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DEVELOPMENTS IN RESEARCH AND UNDERSTANDING.

Within the diagnosis of C.F.S. there are essentially three major sub-groups: 

 I will suggest that all three of these fatigue states are almost invariably associated with long standing negatively directed pre-morbid stressor factors.  In my earlier days in the mid and late eighties I believed that these illness processes especially the acute onset variety of C.F.S. were caused and perpetuated by a virus infection.  The reason for my bringing this up now is that a large number of doctors, patients and support groups believe that this is still the case. 

In ‘89 I published with others a paper entitled ‘Chronic Enterovirus Infection in Patients with Post-Viral Fatigue Syndrome’ in the Lancet, January 23^rd, pages 146-149 and it demonstrated very clearly that even after a number of years we could not only demonstrate the presence of bits of viral protein inside blood samples but we could even recover live infective virus from the gut of patients with this illness.  Others, around this time also, were able to demonstrate that these viral particles could be found in muscle biopsies and that physical and physiological abnormalities were demonstrable in muscle tissue.  This being the case means that there would be absolutely nothing anybody could do to help a person with C.F.S. if their illness was caused by a virus because at that time, and indeed to date, we do not have anti-viral medications which can penetrate into cells and kill a persistent virus infection of any kind. So around this time I was seeing patients and telling them that there was essentially nothing I could do to make their illness better but hopefully it would go away in time or they would tend to improve and statistically that was true.

It was also true that a large number of patients not only had the acute variety that was not associated with enterovirus but they were giving a story suggestive of glandular fever as a start.  96% of glandular fever is associated with Epstein-Barr virus.  I approached and started to do some work with Professor Dorothy Crawford in 1989. With others we wrote a paper entitled ‘Active Epstein-Barr Virus Infection in Post-viral Fatigue Syndrome’, (Journal of Infection (1989) 18, 143-150).  This showed that approximately 25% of patients with this acute onset variety could be shown to have antibody responses in their blood directed towards the Epstein-Barr virus and that these abnormalities were persistent.

This all led me to write an article summarising the patients that I had been studying, those that were associated with enterovirus and those that were associated with Epstein-Barr virus and to tabulate the various abnormalities that one could find. This was published in The Royal College of General Practitioners Members Reference Book in 1989.  Two things then happened that were to change my entire understanding and for a year or so would leave me with a headache and an internalised dichotomy.

Firstly there was a paper written by Professor Edwards at Liverpool that suggested that patients with C.F.S. had nothing wrong with their muscles and that there was no fatigue that could be demonstrated anywhere in any of the muscles in any part of the body.

I have long since learnt not just to read papers but if anything is really of great significance then one should go and see the author and discuss it and this is what I did.  I also took some patients of mine with me and I spent ten days with Professor Edwards studying his techniques and the methodology behind the statement that there was no peripheral fatigue demonstrable.  I came away from Liverpool totally convinced that there was no demonstration of any fatigue in skeletal muscles and that, whilst patients often felt worse after exercise or physical activity, the muscles could be made to work normally over long periods of time.  This then must, of course, bring into doubt whether there is any pathological process going on inside the skeletal muscles that affects their function.  The abnormalities that are demonstrated in electrical activity, or structurally in muscle biopsies, or the presence of virus particles inside the muscle have no demonstrably abnormal impact in the muscles power or work output.

Secondly, and much more importantly from my point of view, was the fact that, by the time I had reached the end of writing this article for The Royal College of Practitioners, I couldn’t tell the difference clinically between the patients that were made ill by enteroviruses and those that were made ill by Epstein-Barr virus; they seemed to me to be totally identical.  I went back to one of my previous authors and one of my most important mentors and pointed this out but I am afraid that this did not go down well and we ended up with a blazing row.  It was suggested to me that patients with enterovirus infection had much more in the way of muscle pain than those that had Epstein-Barr virus who were complaining mainly of just simple tiredness and fatigue.  I had to disagree.  I then came across the Department of Cellular Research at Northwick Park, which at the time was run by Dr Timothy Peters, so I went to see him and told him my story. He admitted to being a C.F.S. sceptic but agreed to admit twelve patients for intense investigation.  By the end of this process the patients had been taken apart by Physicians, Psychiatrists, Neurologists and Immunologists and the summary was that they all agreed that these patients were ill, that they were not psychologically disturbed, that there appeared to be nothing in the body that was abnormal and the problem had to have a different explanation as yet unknown.  Now I knew, and they didn’t, that some of these patients were ill with enterovirus abnormalities in the blood and others were those that had active antibodies to Epstein-Barr virus and none of them could tell the difference between them.

If one now stands a little further back from this picture and starts to apply a little bit of lateral thinking, when you have patients that you cannot differentiate between or tell apart, then they must be the same. They may, however, have different degrees of severity but if all the investigations are normal and all of the Physicians looking at them cannot tell the difference then there is probably and most likely to be only one disease process going on and that process must lie somewhere outwith the body and inside the brain.  Also it is quite a straightforward step to state that you cannot get one single process within the brain being caused by two or possibly more different viral agents.

Viruses cause one illness. Certainly the majority do exactly this, although, of course, chicken pox is also associated with later reactivation and causes shingles, but it is the same single virus.  Mumps virus causes mumps, influenza virus causes influenza, Coxsackie’s B virus and the other enteroviruses cause some a flu-like illness and Epstein Barr virus causes glandular fever.  If you have one illness caused by two, three or even more different viruses (and there are a lot of patients with C.F.S. who associate their illness onset with other types of viruses, generally a non-specific ‘flu)’ then this particular illness can only be triggered by the virus and the virus is not the cause.

If the virus is only the trigger not the cause, is not perpetuating the illness and is not pathological then, of course, one has an enormously important statement to make and that is that you do not have to kill the virus to get the patient better. Indeed even if the virus is present in the body, and there is no doubt we could demonstrate this in the two papers that I published, then the presence of these viruses is irrelevant. So now suddenly the virus ‘disappears’; it is of no importance.  It then took me a long time to try to clear my head of all the work that I had done previously and put it into my psychological dustbin, although of course at the same time not totally discarding it because there was one unanswered problem and that was the fact that all of the patients that I had studied had a turned on immune system. Their immune system seemed to be fighting a virus on what appeared to be an almost constant basis.  What was happening?  Why was this occurring?  I wasn’t the only person who found this particular immunological abnormality.  By this time in the very early part of 1990 there were at least one hundred papers demonstrating a non-specific immunological turn on directed mainly and principally towards a viral or anti-viral reaction.

I had by now come to the opinion that this illness had nothing to do with viruses but I wasn’t quite sure what it was caused by and of course as I was working as Medical Advisor to the M.E. Association they quite rightly and properly asked me to leave. I felt a little aggrieved at the time but have long since seen that that was inevitable.  It wasn’t until much later, I am not quite sure when but I believe probably by 1993, that it became much clearer to me that patients with this illness process invariably had a long story of negative stress.

Psychoneuroimmunology

 In the Annals of Medicine 25: 473-479,1993 was the first article that I read on the basics in Psychoneuroimmunology.  This coupled with a paper entitled the Psychotropic Treatment of Chronic Fatigue Syndrome and Related Disorders published in the Journal of Clinical Psychiatry Volume 54, Number 1. January 1993, gave me the understanding of the basis of where I am working from today.  Later when I was able to show some abnormalities in the fluid surrounding the brain by lumbar puncture the whole situation became clearer and the story is neat, tidy and scientifically waterproof.  From this base I have been able to build a model of the cause of C.F.S., which has led to vast improvement in treatment outcome and which for the last six years has been indestructible, no matter how hard I try to knock this model down I cannot do so.