Is that revolver loaded?


Barts-MS rose-tinted-odometer: ★★

Are you lonely? Have you lost a loved on during COVID-19? Have you lost your job or had to reduce your income because of COVID-19? Can you make ends meet at the end of the month? Are you worried about your future? How is your relationship with your partner? Are you depressed? Anxious? Are you sleeping well? Are you drinking too much alcohol? Are you feeling guilty? Self-loathing? Failed ambitions? …..

These sorts of questions rarely come up in a standard MSology consultation because most classically trained HCPs working in a secondary or tertiary care environment haven’t been trained to deal with what we refer to as the Social Determinants of Health (SDoH). However, it is clear the SDoH have an outsized impact on health outcomes, which is likely to include MS outcomes. This is why we launched our #ThinkSocial campaign several years ago and have started several activities to see if there is anything we can do to help tackle the SDoH. 

A story: Recently one of my patients chastised me for telling her off for her poor diet, which consisted mainly of bread. She lives alone, which may explain why she eats so poorly. She has marmite or jam on toast for breakfast, a sandwich for lunch and if she feels hungry another piece of toast for dinner…..

What should Prof G do to manage this patient?….. find out

I can clearly see the cynics saying ‘focus on what you are trained to do and leave the SDoH to general practice, social care and the charitable sector’. Yes and no. Yes, it is easy to say this is not my responsibility, but when you are trying to do your best medically to improve MS outcomes only to get trumped by the SDoH it makes it look like your service is failing. Our patient population in the east end of London is one of the most deprived populations in England. When we recently analysed deprivation data from HES (hospital episode statistics) the only area worse off than us in England was Liverpool. On the other end of the scale were Cambridge and Oxford. So if we compared outcomes of the MS patient populations in Liverpool and east London and note they are doing worse than pwMS living in Oxford and Cambridge it may not have anything to do with our MS and other services, but simply represent levels of deprivation and its associated poorer outcomes.

How SDoH result in poor outcomes is likely to be due to the effects of chronic stress on the brain. Stress is a well-defined biological or physiological response of the body. Stress results in high levels of so-called stress hormones. These stress hormones have a direct and negative effect on the brain and other organ systems, which causes them to age prematurely and malfunction. Ask anyone who is stressed and they will tell they don’t feel well. Stressed people and stressed populations are more forgetful, more tired, have poorer sleep and tend to engage in unhealthy behaviours (smoking, alcohol, poor diet, sedentary) and have much higher mental health problems (depression, anxiety, addiction, suicide). In general, pwMS are more stressed and the reasons for this are not only obvious but potentially modifiable.   

The main stress hormone is cortisol. Cortisol works via glucocorticoid receptors, which are found all over the body including the hippocampus, amygdala and frontal cortex, three brain regions involved in memory and emotions. Chronic stress is associated with reduced volume and malfunction of these areas. In pwMS, these areas may already be damaged from MS lesions, which increases the MS brain’s vulnerability to chronic stress. So if you want to improve MS outcomes you can’t ignore the SDoH and chronic stress. Do you agree? 

This is why I have been promoting the marginal gains philosophy to the management of MS, which is based on Sir David Brailsford approach to competitive cycling and is the reason why the British cycling teams has been so dominant in the last two decades.  

“The whole principle came from the idea that if you broke down everything you could think of that goes into riding a bike, and then improved it by 1%, you will get a significant increase when you put them all together.”

Sir David Brailsford

“If we break down everything we can think of that goes into improving MS outcomes, and then improving each one by 1%, we will get a significant increase when we put them all together.”

Prof. Gavin Giovannoni

So when we launched our ‘no patient left behind’ motto at the first MS Academy ‘Raising-the-Bar’ meeting to address variation and inequalities in access to MS healthcare in the UK we included a workstream to tackle the SDoH. How we do this is currently being defined, but we have an ambitious programme of work. Whatever happens, we will need to involve the whole MS community, which includes readers of this blog. So if you have any ideas to tackle the SDoH please share them with us. 

Lupien et al. The effects of chronic stress on the human brain: from neurotoxicity, to vulnerability, to opportunity. Frontiers in Neuroendocrinology April 2018, 49:91-105.

For the last five decades, science has managed to delineate the mechanisms by which stress hormones can impact on the human brain. Receptors for glucocorticoids are found in the hippocampus, amygdala and frontal cortex, three brain regions involved in memory processing and emotional regulation. Studies have shown that chronic exposure to stress is associated with reduced volume of the hippocampus and that chronic stress can modulate volumes of both the amygdala and frontal cortex, suggesting neurotoxic effects of stress hormones on the brain. Yet, other studies report that exposure to early adversity and/or familial/social stressors can increase vulnerability to stress in adulthood. Models have been recently developed to describe the roles that neurotoxic and vulnerability effects can have on the developing brain. These models suggest that developing early stress interventions could potentially counteract the effects of chronic stress on the brain and results going along with this hypothesis are summarized.

CoI: multiple

Twitter: @gavinGiovannoni                                              Medium: @gavin_24211

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.


  • Both my main attacks were a few months after an extremely stressful situation with a sickness of a family member. I would imagine this is common.

    Prof. G would it be possible to give some anti stress med such as a Benzo temporarily to ms patients (premtively) when they are in a highly stressful situation? Or is there any other way? If it is cortisol why not go on a anticorticosteroid drugs temporarily during times of great stress?

    • Benzos are bad. Even relatively short term use can result in dependence and withdrawal. Just ask poor old Jordan Peterson (a Canadian psychologists, author, and wordsmith). Benzos also affect cognition which isn’t good if you already have some problems with cognition. Avoid if possible.

      • Not sure poor is the correct word to describe Jordan Peterson. Also think you might have omitted the word grifter from your list of descriptors.

        • Poor in the sense he became dependant after being prescribed benzos to treat anxiety associated with his wife’s cancer diagnosis. Clearly he’s not poor financially. His book 12 rules for life isn’t a bad read even if you think Jungian archetypal theory is bollocks.

          Concerning the content of this post, I think the uncertainty of MS also affects those who are caring for someone with this disease. I don’t know how long my wife will be able to work full time. Therefore, I continue to work long hours to ensure we have enough money to survive if she needs to have some respite from the pressures of work. Support services are fractured in Australia and most are means tested. The National Disability Insurance Scheme is a bit of a mess resulting in many services being self funded. This ads more pressure on partners to push through. Every ailment is magnified and stressful, not knowing if it is treatment or disease related. Partners are also the main emotional support for their spouse. I suspect most lack the emotional support they need to fulfil this role. This is certainly the case for me at times. All this is then made worse by COVID. Job uncertainty, stress, and anxiety have surfaced pretty quickly. More services and better access should be top of the list in Australia. Australia is very good when it comes to DMT access but no so good when it comes to the additional support services required to support pwMS and their partners. I remain optimistic that things will improve.

      • I know Benzos are very addictive (though one month use at low doses is considered safe), but I would rather that than have an attack with permanent damage.

        If the MS patient is going through a stressful situation, it makes sense to give some drug to prevent an attack, now be it benzos, or some other drug to counteract the stress.

        Who knows which Benzo Petterson used and at what dose and for how long…

      • That said, I don’t even have a clue if Benzos are the way to go. In general, is it known exactly how stress is causing an attack? Is it through weakening of BBB somehow? Someone should look into this.

  • Like another commentator, I suffered the attack that put me into hospital for months and led to diagnosis after extreme stress – serious illness of close relatives, bereavement, relationship break-up and more, all within the space of a year. The stress continued and was worsened after diagnosis, through having to navigate the benefits system and being unable to work, among other things.
    I feel strongly that the benefits system is unnecessarily cruel and demeaning for people who are already very ill and dealing with huge issues. It is necessary to “prove” you are unwell and can’t work to various people of undefined medical ‘experience’, basically that you are are charlatan unless you can somehow convince them otherwise; difficult with a condition that can come and go and sometimes is characterised by invisible symptoms. PwMS live in fear of assessments and reassessments for UC and PIP and are stressed beyond belief waiting for them. I do think that this is one thing that could be changed to make life less stressful for many people with MS. Why not a system that accepts when a person is unable to work, asks how it can help them and sympathetically supports them until they can find suitable work? Not saying that the benefits system is somehow more unfair for those with MS than it is for everyone else – just pointing out that from what I’ve seen it is definitely a major contributor of stress for them.

  • What you say doctor, is very true. But it reminds me of the multitude of untrained quacks running around pretending that they know something special, that others have to learn. And what many of these people have never done is never work on their own “crap”. Before setting out to promote better well-being and health habits, if this is to be done through conversation and with a population that is not asking for it, you really need to be trained. And I’m not talking about MD training, as talk therapy doesn’t come along with training to be a Doc, nor am I talking about a 5 week workshop. The business of changing people is very very difficult and knowing how things work is only a small portion of what is needed to make a difference. Something to be kept in mind, with all due respect.

    • HCPs need to walk-the-talk, which is what I always try to do even when it comes to trying a ketogenic diet, intermittent fasting, rehabilitation, etc. What I have problems with is sleep hygiene and not being able to go teetotal 😉

  • In my own experience, the most stressful time of my life was chasing a diagnosis of MS and action from my neurology team. I remember after a second confirm episode being offered an appointment in 7 months time when every day felt like a marathon. For a condition that thrives on stress, this is simply unacceptable.

  • If you don’t mind I would not mind getting a little bit of hope.. You mentioned a trial of an antiviral happening this year. How far off are we to getting it approved ( how many year ) ?

  • Interesting, completely agree with association with stress, but the glucocorticoid receptor is also expressed by T cells hence use of corticosteroids for relapses. Perhaps it differentially impacts Tregs vs. CD8’s for example or are you suggesting there is a direct impact of cortisol on CNS tissue? I don’t know the data well enough.

  • I think there might be an opportunity to work with less developed regions’ experts and find ways to work around this… hearing from people who deal with far worse SDoH everyday might help you as well as them.

  • “This is why I have been promoting the marginal gains philosophy to the management of MS, which is based on Sir David Brailsford approach to competitive cycling and is the reason why the British cycling teams has been so dominant in the last two decades.”

    Another reason is the bending of rules to their limits and sometimes beyond, as seen with Bradley Wiggins.

    • Bradley Wiggins did it as part of Team Sky; I am not sure if it did when he was in Team GB. But your point is well taken. Sadly it casts a long dark shadow back in time 🙁

    • Good old Bradley “I have a doctors certificate” Wiggins. Sorry, a Sir should have been in front of that. Do we honestly believe that doping no longer occurs in cycling? Seems pretty entrenched to me. I suspect if you pierce the veil of most professional sports you find it is pretty common. They should have a clean olympics and a doping olympics. Level the playing field a bit. Isn’t it great when two cynics connect via a blog??

          • Yeah, that made the Australian papers and I had a good chuckle when I read it. I’m sure Australian cyclists are neck deep in it too.

          • Yeah, it’s getting clearer that the famous “marginal gains” are the usual medical gains. This being cycling, you’d just shrug your shoulders but Brailsford and Sky made such a huge deal about winning squeaky clean. I do wonder how far this has to go and also how much it might put UK cycling as a whole under suspicion. As it is I suspect this story still has a long way to go yet.

          • At least when we promote marginal gains in the management of MS medicinal gains are fine; we are not trying to hide anything 😉

  • Think the answer here is clear, need a monoclonal antibody or mRNA vax against cortisol and other stress hormones. We can dial in an ideal amount of stress. Ha.

  • Tackling the social determinants of health is a bit like fighting cotton wool. It must be done however and having a conversation with those who don’t want it or know about it is a slow route to progress. Necessary though. That’s education, yes? It’s evolution not revolution, but taking the people with you is necessary. Meanwhile levelling up (sorry to use this misused expression, normally used by weasely politicos) is something that should be done more quickly and not necessarily in negotiation with people. That said levelling up is expensive. If a poor community gets a Community Centre they probably welcome it don’t they? Unless it’s built on an AONB or something. Michael Marmot was commissioned to look into this issue but still governments sit on their hands, however influential he is.

    Measuring something like SoDoH; a qualitative issue in a quantitative way. How WOULD you measure and demonstrate even a 5% improvement, let alone a 1% one? The pandemic has revealed to all but the terminally deaf/blind to social justice (another missed expression) huge health inequality.

    Faced with the huge task of raising the bar, baby steps for those living in E. London, Liverpool and not to be forgotten rural Pembrokeshire and Cornwall, which the EU defined as the 2 poorest regions in Europe, needed; simple inexpensive interventions along with hoped for massive investment which may never come. Home visits to housebound before the promised play park for the kids ever comes on stream, if at all; that kind of thing. Raising morale after a stressful event either of individuals or a community, such as a car accident or a fire in a terrace of houses would be protective

  • Do you have any thoughts on quantifying stress?

    My Garmin watch does measure stress based on heart rate variability and I keep thinking I should reduce work load because I am continuously in medium to high band during work hours… My SDoH otherwise are good but this part makes me think.

    I would more generally love to hear some thoughts on making decisions on work load.

    FWIW the first obvious episode (not sure I want to call it relapse because I still can’t quite decide if I am RR or PP) for me came 6 months after a period at work that stressful enough to leave me with burn out…

By Prof G



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