Sunday, 22 October 2017

Temperature

Twists and turns in the MS research trails


Hi, I am Mark Baker, a university lecturer, and I teach neuroscience to medical and science students at QMUL. I am also a member of Barts MS and have maintained an interest in MS over many years. I have been involved in research investigating the mechanisms of excitability in normal and diseased nerve, involved in pain signalling and the effects of demyelination. What do I mean by the mechanisms of excitability? I mean that amazing characteristic that allows some specialized cells to generate impulses that are used for signalling, so in nerve this characteristic allows us to feel things and work our muscles.
Fundamental shifts

MS is a disease targeting nerve fibres in the brain. When I first became interested in what was going on in MS, as a student, the condition was thought of as mainly a demyelinating disease, but no longer. Well within my lifetime, the understanding has evolved, and MS is now thought of a demyelinating disease, but also a neurodegenerative disease. The emphasis now has changed. 
When this kind of thing happens it is important for science and medicine, and ultimately patients, because light can be shed into what were darkened corners and questions asked that had not been asked before. This whole process of discovery is about real people in a lab or clinic somewhere asking questions and noticing something perhaps for the first time, and then reporting it, but the question asked arises out of the knowledge base, at that time, and I guess it is important to appreciate that. I can think of another example in MS research when ideas have fundamentally changed, and of course, there may be others.
Temperature-dependent symptoms

An idea that was of some importance in the 1980s developed directly from the known temperature-dependent symptoms in MS. Many people reading this post will have temperature dependent symptoms that are serious enough for them to have to try to keep out of hot places, for example. 

One result that is not disputed and had stemmed from the basic science of physiology was that the nerve impulse got briefer when the temperature increased, and what was shown in elegant experiments was that when the myelin was damaged in nerve, having a briefer impulse made the impulse more likely to fail. 

This failure of impulse conduction along nerves in the brain and spinal cord with raised temperature, following demyelination, is the classical explanation for the appearance of new symptoms and exacerbation of existing ones with a rising core body temperature. 
One way of trying to do something about this was to try to make the nerve impulse longer by using drugs that block proteins in nerves called potassium channels. There have been several clinical trials and potassium channel blockers are still under investigation to determine any useful effects. 

The irony is that the widening of nerve impulses that provided the way into this area of research cannot be the basis of the useful therapeutic effect under investigation now, because the concentration of the drug that is necessary and safe for beneficial effects on walking is far lower than that required to make the nerve impulse longer.

Comments please:

Do you have temperature-dependent symptoms? 

If so, what do you do about them? Have you found any strategy or treatment effective?

Let me know in the comments 

What else you would like to know about the basic science behind MS? 

Thank you!

13 comments:

  1. "Let me know in the comments what else you would like to know about the basic science behind MS."

    Does simple repition of motion lead to remyelination..because have heard that musicians have denser thicker myelin which comes from repeated motions and leads to more efficient and faster movements.
    We're talking about thousands of times over and over.

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    1. Dear Adam,
      Myelination in the central nervous system is happening at birth and also for a time after we are born. Normal reflexes associated with the feet and our normal upright posture only come about following completion of myelination in the corticospinal tract, when we are babies. So at least this developmentally crucial phase of central myelination occurs without us having to exercise in a particular way at all. It is a part of normal development.
      Another thing that might be relevant to add is that the fastest impulse conduction pathways are those involved in reflexes, that are not learned, but are automatic. These reflexes involve pathways with the largest diameter axons, and the most myelination. Such reflexes may be modified I guess, but this reflex activity is a facet of the nervous system doing the really important stuff automatically without having to bother us at all. These reflexes are going on all the time and allow us to take up gravity defying postures (such as standing up) without falling over. These sort of things have real survival value, in a way that playing the violin does not. Clearly playing a musical instrument may improve quality of life, or be involved in sexual selection, for example.
      I recall that when I was at school in the 1970s, the newspapers were suggesting that the amount of myelin you had in your brain was determining how clever you were (this was also the time of anti-gravity machines discussed on the 10 o’clock news). Now I look back on this I find I do not know the evidence for this nor do I really understand the claim that is being made. Much of what we would call clever stuff going on in our brains will involve nerve fibres that are only small and normally thinly myelinated, for example our ability to see in colour. Finally, I think that abnormalities of peripheral myelin can come about when we hurt ourselves by applying pressure to peripheral nerves or by mechanical injury. This will be related to temporary demyelination, followed by some repair. So if you damage your peripheral nerves, by mechanical pressure, there may be some remyelination going on. A classic place for this is the ulnar nerve at the elbow.
      Mark

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  2. So many of us suffer when the sun shines and it gets too hot, I do. In the winter my feet are now cold, especially my toes and when I go outside I must put on extra layers. I'm sure this is not just because I am in a mobility scooter. An I unique?

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    1. Dear Patrick, On two counts I think you are not unique regarding these sensitivities to temperature. Firstly, the sensitivity to heat exposure is common in MS, and has been noted over very many years. It is said that most pwMS are sensitive to a small rise in core body temperature that can exacerbate existing symptoms, or make new symptoms appear, and there is some literature on that explaining the phenomenon. Secondly, a sensitivity to cold on first hearing sounds normal, and linked to changes in peripheral circulation that may be nothing to do with your condition. There is the possibility, however, that feeling cold might exacerbate some latent spasticity, but that is pure guesswork on my part

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  3. On a good day I can walk on a treadmill at 1.5mph for 5 minutes. After swimming in a cold pool (65 degrees F) for 20 minutes I am able to go for 30 minutes at 1.9mph. The change is so dramatic. Cooling vests, caps and soaking in a cold bath help a bit but do not drop my core temperature like swimming in a cold pool.

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    1. Dear Mark, Thank you very much for sharing this with me.

      Mark

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  4. I also have temperature related issues. When my core temperature increases due to exercise or external temperatures I feel wonky. Balance is off ( more than usual), and gait as well. What helps... cooling off and resting for a few minutes.

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    1. Thanks for sharing your experience

      Mark

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  5. I am an MS sufferer living in Spain and so I struggle with warm weather most of the year. Prior to MS I was generally always cool or cold in the winter months. Now I find I feel hot all year, however, I have noticed a marked deterioration in my walking and balance from May to September which obviously coincides with the hotter weather. One thing that really helps is swapping from walking for exercise, to swimming. In fact I actually would prefer to swim all year around but the water gets a bit too cold for me. I certainly feel more able to walk once I have swam my lengths. (50+ laps of 10meters length)

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    1. Many thanks for making this contribution. It seems that swimming offers advantages

      Mark

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  6. When the temperature went above 23C my walking and bladder control both deteriorated. This was true until June this year, when I stopped being able to walk very much at all. I've been using a wheelchair pretty much full time since then and we haven't had any hot weather.
    When it was hot earlier this year, as long as I wore a cooling vest, I didn't see any deterioration in my symptoms. I have two, so that one can be cooling in the freezer while the other is absorbing heat on me. When it was hot last year, before I had the cooling vests, I kept my symptoms under control by drinking lots of iced water.

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    1. Dear Cordelia, I am very grateful for your practical insights into temperature control, and to hear about your experiences. Because our bodies normally control core temperature within tight boundaries, one thing that is underlined by your observations is that the change in core body temperature that ends up affecting your symptoms must be small, a fraction of a degree centigrade. Such a small change may be rectified at least partially by the suit and the iced water. One scientific challenge is to find, if possible, some convenient means of providing the beneficial effects of cooling (once we have understood them) and so improve quality of life. Clearly if this could be done without having to have a swimming pool on hand and a cooling suit, then such relief might be more widely felt, and in more commonplace circumstances. That would be something.

      Mark

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  7. I am already aching from the shivering and tingling that starts when the temperature drops. Multiple layers of clothing don't help as I can't generate heat from the inside. It comes with the restless leg feeling that spreads up into my back. I can feel warmth against my skin, but it can't seem to register inside my body. I look forward to the summer, till it gets here and I get overheated and lethargic, then I look forward to the winter!

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