Spectral analysis of all-night human sleep EEG in narcoleptic patients and normal subjects

To investigate the pathophysiology of narcoleptic patients' sleep in detail, we analysed and compared the whole-night polysomnograms of narcoleptic patients and normal human subjects. Eight drug-naive narcoleptic patients and eight age-matched normal volunteers underwent polysomnography (PSG) on two consecutive nights. In addition to conventional visual scoring of the polysomnograms, rapid eye movement (REM)-density and electroencephalograph (EEG) power spectra analyses were also performed. Sleep onset REM periods and fragmented nocturnal sleep were observed as expected in our narcoleptic patients. In the narcoleptic patients, REM period duration across the night did not show the significant increasing trend that is usually observed in normal subjects. In all narcoleptic patient REM periods, eye movement densities were significantly increased. The power spectra of narcoleptic REM sleep significantly increased between 0.3 and 0.9 Hz and decreased between 1.0 and 5.4 Hz. Further analysis revealed that non-rapid eye movement (NREM) period duration and the declining trend of delta power density in the narcoleptic patients were not significantly different from the normal subjects. Compared with normal subjects, the power spectra of narcoleptic NREM sleep increased in the 1.0-1.4 Hz and 11.0-11.9 Hz frequency bands, and decreased in a 24.0-26.9 Hz frequency band. Thus, increased EEG delta and decreased beta power densities were commonly observed in both the NREM and REM sleep of the narcoleptic patients, although the decrease in beta power during REM sleep was not statistically significant. Our visual analysis revealed fragmented nocturnal sleep and increased phasic REM components in the narcoleptic patients, which suggest the disturbance of sleep maintenance mechanism(s) and excessive effects of the mechanism(s) underlying eye movement activities during REM sleep in narcolepsy. Spectral analysis revealed significant increases in delta components and decreases in beta components, which suggest decreased activity in central arousal mechanisms. These characteristics lead us to hypothesize that two countervailing mechanisms underlie narcoleptic sleep pathology.     

Periodic leg movements during sleep and wakefulness in narcolepsy

The objectives of the study were to measure the prevalence of periodic leg movements during NREM and REM sleep (PLMS) and while awake (PLMW) and to assess the impact of PLMS on nocturnal sleep and daytime functioning in patients with narcolepsy. One hundred and sixty-nine patients with narcolepsy and 116 normal controls matched for age and gender were included. Narcoleptics with high and low PLMS indices were compared to assess the impact of PLMS on sleep and Multiple Sleep Latency Test (MSLT) variables. More narcoleptics than controls had a PLMS index greater than 5 per hour of sleep (67% versus 37%) and an index greater than 10 (53% versus 21%). PLMS indices were higher both in NREM and REM sleep in narcoleptic patients, but the between-group difference was greater for REM sleep. A significant increase of PLMS index was also found with aging in both narcoleptic patients and controls. PLMW indices were also significantly higher in narcoleptic patients. Patients with an elevated index of PLMS had a higher percentage of stage 1 sleep, a lower percentage of REM sleep, a lower REM efficiency and a shorter MSLT latency. The present study demonstrates a high frequency of PLMS and PLMW in narcolepsy, an association between the presence of PLMS and measures of REM sleep and daytime functioning disruption. These results suggest that PLMS represent an intrinsic feature of narcolepsy.     

A sedentary day: effects on subsequent sleep and body temperatures in trained athletes

Exercise effects on sleep in fit healthy people have been difficult to determine because their sleep is close to optimal, leaving little room for improvement. Another method for assessing exercise effects on sleep is to significantly reduce the degree of activity in highly active people. Fifteen trained athletes who exercised daily at a moderate to high intensity were employed. By requesting that subjects remain sedentary in the laboratory for an entire day, the effect of reduced exercise on subsequent sleep parameters was assessed. Sleep and temperature were recorded after a sedentary day and after a normal day of moderate to high activity (control condition) in a counterbalanced design. In the sedentary condition, slow-wave sleep (SWS) decreased by a mean of 15.5+/-7.0 min and slow-wave activity (SWA) differed significantly (P<.05) between conditions in the first hour of sleep only. Rapid eye movement (REM) sleep increased by a mean of 17.9+/-5.7 min in the sedentary condition, while sleep onset latency (SOL) to Stages 1 and 2 increased by 10.2 and 10.7 min, respectively, and REM sleep latency decreased by 24.0+/-6.8 min (all P<.05). Between conditions, there was no overall effect on total sleep time (TST), sleep efficiency, wake after sleep onset or core or foot temperatures (P>.05). With reduced exercise load, SWS pressure may have been reduced, resulting in lower levels of SWS and increased REM sleep. Thus, the data indicate that reducing exercise has significant effects on sleep that may have implications for athletes tapering for competition.     

Sleep cycle organization in narcoleptic and normal dogs.

The normal sleep-wake patterns of four narcoleptic and four normal dogs were recorded electrographically for 48 hours in a laboratory setting. The amount of the various stages of vigilance (wake, light slow wave sleep, deep slow wave sleep and REM sleep) were similar for both sets of dogs except that narcoleptic dogs has significantly less REM sleep and had an additional state scored as cataplexy. Mean episode durations and the number of episodes per 48 hr were not significantly different except that narcoleptic dogs had fewer REM episodes and a trend toward more waking episodes. There was a significant difference in the state progression between normal and narcoleptic dogs before and after REM episodes. Narcoleptic dogs had an increase in LSWS and a decrease in DSWS during the last 5 min before REM sleep onset in comparison to the reverse pattern in controls. In the stages following REM there was a marked elevation of wakefulness in narcoleptic dogs. These data support the notion that narcolepsy is a sleep disorder characterized by a disruption of the normal sleep-wake cycle. These results parallel similar findings in humans and provide strong evidence that this disease entity is similar in man and dog.     

Plasma renin activity and sleep-wake structure of narcoleptic patients and control subjects under continuous bedrest.

In order to determine if renin release would be affected by a dysfunction of the circadian and ultradian organization of sleep, 24-hour profiles of plasma renin activity (PRA) concomitant with sleep stages were established in 10 normal subjects and nine narcoleptic patients, with 10-minute blood sampling intervals. Mean PRA levels were similar in control subjects and narcoleptic patients. Individual 24-hour profiles revealed that the previously described association between renin oscillations and sleep stage alternations was preserved. Increased PRA release was observed during the transition from rapid eye movement (REM) sleep or waking periods to nonrapid eye movement (NREM) sleep, and REM sleep occurred as PRA levels were decreasing. Thus, PRA curves exactly reflected the irregularities and disturbances in the sleep structure of the narcoleptic patients. The 24-hour PRA profiles of the patients did not show the general upward trend during nighttime sleep, which is probably induced in the control subjects by the repetitive recurrence of longer episodes of undisturbed NREM sleep. Because of marked sleep fragmentation in the patients, the duration of NREM sleep was often insufficient to allow for the occurrence of a significant PRA increase. Because sleep onset REM (SOREM) episodes, characteristic of narcolepsy, are not preceded by NREM sleep and its associated increase in PRA, no relative PRA decline occurred during this type of REM sleep. In conclusion, the 24-hour PRA profiles of the narcoleptic patients reflected exactly their sleep stage distribution, confirming previous findings that PRA oscillations appear to be inseparable from the NREM-REM sleep cycle.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sleepiness and Sleep State on a 90-Min Schedule

The effects of REM and slow wave sleep (SWS) on subjective sleepiness were studied in 10 subjects placed on a 90-min sleep-wakefulness schedule for either 5^1/3 or 6 (24-hr) days. Subjects were permitted to sleep for 30-min periods separated by 60 min of enforced wakefulness. Sleep recordings showed that sleep onset REM periods occurred frequently; REM and SWS appeared during the same sleep period only 27 times; and REM sleep tended to occur on sleep periods that alternated with SWS periods. Sleepiness was measured using the Stanford Sleepiness Scale (SSS) given 15 min before (pre-sleep) and 15 min after (post-sleep) each sleep period. Average SSS ratings showed a 24-hr fluctuation in sleepiness. In addition, negative and positive SSS changes tended to alternate with each 90-min period. Significant correlations were found with post-sleep SSS ratings and SWS and with pre-sleep SSS ratings and REM sleep. Differences between pre- and post-sleep SSS scores were also correlated with the sleep states: increased sleepiness was correlated with SWS and decreased sleepiness with REM sleep.     

REM sleep characteristics in narcolepsy and REM sleep behavior disorder

STUDY OBJECTIVES: To assess the presence of polysomnographic characteristics of REM sleep behavior disorder (RBD) in narcolepsy; and to quantify REM sleep parameters in patients with narcolepsy, in patients with "idiopathic" RBD, and in normal controls. DESIGN: Sleep laboratory study PARTICIPANTS: Sixteen patients with narcolepsy and cataplexy matched for age and sex with 16 patients with "idiopathic" RBD and with 16 normal controls were studied. MEASUREMENTS AND RESULTS: Higher percentages of REM sleep without atonia, phasic electromyographic (EMG) activity, and REM density were found in patients with narcolepsy than normal controls. In contrast, RBD patients had a higher percentage of REM sleep without atonia but a lower REM density than patients with narcolepsy and normal controls. Based on a threshold of 80% for percentage of REM sleep with atonia, 50% of narcoleptics and 87.5% of RBD patients had abnormal REM sleep muscle activity. No significant behavioral manifestation in REM sleep was noted in either narcoleptics or controls. We also found a higher frequency of periodic leg movements during wake (PLMW) and during sleep (PLMS) in narcoleptic patients compared to controls. CONCLUSIONS: The present study demonstrates abnormalities in REM sleep motor regulation with an increased frequency of REM sleep without atonia, phasic EMG events and PLMS in narcoleptic patients when compared to controls. These abnormalities were seen more prominently in patients with RBD than in narcoleptics, with the exception of the PLMS index. We proposed that dysfunctions in hypocretin/dopaminergic system may lead to motor dyscontrol in REM sleep that results in dissociated sleep/wake states.     

The diurnal distribution of sleep propensity: experimental data about the interaction of the propensities for slow-wave sleep and REM sleep

The aim of the present study was to assess the diurnal variation of sleep propensity by evaluating the temporal distribution of sleep onset latency (SOL) and REM- and slow-wave sleep (SWS) parameters in systematically scheduled daytime naps for 12 young males. To reduce the effect of prior SWS on subsequent REM sleep, a double-nap technique was used, i.e. two adjacent naps A and B, which were separated by a 10-min break. Nap duration was adjusted in such a way that nap A allowed 30 min of sleep and nap B one complete NREM–REM cycle. EEG slow wave activity (SWA, power density from 0.5–4 Hz) was estimated from nap A and REM sleep parameters from nap B. The time span between 08.00 hours and 24.00 hours was covered by nine double-naps at 2 h intervals. The order of the nap sessions was systematically varied within and across subjects. For each subject, the time between successive double-nap recordings was at least three days. SOL was shortest in the time interval 12.00 hours to 16.00 hours and significantly longer between 20.00 hours and 24.00 hours. REM sleep duration and the percentage of sleep onset REM episodes decreased continuously from 08.00 hours to the interval 18.00–20.00 hours and increased thereafter, with a time course inversely related to the one of body temperature, which was also measured continuously. SWA showed a steady, threefold increase from 08.00 hours to 24.00 hours. The study offers new data on the diurnal variation of sleep propensity which seems to be a composite function of the drives for SWS and REM sleep.     

Reversal of the sleep/wake cycle disorder of sleeping sickness after trypanosomicide treatment

To determine whether the circadian disruption of the sleep/wake cycle observed in sleeping sickness, human African trypanosomiasis (HAT), can be reversed after trypanosomicide treatment, 10 Congolese patients infected by Trypanosoma brucei gambiense underwent 24-h polysomnographic recordings before treatment with melarsoprol and after each of three weekly treatment sessions. Polysomnography consisted of a continuous recording of the electroencephalogram, electromyogram and electro-oculogram on a Minidix Alvar polygraph. Sleep traces were analysed in 20-sec epochs for wakefulness, REM sleep, and NREM sleep [stages 1, 2, 3, 4; stages 3 and 4 representing slow-wave sleep (SWS)]. As previously described (Buguet et al. 1993), the 24-h distribution of the sleep/wake cycle was disturbed proportionally to the severity of the illness. The overall amounts of each sleep/wake stage did not change after treatment. However, the patterns of occurrence of sleep episodes, REM sleep and SWS phases were determinant in the evaluation of treatment efficacy. The trypanosomicide action of melarsoprol led to a reduction in the number of sleep episodes, except in one patient whose health condition worsened during the third treatment session: sleep onset REM sleep phases (SOREMPs) decreased and the number of SWS episodes during a sleep episode increased. We conclude that in HAT, the reversibility of the sleep/wake cycle alteration and that of sleep structure constitute the basis for an evaluation of the healing process.     

Sleep During and After Gradual Sleep Reduction

To determine: 1) the minimum amounts of sleep subjects would tolerate, 2) the changes in EEG sleep measures, and 3) whether subjects would revert to baseline sleep after study termination, 4 couples gradually reduced their sleep. Three couples reduced their TST in 30-min steps from a baseline of 8 hrs and one couple from a baseline of 6.5 hrs. Subjective estimates of sleep time, sleep quality, and mood were collected daily. Home EEG sleep recordings were obtained 3 nights a week. Two of the 8-hr sleepers reduced their sleep to 5.5 hrs, 2 to 5.0 hrs, and 2 reached 4.5 hrs. These 6 subjects continued sleeping 1 to 2.5 hrs below baseline amounts a year after reduction terminated. The 6.5-hr baseline couple reached 5.0 hrs and returned to 6.5 hrs TST during follow-up. Stages W, 2, and REM decreased significantly in absolute amounts. Percentage of stages W and 2 also decreased significantly. REM percent remained constant. Stage 3 was constant while stage 4 increased in both absolute and relative amounts. REM cycle length remained constant. Stage 4 rebound on 7-hr nights was not observed during times of greatest sleep reduction. Occurrences of stage REM within 10 min of stage 1 onset were observed in 2 subjects when their TST was below 6.5 hrs. Our results are consistent with other studies of shortened sleep, indicating that TST is the major determinant of sleep-stage characteristics.     

Effects of Exhaustive Exercise on the Sleep of Men and Women

The effects of exhaustive exercise on sleep were examined in 5 women and 4 men who performed an acute bout of submaximal exercise (50–70% Vo_2max) to the point of volitional exhaustion. Significant changes were observed in the quantity and temporal distribution of slow-wave sleep (SWS) on the exercise night. The duration of SWS prior to rapid eye movement (REM) sleep onset increased markedly, along with a moderate increase in stage 4 and total SWS. REM sleep variables were affected in the early portion of the night, with an increased latency to first REM onset and a decrease in the duration of the first REM period. Initial REM cycle length (from first to second REM period onset) decreased as well. The magnitude of the SWS increase prior to REM onset was sex-related, averaging 24 min for women and 5.7 min for men. A correlation of .85 was observed between this increase and total caloric expenditure during exercise for the women. Cardiovascular measures indicated significant elevations of heart rate and cardiac output during sleep on the exercise night. Analysis of urine samples revealed a significant drop in nocturnal cortisol excretion rates after exercise. The results suggest that exhaustive exercise affects sleep primarily in the early portion of the night, inducing an increase in SWS pressure at the expense of REM sleep.     

Electroencephalogram and cardiovascular responses to noise during daytime sleep in shiftworkers

Summary Intermittent noise occurring during sleep has been found to induce heart rate, peripheral vasomotor and electroencephalogram (EEG) changes. This study analysed these responses during the daytime and night-time sleep of shiftworkers doing a three shift system, to determine the influence of the inversion of the sleep-wake cycle on the sensitivity to noise. A group of 14 shiftworkers [aged 37 (SD 5) years] underwent an habituation daytime sleep, two experimental daytime sleeps and a night-time sleep. Traffic noises were presented during sleep [truck, 71 dB(A); motorbike, 67 dB(A); and car, 64 dB(A)] at a rate of nine each hour. The EEG measurements of sleep, electrocardiogram and finger pulse amplitude were recorded continuously. The results were expressed by computing the percentage of observed cardiac response (%HRR) and vasoconstrictive response (%FPR), magnitude of heart rate variation (heart rate response; HRR), percentage of reduction of the digital blood flow (finger pulse response, FPR), cardiac cost (CC = % HRR x HRR) and vasomotor cost (VC = % FPR x FPR). The results showed that, compared to night-time sleep, there was change in the structure of daytime sleep, that is an increase in slow wave sleep (SWS), especially stage 4 sleep decrease of stage 2 and rapid eye movement (REM) sleep latencies, and an earlier SWS and REM sleep barycentric point. During daytime sleep the % FPR was significantly smaller in SWS than in stage 2 or REM sleep. Large differences were observed in % HRR, HRR and CC between daytime sleep stages (SWS less than stage 2 less than REM sleep). These differences were not observed during night-time sleep. Moreover, compared to night-time sleep, CC was increased during daytime REM sleep and decreased during daytime SWS. The inversion of the sleep-wake cycle in shiftworkers, did not influence the overall cardiovascular reactivity to noise. This was explained by a compensatory effect due to an increase in this reactivity during daytime REM sleep and its decrease in daytime SWS. The second reason is due to an increase in the percentage of stage 4 sleep during daytime sleep (less disturbed by noise than other sleep stages). This increased percentage of stage 4 sleep was probably a consequence of the partial sleep deprivation occurring after a week working on nightshift.     

Emotional experience during rapid-eye-movement sleep in narcolepsy

STUDY OBJECTIVES: To describe emotional experience during sleep-onset rapid-eye-movement [(REM) SOREM] sleep and nighttime REM in narcoleptic patients and to relate any differences in REM emotion to the more general abnormalities of this disorder. DESIGN: Awakenings were performed from SOREM (REM at the onset of daytime naps and nighttime sleep) and nighttime emergent (ascending) REM in 15 patients with narcolepsy and from nighttime REM in 9 normal healthy participants. Subjects rated the occurrence and intensity of discrete emotion types for each line in their REM-mentation reports. Fragmentation of REM was measured and related to emoton. SETTING: Subjects were studied in their own homes over 2 consecutive days and nights (3 nights for normals) and were monitored by ambulatory polysomnography. PARTICIPANTS: Fifteen patients with narcolepsy, aged 17 to 70 years (mean = 45.3) and 9 normal healthy subjects, aged 31 to 60 years (mean = 43.0). Results: Emotions were found more often and were more intense in narcoleptic SOREM than in nighttime REM of either narcoleptic or normal subjects, with anxiety/fear exhibiting the strongest increase, followed by joy/elation. Comparing nighttime REM in narcoleptic and normal subjects, narcoleptics were found to have more intense feelings of anxiety/fear and of joy/elation but to have a less frequent experience of surprise and anger. Positive and negative emotions occurred in a balanced fashion in SOREM and nighttime REM in narcoleptic subjects. In the SOREM of narcoleptic patients, high levels of positive emotions, in particular of joy/elation, were associated with a less fragmented (more stable) REM sleep. CONCLUSION: The REM sleep of patients with narcolepsy affords a unique opportunity to study emotion and to analyze its psychophysiology. Narcolepsy intensifies REM-dream emotion, especially anxiety/fear and joy/elation, and this is most clearly seen during SOREM sleep. The changes in REM emotion of narcoleptic patients could reflect the effect of the fundamental pathology of this disorder upon neurobiologic systems that support cognitive-emotional functions.     

A Dose-Response Study of Sleep Loss and Spontaneous Sleep Termination

Recent concepts of sleep/wake regulation have emphasized circadian influences and largely disregarded homeostatic ones. The present experiment was designed to study sleep loss homeostasis while minimizing confounding circadian influences. Eight male subjects participated in the study. Night sleep was curtailed across four conditions to yield 0, 2, 4, or 8 hrs of sleep. The effects were studied on subsequent day sleep begun at 1100h and spontaneously terminated. Total sleep time (TST), Stage 2 (S2), and Stages 3+4 (SWS) showed very strong dose-dependent increases with increasing loss. REM sleep did not respond. After maximum sleep loss TST and S2 doubled whereas SWS increased fivefold. Sleep did not terminate until the prior loss of SWS had been recovered. The total SWS recovery approximately matched the loss. TST, S2, and REM failed to recover more than limited amounts of the loss. The results show that homeostatic influences on sleep may be much larger than usually acknowledged and that SWS closely, although not perfectly, reflects the “active component’ of sleep homeostasis.     

Narcolepsy without cataplexy: 2 subtypes based on CSF hypocretin-1/orexin-A findings

STUDY OBJECTIVES: Cerebrospinal fluid (CSF) hypocretin-1 levels and their relationship with the clinical characteristics of narcolepsy without cataplexy have not been well elucidated. Our aim was to examine whether clinical characteristics vary with CSF hypocretin-1 levels among narcoleptic patients without cataplexy. DESIGN: Clinical features, variables on the multiple sleep latency test, and results of HLA typing were correlated with CSF hypocretin-1 levels. SETTING: University-based sleep laboratories and a sleep disorders center. PATIENTS: Seventeen patients (5 male, 12 female) who fulfilled the diagnostic criteria of narcolepsy without cataplexy according to the International Classification of Sleep Disorders. INERVENTIONS: Patients underwent lumbar puncture for CSF sampling. MEASUREMENTS AND RESULTS: Five patients showed a markedly decreased CSF hypocretin-1 level, whereas the remaining 12 patients showed almost normal levels. The mean rapid eye movement (REM) latency was significantly shorter and the age at onset was significantly earlier in the low CSF hypocretin-1 group compared with the normal CSF hypocretin-1 group. HLA-DR2 was positive in all of the patients with low CSF hypocretin-1, whereas only 33.3% of patients with normal CSF hypocretin-1 were DR2 positive. CONCLUSIONS: Some narcoleptic patients without cataplexy have low CSF hypocretin-1 levels. In patients who have narcolepsy without cataplexy, short mean REM latency, younger age at onset, and HLA-DR2 are associated with CSF hypocretin-1 deficiency. Markedly decreased CSF hypocretin-1 levels could be a significant marker for identifying subgroups of narcolepsy patients without cataplexy.     

Motor dyscontrol in sleep of narcoleptic patients (a lifelong development?)

In our retrospective study 27 narcoleptic patients were divided into two groups: Group A comprised 14 patients (10 male, 4 female) with a history of REM behaviour disorder (RBD) and Group B comprised 13 age- and sex-matched patients (10 male, 3 female) without a history of RBD. Polygraphic and videometry data, medical history, medication, blood chemistry, psychological and neuroradiological data of the two groups of patients were compared. The narcoleptic patients with a history of RBD differed from the narcoleptic control group without history of RBD in that they had: (a) a higher frequency of parasomnias in their history; (b) a higher percentage of stage 1 REM (P < 0.01); (c) a lower number of arousals during REM sleep; (d) fewer sleep stage changes. Compared to the heterogenous RBD patient group of Mahowald and Schenck, the REM behaviour of most of our narcoleptic patients was less violent. Thus it can be speculated that the motor disorder in REM sleep might still be in the process of developing towards a full-blown REM sleep behaviour disorder. In a possible lifelong development of a motor disorder starting in NREM sleep, the onset of narcolepsy might represent the turning point for its intrusion into REM sleep.     

Altered skin-temperature regulation in narcolepsy relates to sleep propensity

STUDY OBJECTIVES: In healthy subjects, sleep propensity increases when the distal skin temperature increases relative to the proximal skin temperature. This increase results from increased blood flow in the skin of the extremities and is, among other factors, controlled by the hypothalamic circadian clock, as is sleep. Because narcolepsy is characterized by hypothalamic alterations, we studied skin temperature in narcoleptic patients in relation to their characteristically increased sleep propensity during the day. DESIGN: Distal and proximal skin temperature and their gradient (DPG) were measured during a Multiple Sleep Latency Test. This allowed temperature to be studied during wakefulness, at sleep onset and during sleep. SETTING: Tertiary narcolepsy referral center in a university hospital. PATIENTS: Fifteen unmedicated narcolepsy patients with cataplexy and 15 controls. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: In subjects in the waking state, DPG was higher in narcoleptics than in controls throughout the day (time by group interaction, p < .0001), due to increased distal skin temperature and decreased proximal skin temperature. The increase in DPG was related to a shorter subsequent sleep-onset latency (p = .02). Once asleep, narcoleptics maintained their elevated distal skin temperature and DPG (p < .0001), whereas proximal skin temperature increased to reach normal levels. CONCLUSIONS: This is the first demonstration of a dramatic alteration of daytime skin temperature control in narcolepsy. Even awake narcoleptic patients showed a DPG higher than that which healthy controls achieve when asleep. This observation suggests that hypocretin deficiency in narcolepsy affects skin-temperature regulation and invites further examination. Skin-temperature control might ultimately even have therapeutic implications for the alleviation of narcoleptic symptoms.     

Sleep‐disordered breathing in children is associated with impairment of sleep stage‐specific shift of cardiac autonomic modulation

We examined the effects of sleep stages and sleep‐disordered breathing (SDB) on autonomic modulation in 700 children. Apnea hypopnea index (AHI) during one 9 h night‐time polysomnography was used to define SDB. Sleep stage‐specific autonomic modulation was measured by heart rate variability (HRV) analysis of the first available 5 min RR intervals from each sleep stage. The mean [standard deviation (SD)] age was 112 (21) months (49% male and 25% non‐Caucasian). The average AHI was 0.79 (SD = 1.03) h^?1, while 73.0%, 25.8% and 1.2% of children had AHI <1 (no SDB), 1–5 (mild SDB) and ≥5 (moderate SDB), respectively. In the no SDB group, the high frequency (HF) and root mean square SD (RMSSD) increased significantly from wake to Stage 2 and slow wave sleep (SWS), and then decreased dramatically when shifting into rapid eye movement (REM) sleep. In the moderate SDB group, the pattern of HRV shift was similar to that of no SDB. However, the decreases in HF and RMSSD from SWS to REM were more pronounced in moderate SDB children [between‐group differences in HF (?24% in moderate SDB versus ?10% in no SDB) and RMSSD (?27% versus ?12%) were significant (P < 0.05)]. The REM stage HF is significantly lower in the moderate SDB group compared to the no SDB group [mean (standard error): 4.49 (0.43) versus 5.80 (0.05) ms², respectively, P < 0.05]. Conclusions are that autonomic modulation shifts significantly towards higher parasympathetic modulation from wake to non‐rapid eye movement sleep, and reverses to a less parasympathetic modulation during REM sleep. However, the autonomic modulation is impaired among children with moderate SDB in the directions of more reduction in parasympathetic modulation from SWS to REM sleep and significantly weaker parasympathetic modulation in REM sleep, which may lead to higher arrhythmia vulnerability, especially during REM sleep.     

EEG arousals in normal sleep: variations induced by total and selective slow-wave sleep deprivation

STUDY OBJECTIVES: Aim of the present study was to assess changes in arousal rates after selective slow-wave (SWS) and total sleep deprivations. DESIGN: Two-way mixed design comparing the arousal index (Al), as expressed by the number of EEG arousals divided by sleep duration, in totally or selectively sleep deprived subjects. SETTING: Sleep laboratory. PATIENTS OR PARTICIPANTS: Nineteen normal male subjects [mean age=23.3 years (S.E.M.=0.55)]. INTERVENTIONS: Al was measured in baseline nights and after selective SWS (N=10) and total sleep deprivation (N=9). MEASUREMENTS AND RESULTS: During the baseline nights AI values changed across sleep stages as follows: stage 1 > stage 2 and REM > SWS, but did not present any significant variations as a function of time elapsed from sleep onset. The recovery after deprivation showed a reduction in EEG arousals, more pronounced after total sleep deprivation; this decrease affected NREM but not REM sleep. During the baseline nights Al showed a close-to-significance negative correlation with REM duration, while during the recovery nights a significant positive relation with stage 1 duration was found. CONCLUSIONS: The present results suggest that recuperative processes after sleep deprivation are also associated with a higher sleep continuity as defined by the reduction of EEG arousals.     

Is narcolepsy a REM sleep disorder? Analysis of sleep abnormalities in narcoleptic Dobermans

Narcolepsy is a chronic sleep disorder marked by excessive daytime sleepiness, cataplexy, sleep paralysis, and hypnagogic hallucinations. Since the discovery of sleep onset REM periods (SOREMPs) in narcoleptic patients, narcolepsy has often been regarded as a disorder of REM sleep generation: REM sleep intrudes in active wake or at sleep onset, resulting in cataplexy, sleep paralysis, or hypnagogic hallucinations. However, this hypothesis has not been experimentally verified. In the current study, we characterized the sleep abnormalities of genetically narcoleptic-cataplectic Dobermans, a naturally occurring animal model of narcolepsy, in order to verify this concept. Multiple sleep latency tests during the daytime revealed that narcoleptic Dobermans exhibit a shorter sleep latency and a higher frequency of SOREMPs, compared to control Dobermans. The total amount of time spent in wake and sleep during the daytime is not altered in narcoleptic dogs, but their wake and sleep patterns are fragmented, and state transitions into and from wake and other sleep stages are altered. A clear 30 min REM sleep cyclicity exists in both narcoleptic and control dogs, suggesting that generation of the ultradian rhythm of REM sleep is not altered in narcoleptics. In contrast, cataplexy displays no cyclicity and can be elicited in narcoleptic animals anytime with emotional stimulation and displays no cyclicity. Stimulation of a cholinoceptive site in the basal forebrain induces a long-lasting attack of cataplexy in narcoleptic dogs; however, bursts of rapid eye movements during this state still occur with a 30 min cyclicity. Sites and mechanisms for triggering cataplexy may therefore be different from those for REM sleep. Cataplexy and a dysfunction in the maintenance of vigilance states, but not abnormal REM sleep generation, may therefore be central to narcolepsy.