Panagis Drakatos

Epidemiological aspects of obstructive sleep apnea

Obstructive sleep apnea (OSA) is probably the most common respiratory disorder, with recent data from the United States and Europe suggesting that between 14% and 49% of middle-aged men have clinically significant OSA. The intimate relationship between OSA and obesity means that its prevalence will only increase as the global obesity epidemic evolves. At an individual level, OSA leads to a significant decrease in quality of life (QOL) and functional capacity, alongside a markedly increased risk of cardiovascular disease and death. Emerging data also suggest that the presence and severity of OSA and associated nocturnal hypoxemia are associated with an increased risk of diabetes and cancer. At a societal level, OSA not only leads to reduced economic productivity, but also constitutes a major treatable risk factor for hypertension, coronary artery disease (CAD) and stroke. This article addresses OSA from an epidemiological perspective, from prevalence studies to economic aspects to co-morbidity.

First rapid eye movement sleep periods and sleep-onset rapid eye movement periods in sleep-stage sequencing of hypersomnias

OBJECTIVES Discrimination between narcolepsy, idiopathic hypersomnia, and behavior-induced inadequate sleep syndrome (BIISS) is based on clinical features and on specific nocturnal polysomnography (NPSG) and multiple sleep latency test (MSLT) results. However, previous studies have cast doubt on the specificity and sensitivity of these diagnostic tools. METHODS Eleven variables of the NPSG were analyzed in 101 patients who were retrospectively diagnosed with narcolepsy with cataplexy (N+C) (n=24), narcolepsy without cataplexy (N-C) (n=38), idiopathic hypersomnia with long sleep period (IHL) (n=21), and BIISS (n=18). RESULTS Fifteen out of 24 N+C and 8 out of 38 N-C entered the first rapid eye movement (REM) sleep period (FREMP) from sleep stage 1 (N1) or wake (W), though this sleep-stage sequence did not arise in the other patient groups. FREMP stage sequence was a function of REM sleep latency (REML) for both N+C and N-C groups. FREMP stage sequence was not associated with mean sleep latency (MSL) in N+C but was associated in N-C, which implies heterogeneity within the N-C group. REML also was a useful discriminator. Depending on the cutoff period, REML had a sensitivity and specificity of up to 85.5% and 97.4%, respectively. CONCLUSIONS The FREMP stage sequence may be a useful tool in the diagnosis of narcolepsy, particularly in conjunction with sleep-stage sequence analysis of sleep-onset REM periods (SOREMPs) in the MSLT; it also may provide a helpful intermediate phenotype in the clarification of heterogeneity in the N-C diagnostic group. However, larger prospective studies are necessary to confirm these findings.

Sleep stage sequence analysis of sleep onset REM periods in the hypersomnias

Background The Multiple Sleep Latency Test (MSLT) remains an important diagnostic tool in the diagnosis of hypersomnias. However, a positive MSLT may be found in other sleep disorders, such as behaviourally induced inadequate sleep syndrome (BIISS). It has been demonstrated that in sleep onset rapid eye movement (SOREM) periods in BIISS, REM sleep tends to arise from stage 2 sleep (non-REM (NREM) 2), rather than stage 1 sleep (NREM1), as in narcolepsy. Methods We performed sleep stage sequence analysis on 127 patients with nocturnal polysomnography and MSLT, including 25 with narcolepsy with cataplexy (N+C), 41 with narcolepsy without cataplexy (N−C), 21 with idiopathic hypersomnia with long sleep time (IHL), 20 with BIISS and 20 with periodic limb movement disorder (PLMD). 537 naps were recorded, containing 176 SOREM periods. Results All SOREM periods in the IHL, BIISS and PLMD groups arose from NREM2 sleep, 75% of those in N+C arose from NREM1 and in N−C only 52% arose from NREM1. Within the N−C group, those with SOREM periods all arising from stage 1 had a shorter MSL (p=0.02). Conclusions These results suggest that SOREM periods arising from NREM1 have high sensitivity for the diagnosis of narcolepsy and that SOREM periods from NREM1 are a marker of severity, either of sleepiness or REM instability. Sleep stage sequence analysis of SOREM periods may also aid more accurate phenotyping of the hypersomnias and in particular clarify heterogeneity among patients with narcolepsy without cataplexy.

Targeting Leukotrienes for the Treatment of COPD

New drugs and new approaches of the treatment of chronic obstructive pulmonary disease (COPD) are needed. Despite recent advances in medical therapeutics, treatment of patients with COPD remains largely symptomatic. Although inhaled corticosteroids are currently the drug of choice for anti-inflammatory therapy, the inflammatory process in COPD is essentially steroid resistant. By now, COPD has been increasingly recognized as an inflammatory disease characterized by sputum neutrophilia and, in some cases, eosinophilia. Moreover other cell types thought to play the predominant role in COPD, are cytotoxic T lymphocytes (CD8+ T) cells and macrophages. Leukotriene B4, (LTB 4), a neutrophil and T cell chemoattractant which is produced by macrophages, neurophils and epithelial cells, is a potent inflammatory mediator. Also cysteinyl leukotrienes (LTC4, LTD4 and LTE4) are known to induce mucus secretion, inflammatory cell infiltration, increase vascular permeability and tissue edema, damage ciliary clirens, and cause severe bronchoconstriction. These are derivatives of arachidonic acid, metabolized via 5-lypoxygenase (5-LO) pathway. There are several sites along this pathway that antileukotriene agents exert their action and at the end-organ receptors. They are classified into two major categories: receptor antagonists and synthesis inhibitors. Beneficial effects on therapy of patients with COPD have already derived from studies, while they seem well tolerated. More studies are underway.

Derived Arterial Stiffness is Increased in Patients with Obstructive Sleep Apnea and Periodic Limb Movements during Sleep.

STUDY OBJECTIVES Both periodic limb movements during sleep (PLMS) and obstructive sleep apnea (OSA) have been associated with increased risk of cardiovascular disease (CVD). OSA has also been linked to increased large arterial stiffness, which is considered an independent risk factor for CVD. We utilized a previously validated index of large artery stiffness (SIDVP) derived from the digital volume pulse (DVP) to seek comparison in patients with PLMS and OSA. METHODS Forty-nine adult male subjects, without known comorbidities that could affect arterial stiffness or on vasoactive medication, were retrospectively identified and categorized into controls (n = 8), PLMS (n = 13), OSA (n = 17), and OSA/PLMS (n = 11). The cutoff for PLMS was a periodic limb movement index (PLMI) > 15 events/h, and for OSA an apnea-hypopnea index (AHI) > 10 events/h. SIDVP was derived from the raw data of photoplethysmography of the nocturnal polysomnography, averaged for 2 min prior to sleep study initiation (baseline), after completion in the morning, and every half hour after sleep onset. RESULTS The groups were age/body mass index-matched. Controls showed lower baseline, morning, and overall SIDVP compared to the other groups (p < 0.01). Patients with PLMS (PLMI: 50.69 ± 9.7 events/h) and the OSA group (AHI: 29.7 ± 2 events/h) demonstrated similar overall SIDVP (6.78 ± 0.08 versus 6.94 ± 0.04, respectively, p = 0.5), whereas the OSA/PLMS (AHI: 29.35 ± 8, PLMI: 50.63 ± 7.2) group demonstrated the highest (7.40 ± 0.06, p < 0.001). CONCLUSIONS Based on an easily reproducible and applicable marker of large arterial stiffness, patients with significant PLMS had higher SIDVP when compared to controls and comparable to those with moderate/severe OSA. The OSA/PLMS group had the highest SIDVP, implying a possible additive effect of OSA and PLMS on arterial stiffness.

Safety and efficacy of long-term use of sodium oxybate for narcolepsy with cataplexy in routine clinical practice

Background Sodium oxybate is licensed in Europe for the treatment of narcolepsy with cataplexy in adults. The aim of this study was to assess the efficacy and safety of sodium oxybate in clinical practice in patients with narcolepsy and cataplexy refractory to other treatments. Materials and methods This was a retrospective single centre study including patients with severe narcolepsy with cataplexy refractory to other treatments, who were initiated on sodium oxybate between 2009 and 2015. Patients were allowed to be on other stimulants or/and anti-cataplectic agents. Epworth sleepiness scale (ESS) and weekly cataplexy events were recorded. Side effects (SEs) were recorded at every follow-up visit. Results 90 patients were prescribed sodium oxybate, with a total of 3116 patient-months of drug exposure. ESS and weekly cataplexy events were significantly reduced by sodium oxybate for all patients (ΔESS = 4.3 ± 4.4 and Δcataplexy = 21.8 ± 18.5 events/week; p < 0.0001, respectively). The required maintenance dose could not be predicted based upon gender, body mass index, or clinical factors. 60% of patients were able to reduce or come off other medications. Half of the patients experienced at least one SE, and 26.6% had to stop treatment due to limiting SEs. Nausea, mood swings and enuresis were the most commonly reported SEs. SEs that led to drug discontinuation, particularly psychosis, were associated with increasing age and were observed early after the initiation of the drug. Conclusions Sodium oxybate provides a good clinical efficacy and acceptable safety profile in routine clinical practice for the treatment of patients suffering from narcolepsy with cataplexy. A quarter of patients experience SEs requiring withdrawal of the drug with older patients being more vulnerable to the more serious SEs.

Characterisation of sleep disturbances in postural orthostatic tachycardia syndrome: a polysomnography-based study

BACKGROUND AND AIM Postural orthostatic tachycardia syndrome (PoTS) has been frequently associated with sleep disturbances but objective sleep data are lacking. In addition, although regional autonomic denervation has been described, less is known about autonomic nervous activity overnight in these patients. PATIENTS/METHODS A full polysomnography and heart rate variability were performed on 37 patients diagnosed with PoTS . In addition, a multiple sleep latency test (MSLT) was conducted on a subgroup of patients with excessive daytime sleepiness. RESULTS The polysomnographic data did not show major pathological findings except the percentage spent in rapid eye movement (REM) sleep which was slightly reduced at 18.4%. The MSLT did not confirm excessive daytime sleepiness as median mean sleep latency was 14.4 min (11.8-17.5). When comparing patients with and without subjective daytime sleepiness, it was found that the latter had a reduced parasympathetic activation at night as expressed by the average high frequency [6936.5 ms(2) (6028.2-8675.5) vs. 4689.5 (3922.7-7685.2) p < 0.05]. CONCLUSION Patients with PoTS do not exhibit polysomnographic findings consistent with relevant sleep pathologies nor objective daytime sleepiness. Subjective daytime sleepiness is associated with enhanced activation of the parasympathetic nervous system.

Update on hypersomnias of central origin.

Purpose of review To describe the multiple clinical aspects of hypersomnias of central origin. Emphasis is given to the new pathophysiological pathways and treatment options described in the current literature. Recent findings Narcolepsy is the most recognized of the hypersomnias of central origin. Hypocretin deficiency appears to underlie narcolepsy with cataplexy, and infections and vaccinations have been associated with disease onset. Targeted therapeutic approaches are currently underway. A putative naturally occurring constituent in the cerebrospinal fluid of patients with non-narcoleptic primary hypersomnias, able to stimulate &ggr;-aminobutyric acid alpha receptors and induce sleep, has recently been postulated. Neuroimaging has also provided more insight into the pathophysiology of Kleine–Levin syndrome. Sleep deprivation is currently recognized as a major differential diagnosis. Summary Excessive daytime sleepiness is the cardinal symptom of the hypersomnias of central origin, with major impact on the quality of life. It is important that clinicians be able to recognize these conditions, so that appropriate management or onward referral is expedited.

The reality of sexsomnia.

Purpose of review The purpose of this review is to help further the understanding of the clinical profile of patients with sexsomnia and to better understand the spectrum of the clinical manifestations of sexsomnia. We will review the literature from the past decade on the subject and then compare it with our own clinical experience from patients who were retrospectively identified with sexsomnia at a tertiary sleep clinic over a 6-year period. Recent findings The prevalence of sexual behaviours in sleep remains unknown, but it seems to involve predominantly younger male adults who also frequently exhibit other non-rapid eye movement-related parasomnias. Medication-induced cases have been reported and treatment approach of sexsomnia greatly varies. Of 41 individuals with sexsomnia from our centre with a mean age of 32 (37 men), manifestations of sexsomnia were variable; sexual intercourse was most frequently reported overall, but the majority of women carried out masturbation. Violence and aggression were described on 11 occasions. All patients were amnesic of events. 73% had a history of another parasomnia. Summary Sexsomnia is frequently associated with concurrent sleep conditions or drugs initiation. It is a real clinical disorder which should be properly diagnosed and managed.

Nocturnal pulse rate and symptomatic response in patients with obstructive sleep apnoea treated with continuous positive airway pressure for one year

BACKGROUND Obstructive sleep apnoea (OSA) is the most common form of sleep-disordered breathing and a known risk factor for cardiovascular disease. We hypothesised that in patients with OSA the characteristics of nocturnal pulse rate (PR) are associated with changes in blood pressure and daytime sleepiness, following commencement of continuous positive airway pressure (CPAP) therapy. METHODS Pulse oximetry data, demographics, daytime sleepiness and blood pressure were recorded at baseline and at one year follow up. Patients with OSA were grouped according to positive and negative changes in the PR (ΔPR) response during the first night of pulse oximetry before commencement of CPAP. RESULTS A total of 115 patients (58 with OSA and 57 matched subjects without OSA) were identified and included in the analysis. The scale of improvement in daytime sleepiness could be predicted by a negative or positive ΔPR, as recorded in the initial screening pulse oximetry [ΔESS -5.8 (5.1) vs. -0.8 (7.2) points, P<0.05]. A negative correlation was observed between mean nocturnal PR and changes in systolic blood pressure (SBP) after one year of CPAP treatment (r=-0.42, P<0.05). CONCLUSIONS Mean nocturnal PR prior to CPAP initiation was associated with changes in SBP at one year follow up. A descending nocturnal PR in patients with OSA, prior to CPAP initiation, might help to identify a symptomatic response from long term CPAP treatment.