By Professor Roddy Cowie
“There are no true, simple stories”
Suffering from an obscure disorder brings four kinds of torture. First there is the torture of having it. Then in many, many cases there is the torture of discovering that it is not curable – partly because medicine tends to be better at the obvious than at the obscure. Beyond that, there is the torture of not being believed. People tend to think it is ‘all in the mind’, and may even see your distress as something you are inflicting on them. Last, and not least, is the exhausting, endless effort to understand what on earth is going on.
All of those apply to the disorders that have been called ME, Chronic Fatigue Syndrome, post viral fatigue, Systemic Exertion Intolerance Disease, and other things. Making them less obscure matters, and that is what this blog is about.
One of the ways that people try to fight the obscurity actually makes the problem worse. Every so often, there is a surge of enthusiasm about a new theory or treatment: brain training, biofilm bacteria, the Marshall protocol, and so on. That is almost guaranteed to end in disillusionment: the chances of a dramatic breakthrough are very remote. Worse still, onlookers have an immediate reaction to that kind of enthusiasm: they label it as crank behaviour. That often has a poisonous result – onlookers suspect that the symptoms are no more believable than the explanations.
The alternative is hard work, dull, and full of disappointment, but it is what we have. It is trying to work out where we stand by digging through scientific journals, and particularly scientific journals with high impact (that means other scientific articles quote them). What I say here is where I think we stand on that basis. I encourage other people to take it as a starting point, and dig for themselves.
A sensible starting point is a 2006 report commissioned by the UK National Institute for Health and Clinical Excellence (NICE), summarised at https://www.york.ac.uk/media/crd/crdreport35_summ.pdf. It makes several useful points. First, it is clear medical recognition that there is a problem, and it affects substantial numbers – it estimates 3-4 people per 1,000. Second, it is not true that research has ignored the subject: even a decade ago, the report could list 70 substantial studies, taking a wide variety of approaches. Third, in most categories (immunological, pharmacological, dietary, alternative), hardly any of the treatments meets the standard medical test of effectiveness – other things being equal, people who receive it fare better than people who do not.
That leads to the areas where the test is met. They involve ‘walking and talking’ therapies – Graded Exercise (GET) and Cognitive Behaviour Therapy (CBT). The table in the 2006 report makes it very clear that those do something. To see what they do, we need to go back to the journals. The biggest CBT study, from the Netherlands, gives clear data. 14 months after the beginning of the study, 1/3 of people who received no treatment reported having recovered significantly. With those who had CBT, that rose to 1/2. That means CBT led to self-reported recovery in 1/6 of the patients. That is a real effect, but very far from helping everybody. Similar points about GET come later.
There was outcry when NICE recommended GET and CBT as therapies for ME/CFS. It was challenged in a judicial review, which was highly publicised. The review decided firmly in favour of NICE. However, what lies behind the outcry certainly matters. It involves two huge sources of obscurity: diversity and the mind-body problem.
Take the mind-body problem first. It needs to be put out of the way. When people object to ‘walking and talking’ therapies, one of the key reasons is because they suggest the problem is ‘in the mind’, not ‘real’. The simple answer is that healing involves mind and body working together. That is why walking and talking therapies are recommended for recovery from heart surgery, and nobody thinks the heart is ‘in the mind’ or ‘not real’. If mental levers are the only ones we have, then we should use them. The subtler answer is that a simple separation between mind and body is long out of date. I have said more about that on a video https://www.youtube.com/watch?v=SqCs-JaO7Wc. In particular, we know that there are loops where thoughts affect feelings; feelings affect body processes like circulation, digestion, hormones, and immune function; those feed back into feelings; which in turn feed back into thoughts … and so on. Several things suggest that ME could easily involve that kind of loop going awry. There is no sense in trying to label problems of that kind either ‘body’ or mind’. There is even less sense in thinking that they are not real. Crude theories about mind and body need to be put out of the way.
The problem of diversity is the opposite: it needs to be brought into clear view. A decade ago, the trend was to take a broad brush approach to defining the problem. Lists of symptoms were drawn up, and people who ticked enough boxes were considered to have ME/CFS. There has always been suspicion that that was part of the problem – there were really many partially overlapping problems, and what helped one might not help another. The figures for CBT fit that picture. Others argued that GET might help some groups, but was dangerous for those whose symptoms included ‘post exertional malaise’ – long-lasting, almost flu-like reaction to exercise (it is still not understood – see, for instance, http://www.ncbi.nlm.nih.gov/pubmed/20433584/ ).
It is dangerous to generalise, but recent research seems to emphasise separation more and more. If we want to find specific disorders, we need to look at specific subtypes. A review from 2015 catches what seems to be a growing consensus. It is at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761639/. It proposes core criteria for ME (not ME/CFS), and lists biological correlates that may occur in core and specific groups. They are diverse – problems with ion channels, neural kindling, molecules and brain cells related to immune response, reactive (‘oxidising’) molecules, reduced cerebral blood flow, the way muscles signal to the brain that they are tired, and others in subgroups.
That is not at all the only research. For instance, it was suggested that CFS arose from changes to the HPA axis (hypothalamus-pituitary-adrenal). New work shows nothing specific to CFS there; but there are changes, probably due to multiple factors http://www.ncbi.nlm.nih.gov/pubmed/15036250/. However, there is striking informal evidence that therapies arising from the idea do good (see http://www.meassociation.org.uk/2012/02/me-the-toxic-tiredness-programme-link-to-watch-it-again-facility/). That is absolutely typical of the way things look. There are true stories, and simple stories; but there are no true, simple stories.
As an old University professor, I know painfully well how deeply people long to be given a simple story. I have also learned to respect people’s ability to understand, if it is explained properly, that sometimes there is no simple story. I have tried to give a little of that kind of explanation. I hope at least it helps with the last two tortures; and on balance, I think research that faces up to the complexity probably will piece together genuinely useful responses to the basic torture of having it.