More on heat sensitivity or Uhthoff’s phenomenon

#MSBlog: More on temperature sensitivity; how temperature blocks conduction in demyelinated axons!

Stutzer & Kesselring. Wilhelm Uhthoff: a phenomenon 1853 to 1927. Int MS J. 2008 Sep;15(3):90-3.

The name of Wilhelm Uhthoff is associated with several aspects of progress in neurology in the 19th and 20th Century but is best known for his contribution to the pathophysiology of transient visual disturbance in people previouslt affected by optic neuritis. Uhthoff was born on 31 July 1853 in Klein Warin, Germany and died on 21 March 1927 in Breslau, Germany. This ophthalmologist described for the first time that increased body temperature from physical exertion may lead to transient impairment of vision in MSers.

“This figure shows you the affect of temperature on conduction velocity for a normal nerve fibre (upper curve) and for fibres with increasing loss of myelin (lower curves). For each curve the last point on the right is for the highest temperature at which continuous electrical conduction is possible, the dashed lines and arrows indicate a block of conduction The amount of demyelination in this figure is expressed relative to normal. What this shows that if you have a demyelinated axon it becomes very susceptible to temperature, for example normal fibres only block above 44 degrees C and fibre that is 67% demyelinated blocks at temperature at or slightly above body temperature. What worries me is that these fibres that are maintaining conduction are vulnerable to degenerate in the future. This is why we need to protect them so that they can remyelinate and correct their temperature sensitivity.”

“The following two videos demonstrate how a normal and demyelinated nerve fibre conducts. It is clear  that the demyelinated one uses a lot of energy to transmit an electrical signal. This in itself may damage and cause the nerve fibre to degenerate over time. For those of you who think remyelination strategies will be sufficient to cure or treat MSers need to think again. We think MS is an immune disease that attacks myelin, therefore without supressing the immune attack on myelin and new myelin t hat is formed will simply be damaged again and with time this process fails. This why we need three approaches to treat MS; (1) anti-infammatories, to suppress the inflammation, (2) neuroprotective agents to keep the axon and nerve cell alive so that (3) remyelination can occur. The evidence that we need to augment remyelination in MSers is weak; all the evidence suggests you can do it on your own provided the inflammation is suppressed and the axons are still there to remyelinate. This may be why we see improvements in disabilities occurring when you are treated with more effective treatments.”

“Conduction in a normal axon; note how fast it conducts with minimal effort or energy!” 

“Conduction in a demyelinated axon. It has restored conduction by a process called axonal plasticity. The conduction is slow and laboured and requires a large amount of energy  to conduct the electrical impulse. This axon is very temperature sensitive and is liable to block with a rise or possibly a fall in temperature. This axons is also susceptible to degenerate unless we can protect it long enough so that the body can remyelinate it.”

10 thoughts on “More on heat sensitivity or Uhthoff’s phenomenon”

  1. Re – “The evidence that we need to augment remyelination in MSers is weak; all the evidence suggests you can do it on your own provided the inflammation is suppressed and the axons are still there to remyelinate!”Hold on, this deserves some level of elucidation. What do you mean by this statement? Are you implying the central nervous system can, despite having been ravaged by progressive MS, still remyelinate axons providing they are still alive and void of inflammation? Are you saying that oligodendrocytes, even in those sufferers that have advanced/ malignant MS, still actually sustain its function in the CNS? But how can this be when you don’t yet understand what processes are driving progression and atrophy?What you have argued is the opposite of what the Cambridge Remyelination Centre is proposing, which is discovering a stem cell treatment that will activate oligodendrocyte precursors in the brain and spinal cord that will not naturally function in MSers. You have indicated that such cells will automatically come alive if inflammation is dampened and nerves are made stronger, which is the opposite of everything I’ve heard so far about CNS restoration.Also, did you see Maurice Saatchi on Newsnight last night talking about how a fear of litigation is acting as a deterrent in the development of cutting-edge cancer treatments? He said that innovation is stifled by medical negligence law because no doctor has a defense against negligence claims if they have deviated from standard procedure. He has proposed a Private Member’s Bill to his Tory bum-chum, David Cameron, which aims to clarify the differences between ‘‘responsible innovation and reckless experimentation.'' His efforts are fuelled by the woeful lack of options available to his late wife who died of ovarian cancer last year. Isn’t there a worry that such a Bill will spur neurologists to peddle further toxic DMTs to Msers without the evidence they actually do any good? What will such a measure mean for the world of MS treatment in Britain if it goes through?

    1. John Prineas described shadow plaques and showed large amounts of remylination in MS decades ago. More recently Bruce Trapp has shown quite elegantly that large amounts of remyelination occur in MS. In fact at a meeting he recently said that remyelination, particularly in the gray matter, is the norm. my opinion remyelination strategies will only work when the CNS mircoenvironment is conducive for myelin producing cells to survive and for the new myelin not to be damaged by further autoimmune attacks. For this to happen you have to switch off the inflammation and make sure there are enough surviving demyelinated axons to remyelinate. You can't remyelinate something that is not there. Therefore remyelination comes third in the cascade of treatments: 1. anti-inflammatory therapies to switch off inflammation; 2. neuroprotection therapies to keep the axon alive; and 3. remyelination last. In fact if you get one and two correct the axon may remyelinate without any remyelination therapy necessary. This is also the opinion of two giants in the field; John Prineas and Bruce Trapp.

    2. You don't seem to take into account one major observation of prof Prineas, that demyelination is the result of oligodendrocyte death which happens prior to any inflammation.

    3. You are taking about T cells, but there is more to inflammation than T cells, what about microglial inflammation and what if the lesions you are talking about are not MS but NMO?Are you coming to the researhc day?

    4. I'm Athens with Hans Lassmann-one of the worlds leading pathologistsI can put questions to him if you are quick! Maybe get a different world view.

    5. "what about microglial inflammation"Prof GG says "1. anti-inflammatory therapies to switch off inflammation;" I'm sure he does not mean microglial inflammation. After all, Tysabri, Gilenya, Lemtrada target immune cells of the blood, not the microglia. Which means they can do nothing to stop oligodendrocytes from dying.


  2. Remyelination of demyelinated axons is a well-known and described phenomenon in MS, provided they are still there to demyelinate.The Cambridge team still live in the past when MS was widely thought to be solely a demyelinating disease also reflected in the unrealistic animal models they use. It isn't and whilst the aim of improving remyelination is a good one, first you have to save the neurons so that they can be remyelinated.Maurice Saatchi is understandably bitter about his wife but the fact is that most cases of ovarian cancer are only diagnosed when the cancer is advanced.A similar situation holds with neurological diseases such as motor neurone disease, by the time you're diagnosed, it's too late to do much about it.I suspect the chances of his bill passing are slim to none.

    1. I will sit in the middle but the fact is that after demyelination, remyelination is the default pathway and occurs completelty in most animal models within a few weeks of the insult and some of the remyelinating drugs are simply augmenting what would occur given time. There is some evidence in the white matter in animals that remyelination may not occur well in old animals but this was not the problem of the remyelinating machinery. In the grey matter remyelination was occurring in seventy plus year olds.Although in some MSlesions there is a paucity of cells capable of repair it is common that there are plenty of precursor cells around lesions maybe there are blocks in their maturation which is the approach that is being investigated. However blocking damaging responses is the first important part in the equation

    2. re – "In the grey matter remyelination was occurring in seventy plus year olds."Grey matter demyelination is what is causing disability in MSers, is it not? So if remyelination is constant then that is great news, right?

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