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      Circadian rhythm abnormalities and autonomic dysfunction in patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

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          Abstract

          Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) patients frequently show autonomic symptoms which may be associated with a hypothalamic dysfunction. This study aimed to explore circadian rhythm patterns in rest and activity and distal skin temperature (DST) and their association with self-reported outcome measures, in CFS/ME patients and healthy controls at two different times of year. Ten women who met both the 1994 CDC/Fukuda definition and 2003 Canadian criteria for CFS/ME were included in the study, along with ten healthy controls matched for age, sex and body mass index. Self-reported measures were used to assess fatigue, sleep quality, anxiety and depression, autonomic function and health-related quality of life. The ActTrust actigraph was used to record activity, DST and light intensity, with data intervals of one minute over seven consecutive days. Sleep variables were obtained through actigraphic analysis and from subjective sleep diary. The circadian variables and the spectral analysis of the rhythms were calculated. Linear regression analysis was used to evaluate the relationship between the rhythmic variables and clinical features. Recordings were taken in the same subjects in winter and summer. Results showed no differences in rhythm stability, sleep latency or number of awakenings between groups as measured with the actigraph. However, daily activity, the relative amplitude and the stability of the activity rhythm were lower in CFS/ME patients than in controls. DST was sensitive to environmental temperature and showed lower nocturnal values in CFS/ME patients than controls only in winter. A spectral analysis showed no differences in phase or amplitude of the 24h rhythm, but the power of the second harmonic (12h), revealed differences between groups (controls showed a post-lunch dip in activity and peak in DST, while CFS/ME patients did not) and correlated with clinical features. These findings suggest that circadian regulation and skin vasodilator responses may play a role in CFS/ME.

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          Automatic sleep/wake identification from wrist activity.

          The purpose of this study was to develop and validate automatic scoring methods to distinguish sleep from wakefulness based on wrist activity. Forty-one subjects (18 normals and 23 with sleep or psychiatric disorders) wore a wrist actigraph during overnight polysomnography. In a randomly selected subsample of 20 subjects, candidate sleep/wake prediction algorithms were iteratively optimized against standard sleep/wake scores. The optimal algorithms obtained for various data collection epoch lengths were then prospectively tested on the remaining 21 subjects. The final algorithms correctly distinguished sleep from wakefulness approximately 88% of the time. Actigraphic sleep percentage and sleep latency estimates correlated 0.82 and 0.90, respectively, with corresponding parameters scored from the polysomnogram (p < 0.0001). Automatic scoring of wrist activity provides valuable information about sleep and wakefulness that could be useful in both clinical and research applications.
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            COMPASS 31: a refined and abbreviated Composite Autonomic Symptom Score.

            To develop a concise and statistically robust instrument to assess autonomic symptoms that provides clinically relevant scores of autonomic symptom severity based on the well-established 169-item Autonomic Symptom Profile (ASP) and its validated 84-question scoring instrument, the Composite Autonomic Symptom Score (COMPASS).
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              Bright light therapy: improved sensitivity to its effects on rest-activity rhythms in Alzheimer patients by application of nonparametric methods.

              Sleep-wake rhythm disturbances in patients with Alzheimer's disease (AD) make a strong demand on caregivers and are among the most important reasons for institutionalization. Several previous studies reported that the disturbances improve with increased environmental light, which, through the retinohypothalamic tract, activates the suprachiasmatic nucleus (SCN), the biological clock of the brain. The data of recently published positive and negative reports on the effect of bright light on actigraphically assessed rest-activity rhythms in demented elderly were reanalyzed using several statistical procedures. It was demonstrated that the light-induced improvement in coupling of the rest-activity rhythm to the environmental zeitgeber of bright light is better detected using nonparametric procedures. Cosinor, complex demodulation, and Lomb-Scargle periodogram-derived variables are much less sensitive to this effect because of the highly nonsinusoidal waveform of the rest-activity rhythm. Guidelines for analyses of actigraphic data are given to improve the sensitivity to treatment effects in future studies.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: Project administrationRole: ResourcesRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: Project administrationRole: ResourcesRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                6 June 2018
                2018
                : 13
                : 6
                : e0198106
                Affiliations
                [1 ] Chronobiology Group, Department of Physiology and Biochemistry, Faculty of Pharmacy and Food Sciences, Universitat de Barcelona, Barcelona, Spain
                [2 ] CFS/ME Unit, Vall d’Hebron University Hospital Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain
                [3 ] Clinical Research Department, Laboratorios Viñas, Barcelona, Spain
                CNRS, University of Strasbourg, FRANCE
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-9009-4690
                http://orcid.org/0000-0002-9797-0219
                http://orcid.org/0000-0002-7582-7585
                Article
                PONE-D-18-02695
                10.1371/journal.pone.0198106
                5991397
                29874259
                b7b53755-1850-4d42-9afd-86dc199cf581
                © 2018 Cambras et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 25 January 2018
                : 14 May 2018
                Page count
                Figures: 3, Tables: 3, Pages: 20
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Biology and Life Sciences
                Physiology
                Physiological Processes
                Sleep
                Medicine and Health Sciences
                Physiology
                Physiological Processes
                Sleep
                Biology and Life Sciences
                Chronobiology
                Circadian Rhythms
                Biology and Life Sciences
                Physiology
                Physiological Parameters
                Body Temperature
                Skin Temperature
                Medicine and Health Sciences
                Physiology
                Physiological Parameters
                Body Temperature
                Skin Temperature
                Biology and Life Sciences
                Physiology
                Physiological Parameters
                Body Temperature
                Medicine and Health Sciences
                Physiology
                Physiological Parameters
                Body Temperature
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Fatigue
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Fatigue
                Biology and Life Sciences
                Chronobiology
                Biology and Life Sciences
                Psychology
                Emotions
                Anxiety
                Social Sciences
                Psychology
                Emotions
                Anxiety
                Medicine and Health Sciences
                Mental Health and Psychiatry
                Mood Disorders
                Depression
                Custom metadata
                All relevant data are within the paper and its supporting information files.

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