Long-term continuous positive airway pressure therapy improves cardiac autonomic tone during sleep in patients with obstructive sleep apnea.

BACKGROUND: Cardiac autonomic tone after long-term continuous positive airway pressure therapy in patients with obstructive sleep apnea remains unexplored. METHODS: Thirty patients with obstructive sleep apnea (14 with moderate and 16 with severe obstructive sleep apnea) were studied during a baseline polysomnographic study, after a full night of acute continuous positive airway pressure treatment, and after long-term (~2 years) chronic continuous positive airway pressure therapy. Twenty age- and gender-matched controls with baseline sleep study were selected for comparison purposes. Cross-spectral analysis and the low-frequency (LF) and high-frequency (HF) components of the heart rate variability were computed separately over 10-min ECG epochs during rapid eye movement sleep, non-rapid eye movement sleep, and wakefulness. RESULTS: During the baseline study, obstructive sleep apnea patients exhibited increased LF, decreased HF, and increased LF/HF ratio during sleep when compared to controls. In a multiple regression model, the mean oxygen saturation explained the increased LF during rapid and non-rapid eye movement sleep in obstructive sleep apnea patients. Acute continuous positive airway pressure therapy decreased the LF modulations and the LF/HF ratio and increased the HF modulations during sleep in patients with severe obstructive sleep apnea. Long-term continuous positive airway pressure therapy decreased LF modulations and LF/HF ratio with increased HF modulations during sleep in patients with moderate and severe obstructive sleep apnea. CONCLUSIONS: Long-term continuous positive airway pressure reduces the sympathovagal imbalance in patients with moderate and severe obstructive sleep apnea, both during rapid and non-rapid eye movement sleep. Continuous positive airway pressure seems to exert its changes in cardiac autonomic modulation by decreasing the burden of nocturnal hypoxia.

Prevalence of REM sleep behavior disorder in multiple system atrophy: a multicenter study and meta-analysis.

OBJECTIVE: Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia frequently affecting patients with synucleinopathies, but its exact prevalence in multiple system atrophy (MSA) is unclear. Whether questionnaires alone are sufficient to diagnose RBD is also unknown. METHODS: We performed a cross-sectional study of patients with probable MSA from six academic centers in the US and Europe. RBD was ascertained clinically and with polysomnography; we also performed a meta-analysis according to PRISMA guidelines for studies published before September 2014 that reported the prevalence of RBD in MSA. A random-effects model was constructed using weighted prevalence proportions. Only articles in English were included. Studies were classified into those that ascertained the presence of RBD in MSA clinically and with polysomnography. Case reports or case series (≤ 5 patients) were not included. RESULTS: Forty-two patients completed questionnaires and underwent polysomnography. Of those, 32 (76.1%) had clinically suspected RBD and 34 (81%) had polysomnography-confirmed RBD. Two patients reported no symptoms of RBD but had polysomnography-confirmed RBD. The primary search strategy yielded 374 articles of which 12 met the inclusion criteria. The summary prevalence of clinically suspected RBD was 73% (95 % CI, 62-84%) in a combined sample of 324 MSA patients. The summary prevalence of polysomnography-confirmed RBD was 88 % (95% CI, 79-94%) in a combined sample of 217 MSA patients. INTERPRETATION: Polysomnography-confirmed RBD is present in up to 88% of patients with MSA. RBD was present in some patients that reported no symptoms. More than half of MSA patients report symptoms of RBD before the onset of motor deficits.

Basal cardiac autonomic tone is normal in patients with periodic leg movements during sleep.

The relationship between the autonomic nervous system and periodic leg movements during sleep (PLMS) is not completely understood. We aimed to determine whether patients with PLMS exhibit any changes in their basal heart rate variability (HRV), excluding episodes of leg movements and arousals. To investigate this, we conducted a cross-sectional study including 13 patients with PLMS (PLMS ≥ 20) and 13 matched controls, free of cardiovascular diseases and medications. Time-and frequency-domain HRV measures [mean R-R interval, low frequency (LF), high frequency (HF), LF/HF] were calculated across all sleep stages as well during wakefulness just before and after sleep during one-night polysomnography. We only took ECG segments of sleep without arousals and excluded periods of 30 s before and after the leg movements. No statistical differences between PLMS and control subjects were found in any of the time- or frequency-domain HRV measures across sleep stages. Basal cardiac autonomic modulation in patients with PLMS is similar to that of control subjects. Our results argue against a role for a basal disturbance of the cardiac autonomic nervous system in the pathogenesis of PLMS.

Cortical activation in REM behavior disorder mimics voluntary movement. An electroencephalography study.

OBJECTIVES: Motor symptoms of Parkinson's disease improve during REM sleep behavior disorder movement episodes. Our aim was to study cortical activity during these movement episodes, in patients with and without Parkinson's disease, in order to investigate the cortical involvement in the generation of its electromyographic activity and its potential relationship with Parkinson's disease. METHODS: We looked retrospectively in our polysomnography database for patients with REM sleep behavior disorder, analyzing fifteen patients in total, seven with idiopathic REM sleep behavior disorder and eight associated with Parkinson's disease. We selected segments of REM sleep with the presence of movements (evidenced by electromyographic activation), and studied movement-related changes in cortical activity by averaging the electroencephalographic signal (premotor potential) and by means of time/frequency transforms. RESULTS: We found a premotor potential and an energy decrease of alpha-beta oscillatory activity preceding the onset of electromyographic activity, together with an increase of gamma activity for the duration of the movement. All these changes were similarly present in REM sleep behavior disorder patients with and without Parkinson's disease. CONCLUSIONS: Movement-related changes in electroencephalographic activity observed in REM sleep behavior disorder are similar to those observed during voluntary movements, regardless of the presence of Parkinson's disease motor symptoms. SIGNIFICANCE: These results suggest a main involvement of the cortex in the generation of the movements during REM sleep.

Musicogenic seizures in Dravet syndrome.

Dravet syndrome is an epileptic encephalopathy characterized by multiple types of seizures. We report the first case of musicogenic reflex seizures in a 7-year-old male with a mutation in the SCN1A gene causing Dravet syndrome. Reflex seizures have been reported in patients with Dravet syndrome provoked by body temperature elevation, looking at visual patterns, or under intermittent photic stimulation. The case we report widens the spectrum of reflex seizures recorded in patients with Dravet syndrome. Cortical hyperexcitability of genetic origin could explain the tendency of these patients to experience reflex seizures.

Quality of Life Impact of Hypoglossal Nerve Stimulation with Inspire® Device in Patients with Obstructive Sleep Apnea Intolerant to Continuous Positive Airway Pressure Therapy.

Patients with obstructive sleep apnea (OSA) that do not tolerate/accept continuous positive airway pressure (CPAP) are candidates for surgical alternatives. Hypoglossal nerve stimulation (HNS) through the implantation of the Inspire® device constitutes a minimally invasive operative option. The main objective of this study is to estimate, under real-world clinical practice conditions, the 3-month impact on the quality of life (IQoL) of the HNS in patients with moderate/severe OSA who do not tolerate or accept CPAP, compared to patients who did not receive HNS. As a baseline, the unadjusted EuroQol utility index was 0.764 (SD:0.190) in the intervention group (IGr) and 0.733 (SD:0.205) in the control group (CGr); three months later, the indexes were 0.935 (SD: 0.101) and 0.727 (SD:0.200), respectively. The positive impact on quality of life was estimated to be +0.177 (95% CI: 0.044−0.310; p = 0.010). All dimensions in the IGr improved compared to CGr, especially for usual activities (p < 0.001) and anxiety/depression (p > 0.001). At the end of the follow-up, there was no significant difference in the quality of life between the general Spanish population and the IGr (difference: 0.012; CI95%: −0.03 to −0.057; p = 0.0578) for the same age range; however, there was a difference concerning the CGr (difference: −0.196; CI95%: −0.257 to −0.135; p < 0.001). In conclusion, patients with moderate/severe OSA implanted with the Inspire® device showed a positive IQoL.

An interactive framework for the detection of ictal and interictal activities: Cross-species and stand-alone implementation.

BACKGROUND AND OBJECTIVE: Despite advances on signal analysis and artificial intelligence, visual inspection is the gold standard in event detection on electroencephalographic recordings. This process requires much time of clinical experts on both annotating and training new experts for this same task. In scenarios where epilepsy is considered, the need for automatic tools is more prominent, as both seizures and interictal events can occur on hours- or days-long recordings. Although other solutions have already been proposed, most of them are not integrated on clinical and basic science environments due to their complexity and required specialization. Here we present a pipeline that arises from coordinated efforts between life-science researchers, clinicians and data scientists to develop an interactive and iterative workflow to train machine-learning tools for the automatic detection of electroencephalographic events in a variety of scenarios. METHODS: The approach consists on a series of subsequent steps covering data loading and configuration, event annotation, model training/re-training and event detection. With slight modifications, the combination of these blocks can cope with a variety of scenarios. To illustrate the flexibility and robustness of the approach, three datasets from clinical (patients of Dravet Syndrome) and basic research environments (mice model of the same disease) were evaluated. From them, and in response to researchers' daily needs, four real world examples of interictal event detection and seizure classification tasks were selected and processed. RESULTS: Results show that the current approach was of great aid for event annotation and model development. It was capable of creating custom machine-learning solutions for each scenario with slight adjustments on the analysis protocol, easily accessible to users without programming skills. Final annotator similarity metrics reached values above 80% on all cases of use, reaching 92.3% on interictal event detection on human recordings. CONCLUSIONS: The presented framework is easily adaptable to multiple real world scenarios and the interactive and ease-to-use approach makes it manageable to clinical and basic researches without programming skills. Nevertheless, it is conceived so data scientists can optimize it for specific scenarios, improving the knowledge transfer between these fields.

Simple and Autonomous Sleep Signal Processing System for the Detection of Obstructive Sleep Apneas.

Obstructive sleep apnea (OSA) is a common sleep disorder characterized by repetitive upper airway obstruction, intermittent hypoxemia, and recurrent awakenings during sleep. The most used treatment for this syndrome is a device that generates a positive airway pressure­Continuous Positive Airway Pressure (CPAP), but it works continuously, whether or not there is apnea. An alternative consists on systems that detect apnea episodes and produce a stimulus that eliminates them. Article focuses on the development of a simple and autonomous processing system for the detection of obstructive sleep apneas, using polysomnography (PSG) signals: electroencephalography (EEG), electromyography (EMG), respiratory effort (RE), respiratory flow (RF), and oxygen saturation (SO2). The system is evaluated using, as a gold standard, 20 PSG tests labeled by sleep experts and it performs two analyses. A first analysis detects awake/sleep stages and is based on the accumulated amplitude in a channel-dependent frequency range, according to the criteria of the American Academy of Sleep Medicine (AASM). The second analysis detects hypopneas and apneas, based on analysis of the breathing cycle and oxygen saturation. The results show a good estimation of sleep events, where for 75% of the cases of patients analyzed it is possible to determine the awake/asleep states with an effectiveness of >92% and apneas and hypopneas with an effectiveness of >55%, through a simple processing system that could be implemented in an electronic device to be used in possible OSA treatments.

Sound analysis of catathrenia: a vocal expiratory sound.

PURPOSE: Catathrenia (nocturnal groaning) is a rare and relatively little-understood parasomnia. The characteristics of the sound and the recordings are not similar in all the relevant research papers. Indeed, there is currently some discussion regarding whether or not this is a single entity. For some authors, catathrenia is a particular form of parasomnia; for others, it may be a variant of snoring or a respiratory problem. The goal is to establish whether or not catathrenia may be regarded as an expiratory vocal sound. An attempt was made to classify the origin of this sound according to its sound structure. METHODS: We present the sound analysis of two patients, a man and a woman, with clinically diagnosed catathrenia and we compared them with the analysis of snoring. We use the spectrogram and the oscillogram. We classified the sounds according to the Yanagihara criteria. RESULTS: The vocal nature of the sound was confirmed, and several significant differences to some snoring sounds were discovered. The analysis of the catathrenia samples demonstrated that these signals are type II according to Yanagihara classification; these signals had a very short jitter, and had formants and harmonics. However, snoring is a type III, very irregular and had formants but not harmonics. CONCLUSIONS: The oscillogram and the spectrogram in these patients show that the origins of the sounds are clearly different: catathrenia is laryngeal, while snoring is guttural. Catathrenia cannot be considered as expiratory snoring.

Abnormal brain gamma oscillations in response to auditory stimulation in Dravet syndrome.

OBJECTIVE: To evaluate the capability of children with Dravet syndrome to generate brain γ-oscillatory activity in response to auditory steady-state stimulation. METHODS: Fifty-one subjects were included: 13 with Dravet syndrome with SCN1A gene alterations, 26 with non-Dravet epilepsies and 12 healthy controls. Responses to auditory steady-state stimulation elicited with a chirp-modulated tone between 1 and 120 Hz were collected in subjects and compared across groups. RESULTS: Subjects with Dravet syndrome showed weak or no responses in the 1-120 Hz frequency range. Healthy controls showed oscillatory responses following the frequency of the modulation that were maximal in the low (30-70 Hz) and high (80-120) γ-ranges both, in the power and inter-trial coherence estimates. Non-Dravet epileptic children showed differences in the auditory responses when compared with the healthy controls but were able to generate oscillatory evoked activities following the frequency-varying stimulation. CONCLUSIONS: The ability to generate brain γ-oscillatory activity of children with Dravet in response to a chirp-modulated auditory stimulus is highly impaired, is not due to epilepsy and is consistent with the Nav1.1 channel dysfunction affecting interneuron activity seen in Dravet mouse models. SIGNIFICANCE: The reported deficits in the brain oscillatory activity evoked by chirp modulated tones in children with Dravet is compatible with Dravet syndrome disease mechanisms and constitutes a potential biomarker for future disease-modifying interventions.

Continuous intraocular pressure monitoring in patients with obstructive sleep apnea syndrome using a contact lens sensor.

PURPOSE: To analyse nocturnal intraocular pressure (IOP) fluctuations in patients with obstructive sleep apnea syndrome (OSAS) using a contact lens sensor (CLS) and to identify associations between the OSAS parameters determined by polysomnographic study (PSG) and IOP changes. METHOD: Prospective, observational study. Twenty participants suspected of having OSAS were recruited. During PSG study, IOP was monitored using a CLS placed in the eye of the patient. The patients were classified according to the apnea-hypopnea index (AHI) in two categories, severe (>30) or mild/moderate (<30) OSAS. We evaluated several parameters determined by the IOP curves, including nocturnal elevations (acrophase) and plateau times in acrophase (PTs) defined by mathematical and visual methods. RESULTS: The IOP curves exhibited a nocturnal acrophase followed by PTs of varying extents at which the IOP remained higher than daytime measurement with small variations. We found significant differences in the length of the PTs in patients with severe OSAS compared to those with mild/moderate disease (P = 0.032/P = 0.028). We found a positive correlation between PTs and OSAS severity measured by the total number of apneic events (r = 0.681/0.751 P = 0.004/0.001) and AHI (r = 0.674/0.710, P = 0.004/0.002). Respiratory-related arousal and oxygen saturation also were associated significantly with the IOP PT length. CONCLUSIONS: Periods of nocturnal IOP elevation lasted longer in severe OSAS patients than those with mild/moderate OSAS and correlate with the severity of the disease. The length of the nocturnal PT is also associated to respiratory parameters altered in patients with OSAS.

Beta activity in the subthalamic nucleus during sleep in patients with Parkinson's disease.

The recordings of local field potentials in the subthalamic nucleus in patients with Parkinson's disease (PD), carried out through the stimulators implanted to treat the motor symptoms of the disease, show a prominent basal ("off") activity in the beta range, which is attenuated after dopaminergic therapy. A recent study described improvement of parkinsonian features during rapid eyes movements (REM) sleep. We describe, for the first time, the changes in activity of the subthlamic nucleus (STN) during different sleep stages in Parkinson's disease with special interest in the beta band. Ten patients with PD treated with deep brain stimulation of the STN were studied. Subthalamic local field potentials (LFPs) were recorded through the stimulation electrodes during wakefulness ("off" medication) and different sleep stages. In Stage 2 and slow-wave sleep, a significant decrease of beta activity was recorded. During REM sleep, beta power values were similar to wakefulness values or even higher. These findings indicate that STN activity is modulated and modified during different sleep stages. The increased beta activity during REM sleep is a new but unexpected finding, which requires further analysis.

Late-onset periodic asystolia during vagus nerve stimulation.

Cardiac changes may occasionally occur during vagus nerve stimulation (VNS) used in epileptic patients. As they can be potentially life-threatening, it is important to detect them, and this is why an intraoperative test is performed during the implantation. Few cases of asystole during this test have been described. Only one patient with late-onset bradyarrythmia caused by VNS has been reported. This patient had been implanted 2 years and 4 months before the episode. We present another case of late asystole in a patient whose VNS had been implanted 9 years before the arrhythmia onset. In our patient, each run of stimulation produced bradyarrhythmias and very often severe asystolia due to atrium-ventricular block.

Interictal high-frequency oscillations (100-500 Hz) in the intracerebral EEG of epileptic patients.

Interictal fast oscillations between 100 and 500 Hz have been reported in signals recorded from implanted microelectrodes in epileptic patients and experimental rat models. Oscillations between 250 and 500 Hz, or fast ripples (FR), appeared related to the epileptic focus whereas ripples (80-200 Hz) were not. We report high-frequency oscillations recorded with intracranial macroelectrodes in seven patients with refractory focal epilepsy during slow-wave sleep. We characterize the relation of fast oscillations to the seizure focus and quantify their concordance with epileptiform transients, with which they are strongly associated. The patients were selected because interictal spikes were found within and outside the seizure onset zone. Visual inspection was used to identify and classify the ripples and FRs according to their relation to epileptiform spikes. Continuous-time wavelet analysis was used to compute their power. Ripples were present in all patients while FRs where found in five of the seven patients. Most ripples and FRs occurred at the same time as epileptiform transients. The rate of occurrence of ripples was higher within the seizure onset zone than outside in four of seven patients. The rate of FRs was much higher within the seizure onset zone than outside in four of the five patients with FRs (in these four patients, FRs were almost inexistent outside the seizure onset zone). The power of ripples and FRs tended to be higher in the electrodes where their rate was also higher. These results indicate that FRs were more restricted to the electrodes located within the seizure onset zone, especially to the hippocampus, than ripples. In only one patient, FRs were more frequent outside the seizure onset zone; this patient was the only one with cortical dysplasia and the electrode with a high rate of FRs was inside the lesion. This study demonstrates that interictal ripples and FRs can be recorded with depth macroelectrodes in patients. Most occur at the time of epileptiform spikes but some are isolated. Ripples do not show a clear differentiation between the seizure onset zone and remote areas, whereas FRs have a higher rate and higher power in the seizure onset zone. Our results also suggest a special capacity of the abnormal hippocampus to generate FRs, although they were also recorded in other structures.

Hypoglossal nerve stimulation surgery for obstructive sleep apnoea: Our preliminary experience. / Cirugía de implante de estimulador de nervio hipogloso en el síndrome de apnea obstructiva del sueño: nuestra experiencia preliminar.

The objective of this communication is to describe our preliminary results in upper airway stimulation surgery via hypoglossal nerve stimulation implantation for obstructive sleep apnoea. We describe 4 cases and the outcomes of the surgery were analysed using the Epworth scale, apnoea-hypopnoea index, minimal O2 Sat, average O2 Sat and snoring intensity. In all cases a significant reduction in Epworth scale values and apnoea-hypopnoea index were obtained (P<.05). The minimum and average oxygen saturation had better values after the surgery, however, there was no statistically significant difference. The snoring severity measured subjectively changed from «intense¼ to «absent¼ in all cases. The preliminary results obtained with the upper airway stimulation surgery via hypoglossal nerve stimulation showed objective and subjective improvement after the implant activation.

Independent component analysis separates spikes of different origin in the EEG.

Independent component analysis (ICA) is a novel system that finds independent sources in recorded signals. Its usefulness in separating epileptiform activity of different origin has not been determined. The goal of this study was to demonstrate that ICA is useful for separating different spikes using samples of EEG of patients with focal epilepsy. Digital EEG samples from four patients with focal epilepsy were included. The patients had temporal (n = 2), centrotemporal (n = 1) or frontal spikes (n = 1). Twenty-six samples with two (or more) spikes from two different patients were created. The selection of the two spikes for each mixed EEG was performed randomly, trying to have all the different combinations and rejecting the mixture of two spikes from the same patient. Two different examiners studied the EEGs using ICA with JADE paradigm in Matlab platform, trying to separate and to identify the spikes. They agreed in the correct separation of the spikes in 24 of the 26 samples, classifying the spikes as frontal, temporal or centrotemporal, left or right sided. The demonstration of the possibility of detecting different artificially mixed spikes confirms that ICA may be useful in separating spikes or other elements in real EEGs.

Independent component analysis in the study of focal seizures.

Independent component analysis (ICA) is a novel technique that can separate statistically independent elements from complex signals. It has demonstrated its utility in separating artifacts and analyzing interictal discharges in EEG. ICA has been used recently in ictal recordings, showing the possibility of isolating the ictal activity. The goal of our study was to analyze focal seizures with ICA, decomposing the elements of the seizures to understand their genesis and propagation, and to differentiate between various types of focal seizures. We studied 26 focal seizures of temporal, frontal, or parietal origin. Only seizures with suspected focal onset were included in the study. The EEG recordings were acquired by using standard video-EEG equipment, with scalp electrodes. All the off-line analysis was carried out on a PC by means of specific software developed in the Matlab environment. ICA components were calculated with the use of the JADE (Joint Approximate Diagonalization of Eigen-matrices) algorithm. The decomposition of the seizures varied according to the EEG seizure pattern. In the seizures with focal rhythmic theta slow or sharp waves, the rhythmic activity was separated into one to five components, having an initial component with a clear concordance with the focus, whereas the others had an onset a few milliseconds later and corresponded to neighboring areas. In the 6 frontal seizures with regional rhythmic low voltage fast activity, 4 to 10 components were found, practically with a simultaneous timing, having a frontal distribution. In the three frontal seizures with a diffuse attenuation of the EEG signal, it was not possible to differentiate components of cerebral origin from the components of muscle artifact. ICA is an interesting tool to study the nature of focal seizures. The results depend on the EEG pattern. In the seizures with a clear EEG focal pattern, ICA may be useful to separate components of the ictal onset from the propagated activity.

Sleep-related laryngospasm: a video-polysomnographic recording.

We present a case of laryngospasm in a 12-year-old male who experienced sudden, nocturnal episodes of breathing difficulties and agitation. Apart from laryngospasm, the main differential diagnoses included frontal seizures, sleep-related choking syndrome, sleep asthma, sleep apnoea and REM sleep behaviour disorder. The video and the EEG recordings supported the diagnosis of laryngospasm. The pH-metry confirmed the existence of reflux. Its treatment successfully controlled the episodes. This case illustrates, with a typical video recording, this infrequent type of paroxysmal event with an important differential diagnosis.[Published with video sequences].

Clinical management of sleep disturbances in Alzheimer's disease: current and emerging strategies.

Sleep and circadian disorders in Alzheimer's disease (AD) are more frequent than in the general population and appear early in the course of the disease. Quality of sleep and quality of life are parallel in these patients, and such disorders also represent a heavy burden for caregivers. Although alterations in melatonin and hypocretins (orexins) seem to play a key role in the origin of these disturbances, the etiology of these disorders is multifactorial, including many factors such as environment, behavior, treatments, and comorbidities, among others. A comprehensive evaluation of sleep in each patient is essential in the design of the treatment that includes nonpharmacological and pharmacological approaches. One particularly interesting point is the possibility of a role of sleep disorders in the pathogenesis of AD, raising the possibility that treating the sleep disorder may alter the course of the disease. In this review, we present an update on the role of sleep disorders in AD, the bidirectional influence of sleep problems and AD, and treatment options. Behavioral measures, bright light therapy (BLT), melatonin, and other drugs are likely well known and correctly managed by the physicians in charge of these patients. In spite of the multiple treatments used, evidence of efficacy is scarce and more randomized double-blind placebo-controlled studies are needed. Future directions for treatment are the establishment of BLT protocols and the development of drugs with new mechanisms of action, especially hypocretin receptor antagonists, melatonin receptor agonists, and molecules that modulate the circadian clock.