a result of inspiratory efforts in face of a narrowed upper airway. The response to this type of obstruction is age-dependent, since only in early infancy may these apnoeic spells be life-threatening. A similar pathophysiology is suggested for sudden cot death, which could be considered as a peculiar presentation of this "vacuum-glossoptosis syndrome". This hypothesis could explain why sudden cot death is often associated with nasopharyngitis and occurs always in infancy, almost invariably during sleep.

Adult

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 Servi&#xe7;o 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&#x2009;years (range 27-78), mostly female (70%). Common comorbidities included obesity (n&#x2009;=&#x2009;4), depression (n&#x2009;=&#x2009;2), Parkinson's disease (n&#x2009;=&#x2009;1), and restless legs syndrome (n&#x2009;=&#x2009;1). Six patients (60%) had concomitant obstructive sleep apnoea (OSA). Seven patients had excessive daytime sleepiness (Epworth Sleepiness Scale&#x2009;>&#x2009;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

Vocal cord paralysis in the Shy-Drager syndrome.

Eight out of 12 unselected patients with Shy-Drager syndrome were found to have severe bilateral paresis of vocal cord abduction by fibre-optic laryngoscopy. This commonly presented as increased snoring followed by episodes of inspiratory and expiratory stridor and sometimes by sleep apnoea. Respiratory failure eventually developed in four cases and was reversed by tracheostomy. In another patient tracheostomy relieved severe attacks of sleep apnoea. This complication was not necessarily associated with advanced disease, and it should be considered in all patients with Shy-Drager syndrome as appropriate treatment can lead to a useful extension of life.

Aged

Influence of diffuse brain stimulation (DBS) on human sleep. II. Sleep-induced periodic breathing with apnoea.

The influence of diffuse brain stimulation (DBS), administered just before sleep onset, on the number of apnoeas and of sleep stage changes during the first part of the succeeding night sleep to the end of the first sleep cycle has been studied in 7 patients with sleep-induced periodic breathing with apnorea. When compared with the corresponding period of the baseline night, both phenomena are increased significantly. These results indicate that DBS influences slow periodic sleep phenomena. It is suggested that the target area for this influence might be mesencephalo-pontine reticular structures, which play a role in the generation of these slow periodic phenomena.

Adult

[Sudden death in new-born babies (author's transl)].

This sudden death of a new-born baby, which had been thriving up to then, is a dramatic but not exceptional event. A systematic search for the etiology must be made, and this should include an autopsy in order that the diagnosis of "sudden and unexplained death" is confirmed only after eliminating all other possible causes. Knowledge of this syndrome has benefited from epidemiological surveys which have defined the previous clinical condition, but none of the many etiollotical hypotheses envisaged can take into account the total number of cases reported. One of the most recent cases developed apnoea during sleep, which could explain some unexpected deaths in new-born babies. This was discovered by polygraphic sleep recordings and confirmed by pathological examinations. These demonstrated indirect signs of chronic hypoxia which could have been related to the sudden death of the baby. Though there does not appear to be any relationship between the apnoea syndrome during sleep and these sudden and unexpected deaths, this hypothesis has opened up a new promising line of research which could help to identify new-born babies at risk from "sudden death", and to propose preventative measures.

Apnea

High-flow nasal cannula oxygenation in sedated endoscopy for high-risk obstructive sleep apnea patients: study protocol for a multicentre randomised controlled trial.

BACKGROUND: Hypoxemia is the most common adverse event during sedated gastrointestinal endoscopy. Patients with high obstructive sleep apnea (OSA) risk (STOP-Bang &#x2265;5) are susceptible due to sedation-induced loss of upper airway tone exacerbating airway collapsibility. Although high-flow nasal cannula (HFNC) benefits general at-risk populations, its efficacy in this specific cohort remains uncertain, as its mild positive pressure falls far below therapeutic continuous positive airway pressure levels for moderate-to-severe OSA, questioning its ability to stent the collapsible airway. Our prior proof-of-concept study in this cohort observed a 5% incidence of hypoxemia with HFNC, confirming feasibility and safety and justifying this confirmatory trial. METHODS: This prospective, multicenter, randomized controlled single-blind trial will enroll 600 adults (STOP-Bang score &#x2265;5) undergoing elective sedated gastroenteroscopy across three centers. Participants will be 1:1 randomized (stratified by center) to HFNC (30&#x2009;L/min pre-oxygenation, 60&#x2009;L/min post-induction) or conventional nasal cannula (6&#x2009;L/min). Both groups receive standardized propofol-alfentanil sedation. The primary outcome is the proportion of patients with at least one episode of hypoxemia (SpO2 75%-90% <60&#x2009;s). Secondary outcomes include the proportion of patients with at least one episode of severe hypoxemia (SpO2 <75% or 75%&#x2264;SpO2<90% &#x2265;60&#x2009;s), the proportion with subclinical respiratory depression (90%&#x2264;SpO2<95%), and the frequency of other adverse events. DISCUSSION: This trial will provide definitive evidence on HFNC's efficacy in high-risk OSA patients, addressing whether it can overcome pressure limitations to prevent hypoxemia. Results are expected to inform sedation management guidelines, establish a new standard of care for this subgroup, and enhance procedural safety. TRIAL REGISTRATION: The trial was registered at the ClinicalTrials.gov on 14 December 2025 (NCT07307560).

Humans

Intravenous flunitrazepam as an anesthetic induction agent.

The effects of the fluorinated benzodiazepine compound flunitrazepam were studied in eighty patients. The drug was administered intravenously in a standard dose of 2 mg, 3 mg, or 4 mg to supplement lumbar epidural analgesia. Induction was smooth and pleasant. The sleep onset time was dose related and exceeded one minute in the majority of patients. Sleep was invariably produced in patients receiving 4 mg but at lower dosage some patients failed to become unconscious. Pain in the arm during injection was a common feature. The respiratory rate was slightly increased, but in two patients apnoea occurred at induction. The cardiovascular system was minimally depressed with a small decrease in systolic blood pressure and pulse rate. Recovery from sleep was slow but sequelae were minimal. The sedative and amnesic properties contributed significantly to the high rate of patient acceptance.

Adjuvants, Anesthesia

[Connections between respiratory regulation and paradoxical sleep in a patient with Joubert's syndrome (author's transl)].

This study reports on eight patients whose cases have been described in literature, and two patients treated by the author, showing the typical signs of Joubert's syndrome. This disease pattern is characterised by episodic hyperpnoeas and apnoeas, retardation, muscular hypotension, opsoclonia, complete or partial agenesis of the vermiform process of cerebellum, as well as a dilated fourth ventricle. The clinical symptoms are compared with the characteristic signs of REM sleep and of cataplexy.

Abnormalities, Multiple

Etomidate, a new water-soluble non-barbiturate intravenous induction agent.

This paper describes clinical experimence, in 100 patients, with the new non-barbiturate, water soluble induction agent, etomidate. This drug produces sleep in one arm/brain circulation-time. There was no effect on pulse-rate, a slight fall in blood-pressure, and a low frequency of apnoea. Involuntary movements were noted, and in some patients these were severe. Etomidate warrants further evaluation as an intravenous induction agent.

Adolescent

[The hypnotic effect of fentanyl and sulfentanil. An electro-encephalographic comparison (author's transl)].

1. Electroencephalographic activity was registered in healthy subjects before, during and 90 minutes after intravenous injections of sufentanil and fentanyl. 2. With a dosage of ratio of 1:10, i.e., 0.025 mg/70 kg body weight sufentanil: 0.25 mg/70 kg body weight fentanyl as well as 0.015 mg/70 kg body weight sufentanil: 0.15 mg/70 kg body weight fentanyl, sufentanil was hypnotically more potent from fentanyl. 3. Sufentanil acts more powerfully on the respiratory regulation than does fentanyl. Periods of apnoea occur more frequently but can be interrupted by external psychophysiological stimulation. 4. The evaluation of indices of certain EEG-waves, characterizing well defined electroencephalographic stages corresponding to the waking-sleeping-behaviour confirmed the visual over-all analysis of the EEG-stages. 5. Physiological observations on heartrate, systemic blood pressure, rapid eye movements during wakefulness, and slow eye movements during sleepiness showed no reliable differences between sufentanil and fentanil. The systematically documented symptoms and vegetative signs of subjects also showed neither differences nor side-effects.

Adult