New evidence that ME, CFS in children could be caused by a virus

A University of Dundee study on children has found further evidence that ME, or Chronic Fatigue Syndrome, could be caused by a virus. 

Shortlink: http://wp.me/p5foE-36c 

Additional reporting will be added to the top 

Media Coverage

Scottish Daily Record  |  Lachlan Mackinnon  | 8 September 2010

Chronic fatigue syndrome may be caused by virus, Scottish researchers find

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Radio Scotland  |  Jane Colby  |  7 September 2010

Pick up around 11.00 in from start
http://www.bbc.co.uk/iplayer/episode/b00tmfzs/Scotland_Live_07_09_2010/

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WebMD Health News  |  Peter Russell  |  7 September 2010

Health news

Study links ME to virus
A small-scale investigation has found evidence that the debilitating illness could be caused by a virus

Reviewed by Dr Keith David Barnard

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BBC News 7th September 2010: “Study shows ME/CFS ‘virus link’ found in children”
http://www.bbc.co.uk/news/uk-scotland-tayside-central-11204884  [Extracts already posted below]

BBC Health TV Report 7th September 2010: ME ‘could be caused by a virus’
http://www.bbc.co.uk/news/health-11209605

BBC Radio 4 7th September 2010: Item on Today Programme
http://news.bbc.co.uk/today/hi/default.stm

UKwired 7th Septemebr 2010: Study shows ME/CFS ‘virus link’ found in children
http://www.ukwirednews.com/news.php/87946-Study-shows-ME-CFS-virus-link-found-in-children

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ME Research UK

http://www.meresearch.org.uk/research/projects/children.html

Abstract and commentary also available on MERUK site

Comment by ME Research UK [note this commentary is heavy with links, please refer to site for links]

Illness in youngsters has a particular poignancy; the transformation of a bright, active child into one who is unable to go to school or play with friends is something that touches us all.

Estimates of the numbers of children affected by ME/CFS vary, but with prevalence figures of 60 to 70 cases per 100,000, it is likely that around 9,000 people under the age of 16 in the UK have this diagnosis. As the report to the Chief Medical Officer in 2002 made clear, this illness “represents a substantial problem in the young” and “potentially threatens physical, emotional, and intellectual development of children and young people, and can disrupt education and social and family life, at a particularly vulnerable time of life”.

The results of a previous study on quality of life in children with ME/CFS were recently published in Pediatrics by Dr Gwen Kennedy at the Vascular and Inflammatory Diseases Research Unit in the University of Dundee. In parallel with this work, Dr Kennedy and her colleague Dr Faisel Khan have been investigating biochemical and vascular abnormalities in children with the disease, and their results have just appeared in the US journal Archives of Pediatrics and Adolescent Medicine.

The Dundee group had previously reported a number of biochemical and vascular abnormalities in adults with ME/CFS. These mainly involve the immune and cardiovascular systems, and include an increase in the programmed death (apoptosis) of white blood cells, raised levels of oxidative stress which can damage blood vessels and other organs, increased markers of inflammation, and abnormalities in blood vessel function. All of these are potentially associated with a future risk for cardiovascular problems such as heart disease and stroke.

Drs Kennedy and Khan wanted to investigate whether these abnormalities were also present in children with ME/CFS, given the potential long-term consequences for cardiovascular risk. Risk factors such as high cholesterol and increased blood pressure, which are usually associated with adult diseases, have also been found in children and can progress into adulthood as hypercholesterolaemia and hypertension, so it is important that risks are identified as early in life as possible.

Twenty-five children with ME/CFS (all between the ages of 10 and 18 years) and 23 healthy children matched for age, gender and stage of puberty were recruited from throughout the UK. The diagnosis of ME/CFS had been made according to a revised version of the CDC-1994 case definition, and was confirmed by the researchers from a clinical examination.

A blood sample was taken from each child (using an anaesthetic cream to minimise their discomfort), and this was then subjected to a battery of tests in Dr Kennedy’s laboratory. The child’s blood pressure was measured, and then the pulse at their wrist was detected using a special pen-like probe applied lightly to the skin. This records the fluctuations in pressure as each pulse travels along the artery, and is exactly what you feel with your finger when you take your own pulse. This recording of the pulse is then analysed on a computer to give information on how flexible the artery is, which gives an indication of its health and function.

Overall, compared with healthy control children, the young people with ME/CFS had:

1.Higher levels of oxidative stress, manifested as elevated levels of isoprostanes
2.Reduced levels of vitamins C and E
3.A greater percentage of white blood cells undergoing apoptosis
4.A trend towards increased arterial stiffness, although this was not statistically significant

As Dr Kennedy points out, the increased oxidative stress may be due to a deficiency of antioxidants in the diet (such as vitamins C and E, found to be reduced in this study). However, she feels it is more likely to have been caused by white blood cells releasing an excessive amount of highly reactive free radicals, possibly from exercising muscle. This would tie in with the finding of increased white cell apoptosis, and Dr Kennedy has previously reported increased oxidative stress following exercise in adults with ME/CFS. She does emphasise, however, that more studies, perhaps including an assessment of diet, are needed to determine this mechanism.

The increased apoptosis (or programmed cell death) may be caused by a number of factors, including a persistent viral infection or toxic agent, or an abnormal immunological response. This finding is particularly intriguing given that many patients, including most children in this study, report that their disease started following a viral infection of some kind. At present, however, there is insufficient evidence to make a causal link between infection and increased apoptosis, though the finding is tantalising.

Although there were no other statistically significant changes in the children with ME/CFS, there was a clustering of markers such as arterial stiffness and cholesterol that showed small changes which may indicate the possibility of future cardiovascular risk. This type of clustering has been shown before in healthy children and in young people with diabetes. Although it should be stressed that children with ME/CFS are at no immediate risk of developing cardiovascular problems, we might expect these changes to become greater (closer to the adult pattern) as the children grow older and have been ill for longer.

Dr Kennedy and her team conclude their report by saying that the findings show that many children with ME/CFS “have an underlying, detectable abnormality in the behaviour of their immune cells, consistent with an activated inflammatory process”, and provide evidence of “a persistent or reactivating viral infection triggering apoptosis of white blood cells with an increased production of free radicals”.

It is important that these abnormalities have now been recognised in children with ME/CFS. To date, aside from symptomatic treatments, no specific therapy is available for children or adults with ME/CFS. Based on these and other biomedical findings in the disease, putative therapies could perhaps include both pharmacological and non-pharmacological strategies (to treat dysautonomia, for example), or antioxidant or antiviral interventions.

Co-funders of the study
ME Research UK funds biomedical research into ME/CFS with the aim of finding the cause of the illness and developing effective treatments. It funds the work of a growing number of scientists in the UK and worldwide, and to date has invested over £600,000 to support biomedical research. We are particularly grateful to the ME organisations which have provided larger donations to help us fund specific projects, details of which including some of the resulting scientific papers can be found on our research pages.

The Young ME Sufferers (Tymes) Trust, one of the major co-funders of the study at the University of Dundee, is the longest established national UK service for children and young people with ME and their families. A well-respected national charity, which recently won the Queen’s Award for Voluntary Service, its entire professional team give their time free of charge. It runs an Advice Line, provides access to ME experts for doctors, teachers and social workers, and produces a magazine for children, families and professionals. The Trust played a major role in producing the children’s section of the Department of Health Report on CFS/ME (2002). It promotes interactive virtual education for children with ME, and provides the Tymes Trustcard — a pass card for children in school, endorsed by the Association of School and College Leaders. More information on the Tymes Trust and its work can be obtained at its website.

Search ME, based in Rosyth, Fife, was founded in 2002. Its aims are to improve the lives of people with ME and to provide them with a voice on the Cross Party Group for ME in the Scottish Parliament. The charity has raised the bulk of its donations through organising Rock and Pop Concerts. Search ME became an early supporter of the study at the University of Dundee and helped fund the work carried out there. Members of the charity are very proud of the work carried out at Dundee and of all the people involved. Further information can be found on their website.

Tenovus Scotland has funded world class cancer research across the UK for over 40 years, providing a vital link by funding pilot studies which can attract further support from major funding bodies such as the Wellcome Trust, the MRC, Cancer Research UK, the British Heart Foundation and many others. Further information can be found at its website.

 

Vol. 164 No. 9, September 2010  |  Journal of Archives of  Pediatriatrics & Adolescent Medicine 

Biochemical and Vascular Aspects of Pediatric Chronic Fatigue Syndrome
Gwen Kennedy; Faisel Khan; Alexander Hill; Christine Underwood; Jill J. F. Belch
Arch Pediatr Adolesc Med. 2010;164(9):817-823.
ABSTRACT | FULL TEXT | PDF  [Free Abstract, Payment required for full paper]

http://archpedi.ama-assn.org/cgi/content/abstract/164/9/817 

Abstract 

Biochemical and Vascular Aspects of Pediatric Chronic Fatigue Syndrome
Gwen Kennedy, PhD; Faisel Khan, PhD; Alexander Hill, PhD; Christine Underwood, MBBS; Jill J. F. Belch, MD 

Arch Pediatr Adolesc Med. 2010;164(9):817-823. doi:10.1001/archpediatrics.2010.157   

Objective To evaluate the biochemical and vascular aspects of pediatric chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). 

Design Cross-sectional clinical study. 

Setting Tayside, Scotland, United Kingdom. 

Participants Twenty-five children with CFS/ME and 23 healthy children recruited from throughout the United Kingdom. 

Interventions Participants underwent a full clinical examination to establish a diagnosis of CFS/ME and were asked to describe and score their CFS/ME symptoms. Biochemical markers were measured. Arterial wave reflection was estimated to assess systemic arterial stiffness. 

Main Outcome Measures Markers of oxidative stress and free radicals, C-reactive protein level, white blood cell apoptosis, and arterial wave reflection. 

Results Children with CFS/ME had increased oxidative stress compared with control individuals (isoprostanes: 252.30 vs 215.60 pg/mL, P = .007; vitamin C, mean [SD]: 0.84 [0.26] vs 1.15 [0.28] mg/dL, P < .001; vitamin E, 8.72 [2.39] vs 10.94 [3.46] µg/mL, P = .01) and increased white blood cell apoptosis (neutrophils: 53.7% vs 35.7%, P = .005; lymphocytes: 40.1% vs 24.6%, P = .009). Arterial stiffness variables did not differ significantly between groups (mean augmentation index, –0.57% vs –0.47%, P = .09); however, the derived variables significantly correlated with total (r = 0.543, P = .02) and low-density lipoprotein (r = 0.631, P = .004) cholesterol in patients with CFS/ME but not in controls. 

Conclusions Biomedical anomalies seen in adults with CFS/ME—increased oxidative stress and increased white blood cell apoptosis—can also be observed in children with clinically diagnosed CFS/ME compared with matched controls. Unlike in their adult counterparts, however, arterial stiffness remained within the reference range in these pediatric patients. 

Author Affiliations: Vascular and Inflammatory Diseases Research Unit, The Institute of Cardiovascular Research, Centre for Cardiovascular and Lung Biology, Division of Medical Sciences, Ninewells Hospital and Medical School, Dundee, Scotland, United Kingdom. 

 

Additional papers and Editorial in current edition: 

http://archpedi.ama-assn.org/ 

Adolescent Chronic Fatigue Syndrome: A Follow-up Study
Stefan M. van Geelen; Rob J. Bakker; Wietse Kuis; Elise M. van de Putte
Arch Pediatr Adolesc Med. 2010;164(9):810-814.
ABSTRACT | FULL TEXT | PDF  [Free Abstract, Payment required for full paper]

Abstract

Adolescent Chronic Fatigue Syndrome
A Follow-up Study

Stefan M. van Geelen, MPhil; Rob J. Bakker, MD; Wietse Kuis, PhD, MD; Elise M. van de Putte, PhD, MD

Arch Pediatr Adolesc Med. 2010;164(9):810-814. doi:10.1001/archpediatrics.2010.145

Adolescent Chronic Fatigue Syndrome
A Follow-up Study

Stefan M. van Geelen, MPhil; Rob J. Bakker, MD; Wietse Kuis, PhD, MD; Elise M. van de Putte, PhD, MD

Arch Pediatr Adolesc Med. 2010;164(9):810-814. doi:10.1001/archpediatrics.2010.145

Objective To describe the symptomatic and educational long-term outcomes, health care use, and risk factors of nonrecovery in adolescent chronic fatigue syndrome (CFS).

Design Follow-up study.

Setting Academic pediatric hospital.

Participants Sixty adolescents with CFS.

Interventions Regular care.

Outcome Measures The Checklist Individual Strength, Child Health Questionnaire, and a general questionnaire regarding further symptoms, school attendance, work attendance, and treatment.

Results Complete measurements were returned for 54 adolescents (90%). At initial assessment, their mean (SD) age was 16.0 (1.5) years and 20.4% were male. The mean follow-up duration was 2.2 years. At follow-up, the mean (SD) age was 18.2 (1.5) years; 28 adolescents (51.9%) had nearly complete improvement of symptoms but 26 (48.1%) did not experience improvement. Adolescents who attended school (n = 41) had missed an average of 33% of classes during the last month. The rest (n = 13) had worked an average of 38.7% of a full-time job during the last month. A total of 66.7% of subjects were treated by a physiotherapist, 38.9% were clinically treated in rehabilitation, 48.1% had received psychological support, and 53.7% had used alternative treatment.

Conclusions About half of the adolescents had recovered from CFS at follow-up. The other half was still severely fatigued and physically impaired. Health care use had been high, and school and work attendance were low. Older age at inclusion was a risk factor, and pain, poor mental health, self-esteem, and general health perception at outcome were associated with an unfavorable outcome. Future research should focus on customizing existing treatment and studying additional treatment options.

Author Affiliations: Department of Pediatrics, University Medical Center Utrecht, Utrecht, the Netherlands.

http://archpedi.ama-assn.org/ 

http://archpedi.ama-assn.org/cgi/content/abstract/164/9/803

Postinfectious Fatigue in Adolescents and Physical Activity
Yue Huang, PhD; Ben Z. Katz, MD; Cynthia Mears, DO; Gary W. Kielhofner, DrPH; Renée Taylor, PhD

Arch Pediatr Adolesc Med. 2010;164(9):803-809.doi:10.1001/archpediatrics.2010.144

ABSTRACT | FULL TEXT | PDF | FREE APAM JOURNAL CLUB SLIDES  [All free access]

Abstract

Objective To compare adolescents who do and do not recover from acute infectious mononucleosis in terms of fatigue severity and activity levels before, during, and in the 2 years following infection.

Design Prospective case-control study.

Setting The baseline and 12- and 24-month evaluations occurred in the subjects’ homes. The 6-month outpatient visit occurred at Children’s Memorial Hospital in Chicago, Illinois.

Participants  Three hundred one adolescents (aged 12-18 years) with acute infectious mononucleosis.

Main Exposures All participants were evaluated at baseline (during active infection). Six months following infection, 39 of them met criteria for chronic fatigue syndrome. These subjects were matched by sex and Tanner stage to 39 randomly selected screened-negative subjects. Both groups were reevaluated at 12- and 24-month follow-ups.

Outcome Measures Scores from the Fatigue Severity Scale and the Modifiable Activity Questionnaire.

Results  For both groups, physical activity levels declined and sleep increased as a result of having mononucleosis. Compared with their matched controls, adolescents with chronic fatigue syndrome reported significantly higher levels of fatigue at all points and spent significantly more time sleeping during the day 6 and 12 months following infection. The 2 groups did not differ significantly in terms of physical activity levels before, during, or after infection. There was a consistent trend for decreased physical activity in the chronic fatigue syndrome group.

Conclusions Adolescents with chronic fatigue syndrome appear to be pushing themselves in an attempt to maintain similar activity levels as their peers, but paying for it in terms of fatigue severity and an increased need for sleep, particularly during the day.

Author Affiliations: Department of Occupational Therapy, College of Applied Health Sciences, University of Illinois at Chicago (Drs Huang, Kielhofner, and Taylor); and Department of Pediatrics, Northwestern University Feinberg School of Medicine and Children’s Memorial Hospital (Drs Katz and Mears), Chicago, Illinois.

Editorial Vol. 164 No. 9, September 2010

Full Text

Chronic Fatigue Syndrome in Adolescence: Where to From Here?
Vollmer-Conna
Arch Pediatr Adolesc Med.2010; 164: 880-881. 

Extract Editorial [First 150 words]   

Chronic Fatigue Syndrome in Adolescence: Where to From Here?
Extract | Full Text
http://archpedi.ama-assn.org/cgi/content/short/164/9/880 

Ute Vollmer-Conna, PhD 

Arch Pediatr Adolesc Med. 2010;164(9):880-881. doi:10.1001/archpediatrics.2010.149 

Since this article does not have an abstract, we have provided the first 150 words of the full text and any section headings. 

Chronic fatigue syndrome (CFS) is a disabling disorder that poses a significant personal and economic burden for patients, their families, and the community. It is increasingly recognized that CFS is prevalent in children and adolescents.1-2 In the young, the disability associated with CFS can be exacerbated by the effect of the illness on emotional and social aspects of development including social learning, autonomy, a sense of self, a healthy body image, relationships, sexuality, and academic development.3 

After decades of hypothesis-driven research, the etiology and pathophysiology of CFS remains obscure, and curative therapies are not available. What have we learned from this poor outcome? For one, many now agree that the diagnostic label of CFS encompasses a heterogeneous group. This is supported by evidence from several studies (including one pediatric study2) showing that 3 to 5 distinct subclasses can be delineated from large, cross-sectional samples of individuals . . . [Full Text of this Article]  [Payment required] 

AUTHOR INFORMATION 

School of Psychiatry, University of New South Wales, Sydney, Australia 

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BBC  |  BBC Scotland Health Correspondent  |  7 September 2010  

Study shows ME/CFS ‘virus link’ found in children 

By Eleanor Bradford 

A study on children has found further evidence that ME, or Chronic Fatigue Syndrome, could be caused by a virus. 

Scientists at the University of Dundee study found abnormalities in the white blood cells of children with ME/CFS, suggesting they had been fighting off infection… 

…In the study, funded by ME Research UK and The Young ME Sufferers (Tymes) Trust, 25 children aged between seven and 14 with ME/CFS were assessed, along with 23 children of a similar age in a control group. 

The report, published in the Archives of Paediatrics and Adolescent Medicine, said abnormalities were found in the blood of all the children with ME/CFS. 

The results were similar to those previously identified in adults with the condition. 

Samples taken from youngsters with ME/CFS contained higher than normal levels of free radicals – molecules that can damage cells, tissues and organs… 

Read full article here 

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From Jane Colby  |  The Young ME Sufferers Trust  |  7 September 2010 

MAY BE REPOSTED 

There should be quite a bit of coverage today of the new research in children, which The Young ME Sufferers Trust co-funded. I’ve done Radio 5 Live and BBC Northern Ireland radio so far.  BBC Wales coming up. Prof Jill Belch has done interviews about the science for a number of channels. 

I wasn’t able to say anything about this yesterday due to reporting restrictions. Will send out an Alert about the research later today. 

Jane Colby
Executive Director
The Young ME Sufferers Trust
PO Box 4347
Stock Ingatestone
Essex CM4 9TE
Tel 0845 003 9002
www.tymestrust.org

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