Category: Pediatric ME/CFS

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Diagnosis and Management in Young People: A Primer

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disease that affects children and adolescents as well as adults. The etiology has not been established. While many pediatricians and other health-care providers are aware of ME/CFS, they often lack essential knowledge that is necessary for diagnosis and treatment. Many young patients experience symptoms for years before receiving a diagnosis.

This primer, written by the International Writing Group for Pediatric ME/CFS, provides information necessary to understand, diagnose, and manage the symptoms of ME/CFS in children and adolescents. ME/CFS is characterized by overwhelming fatigue with a substantial loss of physical and mental stamina. Cardinal features are malaise and a worsening of symptoms following minimal physical or mental exertion. These post-exertional symptoms can persist for hours, days, or weeks and are not relieved by rest or sleep.

Other symptoms include cognitive problems, unrefreshing or disturbed sleep, generalized or localized pain, lightheadedness, and additional symptoms in multiple organ systems. While some young patients can attend school, on a full or part-time basis, many others are wheelchair dependent, housebound, or bedbound.

Prevalence estimates for pediatric ME/CFS vary from 0.1 to 0.5%. Because there is no diagnostic test for ME/CFS, diagnosis is purely clinical, based on the history and the exclusion of other fatiguing illnesses by physical examination and medical testing. Co-existing medical conditions including orthostatic intolerance (OI) are common.

Successful management is based on determining the optimum balance of rest and activity to help prevent post-exertional symptom worsening. Medications are helpful to treat pain, insomnia, OI and other symptoms. The published literature on ME/CFS and specifically that describing the diagnosis and management of pediatric ME/CFS is very limited. Where published studies are lacking, recommendations are based on the clinical observations and practices of the authors.

Source: Rowe PC, Underhill RA, Friedman KJ, Gurwitt A, Medow MS, Schwartz MS, Speight N, Stewart JM, Vallings R, Rowe KS. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Diagnosis and Management in Young People: A Primer. Front Pediatr. 2017 Jun 19;5:121. doi: 10.3389/fped.2017.00121. eCollection 2017. http://journal.frontiersin.org/article/10.3389/fped.2017.00121/full

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

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

Source: Chinh Bkrong Nguyen, Lene Alsøe, Jessica M. Lindvall, Dag Sulheim, Even Fagermoen, Anette Winger, Mari Kaarbø, Hilde Nilsen and Vegard Bruun Wyller. 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 2017 15:102. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1201-0 (Full article)

Sleep-wake rhythm disturbances and perceived sleep in adolescent chronic fatigue syndrome

 

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.

© 2017 European Sleep Research Society.

Source: Pedersen M, Ekstedt M, Småstuen MC, Wyller VB, Sulheim D, Fagermoen E, Winger A, Pedersen E, Hrubos-Strøm H. Sleep-wake rhythm disturbances and perceived sleep in adolescent chronic fatigue syndrome. J Sleep Res. 2017 May 4. doi: 10.1111/jsr.12547. [Epub ahead of print]. https://www.ncbi.nlm.nih.gov/pubmed/28470767

Stress vulnerability in adolescents with chronic fatigue syndrome: experimental study investigating heart rate variability and skin conductance responses

Abstract:

BACKGROUND: Stress vulnerability has been implicated in adolescent chronic fatigue syndrome (CFS), but has rarely been investigated directly. This study compared psychological and physiological responses to a laboratory social performance task in adolescents with CFS with chronic illness (asthma) and healthy control groups.

METHODS: Adolescents with CFS (n = 60), adolescents with asthma (n = 31) and healthy adolescents (n = 78) completed questionnaires before and after a social performance task. Skin conductance responses (SCR; mean SCR and Max-Min) and heart rate variability (low frequency/high frequency; LF/HF and root mean square difference of successive RR intervals; RMSSD) was measured before, during and after the task.

RESULTS: Baseline heart rate variability (HRV) (RMSSD) was significantly lower in the CFS and Asthma groups than the HC. During the speech, the CFS and Asthma groups had higher HRV (LF/HF) than the HC, adjusting for baseline LF/HF. Although the asthma group showed a subsequent reduction in HRV during recovery, the CFS group did not. Similarly, during recovery after the task, the CFS group showed a continued increase in skin conductance (Min-Max), unlike the Asthma and HC groups. Compared to control groups, adolescents with CFS expected to find the task more difficult, were more anxious beforehand and afterwards, rated it as more difficult, evaluated their performance more negatively and had lower observer ratings of performance. Parents of adolescents with CFS expected that their child would perform less well in the task than parents of control participants.

CONCLUSIONS: Adolescents with CFS showed autonomic nervous system responses that are consistent with chronic stress vulnerability, difficulty coping with acute stress and slower recovery after acute stress. Self-report measures also indicated greater trait, pre- and posttask anxiety in the CFS group.

© 2017 Association for Child and Adolescent Mental Health.

 

Source: Rimes KA, Lievesley K, Chalder T. Stress vulnerability in adolescents with chronic fatigue syndrome: experimental study investigating heart rate variability and skin conductance responses. J Child Psychol Psychiatry. 2017 Mar 9. doi: 10.1111/jcpp.12711. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28276066

 

Issues in Estimating Rates of Pediatric Chronic Fatigue Syndrome and Myalgic Encephalomyelitis in a Community-based Sample

Abstract:

There is a need to examine the prevalence of pediatric chronic fatigue syndrome (CFS) and Myalgic Encephalomyelitis (ME) in the general community, as well as the relative frequency of CFS and ME among various groups (e.g., different age groups, genders, racial/ethnic groups, and socioeconomic strata) and to compare these individuals with community controls.

In the present study, we describe an ongoing NIH-funded study, which uses a multiple-stage design, beginning with a brief screening for CFS- and ME-like symptomatology, followed by a more rigorous medical and psychiatric diagnostic evaluation to determine the prevalence of pediatric CFS and ME status in the general community. We provide two case studies showing the types of data we are collecting, and how the data are being used to inform diagnostic decisions.

 

Source: Jason LA, Katz BZ, Mears C, Jantke R, Brown A, Sunnquist M, O’Connor K. Issues in Estimating Rates of Pediatric Chronic Fatigue Syndrome and Myalgic Encephalomyelitis in a Community-based Sample. Avicenna J Neuropsychophysiol. 2015 Nov;2(4). pii: e37281. doi: 10.17795/ajnpp-37281. Epub 2015 Nov 21. https://www.ncbi.nlm.nih.gov/pubmed/28261672

 

Important factors to consider when treating children with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): perspectives of health professionals from specialist services

Abstract:

BACKGROUND: Paediatric Chronic Fatigue Syndrome (CFS)/Myalgic Encephalomyelitis (ME) is relatively common and disabling. Improving treatment requires the development of Patient Reported Outcome Measures (PROMs) that enable clinicians and researchers to collect patient-centred evidence on outcomes. Health professionals are well placed to provide clinical insight into the condition, its treatment and possible outcomes. This study aimed to understand the perspectives of specialist paediatric CFS/ME health professionals and identify outcomes that are clinically important.

METHODS: Focus groups and interviews were held with 15 health professionals involved in the care of children with CFS/ME from the four largest specialist paediatric CFS/ME services in the NHS in England. A range of clinical disciplines were included and experience in paediatric CFS/ME ranged from 2 months to 25 years. Ten participants (67%) were female. Focus groups and interviews were recorded, transcribed verbatim and data were analysed using thematic analysis.

RESULTS: All health professionals identified the impact of CFS/ME across multiple aspects of health. Health professionals described four areas used to assess the severity of the illness and outcome in children: 1) symptoms; 2) physical function; 3) participation (school, activities and social life); and 4) emotional wellbeing. They also described the complexity of the condition, contextual factors and considerations for treatment to help children to cope with the condition.

CONCLUSIONS: Clinically important outcomes in paediatric CFS/ME involve a range of aspects of health. Health professionals consider increases in physical function yet maintaining school functioning and participation more widely as important outcomes from treatment. The results are similar to those described by children in a recent study and will be combined to develop a new child-specific PROM that has strong clinical utility and patient relevance.

 

Source: Parslow RM, Shaw A, Haywood KL, Crawley E. Important factors to consider when treating children with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): perspectives of health professionals from specialist services. BMC Pediatr. 2017 Feb 1;17(1):43. doi: 10.1186/s12887-017-0799-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5286567/ (Full article)

 

Children’s experiences of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): a systematic review and meta-ethnography of qualitative studies

Abstract:

OBJECTIVE: To synthesis the qualitative studies of children’s experiences of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).

DESIGN: Systematic review and meta-ethnography.

BACKGROUND: CFS/ME is an important disabling illness, with uncertain cause and prognosis. As a result, children with CFS/ME can find themselves living with greater uncertainty and stigma, exacerbating the impact of the condition. There is a growing body of qualitative research in CFS/ME, yet there has been no attempt to systematically synthesis the studies involving children.

METHODS: Studies exploring the experiences of children diagnosed with CFS/ME, published or unpublished, using qualitative methods were eligible. MEDLINE, EMBASE, PsycINFO and CINAHL databases were searched as well as grey literature, reference lists and contacting authors. Quality assessment was done independently using the Critical Appraisal Skills Programme (CASP) checklist. Studies were synthesised using techniques of meta-ethnography.

RESULTS: Ten studies involving 82 children with CFS/ME aged 8-18 were included. Our synthesis describes four third-order constructs within children’s experiences: (1) disruption and loss: physical, social and the self; (2) barriers to coping: suspension in uncertainty, problems with diagnosis and disbelief; (3) facilitators to coping: reducing uncertainty, credible illness narratives, diagnosis and supportive relationships and (4) hope, personal growth and recovery. CFS/ME introduces profound biographical disruption through its effects on children’s ability to socialise, perform school and therefore how they see their future. Unfamiliarity of the condition, problems with diagnosis and felt stigma prevent children from forming a new illness identity. Children adopt coping strategies such as building credible explanations for their illness.

CONCLUSIONS: Physical, social, emotional and self-dimensions of life should be included when treating and measuring outcomes from healthcare in paediatric CFS/ME. There is a need for greater recognition and diagnosis of childhood CFS/ME, specialist advice on activity management and improved communication between health and education providers to help children cope with their condition.

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: Parslow RM, Harris S, Broughton J, Alattas A, Crawley E, Haywood K, Shaw A. Children’s experiences of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): a systematic review and meta-ethnography of qualitative studies. BMJ Open. 2017 Jan 13;7(1):e012633. doi: 10.1136/bmjopen-2016-012633. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5253584/ (Full article)

 

Chronic Fatigue Syndrome and Chronic Widespread Pain in Adolescence: Population Birth Cohort Study

Abstract:

Although many studies have investigated the overlap between pain phenotypes and chronic fatigue syndrome (CFS) in adults, little is known about the relationship between these conditions in adolescents. The study’s aim was therefore to identify whether a relationship exists between chronic widespread pain (CWP) and CFS in adolescents and investigate whether the two share common associations with a set of covariates.

A questionnaire was administered to offspring of the Avon Longitudinal Study of Parents and Children (ALSPAC) at age 17, asking about site, duration, and pain intensity, from which participants with CWP were identified. At the same research clinic, a computer-based Revised Clinical Interview Schedule was filled out, from which a classification of CFS was obtained. The relationship between selected covariates and CFS and CWP was investigated using a variety of logistic, ordinal logistic, and multinomial regressions.

We identified 3,214 adolescents with complete data for all outcomes and covariates. There were 82 (2.6%) individuals classified as CFS and 145 (4.5%) as CWP. A classification of CFS resulted in an increased likelihood of having CWP (odds ratio = 3.87; 95% confidence interval, 2.05-7.31). Female adolescents were approximately twice as likely to have CFS or CWP, with multinomial regression revealing a greater sex effect for CWP compared with CFS.

Those with exclusive CFS were more likely to report higher levels of pain and greater effect of pain compared with those without CFS, although associations attenuated to the null after adjustment for covariates, which did not occur in those with exclusive CWP. Multinomial regression revealed that relative to having neither CFS nor CWP, a 1-unit increase in the depression and anxiety scales increased the risk of having exclusive CFS and, to a greater extent, the risk of having comorbid CFS and CWP, but not exclusive CWP, which was only related to anxiety.

PERSPECTIVE: In this cohort, 14.6% of adolescents with CFS have comorbid CWP. The likely greater proportion of more mild cases observed in this epidemiological study means that prevalence of overlap may be underestimated compared with those attending specialist services. Clinicians should be aware of the overlap between the 2 conditions and carefully consider treatment options offered.

Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

 

Source: Norris T, Deere K, Tobias JH, Crawley E. Chronic Fatigue Syndrome and Chronic Widespread Pain in Adolescence: Population Birth Cohort Study. J Pain. 2016 Nov 12. pii: S1526-5900(16)30308-X. doi: 10.1016/j.jpain.2016.10.016. [Epub ahead of print] http://www.jpain.org/article/S1526-5900(16)30308-X/fulltext (Full article)

 

Psychological wellbeing and quality-of-life among siblings of paediatric CFS/ME patients: A mixed-methods study

Abstract:

Chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) is a disabling condition known to have a negative impact on all aspects of a child’s life. However, little is understood about the impact of CFS/ME on siblings.

A total of 34 siblings completed questionnaires measuring depression (Hospital Anxiety and Depression Scale (HADS)), anxiety (HADS and Spence Children’s Anxiety Scale (SCAS)) and European Quality-of-life-Youth (EQ-5D-Y). These scores were compared with scores from normative samples. Siblings had higher levels of anxiety on the SCAS than adolescents of the same age recruited from a normative sample; however, depression and quality-of-life were similar. Interviews were undertaken with nine siblings of children with CFS/ME who returned questionnaires. Interview data were analysed using a framework approach to thematic analysis.

Siblings identified restrictions on family life, ‘not knowing’ and lack of communication as negative impacts on their family, and change of role/focus, emotional reactions and social stigma as negative impacts on themselves. They also described positive communication, social support and extra activities as protective factors.

Paediatric services should be aware of the impact of CFS/ME on the siblings of children with CFS/ME, understand the importance of assessing paediatric CFS/ME patients within the context of their family and consider providing information for siblings about CFS/ME.

© The Author(s) 2015.

 

Source: Velleman S, Collin SM, Beasant L, Crawley E. Psychological wellbeing and quality-of-life among siblings of paediatric CFS/ME patients: A mixed-methods study. Clin Child Psychol Psychiatry. 2016 Oct;21(4):618-633. Epub 2015 Sep 22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5094299/ (Full article)

 

‘It’s personal to me’: A qualitative study of depression in young people with CFS/ME

Abstract:

BACKGROUND: Paediatric chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) has a prevalence of 0.4-2.4% and is defined as ‘generalised disabling fatigue persisting after routine tests and investigations have failed to identify an obvious underlying cause’. One-third of young people with CFS/ME have probable depression. Little is known about why depression develops, the relationship between depression and CFS/ME, or what treatment might be helpful.

METHODS: We conducted nine semi-structured interviews with young people with CFS/ME (aged 13-17 years, 8/9 female) and probable depression, covering perceived causes of depression, the relationship between CFS/ME and depression, and treatment strategies.

RESULTS: Most thought CFS/ME caused depression. Many discussed a cyclical relationship: low mood made CFS/ME worse. A sense of loss was common. CFS/ME restricted activities participants valued and changed systemic structures, causing depression. There was no single helpful treatment approach. Individualised approaches using combinations of cognitive behavioural therapy (CBT), medication, activity management and other strategies were described.

CONCLUSION: This study suggests that depression may be secondary to CFS/ME in young people because of the impact of CFS/ME on quality of life. Clinicians treating young people with CFS/ME need to consider strategies to prevent development of depression, and research is needed into approaches that are effective in treating CFS/ME with co-morbid depression.

© The Author(s) 2016.

 

Source: Taylor AK, Loades M, Brigden AL, Collin SM, Crawley E. ‘It’s personal to me’: A qualitative study of depression in young people with CFS/ME. Clin Child Psychol Psychiatry. 2016 Oct 14. pii: 1359104516672507. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/27742756