Measuring School Functioning in Students With Chronic Fatigue Syndrome: A Systematic Review

Abstract:

BACKGROUND: It is often surmised that school functioning is significantly impacted in chronic fatigue syndrome (CFS); however, how this phenomenon manifests itself has rarely been characterized.

METHODS: This systematic review synthesized and critically appraised methods, constructs, and instruments used to assess school functioning in students with CFS. Searches were conducted in electronic databases (CINAHL, MEDLINE, PubMed, ERIC, and PsycINFO) to locate empirical studies that measured school functioning in children and adolescents with CFS.

RESULTS: A total of 36 papers met the inclusion criteria. By far the most commonly reported school functioning construct measured related to school attendance. This was followed by academic functioning, achievement motivation, and educational services received. Little consistency was found in the measurement of these constructs across studies.

CONCLUSIONS: The current review revealed that the school experiences of children and adolescents with CFS have rarely been characterized beyond school absenteeism. Improvements in current assessment methods are required to comprehensively understand the impact of CFS on school functioning. Completely understanding the multiple aspects of school functioning will help to inform targeted strategies to optimize educational outcomes for students with CFS.

© 2018, American School Health Association.

Source: Tollit M, Politis J, Knight S. Measuring School Functioning in Students With Chronic Fatigue Syndrome: A Systematic Review. J Sch Health. 2018 Jan;88(1):74-89. doi: 10.1111/josh.12580. https://www.ncbi.nlm.nih.gov/pubmed/29224219

Transforming growth factor beta (TGF-β) in adolescent chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a prevalent and disabling condition among adolescent. The disease mechanisms are unknown. Previous studies have suggested elevated plasma levels of several cytokines, but a recent meta-analysis of 38 articles found that of 77 different cytokines measured in plasma, transforming growth factor beta (TGF-β) was the only one that was elevated in patients compared to controls in a sufficient number of articles. In the present study we therefore compared the plasma levels of the three TGF-β isoforms in adolescent CFS patients and healthy controls. In addition, the study explored associations between TGF-β levels, neuroendocrine markers, clinical markers and differentially expressed genes within the CFS group.

METHODS: CFS patients aged 12-18 years (n = 120) were recruited nation-wide to a single referral center as part of the NorCAPITAL project (ClinicalTrials ID: NCT01040429). A broad case definition of CFS was applied, requiring 3 months of unexplained, disabling chronic/relapsing fatigue of new onset, whereas no accompanying symptoms were necessary. Healthy controls (n = 68) were recruited from local schools. The three isoforms of TGF-β (TGF-β1, TGF-β2, TGF-β3) were assayed using multiplex technology. Neuroendocrine markers encompassed plasma and urine levels of catecholamines and cortisol, as well as heart rate variability indices. Clinical markers consisted of questionnaire scores for symptoms of post-exertional malaise, inflammation, fatigue, depression and trait anxiety, as well as activity recordings. Whole blood gene expression was assessed by RNA sequencing in a subgroup of patients (n = 29) and controls (n = 18).

RESULTS: Plasma levels of all three isoforms of TGF-β were equal in the CFS patients and the healthy controls. Subgrouping according to the Fukuda and Canada 2003 criteria of CFS did not reveal differential results. Within the CFS group, all isoforms of TGF-β were associated with plasma cortisol, urine norepinephrine and urine epinephrine, and this association pattern was related to fatigue score. Also, TGF-β3 was related to expression of the B cell annotated genes TNFRSF13C and CXCR5.

CONCLUSIONS: Plasma levels of all TGF-β isoforms were not altered in adolescent CFS. However, the TGF-β isoforms were associated with neuroendocrine markers, an association related to fatigue score. Furthermore, TGF-β3 might partly mediate an association between plasma cortisol and B cell gene expression. Trial registration Clinical Trials NCT01040429.

Source: Wyller VB, Nguyen CB, Ludviksen JA, Mollnes TE. Transforming growth factor beta (TGF-β) in adolescent chronic fatigue syndrome. J Transl Med. 2017 Dec 4;15(1):245. doi: 10.1186/s12967-017-1350-1. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-017-1350-1 (Full article)

The presence of co-morbid mental health problems in a cohort of adolescents with chronic fatigue syndrome

Abstract:

OBJECTIVE: To report on the prevalence of mental health disorders in adolescents with chronic fatigue syndrome(CFS) and to compare the diagnoses identified by a brief clinician-administered psychiatric interview with self-report screening questionnaires.

DESIGN: Cross-sectional study.

SETTING: Consecutive attenders to specialist CFS clinics in the United Kingdom.

PATIENTS: N = 52 adolescents, age 12-18 years with CFS.

MEASURES: Self-report questionnaires and a brief structured psychiatric diagnostic interview, administered by a researcher.

RESULTS: On the psychiatric interview, 34.6% met a diagnosis of major depressive disorder and 28.8% had an anxiety disorder. Of these, 15% had co-morbid anxiety and depression. Those with a depression diagnosis reported significantly greater interference on the school and social adjustment scale. They also scored significantly higher on trait anxiety, but not on state anxiety. There were no differences between those who had an anxiety disorder and those who did not on fatigue, disability or depressive symptoms. Children’s Depression Inventory (CDI) score was associated with a depression diagnosis on the psychiatric interview. However, neither the state nor the trait subscale of the State-Trait Anxiety Inventory (STAI) was associated with an anxiety diagnosis.

CONCLUSION: Clinicians should assess for the presence of anxiety and depressive disorders in adolescents with CFS using a validated psychiatric interview. Treatment should be flexible enough to accommodate fatigue, depression and anxiety. Transdiagnostic approaches may suit this purpose. Goals should include pleasurable activities particularly for those who are depressed.

Source: Loades ME, Rimes KA, Ali S, Lievesley K, Chalder T. The presence of co-morbid mental health problems in a cohort of adolescents with chronic fatigue syndrome. Clin Child Psychol Psychiatry. 2017 Oct 1:1359104517736357. doi: 10.1177/1359104517736357. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/29096528

Altered right anterior insular connectivity and loss of associated functions in adolescent chronic fatigue syndrome

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.

Source: Wortinger LA, Glenne Øie M, Endestad T, Bruun Wyller V. Altered right anterior insular connectivity and loss of associated functions in adolescent chronic fatigue syndrome. PLoS One. 2017 Sep 7;12(9):e0184325. doi: 10.1371/journal.pone.0184325. ECollection 2017. https://www.ncbi.nlm.nih.gov/pubmed/28880891

What treatments work for anxiety in children with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME)? Systematic review

Abstract:

OBJECTIVES: Anxiety is more prevalent in children with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) than in the general population. A systematic review was carried out to identify which treatment methods are most effective for children with CFS and anxiety.

DESIGN: Systematic review using search terms entered into the Cochrane library and Ovid to search the databases Medline, Embase and psychINFO.

PARTICIPANTS: Studies were selected if participants were <18 years old, diagnosed with CFS/ME (using US Centers for Disease Control and Prevention, the National Institute for Health and Care Excellence or Oxford criteria) and had a valid assessment of anxiety.

INTERVENTIONS: We included observational studies and randomised controlled trials.

COMPARISON: Any or none.

OUTCOMES: Change in anxiety diagnostic status and/or change in anxiety severity on a validated measure of anxiety from pretreatment to post-treatment.

RESULTS: The review identified nine papers from eight studies that met the inclusion criteria. None of the studies specifically targeted anxiety but six studies tested an intervention and measured anxiety as a secondary outcome. Of these studies, four used a cognitive behavioural therapy (CBT)-type approach to treat CFS/ME, one used a behavioural approach and one compared a drug treatment, gammaglobulin with a placebo. Three of the CBT-type studies described an improvement in anxiety as did the trial of gammaglobulin. As none of the studies stratified outcomes according to anxiety diagnostic status or severity, we were unable to determine whether anxiety changed prognosis or whether treatments were equally effective in those with comorbid anxiety compared with those without.

CONCLUSION: We do not know what treatment should be offered for children with both anxiety and CFS/ME. Further research is therefore required to answer this question.

TRIAL REGISTRATION NUMBER: This review was registered on Prospective Register of Systematic Review Protocols (PROSPERO) and the protocol is available from http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42016043488.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Source: Stoll SVE, Crawley E, Richards V, Lal N, Brigden A, Loades ME. What treatments work for anxiety in children with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME)? Systematic review. BMJ Open. 2017 Sep 5;7(9):e015481. doi: 10.1136/bmjopen-2016-015481. https://www.ncbi.nlm.nih.gov/pubmed/28877941

Sleep Quality in Adolescents With Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME)

Abstract:

STUDY OBJECTIVES: Little is known about the type and severity of sleep disturbances in the pediatric chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) population, compared with healthy adolescents. Using a range of objective and subjective measures, the aim of this study was to investigate sleep quality, the relationship between objective and subjective measures of sleep quality, and their associations with anxiety in adolescents with CFS/ME compared with healthy controls.

METHODS: Twenty-one adolescents with CFS/ME aged 13 to 18 years (mean age 15.57 ± 1.40), and 145 healthy adolescents aged 13 to 18 years (mean age 16.2 ± 1.00) wore actigraphy watches continuously for 2 weeks to collect a number of objective sleep variables. The Pittsburgh Sleep Quality Index was used to obtain a subjective measure of sleep quality. Anxiety was measured by the Spence Children’s Anxiety scale.

RESULTS: On average over the 2-week period, adolescents with CFS/ME were found to have (1) significantly longer objective sleep onset latency, time in bed, total sleep time, and a later rise time (all P< .005), and (2) significantly poorer subjective sleep quality (P< .001), compared with healthy adolescents. The CFS/ME patient group displayed higher levels of anxiety (P< .05), and in both groups, higher levels of anxiety were significantly related to poorer subjective sleep quality (P< .001).

CONCLUSIONS: This study provides objective and subjective evidence of sleep disturbance in adolescents with CFS/ME compared with healthy adolescent controls.

Source: Josev EK, Jackson ML, Bei B, Trinder J, Harvey A, Clarke C, Snodgrass K, Scheinberg A, Knight SJ. Sleep Quality in Adolescents With Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). J Clin Sleep Med. 2017 Jul 28. pii: jc-17-00047. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28760189

Cognition In Young People With ME/CFS

By Dr R. Vallings

One of the main reasons that young people with ME/CFS struggle with school is associated with cognition. Mental confusion, memory problems and difficulties with concentration are all described and may relate to abnormal neurological pathology, sluggish cerebral circulation and generalised fatigue.

Cognitive effort leads to fatigue in the same way that exercise will lead to muscle fatigue and post-exertional malaise. Headaches are frequently a prominent and persistent symptom, and they too will interfere with the student’s cognitive ability. There can be aggravation of symptoms associated with trying to focus and learn from a computer screen. Many will describe visual symptoms with blurring of text or eye fatigue.

A noisy classroom situation may not be conducive to mental effort, and students are often moving from room to room carrying heavy books, this all adding to the burden which the illness poses.

The young person may have problems with sleep, waking feeling unrefreshed, and again cognitive effort may thus be limited. He/she may arrive at school feeling already exhausted due to lack of restorative sleep and having to get up early, and then issues such as travelling, and the anxiety associated with what may lie ahead that day.

Too much exercise, standing for long periods, heat and poor nutrition can all compromise cognition. The student will be motivated to keep up with peers, and push him/herself mentally, physically and socially beyond the comfort zone, and suffer the consequences cognitively.

The teacher may have minimal understanding of the illness and its sequelae, and even the efforts of parents to explain can be brushed aside as “fussiness”. Attention span may be very short and the labels of laziness, attention deficit or learning disorders can be appended inappropriately.

Those with ME/CFS are usually highly motivated to achieve and will be disappointed by failures and lack of encouragement. Ridicule is often reported.

Parents and medical personnel need to communicate with the teachers to enhance their understanding of ME/CFS. To ensure that the student has the best possible opportunities to achieve appropriate education and a feeling of success. This will mean allowing the student to work at their own pace with adequate rest periods.

Management of the Cognitive Difficulties by the Primary Care Physician

Once a firm diagnosis has been made, the young person will feel relieved that there is an explanation for their problems, particularly those experienced by attempts to participate in regular schooling.

Parents need to be involved in this discussion, which should be addressed principally to the patient, so that he/she is also involved in decision making, and feels part of the team approach. Only the young person knows how they feel, and should be encouraged to verbalise their fears and needs. Teenagers will often need opportunity for discussion without a parent present.

Many young people fear getting behind their peers academically. There is a fear of never being able to catch up and consequently losing friends who move on. There needs to be encouragement to participate in ongoing education, however minimally, but without undue pressure.

This may mean limited attendance at school, or if available, correspondence education or home-schooling. The student can then work at their own pace. They should be encouraged to work for short periods with adequate rest periods, recognising when they are ready to rest. Some sort of structure for the days is helpful.

This may be difficult, if at home with parents needing to work. Particular difficulties need to be discussed, such as aggravation from computer screens, and difficulty focusing on written text (sometimes a ruler placed across the page can help with maintaining focus). Aggravating factors such as noise, bright lights, temperature and unpleasant odours may need to be adjusted. Snacks and drinks need to be available and allowed.

If well enough, some gentle outdoor exercise during breaks between cognitive effort should be suggested, and for younger children playing with siblings or friends after school or at weekends should be encouraged.

Focus on symptom control is important, and this may be achieved with attention to sleep difficulties and efficient pain management. Learning good relaxation strategies with the use of music, visualisation, and teaching self hypnosis all have a role. Having their own private space means that these things are more likely to be done, and rest will be undisturbed. Regular snacking with plenty of salt can help overcome symptoms associated with orthostatic intolerance.

Medication such as very low-dose tricyclics or melatonin to help with sleep may be useful. Some young people benefit from use of stimulants such as methylphenidate, but there is a risk of a false sense of wellbeing, leading to overdoing things. If the child is depressed or unduly anxious, this should be addressed and there should be opportunity to talk things through privately with a trusted professional, who has understanding of this illness.

The young person needs to understand the issues that can aggravate cognition, such as overdoing things mentally and physically, learning m to pace carefully, and avoiding situations which have proved detrimental. Planning time carefully and incorporating rewards can all help to ensure a better outcome.

Attention to achieving a regular body clock will mean that a good routine that fits in with family and school is possible. Standing for long periods, getting overheated or dehydrated and not eating adequately should all be avoided.

Above all there needs to be a sense of achievement, (however small), progress and normality if at all possible. Only the young person him/herself know how they really feel, and gaining a sense of control over this illness, rather than letting the illness control them entirely will achieve a growing sense of personal achievement and freedom from stress.

Reprinted with permission from Meeting Place – Autumn 2016 – Number 123: The official quarterly journal of ANZEMS Inc.

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