Prof G how much brain have I lost this year?


How soon will MSers have brain volume measurements as part of their annual assessments?

As a reader of this blog, you may be aware that ‘life is a sexually-transmitted age-dependent terminal neurodegenerative disease’. Homo sapiens, as a species, is pushing its biological capabilities to its limits. We have conquered most diseases that used to cull us before our mid-thirties and the end of our reproductive age. In the same way, as the technology sector has learnt to build in senescence into its products to ensure we upgrade our gadgets every 18-24 months, evolution has selected for biological senescence to make sure the current generation does not freeload on the next generation. When we have finite resources, why should we waste precious food on the older generation when we have to ensure the current generation reproduces to pass on its genes? A counter-argument to this ruthless biological perspective is that cultural evolution now takes precedence over biological evolution and it is societies and not individuals who are driving evolution. Culture and some heritable traits have clearly interacted with our environments, which explains why some isolated populations are enriched for people who are healthy agers. We are learning from studying these populations and unpacking the relevant biology to identify future treatment targets for healthy ageing. Do you want to be a healthy or super ager? If you have MS this is unlikely to happen.

These insights are telling us ageing is a biological process and therefore hackable, i.e. we will at some point learn how to reprogramme ourselves to reverse or at a minimum delay the effects of ageing. The reason I say this that we already do this in the form of reproduction; we produce sperm and eggs that go onto to recombine and form offspring that have their senescence programmes set to zero. Why can’t we do this at any stage of life?

Cellular senescence is accelerated by various stressors, which at the level of the whole organism results in premature ageing. The corollary of this is that certain lifestyle interventions appear to delay ageing mechanisms, or at least increases the resilience of the organism so that the consequences of ageing only become apparent much later on in life. Our increasing ability to manipulate these stressors and/or resilience mechanisms should empower individuals to maximise their health and wellness for future gain.

Is this relevant for MS? Yes, it must be. Firstly, many of the cellular stressors that result in ageing are upregulated in the brains of  MSers. We also know that one of the resilience mechanisms that protects us from age-related cognitive impairment is brain and cognitive reserve. As MSers get old you rely on these exact same mechanism to allow yourselves to age healthily. If you get to old age with a deficit how can you expect to age normally? As MS starts to shred your brain reserve from the earliest stages of the disease the treatment objective should be to address this from the outset? Therefore, how do we get the MS community to shift its treatment target beyond NEDA and to focus on the end-organ and the preservation of brain reserve?

One possible option would be to equip MS healthcare professionals (HCPs) and you the MSers with the tools to monitor end-organ damage more closely. Wouldn’t you want to know what is happening to your brain volume on an annual basis? Would you want to know if you are losing more brain than average?

Several companies are beginning to scale up their image analysis software and providing it online for MS centres and possibly individuals to measure their own brain volume and to get feedback based on a normogram; i.e. a normal distribution of brain volumes for age and to plot where on the standard curve you are. Your brain volume can then be measured and plotted annually to establish your trajectory.

The naysayers will say that this technology can’t be used on an individual basis as it has not been validated in clinical practice. The naysayers are in for a big surprise; I suspect the regulators are will approve these algorithms long before they are ready to incorporate them into routine clinical care. However, these very same naysayers often present group data at meetings with great confidence. Group data is what it is, an academic construct, that is far removed from clinical care and the individual with MS. My personal opinion about biomarkers is that you need to put them out there, with obvious disclaimers, and see how they are used. Technology itself works magic in many different ways.

I think having personal annual brain atrophy data will get both the neurologists, other HCPs and MSers to think differently about managing MS and it may be the nudge we need to treat MS more effectively early on and to change our treatment target. I also have little doubt that the methodology of measuring whole brain volume, grey and white matter volumes, lesion volume and the number and volume of lesions expanding will only get better and more accurate with time. So bring it on!

Do you agree with me? If not, let’s have a debate. End-organ damage and brain volume is very topical at the moment.

CoI: multiple

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.


  • For me personally I cant see much point in measuring anything if nothing can be done ! Why would I want to know? It is easy to generalise …I am sure people with early RRMS might find this useful but certainly not for SPMS

  • “Several companies are beginning to scale up their image analysis software and providing it online for MS centres and possibly individuals to measure their own brain volume”

    Exactly my thoughts. As we get complete MRIs on CDs, and if Neuros don’t want or can’t measure this, maybe patients can start with this and nudge everyone forward. As a comp. scientist I know that once image analysis model is built, this evaluation can be done on a large scale quite easily. I’m not saying that this will have absolute usability in clinical practice, but it can nudge you towards more invasive diagnostic procedures (e.g. measuring NfLs in CSF) much much quicker than just waiting for clinical relapse…

    And, again, if the systems is used a lot on a ton of different data/use cases, it just gets MUCH better in accuracy over time. Just look at how image recognition advanced over last few years. In certain domains, computers are now much more accurate than experts (e.g. Alzheimers, pneumonia, some cancers, etc.)

    What I’m afraid that this will be either too expensive and/or unavailable to patients directly. And time is brain.

  • Spot on!
    I’ve been trying to get my neurologists to evaluate what looked like brain atrophy on my MRI for years. Since I’m clinically an EDSS=0, nobody was very concerned and all agreed I should stay on my weak CRAB drug–even as they were starting all their new patients on the more effective drugs.

    Finally, I had an MRI last month that compared my brain volume to age-matched controls. The results were devastating. My neurologist still seems to think I’ll be just fine, but he’s offering me natalizumab and ocrilizumab now. I think we would have done this years ago if we could have measured what was happening to my brain. I am pushing 60 years old. Even though I feel perfectly normal now (and yeah, I exercise, eat healthy, am learning an instrument, play brain games, have a healthy weight), it’s clear life will get a lot harder in the next 2 or so decades I have left.

  • I’d be very interested in doing this but only if data avaiable to me and my consultant is shared with the MS community for research – a small contribution to big data. As someone with PPMS I’m already at a stage where holding on to what brain volume I have left is critical. This would keep me informed about the effectivness of my current DMT and highlight the potential future need to change onto something else as other treatments come available (note optimism here – something MS can’t take away from me). Never been one for complacency – bring it on.

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  • Thanks for the post Dr. G. 2 questions:

    1) How closely associated is MRI with BVL and GML with disability, including EDSS?

    2) In a patient currently with progressive MS what benefit to the patient is it when there is not one single meaningful approved treatment? What good what it do other than worry the patient more than they are already worried?

    • Re: “How closely associated is MRI with BVL and GML with disability, including EDSS?”

      When using EDSS/disability as the outcome in a big data study BVL comes out near the top; (1) is T1 black holes, (2) baseline cognitive function, (3) QoL – physical component and (4) BVL. I suspect BVL comes lower down the list because it comes after the event, i.e. there is lag before it occurs. In other words, you lose your function (cognition first), this impacts on QoL and only later you lose your brain volume. The reason for this that it takes time for the brain to clear out the dead and dying debris. Interestingly, T1 black holes are the most predictive MRI metric. Why? I suspect it is because it captures those slowly expanding lesions (SELs), which are what MS is all about. Please note that these observations are limited to whole brain volume. Grey matter volume may prove a better predictor.

      At the end of the day if you have MS you want to preserve both your grey matter and your whole brain volume.

  • Nice post building on your recent discussion on how to move from NEDA-3 to NEDA-4 and beyond when monitoring and treating MS patients.
    I raised the point of tracking changes in my brain volume over time last week to a Neurologist of outpatient services at an advanced research center in Germany which even offers haematopoietic stem cell transplantations. I was told that this imagery is simply not done as a matter of policy as long as no clear rationale is presented for the individual patient.

    So what I’m trying to say is that you’re preaching to the converted in this blog. Readers will need you to follow-up with compelling research that you can share at the relevant events in order to convince those who decide on what’s best for treatment in their respective areas of influence.

    I truly hope you manage to generate good results demonstrating the efficacy of NEDA-4 in the near future!

    • I think there is already data out there from the fingolimod trials that trial subjects who are NEDA-4 do better than those are not.

  • This makes such sense. So why aren’t neurologists talking about this more? Why aren’t they educating us about healthy ageing and brain atrophy?

  • Thank you , for another interesting post.

    How would that fit in a decision making algorithm?

    Say you are NEDA 3 on an existing high efficacy DMT, you get yourself tested and see abnormal BVL.
    You have said few weeks ago that there is no evidence that switching to another high efficacy will improve things. Would you still advice your patients to switch?

    • Unfortunately, we have no data on this. We tend to do an LP to measure CSF NFL levels to screen for smouldering MS, but outside of this biomarker we have no idea of going for a more efficacious therapy will have any impact. What we need are clinical trials; add-on therapies to target the processes resulting in the end-organ damage.

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