Science Interviews

Interview

Tue, 15th May 2012

What is Chronic Fatigue Syndrome?

Dr. Esther Crawley, Bristol University

Listen Now    Download as mp3 from the show Cracking Chronic Fatigue

Kat -  Let’s start by just really going back to basics, what exactly do we mean by chronic fatigue syndrome?  What is this disorder?

Esther -  Well, patients with chronic fatigue syndrome are first of all very disabled by very significant and difficult fatigue, and then they usually have a variety of other symptoms.  So, one of the most common symptoms for example is headaches which are very difficult and often constant.  They often have muscle and joint aches and pains.  I mainly see children and teenagers and they often start off by feeling very, very sick, particularly first thing in the morning and dizzy, and sore throats and swollen lymph nodes are also some of the symptoms.  One of the problems with this illness is it comes and goes and it affects people differently in different days.  It can cycle by days or by weeks, or by months.  It’s a very, very difficult and disabling condition.

Kat -  Who normally gets this disorder because I remember when it sort of rose to prominence, a couple of decades ago, people referred to it as “yuppie flu”, but I understand that's not actually really the sort of people that it affects?

Esther -  Well, it can affect everybody.  It tends to be more common in women.  In fact, it tends to be more common in those of lower socio-economic class, so more deprived families.  And there's reasonable evidence now that it’s also, certainly in this country, it’s more common in ethnic minorities.  And you can look for this condition everywhere and every country that you look for it, you're going to find it, and the poorer the country, the more common it seems to be.  So, in fact, it’s quite the reverse of yuppie flu.  It’s an illness of social deprivation not of wealth.  It’s just the yuppies, the rich people are more likely to be successful in seeking healthcare.

A child sleepingKat -  And what sort of healthcare is available?  There's no medical treatment.  What sort of treatments or interventions might be available for it at the moment?

Esther -  Well, there are no magic pills for it at the moment.  There are some medications that help with pain and there are some medications that some patients find helpful with sleep.  But mainly, treatment focuses on improving quality of sleep and improving activity and exercise in a very, very gentle way to get patients back to doing the things they want to do.

Kat -  What’s actually causing CFS?  What makes someone develop this disorder?

Esther -  We don't know the cause is and I think it’s really important to start at the beginning of your programme by saying it’s quite likely that it’s not just one illness.  Certainly, all the research in adults have shown that there's probably between 3 and 5 different types of illness that present with different groups of symptoms.  So it may well be that fatigue and the symptoms I described might be the sort of end pathway.  In children, we’ve also described between 3 and 4 different types of illness.  

And so, what do we know about it?  Well, we know that in many people, it’s triggered off by an infection and some research has shown that it’s the severity of the initial infection, rather than the actual type of infection, that's important.  

But we also see a similar problem with fatigue after other types of insults.  So for example, we’re quite interested in what happens to patients after they have treatment for cancer.  Also, we quite often see it in other illnesses.  So, if you get very, very ill with diabetes for example, quite a lot of children after that develop a very similar looking illness.  

So, I think that you need a big hit, but also, there's good evidence to show that in both children and adults, people are what we call ‘genetically vulnerable’.  So you’re probably born with genes that make you vulnerable to fatigue and then you need an environmental insult to set it all off.

Kat -  What kind of evidence do you have that there may be a genetic component to this?

Esther -  There's different types of studies and the most convincing are twin studies.  Interestingly, it looks like children are more genetically vulnerable than adults.  So, if you're monozygotic twins, if you’re identical twins and one of you gets it, you're much more likely that the other one will get it than if you're dizygotic, where you're only going to share half the DNA.

Kat -  So basically, if you develop it as a child, it’s more likely that it had a stronger genetic component to it.

Esther -  Yes, so you only needed 1 or 2 viruses and then you set the whole thing off whereas as an adult, it looks like probably, you need to have the genes and then you need other things.  So for example, we know that in adults, if you're depressed in your 40s, you're more likely to get it in your 50s, and that just doesn’t seem to be true in children.  So in adults, you need a variety of things together at the same time as well as the infection to set the whole thing off.

Kat -  What do you think is going on with the infection?  You talked about someone having an infection.  It doesn’t matter what's infected them.  Do we have any clues about what's going on in the immune system?

Esther -  Well, there are a lot of studies that have looked at the immune system and it’s quite difficult to interpret exactly what's going on.  I mean, clearly people with chronic fatigue syndrome, when you look at the immune system, it seems to be very different to controls. It’s difficult to interpret because there are also lots of other differences going on.  So for example, they're more sedentary, so they're not doing as much exercise as healthy controls.  I mean, we believe the way forward is by doing very, very large studies, looking at the genetic material from thousands and thousands of patients.  Of course you need very large studies because there are different types of illness and looking at blood in a large number of patients, but also, we’re using longitudinal cohorts so, looking at DNA and blood, and also other factors before people get ill, to try and work out what the causes are.  And also, what we call the maintenance factor, so what keeps you sick.

Kat -  So if you think you can understand some of the pointers that might be causing it or indicating that it’s about to happen, do you think you could help prevent people developing CFS in the first place?

Esther -  Well I mean, I think that's why we’re looking at it and also, we don't have any medical treatments.  So, understanding more about the causes might help us develop that.  But I think there's other things that you can do as well, so we’re quite interested in what's called early intervention studies.  So, if you – for example in children – if you can identify children as they start to become unwell with this illness, then what teenagers tell us is, if they get the right advice very early on, they believe they could stop it becoming a long-term illness.  So I think there’s definitely a role for looking at early intervention studies in both teenagers and there's also studies in Bristol going on in adults, seeing if you can prevent it becoming a long time problem.

Kat -  What sort of interventions are you talking about in these cases?

Esther -  Well, the teenagers tell us that the most useful thing that they wish they’d known right at the beginning is advice about sleep.  So, what happens when you get chronic fatigue syndrome is you feel very, very awful and very, very tired, and instinctively, when you feel tired, you lengthen your sleep.  And so, a lot of teenagers end up sleeping for between 12 and 20 hours.  The problem with lengthening the time that you're asleep is that the quality of your sleep deteriorates, so you feel more tired, and so you lengthen it again, and that reduces the quality.  

You also end up with change in your wake up time and changing your wake up time changes the cortisol that's released in the brain.  So cortisol is a type of steroid and for those of us without chronic fatigue syndrome, we usually get a cortisol hit in the morning and that helps us feel awake.  

If you're constantly changing your wake up time, then we think that that's one of the reasons why it ends up being quite flat in teenagers with chronic fatigue syndrome.  So we give quite simple advice about keeping your sleep at night very short and making sure you always wake up at the same time.  Teenagers often find that it really makes a big difference to them and what they say is that they wish they'd had that advice very early on because their view is that it prevent them getting as sick as they get.

Kat -  It sounds absolutely fascinating with a disease that's extremely complex.  So, that's Esther Crawley from the University of Bristol.  Thank you.

 

 

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ncbi.nlm.nih.gov defined Chronic fatigue syndrome as severe, continued tiredness that is not relieved by rest and is not directly caused by other medical conditions. smith nai, Sat, 19th May 2012

CFS, also known as M.E., is a whole lot more than 'tiredness'.  If a person with M.E. goes past their very limited capabilities, they make themselves very much more ill. There's a new definition out, published last year.  It was written by a group that in total have 400 years experience in the field, and the references include links to all the important bio-medical research on the disease.

Esther Crawley does not really deal with people with CFS aka ME, as the definition of the disease that she uses (Fukuda, Oxford) are not accurate.  See my previous post, and below:

Myalgic encephalomyelitis: International Consensus Criteria

"Myalgic encephalomyelitis (ME), also referred to in the literature as chronic fatigue syndrome (CFS), is a complex disease involving profound dysregulation of the central nervous system (CNS) and immune system , dysfunction of cellular energy metabolism and ion transport and cardiovascular abnormalities . The underlying pathophysiology produces measurable abnormalities in physical and cognitive function and provides a basis for understanding the symptomatology. Thus, the development of International Consensus Criteria that incorporate current knowledge should advance the understanding of ME by health practitioners and benefit both the physician and patient in the clinical setting as well as clinical researchers.

The problem with broadly inclusive criteria is that they do not select homogeneous sets of patients. The Centers for Disease Control prevalence estimates increased tenfold from 0.24% using the Fukuda criteria to 2.54% using the Reeves empirical criteria . Jason et al. suggest that there are flaws in Reeves’ methodology because it is possible to meet the empirical criteria for ME without having any physical symptoms and it does not discriminate patients with ME/CFS from those with major depressive disorder. Patient sets that include people who do not have the disease lead to biased research findings, inappropriate treatments and waste scarce research funds .

Some symptoms of the Fukuda criteria overlap with depression, whereas the Canadian Consensus Criteria differentiate patients with ME from those who are depressed and identify patients who are more physically debilitated and have greater physical and cognitive functional impairments ."

"A. Postexertional neuroimmune exhaustion (PENE pen’-e): Compulsory

This cardinal feature is a pathological inability to produce sufficient energy on demand with prominent symptoms primarily in the neuroimmune regions. Characteristics are as follows:
1. Marked, rapid physical and/or cognitive fatigability in response to exertion, which may be minimal such as activities of daily living or simple mental tasks, can be debilitating and cause a relapse.
2. Postexertional symptom exacerbation:e.g.acute flu-like symptoms, pain and worsening of other symptoms.
3. Postexertional exhaustion may occur immediately after activity or be delayed by hours or days.
4. Recovery period is prolonged, usually taking 24 h or longer. A relapse can last days, weeks or longer.
5. Low threshold of physical and mental fatigability (lack of stamina) results in a substantial reduction in pre-illness activity level.

B. Neurological impairments
At least one symptom from three of the following four symptom categories
1. Neurocognitive impairments
  a. Difficulty processing information: slowed thought, impaired concentration e.g. confusion, disorientation, cognitive overload, difficulty with making decisions, slowed speech, acquired or exertional dyslexia
  b. Short-term memory loss:e.g. difficulty remembering what one wanted to say, what one was saying, retrieving words, recalling information, poor working memory
2. Pain
  a. Headaches:e.g. chronic, generalized headaches often involve aching of the eyes, behind the eyes or back of the head that may be associated with cervical muscle tension; migraine; tension headaches
  b. Significant pain can be experienced in muscles, muscle-tendon junctions, joints, abdomen or chest. It is noninflammatory in nature and often migrates. e.g. generalized hyperalgesia, widespread pain (may meet fibromyalgia criteria), myofascial or radiating pain
3. Sleep disturbance
  a. Disturbed sleep patterns:e.g. insomnia, prolonged sleep including naps, sleeping most of the day and being awake most of the night, frequent awakenings, awaking much earlier than before illness onset, vivid dreams/nightmares
  b. Unrefreshed sleep:e.g. awaken feeling exhausted regardless of duration of sleep, day-time sleepiness
4. Neurosensory, perceptual and motor disturbances\
   a. Neurosensory and perceptual:e.g. inability to focus vision, sensitivity to light, noise, vibration, odour, taste and touch; impaired depth perception
   b. Motor:e.g. muscle weakness, twitching, poor coordination, feeling unsteady on feet, ataxia
Notes: Neurocognitive impairments, reported or observed, become more pronounced with fatigue.Overload phenomenamay be evident when two tasks are performed simultaneously. Abnormal accommodation responsesof the pupils are common.Sleep disturbancesare typically expressed by prolonged sleep, sometimes extreme, in the acute phase and often evolve into marked sleep reversal in the chronic stage.Motor disturbancesmay not be evident in mild or moderate cases but abnormal tandem gait and positive Romberg test may be observed in severe cases.

C. Immune, gastro-intestinal and genitourinary Impairments
At least one symptom from three of the following five symptom categories
1. Flu-like symptoms may be recurrent or chronic and typically activate or worsen with exertion.e.g. sore throat, sinusitis, cervical and/or axillary lymph nodes may enlarge or be tender on palpitation
2. Susceptibility to viral infections with prolonged recovery periods
3. Gastro-intestinal tract:e.g. nausea, abdominal pain, bloating, irritable bowel syndrome
4. Genitourinary: e.g. urinary urgency or frequency, nocturia
5. Sensitivities to food, medications, odours or chemicals

Notes:Sore throat, tender lymph nodes, and flu-like symptoms obviously are not specific to ME but their activation in reaction to exertion is abnormal. The throat may feel sore, dry and scratchy. Faucial injection and crimson crescents may be seen in the tonsillar fossae, which are an indication of immune activation.

D. Energy production/transportation impairments: At least one symptom
1. Cardiovascular:e.g. inability to tolerate an upright position - orthostatic intolerance, neurally mediated hypotension, postural orthostatic tachycardia syndrome, palpitations with or without cardiac arrhythmias, light-headedness/dizziness
2. Respiratory:e.g. air hunger, laboured breathing, fatigue of chest wall muscles
3. Loss of thermostatic stability:e.g. subnormal body temperature, marked diurnal fluctuations; sweating episodes, recurrent feelings of feverishness with or without low grade fever, cold extremities
4. Intolerance of extremes of temperature
Notes:Orthostatic intolerance may be delayed by several minutes. Patients who have orthostatic intolerance may exhibit mottling of extremities, extreme pallor or Raynaud’s Phenomenon. In the chronic phase, moons of finger nails may recede.

Paediatric considerations
Symptoms may progress more slowly in children than in teenagers or adults. In addition to postexertional neuroimmune exhaustion, the most prominent symptoms tend to be neurological: headaches, cognitive impairments, and sleep disturbances.
1. Headaches: Severe or chronic headaches are often debilitating. Migraine may be accompanied by a rapid drop in temperature, shaking, vomiting, diarrhoea and severe weakness.
2. Neurocognitive impairments: Difficulty focusing eyes and reading are common. Children may become dyslexic, which may only be evident when fatigued. Slow processing of information makes it difficult to follow auditory instructions or take notes. All cognitive impairments worsen with physical or mental exertion. Young people will not be able to maintain a full school programme.
3. Pain may seem erratic and migrate quickly. Joint hypermobility is common.
Notes:Fluctuation and severity hierarchy of numerous prominent symptoms tend to vary more rapidly and dramatically than in adults."

Go to the link to read the references.  bonaboots, Sat, 19th May 2012

Hi I must stress that people with CFS/ME if pushed beyond their capabilities (which is far lower than a normal healthy person) can / will develop issues with vital organs. This raises issues with the inability to control heart rate (POTS), body temperature, sugar levels (Hypoglycaemia), digestion and other devastating conditions that causes irreversible damage; these are daily issues for us. Each one of these issues is bad in itself, let a lone having all of them and more… We are alienated by friends, family, work, Dr’s, Politian’s – trapped in a body that is unwell all the time and totally persecuted by our own Benefits system; which is a travesty. The people I know with CFS/ME are / were all very hard working people that paid their Taxes and National Insurance for years; and have been dropped from society and labelled lazy, depressed and Hypochondriacs. We are not ill because we want to be, that is for sure, but we need serious research as it is an illness / condition far beyond being tired and sleeping too much, or in our heads, but a life threatening condition that 250.000 people have in the UK alone. I think this interview hardly even touched the surface of this condition and feel making it a class issues is utterly inaccurate and lazy. Cazby, Wed, 30th May 2012

Esther Crawely is researching fatigue. Who knows why, everyone gets it. ME on the other hand is a neuro immune disease, which Crawley should know by now. She should also know that depression, tired teens and herpes viruses cause fatigue, but not ME. So why study them all together? Using a mixed cohort is illogical for making discoveries of any kind. Her remark that people are genetically predisposed to fatigue is equally laughable when you don't forget that depression, tired teens and herpes viruses have fatigue and that everyone gets it at some point. It is a symptom, not defined. It is also not ME the neuro immune disease. Rates of secondary depression in ME are also no different than in other neuro immune diseases. Retroviruses also become your DNA. Acquired not born with it. Lioo, Mon, 23rd Jul 2012

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