A dose–response study of total sleep time and the ability to maintain wakefulness

The apparent connection between sleep debt, performance decrements and workplace accidents has generated a need for feasible vigilance tests that focus on the quantification of daytime sleepiness in occupational settings. The objective of this study was to evaluate the sensitivity of the Maintenance of Wakefulness Test (MWT) to acute sleep deprivation of various doses. Eight healthy female volunteers, mean age 28.9 years (range 23–36), participated in this laboratory study. After an adaptation night, the subjects were assigned to four counterbalanced, randomly ordered night sleep conditions. These four conditions allowed for a time in bed (TIB) of 0, 2, 4 or 8 h, producing a total sleep time of 0, 113, 218 and 427 min, respectively. The ability to sustain wakefulness was measured after the TIB period at 11.00 and 17.00 hours by the MWT. Analysis of variance with repeated measures was used to study the dependence of MWT sleep latencies on the immediately prior TIB period. Both the latency of stage 1 sleep onset and the appearance of slow eye movements reduced significantly with increased sleep loss. The quantitative relationship between the previous total sleep time and the subsequent MWT sleep latencies followed an exponentially decaying function showing a high sensitivity to acute, severe night sleep loss but low sensitivity to less severe sleep restrictions. It is concluded that the MWT seems to be a sensitive method for the estimation of acute sleep deprivation. The test results appear, however, non-linearly related to the earlier sleep debt.     

Sleep on the Night Shift: 24-Hour EEG Monitoring of Spontaneous Sleep/Wake Behavior

The present study sought to objectively describe the spontaneous sleep/wakefulness pattern of shift workers during a 24-hour period. Portable Medilog tape-recorders were used for ambulatory EEG monitoring of 25 male papermill workers (25-55 years) during days with night and afternoon work. The results showed that sleep after night work was two hours shorter than after afternoon work. The sleep reduction affected mainly Stage 2 and REM sleep while slow wave sleep was unchanged. In connection with night work 28% of the workers took a nap in the afternoon. These naps contained a large proportion of slow wave sleep and were, apparently, caused by the sleep deficit after the short main sleep period. The EEG recordings also revealed that 20% of the participants had sleep episodes during night work. These naps were as long as the afternoon naps, were experienced as "dozing offs" rather than naps, occurred at the time of the trough of the circadian wakefulness rhythm, and were concomitant with extreme subjective sleepiness and low rated work load. It was concluded that not only the sleep of shift workers was disturbed, but also the wakefulness--to the extent that sleepiness during night work sometimes reached a level where reasonable wakefulness could not be maintained. The latter observation is probably of special importance in work situations demanding a great responsibility for human lives or for great economic values.     

Long-term enhancement of REM sleep by the pituitary adenylyl cyclase-activating polypeptide (PACAP) in the pontine reticular formation of the rat

In rats, rapid eye movement (REM) sleep can be elicited by microinjection of vasoactive intestinal polypeptide (VIP) into the oral pontine reticular nucleus (PnO). In the present study, we investigated whether this area could also be a REM-promoting target for a peptide closely related to VIP: the pituitary adenylyl cyclase-activating polypeptide (PACAP). When administered into the posterior part of the PnO, but not in nearby areas, of freely moving chronically implanted rats, PACAP-27 and PACAP-38 (0.3 and 3 pmol) induced a marked enhancement (60-85% over baseline) of REM sleep for 8 h that could be prevented by prior infusion of the antagonist PACAP-(6-27) (3 pmol) into the same site. Moreover, injections of PACAP into the centre of the posterior PnO resulted in REM sleep enhancement which could last for up to 11 consecutive days. Quantitative autoradiography using [125I]PACAP-27 revealed the presence in the PnO of specific binding sites with high affinity for PACAP-27 and PACAP-38 (IC50 = 2.4 and 3.2 nM, respectively), but very low affinity for VIP (IC50 > 1 microM). These data suggest that PACAP within the PnO may play a key role in REM sleep regulation, and provide evidence for long-term (several days) mechanisms involved in such a control. PAC1 receptors which have a much higher affinity for PACAP than for VIP might mediate this long-term action of PACAP on REM sleep.     

Circadian and sleep/wake dependent aspects of subjective alertness and cognitive performance

Circadian and sleep/wake dependent processes underlying variations in subjective alertness and cognitive performance were assessed in a constant routine protocol and in a protocol in which the sleep/wake cycle was uncoupled from the output of the endogenous circadian pacemaker. In the latter protocol, the contribution of a sleep/wake dependent process and a circadian process to alertness and performance were separated by folding the data at either the period of the sleep/wake cycle or at the period of the endogenous circadian body temperature rhythm. This analysis revealed that prior wakefulness within a range of 0-18 h significantly reduced alertness and performance and that the circadian rhythm of core body temperature paralleled the circadian rhythm of alertness and performance. During the first 16 h of the constant routine protocol, which coincided with the subjects' habitual period of wakefulness, alertness and performance remained at a stable level. The latter finding was explained by assuming that during our usual waking day the circadian system counteracts the detrimental effects of increasing duration of prior wakefulness.     

Heart rate variability during wakefulness as a marker of obstructive sleep apnea severity

Study ObjectivesPatients with obstructive sleep apnea (OSA) exhibit heterogeneous heart rate variability (HRV) during wakefulness and sleep. We investigated the influence of OSA severity on HRV parameters during wakefulness in a large international clinical sample.Methods1247 subjects (426 without OSA and 821 patients with OSA) were enrolled from the Sleep Apnea Global Interdisciplinary Consortium. HRV parameters were calculated during a 5-minute wakefulness period with spontaneous breathing prior to the sleep study, using time-domain, frequency-domain and nonlinear methods. Differences in HRV were evaluated among groups using analysis of covariance, controlling for relevant covariates.ResultsPatients with OSA showed significantly lower time-domain variations and less complexity of heartbeats compared to individuals without OSA. Those with severe OSA had remarkably reduced HRV compared to all other groups. Compared to non-OSA patients, those with severe OSA had lower HRV based on SDNN (adjusted mean: 37.4 vs. 46.2 ms; p < 0.0001), RMSSD (21.5 vs. 27.9 ms; p < 0.0001), ShanEn (1.83 vs. 2.01; p < 0.0001), and Forbword (36.7 vs. 33.0; p = 0.0001). While no differences were found in frequency-domain measures overall, among obese patients there was a shift to sympathetic dominance in severe OSA, with a higher LF/HF ratio compared to obese non-OSA patients (4.2 vs. 2.7; p = 0.009).ConclusionsTime-domain and nonlinear HRV measures during wakefulness are associated with OSA severity, with severe patients having remarkably reduced and less complex HRV. Frequency-domain measures show a shift to sympathetic dominance only in obese OSA patients. Thus, HRV during wakefulness could provide additional information about cardiovascular physiology in OSA patients.Clinical Trial Information: A Prospective Observational Cohort to Study the Genetics of Obstructive Sleep Apnea and Associated Co-Morbidities (German Clinical Trials Register - DKRS, DRKS00003966) https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00003966     

Modafinil in the treatment of idiopathic hypersomnia without long sleep time—a randomized,double‐blind,placebo‐controlled study

In 2010 the European Medicines Agency withdrew the indication of modafinil for the treatment of obstructive sleep apnea, shift work sleep disorder and for idiopathic hypersomnia (IH). In uncontrolled studies, modafinil has been reported to be efficacious in the treatment of sleep disorders. We therefore performed a randomized, placebo‐controlled study with the aim of proving the efficacy of modafinil treatment in these patients. Drug‐free IH patients without long sleep according to ICSD2 criteria, age >18 years and disease duration >2 years were included. After a washout phase, patients at baseline received placebo or 100 mg modafinil in the morning and at noon over 3 weeks, followed by 1 week without medication. At each visit the Epworth Sleepiness Scale (ESS) and Clinical Global Impression (CGI) rating scale were performed. At baseline and on days 8 and 21 four Maintenance of Wakefulness Tests (MWTs)/day or per day were performed. Patients kept a sleep–wake diary throughout the study. Between 2009 and 2011 three sleep centres recruited 33 participants. Compared to placebo, modafinil decreased sleepiness significantly and improved mean sleep latency in the MWT non‐significantly. The CGI improved significantly from baseline to the last visit on treatment. The most frequent adverse events were headaches and gastrointestinal disorders; skin and psychiatric reactions were not reported. The number of reported naps and duration of daytime sleepiness decreased significantly. Total sleep time of nocturnal sleep was slightly reduced. The sleep diaries showed increases in feeling refreshed in the morning; the diurnal diaries showed significant improvement of performance and of exhaustion. Modafinil is an effective and safe medication in the treatment of IH. Adverse events are mild to moderate.     

Assessment of Nociception and Pain in Participants in an Unresponsive or Minimally Conscious State After Acquired Brain Injury: The Relation Between the Coma Recovery Scale–Revised and the Nociception Coma Scale–Revised

Objectives

To investigate the relation between consciousness and nociceptive responsiveness (ie, Nociception Coma Scale–Revised [NCS-R]), to examine the suitability of the NCS-R for assessing nociception in participants with disorders of consciousness (DOC), and to replicate previous findings on psychometric properties of the scale.

Late recovery of awareness in prolonged disorders of consciousness –a cross-sectional cohort study

Purpose: To detect any improvement of awareness in prolonged disorders of consciousness in the long term.

Methods: A total of 34 patients with prolonged disorders of consciousness (27 vegetative state and seven minimally conscious state; 16 males; aged 21–73) were included in the study. All patients were initially diagnosed with vegetative/minimally conscious state on admission to our specialist neurological rehabilitation unit. Re-assessment was performed 2–16?years later using Coma Recovery Scale-Revised.

Results: Although remaining severely disabled, 32% of the patients showed late improvement of awareness evidenced with development of non-reflexive responses such as reproducible command following and localization behaviors. Most of the late recoveries occurred in patients with subarachnoid hemorrhage (5/11, 45.5%). The ages of patients within the late recovery group (Mean?=?45, SD?=?11.4) and non-recovery group (Mean?=?43, SD?=?15.5) were not statistically different (p?=?0.76).

Conclusions: This study shows that late improvements in awareness are not exceptional in non-traumatic prolonged disorders of consciousness cases. It highlights the importance of long-term follow up of patients with prolonged disorders of consciousness, regardless of the etiology, age, and time passed since the brain injury. Long-term follow up will help clinicians to identify patients who may benefit from further assessment and rehabilitation. Although only one patient achieved recovery of function, recovery of awareness may have important ethical implications especially where withdrawal of artificial nutrition and hydration is considered.

• Implications for rehabilitation

• Long-term regular follow-up of people with prolonged disorders of consciousness is important.

• Albeit with poor functional outcomes late recovery of awareness is possible in both traumatic and non-traumatic prolonged disorders of consciousness cases.

• Recovery of awareness has significant clinical and ethical implications especially where withdrawal of artificial nutrition and hydration is considered.

     

Suicidal ideation is associated with nighttime wakefulness in a community sample

Study ObjectivesNocturnal wakefulness is a risk factor for suicide and suicidal ideation in clinical populations. However, these results have not been demonstrated in general community samples or compared to sleep duration or sleep quality. The present study explored how the timing of wakefulness was associated with suicidal ideation for weekdays and weekends.MethodsData were collected from 888 adults aged 22–60 as part of the Sleep and Healthy Activity, Diet, Environment, and Socialization study. Suicidal ideation was measured by the Patient Health Questionnaire-9, while timing of wakefulness was estimated from the Sleep Timing Questionnaire. Binomial logistic regressions estimated the association between nocturnal (11 pm–5 am) and morning (5 am–11 am) wakefulness and suicidal ideation.ResultsNocturnal wakefulness was positively associated with suicidal ideation on weekdays (OR: 1.44 [1.28–1.64] per hour awake between 11:00 pm and 05:00 am, p < 0.0001) and weekends (OR: 1.22 [1.08–1.39], p = 0.0018). Morning wakefulness was negatively associated with suicidal ideation on weekdays (OR: 0.82 [0.72–0.92] per hour awake between 05:00 am and 11:00 am, p = 0.0008) and weekends (OR: 0.84 [0.75–0.94], p = 0.0035). These associations remained significant when adjusting for sociodemographic factors. Additionally, nocturnal wakefulness on weekdays was associated with suicidal ideation when accounting for insomnia, sleep duration, sleep quality, and chronotype (OR 1.25 [1.09–1.44] per hour awake, p = 0.002).ConclusionWakefulness at night was consistently associated with suicidal ideation. Additionally, morning wakefulness was negatively associated with suicidal ideation in some models. Although these findings are drawn from a non-clinical sample, larger longitudinal studies in the general population are needed to confirm these results.