Does Chaos Theory apply to our illness?

[Dr.Patient]

I've been thinking for a long time about this and becoming convinced that Chaos Theory applies to our illness.

Chaos Theory is " the branch of mathematics that deals with complex systems whose behavior is highly sensitive to slight changes in conditions, so that small alterations can give rise to strikingly great consequences"

A little thing that I do, like eat something that I think is ok, or do something that I think will be fine, will lead to drastic downturns in my strength levels.

They all seem pretty random, but apparently there is a science behind all this.

From Wikipedia:

Chaos theory is the field of study in mathematics that studies the behavior of dynamical systems that are highly sensitive to initial conditions—a response popularly referred to as the butterfly effect. Small differences in initial conditions (such as those due to rounding errors in numerical computation) yield widely diverging outcomes for such dynamical systems, rendering long-term prediction impossible in general. (My bolding).

What is happening in our bodies with this illness---may be we are not at the mercy of this illness after all---there seems to be chaos theory in operation, something that can be explained mathematically.

Any mathematicians out there?

@alex3619 @Mij @charles shepherd @Jonathan Edwards @Gingergrrl @jeff_w

 

[Effi]

My brother is finishing his PhD on complexity in urban structuring. He always talks about me/cfs as a perfect example of a complex system. Problem is that complexity theory is pretty new and most scientists are not up to the challenge yet. I see it as the answer to a lot of today's supposedly unsolvable problems.

I'll leave it to the mathematicians to explain the details.

I'm sure @alex3619 can give you some more insight.

 

[alex3619]

I am not a mathematician, and I have a now very defunct math brain, but I have looked into this more than once, starting decades ago. I was into complexity from about 1990, and was thinking about this for CFS in about 1993 and later.

Chaos theory is not just about wild variations in outcome from small starting variations. It turns out that in many chaotic systems, and in particular all living systems, there are stable zones that things gravitate towards. That stability is what makes life possible, and this was discussed initially by Maturana and Varella. (I actually met Maturana in about 1993.)

Those stable zones have a central point of attraction that is labelled a strange attractor. One of the ideas that has been kicking around in CFS for many many years is the notion that we had one or more healthy strange attractors, but that a severe insult (e.g. infection) kicked the system and it moved to a new strange attractor ... one considerably less healthy.

Please note these are abstract mathematical descriptions of reality. You still need empirical and real world evidence to work with these.

 

[Research 1st]

A little thing that I do, like eat something that I think is ok, or do something that I think will be fine, will lead to drastic downturns in my strength levels.

Hello there.

ME undeniably causes 'chaos' in the human body (as does any other chronic life limiting disease process with no proven treatment), however, this cannot be left to a mathematical model to do the explaining, when biomedical science is already explaining what is wrong in patients. (The Public may not be aware of this, if they read the CDC website on CFS).

You say when you eat, you can 'drastically' worse. What you describe, is one of the most common symptoms of ME, MS, Parkinson's Disease, Diabetes, forms of Cancer, Head Injury and has many reasons why it can occur, and in which tests can be run by a doctor to see if there are reasons behind the patient feeling worse. I am guessing you have never been offered the tests to help you explain your symptoms. This is normal, as doctors themselves don't understand the basic pathology in ME or CFS. It doesn't help the patients understand their condition though.

I will try to help you understand and I hope it's useful to you.


Feeling worse after food is explained by Biomedical Science not a Mathematical Model of 'Chaos':

1*Eating requires energy (ATP) to digest food. If you are energy depleted at rest, eating will make you feel worse because in a disease in which mitochondrial reserve is poor, then naturally, eating uses more energy as metabolic process are required to digest food.

2*Eating affects the central nervous system. If you have autonomic dysfunction (very common in ME), you will feel worse for reasons of neurological and vascular dysfunction from eating, as blood pooling is worsened. When blood pools in your lower limbs your brain has less blood flow and this will be sense by the host. For example, a 'food challenge' is a test that is run in autonomic units. Alterations in blood pressure can occur. There is a name for this dysfunction associated to eating, it's called: 'Post prandial hypotension'.

3*Eating can provoke allergic reactions. Allergies are very common in ME. One symptom of allergy is 'fatigue' or exhaustion. Allergies can be measured in a first step, by measuring IgE levels in the blood. If possible, then specific IgE to individual foods can be measured. Histamine can also be looked at, and mast cell release.

4*Eating can trigger forms of seizures. Some seizures are partial and can cause odd sensations or changes in energy levels, muscle weakness, and temporary drowsiness and worsening fatigue and confusion.


A test I would advise if your health allows, it to have a 'TILT' test. This could explain your symptoms, and you may also obtain a diagnosis of vasovagal syncope.

Simple interventions you could try to not feeling so ill when eating could be:

1) Eat small portions.
2) Lay down or slump in a chair when eating instead of having upright posture, so more blood is kept in your brain.
3) Support stockings to try and squeeze the blood vessels in your lower limbs.
4) Lower the room temperature to reduce vasodilation, e.g. in summer use air-con if possible.
5) Do not have a warm bath or shower before eating.

More complex to ask a doctor if you have a diagnosis of autonomic dysfunction:

1) A medication to affect the CNS, called Midodrine. This needs careful and professional advice on.
2) Octreotide. Again, rather complex and not without side effects or risk.

I hope that helps a little.

 

[SOC]

ME undeniably causes 'chaos' in the human body (as does any other chronic life limiting disease process with no proven treatment), however, this cannot be left to a mathematical model to do the explaining, when biomedical science is already explaining what is wrong in patients.

Mathematical models are not pure abstractions. They are models, based on (and describing) physical realities. They don't ignore measurable data, they use the measurable data. A mathematical model is a way to combine the measured data from multiple complex and interacting factors into one large picture than can help us understand many of the subtleties of interaction that can't be seen by looking as the factors and associated data alone.

One of the many big problems in ME/CFS is that medical science can at present only look at one factor at a time -- orthostatic intolerance, PEM, cognitive dysfunction. In ME/CFS, the factors contributing to, and the results of, those symptoms interact significantly and medicine doesn't have the ability to see down into these subtle, but possibly complex, interactions. That's where mathematical modeling becomes useful. Broderick at INIM is doing some amazing work with systems biology, modeling the interactions. I don't begin to understand it, but it's highlighting a number of interesting lines of investigation and treatment.

Mathematical modeling, including possibly Chaos Theory, has the potential to shed a lot of light on much of ME/CFS research and treatment. Good mathematical models allow you to predict the effect of changes, and to test hypotheses for feasibility before you spend millions on in vivo studies. You can test tens of thousands of potential interventions using a mathematical model in a tenth the time and a tiny fraction of the cost it would take you to do a single in vivo study. That allows you to find the few most promising interventions and only perform in vivo research on those. It could save vast amounts of money, and more importantly to those currently suffering from ME/CFS, decades of research. Mathematical modeling doesn't replace knowledge of the physical realities. It enhances it.

Complex dynamic systems (and the human body certainly is one) need complex dynamic models to clarify what's going on. Looking at single factors and single data points, as medicine does now, does not give a clear picture of a complex system.

 

[Dr.Patient]

What underlies here is the very tiny changes that I make in my every day life seem to "amplify" my fatigue a thousand fold.

Also, the time from when we do something, to when we actually experience something, are so far apart that, though we can make some connections several months or years into this illness---some things we probably cannot, and means that we should look into every microscopic thing of what is happening to us or what we are doing. If the flap of a butterfly wing in Brazil can cause a tornado in Texas (the butterfly effect of chaos theory), we should be looking at things in excruciating detail. And remember that even the tiniest change that we can make will help us heal!

@Effi - I agree with your brother in that mecfs is one of the most perfect examples of chaos operating in medical illnesses.

@Research 1st I am aware of most things that you mentioned, but I did learn a few things, thank you! This is not just a mathematical model, it's also worth pondering by physicians, scientists, and patients alike.

 

[ahmo]

@SOC your post reminds me that a few years ago US National Cancer Institute got physicist Paul Davies to head a team, looking for an outsider's views on cancer, the possibility of a new paradigm.

 

[SOC]

@SOC your post reminds me that a few years ago US National Cancer Institute got physicist Paul Davies to head a team, looking for an outsider's views on cancer, the possibility of a new paradigm.

I think this is a next big step in medicine. Most advanced technologies have used mathematical modeling in some form or other to help understand the interactions and complexities of dynamic systems for many decades. Since many medical people are math-averse, medicine is now decades behind other technologies in applying useful computational techniques. We're just starting to see math/physics/computer science applied to medicine. There's a lot in the problem-solving techniques and understanding of dynamic systems (medicine is very poor at that presently) in these fields that could be of huge benefit to medicine. The best researchers are coming to that realization to the benefit of us all.

Every field needs new viewpoints, fresh eyes. We get stuck in our historical ways of thinking, so it sometimes takes an outsider's view to see the forest (or the trees) we've been missing. It's encouraging that NCI recognized this and took steps to put new eyes on the picture.

 

[Effi]

@Dr.Patient Right now in medical research what scientists try to find is the one detail that explains it all, the smoking gun. With complexity theory in mind this might not be the way to solve every single medical issue. Rather than finding the one smoking gun, it might be more useful to try to understand the system behind an illness like me/cfs.

E.g. looking at blood results the answer might not be in finding the one pathogen or dysfunctional protein, like it is in other illnesses. It could be a question of looking at every single aspect in the blood (and other bodily fluids and tissues) and connecting the dots: various slight deviations together, instead of one single marker that is abnormally high or low.

The only way to check this theory is by compiling big data. And that is why I was thrilled to read about this study:http://www.openmedicinefoundation.org/mecfs-severely-ill-big-data-study/

 

[Gingergrrl]

Any mathematicians out there?

@alex3619 @Mij @charles shepherd @Jonathan Edwards @Gingergrrl @jeff_w

@Dr.Patient did you really think that I was a mathematician or was that a joke? The thought made me laugh though!

 

[Marco]

As Alex said, this is a concept we've discussed here previously and I feel there's some support for the notion that the state of ME is due to having switched to an alternative (dysfunctional) atttactor (perhaps the initial viral or other insult represents the basin of attraction - the initial conditions that favour the shift to the new attractor).

Two aspects of ME/CFS that might support the concept are how resistant the illness is to change/improvement. Many of us report initial successes with various treatments etc but we always seem to be dragged back to the same state of unwellness. Secondly, some of report occasional spontaneous short term 'remissions' or even absence of symptoms for a short period which would seem to suggest a temporary resetting of the system back to normal rather than some sort of spontaneous reversal of an underlying pathology.

The problem is, while it may be a useful concept it's difficult to see how it can be of practical help unless we could be somehow temporarily knocked 'off-line' and 'rebooted'.

 

[alex3619]

I have had those temporary full remissions while on Immunocal. A few every year at that time., and typically about six hours for me. Sadly, none since I stopped taking it due to side effects.

Systems biology is one big avenue that may lead to major gains in understanding. Its all about how the pieces fit together. Systems approaches are what I have been interested in since before I was ever diagnosed with CFS, let alone ME. I was trying to use these approaches for neural modelling in my PhD candidacy.

I think that a big issue with most long term chronic diseases is that we love to oversimplify, whereas they are really manifestations of layers of complex interacting biochemistry. We still do not have the tools to fully figure this stuff out, but there are a lot of researchers working on this outside of ME or CFS research.

For example, a century of type 2 diabetes research, and what do we have? Pieces of a model. I am not even sure that diabetes is one disease. I think its a common name for many diseases with overlapping symptoms and mechanisms. Its not one disease. These kinds of fuzzy non-discrete diseases create havoc with traditional reductionist science, because by excessively isolating factors you essentially remove much of the complexity and can easily lose track of complex interactions.

The big change that medicine needs is to get away from simplistic categorizations and start working on mechanisms. This is going to make things very hard for doctors. Its no surprise that (in my opinion) many doctors do not want to even think about the detailed interactions that functional medicine is trying to use. Its also correct to say that to a large extent the science is not evolved enough for this to be very useful ... but that is changing, fast.

 

[user9876]

I've not read the thread but its something that has been crossing my mind recently.

We talk of a number of complex cycles and feedback loops which are being disturbed as a secondary thing to the main problem. Then feedback loops are naturally complex non-linear systems and hence may exhibit chaotic behaviour. So could this be a reason for a lack of consistency over measurements made in say of immune system markers. That is for each person the systems are perturbed but not in a necessarily predictable way.

 

[eafw]

The problem is, while it may be a useful concept it's difficult to see how it can be of practical help unless we could be somehow temporarily knocked 'off-line' and 'rebooted'.

There have been experiments in RA, from a while ago so don't if it was ever followed up in this form (*), to knock out the immune system and go again.

http://onlinelibrary.wiley.com/doi/10.1002/art.10093/full

http://www.donotlink.com/fnlv (Daily Mail link but gives basic overview)

it's very drastic and not sure how practical it would be, or even if it would work for ME immune issues.

(*) my vague understanding of the rituximab stuff is that is does something similar ?

 

[Dr.Patient]

@Dr.Patient did you really think that I was a mathematician or was that a joke? The thought made me laugh though!

Just to inform, not all of them tagged are mathematicians...

 

[Dr.Patient]

PEM is pathognomonic of mecfs---no other illness has this.

A small activity like going out, or taking a shower, leads to weeks, months, and years of worsening of fatigue and other symptoms. This is "amplification" at it's best--small alterations giving rise to strikingly great consequences.

No other illness lends itself to classic chaos theory as much as mecfs does.

 

[anciendaze]

@Dr.Patient

Before you can have deterministic chaos you need to have some kind of dynamics. This is nearly impossible when current medicine treats virtually all variation as random, a subject I tackled in a blog post. There is no lack of applicable theory, as was demonstrated by work on heart dynamics done in the 1980s. This has yet to change most of the practice of cardiology. About half of all heart attacks come as a surprise to doctors as well as patients. This is not good evidence of medicine as a science.

(If you want to see what understanding of random variation passes muster among physicians you can find howlers almost everywhere. I've repeatedly been over the absurdities committed in the PACE study, which applied parametric statistics to distributions that were manifestly not normal, then claimed to have hard objective data showing their preferred approach was both valid and useful. Except in the sense of being a basis for denying disability claims, their limited objective data failed to show clinically-significant improvements in performance. The bulk of their data were simply subjective, and only make sense if you assume the disease is purely subjective. That study alone is a blot on the profession.)

You have singled out one aspect of complex dynamics which shows up in chaos: sensitive dependence on initial conditions. This can appear in non-chaotic situations, and medicine has already seen some. This also showed up in engineering aspects of important applications such as the analysis of aircraft "flutter". There is a critical speed at which dynamic behavior changes, and computing and avoiding this keeps you out of the domain of fully-developed chaos, something to be avoided in airplanes.

In medicine the dynamics of glucose metabolism were poorly understood, with the result that diabetics continued to suffer crises and amputations which carefully-controlled diabetic laboratory animals did not. (I can remember people from this period who suffered such consequences.)

The obvious answer was to sample frequently, especially at times when the doctor's office was closed, and adjust insulin doses accordingly. The time it took to implement this simple change was substantial. Even after glucose meters were available, it involved a power struggle over patients running tests and making treatment decisions.

If you designed an airplane without doing a control-sensitivity analysis you would be held responsible for everything that went wrong as a result. Sensitivity is an important aspect of biological control systems, and I know a diabetic who is 30 times as sensitive to insulin as a healthy person. When he speaks about his multiple problems at medical conferences one common question is "how have you survived?" The answer is that he learned about his own problems, and took control of many treatment decisions. Somehow, the idea that other patients with this combination of conditions are being killed by doctors giving advice suitable for generic patients with different problems doesn't get through.

 

[Dr.Patient]

@anciendaze Loved your blog post! "All reports of the "natural history" of this disease emphasize the importance of variation and stressors, though patients may not be correctly attributing causes to effects". -agree. This is where computers should take over, human brains fall inadequate, and especially with this illness.

Few intelligent physicians think variations to the mean are random, most certainly somebody with the depth to understand this illness. However, they don't have the energy required to be the patient, even for short periods of time, as written by M. Scott Peck in his The Road Less Travelled.

That leaves the burden of finding the tiniest variables to the patient, unless such dynamics of complexities can be taken over by computer algorithms.

 

[alex3619]

So could this be a reason for a lack of consistency over measurements made in say of immune system markers. That is for each person the systems are perturbed but not in a necessarily predictable way.

Definitely. Its also why, in my opinion, many interventions have temporary effect. You push the system. You feel better. But its a stable system and pushes back. Medication "stops" working. Actually its still working, you have just moved to a slightly different stable state.

 

[alex3619]

Somehow, the idea that other patients with this combination of conditions are being killed by doctors giving advice suitable for generic patients with different problems doesn't get through.

I think this is a broad and critical issue in medicine. Patients are not theoretical average cases.