Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Chronic Fatigue Syndrome: HELP
Articles by Vegard Bruun Bratholm Wyller
Based on 35 articles published since 2010
(Why 35 articles?)
||||

Between 2010 and 2020, V. B. Wyller wrote the following 35 articles about Fatigue Syndrome, Chronic.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Editorial Pain is common in chronic fatigue syndrome - current knowledge and future perspectives. 2019

Wyller, Vegard Bruun Bratholm. ·Institute of Clinical Medicine, University of Oslo, Oslo, Norway. · Department of Pediatrics and Adolescent Medicine, Akershus University Hospital, Sykehusveien 25, PO Box 1000, 1478 Lørenskog, Norway, Phone: +47 91 16 66 81. ·Scand J Pain · Pubmed #30864384.

ABSTRACT: -- No abstract --

2 Clinical Trial Predictors of chronic fatigue in adolescents six months after acute Epstein-Barr virus infection: A prospective cohort study. 2019

Pedersen, Maria / Asprusten, Tarjei Tørre / Godang, Kristin / Leegaard, Truls Michael / Osnes, Liv Toril / Skovlund, Eva / Tjade, Trygve / Øie, Merete Glenne / Wyller, Vegard Bruun Bratholm. ·Institute of Clinical Medicine, University of Oslo, Norway; Dept. of Pediatrics, Akershus University Hospital, Norway. · Section of Specialized Endocrinology, Dept. of Endocrinology, Oslo University Hospital, Norway. Electronic address: kgodang@ous-hf.no. · Institute of Clinical Medicine, University of Oslo, Norway; Dept. of Microbiology and Infection Control, Akershus University Hospital, Norway. Electronic address: truls.michael.leegaard@ahus.no. · Dept. of Immunology and Transfusion Medicine, Oslo University Hospital, Norway. Electronic address: uxlios@ous-hf.no. · Dept. of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway; Norwegian Institute of Public Health, Norway. Electronic address: eva.skovlund@ntnu.no. · Fürst Medical Laboratory, Norway. Electronic address: ttjade@furst.no. · Dept. of Psychology, University of Oslo, Norway; Dept. of Research, Innlandet Hospital Trust, Norway. Electronic address: m.g.oie@psykologi.uio.no. · Institute of Clinical Medicine, University of Oslo, Norway; Dept. of Pediatrics, Akershus University Hospital, Norway. Electronic address: v.b.b.wyller@medisin.uio.no. ·Brain Behav Immun · Pubmed #30261303.

ABSTRACT: INTRODUCTION: Acute Epstein-Barr virus (EBV) infection is a trigger of chronic fatigue and Chronic Fatigue Syndrome (CFS). This study investigated baseline predictors of chronic fatigue six months after an acute EBV infection. MATERIALS AND METHODS: A total of 200 adolescents (12-20 years old) with acute EBV infection were assessed for 149 possible baseline predictors and followed prospectively. We performed linear regression to assess possible associations between baseline predictors and fatigue (Chalder Fatigue Questionnaire total score) six months after the acute EBV infection. A total of 70 healthy controls were included for cross-sectional reference. This study is part of the CEBA-project (Chronic fatigue following acute Epstein-Barr virus infection in adolescents). RESULTS: In the final multiple linear regression model, fatigue six months after acute EBV infection was significantly and independently predicted by the following baseline variables (regression coefficient B[95% CI]): Sensory sensitivity (0.8[0.09-1.6]), pain severity (0.2[0.02-0.3]), functional impairment (1000 steps/day) (-0.3[-0.5 to -0.08]), negative emotions (anxiety) (0.4[0.2-0.6]), verbal memory (correct word recognition) (1.7[0.1-3.3]), plasma C-reactive protein (2.8[1.1-4.4] for CRP values >0.86) and plasma Vitamin B CONCLUSIONS: Development of fatigue after acute EBV infection is to a larger extent predicted by baseline variables related to symptoms and functions than to baseline variables reflecting infectious and immune processes. TRIAL REGISTRATION: ClinicalTrials, ID: NCT02335437, https://clinicaltrials.gov/ct2/show/NCT02335437.

3 Clinical Trial Clonidine in the treatment of adolescent chronic fatigue syndrome: a pilot study for the NorCAPITAL trial. 2012

Fagermoen, Even / Sulheim, Dag / Winger, Anette / Andersen, Anders M / Vethe, Nils Tore / Saul, J Philip / Thaulow, Erik / Wyller, Vegard Bruun. ·Department of Pediatrics, Oslo University Hospital and University of Oslo, Oslo, Norway. ·BMC Res Notes · Pubmed #22871021.

ABSTRACT: BACKGROUND: This pilot study (ClinicalTrials.gov ID: NCT01507701) assessed the feasibility and safety of clonidine in adolescent chronic fatigue syndrome (CFS). Specifically, we assessed clonidine dosage in relation to a) plasma concentration levels, b) orthostatic cardiovascular responses, and c) possible adverse effects. FINDINGS: Five adolescent CFS patients (14-19 years old) received 50 μg clonidine twice per day during 14 days in an open, uncontrolled design. Plasma concentration of clonidine was assayed by standard laboratory methods. Changes in orthostatic cardiovascular responses were assessed by a 20o head-up tilt-test (HUT). Adverse effects were mapped by a questionnaire.After 14 days, C0 median (range) of clonidine was 0.21 (0.18-0.36) μg/L, and Cmax median (range) of clonidine was 0.41 (0.38-0.56) μg/L. Also, supine blood pressures and heart rate were lower during clonidine treatment, and the HUT response was closer to the normal response. No serious adverse effects were registered. CONCLUSION: Clonidine 50 μg BID seems to be safe enough to proceed from a pilot study to a controlled trial in a select group of adolescents with CFS (ClinicalTrials.gov ID: NCT01040429).

4 Article EBV-requisitioning physicians' guess on fatigue state 6 months after acute EBV infection. 2019

Asprusten, Tarjei Tørre / Pedersen, Maria / Skovlund, Eva / Wyller, Vegard Bruun. ·Institute of Clinical Medicine, Medical Faculty, University of Oslo, Oslo, Norway. · Department of Pediatrics and Adolescent Medicine, Akershus University Hospital, Akershus, Norway. · Department of Public Health and Nursing, NTNU - Norwegian University of Science and Technology, Trondheim, Norway. · Division of Mental and Physical Health, Norwegian Institute of Public Health, Oslo, Norway. ·BMJ Paediatr Open · Pubmed #30957026.

ABSTRACT: We assessed referring medical practitioner's ability to predict chronic fatigue development in adolescents presenting with acute infectious mononucleosis. Compared with

5 Article Associations between clinical symptoms, plasma norepinephrine and deregulated immune gene networks in subgroups of adolescent with Chronic Fatigue Syndrome. 2019

Nguyen, Chinh Bkrong / Kumar, Surendra / Zucknick, Manuela / Kristensen, Vessela N / Gjerstad, Johannes / Nilsen, Hilde / Wyller, Vegard Bruun. ·Institute of Clinical Medicine, University of Oslo, 0372 Oslo, Norway; Department of Pediatrics and Adolescent Health, Akershus University Hospital, 1478 Lørenskog, Norway. Electronic address: c.b.nguyen@medisin.uio.no. · Department of Genetics, Institute of Cancer Research, Oslo University Hospital Radiumhospitalet, 0310 Oslo, Norway. · Oslo Centre for Biostatistics and Epidemiology, Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway. · Institute of Clinical Medicine, University of Oslo, 0372 Oslo, Norway; Department of Genetics, Institute of Cancer Research, Oslo University Hospital Radiumhospitalet, 0310 Oslo, Norway; Department of Clinical Molecular Biology, Akershus University Hospital, 1478 Lørenskog, Norway. · National Institute of Occupational Health, P.O. Box 8149 Dep., N-0033 Oslo, Norway. · Institute of Clinical Medicine, University of Oslo, 0372 Oslo, Norway; Department of Clinical Molecular Biology, Akershus University Hospital, 1478 Lørenskog, Norway. · Institute of Clinical Medicine, University of Oslo, 0372 Oslo, Norway; Department of Pediatrics and Adolescent Health, Akershus University Hospital, 1478 Lørenskog, Norway. ·Brain Behav Immun · Pubmed #30419269.

ABSTRACT: BACKGROUND: Chronic Fatigue Syndrome (CFS) is one of the most important causes of disability among adolescents while limited knowledge exists on genetic determinants underlying disease pathophysiology. METHODS: We analyzed deregulated immune-gene modules using Pathifier software on whole blood gene expression data (29 CFS patients, 18 controls). Deconvolution of immune cell subtypes based on gene expression profile was performed using CIBERSORT. Supervised consensus clustering on pathway deregulation score (PDS) was used to define CFS subgroups. Associations between PDS and immune, neuroendocrine/autonomic and clinical markers were examined. The impact of plasma norepinephrine level on clinical markers over time was assessed in a larger cohort (91 patients). RESULTS: A group of 29 immune-gene sets was shown to differ patients from controls and detect subgroups within CFS. Group 1P (high PDS, low norepinephrine, low naïve CD4+ composition) had strong association with levels of serum C-reactive protein and Transforming Growth Factor-beta. Group 2P (low PDS, high norepinephrine, high naïve CD4+ composition) had strong associations with neuroendocrine/autonomic markers. The corresponding plasma norepinephrine level delineated 91 patients into two subgroups with significant differences in fatigue score. CONCLUSION: We identified 29 immune-gene sets linked to plasma norepinephrine level that could delineate CFS subgroups. Plasma norepinephrine stratification revealed that lower levels of norepinephrine were associated with higher fatigue. Our data suggests potential involvement of neuro-immune dysregulation and genetic stratification in CFS.

6 Article Systemic exertion intolerance disease diagnostic criteria applied on an adolescent chronic fatigue syndrome cohort: evaluation of subgroup differences and prognostic utility. 2018

Asprusten, Tarjei Tørre / Sulheim, Dag / Fagermoen, Even / Winger, Anette / Skovlund, Eva / Wyller, Vegard Bruun. ·Institute of Clinical Medicine, Medical Faculty, University of Oslo, Oslo, Norway. · Department of Pediatrics and Adolescent Medicine, Innlandet Hospital Trust, Lillehammer, Norway. · Department of Anesthesiology and Critical Care, Oslo University Hospital, Oslo, Norway. · Department of Nursing and Health Promotion, Oslo University College of Applied Sciences, Oslo, Norway. · Department of Public Health and Nursing, NTNU - Norwegian University of Science and Technology, Trondheim, Norway. · Department of Pharmacoepidemiology, Mental and Physical Health, Norwegian Institute of Public Health, Oslo, Norway. · Department of Pediatrics and Adolescent Medicine, Akershus University Hospital, Akershus, Norway. ·BMJ Paediatr Open · Pubmed #29637195.

ABSTRACT: Objective: Existing case definitions for chronic fatigue syndrome (CFS) all have disputed validity. The present study investigates differences between adolescent patients with CFS who satisfy the systemic exertion intolerance disease (SEID) diagnostic criteria (SEID-positive) and those who do not satisfy the criteria (SEID-negative). Methods: 120 adolescent patients with CFS with a mean age of 15.4 years (range 12-18 years) included in the NorCAPITAL project (ClinicalTrials ID: NCT01040429) were post-hoc subgrouped according to the SEID criteria based on a comprehensive questionnaire. The two subgroups were compared across baseline characteristics, as well as a wide range of cardiovascular, inflammatory, infectious, neuroendocrine and cognitive variables. Data from 30-week follow-up were used to investigate prognostic differences between SEID-positive and SEID-negative patients. Results: A total of 45 patients with CFS were SEID-positive, 69 were SEID-negative and 6 could not be classified. Despite the fact that clinically depressed patients were excluded in the NorCAPITAL project, the SEID-positive group had significantly higher score on symptoms suggesting a mood disorder (Mood and Feelings Questionnaire): 23.2 vs 13.4, difference 9.19 (95% CI 5.78 to 12.6). No other baseline characteristics showed any group differences. When accounting for multiple comparisons, there were no statistically significant differences between the groups regarding cardiovascular, inflammatory, infectious, neuroendocrine and cognitive variables. Steps per day and Chalder Fatigue Questionnaire at week 30 showed no differences between the groups. Conclusion: The findings question the discriminant and prognostic validity of the SEID diagnostic criteria in adolescent CFS, and suggest that the criteria tend to select patients with depressive symptoms.

7 Article Transforming growth factor beta (TGF-β) in adolescent chronic fatigue syndrome. 2017

Wyller, Vegard Bruun / Nguyen, Chinh Bkrong / Ludviksen, Judith Anita / Mollnes, Tom Eirik. ·Department of Pediatrics and Adolescent Health, Akershus University Hospital, 1478, Lørenskog, Norway. brwylle@online.no. · Division of Medicine and Laboratory Sciences, University of Oslo, Oslo, Norway. brwylle@online.no. · Department of Pediatrics and Adolescent Health, Akershus University Hospital, 1478, Lørenskog, Norway. · Research Laboratory, Nordland Hospital, Bodø, Norway. · Faculty of Health Sciences, K.G. Jebsen TREC, University of Tromsø, Tromsø, Norway. · Department of Immunology, Oslo University Hospital, Oslo, Norway. · K.G. Jebsen IRC, University of Oslo, Oslo, Norway. · Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway. ·J Transl Med · Pubmed #29202780.

ABSTRACT: BACKGROUND: Chronic fatigue syndrome (CFS) is a prevalent and disabling condition among adolescent. The disease mechanisms are unknown. Previous studies have suggested elevated plasma levels of several cytokines, but a recent meta-analysis of 38 articles found that of 77 different cytokines measured in plasma, transforming growth factor beta (TGF-β) was the only one that was elevated in patients compared to controls in a sufficient number of articles. In the present study we therefore compared the plasma levels of the three TGF-β isoforms in adolescent CFS patients and healthy controls. In addition, the study explored associations between TGF-β levels, neuroendocrine markers, clinical markers and differentially expressed genes within the CFS group. METHODS: CFS patients aged 12-18 years (n = 120) were recruited nation-wide to a single referral center as part of the NorCAPITAL project (ClinicalTrials ID: NCT01040429). A broad case definition of CFS was applied, requiring 3 months of unexplained, disabling chronic/relapsing fatigue of new onset, whereas no accompanying symptoms were necessary. Healthy controls (n = 68) were recruited from local schools. The three isoforms of TGF-β (TGF-β1, TGF-β2, TGF-β3) were assayed using multiplex technology. Neuroendocrine markers encompassed plasma and urine levels of catecholamines and cortisol, as well as heart rate variability indices. Clinical markers consisted of questionnaire scores for symptoms of post-exertional malaise, inflammation, fatigue, depression and trait anxiety, as well as activity recordings. Whole blood gene expression was assessed by RNA sequencing in a subgroup of patients (n = 29) and controls (n = 18). RESULTS: Plasma levels of all three isoforms of TGF-β were equal in the CFS patients and the healthy controls. Subgrouping according to the Fukuda and Canada 2003 criteria of CFS did not reveal differential results. Within the CFS group, all isoforms of TGF-β were associated with plasma cortisol, urine norepinephrine and urine epinephrine, and this association pattern was related to fatigue score. Also, TGF-β3 was related to expression of the B cell annotated genes TNFRSF13C and CXCR5. CONCLUSIONS: Plasma levels of all TGF-β isoforms were not altered in adolescent CFS. However, the TGF-β isoforms were associated with neuroendocrine markers, an association related to fatigue score. Furthermore, TGF-β3 might partly mediate an association between plasma cortisol and B cell gene expression. Trial registration Clinical Trials NCT01040429.

8 Article HPV vaccination and risk of chronic fatigue syndrome/myalgic encephalomyelitis: A nationwide register-based study from Norway. 2017

Feiring, Berit / Laake, Ida / Bakken, Inger Johanne / Greve-Isdahl, Margrethe / Wyller, Vegard Bruun / Håberg, Siri E / Magnus, Per / Trogstad, Lill. ·Department of Infectious Disease Epidemiology and Modelling, Norwegian Institute of Public Health, PO Box 4404 Nydalen, 0403 Oslo, Norway. Electronic address: berit.feiring@fhi.no. · Department of Infectious Disease Epidemiology and Modelling, Norwegian Institute of Public Health, PO Box 4404 Nydalen, 0403 Oslo, Norway. Electronic address: ida.laake@fhi.no. · Department of Child Health, Norwegian Institute of Public Health, PO Box 4404 Nydalen, 0403 Oslo, Norway. Electronic address: inger.johanne.bakken@fhi.no. · Department of Vaccine Preventable Diseases, Norwegian Institute of Public Health, PO Box 4404 Nydalen, 0403 Oslo, Norway. Electronic address: margrethe.greve-isdahl@fhi.no. · Department of Paediatrics and Adolescent Health, Akershus University Hospital, 1478 Lørenskog, Norway. Electronic address: brwylle@online.no. · Division of Physical and Mental Health, Norwegian Institute of Public Health, PO Box 4404 Nydalen, 0403 Oslo, Norway. Electronic address: sirieldevik.haberg@fhi.no. · Division of Health Data and Digitalisation, Norwegian Institute of Public Health, PO Box 4404 Nydalen, 0403 Oslo, Norway. Electronic address: per.magnus@fhi.no. · Department of Infectious Disease Epidemiology and Modelling, Norwegian Institute of Public Health, PO Box 4404 Nydalen, 0403 Oslo, Norway. Electronic address: lill.trogstad@fhi.no. ·Vaccine · Pubmed #28648542.

ABSTRACT: BACKGROUND: Vaccination has been suggested to be involved in the aetiology of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). HPV vaccine was introduced in the Norwegian Childhood Immunisation Programme and offered 12year old girls from 2009. We studied the association between HPV vaccination and risk of CFS/ME and also assessed medical history in relation to both risk of CFS/ME and HPV vaccine uptake. METHODS: Individual data from national registries, including the Norwegian Population Registry, the Norwegian Patient Registry and the Norwegian Immunisation Registry were linked using the unique personal identification number. Yearly incidence rates of CFS/ME for 2009-2014 were calculated among the 824,133 boys and girls, aged 10-17 living in Norway during these 6years. A total of 176,453 girls born 1997-2002 were eligible for HPV vaccination and included in further analyses. Hazard ratios (HRs) of CFS/ME were estimated using Cox regression. Risk differences (RDs) of vaccine uptake were estimated with binomial regression. RESULTS: A similar yearly increase in incidence rate of CFS/ME was observed among girls and boys, IRR=1.15 (95% confidence interval (CI) 1.10-1.19) and 1.15 (95% CI 1.09-1.22), respectively. HPV vaccination was not associated with CFS/ME, HR=0.86 (95% CI 0.69-1.08) for the entire follow-up period and 0.96 (95% CI 0.64-1.43) for the first two years after vaccination. The risk of CFS/ME increased with increasing number of previous hospital contacts, HR=5.23 (95% CI 3.66-7.49) for 7 or more contacts as compared to no contacts. Girls with 7 or more hospital contacts were less likely to be vaccinated than girls with no previous hospital contacts, RD=-5.5% (95% CI -6.7% to -4.2%). CONCLUSIONS: No indication of increased risk of CFS/ME following HPV vaccination was observed among girls in the first 6 birth cohorts offered HPV vaccine through the national immunisation programme in Norway.

9 Article Whole blood gene expression in adolescent chronic fatigue syndrome: an exploratory cross-sectional study suggesting altered B cell differentiation and survival. 2017

Nguyen, Chinh Bkrong / Alsøe, Lene / Lindvall, Jessica M / Sulheim, Dag / Fagermoen, Even / Winger, Anette / Kaarbø, Mari / Nilsen, Hilde / Wyller, Vegard Bruun. ·Department of Paediatrics and Adolescent Health, Akershus University Hospital, 1478, Lørenskog, Norway. · Division of Medicine and Laboratory Sciences, Medical Faculty, University of Oslo, Oslo, Norway. · Institute of Clinical Medicine, Department of Clinical Molecular Biology, University of Oslo, and Akershus University Hospital, Lørenskog, Norway. · National Bioinformatics Infrastructure Sweden (NBIS), Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden. · Department of Paediatrics, Lillehammer County Hospital, Lillehammer, Norway. · Department of Anesthesiology and Critical Care, Oslo University Hospital, Oslo, Norway. · Institute of Nursing Sciences, Oslo and Akershus University College of Applied Sciences, Oslo, Norway. · Department of Microbiology, Oslo University Hospital, Oslo, Norway. · Department of Paediatrics and Adolescent Health, Akershus University Hospital, 1478, Lørenskog, Norway. brwylle@online.no. · Division of Medicine and Laboratory Sciences, Medical Faculty, University of Oslo, Oslo, Norway. brwylle@online.no. ·J Transl Med · Pubmed #28494812.

ABSTRACT: BACKGROUND: Chronic fatigue syndrome (CFS) is a prevalent and disabling condition affecting adolescents. The pathophysiology is poorly understood, but immune alterations might be an important component. This study compared whole blood gene expression in adolescent CFS patients and healthy controls, and explored associations between gene expression and neuroendocrine markers, immune markers and clinical markers within the CFS group. METHODS: CFS patients (12-18 years old) were recruited nation-wide to a single referral center as part of the NorCAPITAL project. A broad case definition of CFS was applied, requiring 3 months of unexplained, disabling chronic/relapsing fatigue of new onset, whereas no accompanying symptoms were necessary. Healthy controls having comparable distribution of gender and age were recruited from local schools. Whole blood samples were subjected to RNA sequencing. Immune markers were blood leukocyte counts, plasma cytokines, serum C-reactive protein and immunoglobulins. Neuroendocrine markers encompassed plasma and urine levels of catecholamines and cortisol, as well as heart rate variability indices. Clinical markers consisted of questionnaire scores for symptoms of post-exertional malaise, inflammation, fatigue, depression and trait anxiety, as well as activity recordings. RESULTS: A total of 29 CFS patients and 18 healthy controls were included. We identified 176 genes as differentially expressed in patients compared to controls, adjusting for age and gender factors. Gene set enrichment analyses suggested impairment of B cell differentiation and survival, as well as enhancement of innate antiviral responses and inflammation in the CFS group. A pattern of co-expression could be identified, and this pattern, as well as single gene transcripts, was significantly associated with indices of autonomic nervous activity, plasma cortisol, and blood monocyte and eosinophil counts. Also, an association with symptoms of post-exertional malaise was demonstrated. CONCLUSION: Adolescent CFS is characterized by differential gene expression pattern in whole blood suggestive of impaired B cell differentiation and survival, and enhanced innate antiviral responses and inflammation. This expression pattern is associated with neuroendocrine markers of altered HPA axis and autonomic nervous activity, and with symptoms of post-exertional malaise. Trial registration Clinical Trials NCT01040429.

10 Article Sleep-wake rhythm disturbances and perceived sleep in adolescent chronic fatigue syndrome. 2017

Pedersen, Maria / Ekstedt, Mirjam / Småstuen, Milada C / Wyller, Vegard B / Sulheim, Dag / Fagermoen, Even / Winger, Anette / Pedersen, Edvard / Hrubos-Strøm, Harald. ·Institute of Clinical Medicine, University of Oslo, Oslo, Norway. · Department of Pediatrics, Akershus University Hospital, Lorenskog, Norway. · School of Health and Caring Sciences, Linneaus University, Kalmar, Sweden. · Department of Learning, Informatics, Management and Ethics, Karolinska Institutet, Stockholm, Sweden. · Faculty of Health, Akershus University College of Applied Sciences, Oslo, Norway. · Department of Pediatrics, Innlandet Hospital Trust, Brumunddal, Norway. · Department of Anesthesiology and Critical Care, Oslo University Hospital, Oslo, Norway. · Department of Computer Science, UiT-The Arctic University of Norway, Tromso, Norway. · Division of Surgery, Department of Otorhinolaryngology, Akershus University Hospital, Lorenskog, Norway. ·J Sleep Res · Pubmed #28470767.

ABSTRACT: Chronic fatigue syndrome (CFS) is characterized by long-lasting, disabling and unexplained fatigue that is often accompanied by unrefreshing sleep. The aim of this cross-sectional study was to investigate sleep-wake rhythm and perceived sleep in adolescent CFS patients compared to healthy individuals. We analysed baseline data on 120 adolescent CFS patients and 39 healthy individuals included in the NorCAPITAL project. Activity measures from a uniaxial accelerometer (activPAL) were used to estimate mid-sleep time (mid-point of a period with sleep) and time in bed. Scores from the Karolinska Sleep Questionnaire (KSQ) were also assessed. The activity measures showed that the CFS patients stayed significantly longer in bed, had a significantly delayed mid-sleep time and a more varied sleep-wake rhythm during weekdays compared with healthy individuals. On the KSQ, the CFS patients reported significantly more insomnia symptoms, sleepiness, awakening problems and a longer sleep onset latency than healthy individuals. These results might indicate that disrupted sleep-wake phase could contribute to adolescent CFS; however, further investigations are warranted.

11 Article Emotional conflict processing in adolescent chronic fatigue syndrome: A pilot study using functional magnetic resonance imaging. 2017

Wortinger, Laura Anne / Endestad, Tor / Melinder, Annika Maria D / Øie, Merete Glenne / Sulheim, Dag / Fagermoen, Even / Wyller, Vegard Bruun. ·a Department of Pediatrics , Akershus University Hospital , Nordbyhagen , Norway. · b Department of Psychology , University of Oslo , Oslo , Norway. · c Cognitive Developmental Research Unit, Department of Psychology , University of Oslo , Oslo , Norway. · d Research Department , Innlandet Hospital Trust , Lillehammer , Norway. · e Department of Pediatrics , Oslo University Hospital , Oslo , Norway. · f Department of Pediatrics , Innlandet Hospital Trust , Lillehammer , Norway. · g Department of Anesthesiology and Critical Care , Oslo University Hospital , Oslo , Norway. ·J Clin Exp Neuropsychol · Pubmed #27647312.

ABSTRACT: INTRODUCTION: Studies of neurocognition suggest that abnormalities in cognitive control contribute to the pathophysiology of chronic fatigue syndrome (CFS) in adolescents, yet these abnormalities remain poorly understood at the neurobiological level. Reports indicate that adolescents with CFS are significantly impaired in conflict processing, a primary element of cognitive control. METHOD: In this study, we examine whether emotional conflict processing is altered on behavioral and neural levels in adolescents with CFS and a healthy comparison group. Fifteen adolescent patients with CFS and 24 healthy adolescent participants underwent functional magnetic resonance imaging (fMRI) while performing an emotional conflict task that involved categorizing facial affect while ignoring overlaid affect labeled words. RESULTS: Adolescent CFS patients were less able to engage the left amygdala and left midposterior insula (mpINS) in response to conflict than the healthy comparison group. An association between accuracy interference and conflict-related reactivity in the amygdala was observed in CFS patients. A relationship between response time interference and conflict-related reactivity in the mpINS was also reported. Neural responses in the amygdala and mpINS were specific to fatigue severity. CONCLUSIONS: These data demonstrate that adolescent CFS patients displayed deficits in emotional conflict processing. Our results suggest abnormalities in affective and cognitive functioning of the salience network, which might underlie the pathophysiology of adolescent CFS.

12 Article Genetic variation in catechol-O-methyltransferase modifies effects of clonidine treatment in chronic fatigue syndrome. 2016

Hall, K T / Kossowsky, J / Oberlander, T F / Kaptchuk, T J / Saul, J P / Wyller, V B / Fagermoen, E / Sulheim, D / Gjerstad, J / Winger, A / Mukamal, K J. ·Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. · Harvard Medical School, Boston, MA, USA. · Department of Anesthesiology Perioperative and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. · Department of Clinical Psychology and Psychotherapy, University of Basel, Basel, Switzerland. · Child and Family Research Institute, Department of Pediatrics, and School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada. · Division of General Medicine and Primary Care, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. · Program in Placebo Studies, Beth Israel Deaconess Medical Center, Boston, MA, USA. · Division of Cardiology, Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA. · Department of Paediatrics, Akershus University Hospital, Lørenskog, Norway. · Department of Anesthesiology and Critical Care, Oslo University Hospital, Oslo, Norway. · Department of Pediatrics, Lillehammer County Hospital, Brumunddal, Norway. · National Institute of Occupational Health, Department, Oslo, Norway. · Department of Nursing and Health Promotion, Faculty of Health, Oslo University College of Applied Sciences, Oslo, Norway. ·Pharmacogenomics J · Pubmed #27457818.

ABSTRACT: Clonidine, an α2-adrenergic receptor agonist, decreases circulating norepinephrine and epinephrine, attenuating sympathetic activity. Although catechol-O-methyltransferase (COMT) metabolizes catecholamines, main effectors of sympathetic function, COMT genetic variation effects on clonidine treatment are unknown. Chronic fatigue syndrome (CFS) is hypothesized to result in part from dysregulated sympathetic function. A candidate gene analysis of COMT rs4680 effects on clinical outcomes in the Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial (NorCAPITAL), a randomized double-blinded clonidine versus placebo trial, was conducted (N=104). Patients homozygous for rs4680 high-activity allele randomized to clonidine took 2500 fewer steps compared with placebo (Pinteraction=0.04). There were no differences between clonidine and placebo among patients with COMT low-activity alleles. Similar gene-drug interactions were observed for sleep (Pinteraction=0.003) and quality of life (Pinteraction=0.018). Detrimental effects of clonidine in the subset of CFS patients homozygous for COMT high-activity allele warrant investigation of potential clonidine-COMT interaction effects in other conditions.

13 Article Altered neuroendocrine control and association to clinical symptoms in adolescent chronic fatigue syndrome: a cross-sectional study. 2016

Wyller, Vegard Bruun / Vitelli, Valieria / Sulheim, Dag / Fagermoen, Even / Winger, Anette / Godang, Kristin / Bollerslev, Jens. ·Division of Medicine and Laboratory Sciences, Medical Faculty, University of Oslo, Oslo, Norway. brwylle@online.no. · Department of Paediatrics, Akershus University Hospital, Nordbyhagen, 1478, Lørenskog, Norway. brwylle@online.no. · Department of Biostatistics, Institute of Basic Medical Sciences, Oslo Centre for Biostatistics and Epidemiology, University of Oslo, Oslo, Norway. · Department of Paediatrics, Oslo University Hospital, Oslo, Norway. · Department of Paediatrics, Lillehammer County Hospital, Lillehammer, Norway. · Institute of Clinical Medicine, Medical Faculty, University of Oslo, Oslo, Norway. · Department of Anesthesiology and Critical Care, Oslo University Hospital, Oslo, Norway. · Institute of Nursing Sciences, Oslo and Akershus University College of Applied Sciences, Oslo, Norway. · Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital Rikshospitalet, Oslo, Norway. ·J Transl Med · Pubmed #27149955.

ABSTRACT: BACKGROUND: Chronic fatigue syndrome (CFS) is a common and disabling disorder, and a major threat against adolescent health. The pathophysiology is unknown, but alteration of neuroendocrine control systems might be a central element, resulting in attenuation of the hypothalamus-pituitary-adrenalin (HPA) axis and enhancement of the sympathetic/adrenal medulla (SAM) system. This study explored differences in neuroendocrine control mechanisms between adolescent CFS patients and healthy controls, and whether characteristics of the control mechanisms are associated with important clinical variables within the CFS group. METHODS: CFS patients 12-18 years of age were recruited nation-wide to a single referral center as part of the NorCAPITAL project. A broad case definition of CFS was applied. A comparable group of healthy controls were recruited from local schools. A total of nine hormones were assayed and subjected to network analyses using the ARACNE algorithm. Symptoms were charted by a questionnaire, and daily physical activity was recorded by an accelerometer. RESULTS: A total of 120 CFS patients and 68 healthy controls were included. CFS patients had significantly higher levels of plasma norepinephrine, plasma epinephrine and plasma FT4, and significantly lower levels of urine cortisol/creatinine ratio. Subgrouping according to other case definitions as well as adjusting for confounding factors did not alter the results. Multivariate linear regression models as well as network analyses revealed different interrelations between hormones of the HPA axis, the SAM system, and the thyroid system in CFS patients and healthy controls. Also, single hormone degree centrality was associated with clinical markers within the CFS group. CONCLUSION: This study reveals different interrelation between hormones of the HPA axis, the SAM system, and the thyroid system in CFS patients and healthy controls, and an association between hormone control characteristics and important clinical variables in the CFS group. These results add to the growing insight of CFS disease mechanisms. Trial registration Clinical Trials NCT01040429.

14 Article Chronic fatigue syndrome/myalgic encephalo-myelitis--pathophysiology, diagnosis and treatment. 2015

Wyller, Vegard Bruun / Reme, Silje Endresen / Mollnes, Tom Eirik. · ·Tidsskr Nor Laegeforen · Pubmed #26674040.

ABSTRACT: -- No abstract --

15 Article Maintenance of Chronic Fatigue Syndrome (CFS) in Young CFS Patients Is Associated with the 5-HTTLPR and SNP rs25531 A > G Genotype. 2015

Meyer, Benedicte / Nguyen, Chinh Bkrong Thuy / Moen, Aurora / Fagermoen, Even / Sulheim, Dag / Nilsen, Hilde / Wyller, Vegard Bruun / Gjerstad, Johannes. ·Dept. of Paediatrics, Akershus University Hospital, Oslo, Norway. · Dept. of Physical Medicine and Rehabilitation, Oslo University Hospital, Oslo, Norway; National Institute of Occupational Health, Oslo, Norway; Department of Biosciences, University of Oslo, Oslo, Norway. · Dept. of Anaesthesiology and Critical Care, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, Medical Faculty, University of Oslo, Oslo, Norway. · Dept. of Paediatrics, Lillehammer County Hospital, Lillehammer, Norway; Dept. of Paediatrics, Oslo University Hospital, Oslo, Norway. · Institute of Clinical Medicine, Medical Faculty, University of Oslo, Oslo, Norway; Section for Clinical Molecular Biology, Akershus University Hospital, Oslo, Norway. · Dept. of Paediatrics, Akershus University Hospital, Oslo, Norway; Institute of Clinical Medicine, Medical Faculty, University of Oslo, Oslo, Norway. ·PLoS One · Pubmed #26473596.

ABSTRACT: Earlier studies have shown that genetic variability in the SLC6A4 gene encoding the serotonin transporter (5-HTT) may be important for the re-uptake of serotonin (5-HT) in the central nervous system. In the present study we investigated how the 5-HTT genotype i.e. the short (S) versus long (L) 5-HTTLPR allele and the SNP rs25531 A > G affect the physical and psychosocial functioning in patients with chronic fatigue syndrome (CFS). All 120 patients were recruited from The Department of Paediatrics at Oslo University Hospital, Norway, a national referral center for young CFS patients (12-18 years). Main outcomes were number of steps per day obtained by an accelerometer and disability scored by the Functional Disability Inventory (FDI). Patients with the 5-HTT SS or SLG genotype had a significantly lower number of steps per day than patients with the 5-HTT LALG, SLA or LALA genotype. Patients with the 5-HTT SS or SLG genotype also had a significantly higher FDI score than patients with the 5-HTT LALG, SLA or LALA genotype. Thus, CFS patients with the 5-HTT SS or SLG genotype had worse 30 weeks outcome than CFS patients with the 5-HTT LALG, SLA or LALA genotype. The present study suggests that the 5-HTT genotype may be a factor that contributes to maintenance of CFS.

16 Article Effects of low-dose clonidine on cardiovascular and autonomic variables in adolescents with chronic fatigue: a randomized controlled trial. 2015

Fagermoen, Even / Sulheim, Dag / Winger, Anette / Andersen, Anders M / Gjerstad, Johannes / Godang, Kristin / Rowe, Peter C / Saul, J Philip / Skovlund, Eva / Wyller, Vegard Bruun. ·Institute of Clinical Medicine, Medical Faculty, University of Oslo, P.O.Box 1171, Blindern, 0318, Oslo, Norway. feef@online.no. · Department of Anaesthesiology and Critical Care, Oslo University Hospital, P.O.Box 4950, Nydalen, 0424, Oslo, Norway. feef@online.no. · Department of Paediatrics, Oslo University Hospital, P.O.Box 4950, Nydalen, 0424, Oslo, Norway. dag.sulheim@medisin.uio.no. · Department of Paediatrics, Lillehammer County Hospital, P.O.Box 104, 2381, Brumunddal, Norway. dag.sulheim@medisin.uio.no. · Institute of Nursing Sciences, Oslo and Akershus University College of Applied Sciences, P.O. Box 4 St., Olavs plass, 0130, Oslo, Norway. Anette.Winger@hioa.no. · Department of Pharmacology, Oslo University Hospital, P.O.Box 4950, Nydalen, 0424, Oslo, Norway. Anders.Andersen2@oslo-universitetssykehus.no. · National Institute of Occupational Health, P.O Box 8149, Dep, 0033, Oslo, Norway. johannes.gjerstad@stami.no. · Department of Biosciences, University of Oslo, P.O.Box 1066, Blindern, 0316, Oslo, Norway. johannes.gjerstad@stami.no. · Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital Rikshospitalet, P.O.Box 4950, Nydalen, 0424, Oslo, Norway. kgodang@ous-hf.no. · Department of Paediatrics, Johns Hopkins University School of Medicine, 200 N. Wolfe Street, Baltimore, MD, 21287, USA. prowe@jhmi.edu. · Department of Paediatrics, Medical University of South Carolina, 169 Ashley Avenue, Charleston, SC, 29425, USA. Phil.Saul@nationwidechildrens.org. · Department of Pharmaceutical Science, University of Oslo, P.O.Box 1068, Blindern, 0316, Oslo, Norway. eva.skovlund@farmasi.uio.no. · Norwegian Institute of Public Health, P.O.Box 4404, Nydalen, 0403, Oslo, Norway. eva.skovlund@farmasi.uio.no. · Institute of Clinical Medicine, Medical Faculty, University of Oslo, P.O.Box 1171, Blindern, 0318, Oslo, Norway. brwylle@online.no. · Department of Paediatrics, Akershus University Hospital, P.O.Box 1000, 1478, Lørenskog, Norway. brwylle@online.no. ·BMC Pediatr · Pubmed #26357864.

ABSTRACT: BACKGROUND: Chronic Fatigue Syndrome (CFS) is a common and disabling condition in adolescence with few treatment options. A central feature of CFS is orthostatic intolerance and abnormal autonomic cardiovascular control characterized by sympathetic predominance. We hypothesized that symptoms as well as the underlying pathophysiology might improve by treatment with the alpha2A-adrenoceptor agonist clonidine. METHODS: A total of 176 adolescent CFS patients (12-18 years) were assessed for eligibility at a single referral center recruiting nation-wide. Patients were randomized 1:1 by a computer system and started treatment with clonidine capsules (25 μg or 50 μg twice daily, respectively, for body weight below/above 35 kg) or placebo capsules for 9 weeks. Double-blinding was provided. Data were collected from March 2010 until October 2012 as part of The Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial (NorCAPITAL). Effect of clonidine intervention was assessed by general linear models in intention-to-treat analyses, including baseline values as covariates in the model. RESULTS: A total of 120 patients (clonidine group n = 60, placebo group n = 60) were enrolled and started treatment. There were 14 drop-outs (5 in the clonidine group, 9 in the placebo group) during the intervention period. At 8 weeks, the clonidine group had lower plasma norepinephrine (difference = 205 pmol/L, p = 0.05) and urine norepinephrine/creatinine ratio (difference = 3.9 nmol/mmol, p = 0.002). During supine rest, the clonidine group had higher heart rate variability in the low-frequency range (LF-HRV, absolute units) (ratio = 1.4, p = 0.007) as well as higher standard deviation of all RR-intervals (SDNN) (difference = 12.0 ms, p = 0.05); during 20° head-up tilt there were no statistical differences in any cardiovascular variable. Symptoms of orthostatic intolerance did not change during the intervention period. CONCLUSIONS: Low-dose clonidine reduces catecholamine levels in adolescent CFS, but the effects on autonomic cardiovascular control are sparse. Clonidine does not improve symptoms of orthostatic intolerance. TRIAL REGISTRATION: Clinical Trials ID: NCT01040429, date of registration 12/28/2009.

17 Article Health related quality of life in adolescents with chronic fatigue syndrome: a cross-sectional study. 2015

Winger, Anette / Kvarstein, Gunnvald / Wyller, Vegard Bruun / Ekstedt, Mirjam / Sulheim, Dag / Fagermoen, Even / Småstuen, Milada Cvancarova / Helseth, Sølvi. ·Institute of Nursing, Faculty of Health Sciences, Oslo and Akershus University College of Applied Sciences, Postboks 4 St. Olavs plass, NO-0130, Oslo, Norway. anette.winger@hioa.no. · Department of Clinical Medicine, UIT The Arctic University of Norway, Tromso, Norway. gunnvald.kvarstein@uit.no. · Institute of Clinical Medicine, Medical Faculty, University of Oslo, Oslo, Norway. brwylle@online.no. · Department of Pediatrics, Oslo University Hospital, Oslo, Norway. brwylle@online.no. · Department of Pediatrics, Akershus University Hospital, Lørenskog, Norway. brwylle@online.no. · KTH, Royal Institute of Technology, School for Technology and Health, Stockholm, Sweden. mirj@kth.se. · Center for Shared Decision Making and Collaborative Care, Oslo University Hospital, Oslo, Norway. mirj@kth.se. · Department of Pediatrics, Oslo University Hospital, Oslo, Norway. dag.sulheim@medisin.uio.no. · Department of Pediatrics, Innlandet Hospital Trust, Lillehammer, Norway. dag.sulheim@medisin.uio.no. · Institute of Clinical Medicine, Medical Faculty, University of Oslo, Oslo, Norway. feef@online.no. · Institute of Nursing, Faculty of Health Sciences, Oslo and Akershus University College of Applied Sciences, Postboks 4 St. Olavs plass, NO-0130, Oslo, Norway. Milada-Cvancarova.Smastuen@hioa.no. · Institute of Nursing, Faculty of Health Sciences, Oslo and Akershus University College of Applied Sciences, Postboks 4 St. Olavs plass, NO-0130, Oslo, Norway. solvi.helseth@hioa.no. ·Health Qual Life Outcomes · Pubmed #26138694.

ABSTRACT: AIM: To study health related quality of life (HRQOL) and depressive symptoms in adolescents with chronic fatigue syndrome (CFS) and to investigate in which domains their HRQOL and depressive symptoms differ from those of healthy adolescents. BACKGROUND AND OBJECTIVE: Several symptoms such as disabling fatigue, pain and depressive symptoms affect different life domains of adolescents with CFS. Compared to adolescents with other chronic diseases, young people with CFS are reported to be severely impaired, both physiologically and mentally. Despite this, few have investigated the HRQOL in this group. METHOD: This is a cross-sectional study on HRQOL including 120 adolescents with CFS and 39 healthy controls (HC), between 12 and 18 years. The Pediatric Quality of Life Inventory™, 4.0 (PedsQL) was used to assess HRQOL. The Mood and Feelings Questionnaire assessed depressive symptoms. Data were collected between March 2010 and October 2012 as part of the NorCAPITAL project (Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial). Linear and logistic regression models were used in analysis, and all tests were two-sided. RESULTS: Adolescents with CFS reported significantly lower overall HRQOL compared to HCs. When controlling for gender differences, CFS patients scored 44 points lower overall HRQOL on a scale from 0-100 compared to HCs. The domains with the largest differences were interference with physical health (B = -59, 95 % CI -54 to -65) and school functioning (B = -52, 95 % CI -45 to -58). Both depressive symptoms and being a patient were independently associated with lower levels of HRQOL CONCLUSION: The difference in HRQOL between CFS patients and healthy adolescents was even larger than we expected. The large sample of adolescents with CFS in our study confirms previous findings from smaller studies, and emphasizes that CFS is a seriously disabling condition that has a strong impact on their HRQOL. Even though depressive symptoms were found in the group of patients, they could not statistically explain the poor HRQOL.

18 Article Cognitive dysfunction in adolescents with chronic fatigue: a cross-sectional study. 2015

Sulheim, Dag / Fagermoen, Even / Sivertsen, Øyvind Stople / Winger, Anette / Wyller, Vegard Bruun / Øie, Merete Glenne. ·Department of Paediatrics, Oslo University Hospital, Oslo, Norway Department of Paediatrics, Innlandet Hospital Trust, Lillehammer, Norway. · Medical Faculty, Institute of Clinical Medicine, University of Oslo, Oslo, Norway Department of Anesthesiology and Critical Care, Oslo University Hospital, Oslo, Norway. · Medical Faculty, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway. · Medical Faculty, Institute of Nursing Sciences, Oslo and Akershus University College of Applied Sciences, Norway and Institute of Clinical Medicine, University of Oslo, Oslo, Norway. · Department of Paediatrics, Oslo University Hospital, Oslo, Norway Division of Medicine and Laboratory Sciences, Medical Faculty, University of Oslo, Oslo, Norway Department of Paediatrics, Akershus University Hospital, Nordbyhagen, Norway. · Innlandet Hospital Trust, Lillehammer, Norway Institute of Psychology, University of Oslo, Oslo, Norway. ·Arch Dis Child · Pubmed #25791841.

ABSTRACT: OBJECTIVE: To compare cognitive function in adolescents with chronic fatigue with cognitive function in healthy controls (HC). STUDY DESIGN: Cross-sectional study. SETTING: Paediatric department at Oslo University Hospital, Norway. PARTICIPANTS: 120 adolescents with chronic fatigue (average age 15.4 years; range 12-18) and 39 HC (average age 15.2 years; range 12-18). METHODS: The adolescents completed a neurocognitive test battery measuring processing speed, working memory, cognitive inhibition, cognitive flexibility, verbal learning and verbal memory, and questionnaires addressing demographic data, depression symptoms, anxiety traits, fatigue and sleep problems. Parents completed the Behaviour Rating Inventory of Executive Function (BRIEF), which measures the everyday executive functions of children. RESULTS: Adolescents with chronic fatigue had impaired cognitive function compared to HC regarding processing speed (mean difference 3.3, 95% CI 1.1 to 5.5, p=0.003), working memory (-2.4, -3.7 to -1.1, p<0.001), cognitive inhibition response time (6.2, 0.8 to 11.7, p=0.025) and verbal learning (-1.7, -3.2 to -0.3, p=0.022). The BRIEF results indicated that everyday executive functions were significantly worse in the chronic fatigue group compared to the HC (11.2, 8.2 to 14.3, p<0.001). Group differences remained largely unaffected when adjusted for symptoms of depression, anxiety traits and sleep problems. CONCLUSIONS: Adolescents with chronic fatigue had impaired cognitive function of clinical relevance, measured by objective cognitive tests, in comparison to HC. Working memory and processing speed may represent core difficulties.

19 Article Study findings challenge the content validity of the Canadian Consensus Criteria for adolescent chronic fatigue syndrome. 2015

Asprusten, Tarjei Tørre / Fagermoen, Even / Sulheim, Dag / Skovlund, Eva / Sørensen, Øystein / Mollnes, Tom Eirik / Wyller, Vegard Bruun. ·Division of Medicine and Laboratory Sciences, Medical Faculty, University of Oslo, Oslo, Norway. ·Acta Paediatr · Pubmed #25640602.

ABSTRACT: AIM: The 2003 Canadian Consensus Criteria for chronic fatigue syndrome (CFS) are often assumed to suggest low-grade systemic inflammation, but have never been formally validated. This study explored the content validity of the Criteria in a sample of adolescents with CFS selected according to a wide case definition. METHODS: A total of 120 patients with CFS with a mean age of 15.4 years (range 12-18 years) included in the NorCAPITAL project were post hoc subgrouped according to the Canadian Consensus Criteria. Those who satisfied the criteria (Criteria positive) and those who did not (Criteria negative) were compared across a wide range of disease markers and markers of prognosis. RESULTS: A total of 46 patients were classified as Criteria positive, 69 were classified as Criteria negative, and five could not be classified. All disease markers were equal across the two groups, except the digit span backward test of cognitive function, which showed poorer performance in the Criteria-positive group. Also, the prognosis over a 30-week period was equal between the groups. CONCLUSION: This study questions the content validity of the Canadian Consensus Criteria, as few differences were found between adolescent patients with CFS who did and did not satisfy the Criteria.

20 Article Plasma cytokine expression in adolescent chronic fatigue syndrome. 2015

Wyller, Vegard Bruun / Sørensen, Øystein / Sulheim, Dag / Fagermoen, Even / Ueland, Thor / Mollnes, Tom Eirik. ·Dept. of Paediatrics, Oslo University Hospital, Norway; Division of Medicine and Laboratory Sciences, Medical Faculty, University of Oslo, Norway; Dept. of Paediatrics, Akershus University Hospital, Nordbyhagen, Norway. Electronic address: brwylle@online.no. · Oslo Centre for Biostatistics and Epidemiology, Department of Biostatistics, University of Oslo, Norway. · Dept. of Paediatrics, Oslo University Hospital, Norway; Dept. of Paediatrics, Lillehammer County Hospital, Norway. · Institute of Clinical Medicine, Medical Faculty, University of Oslo, Norway; Dept. of Anesthesiology and Critical Care, Oslo University Hospital, Norway. · Research Institute for Internal Medicine, Oslo University Hospital Rikshospitalet, and Faculty of Medicine, K.G. Jebsen IRC, University of Oslo, Oslo, Norway; K.G. Jebsen TREC, University of Tromsø, Norway. · Department of Immunology, Oslo University Hospital, and K.G. Jebsen IRC, University of Oslo, Norway; Research Laboratory, Nordland Hospital, Bodø, and Faculty of Health Sciences, K.G. Jebsen TREC, University of Tromsø, Norway; Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway. ·Brain Behav Immun · Pubmed #25555530.

ABSTRACT: Chronic fatigue syndrome (CFS) is a prevalent and disabling condition among adolescents. The pathophysiology is poorly understood, but low-grade systemic inflammation has been suggested as an important component. This study compared circulating levels of individual cytokines and parameters of cytokine networks in a large set of adolescent CFS patients and healthy controls, and explored associations between cytokines and symptoms in the CFS group. CFS patients (12-18years old) were recruited nation-wide to a single referral center as part of the NorCAPITAL project (ClinicalTrials ID: NCT01040429). A broad case definition of CFS was applied, requiring three months of unexplained, disabling chronic/relapsing fatigue of new onset, whereas no accompanying symptoms were necessary. Thus, the case definition was broader than the Fukuda-criteria of CFS. Healthy controls having comparable distribution of gender and age were recruited from local schools. Twenty-seven plasma cytokines, including interleukins, chemokines and growth factors were assayed using multiplex technology. The results were subjected to network analyses using the ARACNE algorithm. Symptoms were charted by a questionnaire, and patients were subgrouped according to the Fukuda-criteria. A total of 120 CFS patients and 68 healthy controls were included. CFS patients had higher scores for fatigue (p<0.001) and inflammatory symptoms (p<0.001) than healthy controls. All cytokine levels and cytokine network parameters were similar, and none of the differences were statistically different across the two groups, also when adjusting for adherence to the Fukuda criteria of CFS. Within the CFS group, there were no associations between aggregate cytokine network parameters and symptom scores. Adolescent CFS patients are burdened by symptoms that might suggest low-grade systemic inflammation, but plasma levels of individual cytokines as well as cytokine network measures were not different from healthy controls, and there were no associations between symptoms and cytokine expression in the CFS group. Low-grade systemic inflammation does not appear to be a central part of adolescent CFS pathophysiology.

21 Article Pain and pressure pain thresholds in adolescents with chronic fatigue syndrome and healthy controls: a cross-sectional study. 2014

Winger, Anette / Kvarstein, Gunnvald / Wyller, Vegard Bruun / Sulheim, Dag / Fagermoen, Even / Småstuen, Milada Cvancarova / Helseth, Sølvi. ·Faculty of Health Sciences, Institute of Nursing, Oslo and Akershus University College of Applied Sciences, Oslo, Norway. · Department of Clinical Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. · Medical Faculty, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. · Department of Pediatrics, Oslo University Hospital, Norway. · Department of Pediatrics, Akershus University Hospital, Norway. · Department of Pediatrics, Lillehammer County Hospital, Lillehammer, Norway. ·BMJ Open · Pubmed #25287104.

ABSTRACT: OBJECTIVES: Although pain is a significant symptom in chronic fatigue syndrome (CFS), pain is poorly understood in adolescents with CFS. The aim of this study was to explore pain distribution and prevalence, pain intensity and its functional interference in everyday life, as well as pressure pain thresholds (PPT) in adolescents with CFS and compare this with a control group of healthy adolescents (HC). METHODS: This is a case-control, cross-sectional study on pain including 120 adolescents with CFS and 39 HCs, aged 12-18 years. We measured pain frequency, pain severity and pain interference using self-reporting questionnaires. PPT was measured using pressure algometry. Data were collected from March 2010 until October 2012 as part of the Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial. RESULTS: Adolescents with CFS had significantly lower PPTs compared with HCs (p<0.001). The Pain Severity Score and the Pain Interference Score were significantly higher in adolescents with CFS compared with HCs (p<0.001). Almost all adolescents with CFS experienced headache, abdominal pain and/or pain in muscles and joints. Moreover, in all sites, the pain intensity levels were significantly higher than in HCs (p<0.001). CONCLUSIONS: We found a higher prevalence of severe pain among adolescents with CFS and lowered pain thresholds compared with HCs. The mechanisms, however, are still obscure. Large longitudinal population surveys are warranted measuring pain thresholds prior to the onset of CFS. TRIAL REGISTRATION NUMBER: Clinical Trials, NCT01040429; The Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial (NorCAPITAL) http://www.clinicaltrials.gov.

22 Article Orthostatic responses in adolescent chronic fatigue syndrome: contributions from expectancies as well as gravity. 2014

Wyller, Vegard Bruun / Fagermoen, Even / Sulheim, Dag / Winger, Anette / Skovlund, Eva / Saul, Jerome Philip. ·Department of Pediatrics, Oslo University Hospital, N-1478 Oslo, Norway ; Division of Medicine and Laboratory Sciences, Medical Faculty, University of Oslo, Oslo, Norway ; Department of Pediatrics, Akershus University Hospital, Nordbyhagen, Norway. · Institute of Clinical Medicine, Medical Faculty, University of Oslo, Oslo, Norway ; Department of Anesthesiology and Critical Care, Oslo University Hospital, Oslo, Norway. · Department of Pediatrics, Oslo University Hospital, N-1478 Oslo, Norway ; Department of Pediatrics, Lillehammer County Hospital, Lillehammer, Norway. · Institute of Nursing Sciences, Oslo and Akershus University College of Applied Sciences, Oslo, Norway ; Institute of Clinical Medicine, Medical Faculty, University of Oslo, Oslo, Norway. · School of Pharmacy, University of Oslo, Oslo, Norway ; Norwegian Institute of Public Health, Oslo, Norway. · Department of Pediatrics, Medical University of South Carolina, Charleston, USA. ·Biopsychosoc Med · Pubmed #25237387.

ABSTRACT: BACKGROUND: Orthostatic intolerance is common in chronic fatigue syndrome (CFS), and several studies have documented an abnormal sympathetic predominance in the autonomic cardiovascular response to gravitational stimuli. The aim of this study was to explore whether the expectancies towards standing are contributors to autonomic responses in addition to the gravitational stimulus itself. METHODS: A total of 30 CFS patients (12-18 years of age) and 39 healthy controls underwent 20° head-up tilt test and a motor imagery protocol of standing upright. Beat-to-beat cardiovascular variables were recorded. RESULTS: At supine rest, CFS patients had significantly higher heart rate, diastolic blood pressure, and mean arterial blood pressure, and lower stroke index and heart rate variability (HRV) indices. The response to 20° head-up tilt was identical in the two groups. The response to imaginary upright position was characterized by a stronger increase of HRV indices of sympathetic predominance (power in the low-frequency range as well as the ratio low-frequency: high-frequency power) among CFS patients. CONCLUSIONS: These results suggest that in CFS patients expectancies towards orthostatic challenge might be additional determinants of autonomic cardiovascular modulation along with the gravitational stimulus per se.

23 Article Disease mechanisms and clonidine treatment in adolescent chronic fatigue syndrome: a combined cross-sectional and randomized clinical trial. 2014

Sulheim, Dag / Fagermoen, Even / Winger, Anette / Andersen, Anders Mikal / Godang, Kristin / Müller, Fredrik / Rowe, Peter C / Saul, J Philip / Skovlund, Eva / Øie, Merete Glenne / Wyller, Vegard Bruun. ·Department of Paediatrics, Oslo University Hospital, Oslo, Norway2Department of Paediatrics, Lillehammer County Hospital, Lillehammer, Norway. · Institute of Clinical Medicine, Medical Faculty, University of Oslo, Oslo, Norway4Department of Anesthesiology and Critical Care, Oslo University Hospital, Oslo, Norway. · Institute of Clinical Medicine, Medical Faculty, University of Oslo, Oslo, Norway5Institute of Nursing Sciences, Oslo and Akershus University College of Applied Sciences, Oslo, Norway. · Department of Pharmacology, Oslo University Hospital, Oslo, Norway. · Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital Rikshospitalet, Oslo, Norway. · Department of Microbiology, Oslo University Hospital, Oslo, Norway. · Department of Pediatrics, the Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Pediatrics, Medical University of South Carolina, Charleston. · School of Pharmacy, University of Oslo, Oslo, Norway12Norwegian Institute of Public Health, Oslo, Norway. · Department of Psychology, University of Oslo, Oslo, Norway14Innlandet Hospital Trust, Lillehammer, Norway. · Department of Paediatrics, Oslo University Hospital, Oslo, Norway15Division of Medicine and Laboratory Sciences, Medical Faculty, University of Oslo, Oslo, Norway16Department of Paediatrics, Akershus University Hospital, Nordbyhagen, Norway. ·JAMA Pediatr · Pubmed #24493300.

ABSTRACT: IMPORTANCE: Chronic fatigue syndrome (CFS) is a disabling condition with unknown disease mechanisms and few treatment options. OBJECTIVE: To explore the pathophysiology of CFS and assess clonidine hydrochloride pharmacotherapy in adolescents with CFS by using a hypothesis that patients with CFS have enhanced sympathetic activity and that sympatho-inhibition by clonidine would improve symptoms and function. DESIGN, SETTING, AND PARTICIPANTS: Participants were enrolled from a single referral center recruiting nationwide in Norway. A referred sample of 176 adolescents with CFS was assessed for eligibility; 120 were included (34 males and 86 females; mean age, 15.4 years). A volunteer sample of 68 healthy adolescents serving as controls was included (22 males and 46 females; mean age, 15.1 years). The CSF patients and healthy controls were assessed cross-sectionally at baseline. Thereafter, patients with CFS were randomized 1:1 to treatment with low-dose clonidine or placebo for 9 weeks and monitored for 30 weeks; double-blinding was provided. Data were collected from March 2010 until October 2012 as part of the Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial. INTERVENTIONS: Clonidine hydrochloride capsules (25 µg or 50 µg twice daily for body weight <35 kg or >35 kg, respectively) vs placebo capsules for 9 weeks. MAIN OUTCOMES AND MEASURES: Number of steps per day. RESULTS: At baseline, patients with CFS had a lower number of steps per day (P < .001), digit span backward score (P = .002), and urinary cortisol to creatinine ratio (P = .001), and a higher fatigue score (P < .001), heart rate responsiveness (P = .02), plasma norepinephrine level (P < .001), and serum C-reactive protein concentration (P = .04) compared with healthy controls. There were no significant differences regarding blood microbiology evaluation. During intervention, the clonidine group had a lower number of steps per day (mean difference, -637 steps; P = .07), lower plasma norepinephrine level (mean difference, -42 pg/mL; P = .01), and lower serum C-reactive protein concentration (mean ratio, 0.69; P = .02) compared with the CFS placebo group. CONCLUSIONS AND RELEVANCE: Adolescent CFS is associated with enhanced sympathetic nervous activity, low-grade systemic inflammation, attenuated hypothalamus-pituitary-adrenal axis function, cognitive impairment, and large activity reduction, but not with common microorganisms. Low-dose clonidine attenuates sympathetic outflow and systemic inflammation in CFS but has a concomitant negative effect on physical activity; thus, sympathetic and inflammatory enhancement may be compensatory mechanisms. Low-dose clonidine is not clinically useful in CFS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01040429.

24 Article 'Sometimes it feels as if the world goes on without me': adolescents' experiences of living with chronic fatigue syndrome. 2014

Winger, Anette / Ekstedt, Mirjam / Wyller, Vegard B / Helseth, Sølvi. ·Faculty of Nursing, Oslo and Akershus University College of Applied Sciences, Oslo, Norway; Medical Faculty, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. ·J Clin Nurs · Pubmed #24354631.

ABSTRACT: AIMS AND OBJECTIVES: To explore the experience of being an adolescent with chronic fatigue syndrome. BACKGROUND: Despite ample research, chronic fatigue syndrome is still poorly understood, and there are still controversies related to the illness. Adolescents with chronic fatigue syndrome are often unable to attend school and lose social relations with friends. The challenges they face will affect their quality of life. DESIGN: A qualitative, phenomenological hermeneutical design. METHOD: Six boys and twelve girls, aged 12-18, were interviewed, emphasising their own experiences living with chronic fatigue syndrome. Analyses were performed using a phenomenological hermeneutical method. RESULTS: The core theme, 'Sometimes it feels as if the world goes on without me', encompasses the feelings an adolescent living with chronic fatigue syndrome might have about life. The core theme was supported by four subthemes: 'On the side of life--locked in and shut out'; 'the body, the illness and me'; 'if the illness is not visible to others, does it exist?'; and 'handling life while hoping for a better future'. The subthemes reflect the experience of social isolation, their own and others' understanding of the illness and hope for the future. CONCLUSIONS: Not being able to be with friends, or attend school, made the adolescents feel different and forgotten. They felt alienated in their own bodies and were struggling to be visible to themselves and to their surroundings. Spending less time with friends and more time with their parents constituted a threat to independence and development. Yet they managed to envision a better future despite all the difficulties. RELEVANCE FOR CLINICAL PRACTICE: To provide effective support and constructive relations to adolescents with chronic fatigue syndrome, all health professions involved need insight from the persons who are themselves ill. Health centres could function as resource centres for patients and healthcare professionals.

25 Article Chronic fatigue in long-term survivors of childhood lymphomas and leukemia: persistence and associated clinical factors. 2014

Zeller, Bernward / Loge, Jon H / Kanellopoulos, Adriani / Hamre, Hanne / Wyller, Vegard B / Ruud, Ellen. ·Departments of *Pediatric Medicine †Oncology, National Resource Center for Late Effects after Cancer Treatment ‡Department of Behavioural Sciences in Medicine, University of Oslo, Oslo, Norway. ·J Pediatr Hematol Oncol · Pubmed #24276036.

ABSTRACT: BACKGROUND: Chronic fatigue (CF) is an important late effect after childhood malignancies. Our aim was to assess CF persistence over time, concurrent comorbidities, and associations with clinical symptoms. PROCEDURE: A total of 102 long-term survivors of childhood lymphomas and acute lymphoblastic leukemia, 53 and 49 reporting CF and no CF, respectively, at time point (TP)1, were evaluated for CF at a second TP after a median interval of 2.7 years. At TP2 a survey, including self-reported and objectively measured variables, assessed depressive symptoms, pain, and physical activity. RESULTS: A total of 32 of the 53 reported CF cases at both TPs and 40/49 survivors had no CF at both TPs, whereas 30 had changed their fatigue status between first and second assessment (converters). Major somatic comorbidities were equally distributed among the groups. After exclusion of converters and survivors with major comorbidity/pregnancy, 27 persistent CF (PCF) cases and 35 controls were compared. PCF cases reported significantly more depression, sleeping problems, anxiety, pain, and reduced physical function. Further, they were less physically active than controls (steps/d; P=0.009). In a multiple regression analysis, depressive symptoms remained the only significant predictor of PCF. CONCLUSIONS: Long-term survivors of childhood cancer with PCF are characterized by more depressive symptoms, anxiety, pain, insomnia, and less physical activity.

Next