Johannes Mathis

• Laboratory Head at sleep-wake-centre

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, nar...

Background 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 videogame,...

Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix®. Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals withi...

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 laten...

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 setti...

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,...

Increased incidence rates of narcolepsy type-1 (NT1) have been reported world-wide after the 2009-2010 H1N1 influenza pandemic (pH1N1). While some European countries found an association between the NT1 incidence increase and the H1N1 vaccination Pandemrix, reports from Asian countries suggested the H1N1 virus itself to be linked to the increased N...

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. The maintenance of wakefulness test (MWT) is often used to assess vigilance. Scoring of the MWT in most sl...

Study Objectives: Microsleep episodes (MSEs) are short fragments of sleep (1–15 s) that can cause dangerous situations with potentially fatal outcomes. In the diagnostic sleep-wake and fitness-to-drive assessment, accurate and early identification of sleepiness is essential. However, in the absence of a standardised definition and a time-efficient...

Increased incidence rates of narcolepsy type 1 (NT1) after the 2009-2010 H1N1 influenza pandemic (pH1N1) have been reported world-wide. While some European countries found an association between the NT1 increase and H1N1 vaccination Pandemrix, reports from Asian countries suggested the H1N1 virus rather than Pandemrix to be linked with the increase...

Study Objectives Microsleep episodes (MSEs) are brief episodes of sleep, mostly defined to be shorter than 15 s. In the electroencephalogram (EEG), MSEs are mainly characterized by a slowing in frequency. The identification of early signs of sleepiness and sleep (e.g. MSEs) is of considerable clinical and practical relevance. Under laboratory condi...

Previous studies reported high sensitivity and specificity of the Swiss Narcolepsy Scale (SNS) for the diagnosis of narcolepsy type 1. We used data from the Bern Sleep–Wake Database to investigate the discriminating capacity of both the SNS and the Epworth Sleepiness Scale (ESS) to identify narcolepsy type 1 and type 2 in patients with central diso...

Study objectives The wake-sleep transition zone represents a poorly defined borderland, containing e.g. microsleep episodes (MSEs) which are of potential relevance for diagnosis and may have consequences while driving. Yet, the scoring guidelines of the American Academy of Sleep Medicine (AASM) completely neglect it. We aimed to explore the borderl...

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 p...

Since the discovery of electrical activity of the brain electroencephalographic recordings (EEG) constitute one of the most popular techniques of brain research. However, EEG-signals are highly non-stationary and one should expect that averages of the cross-correlation coefficient, which may take positive and negative values with equal probability,...

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...

Type 1 narcolepsy (T1N) is a neurological condition, in which the death of hypocretin-producing neurons in the lateral hypothalamus leads to excessive daytime sleepiness and symptoms of abnormal Rapid Eye Movement (REM) sleep. Known triggers for narcolepsy are influenza-A infection and associated immunization during the 2009 H1N1 influenza pandemic...

Study Objectives Sleep disturbances are common in acute stroke patients and are linked with a negative stroke outcome. However, it is also unclear which and how such changes may be related to stroke outcome. To explore this link, we performed a sleep-EEG study in animals and humans after ischemic stroke. Methods (1) Animal-study: 12 male rats were...

Narcolepsy is a rare life-long disease that exists in two forms, narcolepsy type-1 (NT1) or type-2 (NT2), but only NT1 is accepted as clearly defined entity. Both types of narcolepsies belong to the group of central hypersomnias (CH), a spectrum of poorly defined diseases with excessive daytime sleepiness as a core feature. Due to the considerable...

Die Beurteilung der Fahreignung bzw. der Fahrfähigkeit bei vermehrter Einschlafneigung ist Bestandteil der ärztlichen Sorgfaltspflicht und eine wichtige und alltägliche Aufgabe der praktizierenden Ärzte und auch der akkreditierten Zentren für Schlafmedizin (AZSM). Der Anteil der Verkehrsunfälle, die durch einen Sekundenschlaf verursacht werden, wir...

Study objective: We sought to examine how much of the heritability of self-report sleep duration is tagged by common genetic variation in populations of European ancestry and to test if the common variants contributing to sleep duration are also associated with other diseases and traits. Methods: We utilized linkage disequilibrium (LD)-score reg...

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 irres...

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 i...

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 cas...

Objective: Narcolepsy with cataplexy is tightly associated with the HLA class II allele DQB1*06:02. Evidence indicates a complex contribution of HLA class II genes to narcolepsy susceptibility with a recent independent association with HLA-DPB1. The cause of narcolepsy is supposed be an autoimmune attack against hypocretin-producing neurons. Despi...

To test whether sleep-deprived, healthy subjects who do not always signal spontaneously perceived sleepiness (SPS) before falling asleep during the Maintenance of Wakefulness Test (MWT) would do so in a driving simulator. Twenty-four healthy subjects (20-26 years old) underwent a MWT for 40 min and a driving simulator test for 1 h, before and after...

To test whether humans can encode words during sleep we played everyday words to men while they were napping and assessed priming from sleep-played words following waking. Words were presented during non-rapid eye movement (NREM) sleep. Priming was assessed using a semantic and a perceptual priming test. These tests measured differences in the proc...

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 multi...

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...

In a cohort study among 2751 members (71.5% females) of the German and Swiss RLS patient organizations changes in restless legs syndrome (RLS) severity over time was assessed and the impact on quality of life, sleep quality and depressive symptoms was analysed. A standard set of scales (RLS severity scale IRLS, SF-36, Pittsburgh Sleep Quality Index...

Study objective: Prior research has identified five common genetic variants associated with narcolepsy with cataplexy in Caucasian patients. To replicate and/or extend these findings, we have tested HLA-DQB1, the previously identified 5 variants, and 10 other potential variants in a large European sample of narcolepsy with cataplexy subjects. Des...

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 rapid...

Artikel basiert auf Antrittsvorlesung gleichen Titels des Erstautors vom 30.06.2010 im Rahmen des Epilepsiechirurgiesymposiums der Universitäten Bern und Basel Bei Patienten, die an pharmakoresistenter Epilepsie mit fokal beginnenden Anfällen leiden, sollte möglichst früh im Krankheitsverlauf die Möglichkeit eines epilepsiechirurgischen Eingriffes...

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 (30...

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 S...

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 S...

To compare efficacy and safety of the dopamine agonist pramipexole (PPX) versus reference treatment with dual release levodopa/benserazide (L/B) in de novo patients with restless legs syndrome (RLS). A total of 39 men and women between 25 and 85 years old, fulfilling all clinical criteria for diagnosis of idiopathic RLS, previously untreated, parti...

Background and purpose Long obstructive sleep apnoeas (LOSAs) can cause brain ischaemia through paradoxical embolism since they can lead to right to left shunting (RLSh) but this has never been assessed as a risk factor for stroke. We investigated whether the combination of LOSA and RLSh is associated with ischaemic stroke or transient ischaemic at...

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...

According to projections by the World Health Organisation (WHO), road traffic injuries will be the third leading cause of global burden of disease and injury by the year 2020 [1] – in 50% of these accidents, the driver will be at fault. The main causes of death- or injury-producing accidents are excessive speed, alcohol consumption, inattention, an...

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 i...

To investigate whether there are any objective EEG characteristics that change significantly between specific time periods during maintenance of wakefulness test (MWT) and whether such changes are associated with the ability to appropriately communicate sleepiness. After a night of total sleep deprivation, 12 healthy young subjects underwent a MWT...

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 classifie...

Motor-evoked potentials (MEP) from abductor digiti minimi (ADM), biceps brachii (BB) and tibialis anterior (TA) muscle were analysed in 101 patients with multiple sclerosis (MS) and in 72 patients with compressive cervical myelopathy (CM). In definite MS the results were abnormal in 82% and in probable or possible MS in 64% of patients. In CM resul...

Gallup (this issue) believes that our recent review on the function of yawning (Guggisberg et al., 2010) is unbalanced and that it ignores evidence for his thermoregulation hypothesis. Here we address these criticisms and show them to be untenable. While we never claimed that the social hypothesis of yawning has "definite experimental support", we...

To assess frequency and characteristics of excessive daytime sleepiness (EDS) in restless legs syndrome (RLS) and the evolution of EDS under different RLS therapies. We analyzed data from the "Swiss RLS" study, which was conducted to compare treatment efficacy and safety of the dopamine agonist pramipexole (PPX) versus L-dopa/benserazide (L/B) in d...

Background: Periodic leg movements (PLM) during sleep consist of involuntary periodic movements of the lower extremities. The debated functional relevance of PLM during sleep is based on correlation of clinical parameters with the PLM index (PLMI). However, periodicity in movements may not be reflected best by the PLMI. Here, an approach novel to t...

A task force to develop guidelines for diagnostic evaluation and treatment of sleep disorders in degenerative neurological disorders and stroke was initiated by the European Federation of Neurological Societies (EFNS). The aims were to provide evidence-based recommendations in the management of sleep disorders associated with degenerative neurologi...

To test whether subjects spontaneously signal sleepiness before falling asleep under monotonous conditions. Twenty-eight healthy students were deprived of sleep for one night and then underwent a "maintenance-of-wakefulness test" (MWT) consisting of four 40-min trials. They were told to give a signal as soon as they felt sleepy and to try to stay a...

Narcolepsy is a rare sleep disorder with the strongest human leukocyte antigen (HLA) association ever reported. Since the associated HLA-DRB1*1501-DQB1*0602 haplotype is common in the general population (15-25%), it has been suggested that it is almost necessary but not sufficient for developing narcolepsy. To further define the genetic basis of na...

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 base...

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...

Yawning is a phylogenetically old behaviour that can be observed in most vertebrate species from foetal stages to old age. The origin and function of this conspicuous phenomenon have been subject to speculations for centuries. Here, we review the experimental evidence for each of these hypotheses. It is found that theories ascribing a physiological...

Yawning is a phylogenetically old behavior of ubiquitous occurrence. The origin and function of this conspicuous phenomenon have been subject to speculation for centuries. A widely held hypothesis posits that yawning increases the arousal level during sleepiness; thus, providing a homeostatic regulation of vigilance. This chapter reviews experiment...

Am Beispiel der Frontallappenepilepsie diskutieren wir zuerst die grundlegende Frage, weshalb Epilepsien so häufig vorkommen. Unter anderem anhand moder-ner Konzepte aus dem Gebiet komplexer Netzwerke spekulieren wir, dass diejenigen strukturellen und funk-tionellen Eigenschaften, welche uns die überlebensnot-wendige, rasche, energetisch effiziente...

Objective assessments of subjective complaints such as sleepiness, tiredness or fatigue using sleepiness and vigilance tests aim to identify its causes and to judge the fitness to drive or to work of the affected person. "Vigilance" comprises wakefulness, alertness and attention and is therefore not merely reciprocal to sleepiness. Since it is a co...

Combined EEG/fMRI recordings offer a promising opportunity to detect brain areas with altered BOLD signal during interictal epileptic discharges (IEDs). These areas are likely to represent the irritative zone, which is itself a reflection of the epileptogenic zone. This paper reports on the imaging findings using independent component analysis (ICA...

Theta burst transcranial magnetic stimulation (TBS) may induce behavioural changes that outlast the stimulation period. The neurophysiological basis of these behavioural changes are currently under investigation. Given the evidence that cortical information processing relies on transient synchronization and desynchronization of neuronal assemblies,...

The clinical features and natural course of paramedian thalamic stroke is poorly known. The aim of this study was to characterize the evolution of neurological, neuropsychological, and sleep-wake deficits after paramedian thalamic stroke. Forty-six consecutive patients, aged 48.4+/-16.6 years, were studied. Fourteen had bilateral, 16 left-sided, an...

To compare electroencephalogram (EEG) dynamics during nocturnal sleep in patients with narcolepsy-cataplexy and healthy controls. Fragmented nocturnal sleep is a prominent feature and contributes to excessive daytime sleepiness in narcolepsy-cataplexy. Only 3 studies have addressed changes in homeostatic sleep regulation as a possible mechanism und...

Periodic leg movements in sleep (PLMS) are frequently accompanied by arousals and autonomic activation, but the pathophysiologic significance of these manifestations is unclear. Changes in heart rate variability (HRV), HRV spectra, and electroencephalogram (EEG) spectra associated with idiopathic PLMS were compared with changes associated with isol...

Narcolepsy is usually an idiopathic disorder, often with a genetic predisposition. Symptomatic cases have been described repeatedly, often as a consequence of hypothalamic lesions. Conversely, REM (rapid eye movement) sleep behaviour disorder (RBD) is usually a secondary disorder, often due to degenerative brain stem disorders or narcolepsy. The ca...

Although yawning is a ubiquitous and phylogenetically old phenomenon, its origin and purpose remain unclear. The study aimed at testing the widely held hypothesis that yawning is triggered by drowsiness and brings about a reversal or suspension of the process of falling asleep. Subjects complaining of excessive sleepiness were spontaneously yawning...

The aim of the study was to assess sleep-wake habits and disorders and excessive daytime sleepiness (EDS) in an unselected outpatient epilepsy population. Sleep-wake habits and presence of sleep disorders were assessed by means of a clinical interview and a standard questionnaire in 100 consecutive patients with epilepsy and 90 controls. The questi...

The prevalence and characteristics of sleep-wake disturbances in sporadic Creutzfeldt-Jakob disease (sCJD) are poorly understood. Seven consecutive patients with definite sCJD underwent a systematic assessment of sleep-wake disturbances, including clinical history, video-polysomnography, and actigraphy. Extent and distribution of neurodegeneration...

In healthy subjects, arousability to inspiratory resistive loading is greater during rapid eye movement (REM) sleep compared with non-REM (NREM) sleep but is poorest in REM sleep in patients with sleep apnea. We therefore examined the hypothesis that sleep fragmentation impairs arousability, especially from REM sleep. Two blocks of 3 polysomnograph...

Sleep disturbances are prevalent but often overlooked or underestimated. We suspected that sleep disorders might be particularly common among pharmacy customers, and that they could benefit from counselling. Therefore, we described the prevalence and severity of symptoms associated with sleep and wakefulness disorders among Swiss pharmacy customers...

Background: In 2003 the Swiss federation of pharmacists organized a campaign "sleep disturbances--daytime sleepiness". The goal was to assist pharmacy clients in detecting likely causes of any sleep disturbance or daytime sleepiness through a free of charge screening, and to deliver targeted counselling. For pharmacy practice there are no screenin...

Restless Legs Syndrome (RLS) has become a well known disorder in the medical community in Switzerland within the last ten years, particularly since the official introduction of dopaminergic drugs as first line treatment. However, even today, in some patients a correct diagnosis is delayed, preventing specific therapy and prolonging discomfort or ev...

While voxel-based 3-D MRI analysis methods as well as assessment of subtracted ictal versus interictal perfusion studies (SISCOM) have proven their potential in the detection of lesions in focal epilepsy, a combined approach has not yet been reported. The present study investigates if individual automated voxel-based 3-D MRI analyses combined with...