Despite a definitive description of Myalgic Encephalomyelitis being published in the 1980s, very little is known about the disease – with some professionals even questioning whether it is a real illness. Researchers and medical professionals don’t know what causes the disease, and so cannot treat the illness itself – all they can do is treat the symptoms. Here, Kerry Taylor Smith explores this mysterious disease
Research has focussed on the psychological aspects of the disease, but scientists are gradually moving away from this idea. Many now believe the illness is caused by viral infections, with some now looking for genetic predispositions to the disease.
The term Myalgic Encephalomyelitis or ME is often used synonymously with Chronic Fatigue Syndrome or CFS. Although different diseases – ME is associated with an inflammation in the brain and easy fatigue following minimal exertion, while CFS denotes a significantly debilitating disorder defined by persistent fatigue, plus other specific symptoms – the terms are used interchangeably, with CFS/ME becoming a widely accepted compromise.
In 1986, A. Melvin Ramsay published a definitive description of ME which also describes many of the symptoms associated with CFS.
“Although the onset of the disease may be sudden and without apparent cause, there is practically always a history of recent virus infection associated with upper respiratory tract symptoms though occasionally there is gastro-intestinal upset with nausea and vomiting. Instead of making a normal recovery, the patient is dogged by persistent profound fatigue accompanied by a medley of symptoms.”
These symptoms include headache, dizziness, neck pain, muscle weakness, frequent urination, blurred vision and a general sense of feeling awful, many of which are found in other diseases – making CFS/ME difficult to diagnose and treat.
Perhaps as a result, research in the UK has shown that only 52% of GPs feel confident in diagnosing CFS/ME2. The NHS believes approximately 250,000 people suffer from the disease, but the figure maybe higher as many cases remain undiagnosed and untreated. The disease is more prevalent in women, but it’s likely it is hugely under-reported in men.
Despite a good understanding of the associated symptoms, scientists still don’t know what causes CFS/ME. Ramsay attributed it to a recent viral infection.
“Although the aetiological factor or factors have yet to be established, there are good grounds for postulating that persistent virus infection could be responsible,” he wrote. “There should surely be no difficulty in considering the possibility that other viruses may also be persistent in the tissues.”
In 2009, Science published a study linking retrovirus xenotropic murine leukaemia virus-related virus (XMRV) to CFS. XMRV was found in blood cells of 68 of 101 patients with CFS/ME, compared to eight of 218 healthy controls. Researchers said XMRV proteins were expressed in blood cells from CFS/ME patients at high levels, and showed through cell culture experiments that patient-derived XMRV was infectious and transmissible.
This seemed to fit nicely with what was known about the disease, and researchers thought XMRV could activate other latent viruses, which could explain why CFS/ME is linked to different viral triggers.
However, the study was partially retracted in 2011 after more than 20 studies in different countries failed to detect significant levels of the retrovirus in patient groups. Two co-authors of the original study found that their samples were contaminated – it is thought there was a chance recombination of mouse viruses in the cell lines during laboratory experiments.
Dr Esther Crawly is a consultant senior lecturer in the School of Social and Community Medicine at the University of Bristol. Her research focusses on CFS/ME, specifically the epidemiology of the disease, and prognosis and outcome in children. She thinks that although the cause of the disease is unknown, it’s quite likely that it’s actually between three and five different illnesses that present with different groups of symptoms.
“We know that in many people, it’s triggered by an infection, and some research has shown that it’s the severity of the initial infection, rather than the actual type of infection, that’s important,” she said.
However, it’s difficult to determine exactly what is happening. A person with CFS/ME has a very different looking immune system to healthy controls – which may also be affected by other factors associated with the disease, like a lack of exercise compared to healthy controls.
Norwegian researchers believe that CFS/ME may be caused by the immune system attacking the body, and in November 2011 published results that suggest that they may have touched on one of the central mechanisms of the disease.
In a trial of 30 patients, half were given cancer drug Rituximab, and half were given a placebo. The cancer treatment proved beneficial for those with CFS/ME with a major or moderate improvement in 10 of the 15 patients. Researchers believe the drug inhibited the immune system by wiping out white blood cells called B lymphocytes, which produce an antibody that attacks the body. They believe the immune system may be reset by the drug.
“I think the fact that patients responded to treatment, improved cognitive function, fatigue and pain makes us believe we’re touching on of the central mechanisms,” said Øystein Fluge, oncology consultant at Haukeland University Hospital, where the research was conducted. “But we’re scratching the surface, I would not characterise this as a major breakthrough.”
Research is on-going, as the team are now looking at giving more doses over a longer period of time. If their initial instinct is correct, it will throw up more questions such as what the immune system is attacking, and whether a test for the disease can be developed.
In the 1980s, Ramsay’s definition detailed a problem with the circulatory system. The extremities were often cold, and recovery of muscle power after exertion was unduly prolonged. Professor Julia Newton studies the association between those who black out or feel faint to those with CFS/ME. She believes that there is an underlying pathophysiological phenomenon that is common in both.
“The common thing is blood pressure regulation, and I’m particularly interested in the autonomic nervous system, so that’s the subconscious nervous system that controls things like your respiration, your heart pumping, your bowels and your bladder working,” said Newton, Associate Dean for Clinical Developments and Clinical Professor of Ageing and Medicine at Newcastle University.
“Blood pressure keeps your blood pumping around the body and if that doesn’t happen effectively enough, it drops; at the extreme end of things you’ll black out, and at the more subtle end of things not enough blood gets to – not only your brain – but your heart, your muscles and the other organs, and that’s what I believe leads to the symptoms of fatigue.”
Simon Taylor was diagnosed with CFS/ME in 2011, over a year after he inexplicably passed out. Afterwards he suffered from constant fatigue, yawning fits and was unable to even walk up a flight of stairs without his muscles aching. After several visits to the doctor and undergoing various test to check his heart and rule out other illnesses, Simon received a diagnosis of CFS/ME.
“It was quite a frustrating process, and I encountered a lot of negativity and disbelief while waiting to be diagnosed. I’d gone from being a healthy 25-year-old trainee teacher who enjoyed playing football, to the complete opposite,” Simon said. “I didn’t like to go out in case I was unable to make it home again, I slept a lot because I always felt tired, and had to give up my teaching course as I physically couldn’t keep up with the demands.”
And Simon isn’t alone – Newton says that 90% of patients with CFS/ME report symptoms of dizziness and light-headedness when they stand up, and 56% of patients describe a history of a loss of consciousness.
Newton also believes that changes in blood flow can affect the muscles. She has conducted MRI-based studies in which patients with CFS/ME and other fatigue associated disease have been exercising in the scanner.
“Using that technology, we’ve been able to show that patients with fatigue accumulate lots of acid within their muscles when they exercise, and have difficulty getting rid of that acid from their muscles when they finish exercising,” she said. “We’ve begun to take cells from muscle biopsies in patients with CFS/ME and grow these muscles in the laboratory.”
These cells are exercised to a known amount to see how they respond and will enable researchers to see fluxes in acid according to how the blood flow is changing. Importantly they are not influenced by anything else within the human body and so can’t be deconditioned – a problem in patients with CFS/ME.
“MRI studies have allowed us to show that the severity of the acid accumulation is directly related to the degree of abnormality within the autonomic nervous system,” said Newton, who believes more research is needed to see where the abnormality lies and where treatment could be targeted.
However, it is only recently that research into the disease has begun to concentrate on factors such as this – much of the early research focussed on the psychological factors of the disease. Between April 2003 and November 2006, the Medical Research Council (MRC) turned down 10 biomedical applications relating to CFS/ME and funded five applications relating to CFS/ME in the psychiatric/psychological field.
The MRC has since encouraged new high-quality research into CFS/ME and partnerships with researchers already working in the area. In 2010, the All-Party Parliamentary Group on ME (APPG on ME) produced a legacy paper which welcomed the initiative but stated that too much emphasis had been placed on psychological research in the past. They felt research should focus on biomedical factors, which could discover a cause and more effective treatments.
But why has research into the psychological factors of the disease received so much attention? Even in the 1980s, Ramsay argued that the disease had no psychological basis. He said that after routine examination failed to find anything, patients were referred for a psychiatric assessment, but were often bounced back with a note saying: “This patient’s problem does not come within my field.”
Part of the problem may lie in the fact that many people diagnosed with CFS/ME also have depression, irritability, mood swings, anxiety and panic attacks. The likelihood is that these problems are identified before CFS/ME is diagnosed – since it can take several months to rule out all other illnesses. The disease has often been misdiagnosed as hypochondria or a psychosomatic illness.
Impaired memory or concentration – or brain fog – can also be another symptom of the disease, which has led to the belief that CFS/ME is a neurological condition. Patients can have difficulty with speech and choosing words, often failing to recall the correct word or substituting hot for cold for example.
“Brain fog and a lack of concentration can make having a simple conversation really difficult, especially on the phone,” said Simon. “I used to find it difficult to have even a five-minute chat with family without forgetting a word or getting distracted – sometimes I still do!”
“It’s annoying for them as they have to wait for me to remember the word, or realise that I’m not listening to them – but it’s hard for me as combined with this, sometimes I can’t even hold up the phone.”
Once diagnosed, Simon received help from a specialist who recommended that he try pacing – an energy management strategy which encourages behavioural changes. He was advised to set daily exercise or activity goals – and rest to avoid over-exertion – and gradually increase these targets.
Pacing has consistently been rated as one of the most helpful strategies by CFS/ME patient groups as it can be adapted to suit individual symptoms, needs and abilities, but it doesn’t suit everyone. The therapy is appropriate for those at or near their maximum levels of functioning and can help to stabilise the condition and avoid post-exertional malaise.
In a similar vein, graded exercise therapy (GET) sees exercise and activity start off slowly and gradually increase. The idea is to avoid the ‘boom-or-bust’ cycle in which patients over-exert themselves when they feel able to, and crash when they are unwell. Avoiding over-exertion is the key and many patients find the guided physical activity can be beneficial. However, many doubt this strategy, with patient organisations reporting adverse effects – the ME Association report that between 30 and 50% of patients were actually made worse by GET.
Another widely recommended treatment is cognitive behavioural therapy (CBT) – a form of psychological treatment which aims to help patients understand their symptoms and develop strategies to improve day-to-day functioning.
Many trials suggest that CBT is an effective treatment to reduce fatigue and should be recommended to treat all patients with CFS/ME, but patient organisations say the treatment can often make people worse, with the effects diminishing after therapy is completed.
Ramsay wrote that prognosis was dependent on the management of patients in early stages – those with complete rest often do well, but treating the disease can be a long and arduous process. Crawley agrees:
“One of the problems with this illness is it comes and goes and it affects people differently on different days. It can cycle by days or by weeks, or by months. It’s a very difficult and disabling condition,” she said.
CBT and GET have a moderate effect in helping patients manage the symptoms of fatigue, and pacing is most favoured by patient groups, but this doesn’t treat all the symptoms. Medication is often used to manage pain, and help with sleep, while anti-depressants are used to treat depression, which frequently goes hand-in-hand with CFS/ME.
Recovering from CFS/ME is a possibility: for some it can be a very long process, while others get better as suddenly as they became sick. Children are more likely to make a full recovery than adults, with between 54 and 94% of children recovering, compared to 10% of adults9. Many people learn to live with their symptoms and return to a somewhat normal life, but others remain too unwell to even get out of bed. More research into this severely debilitating disease is necessary, and more should be done to educate not just the general public but medical professionals on a disease which they feel unable to diagnose.
1. Myalgic Encephalomyelitis: A baffling syndrome with a tragic aftermath http://www.meactionuk.org.uk/ramsey.html
2. Is chronic fatigue a major source of school absence? http://www.bristol.ac.uk/news/2011/8108.html
3. XMRV and ME/CFS – The quest continues continues http://www.meresearch.org.uk/information/publications/xmrvfind.html
4. What is Chronic Fatigue Syndrome? http://www.thenakedscientists.com/HTML/content/interviews/interview/2097/
5. Immune system defect may cause ME http://www.bbc.co.uk/news/health-15401746
6. Looking at muscle cells in Chronic Fatigue Syndrome http://www.thenakedscientists.com/HTML/content/interviews/interview/2098/
7. Pacing as a strategy to improve energy management in ME/CFS – a consensus document http://informahealthcare.com/doi/abs/10.3109/09638288.2011.635746
8. ME Association position on graded exercise therapy (GET) http://www.meassociation.org.uk/?p=374
9. The prognosis of chronic fatigue and chronic fatigue syndrome; a systematic review http://qjmed.oxfordjournals.org/content/90/3/223