CSF Histamine Contents in Narcolepsy,Idiopathic Hypersomnia and Obstructive Sleep Apnea Syndrome

Study Objective:

To (1) replicate our prior result of low cerebrospinal fluid (CSF) histamine levels in human narcolepsy in a different sample population and to (2) evaluate if histamine contents are altered in other types of hypersomnia with and without hypocretin deficiency.

Design:

Cross sectional studies.

Setting and Patients:

Sixty-seven narcolepsy subjects, 26 idiopathic hypersomnia (IHS) subjects, 16 obstructive sleep apnea syndrome (OSAS) subjects, and 73 neurological controls were included. All patients were Japanese. Diagnoses were made according to ICSD-2.

Results:

We found significant reductions in CSF histamine levels in hypocretin deficient narcolepsy with cataplexy (mean ± SEM; 176.0 ± 25.8 pg/mL), hypocretin non-deficient narcolepsy with cataplexy (97.8 ± 38.4 pg/mL), hypocretin non-deficient narcolepsy without cataplexy (113.6 ± 16.4 pg/mL), and idiopathic hypersomnia (161.0 ± 29.3 pg/mL); the levels in OSAS (259.3 ± 46.6 pg/mL) did not statistically differ from those in the controls (333.8 ± 22.0 pg/mL). Low CSF histamine levels were mostly observed in non-medicated patients; significant reductions in histamine levels were evident in non-medicated patients with hypocretin deficient narcolepsy with cataplexy (112.1 ± 16.3 pg/mL) and idiopathic hypersomnia (143.3 ± 28.8 pg/mL), while the levels in the medicated patients were in the normal range.

Conclusion:

The study confirmed reduced CSF histamine levels in hypocretin-deficient narcolepsy with cataplexy. Similar degrees of reduction were also observed in hypocretin non-deficient narcolepsy and in idiopathic hypersomnia, while those in OSAS (non central nervous system hypersomnia) were not altered. The decrease in histamine in these subjects were more specifically observed in non-medicated subjects, suggesting CSF histamine is a biomarker reflecting the degree of hypersomnia of central origin.

Citation:

Kanbayashi T; Kodama T; Kondo H; Satoh S; Inoue Y; Chiba S; Shimizu T; Nishino S. CSF histamine contents in narcolepsy, idiopathic hypersomnia and obstructive sleep apnea syndrome. SLEEP 2009;32(2):181–187.     

Time-course of cerebrospinal fluid histamine in the wake-consolidated squirrel monkey

Central nervous system (CNS) histamine is low in individuals with narcolepsy, a disease characterized by severe fragmentation of both sleep and wake. We have developed a primate model, the squirrel monkey, with which we can examine the role of the CNS in the wake‐consolidation process, as these primates are day‐active, have consolidated wake and sleep and have cerebrospinal fluid (CSF) that is readily accessible. Using this model and three distinct protocols, we report herein on the role of CNS histamine in the wake consolidation process. CSF histamine has a robust daily rhythm, with a mean of 24.9 ± 3.29 pg mL^?1, amplitude of 31.7 ± 6.46 pg mL^?1 and a peak at 17:49 ± 70.3 min (lights on 07:00–19:00 hours). These levels are not significantly affected by increases (up to 161 ± 40.4% of baseline) or decreases (up to 17.2 ± 2.50% of baseline) in locomotion. In direct contrast to the effects of sleep deprivation in non‐wake‐consolidating mammals, in whom CSF histamine increases, pharmacologically induced sleep (γ‐hydroxybutyrate) and wake (modafinil) have no direct effects on CSF histamine concentrations. These data indicate that the time–course of histamine in CSF in the wake‐consolidated squirrel monkey is robust against variation in activity and sleep and wake‐promoting pharmacological compounds, and may indicate that histamine physiology plays a role in wake‐consolidation such as is present in the squirrel monkey and humans.     

Decreased CSF Histamine in Narcolepsy With and Without Low CSF Hypocretin-1 in Comparison to Healthy Controls

Study Objective:

To examine whether cerebrospinal fluid (CSF) histamine contents are altered in human narcolepsy and whether these alterations are specific to hypocretin deficiency, as defined by low CSF hypocretin-1.

Methods:

Patients meeting the ICSD-2 criteria for narcolepsy with and without cataplexy and who had CSF hypocretin-1 results available were selected from the Stanford Narcolepsy Database on the basis of CSF availability and adequate age and sex matching across 3 groups: narcolepsy with low CSF hypocretin-1 (n = 34, 100% with cataplexy), narcolepsy without low CSF hypocretin-1 (n = 24, 75% with cataplexy), and normal controls (n = 23). Low CSF hypocretin-1 was defined as CSF ≤ 110 pg/mL (1/3 of mean control values). Six of 34 patients with low CSF hypocretin-1, six of 24 subjects with normal CSF hypocretin-1, and all controls were unmedicated at the time of CSF collection. CSF histamine was measured in all samples using a fluorometric HPLC system.

Results:

Mean CSF histamine levels were: 133.2 ± 20.1 pg/mL in narcoleptic subjects with low CSF hypocretin-1, 233.3 ± 46.5 pg/mL in patients with normal CSF hypocretin-1 (204.9 ± 89.7 pg/mL if only patients without cataplexy are included), and 300.5 ± 49.7 pg/mL in controls, reaching statistically significant differences between the 3 groups.

Conclusion:

CSF histamine levels are reduced in human narcolepsy. The reduction of CSF histamine levels was more evident in the cases with low CSF hypocretin-1, and levels were intermediate in other narcolepsy cases. As histamine is a wake-promoting amine known to decrease during sleep, decreased histamine could either passively reflect or partially mediate daytime sleepiness in these pathologies.

Citation:

Nishino S; Sakurai E; Nevsimalova S; Yoshida Y; Watanabe T; Yanai K; Mignot E. Decreased CSF histamine in narcolepsy with and without low CSF hypocretin-1 in comparison to healthy controls. SLEEP 2009;32(2):175-180.     

Daytime continuous polysomnography predicts MSLT results in hypersomnias of central origin

In the diagnostic work‐up of hypersomnias of central origin, the complaint of excessive daytime sleepiness should be objectively confirmed by MSLT findings. Indeed, the features and diagnostic utility of spontaneous daytime sleep at 24 h continuous polysomnography (PSG) have never been investigated. We compared daytime PSG features to MSLT data in 98 consecutive patients presenting with excessive daytime sleepiness and with a final diagnosis of narcolepsy with cataplexy/hypocretin deficiency (n = 39), narcolepsy without cataplexy (n = 7), idiopathic hypersomnia without long sleep time (n = 19), and ‘hypersomnia’ with normal sleep latency at MSLT (n = 33). Daytime sleep time was significantly higher in narcolepsy‐cataplexy but similar in the other groups. Receiver operating characteristics (ROC) curves showed that the number of naps during daytime PSG predicted a mean sleep latency ≤8 min at MSLT with an area under the curve of 0.67 ± 0.05 (P = 0.005). The number of daytime sleep‐onset REM periods (SOREMPs) in spontaneous naps strikingly predicted the scheduled occurrence of two or more SOREMPs at MSLT, with an area under the ROC curve of 0.93 ± 0.03 (P < 10^?12). One spontaneous SOREMP during daytime had a sensitivity of 96% with specificity of 74%, whereas two SOREMPs had a sensitivity of 75%, with a specificity of 95% for a pathological REM sleep propensity at MSLT. The features of spontaneous daytime sleep well correlated with MSLT findings. Notably, the occurrence of multiple spontaneous SOREMPs during daytime clearly identified patients with narcolepsy, as well as during the MSLT.     

Progressive dopamine and hypocretin deficiencies in Parkinson’s disease: is there an impact on sleep and wakefulness?

Sleep–wake disturbances are frequent in patients with Parkinson’s disease, but prospective controlled electrophysiological studies of sleep in those patients are surprisingly sparse, and the pathophysiology of sleep–wake disturbances in Parkinson’s disease remains largely elusive. In particular, the impact of impaired dopaminergic and hypocretin (orexin) signalling on sleep and wakefulness in Parkinson’s disease is still unknown. We performed a prospective, controlled electrophysiological study in patients with early and advanced Parkinson’s disease, e.g. in subjects with presumably different levels of dopamine and hypocretin cell loss. We compared sleep laboratory tests and cerebrospinal fluid levels with hypocretin‐deficient patients with narcolepsy with cataplexy, and with matched controls. Nocturnal sleep efficiency was most decreased in advanced Parkinson patients, and still lower in early Parkinson patients than in narcolepsy subjects. Excessive daytime sleepiness was most severe in narcolepsy patients. In Parkinson patients, objective sleepiness correlated with decrease of cerebrospinal fluid hypocretin levels, and repeated hypocretin measurements in two Parkinson patients revealed a decrease of levels over years. This suggests that dopamine and hypocretin deficiency differentially affect sleep and wakefulness in Parkinson’s disease. Poorer sleep quality is linked to dopamine deficiency and other disease‐related factors. Despite hypocretin cell loss in Parkinson’s disease being only partial, disturbed hypocretin signalling is likely to contribute to excessive daytime sleepiness in Parkinson patients.     

Validation of the ICSD-2 Criteria for CSF Hypocretin-1 Measurements in the Diagnosis of Narcolepsy in the Danish Population

Study Objectives:

The International Classification of Sleep Disorders (ICSD-2) criteria for low CSF hypocretin-1 levels (CSF hcrt-1) still need validation as a diagnostic tool for narcolepsy in different populations because inter-assay variability and different definitions of hypocretin deficiency complicate direct comparisons of study results.

Design and Participants:

Interviews, polysomnography, multiple sleep latency test, HLA-typing, and CSF hcrt-1 measurements in Danish patients with narcolepsy with cataplexy (NC) and narcolepsy without cataplexy (NwC), CSF hcrt-1 measurements in other hypersomnias, neurological and normal controls. Comparisons of hypocretin deficiency and frequency of HLA-DQB1*0602-positivity in the Danish and eligible NC and NwC populations (included via MEDLINE search), by (re)calculation of studyusing the ICSD-2 criterion for low CSF hcrt-1 (<30% of normal mean).

Measurements and Results:

In Danes, low CSF hcrt-1 was present in 40/46 NC, 3/14 NwC and 0/106 controls (P < 0.0001). Thirty-nine of 41 NC and 4/13 NwC patients were HLA-DQB1*0602-positive (P < 0.01). Hypocretin-deficient NC patients had higher frequency of cataplexy, shorter mean sleep latency, more sleep onset REM periods (P < 0.05) and more awakenings (NS) than did NC patients with normal CSF hcrt-1. Across populations, low CSF hcrt-1 and HLA-DQB1*0602-positivity characterized the majority of NC (80% to 100%, P = 0.53; 80% to 100%, P = 0.11) but a minority of NwC patients (11% to 29%, P = 0.75; 29% to 89%, P = 0.043).

Conclusion:

The study provides evidence that hypocretin deficiency causes a more severe NC phenotype. The ICSD-2 criterion for low CSF hcrt-1 (<30% of normal mean) is valid for diagnosing NC, but not NwC. HLA-typing should precede CSF hcrt-1 measurements because hypocretin deficiency is rare in HLA-DQB1*0602-negative patients.

Citation:

Knudsen S; Jennum PJ; Alving J; Sheikh SP; Gammeltoft S. Validation of the ICSD-2 criteria for CSF hypocretin-1 measurements in the diagnosis of narcolepsy in the Danish population. SLEEP 2010;33(2):169-176.     

White matter alterations in narcolepsy patients with cataplexy: tract‐based spatial statistics

Functional imaging studies and voxel‐based morphometry analysis of brain magnetic resonance imaging showed abnormalities in the hypothalamus–thalamus–orbitofrontal pathway, demonstrating altered hypocretin pathway in narcolepsy. Those distinct morphometric changes account for problems in wake–sleep control, attention and memory. It also raised the necessity to evaluate white matter changes. To investigate brain white matter alterations in drug‐naïve narcolepsy patients with cataplexy and to explore relationships between white matter changes and patient clinical characteristics, drug‐naïve narcolepsy patients with cataplexy (n = 22) and healthy age‐ and gender‐matched controls (n = 26) were studied. Fractional anisotropy and mean diffusivity images were obtained from whole‐brain diffusion tensor imaging, and tract‐based spatial statistics were used to localize white matter abnormalities. Compared with controls, patients showed significant decreases in fractional anisotropy of white matter of the bilateral anterior cingulate, fronto‐orbital area, frontal lobe, anterior limb of the internal capsule and corpus callosum, as well as the left anterior and medial thalamus. Patients and controls showed no differences in mean diffusivity. Among patients, mean diffusivity values of white matter in the bilateral superior frontal gyri, bilateral fronto‐orbital gyri and right superior parietal gyrus were positively correlated with depressive mood. This tract‐based spatial statistics study demonstrated that drug‐naïve patients with narcolepsy had reduced fractional anisotropy of white matter in multiple brain areas and significant relationship between increased mean diffusivity of white matter in frontal/cingulate and depression. It suggests the widespread disruption of white matter integrity and prevalent brain degeneration of frontal lobes according to a depressive symptom in narcolepsy.     

Interactions of the orexin/hypocretin neurones and the histaminergic system

Histaminergic and orexin/hypocretin systems are components in the brain wake‐promoting system. Both are affected in the sleep disorder narcolepsy, but the role of histamine in narcolepsy is unclear. The histaminergic neurones are activated by the orexin/hypocretin system in rodents, and the development of the orexin/hypocretin neurones is bidirectionally regulated by the histaminergic system in zebrafish. This review summarizes the current knowledge of the interactions of these two systems in normal and pathological conditions in humans and different animal models.     

HLA-DQB1 allele and hypocretin in Korean narcoleptics with cataplexy

Cataplexy is one of the most pathognomonic symptoms in narcolepsy. This study was designed to investigate the frequency of the HLA-DQB1 allele and cerebrospinal fluid (CSF) hypocretin levels in Korean narcoleptics with cataplexy as compared with those who do not have cataplexy. Seventy-two narcoleptics were selected based on polysomnography and multiple sleep latency test as well as their history and clinical symptoms at Sleep Disorders Clinic. The patients were divided into a narcolepsy with cataplexy group (n=56) and a narcolepsy without cataplexy group (n=16). All patients were subjected to HLA typing to determine the frequency of DQB1 allele and to spinal tapping to measure the level of CSF hypocretin. In cataplexy-positive patients, as compared with cataplexy-negative patients, the frequency of HLA-DQB1*0602 was found to be significantly high (89.3% vs. 50.0%) (p=0.003). On the other hand, the frequency of HLA-DQB1*0601 was found to be significantly low (0% vs. 43.8%) (p<0.001). In 48 of 56 cataplexy-positive patients (85.7 %), hypocretin levels were decreased (相似文献   

A critical role of hypocretin deficiency in pregnancy

Hypocretin/orexin peptides are known for their role in the control of the wake–sleep cycle and narcolepsy–cataplexy pathophysiology. Recent studies suggested that hypocretin peptides also have a role in pregnancy. We tested this hypothesis by conducting a retrospective analysis on pregnancy complications in two different mouse models of hypocretin deficiency. We recorded 85 pregnancies of mice lacking either hypocretin peptides (knockout) or hypocretin‐releasing neurons (transgenic) and their wild‐type controls. Pregnancy was associated with unexplained dam death before delivery in 3/15 pregnancies in knockout mice, and in 3/23 pregnancies in transgenic mice. No casualties occurred in wild‐type pregnant dams (P < 0.007 versus hypocretin‐deficient mice as a whole). Hypocretin deficiency did not impact either on litter size or the number of weaned pups per litter. These data provide preliminary evidence of a critical role of hypocretin deficiency in pregnancy.     

Sleep‐stage sequencing of sleep‐onset REM periods in MSLT predicts treatment response in patients with narcolepsy

Current treatment recommendations for narcolepsy suggest that modafinil should be used as a first‐line treatment ahead of conventional stimulants or sodium oxybate. In this study, performed in a tertiary sleep disorders centre, treatment responses were examined following these recommendations, and the ability of sleep‐stage sequencing of sleep‐onset rapid eye movement periods in the multiple sleep latency test to predict treatment response. Over a 3.5‐year period, 255 patients were retrospectively identified in the authors' database as patients diagnosed with narcolepsy, type 1 (with cataplexy) or type 2 (without) using clinical and polysomnographic criteria. Eligible patients were examined in detail, sleep study data were abstracted and sleep‐stage sequencing of sleep‐onset rapid eye movement periods were analysed. Response to treatment was graded utilizing an internally developed scale. Seventy‐five patients were included (39% males). Forty (53%) were diagnosed with type 1 narcolepsy with a mean follow‐up of 2.37 ± 1.35 years. Ninety‐seven percent of the patients were initially started on modafinil, and overall 59% reported complete response on the last follow‐up. Twenty‐nine patients (39%) had the sequence of sleep stage 1 or wake to rapid eye movement in all of their sleep‐onset rapid eye movement periods, with most of these diagnosed as narcolepsy type 1 (72%). The presence of this specific sleep‐stage sequence in all sleep‐onset rapid eye movement periods was associated with worse treatment response (P = 0.0023). Sleep‐stage sequence analysis of sleep‐onset rapid eye movement periods in the multiple sleep latency test may aid the prediction of treatment response in narcoleptics and provide a useful prognostic tool in clinical practice, above and beyond their classification as narcolepsy type 1 or 2.     

Systemic exertion intolerance disease/chronic fatigue syndrome is common in sleep centre patients with hypersomnolence: A retrospective pilot study

Symptoms of the central disorders of hypersomnolence extend beyond excessive daytime sleepiness to include non‐restorative sleep, fatigue and cognitive dysfunction. They share much in common with myalgic encephalomyelitis/chronic fatigue syndrome, recently renamed systemic exertion intolerance disease, whose additional features include post‐exertional malaise and orthostatic intolerance. We sought to determine the frequency and correlates of systemic exertion intolerance disease in a hypersomnolent population. One‐hundred and eighty‐seven hypersomnolent patients completed questionnaires regarding sleepiness and fatigue; questionnaires and clinical records were used to assess for systemic exertion intolerance disease. Sleep studies, hypocretin and cataplexy were additionally used to assign diagnoses of hypersomnolence disorders or sleep apnea. Included diagnoses were idiopathic hypersomnia (n = 63), narcolepsy type 2 (n = 25), persistent sleepiness after obstructive sleep apnea treatment (n = 25), short habitual sleep duration (n = 41), and sleepiness with normal sleep study (n = 33). Twenty‐one percent met systemic exertion intolerance disease criteria, and the frequency of systemic exertion intolerance disease was not different across sleep diagnoses (p = .37). Patients with systemic exertion intolerance disease were no different from those without this diagnosis by gender, age, Epworth Sleepiness Scale, depressive symptoms, or sleep study parameters. The whole cohort reported substantial fatigue on questionnaires, but the systemic exertion intolerance disease group exhibited more profound fatigue and was less likely to respond to traditional wake‐promoting agents (88.6% versus 67.7%, p = .01). Systemic exertion intolerance disease appears to be a common co‐morbidity in patients with hypersomnolence, which is not specific to hypersomnolence subtype but may portend a poorer prognosis for treatment response.     

Multiple sleep latency test in narcolepsy type 1 and narcolepsy type 2: A 5‐year follow‐up study

Excessively sleepy teenagers and young adults without sleep‐disordered breathing are diagnosed with either narcolepsy type 1 or narcolepsy type 2, or hypersomnia, based on the presence/absence of cataplexy and the results of a multiple sleep latency test. However, there is controversy surrounding this nomenclature. We will try to find the differences between different diagnoses of hypersomnia from the results of the long‐term follow‐up evaluation of a sleep study. We diagnosed teenagers who had developed excessive daytime sleepiness based on the criteria of the International Classification of Sleep Disorders, 3rd edition. Each individual received the same clinical neurophysiologic testing every year for 5 years after the initial diagnosis of narcolepsy type 1 (n = 111) or type 2 (n = 46). The follow‐up evaluation demonstrated that narcolepsy type 1 (narcolepsy‐cataplexy) is a well‐defined clinical entity, with very reproducible clinical neurophysiologic findings over time, whereas patients with narcolepsy type 2 presented clear clinical and test variability. By the fifth year of the follow‐up evaluation, 17.6% of subjects did not meet the diagnostic criteria of narcolepsy type 2, and 23.9% didn't show any two sleep‐onset rapid eye movement periods in multiple sleep latency during the 5‐year follow‐up. Therefore narcolepsy type 1 (narcolepsy‐cataplexy) is a well‐defined syndrome, with the presentation clearly related to the known consequences of destruction of hypocretin/orexin neurons. Narcolepsy type 2 covers patients with clinical and test variability over time, thus bringing into question the usage of the term “narcolepsy” to label these patients.     

Hypocretin/orexin and narcolepsy: new basic and clinical insights

Narcolepsy is a chronic sleep disorder, characterized by excessive daytime sleepiness (EDS), cataplexy, sleep paralysis and hypnagogic hallucinations. Both sporadic (95%) and familial (5%) forms of narcolepsy exist in humans. The major pathophysiology of human narcolepsy has been recently discovered based on the discovery of narcolepsy genes in animals; the genes involved in the pathology of the hypocretin/orexin ligand and its receptor. Mutations in hypocretin-related genes are rare in humans, but hypocretin ligand deficiency is found in a large majority of narcolepsy with cataplexy. Hypocretin ligand deficiency in human narcolepsy is probably due to the post-natal cell death of hypocretin neurones. Although a close association between human leucocyte antigen (HLA) and human narcolepsy with cataplexy suggests an involvement of autoimmune mechanisms, this has not yet been proved. Hypocretin deficiency is also found in symptomatic cases of narcolepsy and EDS with various neurological conditions, including immune-mediated neurological disorders, such as Guillain–Barre syndrome, MA2-positive paraneoplastic syndrome and neuromyelitis optica (NMO)-related disorder. The findings in symptomatic narcoleptic cases may have significant clinical relevance to the understanding of the mechanisms of hypocretin cell death and choice of treatment option. The discoveries in human cases lead to the establishment of the new diagnostic test of narcolepsy (i.e. low cerebrospinal fluid hypocretin-1 levels for ‘narcolepsy with cataplexy’ and ‘narcolepsy due to medical condition’). As a large majority of human narcolepsy patients are ligand deficient, hypocretin replacement therapy may be a promising new therapeutic option, and animal experiments using gene therapy and cell transplantations are in progress.     

CSF versus serum leptin in narcolepsy: is there an effect of hypocretin deficiency?

STUDY OBJECTIVE: To determine if hypocretin deficiency is associated with abnormally low serum leptin levels, a putative cause of increased body mass index in narcoleptics. DESIGN: Cross-sectional controlled study. PARTICIPANTS: Three hundred seventy subjects, including 111 healthy controls, 93 narcoleptic subjects with hypocretin deficiency (cerebrospinal fluid [CSF] hypocretin-1 levels < 110 pg/mL), 72 narcoleptic subjects with normal hypocretin levels, and 89 subjects with other sleep disorders INTERVENTION: After completing the Stanford Sleepiness Inventory, participants underwent spinal taps and blood sampling for measurement of CSF leptin and hypocretin-1 levels, HLA DQB1*0602 phenotyping, and serum leptin and C-reactive protein levels. RESULTS: Serum leptin levels were similar in narcoleptic subjects, whether hypocretin-deficient (13.2 +/- 1.7 ng/mL, mean +/- SEM) or not (13.0 +/- 1.8 ng/mL), controls (10.1 +/- 1.1 ng/mL) and subjects with other sleep disorders (11.5 +/- 1.6 ng/mL). Similarly, the CSF leptin levels and the CSF: serum leptin ratios (an indicator of brain leptin uptake) were not different between groups. Serum and CSF leptin levels were higher in women and in subjects with higher body mass indexes. Leptin brain uptake decreased in women, in the aged, and in more-obese subjects. In contrast with a presumed inhibitory effect of leptin on hypocretin-containing cells, CSF leptin levels tended to correlate positively with CSF hypocretin-1 levels. C-reactive protein was higher (4.2 +/- 0.9 mg/L) in narcoleptic subjects with hypocretin deficiency than in controls (1.4 +/- 0.3 mg/L, p = .0055), a difference still significant after adjustment on confounding factors. DISCUSSION: Our data do not support a role for leptin in mediating increased body mass index in narcolepsy. A moderate but selective increase in C-reactive protein in hypocretin-1 deficient subjects should prompt research on inflammation in narcolepsy.     

The prevalence of excessive sleepiness is higher in shift workers than in patients with obstructive sleep apnea

Excessive daytime sleepiness (EDS) is a common feature among shift workers as well as in obstructive sleep apnea (OSA) patients. There are several important accidents related to sleep disturbances causing EDS. The aim of this study was to evaluate EDS in a group of shift workers (regular rotating) from civil aviation and to compare them with OSA patients (n = 300) and with a group of regular workers (RW) (n = 140). Our sample was composed of 730 working‐age individuals (aged 18–67 years). The regular rotating shift workers (SW) sample was composed of 290 aeronautical mechanics. EDS was evaluated with the Epworth Sleepiness Scale (ESS) and defined as a score ≥ 11. The prevalence value obtained for the EDS of RW was 37.1%, for SW it was 60.7% and for OSA patients it was 40.7%. A logistic regression model for EDS in a subsample composed of men and matched for age and BMI, controlling for self‐reported sleep duration, showed an increased risk of EDS for SW (OR = 3.91, p = .001), with the RW group as reference. OSA patients did not differ from RW on EDS levels. This study emphasizes the presence of EDS in a shift work group of civil aviation professionals, which exceeded the EDS level of a positive control group of OSA patients. Sleep hygiene education for companies' workers and management is important and mitigation strategies should be implemented to reduce excessive sleepiness among workers.     

Gross motor adaptation benefits from sleep after training

Sleep has been shown to facilitate the consolidation of newly acquired motor memories. However, the role of sleep in gross motor learning, especially in motor adaptation, is less clear. Thus, we investigated the effects of nocturnal sleep on the performance of a gross motor adaptation task, i.e. riding an inverse steering bicycle. Twenty‐six male participants (M = 24.19, SD = 3.70 years) were randomly assigned to a PM‐AM‐PM (n = 13) or an AM‐PM‐AM (n = 13) group, i.e. they trained in the evening/morning and were re‐tested the next morning/evening and the following evening/morning (PM‐AM‐PM/AM‐PM‐AM group) so that every participant spent one sleep as well as one wake interval between the three test sessions. Inverse cycling performance was assessed by speed (riding time) and accuracy (standard deviation of steering angle) measures. Behavioural results showed that in the PM‐AM‐PM group a night of sleep right after training stabilized performance (accuracy and speed) and was further improved over the subsequent wake interval. In the AM‐PM‐AM group, a significant performance deterioration after the initial wake interval was followed by the restoration of subjects' performance levels from right after training when a full night of sleep was granted. Regarding sleep, right hemispheric fast N2 sleep spindle activity was related to better stabilization of inverse cycling skills, thus possibly reflecting the ongoing process of updating the participants' mental model from “how to ride a bicycle” to “how to ride an inverse steering bicycle”. Our results demonstrate that sleep facilitates the consolidation of gross motor adaptation, thus adding further insights to the role of sleep for tasks with real‐life relevance.     

Time‐ and state‐dependent analysis of autonomic control in narcolepsy: higher heart rate with normal heart rate variability independent of sleep fragmentation

Narcolepsy with hypocretin deficiency is known to alter cardiovascular control during sleep, but its aetiology is disputed. As cardiovascular control differs between sleep states, and narcolepsy affects sleep architecture, controlling for both duration and transitions of sleep states is necessary. This study therefore aimed to assess heart rate and its variability in narcolepsy during sleep taking these factors into account. The study included 12 medication‐naïve patients with narcolepsy with cataplexy and hypocretin deficiency (11 male, 16–53 years old), and 12 sex‐ and age‐matched healthy controls (11 male, 19–55 years). All subjects underwent 1‐night ambulatory polysomnography recording. Cardiovascular parameters were calculated for each 30‐s epoch. Heart rate was significantly higher in patients with narcolepsy than in controls in all sleep states and during wakefulness prior to sleep. Groups did not differ in heart rate variability measures. The effects of sleep state duration on heart rate and its variability were similar between patients and controls. In conclusion, heart rate was consistently higher in patients with narcolepsy than controls, independent of sleep stage and sleep fragmentation. A direct effect of hypocretin deficiency therefore seems probable.