T cells in patients with narcolepsy target self-antigens of hypocretin neurons.

Narcolepsy is a chronic sleep disorder caused by the loss of neurons that produce hypocretin. The close association with HLA-DQB1*06:02, evidence for immune dysregulation and increased incidence upon influenza vaccination together suggest that this disorder has an autoimmune origin. However, there is little evidence of autoreactive lymphocytes in patients with narcolepsy. Here we used sensitive cellular screens and detected hypocretin-specific CD4+ T cells in all 19 patients that we tested; T cells specific for tribbles homologue 2-another self-antigen of hypocretin neurons-were found in 8 out of 13 patients. Autoreactive CD4+ T cells were polyclonal, targeted multiple epitopes, were restricted primarily by HLA-DR and did not cross-react with influenza antigens. Hypocretin-specific CD8+ T cells were also detected in the blood and cerebrospinal fluid of several patients with narcolepsy. Autoreactive clonotypes were serially detected in the blood of the same-and even of different-patients, but not in healthy control individuals. These findings solidify the autoimmune aetiology of narcolepsy and provide a basis for rapid diagnosis and treatment of this disease.

K-band Doppler radar for contact-less overnight sleep marker assessment: a pilot validation study.

An estimated 45 million persons in Europe are annually subjected to sleep-wake disorders. State-of-the-art polysomnography provides sophisticated insights into sleep (patho)physiology. A drawback of the method, however, is the obtrusive setting dependent on a clinical-based sleep laboratory with high operational costs. A contact-less prototype was developed to monitor limb movements and vital signs during sleep. A dual channel K-band Doppler radar transceiver captured limb movements and periodic chest wall motion due to respiration and heart activity. A wavelet transform based multi-resolution analysis (MRA) approach isolated limb movements, respiration, and heart rate from the demodulated signal. A test bench setup characterized the prototype simulating near physiological chest wall motions caused by periodic respiration and heartbeats in humans. Single- and multi-tone test bench simulations showed extremely low relative percentage errors of the prototype for respiratory and heart rate within -2 and 1%. The performance of the prototype was validated in overnight comparative studies, involving two healthy volunteers, with polysomnography as the reference. The prototype has successfully classified limb movements, with a sensitivity and specificity of 88.9 and 76.8% respectively, and has achieved accurate respiratory and heart rate measurement performance with overall absolute errors of 1 breath per minute for respiration and 3 beats per minute for heart rate. This pilot study shows that K-band Doppler radar and wavelet transform MRA seem to be valid for overnight sleep marker assessment. The contact-less approach might offer a promising solution for home-based sleep monitoring and assessment.

Virtual car accidents of epilepsy patients, interictal epileptic activity, and medication.

OBJECTIVE: To investigate effects of interictal epileptic activity (IEA) and antiepileptic drugs (AEDs) on reactivity and aspects of the fitness to drive for epilepsy patients. METHODS: Forty-six adult patients with demonstration of focal or generalized bursts of IEA in electroencephalography (EEG) readings within 1 year prior to inclusion irrespective of medication performed a car driving computer test or a single light flash test (39 patients performed both). Reaction times (RTs), virtual crashes, or lapses (RT ≥ 1 s in the car or flash test) were measured in an IEA burst-triggered fashion during IEA and compared with RT-measurements during unremarkable EEG findings in the same session. RESULTS: IEA prolonged RTs both in the flash and car test (p < 0.001) in individual patients up to 200 ms. Generalized IEA with spike/waves (s/w) had the largest effect on RT prolongation (p < 0.001, both tests), whereas mean RT during normal EEG, age, gender, and number of AEDs had no effect. The car test was better than the flash test in detecting RT prolongations (p = 0.030). IEA increased crashes/lapses >26% in sessions with generalized IEA with s/w. The frequency of IEA-associated RT >1 s exceeded predictions (p < 0.001) based on simple RT shift, suggesting functional impairment beyond progressive RT prolongation by IEA. The number of AEDs correlated with prolonged RTs during normal EEG (p < 0.021) but not with IEA-associated RT prolongation or crashes/lapses. SIGNIFICANCE: IEA prolonged RTs to varying extents, dependent on IEA type. IEA-associated RTs >1 s were more frequent than predicted, suggesting beginning cerebral decompensation of visual stimulus processing. AEDs somewhat reduced psychomotor speed, but it was mainly the IEA that contributed to an excess of virtual accidents.

The European Narcolepsy Network (EU-NN) database.

Narcolepsy with cataplexy is a rare disease with an estimated prevalence of 0.02% in European populations. Narcolepsy shares many features of rare disorders, in particular the lack of awareness of the disease with serious consequences for healthcare supply. Similar to other rare diseases, only a few European countries have registered narcolepsy cases in databases of the International Classification of Diseases or in registries of the European health authorities. A promising approach to identify disease-specific adverse health effects and needs in healthcare delivery in the field of rare diseases is to establish a distributed expert network. A first and important step is to create a database that allows collection, storage and dissemination of data on narcolepsy in a comprehensive and systematic way. Here, the first prospective web-based European narcolepsy database hosted by the European Narcolepsy Network is introduced. The database structure, standardization of data acquisition and quality control procedures are described, and an overview provided of the first 1079 patients from 18 European specialized centres. Due to its standardization this continuously increasing data pool is most promising to provide a better insight into many unsolved aspects of narcolepsy and related disorders, including clear phenotype characterization of subtypes of narcolepsy, more precise epidemiological data and knowledge on the natural history of narcolepsy, expectations about treatment effects, identification of post-marketing medication side-effects, and will contribute to improve clinical trial designs and provide facilities to further develop phase III trials.

Post-H1N1 Flu Vaccination Narcolepsy in Switzerland: A Retrospective Survey in the 30 Sleep-Certified Swiss Centers.

Narcolepsy-cataplexy is a sleep-wake disorder and suggested to be immune-mediated, involving genetic and environmental factors. The autoimmune process eventually leads to a loss of hypocretin neurons in the lateral hypothalamus. Epidemiological studies in several countries proved an increased incidence of narcolepsy after H1N1 flu vaccination and infection. This survey in 30 sleep centers in Switzerland led to the identification of 9 H1N1-vaccinated children and adults as newly diagnosed narcolepsy. Clinical features included the abrupt and severe onset of sleepiness, cataplexy and sleep fragmentation.

Epileptic seizures as condensed sleep: an analysis of network dynamics from electroencephalogram signals.

Both deepening sleep and evolving epileptic seizures are associated with increasing slow-wave activity. Larger-scale functional networks derived from electroencephalogram indicate that in both transitions dramatic changes of communication between brain areas occur. During seizures these changes seem to be 'condensed', because they evolve more rapidly than during deepening sleep. Here we set out to assess quantitatively functional network dynamics derived from electroencephalogram signals during seizures and normal sleep. Functional networks were derived from electroencephalogram signals from wakefulness, light and deep sleep of 12 volunteers, and from pre-seizure, seizure and post-seizure time periods of 10 patients suffering from focal onset pharmaco-resistant epilepsy. Nodes of the functional network represented electrical signals recorded by single electrodes and were linked if there was non-random cross-correlation between the two corresponding electroencephalogram signals. Network dynamics were then characterized by the evolution of global efficiency, which measures ease of information transmission. Global efficiency was compared with relative delta power. Global efficiency significantly decreased both between light and deep sleep, and between pre-seizure, seizure and post-seizure time periods. The decrease of global efficiency was due to a loss of functional links. While global efficiency decreased significantly, relative delta power increased except between the time periods wakefulness and light sleep, and pre-seizure and seizure. Our results demonstrate that both epileptic seizures and deepening sleep are characterized by dramatic fragmentation of larger-scale functional networks, and further support the similarities between sleep and seizures.

Sleepiness and performance is disproportionate in patients with non-organic hypersomnia in comparison to patients with narcolepsy and mild to moderate obstructive sleep apnoea.

BACKGROUND/AIMS: Clinical differentiation between organic hypersomnia and non-organic hypersomnia (NOH) is challenging. We aimed to determine the diagnostic value of sleepiness and performance tests in patients with excessive daytime sleepiness (EDS) of organic and non-organic origin. METHODS: We conducted a retrospective comparison of the multiple sleep latency test (MSLT), pupillography, and the Steer Clear performance test in three patient groups complaining of EDS: 19 patients with NOH, 23 patients with narcolepsy (NAR), and 46 patients with mild to moderate obstructive sleep apnoea syndrome (OSAS). RESULTS: As required by the inclusion criteria, all patients had Epworth Sleepiness Scale (ESS) scores >10. The mean sleep latency in the MSLT indicated mild objective sleepiness in NOH (8.1 ± 4.0 min) and OSAS (7.2 ± 4.1 min), but more severe sleepiness in NAR (2.5 ± 2.0 min). The difference between NAR and the other two groups was significant; the difference between NOH and OSAS was not. In the Steer Clear performance test, NOH patients performed worst (error rate = 10.4%) followed by NAR (8.0%) and OSAS patients (5.9%; p = 0.008). The difference between OSAS and the other two groups was significant, but not between NOH and NAR. The pupillary unrest index was found to be highest in NAR (11.5) followed by NOH (9.2) and OSAS (7.4; n.s.). CONCLUSION: A high error rate in the Steer Clear performance test along with mild sleepiness in an objective sleepiness test (MSLT) in a patient with subjective sleepiness (ESS) is suggestive of NOH. This disproportionately high error rate in NOH may be caused by factors unrelated to sleep pressure, such as anergia, reduced attention and motivation affecting performance, but not conventional sleepiness measurements.

[Daytime sleepiness and driving behaviour]. / Tagesschläfrigkeit und Fahrverhalten.

Daytime sleepiness is reported by 10-15 % within the general population of industrialised countries. According to federal statistics in Switzerland, only ~1.5 % of motor vehicle crashes are caused by excessive daytime sleepiness, which is in sharp contrast to the scientific literature, indicating a figure of 10 to 30 %. This is most likely related to the difficulty to detect the underlying sleepiness by police officers and their low awareness of this cause in case of car accidents. As a consequence of this massively reduced figure, the real problem is underestimated and countermeasures as well as examinations of drivers at fault are inadequately realised in our country. The risk factors for sleepiness induced accidents are young age, male sex, driving at night or long distances and a number of diseases or sedative drugs. The most prevalent cause of sleepiness related accidents is the behaviourally induced sleep insufficiency syndrome or irregular sleep-wake rhythm in otherwise healthy subjects. Disease related sleepiness which may also cause motor vehicle accidents must be managed by physicians. In the diagnostic work-up sedative drugs, medical causes of sleepiness or tiredness as well as primary sleep-wake disorders must be considered. The most important duty of the treating physician, in addition to correct diagnosis and treatment, is to inform the affected patient of his or her responsibility not to drive while sleepy, about the theoretical legal consequences in case of an accident and about efficient countermeasures such as stopping in a rest area, drinking coffee, and taking a nap. For legal reasons, this information must be written in the patient's notes. Professional drivers suffering from sleep apnoea syndrome or other disorders with excessive daytime sleepiness, or private drivers who have already experienced a sleepiness induced accident, should be referred to a sleep-wake-centre for objective assessment of their sleepiness in the maintenance of wakefulness test or a driving simulator before they continue to drive.

Clinical, polysomnographic and genome-wide association analyses of narcolepsy with cataplexy: a European Narcolepsy Network study.

The aim of this study was to describe the clinical and PSG characteristics of narcolepsy with cataplexy and their genetic predisposition by using the retrospective patient database of the European Narcolepsy Network (EU-NN). We have analysed retrospective data of 1099 patients with narcolepsy diagnosed according to International Classification of Sleep Disorders-2. Demographic and clinical characteristics, polysomnography and multiple sleep latency test data, hypocretin-1 levels, and genome-wide genotypes were available. We found a significantly lower age at sleepiness onset (men versus women: 23.74 ± 12.43 versus 21.49 ± 11.83, P = 0.003) and longer diagnostic delay in women (men versus women: 13.82 ± 13.79 versus 15.62 ± 14.94, P = 0.044). The mean diagnostic delay was 14.63 ± 14.31 years, and longer delay was associated with higher body mass index. The best predictors of short diagnostic delay were young age at diagnosis, cataplexy as the first symptom and higher frequency of cataplexy attacks. The mean multiple sleep latency negatively correlated with Epworth Sleepiness Scale (ESS) and with the number of sleep-onset rapid eye movement periods (SOREMPs), but none of the polysomnographic variables was associated with subjective or objective measures of sleepiness. Variant rs2859998 in UBXN2B gene showed a strong association (P = 1.28E-07) with the age at onset of excessive daytime sleepiness, and rs12425451 near the transcription factor TEAD4 (P = 1.97E-07) with the age at onset of cataplexy. Altogether, our results indicate that the diagnostic delay remains extremely long, age and gender substantially affect symptoms, and that a genetic predisposition affects the age at onset of symptoms.

Narcolepsy and pregnancy: a retrospective European evaluation of 249 pregnancies.

In a retrospective cohort study undertaken in 12 European countries, 249 female narcoleptic patients with cataplexy (n = 216) and without cataplexy (n = 33) completed a self-administrated questionnaire regarding pregnancy and childbirth. The cohort was divided further into patients whose symptoms of narcolepsy started before or during pregnancy (308 pregnancies) and those in whom the first symptoms of narcolepsy appeared after delivery (106 pregnancies). Patients with narcolepsy during pregnancy were older during their first pregnancy (P < 0.001) and had a higher body mass index (BMI) prior to pregnancy (P < 0.01). Weight gain during pregnancy was higher in narcoleptic patients with cataplexy (P < 0.01). More patients with narcolepsy-cataplexy during pregnancy had impaired glucose metabolism and anaemia. Three patients experienced cataplexy during delivery. The rate of caesarean sections was higher in the narcolepsy-cataplexy group compared to the narcolepsy group (P < 0.05). The mean birth weight and gestational age of neonates were within the normal range and did not differ across groups. Neonatal care was affected adversely by symptoms of narcolepsy in 60.1% of those with narcolepsy during pregnancy. This study reports more obstetric complications in patients with narcolepsy-cataplexy during pregnancy; however, these were not severe. This group also had a higher BMI and higher incidence of impaired glucose metabolism during pregnancy. Caesarian section was conducted more frequently in narcolepsy-cataplexy patients, despite cataplexy being a rare event during delivery. Furthermore, symptoms of narcolepsy may render care of the infant more difficult.

Eyelid Closure Behavior of Patients with Idiopathic and Nonorganic Hypersomnia, Narcolepsy-Cataplexy, and Healthy Controls in the Maintenance of Wakefulness Test.

Purpose: Differential diagnosis of central disorders of hypersomnolence remains challenging, particularly between idiopathic (IH) and nonorganic hypersomnia (NOH). We hypothesized that eyelid closure behavior in the maintenance of wakefulness test (MWT) could be a valuable biomarker. Patients and Methods: MWT recordings of patients with IH, NOH, narcolepsy-cataplexy (NC), and healthy sleep-deprived controls (H) were retrospectively analyzed (15 individuals per group). For each MWT trial, visual scoring of face videography for partial (50-80%) and full eyelid closure (≥80%) was performed from "lights off" to the first microsleep episode (≥3 s). Results: In all groups, the frequency and cumulative duration of periods with partial and full eyelid closure gradually increased toward the first microsleep episode. On the group level, significant differences occurred for the latency to the first microsleep episode (IH 21 min (18-33), NOH 23 min (17-35), NC 11 min (7-19), H 10 min (6-25); p = 0.009), the ratio between partial and full eyelid closure duration (IH 2.2 (0.9-3.1), NOH 0.5 (0-1.2), NC 2.8 (1.1-5), H 0.7 (0.4-3.3); p = 0.004), and the difference between full and partial eyelid closure duration in the five minutes prior to the first microsleep episode (∆full - partial eyelid closure duration: IH -16 s (-35 to 28); NOH 46 s (9-82); NC -6 s (-26 to 5); H 10 s (-4 to 18); p = 0.007). IH and NOH significantly differed comparing the ratio between partial and full eyelid closure (p = 0.005) and the difference between ∆full - partial eyelid closure duration in the five minutes prior to the first microsleep episode (p = 0.006). Conclusion: In the MWT, eyelid closure behavior (∆full - partial) in the period prior to the first microsleep episode could be of value for discriminating NOH from other etiologies of excessive daytime sleepiness, particularly IH.

Predictive Power of Interictal Epileptiform Discharges in Fitness-to-Drive Evaluation.

BACKGROUND AND OBJECTIVES: This study aimed to evaluate and predict the effects of interictal epileptiform discharges (IEDs) on driving ability using simple reaction tests and a driving simulator. METHODS: Patients with various epilepsies were evaluated with simultaneous EEGs during their response to visual stimuli in a single-flash test, a car-driving video game, and a realistic driving simulator. Reaction times (RTs) and missed reactions or crashes (miss/crash) during normal EEG and IEDs were measured. IEDs, as considered in this study, were a series of epileptiform potentials (>1 potential) and were classified as generalized typical, generalized atypical, or focal. RT and miss/crash in relation to IED type, duration, and test type were analyzed. RT prolongation, miss/crash probability, and odds ratio (OR) of miss/crash due to IEDs were calculated. RESULTS: Generalized typical IEDs prolonged RT by 164 ms, compared with generalized atypical IEDs (77.0 ms) and focal IEDs (48.0 ms) (p < 0.01). Generalized typical IEDs had a session miss/crash probability of 14.7% compared with a zero median for focal and generalized atypical IEDs (p < 0.01). Long repetitive bursts of focal IEDs lasting >2 seconds had a 2.6% miss/crash probabilityIED. Cumulated miss/crash probability could be predicted from RT prolongation: 90.3 ms yielded a 20% miss/crash probability. All tests were nonsuperior to each other in detecting miss/crash probabilitiesIED (zero median for all 3 tests) or RT prolongations (flash test: 56.4 ms, car-driving video game: 75.5 ms, simulator 86.6 ms). IEDs increased the OR of miss/crash in the simulator by 4.9-fold compared with normal EEG. A table of expected RT prolongations and miss/crash probabilities for IEDs of a given type and duration was created. DISCUSSION: IED-associated miss/crash probability and RT prolongation were comparably well detected by all tests. Long focal IED bursts carry a low risk, while generalized typical IEDs are the primary cause of miss/crash. We propose a cumulative 20% miss/crash risk at an RT prolongation of 90.3 ms as a clinically relevant IED effect. The IED-associated OR in the simulator approximates the effects of sleepiness or low blood alcohol level while driving on real roads. A decision aid for fitness-to-drive evaluation was created by providing the expected RT prolongations and misses/crashes when IEDs of a certain type and duration are detected in routine EEG.

The diagnostic value of sleep and vigilance tests in central disorders of hypersomnolence.

STUDY OBJECTIVES: This retrospective cross-sectional observational study explored the diagnostic value of selected sleep and vigilance tests (SVT) beyond the multiple sleep latency test to differentiate between various central disorders of hypersomnolence (CDH) and fatigue syndromes. METHODS: Data from patients who underwent the multiple sleep latency test and at least one additional SVT were extracted from the Bern sleep database (1997-2018). One thousand three hundred fifty-two patients with a CDH (106 narcolepsy type 1, 90 narcolepsy type 2, 119 idiopathic hypersomnia, 192 nonorganic hypersomnia, 205 insufficient sleep syndrome), fatigue syndromes (n = 183), and a subgroup of patients with sleep apnea (n = 457) were analyzed. Classification based on SVT parameters was compared with the final clinical diagnosis serving as a reference. RESULTS: An overall model predicted the final diagnosis in 49.5% of patients. However, for the pairwise differentiation of two clinically suspected diagnoses, many SVT parameters showed a sensitivity and specificity above 70%. While the overall discrimination power of the multiple sleep latency test was slightly better than the one of the maintenance of wakefulness test, the latter differentiated best between narcolepsy and idiopathic hypersomnia with prolonged sleep need. Disproportionally poor results in reaction tests (e.g. steer clear test), despite comparable or lower sleepiness levels (SLAT, WLAT), were valuable for differentiating nonorganic hypersomnia from idiopathic hypersomnia/sleep insufficiency syndrome. CONCLUSION: This study demonstrates how the combination of a careful clinical assessment and a selection of SVTs can improve the differentiation of CDH, whereas it was not possible to establish an overall prediction model based on SVTs alone.

Spike-triggered reaction-time EEG as a possible assessment tool for driving ability.

The impact of interictal epileptic activity (IEA) on driving is a rarely investigated issue. We analyzed the impact of IEA on reaction time in a pilot study. Reactions to simple visual stimuli (light flash) in the Flash test or complex visual stimuli (obstacle on a road) in a modified car driving computer game, the Steer Clear, were measured during IEA bursts and unremarkable electroencephalography (EEG) periods. Individual epilepsy patients showed slower reaction times (RTs) during generalized IEA compared to RTs during unremarkable EEG periods. RT differences were approximately 300 ms (p < 0.001) in the Flash test and approximately 200 ms (p < 0.001) in the Steer Clear. Prior work suggested that RT differences >100 ms may become clinically relevant. This occurred in 40% of patients in the Flash test and in up to 50% in the Steer Clear. When RT were pooled, mean RT differences were 157 ms in the Flash test (p < 0.0001) and 116 ms in the Steer Clear (p < 0.0001). Generalized IEA of short duration seems to impair brain function, that is, the ability to react. The reaction-time EEG could be used routinely to assess driving ability.

Selective REM sleep deprivation in narcolepsy.

Narcolepsy is characterized by excessive daytime sleepiness and rapid eye movement (REM) sleep abnormalities, including cataplexy. The aim of this study was to assess REM sleep pressure and homeostasis in narcolepsy. Six patients with narcolepsy and six healthy controls underwent a REM sleep deprivation protocol, including one habituation, one baseline, two deprivation nights (D1, D2) and one recovery night. Multiple sleep latency tests (MSLTs) were performed during the day after baseline and after D2. During D1 and D2 REM sleep was prevented by awakening the subjects at the first polysomnographic signs of REM sleep for 2 min. Mean sleep latency and number of sleep-onset REM periods (SOREMs) were determined on all MSLT. More interventions were required to prevent REM sleep in narcoleptics compared with control subjects during D1 (57 ± 16 versus 24 ± 10) and D2 (87 ± 22 versus 35 ± 8, P = 0.004). Interventions increased from D1 to D2 by 46% in controls and by 53% in narcoleptics (P < 0.03). Selective REM sleep deprivation was successful in both controls (mean reduction of REM to 6% of baseline) and narcoleptics (11%). Both groups had a reduction of total sleep time during the deprivation nights (P = 0.03). Neither group had REM sleep rebound in the recovery night. Narcoleptics had, however, an increase in the number of SOREMs on MSLT (P = 0.005). There was no increase in the number of cataplexies after selective REM sleep deprivation. We conclude that: (i) REM sleep pressure is higher in narcoleptics; (ii) REM sleep homeostasis is similar in narcoleptics and controls; (iii) in narcoleptics selective REM sleep deprivation may have an effect on sleep propensity but not on cataplexy.

Problems in functioning from the patient perspective using the International Classification of Functioning, Disability and Health (ICF) as a reference.

We conducted a qualitative, multicenter study using a focus group design to explore the lived experiences of persons with any kind of primary sleep disorder with regard to functioning and contextual factors using six open-ended questions related to the International Classification of Functioning, Disability and Health (ICF) components. We classified the results using the ICF as a frame of reference. We identified the meaningful concepts within the transcribed data and then linked them to ICF categories according to established linking rules. The six focus groups with 27 participants yielded a total of 6986 relevant concepts, which were linked to a total of 168 different second-level ICF categories. From the patient perspective, the ICF components: (1) Body Functions; (2) Activities & Participation; and (3) Environmental Factors were equally represented; while (4) Body Structures appeared poignantly less frequently. Out of the total number of concepts, 1843 concepts (26%) were assigned to the ICF component Personal Factors, which is not yet classified but could indicate important aspects of resource management and strategy development of those who have a sleep disorder. Therefore, treatment of patients with sleep disorders must not be limited to anatomical and (patho-)physiological changes, but should also consider a more comprehensive view that includes patient's demands, strategies and resources in daily life and the contextual circumstances surrounding the individual.

Identification of problems in functioning of people with sleep disorders in a clinical setting using the International Classification of Functioning Disability and Health (ICF) Checklist.

We conducted an explorative, cross-sectional, multi-centre study in order to identify the most common problems of people with any kind of (primary) sleep disorder in a clinical setting using the International Classification of Functioning, Disability and Health (ICF) as a frame of reference. Data were collected from patients using a structured face-to-face interview of 45-60 min duration. A case record form for health professionals containing the extended ICF Checklist, sociodemographic variables and disease-specific variables was used. The study centres collected data of 99 individuals with sleep disorders. The identified categories include 48 (32%) for body functions, 13 (9%) body structures, 55 (37%) activities and participation and 32 (22%) for environmental factors. 'Sleep functions' (100%) and 'energy and drive functions', respectively, (85%) were the most severely impaired second-level categories of body functions followed by 'attention functions' (78%) and 'temperament and personality functions' (77%). With regard to the component activities and participation, patients felt most restricted in the categories of 'watching' (e.g. TV) (82%), 'recreation and leisure' (75%) and 'carrying out daily routine' (74%). Within the component environmental factors the categories 'support of immediate family', 'health services, systems and policies' and 'products or substances for personal consumption [medication]' were the most important facilitators; 'time-related changes', 'light' and 'climate' were the most important barriers. The study identified a large variety of functional problems reflecting the complexity of sleep disorders. The ICF has the potential to provide a comprehensive framework for the description of functional health in individuals with sleep disorders in a clinical setting.

[Driving ability and daytime sleepiness]. / Fahreignung bei Tagesschläfrigkeit.

Daytime sleepiness is a complaint of about 5-10% in a normal population. The consequences, such as impaired performance and accidents at the workplace and while driving, have major impact on the affected and on society. According to Swiss federal statistics only 1-3% of all motor vehicle accidents are due to excessive daytime sleepiness, which is in great contrast to a figure of 10 to 20% of all accidents derived from scientific studies. Due to the inadequate statistical representation of the problem, insufficient countermeasures have been realized, and the state of drivers breaching traffic regulations is not adequately investigated in this respect. The most prevalent cause of microsleep induced accidents is certainly lack of sleep due to social or professional reasons. A treating physician must also consider sedating drugs and various diseases. The typical characteristics of accidents due to falling asleep at the wheel and the risk factors involved are well established, so that informing the general public, taking prophylactic countermeasures and a targeted investigation in this respect of drivers who have breached the law are all feasible. Since symptoms of sleepiness can be recognized well before any impairment of performance occurs, the most important countermeasure is information of the drivers on the risk factors and on efficient countermeasures against sleepiness at the wheel. Besides correct diagnosis and treatment, the primary goal of physicians treating patients with pathological daytime sleepiness is to inform them at an early stage about the risks of sleepiness and the large responsibility they bear while driving. This information should be written down in the patients' records. Professional drivers suffering from daytime sleepiness, drivers who have already had an accident due to microsleep and unreasonable drivers should be referred to a centre of sleep disorders for objective measurements of sleepiness.

Multiple sleep latency test and polysomnography in patients with central disorders of hypersomnolence.

A multiple sleep latency test (MSLT) with occurrence of sleep onset REM periods (SOREMP) is considered one of the central diagnostic criteria for narcolepsy according to the International Classification of Sleep Disorders, but its sensitivity and specificity have been questioned. This study aims to describe MSLT and polysomnography (PSG) findings, including frequency and distribution of SOREMP during the day, in a large cohort of patients with central disorders of hypersomnolence (CDH). We retrospectively analyzed electrophysiological data from MSLT and PSG in 370 consecutive patients with narcolepsy type 1 (NT1, n = 97), type 2 (NT2, n = 31), idiopathic hypersomnia (IH, n = 48), nonorganic hypersomnia (NOH, n = 116) and insufficient sleep syndrome (ISS, n = 78). NT1 and NT2 patients had a significantly shorter mean Sleep Latency (mSL) and REM-Latency (REML) in MSLT and PSG. SOREMP occurred more frequently in narcoleptic vs. non-narcoleptic patients in MSLT and PSG. Occurrence of 3 or more SOREMP in MSLT and a SOREMP in PSG had a very high specificity and positive predictive value (98%/96% and 100% respectively), however relatively low sensitivity (65% and 45% respectively). NT1 more than NT2 patients have shorter mSL and more frequent SOREMP in MSLT and shorter SL as well as REML during nocturnal PSG. Increasing numbers of SOREMP in MSLT and especially SOREMP during PSG increase specificity on the expense of sensitivity in diagnosing narcolepsy. Therefore, frequency of SOREMP in MSLT naps and PSG can help to discriminate but not clearly separate narcoleptic from non-narcoleptic patients.

Automatic Detection of Microsleep Episodes With Deep Learning.

Brief fragments of sleep shorter than 15 s are defined as microsleep episodes (MSEs), often subjectively perceived as sleepiness. Their main characteristic is a slowing in frequency in the electroencephalogram (EEG), similar to stage N1 sleep according to standard criteria. The maintenance of wakefulness test (MWT) is often used in a clinical setting to assess vigilance. Scoring of the MWT in most sleep-wake centers is limited to classical definition of sleep (30 s epochs), and MSEs are mostly not considered in the absence of established scoring criteria defining MSEs but also because of the laborious work. We aimed for automatic detection of MSEs with machine learning, i.e., with deep learning based on raw EEG and EOG data as input. We analyzed MWT data of 76 patients. Experts visually scored wakefulness, and according to recently developed scoring criteria MSEs, microsleep episode candidates (MSEc), and episodes of drowsiness (ED). We implemented segmentation algorithms based on convolutional neural networks (CNNs) and a combination of a CNN with a long-short term memory (LSTM) network. A LSTM network is a type of a recurrent neural network which has a memory for past events and takes them into account. Data of 53 patients were used for training of the classifiers, 12 for validation and 11 for testing. Our algorithms showed a good performance close to human experts. The detection was very good for wakefulness and MSEs and poor for MSEc and ED, similar to the low inter-expert reliability for these borderline segments. We performed a visualization of the internal representation of the data by the artificial neuronal network performing best using t-distributed stochastic neighbor embedding (t-SNE). Visualization revealed that MSEs and wakefulness were mostly separable, though not entirely, and MSEc and ED largely intersected with the two main classes. We provide a proof of principle that it is feasible to reliably detect MSEs with deep neuronal networks based on raw EEG and EOG data with a performance close to that of human experts. The code of the algorithms (https://github.com/alexander-malafeev/microsleep-detection) and data (https://zenodo.org/record/3251716) are available.