Postural orthostatic tachycardia is not a useful diagnostic marker for chronic fatigue syndrome

Abstract:

BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is considered a diagnostic marker for chronic fatigue syndrome (CFS).

OBJECTIVES: The aims of this study were to (i) compare POTS prevalence in a CFS cohort with fatigued patients not meeting CFS criteria, and (ii) assess activity, impairment and response to cognitive behavioural therapy (CBT) in CFS patients with POTS (POTS-CFS) and without POTS (non-POTS-CFS).

METHODS: Prospective cohort study at the Radboud University Medical Centre in the Netherlands. Between June 2013 and December 2014, 863 consecutive patients with persistent fatigue were screened. Patients underwent an active standing test, filled out questionnaires and wore an activity-sensing device for a period of 12 days.

RESULTS: A total of 419 patients with CFS and 341 non-CFS fatigued patients were included in the study. POTS prevalence in adult patients with CFS was 5.7% vs. 6.9% in non-CFS adults (P = 0.54). In adolescents, prevalence rates were 18.2% and 17.4%, respectively (P = 0.93). Adult patients with POTS-CFS were younger (30 ± 12 vs. 40 ± 13 years, P = 0.001) and had a higher supine heart rate (71 ± 11 vs. 65 ± 9 beats per min, P = 0.009) compared with non-POTS-CFS patients. Severity and activity patterns did not differ between groups. In patients with CFS, criteria for Systemic Exertion Intolerance Disease (SEID) were met in 76% of adults and 67% of adolescents. In these patients with CFS fulfilling the SEID criteria, the prevalence of POTS was not different from that in the overall CFS population. POTS-CFS adolescents had less clinically significant improvement after CBT than non-POTS-CFS adolescents (58% vs. 88%, P = 0.017).

CONCLUSION: In adults with CFS, the prevalence of POTS was low, was not different from the rate in non-CFS fatigued patients and was not related to disease severity or treatment outcome. In POTS-CFS adolescents, CBT was less successful than in non-POTS-CFS patients. The evaluation of POTS appears to be of limited value for the diagnosis of CFS.

© 2016 The Association for the Publication of the Journal of Internal Medicine.

 

Source: Roerink ME, Lenders JW, Schmits IC, Pistorius AM, Smit JW, Knoop H, van der Meer JW. Postural orthostatic tachycardia is not a useful diagnostic marker for chronic fatigue syndrome. J Intern Med. 2017 Feb;281(2):179-188. doi: 10.1111/joim.12564. Epub 2016 Oct 2. https://www.ncbi.nlm.nih.gov/pubmed/27696568

 

Obesity in adolescents with chronic fatigue syndrome: an observational study

Abstract:

OBJECTIVE: Identify the prevalence of obesity in patients with chronic fatigue syndrome (CFS) compared with healthy adolescents, and those identified with CFS in a population cohort.

DESIGN: Cross-sectional analysis of multiple imputed data.

SETTING: Data from UK paediatric CFS/myalgic encephalomyelitis (CFS/ME) services compared with data collected at two time points in the Avon Longitudinal Study of Parents and Children (ALSPAC).

PATIENTS: 1685 adolescents who attended a CFS/ME specialist service between 2004 and 2014 and 13 978 adolescents aged approximately 13 years and 16 years participating in the ALSPAC study.

MAIN OUTCOME MEASURES: Body mass index (BMI) (kg/m2), sex-specific and age-specific BMI Z-scores (relative to the International Obesity Task Force cut-offs) and prevalence of obesity (%).

RESULTS: Adolescents who had attended specialist CFS/ME services had a higher prevalence of obesity (age 13 years: 9.28%; age 16 years: 16.43%) compared with both adolescents classified as CFS/ME in ALSPAC (age 13 years: 3.72%; age 16 years: 5.46%) and those non-CFS in ALSPAC (age 13 years: 4.18%; age 16 years: 4.46%). The increased odds of obesity in those who attended specialist services (relative to non-CFS in ALSPAC) was apparent at both 13 years (OR: 2.31 (1.54 to 3.48)) and 16 years, with a greater likelihood observed at 16 years (OR: 4.07 (2.04 to 8.11)).

CONCLUSIONS: We observed an increased prevalence of obesity in adolescents who were affected severely enough to be referred to a specialist CFS/ME service. Further longitudinal research is required in order to identify the temporal relationship between the two conditions.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

 

Source: Norris T, Hawton K, Hamilton-Shield J, Crawley E. Obesity in adolescents with chronic fatigue syndrome: an observational study. Arch Dis Child. 2017 Jan;102(1):35-39. doi: 10.1136/archdischild-2016-311293. Epub 2016 Sep 21. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5256402/ (Full article)

 

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

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.

 

Source: Wortinger LA, Endestad T, Melinder AM, Øie MG, Sulheim D, Fagermoen E, Wyller VB. Emotional conflict processing in adolescent chronic fatigue syndrome: A pilot study using functional magnetic resonance imaging. J Clin Exp Neuropsychol. 2016 Sep 20:1-14. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/27647312

 

Comorbidities treated in primary care in children with chronic fatigue syndrome / myalgic encephalomyelitis: A nationwide registry linkage study from Norway

Abstract:

BACKGROUND: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a complex condition. Causal factors are not established, although underlying psychological or immunological susceptibility has been proposed. We studied primary care diagnoses for children with CFS/ME, with children with another hospital diagnosis (type 1 diabetes mellitus [T1DM]) and the general child population as comparison groups.

METHODS: All Norwegian children born 1992-2012 constituted the study sample. Children with CFS/ME (n = 1670) or T1DM (n = 4937) were identified in the Norwegian Patient Register (NPR) (2008-2014). Children without either diagnosis constituted the general child population comparison group (n = 1337508). We obtained information on primary care diagnoses from the Norwegian Directorate of Health. For each primary care diagnosis, the proportion and 99 % confidence interval (CI) within the three groups was calculated, adjusted for sex and age by direct standardization.

RESULTS: Children with CFS/ME were more often registered with a primary care diagnosis of weakness/general tiredness (89.9 % [99 % CI 88.0 to 91.8 %]) than children in either comparison group (T1DM: 14.5 % [99 % CI: 13.1 to 16.0 %], general child population: 11.1 % [99 % CI: 11.0 to 11.2 %]). Also, depressive disorder and anxiety disorder were more common in the CFS/ME group, as were migraine, muscle pain, and infections. In the 2 year period prior to the diagnoses, infectious mononucleosis was registered for 11.1 % (99 % CI 9.1 to 13.1 %) of children with CFS/ME and for 0.5 % (99 % CI (0.2 to 0.8 %) of children with T1DM. Of children with CFS/ME, 74.6 % (1292/1670) were registered with a prior primary care diagnosis of weakness / general tiredness. The time span from the first primary care diagnosis of weakness / general tiredness to the specialist health care diagnosis of CFS/ME was 1 year or longer for 47.8 %.

CONCLUSIONS: This large nationwide registry linkage study confirms that the clinical picture in CFS/ME is complex. Children with CFS/ME were frequently diagnosed with infections, supporting the hypothesis that infections may be involved in the causal pathway. The long time span often observed from the first diagnosis of weakness / general tiredness to the diagnosis of CFS/ME might indicate that the treatment of these patients is sometimes not optimal.

 

Source: Bakken IJ, Tveito K, Aaberg KM, Ghaderi S, Gunnes N, Trogstad L, Magnus P, Stoltenberg C, Håberg SE. Comorbidities treated in primary care in children with chronic fatigue syndrome / myalgic encephalomyelitis: A nationwide registry linkage study from Norway. BMC Fam Pract. 2016 Sep 2;17(1):128. doi: 10.1186/s12875-016-0527-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5010760/ (Full article)

 

Aberrant Resting-State Functional Connectivity in the Salience Network of Adolescent Chronic Fatigue Syndrome

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.

 

Source: Wortinger LA, Endestad T, Melinder AM, Øie MG, Sevenius A, Bruun Wyller V. Aberrant Resting-State Functional Connectivity in the Salience Network of Adolescent Chronic Fatigue Syndrome. PLoS One. 2016 Jul 14;11(7):e0159351. doi: 10.1371/journal.pone.0159351. ECollection 2016. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944916/ (Full article)

 

Managed Activity Graded Exercise iN Teenagers and pre-Adolescents (MAGENTA) feasibility randomised controlled trial: study protocol

Abstract:

INTRODUCTION: Paediatric chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) is a relatively common and disabling condition, yet there is a limited evidence base for treatment. There is good evidence that graded exercise therapy is moderately effective in adults with CFS/ME, but there is little evidence for the effectiveness, cost-effectiveness, acceptability or best method of delivery for paediatric CFS/ME. This study aims to investigate the acceptability and feasibility of carrying out a multicentre randomised controlled trial investigating the effectiveness of graded exercise therapy compared with activity management for children/teenagers who are mildly or moderately affected with CFS/ME.

METHODS AND ANALYSIS: 100 paediatric patients (8-17 years) with CFS/ME will be recruited from 3 specialist UK National Health Service (NHS) CFS/ME services (Bath, Cambridge and Newcastle). Patients will be randomised (1:1) to receive either graded exercise therapy or activity management. Feasibility analysis will include the number of young people eligible, approached and consented to the trial; attrition rate and treatment adherence; questionnaire and accelerometer completion rates. Integrated qualitative methods will ascertain perceptions of feasibility and acceptability of recruitment, randomisation and the interventions. All adverse events will be monitored to assess the safety of the trial.

ETHICS AND DISSEMINATION: The trial has received ethical approval from the National Research Ethics Service (South West-Frenchay 15/SW/0124).

TRIAL REGISTRATION NUMBER: ISRCTN23962803; Pre-results.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

 

Source: Brigden A, Beasant L, Hollingworth W, Metcalfe C, Gaunt D, Mills N, Jago R, Crawley E. Managed Activity Graded Exercise iN Teenagers and pre-Adolescents (MAGENTA) feasibility randomised controlled trial: study protocol. BMJ Open. 2016 Jul 4;6(7):e011255. doi: 10.1136/bmjopen-2016-011255. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947787/ (Full article)

 

Chronic fatigue syndrome in adolescents

Dear Editor:

Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is a rare disease in adolescents, in whom the incidence is 0.5%. In adults, it has a multifactorial aetiology with no determining factor, primarily affects women (ratio, 2–3:1) aged 20–40 years, and in some cases its onset is associated with an infectious cause (usually viral). In adulthood, CFS is diagnosed based on clinical manifestations and is a diagnosis of exclusion (Table 1),1 and while the literature includes descriptions of differences in the paediatric population, few series present data on its particular features in this age group. The management is symptomatic with the goal of improving quality of life. Treatment with selective serotonin reuptake inhibitors (SSRIs), melatonin, methylphenidate, cognitive-behavioural therapy (CBT) and graded exercise has been proven to be effective in these patients.

You can read the full letter here: http://www.analesdepediatria.org/en/chronic-fatigue-syndrome-in-adolescents/articulo/S2341287916301168/

 

Source: Calle Gómez Á, Delgado Díez B, Campillo I López F, Salmerón Ruiz MA, Casas Rivero J. Chronic fatigue syndrome in adolescents. An Pediatr (Barc). 2016 Dec;85(6):318-320. doi: 10.1016/j.anpedi.2016.03.010. Epub 2016 May 20. [Article in Spanish] http://www.analesdepediatria.org/en/chronic-fatigue-syndrome-in-adolescents/articulo/S2341287916301168/ (Full article)

 

A qualitative investigation of eating difficulties in adolescents with chronic fatigue syndrome/myalgic encephalomyelitis

Abstract:

BACKGROUND: An estimated 10% of children and adolescents with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) experience eating difficulties; however, little is known about why these difficulties develop, what the impact is or how to manage them.

METHODS: Semi-structured interviews were conducted with adolescents (aged 12-17 years) attending a specialist service who have a primary diagnosis of CFS/ME and experience nausea, abdominal pain and/or eating difficulties. A total of 11 adolescents were interviewed (eight female, mean age: 15 years). Transcripts were analysed thematically using techniques of constant comparison which commenced soon after data collection and informed further interview protocols.

RESULTS: Adolescents perceived their eating difficulties were caused by abdominal symptoms, being too fatigued to eat and changes to their senses of taste and smell. Some of the adolescents recognised how their eating difficulties were exacerbated and maintained by psychological factors of low mood and anxiety. The adolescents eating difficulties had a negative impact on their weight, fatigue, socialising and family life. They perceived helpful interventions to include modifying their diets, families adjusting and also medical interventions (e.g. medication). Adolescents identified that early education and support about diet and eating habits would have been helpful.

CONCLUSIONS: If adolescents diagnosed with CFS/ME develop eating difficulties, this has a significant impact on their quality of life, illness and on their families. Not eating increases fatigue, low mood and anxiety which further exacerbates the eating difficulties. Clinicians should screen for eating difficulties in those with symptoms of nausea and abdominal pain, warn adolescents and their families of the risk of developing eating difficulties and provide interventions and support as early as possible.

 

Source: Harris S, Gilbert M, Beasant L, Linney C, Broughton J, Crawley E. A qualitative investigation of eating difficulties in adolescents with chronic fatigue syndrome/myalgic encephalomyelitis. Clin Child Psychol Psychiatry. 2017 Jan;22(1):128-139. doi: 10.1177/1359104516646813. Epub 2016 Jul 26. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5207298/ (Full article)

 

Cow’s milk protein intolerance in adolescents and young adults with chronic fatigue syndrome

Abstract:

AIM: To examine the prevalence, clinical features and influence on illness severity of cow’s milk protein intolerance in young people with chronic fatigue syndrome.

METHODS: In a two-year prospective study of 55 adolescents and young adults with chronic fatigue syndrome, we defined intolerance to milk protein if subjects reported (i) no evidence of immediate or anaphylactic reactions to milk, (ii) at least 2 of the following 3 chronic symptoms: gastroesophageal reflux, early satiety and epigastric/abdominal pain, (iii) improvement in upper gastrointestinal symptoms on a milk protein elimination diet and (iv) at least 2 recurrences of upper gastrointestinal symptoms >two hours following open re-exposure to milk protein. Subjects completed three quality of life surveys at baseline and at six months.

RESULTS: The mean (SD) age of the 55 participants was 16.5 (2.1) years. Seventeen (31%; 95% CI, 19-43%) met study criteria for cow’s milk protein intolerance. Compared to milk-tolerant subjects, milk-sensitive participants had significantly worse health-related quality of life at baseline but not at six months (after institution of the milk-free diet).

CONCLUSION: Cow’s milk protein intolerance is a common problem in young people with chronic fatigue syndrome and is a treatable contributor to their symptoms.

©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

 

Source: Rowe PC, Marden CL, Jasion SE, Cranston EM, Flaherty MA, Kelly KJ. Cow’s milk protein intolerance in adolescents and young adults with chronic fatigue syndrome. Acta Paediatr. 2016 Sep;105(9):e412-8. doi: 10.1111/apa.13476. Epub 2016 Jun 3. https://www.ncbi.nlm.nih.gov/pubmed/27177188

 

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

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 NCT010404

 

Source: Wyller VB, Vitelli V, Sulheim D, Fagermoen E, Winger A, Godang K, Bollerslev J. Altered neuroendocrine control and association to clinical symptoms in adolescent chronic fatigue syndrome: a cross-sectional study. J Transl Med. 2016 May 5;14(1):121. doi: 10.1186/s12967-016-0873-1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4858924/ (Full article)