Friday, 25 March 2016

ClinicSpeak & BrainHealth: what does the 'New Normal' look like

Do you feel normal? #ResearchSpeak #BrainHealth #MSBlog #MSResearch

"Yesterday, when I got home and picked-up our post, which included the Economist, the headline on its cover was 'Europe's New Normal' with reference to its war with terrorism. Simultaneously, sitting in my inbox was an email from a colleague asking me whether or not pwMS who are NEDA feel 'normal' and is  there a way of defining a 'new normal' for pwMS? I don't know the answer to this question, but said I would ask you the community.




The current dogma states that MS is an autoimmune disease of the central nervous system that is driven by focal inflammatory lesions or MS plaques. We think the MS lesion is responsible for both acute (now) and delayed (in the future) damage. Permanent loss of function (impairment or disability) is due to neuronal loss, which can be measured clinically, electrically, on MRI and biochemically in the spinal fluid. If we measure all these things and find no evident disease activity have we reset things back to normal, i.e. a 'new normal' state for pwMS?


Inflammation transects neuronal processes, or axons, acutely that results in loss of function. If the lesion is an eloquent site it causes a relapse. Loss of function is then restored by the surviving axons taking over the function of the lost axons, or other areas of the brain taking on new functions, we call this axonal and cortical plasticity, respectively. Recovery can only occur if there is sufficient reserve capacity. The accumulation of damage and ageing reduces reserve capacity, which explains why recovery from relapses tends to fail with more advanced disease and with age. This is why it is important to treat MS early so as to protect reserve capacity. The 'new normal' would need to take into account existing damage.

Neuronal processes (axons) that survive being transected are compromised and never recover back to full health. These axons may remain demyelinated, or if they are remyelinated the myelin sheath is never as thick as it was in health. In addition, the so called microenvironment within the chronic MS lesion is stressful to the axon. All this programmes the previously damaged axons to die off over time. This is why anti-inflammatory therapies that switch off the development of new focal inflammatory lesions may not prevent the delayed neuronal loss that characterises progressive MS. Even if we were able to cure MS as an autoimmune disease we may not be able to stop, or prevent, progressive disease from occurring in the future as it may already be programmed to occur from previous damage that has accumulated in the past. In other words progressive MS is like a ticking ‘time bomb’. If we define a 'new normal' state would this be compatible with delayed onset of clinical worsening?

We seem to forget that as we get older we lose brain this is what we call age-related cognitive, or neuronal, decline. From the age of 35 our brains start to shrink and our neuronal systems start to fail; this is normal. The manifestations of this are not that subtle; how often do you battle to find the right word, or remember an important fact, only to find that your memory has failed you. Similarly, your balance is just not as good as it once was; you realise that you can’t put on your trousers standing-up unsupported and you have to resort to sitting down, or holding onto to a piece of furniture, for balance. If we all lived long enough we would all dement from natural ageing. Evolution never designed our brains to live as long as we are living today. What protects us from the ageing process is brain reserve; the more brain reserve we have the later we will present with our dementia. As MS reduces brain reserve we hypothesise that people with MS (pwMS) will notice age-related cognitive decline earlier than the general population. So even if we cure you of your MS you may still get a drop off in neuronal function earlier than expected that is simply due to ageing. However, this drop-off in neuronal function will interpreted as MS-, and not age-, related decline. Is the loss of reserve compatible with defining a 'new normal' for pwMS?

The insights above highlight some of the reasons why we started the ‘Brain Health: Time is Brain’ campaign and is tempting to suggest that if we treat pwMS early enough and effectively enough we may be give you an opportunity to be normal, or at least a chance of a 'new normal'.


Is it futile to think of the concept of a 'new normal'? May be it is simply because of the psychological burden that goes along with having a diagnosis of MS. However, I know many cancer survivors who are essentially cured of their disease who describe themselves as being normal. Why can't MSers do the same?"



CoI: multiple

18 comments:

  1. I feel normal (like before I got MS) when I have just woken up from a good nights sleep and am in bed. Then when I get up and walk around and the pains and sensations begin. It's a tease as I often feel excited with this 'normal' feeling in bed and wonder am I back to normal again for good. Sadly no.

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    1. I was diagnosed two years ago and I feel the exact same way most days. It is an emotional roller coaster and one of the hardest aspects of the disease to deal with right now.

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    2. Anon at 7.13am - absolutely! I also feel normal until I get out of bed. I don't have any significant pain (yet) but my cranky legs remind me of my mobility problems the minute I get up and try to get to the loo before my stroppy MS affected bladder decides to let go. The problem with MS progression is that your normal keeps shifting - it's a battle of constant adjustment to an endless succession of "new normals".

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  2. I'm a doctor and was able to grasp what was going on clinical onset of my MS, to firm diagnosis it took about a month, had a full recovery, started 1 line treatments, relapse, again full recovery, then another relapse. (This on less than a year)
    It's easy to feel "normal" between relapses and you easily forget what you are against. So after 3 relapses went for alemtuzumab even tou I was jc- (the idea of an induction just seems more appealing to me), no relapses since then... but just some months since treatment. What I want to say is: don't let the guard down because you feel "normal" or having a good week, this can be a dangerous train of thought, take your vitD, escalate dnt quickly or just start from the top. And yes, at some point i hope to gain the confidence to say again: "hey you know what, I feel normal" only time will tell.

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  3. You always mention brain when talking about MS, Brain reserve, effects of atrophy whether due to aging or MS. But what about spinal damage? Does the body recover or use the same mechanisms as the brain? Do you 'ignore' spinal lesions because they are less significant or because they are (I'm told) a pre cursor to a less favourable outcome?

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    1. Brain = spinal cord in this context, we use brain to = CNS

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  4. Regarding lesions acquired during the inflammatory phase being the site of neurodegeneration in the secondary progressive phase...

    Even if SPMS is virtually inevitable, surely shutting down further inflammation with a highly effective treatment whilst still in the RR phase = fewer lesions = being in a better condition entering SPMS with fewer areas primed for neurodegeneration.

    Take a patient with zero symptoms and a mild to moderate lesion load (brain only, which offers more reserve capacity than the cord)... if they were to get onto a highly effective treatment (eg: Alemtuzumab) prior to significant symptoms, would this mean that they could expect no or limited symptoms when they enter the secondary progressive phase?

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  5. MSers cannot describe themselves as normal as they are never free of their disease. Cancer survivors have gone through years of tests to ascertain when their illness has returned. They take each stage as it is handed to them. The difference is that many don't wait around for what might happen and make the most of the time they have. MSers tend to fear what might happen and have a different outlook. MS is scary, but the important thing is to live life to the full and not wait for the miracle cure. The negative psychological side to MS is a crippling as the disease itself.

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  6. Normal or not... that is a very interesting question, actually. I think MS has been with me from my teenage years, even though I had my first official relapse when I was 35 (but at that point MRI showed over 10 MS lesions already). So how does normal feel, really? :-)
    I can walk and run and talk - a stranger would not notice anything wrong with me. But am I free of disease activity if my MRI (1,5 Tesla) does not show any new or Gad-enhancing lesions but I feel the disease is active ( I get sensory problems that come and go, usually lasting up to a month)? My neurologist is happy with that, no need to intensify treatment. Is that normal then?

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  7. Brazilian pwMS seem to be normal again and very happy to have their life back after taking Vitamin D3 1000 IU/kg/day for 2 years or more.

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    1. Vitamin D3 1000IU a day for two years. Did you mean to say more? 1000IU is not that high. 4000 or 5000IU a day is recommended by many UK neurologists.

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    2. Understand what you might mean now 1000IU a day per kg of a persons body weight?

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  8. In my 44 years with RRMS, I have had four exacerbations. The first interval between relapses lasted 3 years; the second, 10 years; the third, 20 years; the fourth, 11 years. Starting with the second exacerbation, I was left with lasting damage (gait, fatigue, balance et al.) The intervals were long enough, though, that I could hope that my MS was "stable." The emergence of yet another exacerbation dashed those hopes. So, I could never feel normal for two reasons. First, I was left with lasting deficits. Two, the possibility of another relapse remains ever present. Incidentally, I only used one DMD (Avonex) for two years prior to my third exacerbation. I will continue to follow my program of an organic diet (free of substances like beef I tested as being allergic to), 3g Vit D, B complex, d- ribose 5gr, essential oils (frankincense, copaiba, helichrysum), daily targeted exercises, and mental and spiritual health work. After that, I can only hope for the best. But, I am never free of MS, both of its past impact and of its possible future impact.

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  9. I don't think "new normal" is an appropriate term at all. I would interpret normal as 100% normal functioning with no physical symptoms, even if MRI shows lesions - i.e. EDSS of 0. Normal is being able to run, jump, no pain, and work commitments and leisure activities being governed by what you want to do, not by what you are able to do. The same could be said for any health condition which impacts on you - e.g. RA, diabetes etc.

    A better term would be along the lines of plateau - i.e. stability has been achieved in your level of functioning, with no further deterioration or loss of function. The concept of a "new normal" is only of use if you are going to use that state as a point to measure from in relation to whether there is further deterioration or loss of function, in which case a word such a plateau works just as well.

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  10. In the survey I've just written "I don't want a new normal - I want my original and real normal (i.e. before MS) back again." I think that's worth repeating here, as I'm sure most PwMS would agree with me on this one (apart from those stupid idiots on some sites and forums who write that having MS has made them a "better person"!)

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  11. I don't have any symptoms or disability at present so my day to day life is normal. I look normal and feel normal. Yes I have MS and have faced situations which are outside the normal day to day life but so do many people who don't have MS. In respect of treatment I think we should be aiming for nothing less than normal.

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  12. Are the results of this survey going to be released? I normally agree with most of what ProfG says, but not this "new normal" concept.

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