Tuesday, 17 January 2012

Research: MS Fatigue

It is not just Docs and Academics that do surveys. The International Multiple sclerosis Federation has just done a survey of about 10,000 MSers in 100 countries reported in MS in Focus 2012


This reported that 86% of people said that FATIGUE was one of their 3 main symptoms and 62% of people recieved no medications for this symptom.

We are aware that there is a real unmet need for the treatment of fatigue. However understanding this and doing research on this subject is difficult and is near impossible in our furry friends. However the best thing to sort out fatigue is going to be getting decent drugs that stop disease. This was one of the noticable pluses with tysabri, which help offset some of the negatives

17 comments:

  1. Wow, a light just went on. I was taken off tysabri in June, and my exhaustion has since taken over my life :(

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  2. RRMS is better off than PPMS but there are still no 'decent drugs that stop disease'. It can easily happen that you go through almost all of them one by one and have to stop each for some reason or other

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  3. Poor MouseDoctor - all he can think about is ways to co-opt his fellow furry friends into doing research into MORE DRUGS!!! Yes, no wonder research into fatigue is 'poorly understood' in relation to a symptom that has substantial impact upon the lives of people with MS.

    No wonder neurologists are a disappointment in relation to the issue of fatigue. There are off label drugs that can be prescribed - Amatadine, very average, and Modafinil - which works a treat for those who respond to it.

    My major concern is the general narrow nature of neurological thinking when it comes to fatigue. Perhaps the mousedoctor might like to acquaint himself/herself with the benefits of exercise in respect of fatigue, just because you can't 'preacribe it' does not mean that you should have some idea as to where to direct your patients to reap the many benefits of exercise therapy.

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  4. Re 'benefits of exercise in respect of fatigue': Click on MS in Focus 2012 in the post above. It has quite a lot on the subject of how exercise helps with fatigue

    From this blog (on the benefits of exercise in general, not just for fatigue):
    http://multiple-sclerosis-research.blogspot.com/2011/04/effect-of-exercise-therapy-on-fatigue.html
    http://multiple-sclerosis-research.blogspot.com/2012/01/physical-activity-and-ms.html
    http://multiple-sclerosis-research.blogspot.com/2010/12/get-your-walking-shoes-on.html
    http://multiple-sclerosis-research.blogspot.com/2011/12/kick-boxing.html

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  5. Play nice people.

    Yes, fatigue is a major problem, but MouseDoctor is right in saying we need decent drugs that stop disease.

    That's exactly where all our focuss needs to be right now. If we can stop the damage then maybe there will be a way to repair some of it. By stopping damage everyone will be a winner whether you have the type of MS that affects your eye, hands, legs, thinking, hearing or whatever. Stopping MS will be the first time a treatment will have benefitted all MS'ers, regardless of what type of MS they have.

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  6. Let's combine some facts and ideas:
    -Tysabri is said to have positive effect on fatigue.
    -Tysabri prevents white blood cells from adhering to vessel walls in the CNS.
    -Using the forest fire analogy, Tysabri removes the white vans parked on the roadside, thus allowing more cars to pass through. In mechanical terms, it allows faster blood flow through affected areas.

    Conclusion:
    Tysabri increases cerebral perfusion and thus helps in fatigue.
    Prognosis for testing:
    1. Tysabri only helps patients with highly inflammatory cerebral MS.
    2. Tysabri only helps patients whose fatigue improves.
    3. Tysabri has no effect on spinal MS since spinal lesions are unrelated to blood vessels.
    4. Tysabri has no effect on patients with mostly spinal activity (PPMS).

    You 'll say this is fiction, not science, but then again that's exactly what a scientist should do: be able to select the most promising ideas from a bunch of some with phenomenally equal probability. Affirming to data or dogma needs no brains.

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  7. Dear VV
    You are correct. Yes the outcome is probably fiction, because if test your ideas about prognosis, based on the known science, the hypothesis is disproved.

    Therefore, you have to reformulate ideas and retest the hypothesis.

    I have no problem with people having "left field" ideas. I have my own and there are plenty of such ideas every week.

    Do I have to agree with them? If it does not impinge in my interest it does not necessarily matter one way or the other, because often it is not important. But who knows I may change my mind. Likewise you have your interests can they be changed?

    Alemtuzumab removes white cells from the blood in RRMS and works, Alemtuzumab removes the white cells from the blood in SPMS and does not work. So is it all about blood flow?.

    Are there any current drugs that work in MS that does not stop the white cells getting into the brain?

    Are there current drugs that work that do not stop fatigue?

    Although I am not a dogma fan "following dogma needs no brain...." Is this insulting to many people doing research?

    Answers not needed just think about the questions?

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  8. My main point is that whether a drug works or not has to do with its impact on fatigue. Through that may someone reach the source of the disease. Of course, there is no evident reason why this should be accomplished only with drugs. We use glasses for myopia. But insisting on counting enhancing lesions and relapses leads to ineffective drugs as far as disability is concerned.

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  9. VV

    Maybe if you have a useful point, you can say it simply, so that people can understand what you are saying. As you will be probably just posting to them.

    Because of my short sight I will not be able to read your posts to give a one to one response....

    P.S. As is often the case I think you are wrong in your assertions.

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  10. Fatigue is reported by patients as one of the most debilitating symptoms. It usually precedes MS diagnosis. It's always present, even during relapses. There is no way to get rid of it.

    Someone would expect it to be of the primary research targets in MS.

    Yet, it isn't.

    What does neurology know about it? Nothing, beyond that it is a consequence of demyelination and neurodegeneration. So much for the explanation.

    Are there other disease entities that exhibit fatigue? What are the causes there? Are there any similarities to MS fatigue? Have you devised any models to account for it? Have you tested any of these models? Have you taken a wild guess about what it is and where it comes from?

    Fatigue is a blanket tight to the body, getting heavier. Imagine living on a 3g planet, always being woken up during REM and forced to climb 100 stairs. Explain it, please.

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  11. Re: "Fatigue .... Explain it, please."

    It is a complicated story; the problem is that our scale for measuring fatigue are not very good. When you apply psychometric theory to our current fatigue scales they fall short of being good enough for trials. At present Jeremy Hobart in Plymouth is working on a new scale.

    MS-fatigue is not universal; about 15% of MS'ers don't complain of fatigue.

    In brief fatigue can be divided into physical and mental/cognitive fatigue. Physical fatigue is related to exercise induced reduction in function; fampridine (slow release 4-aminopyridine_ has recently been licensed for walking related problems and helps with this type of fatigue. The down side is that only about a third of patients respond.

    Mental fatigue may be related to inflammation and may explain the overlap with other inflammatory disorders; fatigue is a hallmark of inflammation (e.g. flu). What is interesting that a lot of MS'ers find their fatigue improving or even disappearing when they go onto one of the more effective DMTs, for example natalizumab.

    If you want more information on MS-related fatigue, I suggest you read the following Editorial I wrote in 2006; it is fee to download:

    Giovannoni G. Multiple sclerosis related fatigue. J Neurol Neurosurg
    Psychiatry. 2006 Jan;77(1):2-3.

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2117414/?tool=pubmed

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  12. Re: "What is MS fatigue?"

    Fatigue or lack of energy is a core symptom of depression. Depression is very common in MS'ers and needs to addressed. In my experience anti-depressants may help fatigue.

    Another problem is poor sleep. A lot of MS'er don't get a good night's sleep due to bladder problems, pain, leg spasms, restless legs, sleep apnoea etc. Unless you correct the sleep problem fatigue won't respond to treatments. Do you remember how you felt when you last missed a night's sleep?

    Another problem is side effects to medication. Sedating drugs make MS'ers feel thick-headed and this is often interpreted as fatigue. Baclofen is a drug commonly taken by MS'ers for spasticity that is particularly bad when it comes to sedation.

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  13. Re: "I was taken off tysabri in June, and my exhaustion has since taken over my life :("

    This is a common experience; many of my patients have experienced the same recrudescence of their fatigue on stopping natalizumab.

    I don't agree with VV re blood flow. This is related to end inflammation. Patients with rheumatoid arthritis have the same complaint when they have disease flares on withdrawing their DMTs or DMARDs (term used by rheumatologists). TNF-alpha and interleukin-1, cytokines or inflammatory messengers, are probably the main mediators of inflammation-related fatigue. These cytokines result in sickness behaviour, which includes fatigue and is found across the animal kingdom. From an evolutionary perspective sickness behaviour causes animals to conserve energy to allow the body to recover. Unfortunately, when you have a chronic disease this behaviour and hence fatigue becomes a big problem and prevents you from functioning normally.

    Please note people with rheumatoid arthritis and fatigue have no problem with cerebral blood flow. Nor do MS'ers.

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  14. What about people with Chronic Fatigue Syndrome. Is there inflammation too?

    Depression is equally unknown to fatigue. Metonymy adds no further knowledge. There is no good reason to think of the latter as a consequence of the former. The other way round is also plausible. They could also co-exist.

    The 15% without fatigue, what type of MS do they have? Is there a pattern?

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  15. Re: "The 15% without fatigue, what type of MS do they have? Is there a pattern?"

    No pattern! But in my recent experience its MS'ers on natalizumab and those who have been treated with alemtuzumab with the least fatigue. In other words suppressing CNS inflammation with the more effective DMTs seems to be the common theme.

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  16. Re: "What about people with Chronic Fatigue Syndrome. Is there inflammation too?"

    Yes, a subset have evidence of peripheral immune activation; typical of that seen with chronic viral infections. You may be interested to know that 30-40% of subjects with chronic fatigue syndrome are clinically depressed.

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  17. Re: "What about people with Chronic Fatigue Syndrome. Is there inflammation too?"

    Yes, a subset have evidence of peripheral immune activation; typical of that seen with chronic viral infections. You may be interested to know that 30-40% of subjects with chronic fatigue syndrome are clinically depressed.

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