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Ying Huang,1 Steve Hennig,1 Ingo Fietze,1 Thomas Penzel,1,2 Christian Veauthier1 1Interdisciplinary Center of Sleep Medicine, Charité University Medicine Berlin, Berlin 10117, Germany; 2Department of Biology, Saratov State University, Saratow, RussiaCorrespondence: Christian VeauthierInterdisziplinäres Schlafmedizinisches Zentrum, Charité Universitätsmedizin Berlin, Luisenstraße 13, Berlin 10117 Tel +49 30 513 232Fax +49 30 513 959Email christian.veauthier@charite.deBackground: Sleepiness at the wheel affects 10% to 15% of drivers and is one major cause of death on highways with one-third of fatal accidents. Obstructive sleep apnea (OSA) is one of the most common sleep disorders leading to sleepiness at the wheel. The aim of this study was to compare the psychomotor vigilance test reaction time (PVT RT) in OSA patients and controls (morning and afternoon) with the results of a divided attention steering simulator (DASS). A second purpose was to compare these results with the mean sleep latencies in the multiple sleep latency test (MSLT), the Epworth Sleepiness Scale (ESS) values and a neurocognitive test (test of attentional performance, TAP).Patients and Methods: Thirty eight OSA patients and 16 age and sex matched healthy controls were investigated by ESS, PVT, TAP, MSLT, and DASS (response time, failed responses, lane deviation, and off-road-events).Results: With increasing age, the performance in the DASS decreased. There was no correlation between the DASS and the results of the MSLT and ESS. The controls showed a significantly faster DASS response time in the morning compared to OSA patients (median 2.1 versus 3.0; p=0.044) and fewer off-road events (9 versus 37; p=0.042). We found a moderate correlation between the PVT RT and all parameters of the DASS, as well as the TAP “alertness” subtest.Conclusion: The increase of PVT RT as well as the decreased tonic alertness in the TAP in untreated OSA patients correlated with an impairment of simulated driving performance. The PVT and the TAP are both suitable diagnostic tools for measuring impaired driving ability in OSA patients. The MSLT did not correlate with the simulated driving performance. We recommend investigation of a longer version of the PVT in order to increase its sensitivity.Keywords: polysomnography, sustained attention, tonic alertness, vigilance, MSLT, simulated driving performance

Christian Veauthier,1 Sophie K Piper,2,3 Gunnar Gaede,4 Thomas Penzel,1,5 Friedemann Paul6,7 1Interdisciplinary Center of Sleep Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; 2Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Biometry and Clinical Epidemiology, Berlin, Germany; 3Berlin Institute of Health (BIH), Berlin, Germany; 4Department of Neurology, St. Joseph Krankenhaus Berlin-Weissensee, Berlin, Germany; 5International Clinical Research Center, St. Anne’s University Hospital Brno, Brno, Czech Republic; 6NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; 7Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany Background: The first night effect (FNE) is a polysomnography (PSG) habituation effect in the first of several consecutive in-laboratory PSGs (I-PSGs). The FNE is caused by the discomfort provoked by electrodes and cables and the exposure to an unfamiliar environment. A reverse FNE (RFNE) with an improved sleep in the first night is characteristic of insomnia, presumably because the video PSG in the sleep laboratory leads to a decrease in the negatively toned cognitive activity. Therefore, two or more I-PSGs are required for an accurate diagnosis. Although the FNE is well documented in I-PSG, little is known about the FNE and the RFNE in home-based PSGs (H-PSGs).Methods: This is a retrospective analysis of a recently published cross-sectional study using H-PSG. Sixty-three consecutive patients suffering from multiple sclerosis (MS) were investigated by two consecutive H-PSGs without video. The differences between the first and second H-PSGs were analyzed. The patients were classified into four subgroups: no sleep disorder, insomnia, sleep-related breathing disorders (SRBDs), and periodic limb movement disorder or restless legs syndrome (PLMD/RLS).Results: MS patients suffering from insomnia showed no RFNE. MS patients with SRBD or PLMD/RLS showed no reduced sleep efficiency but significantly less slow wave sleep. Furthermore, SRBD patients showed significantly less non-rapid eye movement (NREM) sleep, and PLMD/RLS patients were significantly awake longer in the first night after sleep onset (increased wake-after-sleep-onset time) and showed a higher rapid eye movement (REM) latency.Conclusion: SRBD and PLMD/RLS patients showed a significant FNE. Two consecutive H-PSGs are required in these patients to obtain a precise hypnogram even in the ambulatory field. In MS patients suffering from insomnia, no RFNE was found, and in insomnia patients one H-PSG seems to be sufficient. Keywords: insomnia, multiple sclerosis, outpatient sleep studies, polysomnography, sleep latency, wake after sleep onset

Michael Linden,1,2 Marie Dietz,1 Christian Veauthier,3 Ingo Fietze3 1Research Group Psychosomatic Rehabilitation, Charité University Medicine Berlin, 2Department of Psychosomatic Medicine, Rehabilitation Centre Seehof, Teltow, 3Interdisciplinary Center of Sleep Medicine, Charité University Medicine Berlin, Berlin, Germany Objective: To elucidate the relationship between subjective complaints and polysomnographical parameters in psychosomatic patients.Method: A convenience sample of patients from a psychosomatic inpatient unit were classified according to the Pittsburgh Sleep Quality Index (PSQI) as very poor sleepers (PSQI >10, n=80) and good sleepers (PSQI

Christian Veauthier,1 Gunnar Gaede,2,3 Helena Radbruch,2 Joern-Peter Sieb,4,5 Klaus-Dieter Wernecke,6,7 Friedemann Paul2,8 1Interdisciplinary Center of Sleep Medicine, Charité University Medicine Berlin, Germany; 2NeuroCure Clinical Research Center, Charité University Medicine Berlin, Germany; 3Department of Neurology, St Joseph Hospital Berlin-Weissensee, Berlin, Germany; 4Department of Neurology, HELIOS Hanseklinikum Stralsund, Stralsund, Germany; 5Department of Neurology, University Hospital Bonn, Bonn, Germany; 6CRO SOSTANA GmbH, Berlin, Germany; 7Institute of Medical Biometry, Charité University Medicine Berlin, Berlin, Germany; 8Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité University Medicine Berlin, Berlin, Germany Background: There are few studies describing periodic limb movement syndrome (PLMS) in rapid eye movement (REM) sleep in patients with narcolepsy, restless legs syndrome, REM sleep behavior disorder, and spinal cord injury, and to a lesser extent, in insomnia patients and healthy controls, but no published cases in multiple sclerosis (MS). The aim of this study was to investigate PLMS in REM sleep in MS and to analyze whether it is associated with age, sex, disability, and laboratory findings. Methods: From a study of MS patients originally published in 2011, we retrospectively analyzed periodic limb movements (PLMs) during REM sleep by classifying patients into two subgroups: PLM during REM sleep greater than or equal to ten per hour of REM sleep (n=7) vs less than ten per hour of REM sleep (n=59). A univariate analysis between PLM and disability, age, sex, laboratory findings, and polysomnographic data was performed. Results: MS patients with more than ten PLMs per hour of REM sleep showed a significantly higher disability measured by the Kurtzke expanded disability status scale (EDSS) (P=0.023). The presence of more than ten PLMs per hour of REM sleep was associated with a greater likelihood of disability (odds ratio 22.1; 95% confidence interval 3.5–139.7; P

Christian Veauthier1,21Department of Neurology, Hanse-Klinikum, Stralsund, Germany; 2Department of Neurology, Centre Hospitalier de Belfort-Montbéliard (CHBM), Montbéliard, FranceBackground: The Fatigue Severity Scale (FSS) is widely used to assess fatigue, not only in the context of multiple sclerosis-related fatigue, but also in many other medical conditions. Some polysomnographic studies have shown high FSS values in sleep-disordered patients without multiple sclerosis. The Modified Fatigue Impact Scale (MFIS) has increasingly been used in order to assess fatigue, but polysomnographic data investigating sleep-disordered patients are thus far unavailable. Moreover, the pathophysiological link between sleep architecture and fatigue measured with the MFIS and the FSS has not been previously investigated.Methods: This was a retrospective observational study (n = 410) with subgroups classified according to sleep diagnosis. The statistical analysis included nonparametric correlation between questionnaire results and polysomnographic data, age and sex, and univariate and multiple logistic regression.Results: The multiple logistic regression showed a significant relationship between FSS/MFIS values and younger age and female sex. Moreover, there was a significant relationship between FSS values and number of arousals and between MFIS values and number of awakenings.Conclusion: Younger age, female sex, and high number of awakenings and arousals are predictive of fatigue in sleep-disordered patients. Further investigations are needed to find the pathophysiological explanation for these relationships.Keywords: fatigue, sleep disorders, multiple sclerosis, polysomnography, Modified Fatigue Impact Scale, Fatigue Severity Scale, nocturnal awakening, age

Background: Fatigue is one of the most frequent symptoms of multiple sclerosis (MS) and one of the main reasons for underemployment and early retirement. The mechanisms of MS-related fatigue are unknown but comorbid disorders play a major role. Anemia, diabetes, side effects of medication and depression should be ruled out. Moreover, excessive daytime sleepiness (EDS) should be differentiated from fatigue. No approved medicinal therapy of MS fatigue is currently available. Objective: Presentation of current treatment strategies with a particular focus on secondary fatigue due to sleep disorders. Material and methods: A review of the literature was carried out. Results and conclusion: All MS patients suffering from fatigue should be questioned with respect to EDS and if necessary sleep medical investigations should be carried out; however, pure fatigue without accompanying EDS can also be caused by a sleep disorder. Medications, particularly freely available antihistamines, can also increase fatigue. Furthermore, anemia, iron deficits, diabetes and hypothyroidism should be excluded. Self-assessment questionnaires show an overlap between depression and fatigue. Several studies have shown that cognitive behavioral therapy and various psychotherapeutic measures, such as vertigo training, progressive exercise training and individualized physiotherapy as well as fatigue management interventions can lead to a significant improvement of MS-related fatigue. There is currently no medication which is suitable for treatment of fatigue, with the exception of fampridine for the treatment of motor functions and motor fatigue. [ABSTRACT FROM AUTHOR]

Background: Sleep disorders can cause tiredness. The relationship between sleep disorders and fatigue in patients with multiple sclerosis (MS) has not yet been investigated systematically.Objective: To investigate the relationship between fatigue and sleep disorders in patients with MS.Methods: Some 66 MS patients 20 to 66 years old were studied by overnight polysomnography. Using a cut-off point of 45 in the Modified Fatigue Impact Scale (MFIS), the entire cohort was stratified into a fatigued MS subgroup (n = 26) and a non-fatigued MS subgroup (n = 40).Results: Of the fatigued MS patients, 96% (n = 25) were suffering from a relevant sleep disorder, along with 60% of the non-fatigued MS patients (n = 24) (p = 0.001). Sleep-related breathing disorders were more frequent in the fatigued MS patients (27%) than in the non-fatigued MS patients (2.5%). Significantly higher MFIS values were detected in all (fatigued and non-fatigued) patients with relevant sleep disorders (mean MFIS 42.8; SD 18.3) than in patients without relevant sleep disorders (mean MFIS 20.5; SD 17.0) (p < 0.001). Suffering from a sleep disorder was associated with an increased risk of fatigue in MS (odds ratio: 18.5; 95% CI 1.6–208; p = 0.018).Conclusion: Our results demonstrate a clear and significant relationship between fatigue and sleep disorders. [ABSTRACT FROM AUTHOR]

Abstract Background The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity. Objective To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus. Methods Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%). Results Seropositive patients were found to be predominantly female (p < 0.0003), to more often have signs of co-existing autoimmunity (p < 0.00001), and to experience more severe clinical attacks. A visual acuity of ≤ 0.1 during acute optic neuritis (ON) attacks was more frequent among seropositives (p < 0.002). Similarly, motor symptoms were more common in seropositive patients, the median Medical Research Council scale (MRC) grade worse, and MRC grades ≤ 2 more frequent, in particular if patients met the 2006 revised criteria (p < 0.005, p < 0.006 and p < 0.01, respectively), the total spinal cord lesion load was higher (p < 0.006), and lesions ≥ 6 vertebral segments as well as entire spinal cord involvement more frequent (p < 0.003 and p < 0.043). By contrast, bilateral ON at onset was more common in seronegatives (p < 0.007), as was simultaneous ON and myelitis (p < 0.001); accordingly, the time to diagnosis of NMO was shorter in the seronegative group (p < 0.029). The course of disease was more often monophasic in seronegatives (p < 0.008). Seropositives and seronegatives did not differ significantly with regard to age at onset, time to relapse, annualized relapse rates, outcome from relapse (complete, partial, no recovery), annualized EDSS increase, mortality rate, supratentorial brain lesions, brainstem lesions, history of carcinoma, frequency of preceding infections, oligoclonal bands, or CSF pleocytosis. Both the time to relapse and the time to diagnosis was longer if the disease started with ON (p < 0.002 and p < 0.013). Motor symptoms or tetraparesis at first myelitis and > 1 myelitis attacks in the first year were identified as possible predictors of a worse outcome. Conclusion This study provides an overview of the clinical and paraclinical features of NMOSD in Caucasians and demonstrates a number of distinct disease characteristics in seropositive and seronegative patients.

The study of sleep disorders is best done in a clinical sleep laboratory by polysomnography (PSG), which allows to record all physiological signals necessary to determine sleep macrostructure (sleep stages), sleep microstructure (arousal), as well as related behavior of cardio-respiratory parameters. PSG was extended by 125-channel-magnetoencephalography (MEG) running at the same time. A MEG laboratory consists of a magnetically shielded room (MSR) as MEG requires very low ambient magnetic fields in the range of pT and subjects slept for 3–4 h starting around midnight in the MEG laboratory. The PSG recordings were first analyzed manually to identify sleep stages. In a second step, common spectral properties of EEG and MEG were investigated using measures such as the time-frequency evolution across the scalp. Manual sleep staging served as input to the spectral analysis. Results show both combined and independent patterns in EEG and MEG demonstrating the potential of combined recordings in researching local brain activity during sleep. [ABSTRACT FROM AUTHOR]