Showing papers on "Rapid eye movement sleep published in 2005"

Clues to the functions of mammalian sleep

Abstract: The functions of mammalian sleep remain unclear. Most theories suggest a role for non-rapid eye movement (NREM) sleep in energy conservation and in nervous system recuperation. Theories of REM sleep have suggested a role for this state in periodic brain activation during sleep, in localized recuperative processes and in emotional regulation. Across mammals, the amount and nature of sleep are correlated with age, body size and ecological variables, such as whether the animals live in a terrestrial or an aquatic environment, their diet and the safety of their sleeping site. Sleep may be an efficient time for the completion of a number of functions, but variations in sleep expression indicate that these functions may differ across species.

Discharge of Identified Orexin/Hypocretin Neurons across the Sleep-Waking Cycle

Abstract: Although maintained by multiple arousal systems, wakefulness falters if orexin (hypocretin), orexin receptors, or orexin neurons are deficient; narcolepsy results with hypersomnolence or sudden onset of rapid eye movement sleep [or paradoxical sleep (PS)] and loss of muscle tonus. To learn how orexin neurons maintain wakefulness, we recorded neurons in head-fixed rats across the sleep-waking cycle and then labeled them with Neurobiotin to identify them by immunohistochemistry. We show that identified orexin neurons discharge during active waking, when postural muscle tone is high in association with movement, decrease discharge during quiet waking in absence of movement, and virtually cease firing during sleep, when postural muscle tone is low or absent. During PS, they remain relatively silent in association with postural muscle atonia and most often despite phasic muscular twitches. They increase firing before the end of PS and thereby herald by several seconds the return of waking and muscle tone. The orexin neurons would thus stimulate arousal, while antagonizing sleep and muscle atonia.

Antidepressants and sleep: a qualitative review of the literature.

Abstract: Most antidepressants change sleep; in particular, they alter the physiological patterns of sleep stages recorded overnight with EEG and other physiological measures. These effects are greatest and most consistent on rapid eye movement (REM) sleep, and tend to be in the opposite direction to the sleep abnormalities found in major depression, but are usually of greater degree. Reductions in the amount of REM sleep and increases in REM sleep onset latency are seen after taking antidepressants, both in healthy volunteers and in depressed patients. Antidepressants that increase serotonin function by blocking reuptake or by inhibiting metabolism have the greatest effect on REM sleep. The decrease in amount of REM sleep appears to be greatest early in treatment, and gradually diminishes during long-term treatment, except after monoamine oxidase inhibitors when REM sleep is often absent for many months. Sleep initiation and maintenance are also affected by antidepressants, but the effects are much less consistent between drugs. Some antidepressants such as clomipramine and the selective serotonin receptor inhibitors (SSRIs), particularly fluoxetine, are sleep-disturbing early in treatment and some others such as amitriptyline and the newer serotonin 5-HT2-receptor antagonists are sleep promoting. However, these effects are fairly short-lived and there are very few significant differences between drugs after a few weeks of treatment. In general, the objectively measured sleep of depressed patients improves during 3-4 weeks of effective antidepressant treatment with most agents, as does their subjective impression of their sleep. Sleep improvement earlier in treatment may be an important clinical goal in some patients, perhaps when insomnia is particularly distressing, or to ensure compliance. In these patients, the choice of a safely used and effective antidepressant which improves sleep in short term is indicated. Patients with other sleep disorders such as restless legs syndrome and REM sleep behaviour disorder should be identified before choosing a treatment, as some antidepressants worsen these conditions. Conversely, there is evidence that some antidepressants may be useful in the treatment of sleep disorders such as night terrors.

Characteristics of idiopathic REM sleep behavior disorder and that associated with MSA and PD

Abstract: Objective: To compare the clinical and video-polysomnographic (VPSG) characteristics of idiopathic REM sleep behavior disorder (RBD) vs the RBD seen in multiple system atrophy (MSA) and Parkinson disease (PD). Methods: Clinical features and VPSG measures were evaluated in 110 consecutive nondemented subjects (26 MSA, 45 PD, and 39 idiopathic RBD) free of psychoactive medications referred for suspected RBD to our sleep unit over a 5-year period, with extended follow-up (mean 26.9 ± 21.3 months). Results: Across the three groups studied, logistic regression analysis demonstrated that there were no differences in the quality of RBD symptoms (e.g., nature of unpleasant dream recall or behaviors witnessed by bed partners), most PSG variables, abnormal behaviors captured by VPSG, and clinical response to clonazepam. When compared to subjects with PD, however, patients with MSA had a significantly shorter duration of disease, a higher REM sleep without atonia percentage, a greater periodic leg movement index, and less total sleep time. Subjects with idiopathic RBD, as compared to those with either MSA or PD, were more often male, had greater self-reported clinical RBD severity, and were more often aware of their abnormal sleep behaviors. Conclusions: REM sleep behavior disorder (RBD)-related symptoms and neurophysiologic features are qualitatively similar in RBD subjects with the idiopathic form, multiple system atrophy (MSA), and Parkinson disease (PD). Polysomnographic abnormalities associated with RBD in the setting of MSA are greater than in PD, suggesting a more severe dysfunction in the structures that modulate REM sleep.

Insights from studying human sleep disorders

Abstract: Problems with sleep are one of the commonest reasons for seeking medical attention. Knowledge gained from basic research into sleep in animals has led to marked advances in the understanding of human sleep, with important diagnostic and therapeutic implications. At the same time, research guided by human sleep disorders is leading to important basic sleep concepts. For example, sleep may not be a global, but rather a local, brain phenomenon. Furthermore, contrary to common assumptions, wakefulness, rapid eye movement (REM) and non-REM sleep are not mutually exclusive states. This striking realization explains a fascinating range of clinical phenomena.

Links between the innate immune system and sleep

Abstract: Sleep is a fundamental physiologic process with unknown functions. It is divided into 2 distinct states: non-rapid-eye-movement sleep and rapid-eye-movement sleep. After acute infection with nonneurotropic agents, there are stereotypic changes in non-rapid-eye-movement sleep, particularly increased time spent in slow-wave sleep, and often a reduction of time spent in rapid-eye-movement sleep. It is now recognized that both infection-associated sleep and spontaneous sleep are regulated, in part, by immune mediators called cytokines. This review provides brief tutorials on the elements of the innate immune system that detect infection, how sleep is characterized in the laboratory, issues regarding the interpretation of sleep effects on immune function, the interaction of sleep with circadian rhythms and stress, and some of the microbial products, cytokines, and neuropeptides associated with sleep regulation. We also summarize our current understanding of the role of sleep in host defense and asthma exacerbation.

A double-blind study in healthy volunteers to assess the effects on sleep of pregabalin compared with alprazolam and placebo.

Abstract: Study objectives To assess the effects of pregabalin compared with alprazolam and placebo on aspects of sleep in healthy volunteers. Design Randomized, double-blind, placebo- and active-controlled, 3-way crossover. Setting Single research center. Participants and interventions Healthy adult (12 men) volunteers (N=24) received oral pregabalin 150 mg t.i.d., alprazolam 1 mg t.i.d., and placebo t.i.d. for 3 days. Measurements and results Objective sleep was measured by an 8-channel polysomnograph; subjective sleep was measured using the Leeds Sleep Evaluation Questionnaire. Compared with placebo, pregabalin significantly increased slow-wave sleep both as a proportion of the total sleep period and the duration of stage 4 sleep. Alprazolam significantly reduced slow-wave sleep. Pregabalin and alprazolam produced modest, but significant, reductions in sleep-onset latency compared with placebo. Rapid eye movement sleep latency after pregabalin was no different than placebo but was significantly shorter than that found with alprazolam. Although there were no differences between the active treatments, both pregabalin and alprazolam reduced rapid eye movement sleep as a proportion of the total sleep period compared with placebo. Pregabalin also significantly reduced the number of awakenings of more than 1 minute in duration. Leeds Sleep Evaluation Questionnaire ratings of the ease of getting to sleep and the perceived quality of sleep were significantly improved following both active treatments, and ratings of behavior following awakening were significantly impaired by both drug treatments. Conclusions Pregabalin appears to have an effect on sleep and sleep architecture that distinguishes it from benzodiazepines. Enhancement of slow-wave sleep is intriguing, since reductions in slow-wave sleep have frequently been reported in fibromyalgia and general anxiety disorder.

Sleep disorders in multiple sclerosis.

Abstract: Sleep disorders are pervasive in patients with multiple sclerosis (MS) although clinically underrecognized by most physicians. The most common sleep disorders seen in patients with MS include insomnia, nocturnal movement disorders, sleep-disordered breathing, narcolepsy, and rapid eye movement sleep behavior disorder. Factors that influence the quality of sleep in this patient population include pain, nocturia, depression, medication effect, location of lesions, and disease severity. Disrupted sleep has the potential to cause daytime somnolence, increased fatigue, and nonrefreshing sleep, and it may be associated with dangerous respiratory events. Awareness and treatment of these conditions is vital to improving health and quality of life in patients with MS.

Acute intravenous administration of morphine perturbs sleep architecture in healthy pain-free young adults: a preliminary study.

Abstract: STUDY OBJECTIVES Pain is a leading cause of sleep disturbances in medical illness. Providing effective analgesia is considered an important intervention to reduce these sleep disturbances. Opioids remain the treatment of choice to relieve postoperative pain in hospitalized patients. However, their effects on sleep in pain patients or normal subjects remain unclear, as previous studies have been conducted mainly with former opioid addicts. The purpose of this investigation was to evaluate and describe the effects of acute clinical doses of morphine on sleep in healthy pain-free subjects. DESIGN Subjects were randomly assigned to untreated (baseline), morphine (intravenous injections of 0.1 [DOSAGE ERROR CORRECTED] mg/kg), and placebo (intravenous injections of 0.9% NaCI) conditions. SETTING Sleep laboratory. PARTICIPANTS Seven healthy pain-free, nonaddicts (5 women, 2 men; mean age = 25 +/- 1.6 years). MEASUREMENTS AND RESULTS Standard polysomnographic sleep and respiratory variables were measured during 3 experimental conditions. The treatment effect was analyzed with a Latin square cross-over design followed, when appropriate, by Tukey contrasts. Morphine altered sleep architecture by reducing slow-wave sleep (non-rapid eye movement stages 3-4) and rapid eye movement sleep, and by increasing non-rapid eye movement stage 2 sleep. Results did not reveal any statistical differences for other sleep and respiratory variables. CONCLUSIONS Similar to earlier findings in animals, nondependent opiate addicts, and postoperative patients, morphine was found to reduce duration of slow-wave sleep. Unlike previous reports, however, its acute administration produced a moderate reduction in rapid eye movement sleep and did not increase correlates of arousal (ie, awakenings, electroencephalogram arousals, wake after sleep onset). Future studies should correlate these findings in patients with pain and evaluate whether optimal pain relief with opioid therapy can improve sleep disturbances in pain patients.

Vivid dreams, hallucinations, psychosis and REM sleep in Guillain-Barré syndrome

Abstract: We conducted a prospective controlled study of the clinical and biological determinants of the mental status abnormalities in 139 patients with Guillain-Barre syndrome (GBS) and 55 patients without GBS placed in the intensive care unit (ICU controls). There were mental status changes in 31% of GBS patients and in 16% of controls (odds ratio = 2.3; P = 0.04). In GBS patients, they included vivid dreams (19%), illusions (30%, including an illusory body tilt), hallucinations (60%, mainly visual) and delusions (70%, mostly paranoid). They appeared a median 9 days after disease onset (range 1-40 days, during the progression or the plateau of the disease), and lasted a median 8 days. Seven (16%) patients experienced the symptoms before their admission to the ICU. Hallucinations were frequently hypnagogic, occurring as soon as the patients closed their eyes. Autonomic dysfunction, assisted ventilation and high CSF protein levels were significant risk factors for abnormal mental status in GBS patients. CSF hypocretin-1 (a hypothalamic neuropeptide deficient in narcolepsy) levels, measured in 20 patients, were lower in GBS patients with hallucinations (555 +/- 132 pg/ml) than in those without (664 +/- 71 pg/ml, P = 0.03). Since the mental status abnormalities had dream-like aspects, we examined their association with rapid eye movement sleep (REM sleep) using continuous sleep monitoring in 13 GBS patients with (n = 7) and without (n = 6) hallucinations and 6 tetraplegic ICU controls without hallucinations. Although sleep was short and fragmented in all groups, REM sleep latency was shorter in GBS patients with hallucinations (56 +/- 115 min) than in GBS patients without hallucinations (153 +/- 130 min) and in controls (207 +/- 179 min, P < 0.05). In addition, sleep structure was highly abnormal in hallucinators, with sleep onset in REM sleep periods (83%), abnormal eye movements during non-REM sleep (57%), high percentages of REM sleep without atonia (92 +/- 22%), REM sleep behaviour disorders and autonomic dysfunction (100%), reminiscent of a status dissociatus. The sleep abnormalities, that were almost absent in non-hallucinated GBS patients, were not exclusively related to ICU conditions, since they also appeared out of ICU, and were reversible, disappearing when the mental status abnormalities vanished while the patients were still in ICU. In conclusion, the mental status abnormalities experienced by GBS patients are different from the ICU delirium, are strongly associated with autonomic dysfunction, severe forms of the disease and possibly with a transitory hypocretin-1 transmission decrease. Sleep studies suggest that mental status abnormalities are wakeful dreams caused by a sleep and dream-associated disorder (status dissociatus).

Aggressive dream content without daytime aggressiveness in REM sleep behavior disorder

Abstract: Background: REM sleep behavior disorder (RBD) is characterized by vigorous sleep motor activity associated with dream mentation. Patients with RBD frequently report action-filled and violent dreams. Objective: To systematically assess dream characteristics and daytime aggressiveness in patients with RBD and controls. Methods: Forty-nine patients with polysomnographic-confirmed RBD diagnosis and 71 age- and sex-matched controls were asked to recall the most recent dreams and to complete the Aggression Questionnaire (AQ). Forty-one patients with RBD (81.6%; 36 men, 5 women; mean age: 67.5 ± 7.5 years) and 35 controls (49.3%; 30 men, 5 women; mean age: 69.1 ± 5.9 years) were able to remember their dreams and a total of 98 (RBD) and 69 (controls) dreams were collected in the two groups. Verbatim dream descriptions were scored and analyzed according to the Hall and Van De Castle method. Results: Patients with RBD showed a higher percentage of dream with at least one aggressive episode (DWA) than controls (66% vs 15%; p p p = 0.0001). In contrast to controls, no patient with RBD had dreams with elements of sexuality (0% vs 9%; p p = 0.034). No correlation was observed between dream aggressiveness and age, duration, or frequency of RBD symptoms. Conclusions: Dreams in patients with REM sleep behavior disorder were characterized by an elevated proportion of aggressive contents, despite normal levels of daytime aggressiveness. Dreams with aggressiveness and the known excessive phasic muscle activity during REM sleep may be related to the hyperactivity of a common neuronal generator.

The effect of electromagnetic fields emitted by mobile phones on human sleep.

Abstract: Previous research has suggested that exposure to radiofrequency electromagnetic fields increases electroencephalogram spectral power in non-rapid eye movement sleep. Other sleep parameters have also been affected following exposure. We examined whether aspects of sleep architecture show sensitivity to electromagnetic fields emitted by digital mobile phone handsets. Fifty participants were exposed to electromagnetic fields for 30 min prior to sleep. Results showed a decrease in rapid eye movement sleep latency and increased electroencephalogram spectral power in the 11.5-12.25 Hz frequency range during the initial part of sleep following exposure. These results are evidence that mobile phone exposure prior to sleep may promote rapid eye movement sleep and modify the sleep electroencephalogram in the first non-rapid eye movement sleep period.

How pain and analgesics disturb sleep.

Abstract: Objective Clinical experiences as well as specific investigations show that pain and sleep disturbances are closely correlated. The aims of this review are first to describe sleep disturbances related to painful medical diseases and analgesics and secondly to propose management possibilities for these sleep disturbances. Method The viewpoints presented were based mainly on objective rest activity and sleep studies using actigraphy and polysomnography. Results Polysomnographic and actigraphic studies have described significant sleep disturbances in patients suffering from different pain disorders. These disturbances are: reduced sleep efficiency and altered sleep architecture characterized by increased wakefulness and stage 1 non-rapid eye movement sleep, associated with diminished slow wave sleep and rapid eye movement sleep. Sleep disturbances may be related to pain and to the analgesic or sedative medications administered. Conclusion If many factors, including pain, disease process per se, as well as medication, could disturb sleep, sleep disturbances may also adversely affect the natural course of the painful disease. Improving sleep quantity and quality in patients with painful disorders may break this vicious circle and as consequence enhance the patients' overall health and quality of life.

Chronic REM-sleep deprivation of rats elevates metabolic rate and increases UCP1 gene expression in brown adipose tissue

Abstract: A cluster of unique pathologies progressively develops during chronic total- or rapid eye movement-sleep deprivation (REM-SD) of rats. Two prominent and readily observed symptoms are hyperphagia an...

Sleep enhances explicit recollection in recognition memory.

Abstract: Recognition memory is considered to be supported by two different memory processes, i.e., the explicit recollection of information about a previous event and an implicit process of recognition based on an acontextual sense of familiarity. Both types of memory supposedly rely on distinct memory systems. Sleep is known to enhance the consolidation of memories, with the different sleep stages affecting different types of memory. In the present study, we used the process-dissociation procedure to compare the effects of sleep on estimates of explicit (recollection) and implicit (familiarity) memory formation on a word-list discrimination task. Subjects studied two lists of words before a 3-h retention interval of sleep or wakefulness, and recognition was tested afterward. The retention intervals were positioned either in the early night when sleep is dominated by slow-wave sleep (SWS), or in the late night, when sleep is dominated by REM sleep. Sleep enhanced explicit recognition memory, as compared with wakefulness (P < 0.05), whereas familiarity was not affected by sleep. Moreover, explicit recognition was particularly enhanced after sleep in the early-night retention interval, and especially when the words were presented with the same contextual features as during learning, i.e., in the same font (P < 0.05). The data indicate that in a task that allows separating the contribution of explicit and implicit memory, sleep particularly supports explicit memory formation. The mechanism of this effect appears to be linked to SWS.

Sleep and breathing on the first night after adenotonsillectomy for obstructive sleep apnea

Abstract: Adenotonsillectomy (T&A) has established effectiveness for the treatment of obstructive sleep apnea (OSA). However, more than 20% of children with OSA have respiratory compromise requiring medical intervention in the postoperative period. The reasons for this complication are not well-defined. We aimed to compare the nature and severity of sleep-disordered breathing in children with mild and severe OSA on the first night following adenotonsillectomy. Ten children were classified into groups of mild and severe OSA, based on preoperative testing. On the first night after T&A, they underwent polysomnography, including electroencephalograph, submental electromyography, bilateral electro-oculograms, monitoring of respiratory movements, heart rate, ECG, and oxygen saturation. Sleep-disordered breathing was assessed by the apnea-hypopnea index, the SaO 2 nadir, and the desaturation index, including dips in saturation below 90% (DI 9 0 ). Sleep quality was assessed by sleep efficiency, time spent in each sleep state, and respiratory arousal index. Obstructive events occurred postoperatively in all children, but were more frequent in those with severe OSA preoperatively: the median (interquartile range) mixed/obstructive apnea/hypopnea indicies were 6.9 (2.2-9.8) events/hr and 21.5 (15.1 -112.1) events/hr for the mild OSA group and the severe OSA group, respectively (P=0.009). Obstructive events were the major cause of desaturation during sleep postoperatively. Sleep quality was severely disrupted in both groups, with reductions in both slow-wave sleep and rapid eye movement sleep. In conclusion, despite removal of obstructing lymphoid tissue, upper airway obstruction occurred on the first postoperative night in children with OSA. This study is the first to demonstrate the mechanism of respiratory compromise after adenotonsillectomy, a common postoperative complication in children with severe OSA.

Rapid eye movement-related brain activation in human sleep: a functional magnetic resonance imaging study.

Abstract: In animal models, ponto-geniculo-occipital waves appear as an early sign of rapid eye movement sleep and may be functionally significant for brain plasticity processes. In this pilot study, we use a combined polysomnographic and functional magnetic resonance imaging approach, and show distinct magnetic resonance imaging signal increases in the posterior thalamus and occipital cortex in close temporal relationship to rapid eye movements during human rapid eye movement sleep. These findings are consistent with cell recordings in animal experiments and demonstrate that functional magnetic resonance imaging can be utilized to detect ponto-geniculo-occipital-like activity in humans. Studying intact neuronal networks underlying sleep regulation is no longer confined to animal models, but has been shown to be feasible in humans by a combined functional magnetic resonance imaging and electroencephalograph approach.

The hypocretins and sleep

Abstract: The hypocretins (also called the orexins) are two neuropeptides derived from the same precursor whose expression is restricted to a few thousand neurons of the lateral hypothalamus. Two G-protein coupled receptors for the hypocretins have been identified, and these show different distributions within the central nervous system and differential affinities for the two hypocretins. Hypocretin fibers project throughout the brain, including several areas implicated in regulation of the sleep/wakefulness cycle. Central administration of synthetic hypocretin-1 affects blood pressure, hormone secretion and locomotor activity, and increases wakefulness while suppressing rapid eye movement sleep. Most human patients with narcolepsy have greatly reduced levels of hypocretin peptides in their cerebral spinal fluid and no or barely detectable hypocretin-containing neurons in their hypothalamus. Multiple lines of evidence suggest that the hypocretinergic system integrates homeostatic, metabolic and limbic information and provides a coherent output that results in stability of the states of vigilance.

Influence of swaddling on sleep and arousal characteristics of healthy infants.

Abstract: Objective. Swaddling is an old infant care practice. It was reported to favor sleep and to reduce crying among irritable infants. There are few data on the physiologic effects of swaddling on infants9 sleep-wake characteristics. This study was conducted to evaluate whether swaddling influences infants9 arousal thresholds for environmental auditory stress. Design. Sixteen healthy infants, with a median age of 10 weeks (range: 6–16 weeks), underwent polygraphic recording in their usual supine position during one night. The infants were successively recorded swaddled and nonswaddled, or vice versa. In both conditions, the infants were exposed to white noise of increasing intensity, from 50 to 100 dB(A), during rapid eye movement sleep, to determine their arousal thresholds. Results. Swaddling was associated with increases in the infants9 sleep efficiency and in the time spent in non–rapid eye movement sleep. When swaddled, the infants awakened spontaneously less often. However, significantly less-intense auditory stimuli were needed during rapid eye movement sleep to induce cortical arousals when swaddled than when not swaddled. Conclusions. Swaddling promotes more-sustained sleep and reduces the frequency of spontaneous awakenings, whereas induced cortical arousals are elicited by less-intense stimuli. These findings could indicate that, although swaddling favors sleep continuity, it is associated with increased responsiveness to environmental auditory stress.

Rhythmic movement disorder in sleep persisting into childhood and adulthood.

Abstract: Study objectives To evaluate the type, duration, and distribution of rhythmic movements in sleep stages in school-aged children and young adults; to find out if cases of rhythmic movement disorder persisting beyond infancy are associated with any daytime symptoms or psychopathology. Design All participants underwent neurologic examination, biochemical screening, electroencephalography, neuroimaging, overnight videopolysomnography, and psychologic examination. Setting Department of Neurology and Sleep Laboratory, 1st Medical Faculty, Charles University, Prague. Patients or participants Ten subjects referred to the sleep disorders center because of rhythmic movement disorder. Five males, 5 females; age range, 7-24 years; mean age 14.7 +/- 5.69 years. Interventions None. Measurements and results Biochemical screening, electroencephalogram, and neuroimaging were unremarkable in all cases. According to duration, 2 types of rhythmic movements were observed on polysomnography: longer episodes appeared in wakefulness and in non-rapid eye movement stage 1 sleep, while shorter episodes (2-80 seconds) occurred during non-rapid eye movement stage 2, non-rapid eye movement stage 3-4, and rapid eye movement sleep. According to sleep-stage distribution, we defined (a) rhythmic movements prevailing in the first half of the night and in the morning hours, usually associated with wakefulness or superficial sleep; (b) rhythmic movements occurring throughout the night in all sleep stages; (c) rhythmic movements prevailing in the second half of the night and mainly associated with rapid eye movement sleep. Psychologic examination showed symptoms of the attention-deficit/hyperactivity disorder in 6 cases. Conclusions According to our study, rhythmic movement disorder persisting beyond infancy may be connected with various daytime symptoms; a strong association between rhythmic movement disorder and attention-deficit/hyperactivity disorder was found in school-aged children. We speculate that pathogenetic mechanisms similar to those in attention-deficit/hyperactivity disorder are involved in rhythmic movement disorder or that symptoms of attention-deficit/hyperactivity disorder may be secondary to rhythmic movement disorder.

The number of hypothalamic hypocretin (orexin) neurons is not affected in Prader-Willi syndrome.

Abstract: Context Narcoleptic patients with cataplexy have a general loss of hypocretin (orexin) in the lateral hypothalamus, possibly due to an autoimmune-mediated degeneration of the hypocretin neurons. In addition to excessive daytime sleepiness, Prader-Willi syndrome (PWS) patients may show narcolepsy-like symptoms, such as sleep-onset rapid eye movement sleep and cataplexy, independent of obesity-related sleep disturbances, which suggests a disorder of the hypocretin neurons. Objective We hypothesized that the narcolepsy-like symptoms in PWS are caused by a decline in the number of hypocretin neurons. Design We estimated the number of hypocretin neurons in postmortem hypothalami using immunocytochemistry and an image analysis system. Setting This study was conducted at the Netherlands Institute for Brain Research. Patients Eight PWS adults, three PWS infants, and 11 controls were studied. Main outcome measure The total number of hypocretin neurons in the lateral hypothalamus was measured. Results There was no significant difference in the total number of hypocretin-containing neurons among the seven PWS patients (in whom sufficient hypothalamic material was available to quantify total cell number) and seven age-matched controls, either in adults or in infants. A significant decline with age was found in adult PWS patients (r = -0.9; P = 0.037). Conclusions We conclude that a decrease in the number of hypocretin neurons does not play a major role in the occurrence of narcolepsy-like symptoms in PWS.

Polysomnographic measures of nocturnal sleep in patients on chronic, intermittent daytime haemodialysis vs those with chronic kidney disease.

Abstract: Background Numerous factors probably contribute to the high prevalence of sleep problems in haemodialysis (HD) patients including metabolic changes and treatment-related factors. In contrast, the sleep problems of patients with chronic kidney disease (CKD) may be more related to psychological factors rather than the metabolic changes associated with renal disease. Thus, the objective of this study was to compare polysomnographic measures of nocturnal sleep in a group of stable patients on chronic, intermittent daytime HD and an age- and gender-matched, metabolically comparable group with CKD, and evaluate the role that quality of life (including psychological factors) and the effects of treatment may play in sleep outcomes. Methods The sample included 16 patients on HD and eight patients with CKD all of whom were free from other significant physical and psychological morbidity. To assess for psychological, functional, family and economic responses to the disease and treatment, all subjects took the Ferrans and Powers Quality of Life Index. HD subjects received treatment three times a week and were adequately dialysed [Kt/V >1.2, equivalent to a weekly glomerular filtration rate (GFR) of 10-15 ml/min]; CKD subjects had an estimated GFR of 14.5 (+/-7.2; range 5.4-28.8) ml/min. All subjects underwent one night of laboratory-based polysomnography. Appropriate statistical procedures were used to explore group differences in sleep variables and their relationship to quality of life dimensions and the effect of treatment. Results The CKD patients reported significantly poorer functional and psychological quality of life; both groups had reduced total sleep time and sleep efficiency in comparison with normative data. However, HD subjects had less rapid eye movement sleep (P = 0.032). They also had a higher brief arousal index (P = 0.000), an independent predictor of which was treatment with HD, and respiratory disturbance index (P = 0.061). Less total sleep time, increased wake after sleep onset, lower sleep efficiency, higher periodic limb movement index, and longer latencies to sleep onset and rapid eye movement sleep were also noted in the HD group. Quality of life scores did not predict sleep variables in this small sample. Conclusions The results suggest that the sleep problems of patients with CKD and those receiving chronic, intermittent daytime HD may have different aetiologies; functional and psychological factors may play a more prominent role in the former group, while intrinsic sleep disruption (arousals, apnoeas and limb movements) secondary to the effects of chronic, intermittent daytime HD may play a more significant role in the latter. The findings suggest that further exploration is warranted and that population-specific sleep-promoting interventions may be indicated.

Brief wake episodes modulate sleep-inhibited luteinizing hormone secretion in the early follicular phase.

Abstract: To determine the influence of sleep, sleep stage, and time of day on the dynamics of pulsatile LH secretion in the early follicular phase (EFP) of the menstrual cycle, 11 normal women underwent simultaneous polysomnographic monitoring of sleep and measurement of LH in frequent sampling studies during a 40-h protocol that consisted of one night of normal sleep and one night of sleep deprivation followed by an afternoon nap. The interpulse interval of LH was longer during sleep than wake whether it occurred at night or during the day (P < 0.002), implying a decrease in GnRH pulse frequency associated with sleep in the EFP. LH pulse amplitude was greater during sleep than wake (P < 0.001) and greater pulse amplitudes were associated with longer interpulse intervals during sleep (P < 0.005), but not wake. An interaction between sleep and time of day was observed for mean LH, with lower mean LH levels during sleep than wake at night (P < 0.02), but not during the day. Wakefulness was more likely to be associated with an LH pulse than were stages I/II, III/IV (slow wave), or rapid eye movement sleep (P < 0.005). In addition, the probability of wakefulness within the sleep episode increased 5-15 min before the onset of LH pulses (relative to randomly selected nonpulse LH; P < 0.05), suggesting that wakefulness was the primary event. In the absence of sleep, there was an effect of time of day on mean LH (P < 0.02) and LH pulse amplitude (P < 0.03), with greatest values seen during the evening. In conclusion, in the EFP, inhibition of LH pulse frequency is related to sleep rather than time of day. During periods of sleep, LH pulses occur most commonly in association with brief awakenings, suggesting that interruptions from sleep allow escape from the inhibitory effect of sleep on pulsatile GnRH secretion. A separate effect of time of day on LH pulse dynamics in the absence of sleep was also observed with evening augmentation of LH pulse amplitude and mean level; however, additional studies will be required to determine whether this represents a true circadian effect.

Slow-wave sleep and delta power in rapid eye movement sleep behavior disorder

Abstract: Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by the loss of normal muscle atonia during REM sleep, leading to an increase of phasic muscle activity and complex motor behaviors during the night. There is some evidence that RBD patients have more of slow-wave sleep (SWS) than healthy elderly subjects. No study has looked at quantitative electroencephalogram analysis during non-REM sleep in either primary or secondary RBD. The aim of this study was to assess the increase of SWS and to analyze different electroencephalographic frequency ranges during non-REM sleep in 28 idiopathic RBD patients compared with 28 age- and sex-matched healthy volunteers. Idiopathic RBD patients spent more time in SWS (men: 1.4%; women: 5.9%) than control subjects (men: 0.4%; women: 0.6%; p = 0.004). Spectral analyses demonstrated that idiopathic RBD patients had increased all-night delta power in comparison with control subjects (p = 002). This study shows an increase of SWS and power in the delta band during non-REM sleep in idiopathic RBD patients compared with control subjects. Results are discussed about the possible nigrostriatal dopaminergic impairment in RBD patients and the association between RBD and neurodegenerative disorders.