‘The worst days, many hundreds of them, saw me so ill that I was unable to move my arms and legs, open my eyes or speak. For those hundreds of days, I could do nothing but lie motionless in bed, our house dark and shrouded in silence in order to spare me the agony of light and noise. I felt so terribly ill that even having somebody clean my teeth for me was more than I could bear. Some days my family struggled to tell whether I was conscious or not; it did not seem possible I would survive.
The best days, in more recent years, I have been able to enjoy short outings in my wheelchair, to sit in the garden and feel the sun and fresh air or chat to a friend. Such simple things are so very precious because they are so rare. I cannot count the days when I have been torn apart with grief at seeing life pass me by.’
Naomi is 30. Every day during the last 17 years has been lived under the shadow of ME. Her story is recorded in a powerful iilustrated book called Lost Voices (from a hidden illness), compiled by Natalie Boulton for the charity ‘Invest in ME’.
In the spring of 1955, a strange infectious illness occurred at The Royal Free Hospital in London. It started with a handful of people but then in July of that year, almost 300 members of staff were taken ill (of which 255 had to be hospitalised). As a result, the hospital was forced to close until the early part of October. It was Dr Melvin Ramsay of the hospital’s Infectious Diseases department who coined the term Myalgic Encephalomyelitis, referring to the effects on the muscles, brain and nerves. ‘These included a unique form of muscle fatigue whereby, even after a minor degree of physical effort, three, four or five days or even longer can elapse before full muscle power is restored. Tenderness of the muscle also occurs quite frequently. The extremities are often cold. There is increased sensitivity to climatic change and episodes of copious sweating. Memory and concentration are impaired. There are difficulties in completing a line of thought, mixing up words , sleep disturbance and emotional lability.’ Dr Ramsay also noted that all his patients reported a characteristic variability and fluctuation of symptoms throughout the day an there was a strong possibility that the illness could become chronic and disabling.
Not all cases of ME had the complete range of clinical features or a history of previous infection. So in 1988, the name was changed to Chronic Fatigue Syndrome, though many patients adhere to ME or the hybrid CFS/ME.
There is a marked similarity between CFS/ME and IBS and extensive overlap between the two conditions. About 30% of people with IBS suffer from chronic fatigue and altered bowel habit and abdominal discomfort is common in CFS/ME. Both IBS and CF/ME may be instigated by an infectious illness. Both conditions are controversial and defy a consistent medical explanation, but they show similar changes in immune reactivity and hormonal activity. And, of course, both IBS and CFS/ME can cause severe disability that can last for years, but may recover for no obvious medical reason. One might therefore be forgiven for thinking these are different expressions of the same illness. It has even been suggested that the dyad of IBS/Constipation and IBS/Diarrhoea is analogous and may overlap with the dyad of CFS/ME and Fibromyalgia.
Psychological trauma and stress have been implicated in both conditions. The fact that both commonly start in teenage years might suggest the dramatic life changes and dangers that occur that time might instigate both conditions. But teenage is also a time of travel and greater exposure to novel infections. IBS may be instigated bottom up by infection or broad spectrum antibiotics or top down by trauma (and often both together), resulting in a resetting of immune, endocrine, physiological systems. It is likely that something similar might apply to CFS/ME. Nevertheless the dominant medical treatment for the latter has been cognitive behavioural therapy and graded exercise therapy, in which patients were assigned to a regimen of increasing exercise. The evidence has never been that strong and patients have long objected that these measures are either useless or made them worse.
In the last few years, a team of researchers, led by Professor of Psychiatry, Michael Sharpe from Edinburgh University, have conducted their four way randomised controlled clinical trial, called PACE. The trial, which cost £5 million pounds, compared Cognitive Behavioural Therapy (CBT), Graded Exercise Therapy (GET), Specialist Medical Care (SMC) and Adaptive Pacing Therapy (APT). The results showed that CBT and GET were each successful in 22% of patients, three times as many as in the other limbs. Patients demanded to see the details of the study protocol and the data . When these were eventually revealed under the Freedom of Information Act, a small group of patients and academic statisticians analyzed it and published their findings on Virology Blog. And with that, the PACE trial’s 22 percent recovery rates “went up in smoke,” wrote Julie Rehmeyer, a journalist who is also an ME/CFS patient. In this new independent but hardly unbiased analysis the “recovery” rates fell to single digits, and the results were not statistically significant. There have been demands to the journal and the authors for retraction.
David Tuller, lecturer in public health and journalism at the University of California at Berkeley, published a blistering attack on current treatments for CFS/ME and the PACE trial last week: Worse than the Disease. He not only pointed out that patients knew which treatments they were getting, but also that the researchers biased their results by publishing glowing testimonials in their newsletter while the study was in progress. He also noted discrepancies between the entry criteria and criteria for recovery. He claimed that patients were identified using only fatigue rather than the full diagnostic criteria, raising the possibility that many may have been suffering from depression which is known to respond to CBT. He revealed that the investigators revised their criteria for improvement and recovery after the study began. Finally he detected a conflict of interest, claiming that some of the investigators also worked for disability insurers. Tuller’s comprehensive critique, published just a few days ago has attracted many glowing endorsements, but a deafening silence from the investigators and the medical establishment. We need to hear their rebuttal.
So, it seems from the evidence that Tuller has amassed in his damning indictment, that another study on CFS/ME had generated invalid data. In response to mounting criticism, the Agency for Healthcare Research and Quality, which had previously recommended graded exercise therapy and cognitive behavior therapy, reversed their stance. In a new analysis excluding PACE and other Oxford-criteria studies, the agency found no evidence that graded exercise therapy was effective and minimal evidence for cognitive behavior therapy.
This is very unfortunate, because not only does it leave the treatment of CFS/ME in limbo but it calls into question clinical trials of treatment of other ‘unexplained illnesses’ including IBS, where there are also no measurable endpoints. Clinical trials are only as valid as the measurements of their outcomes; symptom assessments, quality of life, well-being are always going to be subject to observer bias. CFS/ME, like IBS, is, as Dr Melvin Ramsay concluded, a highly individual illness that does not lend itself to RCT studies that assume that patients with the same diagnosis will behave in a similar way.
In the meantime, Naomi remains in bed waiting for something to happen.