Chronic fatigue syndrome

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Chronic fatigue syndrome

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Title: Chronic fatigue syndrome

1
Chronic fatigue syndrome
2
An historical perspective

Explanations of illness through history
Illness as a metaphor
Science and technology
Scientific method

3
What is fatigue?
University of NSW

Fatigue as a symptom
everyday phenomenon
disease associated (infective, inflammatory,
neurological, mood disorder, )
physical and mental components
Fatigue as a sign
failure of force generation in the muscle
physiological or pathological
peripheral and central components

4
What is chronic fatigue syndrome?
Definition

Unexplained, persistent or relapsing fatigue,
that is
of new, definite onset
not due to exertion
not relieved by rest
associated with a substantial reduction in daily
activities

Four or more of
impaired short term memory or concentration
sore throat
tender lymph nodes
muscle pain
joint pain
headaches
unrefreshing sleep
post-exertional malaise

and
Fukuda K et al. Ann Intern Med 1994 121 953-9.
5
Chronic fatigue syndrome
Case-control studies
Neurophysiological fatigue - a failure of
force generation in the muscle
Lloyd A et al. Muscle strength, twitch
properties, voluntary activation and perceived
exertion in normal subjects and patients with
chronic fatigue syndrome Brain 1991 114 85-98.
6
CFS - the state of the art
Case-control studies

CFS is
prevalent (200/100,000)
disabling
costly

CFS is not
a muscle disorder
a psychiatric disorder
a retroviral infection
an auto-immune disorder
a sleep disorder
a metabolic disorder

7
Heterogeneity in the CFS label
Hickie I et al. Can the chronic fatigue syndrome
be defined by distinct clinical features?
Psychological Medicine 1995 25925-936
8
Dubbo Infection Outcomes Study
9
Dubbo study recruitment pathway
Onset of symptoms
Attend general practice
Diagnostic laboratory tests EBV, RRV, QF IgM
Contact by research team and enrolment
Not enroled
Self-report cohort
Main cohort

Interviews
Serological confirmation
Follow-up

Questionnaires
Follow-up

Limited data collection

10
Natural history of symptoms
Confirmed EBV (n68)
11
Post-infective fatigue (PIFS) outcomes
Also met diagnostic criteria for CFS
12
Hypothesis
University of NSW
Infection
Environmental co-factors
Genetic predisposition
Aberrant immune response
Persistence of pathogen
Chronic cytokine production
Brain-mediated fatigue
13
Hypothesis testing

Case-control series
Cases (PIFS) 6 months or more of unexplained
fatigue
Controls recovered uneventfully within 2-3 weeks
of onset
Serologically confirmed infection
Longitudinally collected samples and clinical data

14
EBV cellular viral load
Cases (n8) / controls (n17)
15
Anti-EBV antibody responses
16
T cell responses to EBV
17
Summary
EBV case-control studies

In comparison with subjects who recover promptly,
subjects with PIFS have
No evidence of altered viral load
No significant alteration in the antibody
response
No significant alteration in the cellular immune
response
No significant difference in cytokine production

Cameron B, Bharadwaj M, Burrows J, et al.
Prolonged illness after infectious mononucleosis
is associated with altered immunity but not with
increased viral load. Journal of Infectious
Diseases. 2006193664-671
18
The hypothesis revisited?
University of NSW
Infection
Environmental co-factors
Genes
Aberrant (early) immune response
Persistent antigen
Chronic cytokine production
Brain-mediated fatigue
19
The hypothesis revisited
University of NSW
Infection
Environmental co-factors
Genes
Appropriate immune response
Exaggerated brain response
Brain-mediated fatigue
20
Research team