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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

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.

Contactless measurements during the night by a 3-D-camera are less time-consuming in comparison to polysomnography because they do not require sophisticated wiring. However, it is not clear what might be the diagnostic benefit and accuracy of this technology. We investigated 59 persons simultaneously by polysomnography and 3-D-camera and visual perceptive computing (19 patients with restless legs syndrome (RLS), 21 patients with obstructive sleep apnea (OSA), and 19 healthy volunteers). There was a significant correlation between the apnea hypopnea index (AHI) measured by polysomnography and respiratory events measured with the 3-D-camera in OSA patients (r = 0.823; p < 0.001). The receiver operating characteristic curve yielded a sensitivity of 90% for OSA with a specificity of 71.4%. In RLS patients 72.8% of leg movements confirmed by polysomnography could be detected by 3-D-video and a significant moderate correlation was found between PLM measured by polysomnography and by the 3-D-camera (RLS: r = 0.654; p = 0.004). In total, 95.4% of the sleep epochs were correctly classified by the machine learning approach, but only 32.5% of awake epochs. Further studies should investigate, if this technique might be an alternative to home sleep testing in persons with an increased pre-test probability for OSA.

Study Objectives: Evaluation of apnea detection using a tracheal sound (TS) sensor during sleep in patients with obstructive sleep apnea., Methods: Polysomnographic recordings of 32 patients (25 male, mean age 66.7 ± 15.3 years, and mean body mass index 30.1 ± 4.5 kg/m 2 ) were analyzed to compare the detection of apneas by four different methods of airflow signals: oronasal thermal airflow sensor (thermistor), nasal pressure transducer (NP), respiratory inductance plethysmography (RIPsum) and TS. The four used signals were scored randomly and independently from each other according to American Academy of Sleep Medicine rules. Results of apnea detection using NP, RIPsum and TS signals were compared to those obtained by thermistor as a reference signal., Results: The number of apneas detected by the thermistor was 4,167. The number of apneas detected using the NP was 5,416 (+29.97%), using the RIPsum was 2,959 (-29.71%) and using the TS was 5,019 (+20.45%). The kappa statistics (95% confidence interval) were 0.72 (0.71 to 0.74) for TS, 0.69 (0.67 to 0.70) for NP, and 0.57 (0.55 to 0.59) for RIPsum. The sensitivity/specificity (%) with respect to the thermistor were 99.23/69.27, 64.07/93.06 and 96.06/76.07 for the NP, RIPsum and TS respectively., Conclusions: With the sensor placed properly on the suprasternal notch, tracheal sounds could help detecting apneas that are underscored by the RIPsum and identify apneas that may be overscored by the NP sensor due to mouth breathing. In the absence of thermistor, TS sensors can be used for apnea detection., Clinical Trial Registration: Registry: German Clinical Trials Register (DRKS), Title: Using the tracheal sound probe of the polygraph CID102 to detect and differentiate obstructive, central, and mixed sleep apneas in patients with sleep disordered breathing, Identifier: DRKS00012795, URL: https://www.drks.de/drks&#95;web/navigate.do?navigationId=trial.HTML&TRIAL&#95;ID=DRKS00012795., (© 2019 American Academy of Sleep Medicine.)

More than 80% of multiple sclerosis (MS) patients suffer from fatigue. Despite this, there are few therapeutic options and evidence-based pharmacological treatments are lacking. The associated societal burden is substantial (MS fatigue is a major reason for part-time employment or early retirement), and at least one out of four MS patients view fatigue as the most burdensome symptom of their disease. The mechanisms underlying MS-related fatigue are poorly understood, and objective criteria for distinguishing and evaluating levels of fatigue and tiredness have not yet been developed. A further complication is that both symptoms may also be unspecific indicators of many other diseases (including depression, sleep disorders, anemia, renal failure, liver diseases, chronic obstructive pulmonary disease, drug side effects, recent MS relapses, infections, nocturia, cancer, thyroid hypofunction, lack of physical exercise). This paper reviews current treatment options of MS-related fatigue in order to establish an individualized therapeutic strategy that factors in existing comorbid disorders. To ensure that such a strategy can also be easily and widely implemented, a comprehensive approach is needed, which ideally takes into account all other possible causes and which is moreover cost efficient. Using a diagnostic interview, depressive disorders, sleep disorders and side effects of the medication should be identified and addressed. All MS patients suffering from fatigue should fill out the Modified Fatigue Impact Scale, Epworth Sleepiness Scale, the Beck Depression Inventory (or a similar depression scale), and the Pittsburgh Sleep Quality Index (or the Insomnia Severity Index). In some patients, polygraphic or polysomnographic investigations should be performed. The treatment of underlying sleep disorders, drug therapy with alfacalcidol or fampridine, exercise therapy, and cognitive behavioral therapy-based interventions may be effective against MS-related fatigue. The objectives of this article are to identify the reasons for fatigue in patients suffering from multiple sclerosis and to introduce individually tailored treatment approaches. Moreover, this paper focuses on current knowledge about MS-related fatigue in relation to brain atrophy and lesions, cognition, disease course, and other findings in an attempt to identify future research directions.

Objectives. Pittsburgh Sleep Quality Index (PSQI) values correlate with depression, but studies investigating the relationship between PSQI values and polysomnographic (PSG) data showed inconsistent findings. Methods. Sixty-five consecutive patients with multiple sclerosis (MS) were retrospectively classified as "good sleepers" (GS) (PSQI ≤ 5) and "poor sleepers" (PS) (PSQI > 5). The PSG data and the values of the Visual Analog Scale (VAS) of fatigue, Modified Fatigue Impact Scale (MFIS), Fatigue Severity Scale (FSS), Epworth Sleepiness Scale (ESS), and the Beck Depression Inventory (BDI) were compared. Results. No significant differences were found either for PSG data or for ESS, MFIS, and FSS values; but PS showed significantly increased BDI and VAS values. Conclusions. Poor sleep is associated with increased depression and fatigue scale values.

Quality of Life (QoL) is decreased in multiple sclerosis (MS), but studies about the impact of sleep disorders (SD) on health-related quality of Life (HRQoL) are lacking. From our original cohort, a cross-sectional polysomnographic (PSG) study in consecutive MS patients, we retrospectively analysed the previously unpublished data of the Nottingham Health Profile (NHP). Those MS patients suffering from sleep disorders (n = 49) showed significantly lower HRQoL compared to MS patients without sleep disorders (n = 17). Subsequently, we classified the patients into four subgroups: insomnia (n = 17), restless-legs syndrome, periodic limb movement disorder and SD due to leg pain (n = 24), obstructive sleep apnea (n = 8) and patients without sleep disorder (n = 17). OSA and insomnia patients showed significantly higher NHP values and decreased HRQoL not only for the sleep subscale but also for the "energy" and "emotional" area of the NHP. In addition, OSA patients also showed increased NHP values in the "physical abilities" area. Interestingly, we did not find a correlation between the objective PSG parameters and the subjective sleep items of the NHP. However, this study demonstrates that sleep disorders can reduce HRQoL in MS patients and should be considered as an important confounder in all studies investigating HRQoL in MS.

Unlabelled: Some patients undergoing epilepsy surgery suffer from early postoperative seizures which may have a negative impact on later outcome. Factors contributing to these seizures have not to date been examined systematically. We hypothesized that reduction of postoperative serum levels of antiepileptic drugs (AED) may be one risk factor for early postoperative seizures., Methods: We retrospectively reviewed medical records from 20 patients treated with lamotrigine (LTG) who underwent epilepsy surgery between January 1997 and February 2004. Demographic data, anaesthesiological and surgical procedures, co-medication, and pre- as well as one or more postoperative LTG serum levels were evaluated., Results: We found a significant decrease in LTG serum levels, amounting to more than 20% (mean 46%, range 21.9-69.1%), in 16 of 20 patients (80%). Six patients (30%) suffered from seizures in the first 2 weeks after surgery. In three patients, postoperative seizures occurred isochronically with the LTG serum level nadir. The magnitude of the reduction in serum levels was not influenced by age, sex, duration of the operation, the type of anaesthetic drugs or the postoperative co-medication., Discussion: Reductions in LTG serum levels are a relevant contributing factor for early postoperative seizures. Postoperative alteration of the gastrointestinal motility and transient time leading to delayed absorption and reduced bioavailability of AED may be a major risk factor. Therefore, close monitoring of postoperative LTG serum levels is necessary and should lead to a temporary dose augmentation and/or anticonvulsant co-medication with benzodiazepines in case of a pronounced reduction of serum levels.