EEG biomarkers of activation of the lymphatic drainage system of the brain during sleep and opening of the blood-brain barrier.

The lymphatic drainage system of the brain (LDSB) is the removal of metabolites and wastes from its tissues. A dysfunction of LDSB is an important sign of aging, brain oncology, the Alzheimer's and Parkinson's diseases. The development of new strategies for diagnosis of LDSB injuries can improve prevention of age-related cerebral amyloid angiopathy, neurodegenerative and cerebrovascular diseases. There are two conditions, such as deep sleep and opening of the blood-brain-barrier (OBBB) associated with the LDSB activation. A promising candidate for measurement of LDSB could be electroencephalography (EEG). In this pilot study on rats, we tested the hypothesis, whether deep sleep and OBBB can be an informative platform for an effective extracting of information about the LDSB functions. Using the nonlinear analysis of EEG dynamics and machine learning technology, we discovered that the LDSB activation during OBBB and sleep is associated with similar changes in the EEG θ-activity. The OBBB causes the higher LDSB activation vs. sleep that is accompanied by specific changes in the low frequency EEG activity extracted by the power spectra analysis of the EEG dynamics combined with the coherence function. Thus, our findings demonstrate a link between neural activity associated with the LDSB activation during sleep and OBBB that is an important informative platform for extraction of the EEG-biomarkers of the LDSB activity. These results open new perspectives for the development of technology for the LDSB diagnostics that would open a novel era in the prognosis of brain diseases caused by the LDSB disorders, including OBBB.

Decrease of coherence between the respiration and parasympathetic control of the heart rate with aging.

The study of coordinated behavior between different systems of the human body provides useful information on the functioning of the body. The peculiarities of interaction and coordinated dynamics of the heart rate and respiration are of particular interest. We investigated the coherence of the processes of respiration and autonomic control of the heart rate for people of different ages in the awake state, in sleep with rapid eye movement, and in deep sleep. Our analysis revealed a monotonic decrease in the coherence of these processes with increasing age. This can be explained by age-related changes in the system of autonomic control of circulation. For all age groups, we found a qualitatively similar dynamics of the coherence between the studied processes during a transition from the awake state to sleep.

Effects of optimized heart failure medication on central sleep apnea with Cheyne-Stokes respiration pattern in chronic heart failure with reduced left-ventricular ejection fraction.

Central Sleep Apnea with Cheyne Stokes Respiration (CSA-CSR) is often diagnosed in patients with chronic heart failure (CHF). CSA-CSR displays a periodic breathing pattern with a typical waxing and waning breathing with central sleep apnea phases in between. Optimization of heart failure medication with Angiotensin receptor neprilysin inhibition (ARNi) can effect phenotypic traits of CSA-CSR indicating improvements of both, hemodynamic parameters and central chemosensitivity.

Improved follow-up by peripheral arterial tonometry in CPAP-treated patients with obstructive sleep apnea and persistent excessive daytime sleepiness.

BACKGROUND: OSA-patients with persistent excessive daytime sleepiness (EDS) despite CPAP treatment are challenging in daily clinical life. To rule out residual sleep-disordered breathing (SDB), CPAP device-derived data are used in outpatient setting. In case of no pathological finding, a more intensive work-up with is necessary. 6-channel portable monitoring (6Ch-PM) is frequently used to exclude residual SDB. Peripheral arterial tonometry (PAT), as embodied in the WatchPAT device, represents an alternative technique for detecting SDB based on changes in autonomic tone. We wanted to investigate whether PAT might be a useful tool to improve diagnostic work-up in this specific patient group by better identifying residual SDB due to insufficient CPAP-adjustment. METHODS: Forty-nine OSA patients (39 male, 10 female) with sufficient CPAP treatment according to device-derived data were consecutively recruited. EDS was assessed by Epworth Sleepiness Scale (ESS). All patients underwent home-based CPAP therapy control by 6Ch-PM and portable monitoring using PAT technology on two consecutive nights. A sequence of both types of monitoring was randomized to prevent possible first night effect bias. RESULTS: Twelve out of 49 patients showed persistent EDS according to ESS (ESS > 10 points). 6Ch-PM showed a residually increased AHI under CPAP-treatment in 2 of those 12 subjects (positive predictive value, PPV = 16.7%). PAT-PM revealed 5 patients of those 12 with residual SDB (PPV = 41.7%). CONCLUSION: PAT could detect significantly more residual SDB under CPAP treatment than 6Ch-PM. Diagnostic work-up of CPAP-treated OSA patients with persistent EDS might be optimized, as insufficient pressure level adjustments could be recognized more precisely in time, possibly preventing more resource-consuming procedures, and potentially increased morbidity. CLINICAL TRIAL REGISTRATION: DRKS00007705.

[Positionpaper on Telemonitoring in Sleep-Related Breathing Disorders]. / Positionspapier zum Telemonitoring bei schlafbezogenen Atmungsstörungen.

The use of telemonitoring in the care of patients with Sleep-related Breathing Disorders (SBD) can enhance medical support significantly. Telemonitoring aims at helping physicians to detect therapy problems early and thus improve patients' therapy adherence. Diagnostics and therapy decisions in the telemonitoring process nevertheless remain the responsibility of sleep specialists. The selection of data monitored, their evaluation and resulting consequences fall to the physician, who makes decisions and prescribes therapy in consultation with the patient. In light of professional legal and ethical requirements, it must be ensured that the extensive changes to the process flow in sleep medicine are designed in a way to guarantee high-quality patient care. In this position paper, the German Sleep Society, the German Respiratory Society, the Association of Pneumological Hospitals and the Federal Association of German Pneumologists comment on important aspects for implementation of telemonitoring for SRBD and describe the basic conditions required for its use.

[Lung Health Data of the Study of Health in Pomerania - a Review of Samples, Methods and First Results]. / Pneumologisch relevante Daten aus der "Study of Health in Pomerania" (SHIP) ­ eine Übersicht zu den Kohorten, Methoden und ersten Ergebnissen.

Investigating reasons for differing life expectancy and prevalence of cardiovascular risk factors between old and new states of the Federal Republic of Germany an epidemiological study in Western Pomerania - the population-based project Study of Health in Pomerania (SHIP) - was planned.Prevalence and incidence of common risk factors, subclinical disorders and clinical diseases have been assessed since 1997 in five-year intervals. The third follow up (SHIP-3) was assessed between 2014 and 2016. In addition, an independent representative population sample was investigated between 2008 - 2012 (SHIP-TREND). Recently, the first follow up of this cohort has been started (SHIP-TREND-1). This paper reports the methodological approaches for detecting pneumological relevant morbidities in this population-based study. It aims to offer insights for potential cooperation with interested research groups.

Exposure to light and darkness and its influence on physiological measures of intensive care unit patients-a systematic literature review.

Sleep-wake patterns are often significantly disturbed in critically ill patients. This disturbance is closely linked to secondary brain dysfunctions in these patients. Sedation not only impairs sleep quality in ICU patients but also has detrimental effects on short- and long-term outcome. In other contexts, light therapy has been proven to be effective in maintaining and resynchronizing circadian rhythmicity in humans. The objective of this systematic review was to analyse studies that investigated the effect of exposure to light or darkness on physiological measures and clinical outcomes of adult ICU patients. Studies were systematically identified by searching electronic bibliographic databases (The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 2002) and MEDLINE via PubMed). The search algorithm identified a total of 156 articles, 10 of which were taken into final review. These 10 selected articles included 3 were monocentric RCTs, five prospective cohort studies, one retrospective cohort study, and one manuscript that included a partial systematic review of the literature. Included trials were published between 2007 and 2015. Five of these studies used multiple intervention approaches while four trials used a single intervention approach. Among all studies, 1,278 patients were analysed (489 prospectively). There was a high heterogeneity among the studies in terms of applied intervention and outcome measures. The most frequent methodological limitations were a lack of precise definitions regarding the illuminance and the light spectrum utilised. The analyses indicate that further studies including clearly defined interventions with objective outcome measures, as these are currently lacking, would add significant knowledge to this new field of research.

Feasibility of noise reduction by a modification in ICU environment.

Noise is a proven cause of wakefulness and qualitative sleep disturbance in critically ill patients. A sound pressure level reduction can improve sleep quality, but there are no studies showing the feasibility of such a noise reduction in the intensive care unit (ICU) setting. Considering all available evidence, we redesigned two ICU rooms with the aim of investigating the physiological and clinical impact of a healing environment, including a noise reduction and day-night variations of sound level. Within an experimental design, we recorded 96 h of sound-pressure levels in standard ICU rooms and the modified ICU rooms. In addition, we performed a sound source observation by human observers. Our results show that we reduced A-weighted equivalent sound pressure levels and maximum sound pressure levels with our architectural interventions. During night-time, the modification led to a significant decrease in 50 dB threshold overruns from 65.5% to 39.9% (door side) and from 50% to 10.5% (window side). Sound peaks of more than 60 decibels were significantly reduced from 62.0% to 26.7% (door side) and 59.3% to 30.3% (window side). Time-series analysis of linear trends revealed a significantly more distinct day-night pattern in the modified rooms with lower sound levels during night-times. Observed sound sources during night revealed four times as many talking events in the standard room compared to the modified room. In summary, we show that it is feasible to reduce sound pressure levels using architectural modifications.

Changes of sleep-stage transitions due to ageing and sleep disorder.

Transition patterns between different sleep stages are analysed in terms of probability distributions of symbolic sequences for young and old subjects with and without sleep disorder. Changes of these patterns due to ageing are compared with variations of transition probabilities due to sleep disorder.

Symbolic dynamics marker of heart rate variability combined with clinical variables enhance obstructive sleep apnea screening.

Many sleep centres try to perform a reduced portable test in order to decrease the number of overnight polysomnographies that are expensive, time-consuming, and disturbing. With some limitations, heart rate variability (HRV) has been useful in this task. The aim of this investigation was to evaluate if inclusion of symbolic dynamics variables to a logistic regression model integrating clinical and physical variables, can improve the detection of subjects for further polysomnographies. To our knowledge, this is the first contribution that innovates in that strategy. A group of 133 patients has been referred to the sleep center for suspected sleep apnea. Clinical assessment of the patients consisted of a sleep related questionnaire and a physical examination. The clinical variables related to apnea and selected in the statistical model were age (p < 10(-3)), neck circumference (p < 10(-3)), score on a questionnaire scale intended to quantify daytime sleepiness (p < 10(-3)), and intensity of snoring (p < 10(-3)). The validation of this model demonstrated an increase in classification performance when a variable based on non-linear dynamics of HRV (p < 0.01) was used additionally to the other variables. For diagnostic rule based only on clinical and physical variables, the corresponding area under the receiver operating characteristic (ROC) curve was 0.907 (95% confidence interval (CI) = 0.848, 0.967), (sensitivity 87.10% and specificity 80%). For the model including the average of a symbolic dynamic variable, the area under the ROC curve was increased to 0.941 (95% = 0.897, 0.985), (sensitivity 88.71% and specificity 82.86%). In conclusion, symbolic dynamics, coupled with significant clinical and physical variables can help to prioritize polysomnographies in patients with a high probability of apnea. In addition, the processing of the HRV is a well established low cost and robust technique.

[Consensus paper on the diagnosis and treatment of sleep disordered breathing]. / Konsensuspapier zur Diagnostik und Therapie schlafbezogener Atmungsstörungen bei Erwachsenen.

Diagnosis and treatment of sleep disordered breathing (SDB) undergo substantial changes, both in terms of increasing scientific knowledge and also in terms of patient provision and socio-economic aspects. Increasing evidence shows the relevance of SDB on morbidity and mortality of affected patients. The precise differentiation of different phenotypes of SDBs has improved substantially in recent years. These proceedings influence the approach to the patients suspected of suffering from SDB. The scientific advances on the one hand are facing intentions to simplify diagnostical processes and treatment initiation and intentions to translate duties of physicians to non-medical personnel on the other hand. This consensus paper presents the principals of diagnosis, treatment initiation and provision, including the role of different participants of the healthcare system, and compares different treatment options. Major aspects include the differentiation of the diagnostical process in screening, affirmation of diagnosis and differential diagnosis. In addition, it focusses on the relevance of the pretest probability and describes a therapeutical algorithm.

A review of signals used in sleep analysis.

This article presents a review of signals used for measuring physiology and activity during sleep and techniques for extracting information from these signals. We examine both clinical needs and biomedical signal processing approaches across a range of sensor types. Issues with recording and analysing the signals are discussed, together with their applicability to various clinical disorders. Both univariate and data fusion (exploiting the diverse characteristics of the primary recorded signals) approaches are discussed, together with a comparison of automated methods for analysing sleep.

Investigating relative respiratory effort signals during mixed sleep apnea using photoplethysmogram.

Sleep disordered breathing does show different types of events. These are obstructive apnea events, central apnea events and mixed sleep apnea (MSA) which have a central component with a pause in airflow without respiratory effort followed by an obstructive component with respiratory effort. The esophageal pressure (Pes) is the accurate method to assess respiratory effort. The aim of the present study is to investigate whether the features extracted from photo-plethysmogram (PPG) could relate with the changes in Pes during MSA. Therefore, Pes and PPG signals during 65 pre-scored MSA events and 10 s preceding the events were collected from 8 patients. Pulse intervals (PPI), Pulse wave amplitudes (PWA) and wavelet decomposition (Wv) of PPG signals at level 8 (0.15-0.32 Hz) were derived from PPG signals. Results show that significant correlations (r = 0.63, p < 0.01; r = 0.42, p < 0.05; r = 0.8, p < 0.01 for OSA part) were found between reductions in Pes and that in PPG based surrogate respiratory signals PPI, PWA and Wv. Results suggest that PPG based relative respiratory effort signal can be considered as an alternative to Pes as a means of measuring changes in inspiratory effort when scoring OSA and CSA parts of MSA events.

[Diagnosis of sleep disordered breathing using portable methods]. / Diagnostik schlafbezogener Atmungsstörungen mittels portabler Verfahren.

Portable monitoring of sleep disordered breathing is the first diagnostic method not only in Germany but today in other countries as well. The conditions under which portable monitoring can be done with reliable results are now well defined. The limitations for the use of portable monitoring are specified as well. The devices used for portable monitoring are classified in four categories according to the number and the kind of signals recorded. New technical developments in the field of portable monitoring (polygraphy) use an indirect assessment of sleep disordered breathing based on signals not directly recording respiration. The recording of ECG and deriving respiration, the analysis of the plethysmographically recorded pulse wave, the recording of jaw movements using magnets, and advanced analysis of respiratory sounds are recent approaches. These new methods are presented with few studies until now. More and larger clinical studies are needed in order to show which of these systems is useful in the diagnosis of sleep disordered breathing and which are the specific strengths and weaknesses.

[Portable sleep monitoring in patients with disorders in falling asleep or maintaining sleep]. / Erweiterte ambulante Polygraphie bei Patienten mit Ein- und/oder Durchschlafstörungen.

BACKGROUND: The most common diagnoses in sleep medicine are insomnia, sleep disordered breathing (SDB) and periodic leg movements (PLM). These disorders may coincide. This study examined the role of portable sleep monitoring in the diagnostic process and which sleep medicine diagnoses are additionally found in patients with disorders of initiating and maintaining sleep. METHODS: A total of 217 patients, including 103 men (47.5%) and 114 (52.5%) women aged 52.2 ± 13.6 years with disorders of initiating or maintaining sleep were included in the study. Patients with known SDB were excluded. Patients were investigated using a stepwise diagnostic procedure with clinical interviews, questionnaires, clinical examination and portable sleep recording with electromyography (EMG) of the tibialis anterior muscle to diagnose SDB and PLM. RESULTS: Of the patients 125 (57.6%) were diagnosed with insomnia according to the International Classification of Sleep Disorders (ICSD) and 70 (56%) had no other sleep disorder. Out of the 217 patients SDB was found in 107 (49.3%) patients, PLM in 90 patients (41.5%) and in 78 patients (35.9%) restless legs syndrome (RLS) was diagnosed. Among the 125 patients with insomnia 44 patients had RLS/PLMD and 35 had SDB in addition whereas SDB and RLS/PLMD were found in 33 subjects. All 3 disorders insomnia, RLS/PLMD and SDB were found in 24 subjects. CONCLUSIONS: Out of 217 patients with a complaint of non-restorative sleep only 125 were finally diagnosed with insomnia. As 25.3% of patients showed combinations of sleep disorders, 49.3% with SDB and 41.5% with RLS/PLMD portable monitoring with electromyography of the legs is recommended. The investigation with a portable sleep monitoring system including an EMG of the tibialis muscle is very useful in patients with insomnia in addition to a clinical interview and questionnaires.

Orexin receptor antagonism, a new sleep-enabling paradigm: a proof-of-concept clinical trial.

The orexin system is a key regulator of sleep and wakefulness. In a multicenter, double-blind, randomized, placebo-controlled, two-way crossover study, 161 primary insomnia patients received either the dual orexin receptor antagonist almorexant, at 400, 200, 100, or 50 mg in consecutive stages, or placebo on treatment nights at 1-week intervals. The primary end point was sleep efficiency (SE) measured by polysomnography; secondary end points were objective latency to persistent sleep (LPS), wake after sleep onset (WASO), safety, and tolerability. Dose-dependent almorexant effects were observed on SE , LPS , and WASO . SE improved significantly after almorexant 400 mg vs. placebo (mean treatment effect 14.4%; P < 0.001). LPS (­18 min (P = 0.02)) and WASO (­54 min (P < 0.001)) decreased significantly at 400 mg vs. placebo. Adverse-event incidence was dose-related. Almorexant consistently and dose-dependently improved sleep variables. The orexin system may offer a new treatment approach for primary insomnia.

[Sleep-disordered breathing and atrial fibrillation]. / Schlafbezogene Atmungsstörungen und Vorhofflimmern.

Sleep-disordered breathing is one of the most common sleep disorders. Especially obstructive sleep apnea (OSA) is an independent cardiovascular risk factor. Clinical studies have proven a significant association between OSA and atrial fibrillation, the most common cardiac arrhythmia. Currently, there is no proven evidence for causality. Untreated OSA seems to be a risk factor for failure of rhythm control strategy in atrial fibrillation. The recurrence rate after cardioversion is higher in case of additional untreated OSA. Continuous positive airway pressure (CPAP) therapy in OSA patients could reduce relapse rate. However, there is a lack of randomized controlled clinical trials with defined end points on this topic. A specific sleep medicine interview as well as sleep studies with portable monitoring and cardiorespiratory polysomnography are recommended when sleep-disordered breathing is suspected. Procedures for the management of patients with atrial fibrillation are given.

[Sleep apnoea syndrome in the rehabilitation setting]. / Das Schlafapnoe-Syndrom in der Rehabilitation.

Sleep-related breathing disorders are a common finding in patients undergoing cardiological rehabilitation. Sleep apnoea is recognized as a major risk factor for cardiovascular disorders. The diagnosis of sleep-related breathing disorders begins with taking a thorough sleep medicine-related patient history and answering dedicated questionnaires. The second step involves portable monitoring to assess oxygen saturation, heart rate, respiratory flow and effort. Portable monitoring is able to detect the severity of the breathing disorder and forms the basis on which to refer the patient for further sleep laboratory diagnosis or, in the case of positive results, to initiate appropriate treatment. In order to exclude a sleep-related breathing disorder, to distinguish between obstructive and central sleep apnoea, or to diagnose other sleep disorders a cardiorespiratory polysomnography in a sleep laboratory is required. Polysomnography is also needed if comorbidities are present. Appropriate and prompt treatment of sleep-related breathing disorders can shorten cardiological rehabilitation and improve outcomes in this patient group.

Effect of CPAP therapy on daytime cardiovascular regulations in patients with obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a sleep disorder with a high prevalence that causes pathological changes in cardiovascular regulation during the night and also during daytime. We investigated whether the treatment of OSA at night by means of continuous positive airway pressure (CPAP) improves the daytime consequences. Twenty-eight patients with OSA, 18 with arterial hypertension, 10 with normal blood pressure, were investigated at baseline and with three months of CPAP treatment. Ten age and sex matched healthy control subjects were investigated for comparisons. We recorded a resting period with 20min quiet breathing and an exercise stress test during daytime with ECG and blood pressure (Portapres). The bicycle ergometry showed a significant reduction of the diastolic blood pressure at a work load of 50W and 100W (p<0.05 and p<0.01, respectively) and a decrease of the heart rate recovery time after the stress test (p<0.05). These results indicate a reduction of vascular resistance and sympathetic activity during daytime. The coupling analysis of the resting periods by means of symbolic coupling traces approach indicated an effect of the CPAP therapy on the baroreflex reaction in hypertensive patients where influences of the systolic blood pressure on the heart rate changed from pathological patterns to adaptive mechanisms of the normotensive patients (p<0.05).

ECG signal analysis for the assessment of sleep-disordered breathing and sleep pattern.

The diagnosis of sleep-disordered breathing (SDB) usually relies on the analysis of complex polysomnographic measurements performed in specialized sleep centers. Automatic signal analysis is a promising approach to reduce the diagnostic effort. This paper addresses SDB and sleep assessment solely based on the analysis of a single-channel ECG recorded overnight by a set of signal analysis modules. The methodology of QRS detection, SDB analysis, calculation of ECG-derived respiration curves, and estimation of a sleep pattern is described in detail. SDB analysis detects specific cyclical variations of the heart rate by correlation analysis of a signal pattern and the heart rate curve. It was tested with 35 SDB-annotated ECGs from the Apnea-ECG Database, and achieved a diagnostic accuracy of 80.5%. To estimate sleep pattern, spectral parameters of the heart rate are used as stage classifiers. The reliability of the algorithm was tested with 18 ECGs extracted from visually scored polysomnographies of the SIESTA database; 57.7% of all 30 s epochs were correctly assigned by the algorithm. Although promising, these results underline the need for further testing in larger patient groups with different underlying diseases.