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

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