Evening administration of melatonin and bright light: Interactions on the EEG during sleep and wakefulness

Both the pineal hormone melatonin and light exposure are considered to play a major role in the circadian regulation of sleep. In a placebo- controlled balanced cross-over design, we investigated the acute effects of exogenous melatonin (5 mg p.o. at 20.40 hours) with or without a 3-h bright light exposure (5000 lux from 21.00 hours–24.00 hours) on subjective sleepiness, internal sleep structure and EEG power density during sleep and wakefulness in healthy young men. The acute effects of melatonin, bright light and their interaction were measured on the first day (treatment day), possible circadian phase shifts were assessed on the post-treatment day. On the treatment day, the evening rise in subjective sleepiness was accelerated after melatonin and protracted during bright light exposure. These effects were also reflected in specific changes of EEG power density in the theta/alpha range during wakefulness. Melatonin shortened and bright light increased sleep latency. REMS latency was reduced after melatonin administration but bright light had no effect. Slow-wave sleep and slow-wave activity during the first non-rapid eye movement (NREMS) episode were suppressed after melatonin administration and rebounded in the second NREMS episode, independent of whether light was co-administered or not. Self rated sleep quality was better after melatonin administration whereas the awakening process was rated as more difficult after bright light. On the post-treatment day after evening bright light, the rise in sleepiness and the onset of sleep were delayed, independent of whether melatonin was co-administered or not. Thus, although acute bright light and melatonin administration affected subjective sleepiness, internal sleep structure and EEG power density during sleep and wakefulness in a additive manner, the phase shifting effect of a single evening bright light exposure could not be blocked by exogenous melatonin     

Time course of EEG background activity level before spontaneous awakening in infants

This research aimed to investigate the time course of the cortical activity level preceding spontaneous awakening as a function of age and state. Two groups of infants (1-4 and 9-14 weeks of age) were continuously monitored by polygraphic recording and behavioural observation during the night. The electroencephalographic (EEG) activity recorded by the C3-O1 lead was analysed through an automatic analysis method which provides, for each 30-s epoch, a single measure, time domain based, of the EEG synchronization. The EEG parameter values were computed in the 6 min preceding each awakening out of non-rapid eye movement (NREM) sleep and out of rapid eye movement (REM) sleep. The EEG background activity level did not change in the minutes preceding awakening out of REM sleep. Awakening out of NREM sleep was preceded by a change of EEG activity level in the direction of higher activation with different time course according to the age. Both REM and NREM sleep results suggest that a high level of EEG activity is a prerequisite for the occurrence of a spontaneous awakening.     

Increased sodium-proton antiporter activity in patients with obstructive sleep apnoea

Cytosolic pH (pH(i)) and the activity of the sodium-proton antiporter (Na(+)/H(+) antiporter) were measured in lymphocytes from 22 patients with obstructive sleep apnoea and from 24 age-matched healthy subjects (Controls). The cellular Na(+)/H(+) antiporter was measured spectrophotometrically using a pH-sensitive fluorescent dye after intracellular acidification using sodium propionate. Resting pHi was similar in lymphocytes from patients with obstructive sleep apnoea and from controls (7.36 +/- 0.20, n=22; vs. 7.35 +/- 0.19, n=24; mean +/- SD). The Na(+)/H(+) antiporter activity was significantly higher in patients with obstructive sleep apnoea than in controls (11.87 +/- 3.26 x 10(-3) pH(i)/s vs. 4.38 +/- 1.40 x 10(-3) pH(i)/s; P < 0. 0001). The apparent affinity of the Na+/H+ antiporter was not significantly different between the groups (6.90 +/- 0.23 vs. 6.87 +/- 0.20). In patients with obstructive sleep apnoea the activity of the Na(+)/H(+) antiporter remained stable during the night. The activity of the Na(+)/H(+) antiporter was 13.49 +/- 4.80 x 10(-3) pH(i)/s at 20.00 and 13.26 +/- 6.13 x 10(-3) pH(i)/s at 02.00. From the present results it is concluded that an increased cellular Na(+)/H(+) antiporter activity may be a genetic marker for patients who are predisposed to obstructive sleep apnoea.     

Sleep apnea-related cognitive deficits and intelligence: an implication of cognitive reserve theory

Cognitive deficits in patients with obstructive sleep apnea syndrome (OSAS) are well demonstrated, but the pathophysiology of these deficits is still controversial, as the relationship between OSA severity and cognitive deficits is usually weak. Our study considers the possible relationship between OSA-related cognitive deficits and the overall intellectual function of OSA patients. Forty-seven OSA patients and 36 normal individuals underwent a neuropsychological battery test assessing attention and alertness. According to the resulting IQ score, patients and controls were divided into a high-intelligence group (IQ > or = 90th percentile) and a normal-intelligence group (50 < or = IQ < 90%ile). Between the two patient groups there were no significant differences noticed, regarding OSA severity or sleepiness. High-intelligence patients showed the same attention/alertness performance compared with the high-intelligence controls. On the contrary, patients with normal-intelligence showed attention/alertness decline compared with the normal-intelligence control group. The two patient groups were re-examined with the same battery test after at least 1 year of CPAP treatment. At re-examination neither patient group showed any differences regarding attention and alertness compared with the control groups. We assume that high-intelligence may have a protective effect against OSA-related cognitive decline, perhaps due to increased cognitive reserve.     

Respiration in NREM and REM sleep after upper airway surgery for obstructive sleep apnoea

SUMMARY  To verify whether upper airway surgery in obstructive sleep apnoea syndrome affects differently respiration in NREM and REM sleep, 22 patients were studied by polysomnography before and three months after surgical treatment. On the average, treatment improved respiration during both sleep states, but no significant interaction was found between sleep state and effect of surgical treatment. According to the response to treatment, three groups of patients were identified: the first group ( N = 6), with an improvement in apnoea-hypopnoea index (AHI), percentage of sleep time spent in apnoea and hypopnoea (time in AH) and mean oxyhaemoglobin saturation (SaO₂) in both NREM and REM sleep; the second group ( N = 5), with an improvement in AHI only in NREM sleep, associated with improvement in mean SaO₂ in both sleep states; the third group ( N = 11), without any improvement in AHI and time in AH, either associated ( N = 5) or not ( N = 6) with an improvement in mean SaO₂ in both sleep states. An increase in the percentage of hypopnoeas out of the total AHI after treatment could partly account for the apparent discrepancy between AHI and mean SaO₂ behaviour in the subjects of the second group, but not in the patients of the third group who improved their mean SaO₂. Mixed apnoeas occurred before surgery in six subjects; they remained numerous after surgery only in two subjects who did not show any SaO₂ improvement. In conclusion, the degree of improvement in respiration after upper airway surgery was similar in every patient in NREM and REM sleep.     

阻塞性睡眠呼吸暂停低通气综合征的MRI研究

目的：探讨磁共振成像（MRI）对确定阻塞性睡眠呼吸暂停低通气综合征（OSAHS）病人阻塞部位的作用。方法：通过对35例OSAHS男性患者行多导睡眠仪、MRI及纤维喉镜检查配合Muller’s运动检查（FEMM）、同时对30例男性健康人的上呼吸道进行MRI检查，将两者检查结果进行比较，判定OSAHS患者上呼吸道狭窄的部位及狭窄程度，客观评价MRI对检查OSAHS患者的应用价值。结果：OSAHS患者的上呼吸道截面积明显小于健康人，轻度OSAHS患者多存在腭咽平面狭窄；中重度组OSAHA患者大部分所有平面都存在狭窄，但中度组以腭咽狭窄较明显，而重度组所有平面均存在较明显的狭窄，这种狭窄主要是由于口咽部周围软组织增生及软腭过长、肥厚及舌根宽大、肥厚所致。结论：MRI检查可判定OSAHS患者上呼吸道狭窄的部位及狭窄程度，有助于治疗方案的选择，对预估手术疗效具有重要的意义。     

Sleep-wake rhythm in an irregular shift system

Sleep in shift work has been studied extensively in regular shift systems but to a lesser degree in irregular shifts. Our main aim was to examine the sleep-wake rhythm in shift combinations ending with the night or the morning shift in two irregular shift systems. Three weeks' sleep/work shift diary data, collected from 126 randomly selected train drivers and 104 traffic controllers, were used in statistical analyses including a linear mixed model and a generalized linear model for repeated measurements. The results showed that the sleep-wake rhythm was significantly affected by the shift combinations. The main sleep period before the first night shift shortened by about 2 h when the morning shift immediately preceded the night shift as compared with the combination containing at least 36 h of free time before the night shift (reference combination). The main sleep period before the night shift was most curtailed between two night shifts, on average by 2.9 and 3.5 h among the drivers and the controllers, respectively, as compared with the reference combination. Afternoon napping increased when the morning or the day shift immediately preceded the night shift, the odds being 4.35-4.84 in comparison with the reference combination. The main sleep period before the morning shift became 0.5 h shorter when the evening shift preceded the morning shift in comparison with the sleep period after a free day. The risk for dozing off during the shift was associated only with the shift length, increasing by 17 and 35% for each working hour in the morning and the night shift, respectively. The results demonstrate advantageous and disadvantageous shift combinations in relation to sleep and make it possible to improve the ergonomy of irregular shift systems.     

Exploring the potential association among sleep disturbances,cognitive impairments,and immune activation in 22q11.2 deletion syndrome

22q11.2 deletion syndrome (22q11.DS) is a neurogenetic disorder caused by a microdeletion in chromosome 22. Its phenotype includes high rates of psychiatric disorders, immune system abnormalities, and cognitive impairments. We assessed the quality of sleep in 22q11.2DS and its potential link to inflammatory markers and cognitive deficits. Thirty‐three 22q11.2DS individuals and 24 healthy controls were studied. Sleep parameters were assessed by the Pittsburgh sleep quality index (PSQI) questionnaire and correlated with serum cytokine levels and cognitive functioning, measured using the Penn computerized neurocognitive battery (CNB). The 22q11.2DS individuals had significantly worse sleep quality scores than the controls, unrelated to the psychiatric or physical comorbidities common to 22q11.2DS. Interleukin 6 levels were correlated with the overall score of the PSQI questionnaire for nonpsychotic 22q11.2DS participants only. Several domains of the CNB were associated with poorer sleep quality, suggesting that cognitive impairments in 22q11.2DS may be at least partially explained by poor sleep quality. Our findings confirm sleep impairments in individuals with 22q11.2DS, which might negatively affect their cognitive functioning, and corroborate a potential role of immunological pathways in the 22q11.2DS neuro‐phenotype.     

The effects of levetiracetam on objective and subjective sleep parameters in healthy volunteers and patients with partial epilepsy

Levetiracetam is a novel antiepileptic drug which has recently been released as an adjunctive treatment for partial epilepsy. In the two studies reported here we examined the objective and subjective effects of levetiracetam on sleep in 12 healthy volunteers and 17 patients [16 who could be evaluated for electroencephalogram (EEG) recordings] with a history of partial epilepsy on stable carbamazepine monotherapy. The studies were of a similar double-blind crossover placebo-controlled design with subjects' sleep being recorded in their own homes. The results from the two studies showed considerable similarities. In both, levetiracetam produced an increase in the time spent in stage 2 sleep, which in the patient study was accompanied by a decrease in the time spent in stage 4 sleep and in the volunteer study an increase in rapid eye movement (REM) latency. The subjective changes included reports that sleep was of a better quality with fewer awakenings and patients also reported that their sleep was more restful. Volunteers and patients did, however, feel less alert on waking in the morning. Therefore, both groups reported a decrease in awakenings after levetiracetam despite the finding from the EEG of no change in the actual number of awakenings. It may be concluded from both studies that levetiracetam does affect some indicators of subjective sleep perception, but does not influence objective sleep measures of sleep continuity. The results from the patient study during placebo add-on treatment also showed that patients on carbamazepine had a marked increase in SWS, an increase in stage 2 sleep and an increase in REM latency compared with healthy volunteers. Interestingly, levetiracetam also reduced bilateral epileptiform EEG activity, particularly in patients with more discharges.