CFS is Becoming Respectable

[Guest guest]

The Economist

November 20, 1999 , U.S. Edition

The soul of a new disease

Chronic Fatigue Syndrome is no longer seen as being " all in the mind " . Its

true nature is still unclear, but researchers are slowly closing in

A MYSTERIOUS epidemic spread through the Los Angeles County Hospital, in

California, in 1934. Nurses and doctors succumbed to a strange mix of

fatigue, muscle pain and emotional distress. The first suspect was polio --

the symptoms were similar, and fear of the disease was rampant at the time.

Yet tests for polio revealed nothing and, bizarrely, the hospital's patients

remained unaffected. A similar pattern of events occurred in 1955, at the

Royal Free Hospital in London. Again, patients were untouched. And in both

cases, most of those who succumbed were women.

Many people would now be familiar with these symptoms. They have gone under

a variety of names. In the 19th century, they were referred to as

neurasthenia. In the wake of the 1955 outbreak the term myalgic

encephalomyelitis (or ME) was coined. More recently the complaint has been

derisively referred to as " yuppie flu " . And now Chronic Fatigue Syndrome

(CFS) has become the preferred label. The changes of name have not been

accompanied by much change in understanding, however. Nobody yet knows what

causes CFS. But at a recent meeting in London, held under the auspices of

the Novartis Foundation and the Linbury Trust, a group of experts got

together to exchange their latest theories.

The first problem with CFS is agreeing who has it. Since fatigue cannot be

measured objectively, deciding who crosses the hazy line between normal lack

of energy and abnormal tiredness is tricky. The boom-and-bust appearance of

CFS and its antecedents (neurasthenia was fashionable among the n

upper classes, and often required prolonged rest cures at spas), has led

some doctors to dismiss the whole thing as mass hysteria.

With one recent survey in Britain suggesting that 30% of women and 19% of

men always feel tired, there is plenty of scope for over-diagnosis of CFS.

But the syndrome is more than fatigue, whether physical or mental. Its other

symptoms include weakness, muscular pain, disturbed moods and problems with

sleep. These can be measured -- and they can then be researched.

Know thyself

The first of these problems yields a mystery. CFS patients insist that their

muscles do not respond to their desires. But despite intensive

investigation, researchers have found no particular muscular weakness or

abnormality that could account for the patients' complaints. It is true that

the syndrome takes its toll on a patient's muscles. And as movement consumes

more energy than patients can muster, they opt for inactivity. That plunges

them into a downward spiral of weakness, since unused muscle tends to feel

powerless. But there is no sign of a problem in the muscle itself; so the

disruption must lie in the nervous system that drives it.

Wolpert, a cognitive neuroscientist at the Institute of Neurology in

London, who spoke at the meeting, offered one explanation of why people

suffering from CFS consider themselves to be more tired than the tests

suggest they should be. His theory is based on the widely held idea that the

brain harbours a model of the body that it uses to predict the consequences

of movement. If you wave your arm, the muscles transmit signals to a part of

the brain called the cerebellum, which " examines " the model, makes

predictions and then alerts the rest of the brain about what sensations it

should look out for. This explains, for example, why people cannot tickle

themselves: their brains know what to expect, and can thus cancel out the

sensation.

Dr Wolpert's suggestion is that people with CFS may have lost this

self-predicting loop and so cannot cancel out the sensations returning from

their muscles, even when those muscles are moving under willpower. Every

exertion thus appears to be loaded with unwarranted effort. The natural

reaction is, therefore, to avoid that effort.

Tony , a clinical psychiatrist at the Institute of Psychiatry in

London, is another researcher who thinks that problems of self-awareness are

central to the syndrome. In his view, CFS has a lot in common with anorexia

nervosa. Anorexic people often see themselves as fat even though others find

them almost painfully thin. Anorexics can estimate their height quite

accurately when they stand in front of a mirror. But they tend to

overestimate the width of their hips, waist, legs and faces by around 30%.

Dr reckons that a similar bias in self-perception is present in CFS

patients, who perform much better in tests of strength and intelligence than

they expect.

The notion that CFS is a disorder of perception is also supported by the

fact that around two-thirds of patients with the syndrome can be helped by

cognitive behaviour therapy. Under this approach, they are given small tasks

that gradually get harder as the treatment progresses. By slowly adapting to

the increasing activity, they no longer perceive their effort as excessive.

With this opportunity to gain control gradually, they learn to cope with the

illness.

Another defining symptom of CFS is poor sleep. Patients still need sleep,

but they find it hard to nod off. As a result, they end up spending longer

in bed, probably to compensate for their fragmented sleep patterns. Jim

Waterhouse and his colleagues at Liverpool s University, led by

Gareth , are studying the body's clock -- the circadian rhythm. Dr

Waterhouse is convinced that this clock is involved in CFS.

Although falling asleep requires no conscious effort, it is still a major

physiological feat that requires carefully choreographed body changes. For

drowsiness to set in, the body's temperature must drop. Usually it does so

rapidly, within one or two hours. At the same time, the pineal gland in the

brain pumps out a hormone called melatonin. This combination is the signal

to go to sleep. In people who nod off easily, the two events are tightly

synchronised. In CFS patients, however, they are mismatched. Worse, their

melatonin production is not as efficient as it should be. And when Greg

Tooley, another member of the group, recorded the temperature cycles of such

patients, he found that their evening drop in temperature happened an hour

or two later than normal. An hour's lag may not seem that much, as most

people can function reasonably well if deprived of one or two hours' sleep

for a night. But if the discrepancy persists, it might bring on the

full-blown symptoms of severe sleep deprivation. Fatigue is one of them.

The researchers at s are trying to find out whether melatonin

pills can help CFS patients fall asleep. In an initial trial, they arranged

for 31 subjects to take melatonin every evening at 5 o'clock, for three

months. For comparison, each patient also took a placebo tablet for three

months, without being told which was which. The preliminary results are

promising. The participants slept better, felt less haggard, and even

reported themselves to be more cheerful while taking melatonin. Their

temperature also declined earlier in the evening.

These are promising approaches. But prevention is better than cure -- and

that will only be possible when the cause of CFS is identified. One common

misconception can be discounted. CFS is not a politically correct

alternative name for clinical depression. Depressed patients are

characterised by a lack of motivation; people with CFS want to go about

their daily business, but are frustrated because they cannot summon the

strength to do so. And whereas depression can often be treated with a class

of drugs called selective serotonin-reuptake inhibitors -- the best known of

which is Prozac -- these do not work in people with chronic fatigue.

One persistent idea is that the disease is triggered by an infection.

White, a researcher at St Bartholomew's Hospital in London, reckons

two-thirds of CFS cases may start this way. Dr White studied 250 people with

either glandular fever or (for comparison purposes) a common throat

infection. Six months after the infection, over 9% of the patients who had

had glandular fever were chronically fatigued, against none in the control

group.

The list of suspect infections is, however, a long one. It includes

Epstein-Barr virus (the main cause of glandular fever), hepatitis types A,

B, and C, viral meningitis, toxoplasmosis, cytomegalovirus and a rare

illness called Q fever. (With hepatitis B and C, the continuing infection

may be the cause of fatigue rather than CFS itself.) What such a disparate

collection of diseases has in common is unclear, though they all excite the

immune system into secreting substances called cytokines which are known to

cause fever, disturbed sleep, aches and fatigue.

The mystery of CFS, then, is by no means solved. But at least it seems that

progress is being made in diagnosis -- and the first steps are being taken

towards a cure.