Dr. Ferran J. García

Chronic Fatigue Syndrome is not all in the mind

Changes in the brain and cell activity may be the key to treating CFS

Characteristically, these medical organisations agree: CFS begins with routine flu-like symptoms, but can result in years of chronic, painful fatigue that, crucially, is not improved by bed rest. It can affect anyone of any age — there are estimates that 25,000 children and teenagers in Britain have the condition. A recent survey by the charity Action for ME suggested that 55,000 people are so badly affected that they are either bedbound or housebound.

Yet with no recognised cause, diagnosis and treatment, the illness has remained problematic. Experts cannot even agree on what to call it — most widely known as CFS, it is also called myalgic encephalomyelitis (ME) or post-viral fatigue syndrome (PVFS).

With emerging evidence of its biological basis, however, the way CFS is viewed is changing. "There is no doubt that this is a genuinely physically disabling condition, which is not in the mind," says Dr Charles Shepherd, medical director of the ME Association. "We have long known that many people, although not all, initially get it after a viral infection, such as the Epstein-Barr virus that causes glandular fever. But in the past few years the medical profession's understanding of the biological elements of the illness has progressed considerably." According to the CDC, researchers have analysed the activity levels of 20,000 genes in people with CFS and found abnormalities in genes triggering the brain activity that mediates a stress response.

Anthony Komaroff, a professor of medicine at Harvard Medical School and a spokesman for the CDC campaign, says that brain functioning and cell energy metabolism appear impaired in those with CFS. Dr Nancy Klimas, a researcher at the University of Miami School of Medicine and president of the International Association for Chronic Fatigue Syndrome, and other investigators have shown that different types of cells within the immune system are abnormal either in number or in their capacity to function in these patients.

Another significant advance came last summer when researchers at Georgetown University Medical Centre suggested that CFS may be rooted in distinct neurological abnormalities that can be medically tested. In a paper published by the Neurology Journal, Professor James Baranjuk reported that patients with the condition have a set of proteins in their spinal-cord fluid that were not detected in healthy subjects.

These proteins, Baranjuk proposed, might give insight into the causes of the illness and could be used as markers to diagnose it. "For years patients with CFS have suffered with painful symptoms for which there is no blood test, diagnosable physical condition, or any method for doctors to measure improvement," he says. "Our research provides initial evidence that it may be a legitimate neurological disease and that at least part of the pathology involves the central nervous system."

Shepherd welcomes the glut of new studies into causes, claiming that any new knowledge about CFS can only help to develop better treatments. "To date, most patients are prescribed a graded exercise programme to enable them to manage their lifestyles better," he says. "Pacing — a system in which patients are prescribed physical activity in short bouts — is often effective as long as it is carefully controlled and individually tailored."

Some physicians advocate a more aggressive exercise programme — "a sort of push through the pain barrier approach" — that Shepherd says "is highly controversial and not recommended by ME charities. Around 50 per cent of people trying a more intensive exercise recovery programme experience a significant relapse."

But, equally, Shepherd says "the way out of CFS is not to lie in bed".

Currently, he says, prognosis is "pretty bleak and a full recovery is unlikely. People with CFS generally fall into one of three categories: those who are severely affected (around 25 per cent) are wheelchair or house-bound; the majority find that their condition stabilises, albeit in a remitting fashion, to some extent after one or two years; only a minority get back to 'reason ably good health'."

Around 77 per cent of sufferers in the UK have lost their jobs because of the illness at an annual cost to the country of £6.4 billion. Last year CFS was given as the official cause of death for the first time in the UK when a coroner in Brighton recorded the death of a 32-year-old woman as acute aneuric renal failure (failure to produce urine) because of dehydration as a result of CFS, from which she had suffered for six years.

All of which make the promising signs that some drug treatments might help even more welcome.

Earlier this month Professors Jose Montoya and Andreas Kogelnik, of Stanford University, announced that they were to begin a major study on the drug Valcyte (valganciclovir), an antiviral medication that is often used to treat herpes- related diseases.

During a three-year pilot trial the researchers revealed that 21 of 25 ME patients with symptoms related to the herpes virus responded to Valcyte with significant improvement. Those who responded to the drug had developed ME after an initial flu-like illness, while the non-responders had suffered no initial flu.

At St George's Medical School, London, Dr Jonathan Kerr is planning trials on the well-established drug interferon beta to see if it can restore an imbalance of genes in CFS patients. "We've found that the genes in patients' white blood cells — a key part of the immune system — are switched on and off in an abnormal fashion," he says. "The drug boosts the immune system by enhancing the activity of natural killer cells, which fight viruses. Since viruses are believed to play a role in triggering CFS in many people, beta interferon might clear the infection and help them to shake it off."

Despite the peak of scientific interest in CFS, it remains a subject of much debate. Only last November, an allparty group of British MPs, chaired by Dr Ian Gibson, who was formerly chair of the Science and Technology Select Committee, launched an attack on the medical establishment for clinging to its belief that CFS is "all in the mind". It claimed that a bias against research into its physical cause exists and criticised the Medical Research Council for investigating only psychological causes of the illness. Indeed, many studies persist in linking CFS to psychological triggers. A Miami University study in the Archives of General Psychiatry recently cited childhood trauma as a risk factor after assessments of 43 people with the syndrome found that they reported a much higher incidence of trauma, depression and anxiety when they were children. Those who recalled a troubled youth were said to be eight times more at risk of getting CFS than their peers.

Klimas says that even its name belittles the extent to which it debilitates patients' lives. "If it were called chronic neuroinflammatory disease, then people would understand it," she says. "Until today nobody's been willing to change the name, but now there's proof that inflammation occurs in the brain and there's evidence that patients with this illness experience a level of disability that's equal to that of patients with late-stage Aids, patients undergoing chemotherapy, or patients with multiple sclerosis."

What experts are most keen to change is the public perception that CFS affects those with nothing else to worry about.

"This is not an illness that people can imagine they have. It's not psychological," says Komaroff. "That debate, which has raged for more than 20 years, should be over now."

The Association of Young People with ME (AYME) has produced a DVD for sufferers, available from its website below.

www.ayme.org.uk
www.afme.org.uk
www.meassociation.org.uk

LIVING WITH CHRONIC FATIGUE SYNDROME: 'THE FIRST SYMPTOM THAT I GET IS ITCHY EYEBALLS'

Throughout my twenties and early thirties I have lived with a recurrent dread of waking up with a bizarre complaint: itchy eyeballs. I have come to recognise this symptom — a gritty soreness and a feeling that my eyeballs are being roasted — as a precursor to a week or fortnight of physical and mental gloom. No amount of willpower or self denial, I have learnt, can prevent my body's descent into partial shutdown, at its worst, to the point where I lack the energy to lift a phone or to walk into a room.

I develop a feverish temperature, my joints ache as if I have flu, and energy is flushed from my body. This is not tiredness in the normal sense — no amount of sleep negates the effects — but I am unable to do anything strenuous. I recall an occasion when I dragged myself up to go outside just because I believed that the fresh air and a walk would help, only to find I had so little energy I was unable to summon the energy to cross the road. I had to limp back distraught and downtrodden.

What causes my body to stop in its tracks until it feels ready to resume normal service mystified countless doctors whom I saw in the first few years I experienced the symptoms. A majority suggested that the cause was post-viral and linked to the glandular fever that I suffered many years ago. Without fail, it strikes at times when I feel I have pushed things too far, through work or exercise.

After five years of suffering, CFS was eventually diagnosed and I felt a sense of relief and desperation. What could I do to get rid of it? Was there anything I could take to lift my spirit and energy levels? In both cases the answer was "not much", and as a sporty person it was to be the most frustrating of conditions.

Some doctors suggested that I stop exercising altogether, others that I did a minimum until my body could cope with more. Instead, I tried continuing working and attempting to run or hit the gym every day — with the same disastrous results. Through trial and error, over the past few years, I have realised that I can control the condition to some extent by slowing down. Since I am inclined to tackle everything at full pelt it didn't come easily, but I learnt that to push myself when I felt tired or to plough on relentlessly without rest was a recipe for disaster. Gradually, my "attacks" have reduced from every three weeks to every three months. My "cure" came in the most unlikely form — becoming a mother two years ago at the age of 36.

With less time to spend working out and burning the candle at both ends, I have found that my bouts of CFS have been less severe (lasting three to four days instead of two weeks and nowhere near as debilitating as they were) and strike only every four or five months. Yes, the eyeballs still get itchy but I have learnt that if I treat my body with care it will respond well. PETA BEE