Vegard Bruun Bratholm Wyller

• Asprusten, Tarjei Tørre; Sletner, Line & Wyller, Vegard Bruun Bratholm (2021). Are there subgroups of chronic fatigue syndrome? An exploratory cluster analysis of biological markers. Journal of Translational Medicine.  ISSN 1479-5876.  19:48, s 1- 12 . doi: 10.1186/s12967-021-02713-9
• Wyller, Vegard Bruun Bratholm; Nygaard, Sissel; Christensen, Anders Haugom; Rolid, Katrine; Nytrøen, Kari; Gullestad, Lars; Fiane, Arnt E; Thaulow, Erik; Døhlen, Gaute & Saul, J. Philip (2021). Functional evidence of low-pressure cardiopulmonary baroreceptor reinnervation 1 year after heart transplantation. European Journal of Applied Physiology.  ISSN 1439-6319.  121(3), s 915- 927 . doi: 10.1007/s00421-020-04586-0
• Brodwall, Elias Myrstad; Pedersen, Maria; Asprusten, Tarjei Tørre & Wyller, Vegard Bruun Bratholm (2020). Pain in adolescent chronic fatigue following Epstein-Barr virus infection. Scandinavian Journal of Pain.  ISSN 1877-8860. . doi: 10.1515/sjpain-2020-0031
• Malik, Sadaf; Asprusten, Tarjei Tørre; Pedersen, Maria; Mangersnes, Julie; Trondalen, Gro; Van Roy, Betty; Skovlund, Eva & Wyller, Vegard Bruun Bratholm (2020). Cognitive–behavioural therapy combined with music therapy for chronic fatigue following Epstein-Barr virus infection in adolescents: a randomised controlled trial. BMJ Paediatrics Open.  ISSN 2399-9772.  4:e000797, s 1- 10 . doi: 10.1136/bmjpo-2020-000797 Full text in Research Archive. Show summary

  Abstract Background Cognitive–behavioural therapy (CBT) is effective in chronic fatigue (CF) syndrome. However, CBT has not been investigated in postinfectious CF, nor is it known whether addition of therapeutic elements from other disciplines might be useful. We explored combined CBT and music therapy intervention for CF following Epstein-Barr virus (EBV) infection in adolescents. Methods Adolescents (12–20 years old) participating in a postinfectious cohort study who developed CF 6 months after an acute EBV infection were eligible for the present study. A combined CBT and music therapy programme (10 therapy sessions and related homework) was compared with care as usual in a randomised controlled design. Therapists and participants were blinded to outcome evaluation. Endpoints included physical activity (steps/day), symptom scores, recovery rate and possible harmful effects, but the study was underpowered regarding efficacy. Total follow-up time was 15 months. Power analyses suggested that 120 participants would be needed in order to detect a moderate effect size. Results A total of 91 individuals with postinfectious CF were eligible, and a total of 43 were included (21 intervention group, 22 control group). Concern regarding school absence due to therapy sessions was the main reason for declining participation. Seven individuals left the study during the first 3 months, leaving 15 in the intervention group and 21 in the control group at 3 months follow-up. No harmful effects were recorded, and compliance with appointment was high. In intention-to-treat analyses, the primary endpoint (number of steps/day) did not differ significantly between the intervention group and the control group (difference (95% CI) =–1298 (–4874 to 2278)). Secondary outcome measures were also not significantly different among the two groups. Conclusion An intervention study of combined CBT and music therapy in postinfectious CF is feasible. A fully powered trial is needed to evaluate efficacy; participants’ concern regarding school absence should be properly addressed to secure recruitment. Trial registration number ClinicalTrials ID: NCT02499302, registered July 2015. http://dx.doi.org/10.1136/bmjpo-2020-000797

• Trondalen, Gro; Mangersnes, Julie; Bonde, Lars Ole; Malik, Sadaf; Asprusten, Tarjei Tørre; Rødevand, Linn Nilsen; Pedersen, Maria & Wyller, Vegard Bruun Bratholm (2020). Music Therapy for Chronic Fatigue Following Epstein-Barr Virus Infection in Adolescents. Music and Medicine.  ISSN 1943-863X.  12(2) . doi: 10.47513/mmd.v12i2.679
• Nguyen, Chinh BKrong; Kumar, Surendra; Zucknick, Manuela; Kristensen, Vessela N.; Gjerstad, Johannes; Nilsen, Hilde Loge & Wyller, Vegard Bruun Bratholm (2019). Associations between clinical symptoms, plasma norepinephrine and deregulated immune gene networks in subgroups of adolescent with Chronic Fatigue Syndrome. Brain, behavior, and immunity.  ISSN 0889-1591.  76, s 82- 96 . doi: 10.1016/j.bbi.2018.11.008 Full text in Research Archive. Show summary

  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.

• Asprusten, Tarjei Tørre; Pedersen, Maria; Skovlund, Eva & Wyller, Vegard Bruun Bratholm (2019). EBV-requisitioning physicians' guess on fatigue state 6 months after acute EBV infection. BMJ Paediatrics Open.  ISSN 2399-9772.  3(1) . doi: 10.1136/bmjpo-2018-000390 Full text in Research Archive.
• Hov, Karen Roksund; Neerland, Bjørn Erik; Undseth, Øystein; Wyller, Vegard Bruun Bratholm; MacLullich, Alasdair M.J.; Qvigstad, Eirik; Skovlund, Eva & Wyller, Torgeir Bruun (2019). The Oslo Study of Clonidine in Elderly Patients with Delirium; LUCID: a randomised placebo-controlled trial. International Journal of Geriatric Psychiatry.  ISSN 0885-6230.  34(7), s 974- 981 . doi: 10.1002/gps.5098 Full text in Research Archive.
• Kristiansen, Miriam Skjerven; Stabursvik, Julie; O'Leary, Elise Catriona Solberg; Pedersen, Maria; Asprusten, Tarjei Tørre; Leegaard, Truls Michael; Osnes, Liv T. N.; Tjade, Trygve Olav; Skovlund, Eva; Godang, Kristin & Wyller, Vegard Bruun Bratholm (2019). Clinical symptoms and markers of disease mechanisms in adolescent chronic fatigue following Epstein-Barr virus infection: An exploratory cross-sectional study. Brain, behavior, and immunity.  ISSN 0889-1591.  80, s 551- 563 . doi: 10.1016/j.bbi.2019.04.040 Full text in Research Archive.
• Neerland, Bjørn Erik; Wyller, Torgeir Bruun & Wyller, Vegard Bruun Bratholm (2019). Autonomic cardiovascular control in older patients with acute infection and delirium: a pilot study of orthostatic stress responses. BMC Geriatrics.  ISSN 1471-2318.  19(23), s 1- 8 . doi: 10.1186/s12877-019-1035-0 Full text in Research Archive.
• Nygaard, Sissel Irene; Christensen, Anders Haugom; Rolid, Katrine; Nytrøen, Kari; Gullestad, Lars; Fiane, Arnt E; Thaulow, Erik; Døhlen, Gaute; Godang, Kristin; Saul, J. Philip & Wyller, Vegard Bruun Bratholm (2019). Autonomic cardiovascular control changes in recent heart transplant recipients lead to physiological limitations in response to orthostatic challenge and isometric exercise. European Journal of Applied Physiology.  ISSN 1439-6319.  119(10), s 2225- 2236 . doi: 10.1007/s00421-019-04207-5 Full text in Research Archive.
• Pedersen, Maria; Asprusten, Tarjei Tørre; Godang, Kristin; Leegaard, Truls Michael; Osnes, Liv T. N.; Skovlund, Eva; Tjade, Trygve Olav; Øie, Merete Glenne & Wyller, Vegard Bruun Bratholm (2019). Fatigue in Epstein-Barr virus infected adolescents and healthy controls: A prospective multifactorial association study. Journal of Psychosomatic Research.  ISSN 0022-3999.  121, s 46- 59 . doi: 10.1016/j.jpsychores.2019.04.008
• Pedersen, Maria; Asprusten, Tarjei Tørre; Godang, Kristin; Leegaard, Truls Michael; Osnes, Liv T. N.; Skovlund, Eva; Tjade, Trygve Olav; Øie, Merete Glenne & Wyller, Vegard Bruun Bratholm (2019). Lifestyle factors during acute Epstein-Barr virus infection in adolescents predict physical activity six months later. Acta Paediatrica.  ISSN 0803-5253.  108(8), s 1521- 1526 . doi: 10.1111/apa.14728 Full text in Research Archive.
• Asprusten, Tarjei Tørre; Sulheim, Dag; Fagermoen, Frode Even; Winger, Anette; Skovlund, Eva & Wyller, Vegard Bruun Bratholm (2018). Systemix exertion intolerance disease diagnostic criteria Applied on an adolescent chronic fatigue syndrom cohort: evaluation of subgroup differences and prognostic utility. BMJ Paediatrics Open.  ISSN 2399-9772.  2:e000233, s 1- 8 . doi: 10.1136/bmjpo-2017-000233 Full text in Research Archive.
• Hov, Karen Roksund; Neerland, Bjørn Erik; Andersen, Anders Mikal; Undseth, Øystein; Wyller, Vegard Bruun Bratholm; MacLullich, Alasdair M.J.; Skovlund, Eva; Qvigstad, Eirik & Wyller, Torgeir Bruun (2018). The use of clonidine in elderly patients with delirium; pharmacokinetics and hemodynamic responses. BMC Pharmacology & Toxicology.  ISSN 2050-6511.  19(29) . doi: 10.1186/s40360-018-0218-1 Full text in Research Archive.
• Pedersen, Maria; Asprusten, Tarjei Tørre; Godang, Kristin; Leegaard, Truls Michael; Osnes, Liv T. N.; Skovlund, Eva; Tjade, Trygve Olav; Øie, Merete Glenne & Wyller, Vegard Bruun Bratholm (2018). Predictors of chronic fatigue in adolescents six months after acute Epstein-Barr virus infection: a prospective cohort study. Brain, behavior, and immunity.  ISSN 0889-1591.  75, s 94- 100 . doi: 10.1016/j.bbi.2018.09.023 Full text in Research Archive.
• Valenza, Gaetano; Citi, Luca; Wyller, Vegard Bruun Bratholm & Barbieri, Riccardo (2018). ECG-derived sympathetic and parasympathetic activity in the healthy: An early lower-body negative pressure study using adaptive Kalman prediction. IEEE Engineering in Medicine and Biology Society. Conference Proceedings.  ISSN 1557-170X.  2018:8513512-July, s 5628- 5631 . doi: 10.1109/EMBC.2018.8513512
• Bakke, Laura A Wortinger; Endestad, Tor; Melinder, Annika Maria D; Øie, Merete Glenne; Sulheim, Dag; Fagermoen, Frode Even & Wyller, Vegard Bruun (2017). Emotional conflict processing in adolescent chronic fatigue syndrome: A pilot study using functional magnetic resonance imaging. Journal of Clinical and Experimental Neuropsychology.  ISSN 1380-3395.  39(4), s 355- 368 . doi: 10.1080/13803395.2016.1230180 Full text in Research Archive. Show summary

  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.

• Bakke, Laura A. Wortinger; Øie, Merete Glenne; Endestad, Tor & Wyller, Vegard Bruun Bratholm (2017). Altered right anterior insular connectivity and loss of associated functions in adolescent chronic fatigue syndrome. PLOS ONE.  ISSN 1932-6203.  12(9) . doi: 10.1371/journal.pone.0184325 Full text in Research Archive. Show summary

  Abstract Impairments in cognition, pain intolerance, and physical inactivity characterize adolescent chronic fatigue syndrome (CFS), yet little is known about its neurobiology. The right dorsal anterior insular (dAI) connectivity of the salience network provides a motivational context to stimuli. In this study, we examined regional functional connectivity (FC) patterns of the right dAI in adolescent CFS patients and healthy participants. Eighteen adolescent patients with CFS and 18 aged-matched healthy adolescent control participants underwent resting-state functional magnetic resonance imaging. The right dAI region of interest was examined in a seed-to-voxel resting-state FC analysis using SPM and CONN toolbox. Relative to healthy adolescents, CFS patients demonstrated reduced FC of the right dAI to the right posterior parietal cortex (PPC) node of the central executive network. The decreased FC of the right dAI–PPC might indicate impaired cognitive control development in adolescent CFS. Immature FC of the right dAI–PPC in patients also lacked associations with three known functional domains: cognition, pain and physical activity, which were observed in the healthy group. These results suggest a distinct biological signature of adolescent CFS and might represent a fundamental role of the dAI in motivated behavior.

• Feiring, Berit; Laake, Ida; Bakken, Inger Johanne; Greve-Isdahl, Margrethe; Wyller, Vegard Bruun Bratholm; Håberg, Siri Eldevik; Magnus, Per & Trogstad, Lill (2017). HPV vaccination and risk of chronic fatigue syndrome/myalgic encephalomyelitis: A nationwide register-based study from Norway. Vaccine.  ISSN 0264-410X.  35(33), s 4203- 4212 . doi: 10.1016/j.vaccine.2017.06.031
• Nguyen, Chinh Bkrong Thi Thuy; Alsøe, Lene; Lindvall, Jessica Margareta; Sulheim, Dag; Fagermoen, Frode Even; Winger, Anette; Kaarbø, Mari; Nilsen, Hilde Loge & Wyller, Vegard Bruun Bratholm (2017). Whole blood gene expression in adolescent chronic fatigue syndrome: An exploratory cross-sectional study suggesting altered B cell differentiation and survival. Journal of Translational Medicine.  ISSN 1479-5876.  15 . doi: 10.1186/s12967-017-1201-0 Full text in Research Archive. Show summary

  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.

• Pedersen, Maria; Ekstedt, Mirjam; Småstuen, Milada C; Wyller, Vegard Bruun Bratholm; Sulheim, Dag; Fagermoen, Frode Even; Winger, Anette; Pedersen, Edvard & Hrubos-Strøm, Harald (2017). Sleep-wake rhythm disturbances and perceived sleep in adolescent chronic fatigue syndrome. Journal of Sleep Research.  ISSN 0962-1105.  26(5), s 595- 601 . doi: 10.1111/jsr.12547 Show summary

  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.

• Wyller, Hedda Bratholm; Wyller, Vegard Bruun Bratholm; Crane, Catherine & Gjelsvik, Bergliot (2017). The relationship between sensory processing sensitivity and psychological distress: A model of underpinning mechanisms and an analysis of therapeutic possibilities. Scandinavian Psychologist.  ISSN 1894-5570.  (4), s 16 . doi: 10.15714/scandpsychol.4.e15
• Wyller, Vegard Bruun Bratholm (2017). The bedside rationing paradigm and the shortcomings of modernist ethics. Clinical Ethics.  ISSN 1477-7509.  12(2), s 70- 75 . doi: 10.1177/1477750917691888
• Wyller, Vegard Bruun Bratholm; Nguyen, Chinh Bkrong Thi Thuy; Ludviksen, Judith K & Mollnes, Tom Eirik (2017). Transforming growth factor beta (TGF‑β)in adolescent chronic fatigue syndrome. Journal of Translational Medicine.  ISSN 1479-5876.  15(1) . doi: 10.1186/s12967-017-1350-1 Full text in Research Archive.
• Bakke, Laura A Wortinger; Endestad, Tor; Melinder, Annika Maria D; Øie, Merete Glenne; Nilsen, Andre Sevenius & Wyller, Vegard Bruun (2016). Aberrant resting-state functional connectivity in the Salience Network of adolescent Chronic Fatigue Syndrome. PLOS ONE.  ISSN 1932-6203.  11(7) . doi: 10.1371/journal.pone.0159351 Show summary

  Abstract Neural network investigations are currently absent in adolescent chronic fatigue syndrome (CFS). In this study, we examine whether the core intrinsic connectivity networks (ICNs) are altered in adolescent CFS patients. Eighteen adolescent patients with CFS and 18 aged matched healthy adolescent control subjects underwent resting-state functional magnetic resonance imaging (rfMRI). Data was analyzed using dual-regression independent components analysis, which is a data-driven approach for the identification of independent brain networks. Intrinsic connectivity was evaluated in the default mode network (DMN), salience network (SN), and central executive network (CEN). Associations between network characteristics and symptoms of CFS were also explored. Adolescent CFS patients displayed a significant decrease in SN functional connectivity to the right posterior insula compared to healthy comparison participants, which was related to fatigue symptoms. Additionally, there was an association between pain intensity and SN functional connectivity to the left middle insula and caudate that differed between adolescent patients and healthy comparison participants. Our findings of insula dysfunction and its association with fatigue severity and pain intensity in adolescent CFS demonstrate an aberration of the salience network which might play a role in CFS pathophysiology.

• Hall, Karhryn T.; Kossowsky, Joe; Oberlander, Tim F.; Kaptchuk, Ted J.; Saul, J. Philip; Wyller, Vegard Bruun; Fagermoen, Frode Even; Sulheim, Dag; Gjerstad, Johannes; Winger, Anette & Mukamal, Kenneth Jay (2016). Genetic variation in catechol-O-methyltransferase modifies effects of clonidine treatment in chronic fatigue syndrome. The Pharmacogenomics Journal.  ISSN 1470-269X.  16(5), s 454- 460 . doi: 10.1038/tpj.2016.53 Full text in Research Archive. Show summary

  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.

• Wyller, Vegard Bruun; Vitelli, Valeria; Sulheim, Dag; Fagermoen, Frode Even; Winger, Anette; Godang, Kristin & Bollerslev, Jens (2016). Altered neuroendocrine control and association to clinical symptoms in adolescent chronic fatigue syndrome: a cross-sectional study. Journal of Translational Medicine.  ISSN 1479-5876.  14(121) . doi: 10.1186/s12967-016-0873-1 Full text in Research Archive.
• Asprusten, Tarjei Tørre; Fagermoen, Frode Even; Sulheim, Dag; Skovlund, Eva; Sørensen, Øystein; Mollnes, Tom Eirik & Wyller, Vegard Bruun (2015). Study findings challenge the content validity of the Canadian Consensus Criteria for adolescent chronic fatigue syndrome. Acta Paediatrica.  ISSN 0803-5253.  104(5), s 498- 503 . doi: 10.1111/apa.12950
• Fagermoen, Frode Even; Sulheim, Dag; Winger, Anette; Andersen, Anders Mikal; Gjerstad, Johannes; Godang, Kristin; Rowe, Peter C; Saul, Philip J.; Skovlund, Eva & Wyller, Vegard Bruun (2015). Effects of low-dose clonidine on cardiovascular and autonomic variables in adolescents with chronic fatigue: A randomized controlled trial. BMC Pediatrics.  ISSN 1471-2431.  15 . doi: 10.1186/s12887-015-0428-2 Full text in Research Archive. Show summary

  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.

• Mellingsæter, Marte; Wyller, Torgeir Bruun; Ranhoff, Anette Hylen; Bogdanovic, Nenad & Wyller, Vegard Bruun (2015). Reduced sympathetic response to head-up tilt in subjects with mild cognitive impairment or mild Alzheimer's dementia. Dementia and Geriatric Cognitive Disorders Extra.  ISSN 1664-5464.  5(1), s 107- 115 . doi: 10.1159/000375297 Full text in Research Archive.
• Mellingsæter, Marte; Wyller, Torgeir Bruun; Ranhoff, Anette Hylen & Wyller, Vegard Bruun (2015). Fit elderly men can also stand: orthostatic tolerance and autonomic cardiovascular control in elderly endurance athletes. Aging Clinical and Experimental Research.  ISSN 1594-0667.  27(4), s 499- 505 . doi: 10.1007/s40520-014-0303-2
• Meyer, Benedicte; Nguyen, Chinh Bkrong Thi Thuy; Moen, Aurora; Fagermoen, Frode Even; Sulheim, Dag; Nilsen, Hilde; Wyller, Vegard Bruun & Gjerstad, Johannes (2015). Maintenance of Chronic Fatigue Syndrome (CFS) in young CFS patients is associated with the 5-HTTLPR and SNP rs25531 A > G Genotype. PLOS ONE.  ISSN 1932-6203.  10(10) . doi: 10.1371/journal.pone.0140883 Show summary

  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.

• Neerland, Bjørn Erik; Hov, Karen Roksund; Wyller, Vegard Bruun; Qvigstad, Eirik; Skovlund, Eva; MacLullich, AM & Wyller, Torgeir Bruun (2015). The protocol of the oslo study of clonidine in elderly patients with delirium; LUCID: A randomised placebo-controlled trial. BMC Geriatrics.  ISSN 1471-2318.  15:7, s 1- 14 . doi: 10.1186/s12877-015-0006-3
• Sulheim, Dag; Fagermoen, Frode Even; Sivertsen, Øyvind Stople; Winger, Anette; Wyller, Vegard Bruun & Øie, Merete Glenne (2015). Cognitive dysfunction in adolescents with chronic fatigue: a cross-sectional study. Archives of Disease in Childhood.  ISSN 0003-9888.  100(9), s 838- 844 . doi: 10.1136/archdischild-2014-306764 Full text in Research Archive.
• Winger, Anette; Kvarstein, Gunnvald; Wyller, Vegard Bruun; Ekstedt, Mirjam; Sulheim, Dag; Fagermoen, Frode Even; Småstuen, Milada C & Helseth, Sølvi (2015). Health related quality of life in adolescents with chronic fatigue syndrome: A cross-sectional study. Health and Quality of Life Outcomes.  ISSN 1477-7525.  13:96 . doi: 10.1186/s12955-015-0288-3 Full text in Research Archive.
• Wyller, Vegard Bruun; Sørensen, Øystein; Sulheim, Dag; Fagermoen, Frode Even; Ueland, Thor & Mollnes, Tom Eirik (2015). Plasma cytokine expression in adolescent chronic fatigue syndrome. Brain, behavior, and immunity.  ISSN 0889-1591.  46, s 80- 86 . doi: 10.1016/j.bbi.2014.12.025 Show summary

  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 (12–18 years 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.

• Kristensen, Hanne; Ørbeck, Beate; Torgersen, Halvor; Hansen, Berit Marina Hjelde & Wyller, Vegard Bruun (2014). Somatic symptoms in children with anxiety disorders: an exploratory cross-sectional study of the relationship between subjective and objective measures. European Child and Adolescent Psychiatry.  ISSN 1018-8827.  23(9), s 795- 803 . doi: 10.1007/s00787-013-0512-9 Show summary

  Symptoms of childhood anxiety disorders include activation of bodily stress systems to fear stimuli, indicating alterations of the autonomic nervous system (ANS). Self-reported somatic symptoms are frequently reported, while studies including objective measures of ANS are scarce and show inconsistent results. Even less studied is the relationship between subjective and objective measures of somatic symptoms in anxious children. Increased knowledge of this relationship may have relevance for treatment programmes for anxiety disorders. This cross-sectional study examined subjective and objective measures of ANS responsiveness in a clinical sample of children with anxiety disorders (7–13 years; n = 23) and in healthy controls (HC; n = 22) with equal distributions of gender and age. The subjective measure used was the Multidimensional Anxiety Scale for Children (MASC), which includes a subscale on somatic symptoms. The objective measures consisted of an orthostatic challenge (head-up tilt test, HUT), and an isometric muscular exercise (handgrip) while the participants were attached to the Task Force Monitor, a combined hardware and software device used for continuous, non-invasive recording of cardiovascular variables. The anxiety disorder group reported significantly more somatic symptoms than HCs (both by mother and child reports). In contrast, no relevant differences in cardiovascular variables were demonstrated between the anxiety group and HCs. Finally, there were no significant correlations between subjective and objective measures in either group. Because of the small sample size, the findings must be interpreted carefully, but the results do not support previous reports of functional alterations of the ANS in anxious children.

• Sulheim, Dag; Fagermoen, Frode Even; Winger, Anette; Andersen, Anders Mikal; Godang, Kristin; Müller, Fredrik; Rowe, Peter C; Saul, J. Philip; Skovlund, Eva; Øie, Merete Glenne & Wyller, Vegard Bruun (2014). Disease Mechanisms and Clonidine Treatment in Adolescent Chronic Fatigue Syndrome: A Combined Cross-sectional and Randomized Clinical Trial. JAMA pediatrics.  ISSN 2168-6203.  168(4), s 351- 360 . doi: 10.1001/jamapediatrics.2013.4647 Full text in Research Archive.
• Winger, Anette; Kvarstein, Gunnvald; Wyller, Vegard Bruun; Sulheim, Dag; Fagermoen, Frode Even; Småstuen, Milada Cvancarova & Helseth, Sølvi (2014). Pain and pressure pain thresholds in adolescents with chronic fatigue syndrome and healthy controls: a cross-sectional study. BMJ Open.  ISSN 2044-6055.  4(10) . doi: 10.1136/bmjopen-2014-005920 Full text in Research Archive. Show summary

  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.

• Wyller, Vegard Bruun; Fagermoen, Frode Even; Sulheim, Dag; Winger, Anette; Skovlund, Eva & Saul, J. Philip (2014). Orthostatic responses in adolescent chronic fatigue syndrome: Contributions from expectancies as well as gravity. BioPsychoSocial Medicine.  ISSN 1751-0759.  8 . doi: 10.1186/1751-0759-8-22 Full text in Research Archive. Show summary

  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.

• Zeller, Bernward; Loge, Jon Håvard; Kanellopoulos, Adriani; Hamre, Hanne Mari; Wyller, Vegard Bruun & Ruud, Ellen (2014). Chronic fatigue in long-term survivors of childhood Lymphomas and Leukemia: Persistence and associated clinical factors. Journal of Pediatric Hematology/Oncology.  ISSN 1077-4114.  36(6), s 438- 444 . doi: 10.1097/MPH.0000000000000051
• Elsais, Ahmed; Wyller, Vegard Bruun; Loge, Jon Håvard & Kerty, Emilia (2013). Fatigue in myasthenia gravis: is it more than muscular weakness?. BMC Neurology.  ISSN 1471-2377.  13 . doi: 10.1186/1471-2377-13-132 Full text in Research Archive.
• Mellingsæter, Marte; Wyller, Vegard Bruun; Wyller, Torgeir Bruun & Ranhoff, Anette Hylen (2013). Gender differences in orthostatic tolerance in the elderly. Aging Clinical and Experimental Research.  ISSN 1594-0667.  25(6), s 659- 665 . doi: 10.1007/s40520-013-0092-z
• Winger, Anette; Ekstedt, Mirjam; Wyller, Vegard Bruun & Helseth, Sølvi (2013). Sometimes it feels as if the world goes on without me: adolescents' experiences of living with chronic fatigue syndrome. Journal of Clinical Nursing (JCN).  ISSN 0962-1067. . doi: 10.1111/jocn.12522 Show summary

  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

• Wyller, Vegard Bruun; Gisvold, Sven Erik; Hagen, Egil Ragnar; Heggedal, Rune; Heimdal, Arnulf; Karlsen, Kjetil; Mellin-Olsen, Jannicke; Størmer, Jan; Thomsen, Ivar & Wyller, Torgeir Bruun (2013). Reclaim the profession!. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  (6) . doi: 10.4045/tidsskr.13.0238
• Wyller, Vegard Bruun & Helland, Ingrid B (2013). Relationship between autonomic cardiovascular control, case definition, clinical symptoms, and functional disability in adolescent chronic fatigue syndrome: an exploratory study. BioPsychoSocial Medicine.  ISSN 1751-0759. . doi: 10.1186/1751-0759-7-5
• Fagermoen, Frode Even; Sulheim, Dag; Winger, Anette; Andersen, Anders Mikal; Vethe, Nils Tore; Saul, J P; Thaulow, Erik & Wyller, Vegard Bruun (2012). Clonidine in the treatment of adolescent chronic fatigue syndrome: a pilot study for the NorCAPITAL trial. BMC Research Notes.  ISSN 1756-0500.  5 . doi: 10.1186/1756-0500-5-418 Full text in Research Archive.
• Sulheim, Dag; Hurum, Harald; Helland, Ingrid B; Thaulow, Erik & Wyller, Vegard Bruun (2012). Adolescent chronic fatigue syndrome; a follow-up study displays concurrent improvement of circulatory abnormalities and clinical symptoms. BioPsychoSocial Medicine.  ISSN 1751-0759.  6 . doi: 10.1186/1751-0759-6-10
• Hareide, Live; Finset, Arnstein & Wyller, Vegard Bruun (2011). Chronic fatigue syndrome: a qualitative investigation of young patient's beliefs and coping strategies. Disability and Rehabilitation.  ISSN 0963-8288.  33(23-24), s 2255- 2263 . doi: 10.3109/09638288.2011.568663
• Hurum, Harald; Sulheim, Dag; Thaulow, Erik & Wyller, Vegard Bruun (2011). Elevated nocturnal blood pressure and heart rate in adolescent chronic fatigue syndrome. Acta Paediatrica.  ISSN 0803-5253.  100(2), s 289- 292 . doi: 10.1111/j.1651-2227.2010.02073.x
• Sommerfeldt, Line; Portilla, Helene; Jacobsen, Line Melå; Gjerstad, Johannes & Wyller, Vegard Bruun (2011). Polymorphisms of adrenergic cardiovascular control genes are associated with adolescent chronic fatigue syndrome. Acta Paediatrica.  ISSN 0803-5253.  100(2), s 293- 298 . doi: 10.1111/j.1651-2227.2010.02072.x Show summary

  Aim: To explore the frequency of polymorphisms in adrenergic cardiovascular control genes in adolescent with chronic fatigue syndrome (CFS) and the relation of such polymorphisms to cardiovascular variables. Methods: DNA from 53 patients with CFS, 12–18 years old, was analysed for five single nucleotide polymorphisms (SNPs) in the genes catechol‐O‐methyltransferase (COMT), the β2‐adrenergic receptor (two SNPs), the β1‐adrenergic receptor and the α2a‐adrenergic receptor. Frequencies were compared to a reference population constructed from the National Center for Biotechnology Information (NCBI) database, and associations between frequencies and autonomic cardiovascular responses during a 20° head‐uptilt‐test were explored. Results: For the COMT SNP Rs4680, patients with CFS had a higher frequency of the AA genotype and a lower frequency of the G containing genotypes (AG and GG), when compared to the reference sample (p = 0.046). Also, the AA genotype was associated with a smaller increase in LF/HF ratio (low‐frequency:high‐frequency heart rate variability ratio, an index of cardiac sympathovagal balance) during head‐up tilt when compared to the AG/GG genotypes. For the β2‐adrenergic receptor SNP Rs1042714, patients with CFS had a lower frequency of the GG genotype and a higher frequency of the genotypes containing C (CG and CC) (p = 0.044). Conclusions: CFS might be related to polymorphisms of COMT and the β2‐adrenergic receptor. More details of the molecular mechanisms remain to be investigated.

• Wyller, Vegard Bruun; Aaberge, Lars; Thaulow, Erik & Døhlen, Gaute (2011). Perkutan kateterbasert innsetting av kunstig pulmonalklaff ved medfødt hjertefeil. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  13-14, s 1289- 1293 . doi: 10.4045/tidsskr.10.0920 Show summary

  Bakgrunn. Perkutan kateterbasert innsetting av kunstige hjerteklaffer er en ny teknikk som kan få økende utbredelse i fremtiden og supplere kirurgiske inngrep. Vi rapporterer her våre første erfaringer med innsetting av kunstig pulmonalklaff hos barn med medfødt hjertefeil. Materiale og metode. Teknikken vurderes hos pasienter med hjertesviktsymptomer og stenose og/eller insuffisiens i et kunstig utløp fra høyre ventrikkel. Klaffen føres gjennom et kateter fra lyskevene eller halsvene. Behandlingseffekt vurderes ved symptombeskrivelse, ekkokardiografi, invasive målinger og angiografi. Vi rapporterer her våre behandlingsresultater i perioden april 2007 til september 2009. Resultater. Materialet består av ti pasienter (sju menn og tre kvinner, median alder 17 år). Prosedyren reduserte trykket i høyre ventrikkel (p = 0,008) og opphevet pulmonalinsuffisiensen hos alle ti pasienter. Median liggetid var to dager. Det oppsto ingen komplikasjoner med direkte forbindelse til innsettelsesprosedyren, men én pasient utviklet et pseudoaneurisme i a. femoralis, og en annen pasient fikk kortvarig feber to dager etter prosedyren. Hos én pasient måtte klaffen fjernes kirurgisk etter ni måneder pga. stentbrudd. Etter seks måneder rapporterte samtlige pasienter en symptombedring, trykkgradienten i høyre ventrikkel-utløp var redusert (p = 0,008) og pulmonalinsuffisiensen var bedret (p = 0,006). Disse resultatene vedvarte hos de fire pasientene som er blitt undersøkt etter 24 måneder. Fortolkning. Perkutan kateterbasert innsetting av kunstig pulmonalklaff bedrer høyre ventrikkels hemodynamikk hos utvalgte pasienter med medfødt hjertefeil. For sikrere kunnskap bør det imidlertid gjennomføres en randomisert, kontrollert studie.

• Wyller, Vegard Bruun; Barbieri, Riccardo & Saul, J. Philip (2011). Blood pressure variability and closed-loop baroreflex assessment in adolescent chronic fatigue syndrome during supine rest and orthostatic stress. European Journal of Applied Physiology.  ISSN 1439-6319.  111(3), s 497- 507 . doi: 10.1007/s00421-010-1670-9
• Wyller, Vegard Bruun; Evang, Johan Arild; Godang, Kristin; Solhjell, Kari Kittang & Bollerslev, Jens (2010). Hormonal alterations in adolescent chronic fatigue syndrome. Acta Paediatrica.  ISSN 0803-5253.  99(5), s 770- 773 . doi: 10.1111/j.1651-2227.2010.01701.x
• Gjone, Helene & Wyller, Vegard Bruun (2009). Chronic fatigue in adolescence-autonomic dysregulation and mental health: an exploratory study. Acta Paediatrica.  ISSN 0803-5253.  98(8), s 1313- 1318 . doi: 10.1111/j.1651-2227.2009.01323.x
• Wyller, Vegard Bruun; Saul, JP; Walløe, Lars & Thaulow, E (2008). Sympathetic cardiovascular control during orthostatic stress and isometric exercise in adolescent chronic fatigue syndrome. European Journal of Applied Physiology.  ISSN 1439-6319.  102 . doi: 10.1007/s00421-007-0634-1
• Wyller, Vegard Bruun (2007). The chronic fatigue syndrome - an update. Acta Neurologica Scandinavica.  ISSN 0001-6314.  115, s 7- 14 . doi: 10.1111/j.1600-0404.2007.00840.x Show summary

  Background – In this article, current scientific knowledge on the chronic fatigue syndrome (CFS) is reviewed. The US case definition of CFS (the CDC-definition) is most widespread in research and clinical practice. Estimates of prevalence vary from 0.2% to above 2%. The female–male ratio is approximately 3:1. Clinical Features – Severe fatigue is the dominating complaint; it is worsened from exertions and not substantially relieved by rest. In addition, the patients might have a varying combination of accompanying symptoms. Clinical evaluation should be based upon standardized guidelines, including an assessment of functional impairments. Pathophysiology – The pathophysiology should be interpreted within a biopsychosocial framework. Present knowledge suggests that certain genetic polymorphisms and personality traits might be regarded as predisposing factors, some infections and severe psychosocial stress constitute precipitating factors, whereas disturbances of immunity, skeletal muscle, cognitive abilities, endocrine control and cardiovascular homeostasis are possible perpetuating factors. Treatment – Cognitive behavioural therapy and graded exercise therapy are of proven value in randomized controlled trials. Several pharmaceutical measures have been explored and found to have no beneficial effect. Most patients might expect long-term improvement, but full recovery is rare; however, the prognosis is better among adolescents.

• Wyller, Vegard Bruun; Due, Reidar; Saul, J. Philip; Amlie, Jan Peder & Thaulow, Erik (2007). Usefulness of an Abnormal Cardiovascular Response During Low-Grade Head-Up Tilt-Test for Discriminating Adolescents With Chronic Fatigue from Healthy Controls. American Journal of Cardiology.  ISSN 0002-9149.  99(7), s 997- 1001 . doi: 10.1016/j.amjcard.2006.10.067 Show summary

  Hemodynamic dysfunction is documented in chronic fatigue syndrome (CFS). This study was conducted to investigate cardiovascular responses to orthostatic stress in adolescents with CFS, using a novel procedure for tilt-table testing. A total of 27 adolescents with CFS and 33 healthy control subjects with equal age and gender distribution underwent 15 minutes of 20° head-up tilt testing. Heart rate, systolic blood pressure (BP), mean BP, diastolic BP, stroke index, total peripheral resistance index, end-diastolic volume index, and acceleration index were continuously and noninvasively recorded. At rest, patients with CFS had higher total peripheral resistance index values (p <0.01) and lower stroke index and end-diastolic volume index values (p <0.05) than controls. During 20° head-up tilt testing, patients with CFS had greater increases in heart rate, diastolic BP (p <0.001), mean BP (p <0.01), and total peripheral resistance index (p <0.05) than controls and greater decreases in stroke index (p <0.05). Syncope or near syncope was not observed. In conclusion, this study found that adolescents with CFS have significant abnormalities of cardiovascular regulation in response to mild orthostatic stress, differentiating them from healthy controls

• Wyller, Vegard Bruun; Godang, K; Mørkrid, Lars; Saul, J. Philip; Thaulow, Erik & Walløe, Lars (2007). Abnormal Thermoregulatory Responses in Adolescents With Chronic Fatigue Syndrome: Relation to Clinical Symptoms. Pediatrics.  ISSN 0031-4005.  120(1), s 129- 137 . doi: 10.1542/peds.2006-2759 Show summary

  OBJECTIVES. Chronic fatigue syndrome is a common and disabling disease of unknown etiology. Accumulating evidence indicates dysfunction of the autonomic nervous system. To further explore the pathophysiology of chronic fatigue syndrome, we investigated thermoregulatory responses dependent on catecholaminergic effector systems in adolescent patients with chronic fatigue syndrome. PATIENTS AND METHODS. A consecutive sample of 15 patients with chronic fatigue syndrome aged 12 to 18 years and a volunteer sample of 57 healthy control subjects of equal gender and age distribution were included. Plasma catecholamines and metanephrines were measured before and after strong cooling of 1 hand. Acral skin blood flow, tympanic temperature, heart rate, and mean blood pressure were measured during moderate cooling of 1 hand. In addition, clinical symptoms indicative of thermoregulatory disturbances were recorded. RESULTS. Patients with chronic fatigue syndrome reported significantly more shivering, sweating, sudden change of skin color, and feeling unusually warm. At baseline, patients with chronic fatigue syndrome had higher levels of norepinephrine, heart rate, epinephrine, and tympanic temperature than control subjects. During cooling of 1 hand, acral skin blood flow was less reduced, vasoconstrictor events occurred at lower temperatures, and tympanic temperature decreased more in patients with chronic fatigue syndrome compared with control subjects. Catecholamines increased and metanephrines decreased similarly in the 2 groups. CONCLUSIONS. Adolescent patients with chronic fatigue syndrome have abnormal catecholaminergic-dependent thermoregulatory responses both at rest and during local skin cooling, supporting a hypothesis of sympathetic dysfunction and possibly explaining important clinical symptoms.

• Wyller, Vegard Bruun; Saul, J. Philip; Amlie, Jan Peder & Thaulow, Erik (2007). Sympathetic predominance of cardiovascular regulation during mild orthostatic stress in adolescents with chronic fatigue. Clinical Physiology and Functional Imaging.  ISSN 1475-0961.  27(4), s 231- 238 . doi: 10.1111/j.1475-097X.2007.00743.x Show summary

  Haemodynamic abnormalities have been documented in the chronic fatigue syndrome (CFS), indicating functional disturbances of the autonomic nervous system responsible for cardiovascular control. This study was designed to explore the pathophysiology in adolescent CFS-patients by analysing RR-interval (RRI) variability and diastolic blood pressure (DBP) variability during mild orthostatic stress, using an algorithm which accounts for non-stationary biosignals. A total of 27 adolescents with CFS and 33 healthy control subjects having equal age- and sex distribution underwent 15 min of 20° head-up tilt (HUT). The spectral power densities of RRI and DBP were computed in the low-frequency (LF) band (0·04–0·15 Hz) and the high-frequency (HF) band (0·15–0·4 Hz) using an adaptive autoregressive algorithm to obtain a time-varying spectrum. RMSSD, a time domain index of RRI variability, was also computed. At rest, all indices of variability were similar in the two groups. During tilt, CFS patients had a larger increase in the LF/HF ratio (P≤0·001) and normalized LF power of RRI (P≤0·01), and a larger decrease in normalized HF power (P≤0·01) of RRI than controls. CFS patients also had trends towards a larger decrease in absolute HF power of RRI and a larger increase in normalized LF power of DBP. These findings suggest that adolescents with CFS have sympathetic predominance of cardiovascular regulation during very mild orthostatic stress. Possible underlying mechanisms are moderate hypovolemia, abnormalities of reflex control or physical de-conditioning.

• Wyller, Vegard Bruun; Thaulow, Erik & Amlie, Jan Peder (2007). Treatment of chronic fatigue and orthostatic intolerance with propranolol. Journal of Pediatrics.  ISSN 0022-3476.  150(6), s 654- 655 . doi: 10.1016/j.jpeds.2007.03.012 Show summary

  We describe the effect of propranolol in an adolescent with chronic fatigue syndrome and orthostatic intolerance. Our observations suggest that the head-up tilt-test and beta-blocker treatment might be considered in patients with chronic fatigue syndrome and that enhanced sympathetic nervous activity might be part of the underlying pathophysiology.

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• Wyller, Vegard Bruun (2006). Det friske og Det syke mennesket (1-6). Akribe Forlag.  ISBN 9788279500957.  2410 s. Show summary

  læreverk i naturvitenskapelige og medisinske fag for helsearbeidere. Det består av seks bind og er bygd opp omkring organene og organsystemene. Cellebiologi, anatomi, fysiologi, mikrobiologi, patofysiologi, farmakologi, klinisk medisin

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• Nygaard, Sissel Irene; Rolid, Katrine; Nytrøen, Kari; Fiane, Arnt E; Wyller, Vegard Bruun Bratholm; Gullestad, Lars & Broch, Kaspar (2020). Heart Rate Response after Heart Transplantation. The Journal of Heart and Lung Transplantation.  ISSN 1053-2498.  39(4), s S285- S286 . doi: 10.1016/j.healun.2020.01.630
• Wyller, Vegard Bruun Bratholm (2019). Pain is common in chronic fatigue syndrome-current knowledge and future perspectives. Scandinavian Journal of Pain.  ISSN 1877-8860.  19(1), s 5- 8 . doi: 10.1515/sjpain-2018-2007
• Bratholm, Hedda & Wyller, Vegard Bruun Bratholm (2018). Feilinformasjon om kronisk utmattelsessyndrom. Tidsskrift for Norsk Psykologforening.  ISSN 0332-6470.  55(2), s 126- 127
• Nordin, Succora; Donkor, Hilde Mjell; Wyller, Vegard Bruun Bratholm; Farstad, Teresa; Borthne, Arne Sigmund; Moen, Atle & Solevåg, Anne Lee (2018). Pericarditis in a newborn child. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  138(5) . doi: 10.4045/tidsskr.17.0555
• Wyller, Vegard Bruun Bratholm; Vitelli, Valeria; Sulheim, Dag; Fagermoen, Frode Even; Winger, Anette; Godang, Kristin & Bollerslev, Jens (2017). Altered neuroendocrine control and association to clinical symptoms in adolescent chronic fatigue syndrome: A cross-sectional study. Journal of Translational Medicine.  ISSN 1479-5876.  15(157) . doi: 10.1186/s12967-017-1261-1
• Vogt, Henrik; Ulvestad, Elling & Wyller, Vegard Bruun Bratholm (2016). Metabolic features of chronic fatigue syndrome revisited. Proceedings of the National Academy of Sciences of the United States of America.  ISSN 0027-8424.  113(46), s E7140- E7141 . doi: 10.1073/pnas.1615143113
• Wyller, Vegard Bruun Bratholm (2016). Den brysomme samvittigheten. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  136(7), s 595- 595 . doi: 10.4045/tidsskr.16.0268
• Wyller, Vegard Bruun; Jacobsen, Kristine; Dahl, Mai Britt; Nilsen, Hilde; Proske, Simone; Horter, Thorsten & Brun, Henrik (2016). Interferon gamma may improve cardiac function in Friedreich's ataxia cardiomyopathy. International Journal of Cardiology.  ISSN 0167-5273.  221, s 376- 378 . doi: 10.1016/j.ijcard.2016.06.288
• Wyller, Vegard Bruun; Reme, Silje & Mollnes, Tom Eirik (2016). Kronisk utmattelsessyndrom/myalgisk encefalopati - sykdomsmekanismer, diagnostikk og behandling. Fysioterapeuten.  ISSN 0016-3384.  83(2), s 24- 27
• Wyller, Vegard Bruun (2015). Elefanten i rommet. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  135(6), s 507 . doi: 10.4045/tidsskr.15.0343
• Wyller, Vegard Bruun (2015). Helsepolitikk – mer ideologi enn fornuft? :. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  135(16), s 1423 . doi: 10.4045/tidsskr.15.0882
• Wyller, Vegard Bruun (2015). Re: Hva er egentlig myalgisk encefalopati?. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  135(22), s 2021- 2021 . doi: 10.4045/tidsskr.15.1186
• Wyller, Vegard Bruun (2015). Re: Hva er egentlig myalgisk encefalopati?. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  135(22), s 2020 . doi: 10.4045/tidsskr.15.1184
• Wyller, Vegard Bruun; Reme, Silje & Mollnes, Tom Eirik (2015). Kronisk utmattelsessyndrom/myalgisk encefalopati – sykdomsmekanismer, diagnostikk og behandling. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  135(23/24), s 2172- 2175 . doi: 10.4045/tidsskr.15.1180
• Winger, Anette; Ekstedt, Mirjam; Wyller, Vegard Bruun & Helseth, Sølvi (2013). "Sometimes it Feels as if The World Goes on Without Me" Adolescents experiences of living with chronic fatigue syndrome.
• Njølstad, Berit Widerøe; Sveen, Unni & Wyller, Vegard Bruun (2012). Gradert aktivitetstilpasning hos ungdom med kronisk utmattelsessyndrom - nyttig eller unyttig?. Ergoterapeuten.  ISSN 0800-3475.  55(3), s 25- 30
• Sinnes, Tommy; Melinder, Annika Maria D; Sulheim, Dag; Fagermoen, Frode Even; Winger, Anette; Wessel, Ellen Sofie; Wyller, Vegard Bruun & Endestad, Tor (2012). Emotional Stroop and CFS: An fMRI Study.
• Vogt, Henrik; Getz, Linn; Ulvestad, Elling & Wyller, Vegard Bruun (2011). Det udelte mennesket. Aftenposten (morgenutg. : trykt utg.).  ISSN 0804-3116. . doi: http://www.aftenposten.no/meninger/kronikker/Det-udelte-mennesket-6728808.html
• Winger, Anette; Wyller, Vegard Bruun; Ekstedt, Mirijam & Helseth, Sølvi (2011). Pain and quality of life among adolescents with chronic fatigue syndrome.
• Riska, Oda & Wyller, Vegard Bruun (2007). Kronisk tretthetssyndrom og autonom dysfunksjon. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  127(14), s 1914- 1914 Show summary

  Kronisk tretthetssyndrom, også kalt kronisk utmattelsessyndrom, er karakterisert ved unormale responser i det sympatiske nervesystem og kan dermed betraktes som en stresslidelse. Hos ungdommer med denne sykdommen er det svekket regulering av blodgjennomstrømning og kroppstemperatur, og kroppen reagerer derfor unormalt på dagligdagse belastninger. Slik konkluderer Vegard Bruun Wyller i avhandlingen The pathophysiology of chronic fatigue syndrome in adolescents. Han disputerte for Ph.D.-graden ved Universitetet i Oslo 21.06.2007.

• Wyller, Vegard Bruun (2007, 09. mai). ME - kronisk utmattelsessyndrom. [TV].  God morgen, Norge! TV2.
• Wyller, Vegard Bruun & Saugstad, Ola Didrik (2006, 09. juni). Strid om mystisk sykdom.  Aftenposten. Show summary

  ME-foreningen er nådeløs i sin kritikk av en ny rapport om en uforklarlig sykdom som rammer tusenvis av nordmenn. Legen bak rapporten mener foreningen gjør sine egne en bjørnetjeneste.

• Wyller, Vegard Bruun & Thaulow, Erik (2006, 24. mars). Barnehjerter ikke leget for alltid.  A-Magasinet Aftenposten. Show summary

  Hjertebarna: 40 prosent av alle barn med hjertefeilen Fallots tetrade må opereres på nytt i tenårene.

• Wyller, Vegard Bruun; Thaulow, Erik & Amlie, Jan Peder (2006). Synkope hos barn og unge voksne. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  126(21), s 2831
• Wyller, Vegard Bruun Bratholm; Bjørneklett, Arvid; Brubakk, Oddbjørn; Festvåg, Lillian; Follestad, Inghild; Malt, Ulrik Fredrik; Malterud, Kirsti; Nyland, Harald Inge; Rambøl, Harald; Stubhaug, Bjarte & Larun, Lillebeth (2006). Diagnostisering og behandling av kronisk utmattelsessyndrom/myalgisk encefalopati (CFS/ME).. Rapport fra Kunnskapssenteret. 9. Full text in Research Archive.
• Wyller, Torgeir Bruun & Wyller, Vegard Bruun (2005). Fibromyalgi, vannlating og etablerte sannheter. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  125(1), s 14 Show summary

  En patofysiologisk sammenheng mellom hyppig vannlating og fibromyalgi kan være biologisk plausibel. Holdes nyskapende hypoteser nede fordi de utfordrer autoritetene?

• Wyller, Vegard Bruun (2005, 04. september). 400 barn rammes i Norge.  Verdens Gang. Show summary

  Norske eksperter slår alarm etter at stadig flere norske barn får den mystiske sykdommen kronisk utmattelsessyndrom (ME). - Det er ofte perfeksjonister med høye krav til seg selv som blir rammet. Vi ser to ting som utløser dette. De som blir rammet, har ofte et høyt aktivitetsnivå og kan ha hatt infeksjoner som kyssesyken, sier professor ved nevrologisk avdeling ved Haukeland Universitetssykehus, Harald Nyland, og får støtte av Vegard Bruun Wyller, som er forsker på sykdommen ved Rikshospitalet. - Vi har veldig lite kunnskap om hvor mange barn og unge som er rammet. Men basert på studier i England kan det trolig dreie seg om mellom 300 og 400 barn, sier Wyller. I løpet av høsten skal Wyller avslutte et forskningsprosjekt hvor han har studert 20 ME-barn. - I vår tid opplever ungdommer mye press og forventninger, samtidig som de har mulighet til å ta mange valg. Dette, kombinert med visse infeksjoner, kan forklare hvorfor stadig flere ungdommer får diagnosen.

• Wyller, Vegard Bruun & Wyller, Torgeir Bruun (2004). Kronisk utmattelsessyndrom. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  (18)

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