Disorganization Of Sleep Research Articles

The cation exchanger Letm1, circadian rhythms, and NAD(H) levels interconnect in diurnal zebrafish.

Mitochondria are fundamental for life and require balanced ion exchange to maintain proper functioning. The mitochondrial cation exchanger LETM1 sparks interest because of its pathophysiological role in seizures in the Wolf Hirschhorn Syndrome (WHS). Despite observation of sleep disorganization in epileptic WHS patients, and growing studies linking mitochondria and epilepsy to circadian rhythms, LETM1 has not been studied from the chronobiological perspective. Here we established a viable letm1 knock-out, using the diurnal vertebrate Danio rerio to study the metabolic and chronobiological consequences of letm1 deficiency. We report diurnal rhythms of Letm1 protein levels in wild-type fish. We show that mitochondrial nucleotide metabolism is deregulated in letm1-/- mutant fish, the rate-limiting enzyme of NAD+ production is up-regulated, while NAD+ and NADH pools are reduced. These changes were associated with increased expression amplitude of circadian core clock genes in letm1-/- compared with wild-type under light/dark conditions, suggesting decreased NAD(H) levels as a possible mechanism for circadian system perturbation in Letm1 deficiency. Replenishing NAD pool may ameliorate WHS-associated sleep and neurological disorders.

Evaluation of the structural organization of sleep in obstructive apnea syndrome from the perspective of modern pathophysiology

To evaluate the features of structural organization of sleep in men 35-55 years of age with varying degrees of severity and duration of clinical manifestations of obstructive sleep apnea syndrome (OSAS) from the perspective of modern pathophysiology. The study included 49 male patients, aged 35-55 years (average age was 43.4±9.2 years), with a body mass index (BMI) of 33.64±1.2 kg/m2 with complaints of snoring of varying degrees of intensity, daytime sleepiness, arrest of breathing during sleep (according to others). The control group consisted of 15 healthy men who did not have complaints of sleep disorders and clinical manifestations of OSAS. The Pittsburgh sleep quality index (PSQI) questionnaire and polysomnographic monitoring study (PSG) were used. According to the results of the polysomnographic study, all patients were divided into 2 subgroups: 12 men of group 1with moderate OSAS (duration of clinical manifestations 4.5±1.0 years) and 37 men of group 2 with severe OSAS (duration 1.5±1.5 years). A decrease in the sleep quality was detected in 61.9% of patients in the group 1 and 89.2% of patients in the group 2. Significantly higher scores for the components of «sleep disturbance» and «daytime dysfunction» in patients with a longer duration of clinical manifestations were detected. Changes in the structure of sleep were identified in patients compared with controls. A statistically significant increase in WASO led to the reduction of sleep efficiency. In patients of group 2, a deficiency of the deep stages and REM-sleep was determined. There was a significant increase in the number of arousals in patients of both groups relative to the controls. Moreover, significant between-group differences were found. The short duration of OSAS symptoms causes a restructuring of the physiological system of sleep homeostasis to a different level of functioning with compensatory hyperfunction of the structures responsible for REM sleep and a decrease (economization) in the activity of anabolic processes during sleep due to a decrease in SWS, which is a characteristic feature of long-term adaptation. Severe course of OSAS leads to the appearance of specific phenomena of gross structural disorganization of sleep - «alpha-delta sleep» and disruption of its segmental organization, which shows the depletion and disruption of compensatory-adaptive mechanisms in the system of sleep homeostasis, disintegration and transformation of functional physiological system in the pathological condition.

Inhibition of neural activity depletes orexin from rat hypothalamic slice culture

Orexins (hypocretins) are neuropeptides produced by a small population of hypothalamic neurons whose dysregulation may lead to narcolepsy, a neurological disorder characterized by disorganization of sleep and wakefulness. Excessive stimulation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors causes preferential loss of orexin neurons in the hypothalamus, whereas an adequate level of neuronal excitatory activities is generally known to be important for the maintenance of central neurons. By examining the effect of manipulation of neural activity, we found that 24-72 hr application of tetrodotoxin (TTX) caused a substantial decrease in the number of orexin-immunoreactive neurons, but not of melanin-concentrating hormone-immunoreactive neurons, in hypothalamic slice culture. Similar results were obtained when neural activity was arrested by added extracellular Mg(2+). Reduction of orexin expression by TTX and Mg(2+) was also observed at mRNA level. The decrease of orexin-immunoreactive neurons was attributable to depletion of orexin, because it was reversible after washout of TTX or elevated extracellular Mg(2+) and was not associated with induction of cell death. Blockers of voltage-dependent Ca(2+) channels as well as of NMDA receptors also induced a significant and selective decrease of orexin-immunoreactive neurons. Moreover, TTX-induced decrease of orexin immunoreactivity was largely abrogated by concurrent application of a moderate concentration of NMDA. These results suggest that Ca(2+) entry associated with nontoxic levels of spontaneous activity of glutamatergic inputs plays an important role in the maintenance of orexin neurons in a tissue culture model.

Sleep and time course of consolidation of visual discrimination skills in patients with narcolepsy–cataplexy

The level of procedural skills improves in normal individuals when the acquisition is followed by a period of sleep rather than wake. If sleep plays an important role in the consolidation process the advantage it provides should be reduced or delayed when its organization is altered, as in patients with chronic sleep disorders. To test this prediction in patients with narcolepsy-cataplexy (NC), who usually have a more fragmented organization of sleep than normals, we compared the initial, intermediate and delayed level of consolidation of visual skills. Twenty-two drug-naive NC patients and 22 individually-matched controls underwent training at a texture discrimination task (TDT) and were re-tested on the next morning (after a night spent in laboratory with polysomnography) and after another six nights (spent at home). TDT performance was worse in patients than controls at training and at both retrieval sessions and the time course of consolidation was different in NC patients (who improved mainly from next-day to 7th-day retrieval session) compared with controls. Moreover, the less-improving patients at next-day retrieval had a wider disorganization of sleep, probably because of an episode of rapid eye movement (REM) sleep at sleep onset REM, on post-training night more frequently than more-improving patients. These findings suggest that the time course of the consolidation process of procedural skills may be widely influenced by the characteristics of sleep organization (varying night-by-night much more in NC patients than controls) during post-training night.

Repos de sécurité : quels enjeux ?

In 2003 were promulgated the texts regulating rest and safety, in the USA (approved by the ACGME) and in France (January 9th, 2001 and September 14th, 2001). The institution of the “rest for safety”, an eleven hours duration interruption of activity, immediately after a night-call, can be viewed as a progress in the search for safety. Several studies showed a link between excessive work hours and occurrence of medical incidents related to tiredness. However published data do not show a link between tiredness and patients endangering. The tiredness resulting from sleep deprivation and disturbances in circadian rhythms is a cumulative phenomenon erased by a period of rest. In spite of a large individual variability, tiredness increases anxiety scores, irritability, depression and it deteriorates cognitive performances. The concept of “prophylactic” rest considers that a subject cannot start, rested, a work if he did not sleep at least 5 hours the previous night, or 12 hours during the previous 48 hours. The second important aspect of the rest for safety is the long-term prevention of potential pathologies in medical staff, in particular burnout syndrome. In our profession, night calls are considered most stressful; the psychological stress related to anticipation and night context causes measurable cardiovascular disturbances in anesthesiologists. Shift-work sleep disorders may induce gastric ulcers, heart attacks, metabolic syndrome, depression and accidents related to somnolence. Long duration work-hours, accompanied by sleep deprivation, may double the risk of car accidents in junior physicians, in whom vigilance levels can compare with those of patients concerned by narcolepsy or with the cognitive disturbances induced by alcohol intoxication. Reduced work-hours improve vigilance and divide by three the rate of serious medical errors. True opportunities of sleep and control of sleep duration at the individual level could be suggested. The idea that taking the necessary rest would be synonymous with a decrease of efficiency in patient care is not demonstrated, but the danger of a poorer information transmission should be handed with an optimization of our manpower and organization. Aging is accompanied by a progressive disorganization of sleep. The foreseeable shortage of manpower, synonymous with aging of the medical actors and increased vulnerability to tiredness, is a posteriori the justification of the institution of the rest for safety.

Visual function in infants with West syndrome: correlation with EEG patterns.

Several studies have reported behavioral and electrophysiological evidence of visual impairment during the active stage of West syndrome. The underlying mechanisms are, however, poorly understood, and little has been reported about the correlation between visual impairment, EEG patterns, and brain lesions. The aim of the study was to assess visual function at the onset of spasm and 2 months thereafter and relate visual findings to brain lesions and EEG features. Twenty-five infants with West syndrome were enrolled and studied with (a) a full clinical assessment including a battery of tests specifically designed to assess visual function, (b) a video-polygraphic study, and (c) brain magnetic resonance imaging (MRI). Besides brain neuroimaging and EEG comparison with visual function, an intra-EEG analysis was performed to investigate the possible relation of EEG patterns to fluctuating visual behavior (fixation and following). Twenty-two children had at least one abnormal result on one or more of the tests assessing visual function at T0. Visual impairment at the spasm onset was related to the sleep disorganization rather than to the hypsarrhythmic pattern in awake EEG. After 2 months, both EEG features become significantly linked to visual function. Visual function improved in several cases after 2 months, in parallel with the seizure regression. No relation was found between EEG patterns and fluctuating visual behavior. The study supplies new evidence of the involvement of visual function in West syndrome. The presence of abnormal visual findings in infants without lesions on brain MRI suggests that visual abnormalities are due not only to brain injury but also to epileptic disorder per se. New insight is also provided into the possible mechanisms underlying clinical and EEG abnormalities.

The organization of rapid eye movement activity during rapid eye movement sleep is further impaired in very old human subjects

Rapid eye movement activity (REMA) during rapid eye movement (REM) sleep was studied in seven very old (‘old-old’) subjects. Beyond global quantitative features (REMA density), we evaluated the organizational aspects of REMA, that is its occurrence in burst mode, which were compared to a group of younger elderly subjects (‘young-old’). REMA density in ‘old-old’ subjects is not significantly different from that of ‘young-old’ subjects. The same lack of difference in the two groups is found for the number of REMA bursts. By contrast, the duration of REMA bursts is reduced in the ‘old-old’ subjects, as well as the ‘burst state-to-burst-state’ probability, i.e. the probability for successive inter-REMA time intervals to be part of the same REMA burst. Our results clearly show that the trend towards an impairment of REMA organizational aspects continues with aging. This is consistent with the hypothesis that sleep disorganization keeps worsening with age. However, it is of interest to observe that the capability of producing REMA bursts is preserved despite aging.

Morning recall of verbal material depends on prior sleep organization

Despite the evidence that sleep may facilitate memory, controversial findings concern the role of sleep states (NREM, REM). We put forward the hypothesis that sleep organization, i.e. the regular occurrence of NREM–REM cycles, more than sleep states per se, may be crucial for the retention of verbal material presented before sleep. An experiment was performed in which recall of verbal material was requested of young subjects after three different kinds of night sleep: undisturbed sleep, fragmented sleep without sleep cycles disorganization, and fragmented sleep interrupted with sleep disorganization. Morning recall of verbal material was impaired after the night with disturbed sleep cycles, whereas it was not after the night with preserved sleep cycles; the amount of REM was similar in both cases. We conclude that the recall of verbal material is greatly affected by sleep cycle disorganization.

Sleep disorganization in cocaine-exposed neonates

The purpose of the study was to examine the effect of prenatal cocaine exposure on infant sleep and wakefulness. Four-hour recordings of sleep and wakefulness were obtained from 17 cocaine-exposed neonates and 14 control infants at 2 weeks of age. Each 1-min epoch was classified as quiet sleep, active sleep, indeterminate sleep, or waking based on eye and body movements and respiratory variability. Analyses of variance were performed on durations of total sleep versus wakefulness, and quiet sleep, active sleep, and indeterminate sleep. The cocaine-exposed infants showed proportions of sleep and wake time similar to those of the control infants. Sleep time was, however, distributed differently among the various sleep states in the cocaine-exposed infants. Infants with prenatal cocaine exposure showed significantly more indeterminate sleep and significantly less active sleep than the control infants, even when confounding variables were controlled statistically. Regression analyses indicated that infrequent cocaine use paradoxically increased indeterminate sleep time to a greater extent than frequent use, possibly due to differences in patterns of cocaine use of recency of exposure. These results suggest that active sleep is less organized at 2 weeks of age in infants of cocaine-abusing mothers than in infants without cocaine exposure.