Childhood chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome in childhood and adolescents(CCFS) is a complex and debilitation with severe morbidity and confusion. It is common condition with up to 3-5% of children and adolescents showing strange fatigue and confusion for more than 30 days. In this condition, four major symptoms are important: sleep disorders, easy fatigability, disturbed learning and memorization and immunological problems. Routine laboratory studies are similar to adult CFS, although abnormalities can be seen on serum pyruvic acid level, OGTT pattern, deep body temperature rhythm, hormonal secretion rhythm, and cerebral blood flow. For a diagnosis of CCFS, a research group supported by Japanese ministry of health, labor and welfare developed CCFS case definition on 2004. Treatment focused to correct disrupted circadian rhythms and supply of energy.

 

Source: Miike T. Childhood chronic fatigue syndrome. Nihon Rinsho. 2007 Jun;65(6):1099-104. [Article in Japanese] https://www.ncbi.nlm.nih.gov/pubmed/17561704

 

Longitudinal analysis of pro- and anti-inflammatory cytokine production in severely fatigued adolescents

Abstract:

In the adolescent population, fatigue is associated with somatic complaints, unrefreshing sleep, cognitive disturbances and symptoms of depression and anxiety. This pattern of symptoms resembles the one described in chronic fatigue syndrome (CFS). Since immunological alterations have been reported in CFS patients, we wondered whether also severely fatigued girls from a healthy population would show comparable alterations in psychological and immunological parameters. We tested this hypothesis in a longitudinal design, allowing a reliable assessment of the participants’ characteristic immune status. Groups of severely fatigued (N=67) and non-fatigued (N=61) participants were selected. Severely fatigued girls reported more depressive symptoms, anxiety, reduced sleep quality, and somatic and CFS-related symptoms than non-fatigued participants across three measurements during one year (T1: spring, T2: autumn, T3: spring). In contrast, no group differences in mitogen-induced cytokine production or T-cell proliferation in vitro or in leukocyte subset counts were observed. Although absolute cytokine production and cell counts were affected by seasonal variation, the within-subject values, relatively to the rest of the participants, were fairly stable. Data from a small group of CFS patients (N=11) showed similarities in self-reported complaints between CFS patients and fatigued participants. Interestingly, CFS patients showed a distinct immune profile when compared to the severely fatigued or non-fatigued participants, i.e. increased levels of anti-inflammatory cytokines (IL-10, decreased IFN-gamma/IL-10 ratio) and reduced levels of pro-inflammatory cytokines (IL-6, TNF-alpha) over all three time points analyzed. These results show that, although overlap in symptomatology between the general population and patients with CFS was observed, only CFS patients show a skewing of the cytokine balance towards an anti-inflammatory profile.

 

Source: ter Wolbeek M, van Doornen LJ, Kavelaars A, van de Putte EM, Schedlowski M, Heijnen CJ. Longitudinal analysis of pro- and anti-inflammatory cytokine production in severely fatigued adolescents.Brain Behav Immun. 2007 Nov;21(8):1063-74. Epub 2007 Jun 1. https://www.ncbi.nlm.nih.gov/pubmed/17544255

Treatment of chronic fatigue and orthostatic intolerance with propranolol

Abstract:

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.

 

Source: Wyller VB, Thaulow E, Amlie JP. Treatment of chronic fatigue and orthostatic intolerance with propranolol. J Pediatr. 2007 Jun;150(6):654-5. https://www.ncbi.nlm.nih.gov/pubmed/17517256

 

Usefulness of an abnormal cardiovascular response during low-grade head-up tilt-test for discriminating adolescents with chronic fatigue from healthy controls

Abstract:

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 degrees 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 degrees 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.

 

Source: Wyller VB, Due R, Saul JP, Amlie JP, Thaulow E. Usefulness of an abnormal cardiovascular response during low-grade head-up tilt-test for discriminating adolescents with chronic fatigue from healthy controls. Am J Cardiol. 2007 Apr 1;99(7):997-1001. Epub 2007 Feb 16. https://www.ncbi.nlm.nih.gov/pubmed/17398200

 

Exercise testing in children and adolescents with chronic fatigue syndrome

Abstract:

The objective of this study was to evaluate exercise capacity in children and adolescents diagnosed with Chronic Fatigue Syndrome (CFS). We examined 20 patients (12 girls and 8 boys; mean age 14.9 +/- 3.7 years) diagnosed with CFS.

Exercise capacity was measured using a maximal exercise test on a bicycle ergometer and an expired gas analysis system. Fatigue was assessed using a questionnaire and a daily activity diary was used to describe activities for three days. Z-scores were calculated using age- and sex-matched reference values. Z-scores in children and adolescents with CFS were – 0.33 +/- 1.0 (p = 0.17) for peak oxygen uptake, – 1.13 +/- 1.41 (p = 0.002) for relative peak oxygen uptake [ml/kg/min] and – 0.93 +/- 1.29 (p = 0.07) for maximal work load. Both heart rate and blood pressure at peak performance were significantly reduced compared to reference values.

Fatigue levels were significantly positively associated with age and negatively with blood pressure at peak exercise (p < 0.05). In conclusion maximum exercise testing was feasible in young people with CFS. Maximal exercise capacity was only reduced in a minority of the patients and was related to current physical activity levels.

 

Source: Takken T, Henneken T, van de Putte E, Helders P, Engelbert R. Exercise testing in children and adolescents with chronic fatigue syndrome. Int J Sports Med. 2007 Jul;28(7):580-4. Epub 2007 Mar 15. https://www.ncbi.nlm.nih.gov/pubmed/17357961

 

Incidence, prognosis, and risk factors for fatigue and chronic fatigue syndrome in adolescents: a prospective community study

Abstract:

OBJECTIVE: The objective of this study was to describe the incidence, prevalence, risk factors, and prognosis of fatigue, chronic fatigue, and chronic fatigue syndrome in 11- to 15-year-olds.

METHODS: A random general population sample (n = 842) of British adolescents and their parents were assessed at baseline and 4 to 6 months later. The main outcomes were fatigue, chronic fatigue, and chronic fatigue syndrome, operationally defined.

RESULTS: The incidence over 4 to 6 months was 30.3% for fatigue, 1.1% for chronic fatigue, and 0.5% for chronic fatigue syndrome. The point prevalence was 34.1% and 38.1% for fatigue, 0.4% and 1.1% for chronic fatigue, and 0.1% and 0.5% for chronic fatigue syndrome at time 1 and time 2, respectively. Of participants who were fatigued at time 1, 53% remained fatigued at time 2. The 3 cases of chronic fatigue and 1 case of chronic fatigue syndrome at time 1 had recovered by time 2. Higher risk for development of chronic fatigue at time 2 was associated with time 1 anxiety or depression, conduct disorder, and maternal distress; in multivariate analysis, baseline anxiety or depression remained a significant predictor of chronic fatigue. Increased risk for development of fatigue at time 2 was associated with time 1 anxiety or depression, conduct disorder, and older age; in multivariate analyses, these factors and female gender all were significant predictors of fatigue.

CONCLUSIONS: The incidence rates for chronic fatigue and chronic fatigue syndrome in this adolescent sample were relatively high, but the prognosis for these conditions was good. This prospective study provides evidence for an association between emotional/behavioral problems and subsequent onset of fatigue/chronic fatigue.

 

Source: Rimes KA, Goodman R, Hotopf M, Wessely S, Meltzer H, Chalder T. Incidence, prognosis, and risk factors for fatigue and chronic fatigue syndrome in adolescents: a prospective community study. Pediatrics. 2007 Mar;119(3):e603-9. https://www.ncbi.nlm.nih.gov/pubmed/17332180

 

Special problems of children with myalgic encephalomyelitis/chronic fatigue syndrome and the enteroviral link

Abstract:

Since 1997, it has been known that myalgic encephalomyelitis/chronic fatigue syndrome constitutes the biggest cause of long-term sickness leading to absence from school, in both staff and pupils. The scale of the problem in children is substantial, and the pattern of illness in schools suggests a prominent role for viral infection–for example, the clustering of cases.

The Dowsett-Colby study of 1997, researching long-term sickness, reported on a school roll of 333,024 pupils and 27,327 staff, and found a prevalence of long-term sickness in 70 of 100,000 pupils and 500 of 100,000 staff; 39% of cases were in clusters of three or more. The peak age was 14-16 years. The illness is known to be potentially severe and chronic. In addition, the Tymes Trust has reported that many affected children struggle for recognition of their needs, and are bullied by medical and educational professionals.

Children should have time to recover sufficiently before returning to school; sustainable, energy-efficient and often home-based education is important here to fulfill legal obligations. Research is needed on viruses that trigger childhood myalgic encephalomyelitis–for example, enteroviruses–and on the neurocognitive defects caused by myalgic encephalomyelitis. We should recognise the value of previous biological research and records of outbreaks, and I recommend that myalgic encephalomyelitis be made notifiable owing to the encephalitic nature of the effects commonly reported in this illness.

 

Source: Colby J. Special problems of children with myalgic encephalomyelitis/chronic fatigue syndrome and the enteroviral link. J Clin Pathol. 2007 Feb;60(2):125-8. Epub 2006 Aug 25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1860612/ (Full article)

 

How fatigue is related to other somatic symptoms

Abstract:

AIMS: To assess the relation between fatigue and somatic symptoms in healthy adolescents and adolescents with chronic fatigue syndrome/myalgic encephalopathy (CFS/ME).

METHODS: Seventy two adolescents with CFS were compared within a cross-sectional study design with 167 healthy controls. Fatigue and somatic complaints were measured using self-report questionnaires, respectively the subscale subjective fatigue of the Checklist Individual Strength (CIS-20) and the Children’s Somatization Inventory.

RESULTS: Healthy adolescents reported the same somatic symptoms as adolescents with CFS/ME, but with a lower score of severity. The top 10 somatic complaints were the same: low energy, headache, heaviness in arms/legs, dizziness, sore muscles, hot/cold spells, weakness in body parts, pain in joints, nausea/upset stomach, back pain. There was a clear positive relation between log somatic symptoms and fatigue (linear regression coefficient: 0.041 points log somatic complaints per score point fatigue, 95% CI 0.033 to 0.049) which did not depend on disease status.

CONCLUSIONS: Results suggest a continuum with a gradual transition from fatigue with associated symptoms in healthy adolescents to the symptom complex of CFS/ME.

 

Source: van de Putte EM, Engelbert RH, Kuis W, Kimpen JL, Uiterwaal CS. How fatigue is related to other somatic symptoms. Arch Dis Child. 2006 Oct;91(10):824-7. Epub 2006 Jun 5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2066005/ (Full article)

 

Mirrored symptoms in mother and child with chronic fatigue syndrome

Abstract:

OBJECTIVE: Our aim with this study was to assess the relation between chronic fatigue syndrome in adolescents and fatigue and associated symptoms in their fathers and mothers, more specifically the presence of chronic fatigue syndrome-like symptoms and psychologic distress.

METHOD: In this cross-sectional study, 40 adolescents with chronic fatigue syndrome according to the Centers for Disease Control and Prevention criteria were compared with 36 healthy control subjects and their respective parents. Questionnaires regarding fatigue (Checklist Individual Strength), fatigue-associated symptoms, and psychopathology (Symptom Checklist-90) were applied to the children and their parents.

RESULTS: Psychologic distress in the mother corresponds with an adjusted odds ratio of 5.6 for the presence of CFS in the child. The presence of fatigue in the mother and dimensional assessment of fatigue with the Checklist Individual Strength revealed odds ratios of, respectively, 5.29 and 2.86 for the presence of chronic fatigue syndrome in the child. An increase of 1 SD of the hours spent by the working mother outside the home reduced the risk for chronic fatigue syndrome in their child with 61%. The fathers did not show any risk indicator for chronic fatigue syndrome in their child.

CONCLUSIONS: Mothers of adolescents with chronic fatigue syndrome exhibit fatigue and psychologic symptoms similar to their child in contrast with the fathers. The striking difference between the absent association in fathers and the evident association in mothers suggests that the shared symptom complex of mother and child is the result of an interplay between genetic vulnerability and environmental factors.

Comment in: Potential polygenic influences on chronic fatigue syndrome. [Pediatrics. 2006]

 

Source: van de Putte EM, van Doornen LJ, Engelbert RH, Kuis W, Kimpen JL, Uiterwaal CS. Mirrored symptoms in mother and child with chronic fatigue syndrome. Pediatrics. 2006 Jun;117(6):2074-9. https://www.ncbi.nlm.nih.gov/pubmed/16740850

 

The management of children with chronic fatigue syndrome-like illness in primary care: a cross-sectional study

Abstract:

BACKGROUND: Most studies on children with chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) have been undertaken in tertiary care and little is known about their management in primary care.

AIM: To describe the characteristics of patients aged 5-19 years with CFS-like illness in primary care and to examine how GPs investigate and manage patients.

DESIGN OF STUDY: Descriptive retrospective questionnaire study.

SETTING: Sixty-two UK GP practices in the MRC General Practice Research Framework (GPRF).

METHOD: One hundred and twenty-two practices were approached; 62 identified 116 patients consulting a GP with severe fatigue lasting over 3 months. Practice nurses and GPs completed questionnaires from medical notes and patients completed postal questionnaires.

RESULTS: Ninety-four patients were considered by a clinical panel, blind to diagnosis, to meet the Oxford CFS criteria with a fatigue duration of 3 months. Seventy-three per cent were girls, 94% white, mean age was 12.9 years and median illness duration 3.3 years. GPs had principal responsibility for 62%. A diagnosis of CFS/ME was made in 55%, 30% of these within 6 months. Fifty per cent had a moderate illness severity. Paediatric referrals were made in 82% and psychiatric referrals in 46% (median time of 2 and 13 months respectively). Advice given included setting activity goals, pacing, rest and graded exercise.

CONCLUSIONS: Patient characteristics are comparable to those reported in tertiary care, although fewer are severe cases. GPs have responsibility for the majority of patients, are diagnosing CFS/ME within a short time and applying a range of referral and advice strategies.

 

Source: Saidi G, Haines L. The management of children with chronic fatigue syndrome-like illness in primary care: a cross-sectional study. Br J Gen Pract. 2006 Jan;56(522):43-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1821410/ (Full article)