Times Higher Education Supplement
The medical mystery giving doctors a dose of humility
Published: 14 November 2003
Thousands of people confound the global medical profession with
inexplicable symptoms each year. Steve Farrar reports on the
diagnostic nightmare haunting hospitals and leaving patients in
It was when she started losing her memory and a tingling sensation
spread over her body that Emma started to get really scared. "I
thought it might be Creutzfeldt-Jakob disease," she recalls. "I was
convinced I was going to die and I even began preparing to write my
For some months she had been aware that something was wrong. Her
ordeal began last July with dizzy spells, followed by numbness,
difficulty breathing and heart palpitations. Her doctors were
baffled as to what lay behind the symptoms.
By February this year, her health had deteriorated to the extent
that Emma, a sociable and sports-loving young woman, had to stop
work. She moved back in with her parents so they could care for her
as even the simplest of tasks had become a major undertaking. "I
felt out of control and absolutely terrified," she says. And still
the experts were at a loss to explain what was happening to her.
Nicola's life has been similarly turned upside down by a condition
that has stumped her doctors. She has suffered from pain in both
forearms for the past two-and-a-half years. It rapidly became
unbearable and robbed Nicola of the ability to look after herself.
She broke down and cried the day she couldn't lift the kettle to
make a cup of tea.
The injections she was given made little difference. Then the
experts started giving contradictory advice. "All I wanted was for
the pain to go away," she recalls. "I looked at myself in the mirror
and declared that I would have to take charge of this to a greater
degree." And she has, her pain gradually receding over time.
Both women felt very isolated by their experiences, let down by a
medical profession unable to comprehend what they were enduring. Yet
a growing body of research suggests that they are far from being
alone. In fact, Emma and Nicola may be among the sufferers of one of
the most common debilitating health complaints of all, a problem
that has been swept under the carpet and is only now beginning to be
recognised for what it is.
In a high office overlooking the Edinburgh skyline, a group of
researchers watches a video. A middle-aged woman struggles to
approach the camera. Jon Stone, research fellow in neurology at
Edinburgh University, observes: "She walks as if her left leg
doesn't really belong to her, like it has just been stuck on." Like
Emma and Nicola, the experts she has seen can find nothing
physically wrong with her, no disease or lesion that can be blamed
for her plight. And, like Emma and Nicola, her distress is very
The scientists studying her peculiar gait are among the handful of
experts worldwide who are beginning to probe the mysteries of what
have been labelled "medically unexplained" or "function symptoms".
Some of the particular sets of symptoms have been given their own
names - repetitive strain injury, non-cardiac chest pain or
irritable bowel syndrome, for example. The woman in the video is
suffering with a condition called functional weakness.
The Edinburgh group is probing what links these apparently disparate
conditions. Preliminary results from the largest survey of its kind
among hospital outpatients are revealing that almost a third of the
thousands of patients referred to Scotland's neurology clinics over
the past 18 months have symptoms that are not explained by a
classical disease or recognised medical condition. Previous research
suggests similarly high proportions of medically unexplained or
functional symptoms may be found in almost every other medical
speciality from cardiology to rheumatology.
Mike Sharpe, reader in psychological medicine at Edinburgh,
encountered his first case of medically unexplained symptoms when he
was a junior doctor at Papworth Hospital in Cambridge. A middle-aged
woman had been brought in suffering from breathlessness and muscle
pains. Yet, after conducting a battery of tests, the consultants
were no closer to making a diagnosis or providing a treatment for
Bedridden by her pain, the woman grew increasingly alarmed as
experts failed to come up with any explanation for what was
happening to her.
Sharpe was intrigued. On a hunch that the woman's problem was linked
in some way to her central nervous system, he suggested she take a
course of antidepressant drugs. She responded immediately and was
soon able to leave hospital.
Two decades on, Sharpe's interest in the problem has now drawn a
group of like-minded researchers around him in the Scottish capital.
Stone, who is looking at sufferers of functional weakness, is among
them. Another is Alan Carson, a consultant neuropsychiatrist at the
Royal Edinburgh Hospital and honorary senior lecturer at Edinburgh.
When Emma's case was referred to Carson in May, he diagnosed a
functional neurological disorder and prescribed antidepressants and
behavioural therapy. She is now close to making a full recovery.
Most sufferers, however, have essentially been left to fend for
How could the medical establishment have missed a problem as
significant as this? Sharpe believes it is partly because these
conditions fall into the no-man's land between medicine and
psychiatry. "We have this divide between things that are wrong with
the mind and things that are wrong with the body and these symptoms
occupy the uncomfortable territory which is neither neurology nor
psychiatry but both," he says.
Furthermore, modern medicine developed in an era focused on
combating infection and life-threatening illness and has not yet
adapted to the needs of the chronic illnesses of the 21st century.
It probably does not help that diagnosis of functional symptoms
seems to be a default category, reached when no obvious disease can
be identified. The upshot of this is the sort of confusion that made
Emma and Nicola feel so isolated.
In some cases, it can prompt doctors to conclude the problem is all
in the patient's head. Many GPs are aware of the problem but have no
idea what to do about it. So the sufferer is sent on a fruitless
referral to a hospital specialist in whatever discipline seems most
relevant to the set of symptoms - such as gastroenterology for
irritable bowel syndrome. Unable to identify the cause, the
specialists refer the patient to further specialists, send them back
to their GP and may even simply advise them to pull themselves
With some sets of symptoms, pointless operations are often carried
out. The gall bladder might be removed or an exploratory incision
made to reveal the slenderest hint of a disease. But the symptoms
"Medicine has focused on visible tissue pathology while psychiatry
has focused on madness," Sharpe says. "There is a whole army of
people who feel ill, have symptoms but get left behind. They have
been treated as the undeserving sick."
A study of primary health care patients in 14 countries, from
Nigeria to the UK, carried out by the World Health Organisation and
published in 1997, makes it clear that differences in culture have
little effect on the level of the problem. It is a global
The precise cause of functional symptoms still eludes scientists.
Some sort of neural disturbance seems to be a key aspect. Subtle
differences in patterns of brain activity in some sufferers have
been observed. They tend to have a higher tendency towards anxiety
and depression. And many are afflicted by more than one set of
symptoms. Carson explains: "We view it as the brain's control over
the body becoming dysfunctional." Sharpe suggests that the answer
lies in accepting that all symptoms are an expression of a
combination of biological, psychological and social factors - of
which disease is only one.
Kurt Kroenke, professor of medicine at the Regenstrief Institute in
Indianapolis, is one of the few researchers looking at medically
unexplained symptoms in the US. He notes: "If all you look for are
biomedical explanations, you're missing the whole picture." So while
drugs that affect the brain's chemical pathways have an important
role to play, so do psychological treatments. "I think the lack of
explanation and acceptance stokes the problem," Sharpe says.
Given that the problem seems to be so widespread, finding effective
therapies is vital. Initial work by the Edinburgh group points to
discernable improvements from an explanation followed by a
prescription of drugs usually used to tackle depression and
cognitive therapy. Meanwhile, many people are still suffering - the
symptoms can persist for years - and the cost to the health service
in terms of unhelpful referrals and investigations remains enormous.
Carson notes: "If the government wants to solve the waiting-list
problem, they will have to channel serious funding at this problem."
As yet, few scientists are working to solve the problem, but the new
research could prompt a change.
Sharpe observes: "At the moment, you could probably fit all the
researchers from around the world in my office."