The medical mystery giving doctors a dose of humility

November 14, 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 despair.

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 will."

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 real.

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 her.

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 themselves.

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 together.

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 remain.

"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 phenomenon.

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."

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