Timing matters for accurate identification of the epileptogenic zone.

OBJECTIVE: Interictal biomarkers of the epileptogenic zone (EZ) and their use in machine learning models open promising avenues for improvement of epilepsy surgery evaluation. Currently, most studies restrict their analysis to short segments of intracranial EEG (iEEG). METHODS: We used 2381 hours of iEEG data from 25 patients to systematically select 5-minute segments across various interictal conditions. Then, we tested machine learning models for EZ localization using iEEG features calculated within these individual segments or across them and evaluated the performance by the area under the precision-recall curve (PRAUC). RESULTS: On average, models achieved a score of 0.421 (the result of the chance classifier was 0.062). However, the PRAUC varied significantly across the segments (0.323-0.493). Overall, NREM sleep achieved the highest scores, with the best results of 0.493 in N2. When using data from all segments, the model performed significantly better than single segments, except NREM sleep segments. CONCLUSIONS: The model based on a short segment of iEEG recording can achieve similar results as a model based on prolonged recordings. The analyzed segment should, however, be carefully and systematically selected, preferably from NREM sleep. SIGNIFICANCE: Random selection of short iEEG segments may give rise to inaccurate localization of the EZ.

Hippocampal barques and their manifestation as 14&6 Hz positive spikes during sleep.

OBJECTIVE: This study investigates variations in hippocampal barque occurrence during sleep and compares findings to respective variations of their scalp manifestation as 14&6/sec positive spikes. METHODS: From 11 epilepsy patients, 12 non-epileptogenic hippocampi with barques were identified for this study. Using the first seizure-free whole-night sleep stereo-encephalography (sEEG) recording, we performed sleep staging and measured the occurrence of barques and 14&6/sec positive spikes variants. RESULTS: Hippocampal barques (total count: 9,183; mean count per record: 765.2 ± 251.2) occurred predominantly during non-rapid eye movement (NREM) II sleep (total: 5,744; mean: 478.6 ± 176.1; 62.2 ± 6.0%) and slow-wave sleep (SWS) (total: 2,950; mean: 245.83 ± 92.9; 32.0 ± 6.2%), with rare to occasional occurrence in NREM I (total: 85; mean: 7.0 ± 2.8; 0.9 ± 0.4%), rapid eye movement (REM) (total: 153; mean: 12.75 ± 4.0; 1.7 ± 0.6) and wakefulness (total: 251; mean: 20.9 ± 6.3; 2.9 ± 0.9%). Barque rate increased during SWS (mean: 2.7 ± 1.0 per min) compared to NREM II (2.2 ± 1.0 per min) and other states (wakefulness: 0.1 ± 0.0 per min; NREM I: 0.3 ± 0.1 per min; REM: 0.1 ± 0.0 per min). The 14&6/sec positive spikes variant (total count: 2,406; mean: 343.7 ± 106.7) was present in NREM II (total: 2,059; mean: 249.1 ± 100.2, 84.9 ± 3.6%) and SWS (total: 347; mean: 49.5 ± 12.8, 15.0 ± 3.6%) stages, and absent from the rest of sleep and wakefulness. While all 14&6/sec positive spikes correlated with barques, only 44.7 ± 6.1% of barques manifested as 14&6/sec positive spikes. CONCLUSIONS: Hippocampal barques are predominant in NREM II and SWS, and tend to increase their presence during SWS. Their scalp manifestation as 14&6/sec positive spikes is confounded by wakefulness, REM and NREM I stages, and "masked" by the co-occurrence of NREM II and SWS slow waves, and overlapping reactive micro-arousal elements. SIGNIFICANCE: Our study highlighted the overnight profile of hippocampal barques, in relation to the respective profile of their scalp manifestation, the 14&6/sec positive spikes variant.

Muscle injury induces an increase in total and non-rapid eye movement sleep time.

STUDY OBJECTIVES: This study describes macro- and micro-sleep responses to a myotoxic skeletal muscle injury and investigates possible mechanisms. METHODS: We recorded the electroencephalogram (EEG)/electromyogram (EMG) of 24 Wistar rats before and after induction of tibialis anterior muscle injury (n = 8 per group: control, control + buprenorphine and injured). A top-down analysis of sleep characteristics was processed from total sleep time (TST), sleep stages, sleep stability, spectral analysis, and spindles. To further investigate the mechanisms involved, we analyzed the protein level of sleep regulatory molecules including tumor necrosis factor- α (TNF-α), interleukin-1ß (IL-1ß), insulin-like growth factor-1 (IGF-1), and brain and muscle ARNT-like 1 (BMAL1) in plasma, frontal cortex, hippocampus, and tibialis anterior, collected at day +2 after injury from non-EEG/EMG implanted rats. RESULTS: Muscle injury induces a significant increase in TST at 48 and 72 h post-injury, specific to non-rapid eye movement (NREM) sleep. These increases occur during the dark period and are associated with the higher stability of sleep over 24 h, without change in the different power/frequency spectral bands of NREM/REM sleep. There was no corresponding sleep increase in slow-wave activity or spindle density, nor were there changes in brain levels of the sleep-regulating proinflammatory cytokine IL-1ß, which is otherwise involved in the local response to injury. Conversely, decreased protein levels of brain IGF-1 and muscle BMAL1, a core circadian clock gene, after injury may play a role in increased sleep time. CONCLUSION: Muscle injury induces an increase in total sleep time at 48- and 72-h post-injury, specific to NREM sleep during the dark period in rats and is associated with higher sleep stability over 24 h.

Pediatric sleep apnea: Characterization of apneic events and sleep stages using heart rate variability.

Heart rate variability (HRV) is modulated by sleep stages and apneic events. Previous studies in children compared classical HRV parameters during sleep stages between obstructive sleep apnea (OSA) and controls. However, HRV-based characterization incorporating both sleep stages and apneic events has not been conducted. Furthermore, recently proposed novel HRV OSA-specific parameters have not been evaluated. Therefore, the aim of this study was to characterize and compare classic and pediatric OSA-specific HRV parameters while including both sleep stages and apneic events. A total of 1610 electrocardiograms from the Childhood Adenotonsillectomy Trial (CHAT) database were split into 10-min segments to extract HRV parameters. Segments were characterized and grouped by sleep stage (wake, W; non-rapid eye movement, NREMS; and REMS) and presence of apneic events (under 1 apneic event per segment, e/s; 1-5 e/s; 5-10 e/s; and over 10 e/s). NREMS showed significant changes in HRV parameters as apneic event frequency increased, which were less marked in REMS. In both NREMS and REMS, power in BW2, a pediatric OSA-specific frequency domain, allowed for the optimal differentiation among segments. Moreover, in the absence of apneic events, another defined band, BWRes, resulted in best differentiation between sleep stages. The clinical usefulness of segment-based HRV characterization was then confirmed by two ensemble-learning models aimed at estimating apnea-hypopnea index and classifying sleep stages, respectively. We surmise that basal sympathetic activity during REMS may mask apneic events-induced sympathetic excitation, thus highlighting the importance of incorporating sleep stages as well as apneic events when evaluating HRV in pediatric OSA.

Sleep-Wake Neurochemistry.

Behavioral states naturally alternate between wakefulness and the sleep phases rapid eye movement and nonrapid eye movement sleep. Waking and sleep states are complex processes that are elegantly orchestrated by spatially fine-tuned neurochemical changes of neurotransmitters and neuromodulators including glutamate, acetylcholine, γ-aminobutyric acid, norepinephrine, dopamine, serotonin, histamine, hypocretin, melanin concentrating hormone, adenosine, and melatonin. However, as highlighted in this brief overview, no single neurotransmitter or neuromodulator, but rather their complex interactions within organized neuronal ensembles, regulate waking and sleep states. The neurochemical pathways presented here are aimed to provide a conceptual framework for the understanding of the effects of currently used sleep medications.

Night Photostimulation of Clearance of Beta-Amyloid from Mouse Brain: New Strategies in Preventing Alzheimer's Disease.

The deposition of amyloid-ß (Aß) in the brain is a risk factor for Alzheimer's disease (AD). Therefore, new strategies for the stimulation of Aß clearance from the brain can be useful in preventing AD. Transcranial photostimulation (PS) is considered a promising method for AD therapy. In our previous studies, we clearly demonstrated the PS-mediated stimulation of lymphatic clearing functions, including Aß removal from the brain. There is increasing evidence that sleep plays an important role in Aß clearance. Here, we tested our hypothesis that PS at night can stimulate Aß clearance from the brain more effectively than PS during the day. Our results on healthy mice show that Aß clearance from the brain occurs faster at night than during wakefulness. The PS course at night improves memory and reduces Aß accumulation in the brain of AD mice more effectively than the PS course during the day. Our results suggest that night PS is a more promising candidate as an effective method in preventing AD than daytime PS. These data are an important informative platform for the development of new noninvasive and nonpharmacological technologies for AD therapy as well as for preventing Aß accumulation in the brain of people with disorder of Aß metabolism, sleep deficit, elderly age, and jet lag.

Protocol for recording the discharge of locus coeruleus neurons in free-moving mice during different sleep-wake stages.

Cortical electroencephalography (EEG) is generally used to detect the different sleep-wake states of animals. EEG combined with in vivo multichannel recording provides a powerful tool for decoding the neural network of sleep-wake regulation. Here, we detail a protocol using cortical EEG combined with in vivo multichannel recording to examine the activity of locus coeruleus (LC) neurons in free-moving mice at different sleep-wake stages. The procedures for electrode fabrication, the surgery to implant electrodes, and post-recording data analysis are also included. For complete details on the use and execution of this protocol, please refer to Liang et al. (2021).

Monitoring of Anesthesia by Bispectral Analysis of EEG Signals.

BACKGROUND: In intensive care, monitoring the depth of anesthesia during surgical procedures is a key element in the success of the medical operation and postoperative recovery. However, despite the development of anesthesia thanks to technological and pharmacological advances, its side effects such as underdose or overdose of hypnotics remain a major problem. Observation and monitoring must combine clinical observations (loss of consciousness and reactivity) with tools for real-time measurement of changes in the depth of anesthesia. Methodology. In this work, we will develop a noninvasive method for calculating, monitoring, and controlling the depth of general anesthesia during surgery. The objective is to reduce the effects of pharmacological usage of hypnotics and to ensure better quality recovery. Thanks to the overall activity of sets of neurons in the brain, we have developed a BIS technique based on bispectral analysis of the electroencephalographic signal EEG. Discussion. By collecting the electrical voltages from the brain, we distinguish light sleep from deep sleep according to the values of the BIS indicator (ranging from 0 : sleep to 100 : wake) and also control it by acting on the dosage of propofol and sevoflurane. We showed that the BIS value must be maintained during the operation and the anesthesia at a value greater than 60. CONCLUSION: This study showed that the BIS technology led to an optimization of the anesthetic management, the adequacy of the hypnotic dosage, and a better postoperative recovery.

Altered EEG markers of synaptic plasticity in a human model of NMDA receptor deficiency: Anti-NMDA receptor encephalitis.

Plasticity of synaptic strength and density is a vital mechanism enabling memory consolidation, learning, and neurodevelopment. It is strongly dependent on the intact function of N-Methyl-d-Aspartate Receptors (NMDAR). The importance of NMDAR is further evident as their dysfunction is involved in many diseases such as schizophrenia, Alzheimer's disease, neurodevelopmental disorders, and epilepsies. Synaptic plasticity is thought to be reflected by changes of sleep slow wave slopes across the night, namely higher slopes after wakefulness at the beginning of sleep than after a night of sleep. Hence, a functional NMDAR deficiency should theoretically lead to altered overnight changes of slow wave slopes. Here we investigated whether pediatric patients with anti-NMDAR encephalitis, being a very rare but unique human model of NMDAR deficiency due to autoantibodies against receptor subunits, indeed show alterations in this sleep EEG marker for synaptic plasticity. We retrospectively analyzed 12 whole-night EEGs of 9 patients (age 4.3-20.8 years, 7 females) and compared them to a control group of 45 healthy individuals with the same age distribution. Slow wave slopes were calculated for the first and last hour of Non-Rapid Eye Movement (NREM) sleep (factor 'hour') for patients and controls (factor 'group'). There was a significant interaction between 'hour' and 'group' (p = 0.013), with patients showing a smaller overnight decrease of slow wave slopes than controls. Moreover, we found smaller slopes during the first hour in patients (p = 0.022), whereas there was no group difference during the last hour of NREM sleep (p = 0.980). Importantly, the distribution of sleep stages was not different between the groups, and in our main analyses of patients without severe disturbance of sleep architecture, neither was the incidence of slow waves. These possible confounders could therefore not account for the differences in the slow wave slope values, which we also saw in the analysis of the whole sample of EEGs. These results suggest that quantitative EEG analysis of slow wave characteristics may reveal impaired synaptic plasticity in patients with anti-NMDAR encephalitis, a human model of functional NMDAR deficiency. Thus, in the future, the changes of sleep slow wave slopes may contribute to the development of electrophysiological biomarkers of functional NMDAR deficiency and synaptic plasticity in general.

Chronic Toxoplasma gondii infection and sleep-wake alterations in mice.

AIM: Toxoplasma gondii (Tg) is an intracellular parasite infecting more than a third of the human population. Yet, the impact of Tg infection on sleep, a highly sensitive index of brain functions, remains unknown. We designed an experimental mouse model of chronic Tg infection to assess the effects on sleep-wake states. METHODS: Mice were infected using cysts of the type II Prugniaud strain. We performed chronic sleep-wake recordings and monitoring as well as EEG power spectral density analysis in order to assess the quantitative and qualitative changes of sleep-wake states. Pharmacological approach was combined to evaluate the direct impact of the infection and inflammation caused by Tg. RESULTS: Infected mouse exhibited chronic sleep-wake alterations over months, characterized by a marked increase (>20%) in time spent awake and in cortical EEG θ power density of all sleep-wake states. Meanwhile, slow-wave sleep decreased significantly. These effects were alleviated by an anti-inflammatory treatment using corticosteroid dexamethasone. CONCLUSION: We demonstrated for the first time the direct consequences of Tg infection on sleep-wake states. The persistently increased wakefulness and reduced sleep fit with the parasite's strategy to enhance dissemination through host predation and are of significance in understanding the neurodegenerative and neuropsychiatric disorders reported in infected patients.

Paradoxical anesthesia: Sleep-like EEG during anesthesia induced by mesopontine microinjection of GABAergic agents.

General anesthetic agents are thought to induce loss-of-consciousness (LOC) and enable pain-free surgery by acting on the endogenous brain circuitry responsible for sleep-wake cycling. In clinical use, the entire CNS is exposed to anesthetic molecules with LOC and amnesia usually attributed to synaptic suppression in the cerebral cortex and immobility and analgesia to agent action in the spinal cord and brainstem. This model of patch-wise suppression has been challenged, however, by the observation that all functional components of anesthesia can be induced by focal delivery of minute quantities of GABAergic agonists to the brainstem mesopontine tegmental anesthesia area (MPTA). We compared spectral features of the cortical electroencephalogram (EEG) in rats during systemic anesthesia and anesthesia induced by MPTA microinjection. Systemic administration of (GABAergic) pentobarbital yielded the sustained, δ-band dominant EEG signature familiar in clinical anesthesia. In contrast, anesthesia induced by MPTA microinjection (pentobarbital or muscimol) featured epochs of δ-band EEG alternating with the wake-like EEG, the pattern typical of natural non-rapid-eye-movement (NREM) and REM sleep. The rats were not sleeping, however, as they remained immobile, atonic and unresponsive to noxious pinch. Recalling the paradoxical wake-like quality the EEG during REM sleep, we refer to this state as "paradoxical anesthesia". GABAergic anesthetics appear to co-opt both cortical and spinal components of the sleep network via dedicated axonal pathways driven by MPTA neurons. Direct drug exposure of cortical and spinal neurons is not necessary, and is probably responsible for off-target side-effects of systemic administration including monotonous δ-band EEG, hypothermia and respiratory depression. SIGNIFICANCE STATEMENT: The concept that GABAergic general anesthetic agents induce loss-of-consciousness by substituting for an endogenous neurotransmitter, thereby co-opting neural circuitry responsible for sleep-wake transitions, has gained considerable traction. However, the electroencephalographic (EEG) signatures of sleep and anesthesia differ fundamentally. We show that when the anesthetic state is generated by focal delivery of GABAergics into the mesopontine tegmental anesthesia area (MPTA) the resulting EEG repeatedly transitions between delta-wave-dominant and wake-like patterns much as in REM-NREM sleep. This suggests that systemic (clinical) anesthetic delivery, which indiscriminately floods the entire cerebrum with powerful inhibitory agents, obscures the sleep-like EEG signature associated with the less adulterated form of anesthesia obtained when the drugs are applied selectively to loci where the effective neurotransmitter substitution actually occurs.

Substantia Nigra Abnormalities Provide New Insight on the Neural Mechanisms Underlying the Sleep-Arousal Phase Dysfunctions in Sudden Infant Death Syndrome.

The purpose of this study was to research possible developmental alterations of the substantia nigra (SN) in sudden infant death syndrome (SIDS), a syndrome frequently attributed to arousal failure from sleep. Brain stems of 46 victims of sudden infant death, aged from 1 to about 7 months (4 to 30 postnatal weeks), were investigated. Twenty-six of these cases were diagnosed as SIDS, due to the lack of any pathological finding, while the remaining 20 cases in which the cause of death was determined at autopsy served as controls. Maternal smoking was reported in 77% of SIDS and 10% of controls. Histopathological examination of the SN was done on 5-µm-thick sections of caudal midbrain stained with both hematoxylin-eosin and Klüver-Barrera. Densitometry, immunohistochemistry and histochemistry were applied to highlight the neuronal concentration, the tyrosine hydroxylase (TH) expression, and the presence of neuromelanin (NM) in this structure. Hypoplasia of the pars compacta portion of the SN was observed in 69% of SIDS but never in controls; TH expression was significantly higher in controls than in SIDS; and NM was observed only in 4 infants of the control group but not in SIDS. A significant correlation was found between SIDS, hypoplasia/low neuronal density, low TH expression in the pars compacta, and maternal smoking. Because the SN pars compacta, being the major dopamine brain center, controls many functions, including the sleep-arousal phase, its alterations, especially concurrently with smoking exposure, may contribute to explain the pathogenesis of SIDS that occur in the great part of cases at awakening from sleep.

The retinoid X receptor: a nuclear receptor that modulates the sleep-wake cycle in rats.

RATIONALE: The nuclear receptor retinoid X receptor (RXR) belongs to a nuclear receptor superfamily that modulates diverse functions via homodimerization with itself or several other nuclear receptors, including PPARα. While the activation of PPARα by natural or synthetic agonists regulates the sleep-wake cycle, the role of RXR in the sleep modulation is unknown. OBJECTIVES: We investigated the effects of bexarotene (Bexa, a RXR agonist) or UVI 3003 (UVI, a RXR antagonist) on sleep, sleep homeostasis, levels of neurochemical related to sleep modulation, and c-Fos and NeuN expression. METHODS: The sleep-wake cycle and sleep homeostasis were analyzed after application of Bexa or UVI. Moreover, we also evaluated whether Bexa or UVI could induce effects on dopamine, serotonin, norepinephrine epinephrine, adenosine, and acetylcholine contents, collected from either the nucleus accumbens or basal forebrain. In addition, c-Fos and NeuN expression in the hypothalamus was determined after Bexa or UVI treatments. RESULTS: Systemic application of Bexa (1 mM, i.p.) attenuated slow-wave sleep and rapid eye movement sleep. In addition, Bexa increased the levels of dopamine, serotonin, norepinephrine epinephrine, adenosine, and acetylcholine sampled from either the nucleus accumbens or basal forebrain. Moreover, Bexa blocked the sleep rebound period after total sleep deprivation, increased in the hypothalamus the expression of c-Fos, and decreased NeuN activity. Remarkably, UVI 3003 (1 mM, i.p.) induced opposite effects in sleep, sleep homeostasis, neurochemicals levels, and c-Fos and NeuN activity. CONCLUSIONS: The administration of RXR agonist or antagonist significantly impaired the sleep-wake cycle and exerted effects on the levels of neurochemicals related to sleep modulation. Moreover, Bexa or UVI administration significantly affected c-Fos and NeuN expression in the hypothalamus. Our findings highlight the neurobiological role of RXR on sleep modulation.

NREM sleep is the state of vigilance that best identifies the epileptogenic zone in the interictal electroencephalogram.

OBJECTIVE: Interictal epileptiform anomalies such as epileptiform discharges or high-frequency oscillations show marked variations across the sleep-wake cycle. This study investigates which state of vigilance is the best to localize the epileptogenic zone (EZ) in interictal intracranial electroencephalography (EEG). METHODS: Thirty patients with drug-resistant epilepsy undergoing stereo-EEG (SEEG)/sleep recording and subsequent open surgery were included; 13 patients (43.3%) had good surgical outcome (Engel class I). Sleep was scored following standard criteria. Multiple features based on the interictal EEG (interictal epileptiform discharges, high-frequency oscillations, univariate and bivariate features) were used to train a support vector machine (SVM) model to classify SEEG contacts placed in the EZ. The performance of the algorithm was evaluated by the mean area under the receiver-operating characteristic (ROC) curves (AUCs) and positive predictive values (PPVs) across 10-minute sections of wake, non-rapid eye movement sleep (NREM) stages N2 and N3, REM sleep, and their combination. RESULTS: Highest AUCs were achieved in NREM sleep stages N2 and N3 compared to wakefulness and REM (P < .01). There was no improvement when using a combination of all four states (P > .05); the best performing features in the combined state were selected from NREM sleep. There were differences between good (Engel I) and poor (Engel II-IV) outcomes in PPV (P < .05) and AUC (P < .01) across all states. The SVM multifeature approach outperformed spikes and high-frequency oscillations (P < .01) and resulted in results similar to those of the seizure-onset zone (SOZ; P > .05). SIGNIFICANCE: Sleep improves the localization of the EZ with best identification obtained in NREM sleep stages N2 and N3. Results based on the multifeature classification in 10 minutes of NREM sleep were not different from the results achieved by the SOZ based on 12.7 days of seizure monitoring. This finding might ultimately result in a more time-efficient intracranial presurgical investigation of focal epilepsy.

Aging effect on sleepiness and apneas severity in patients with obstructive sleep apnea syndrome: a meta-analysis study.

PURPOSE: Different authors have reported that aging could be associated with changes in obstructive sleep apnea (OSA) related parameters (apnea/hypopnea index, SpO2, reduction of daytime sleepiness, etc.), type of sleep and pattern of collapse. Regarding OSA severity in elderly patients, it is commonly believed that the AHI score tends to increase with aging. METHODS: In this paper, we reviewed the literature regarding the studies which compared older (> 65 years old) and young (< 65 years old) OSA patients regarding the effect of aging on daytime sleepiness (ESS evaluation) and OSA severity (AHI evaluation). A meta-analysis to evaluate the effect of age on daytime sleepiness and OSAS severity was also performed to corroborate previously reported experience. RESULTS: Meta-analysis showed no statistical (p = 0.8) differences regarding AHI differences emerged from the comparison of the two groups of patients. Elderly patients (> 65 years old) showed less daytime sleepiness, showing a statistical difference in the meta-analysis of data (p = 0.004) CONCLUSION: Although a direct correlation between aging and AHI values would seem to be present, no significant differences in baseline AHI between young (< 65-years-old) and elderly (> 65-years-old) patients emerged in this meta-analysis study. The effects of OSAS on daytime sleepiness seem to be much more prominent in young or middle-aged patients than in elderly patients.

Obstructive sleep apnea and Parkinson's disease: characteristics and associated factors / Apneia obstrutiva do sono e doença de Parkinson: características e fatores relacionados

ABSTRACT Obstructive sleep apnea (OSA) occurs in up to 66% of Parkinson's disease (PD) patients, higher than in the general population. Although it is more prevalent, the relationship between OSA and PD remains controversial, with some studies confirming and others denying the relationship of OSA with some risk factors and symptoms in patients with PD. Objective: To determine the factors associated with OSA in PD patients com DP. Methods: A cross-sectional study was performed with 88 consecutive patients with PD from the outpatient clinic. Participants underwent clinical interviews with neurologists and a psychiatrist, assessment using standardized scales (Epworth Sleepiness Scale, Parkinson's Disease Questionnaire, Pittsburgh Sleep Quality Index and, for individuals with a diagnosis of restless legs syndrome/Willis-Ekbom disease, the International Restless Legs Syndrome Rating Scale), and video-polysomnography. Results: Individuals with PD and OSA were older and had less insomnia than those with PD without OSA. Regarding the polysomnographic variables, we observed a lower percentage of stage N3 sleep, a higher arousal index, and a higher oxygen desaturation index in those individuals with OSA, relative to those without OSA. In the multivariate analysis, only the percentage of stage N3 sleep and the oxygen desaturation index were significantly different. Besides this, most of the PD patients with OSA had a correlation with sleeping in the supine position (58% of OSA individuals). Conclusion: The PD patients showed a high prevalence of OSA, with the supine position exerting a significant influence on the OSA in these patients, and some factors that are associated with OSA in the general population did not seem to have a greater impact on PD patients.

RESUMO A Apneia Obstrutiva do Sono (AOS) chega a acometer até 66% dos pacientes com doença de Parkinson (DP), prevalência maior, portanto, que a da população geral. Embora seja mais prevalente, a relação entre AOS e DP permanence controversa, com trabalhos confirmando e outros afastando a relação de AOS com alguns fatores de risco e sintomas em pacientes com DP. Objetivo: Determinar quais fatores estão relacionados à AOS em pacientes com DP. Métodos: Estudo transversal, observacional, realizado com 88 pacientes com DP, provenientes do ambulatório de hospital público. Os pacientes foram submetidos à entrevista clínica com neurologista e psiquiatra, à aplicação de escalas padronizadas (escala de sonolência de Epworth, questionário de qualidade de vida da DP, índice de qualidade de sono de Pittsburgh e, para os indivíduos com diagnóstico de Síndrome das Pernas Inquietas, a escala internacional de graduação da SPI), e vídeo-polissonografia. Resultados: Indivíduos com DP e AOS apresentaram maior idade e menor prevalência de insônia crônica que os indivíduos com DP, sem AOS. Em relação às variáveis polissonográficas, observamos uma baixa proporção de sono N3, elevado índice de microdespertares e maior índice de desaturações nos indivíduos com AOS, em comparação ao grupo sem AOS. Na análise multivariada, apenas a porcentagem de sono N3 e o índice de dessaturação permaneceu significativo. Além disso, a maior parte dos pacientes tem relação com a posição supina (58% dos pacientes com AOS). Conclusão: Pacientes com DP apresentaram prevalência elevada de AOS, a posição supina exerceu influência importante na AOS destes pacientes e alguns fatores que estão associados à AOS na população geral não mostraram impacto significativo nos pacientes com DP.

Sleep-wake physiology.

This chapter presents hypotheses on the mechanisms responsible for the succession of the three vigilance states, namely waking, nonrapid eye movement (non-REM) (slow-wave sleep-SWS), and REM sleep (paradoxical sleep-PS). It can be proposed that waking is induced by the activity of multiple waking systems, including the serotonergic, noradrenergic, cholinergic, and hypocretin systems. At the onset of sleep, the SWS-active neurons are activated by the circadian clock localized in the suprachiasmatic nucleus and a hypnogenic factor, adenosine, which progressively accumulates in the brain during waking. A number of studies support the hypothesis that SWS results from the activation of GABAergic neurons localized in the ventrolateral preoptic nucleus. However, additional GABAergic systems have been described, localized in the parafacial, accumbens, and reticular thalamic nuclei, and these are also presented. In addition, the chapter discusses the fact that a large body of data strongly suggests that the switch from SWS to PS is due to the interaction of multiple populations of glutamatergic and GABAergic neurons localized in the posterior hypothalamus and the brainstem.

Opioid use, pain intensity, age, and sleep architecture in patients with fibromyalgia and insomnia.

Opioid use and sleep disruption are prevalent in fibromyalgia. Yet, the effects of opioids on physiological sleep in fibromyalgia are unclear. This study assessed associations between opioid use/dosage and polysomnographically assessed sleep in patients with fibromyalgia and insomnia (FMI) and examined moderating effects of age and pain. Participants (N = 193, Mage = 51.7, SD = 11.8, range = 18-77) with FMI completed ambulatory polysomnography and 14 daily diaries. Multiple regression determined whether commonly prescribed oral opioid use or dosage (among users) independently predicted or interacted with age/pain intensity to predict sleep, controlling for sleep medication use and apnea hypopnea index. Opioid use predicted greater %stage 2 and lower %slow-wave sleep (%SWS). Opioid use interacted with age to predict greater sleep onset latency (SOL) in middle-aged/older adults. Among opioid users (n = 65, ∼3 years usage), opioid dose (measured in lowest recommended dosage) interacted with age to predict SOL and sleep efficiency; specifically, higher dosage predicted longer SOL and lower sleep efficiency for older, but not middle-aged/younger adults. Opioid dose interacted with pain to predict %SWS and arousal index. Specifically, higher dosage predicted reduced %SWS and higher arousal index for individuals with lower pain, increased %SWS for individuals with higher pain, and did not predict %SWS for patients with average pain. Opioid use/dosage did not predict wake after sleep onset, total sleep time, %stage 1 or %rapid eye movement sleep. Opioid use prompts changes in sleep architecture among individuals with FMI, increasing lighter sleep and reducing SWS. Sleep disruption is exacerbated at higher opioid doses in older adults and patients with low pain.

Sexsomnia in an Adolescent.

ABSTRACT: Sexsomnia has been reported and is well described in 115 prior cases in the literature. There have been associations with other sleep disorders serving as triggers for confusional arousals, thereby worsening sexsomnia episodes. We present a case of an adolescent boy with a history of resected and treated pineoblastoma who later developed sexsomnia marked by multiple episodes of masturbatory events per night. He had additional suspicions of obstructive sleep apnea. Polysomnography confirmed severe obstructive sleep apnea and captured multiple episodes of sexsomnia from both REM and NREM sleep. The patient also had daytime symptoms of severe anxiety and hypersomnia that required pharmacological intervention, cognitive behavioral techniques, and hypnosis. The patient showed improvement with hypnosis along with a multimodal approach to the treatment of sexsomnia.

c-Fos expression in the limbic thalamus following thermoregulatory and wake-sleep changes in the rat.

A cellular degeneration of two thalamic nuclei belonging to the "limbic thalamus", i.e., the anteroventral (AV) and mediodorsal (MD) nuclei, has been shown in patients suffering from Fatal Familial Insomnia (FFI), a lethal prion disease characterized by autonomic activation and severe insomnia. To better assess the physiological role of these nuclei in autonomic and sleep regulation, c-Fos expression was measured in rats during a prolonged exposure to low ambient temperature (Ta, - 10 °C) and in the first hours of the subsequent recovery period at normal laboratory Ta (25 °C). Under this protocol, the thermoregulatory and autonomic activation led to a tonic increase in waking and to a reciprocal depression in sleep occurrence, which was more evident for REM sleep. These effects were followed by a clear REM sleep rebound and by a rebound of Delta power during non-REM sleep in the following recovery period. In the anterior thalamic nuclei, c-Fos expression was (1) larger during the activity rather than the rest period in the baseline; (2) clamped at a level in-between the normal daily variation during cold exposure; (3) not significantly affected during the recovery period in comparison to the time-matched baseline. No significant changes were observed in either the MD or the paraventricular thalamic nucleus, which is also part of the limbic thalamus. The observed changes in the activity of the anterior thalamic nuclei appear, therefore, to be more specifically related to behavioral activation than to autonomic or sleep regulation.