I’m on treatment, why am I getting worse

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Today someone asked “Selma Blair today tweeted she is getting sicker with her MS. Given her personal wealth and access to the best treatments. And we now have treatments that effectively shutdown ms in rrms. Also given she has had plasma exchange. My question is why is she getting sicker? “

The simple answer is I don’t know because I am not familiar with her particular case.

However, getting worse despite being on treatment does not surprise me because there is biology at work.

At the moment we think that one of the problems with MS are white blood cells entering the brain and causing damage.

This aspect can be treated by current MS drugs. However, some people do not respond to them and so they can get worse. These people may need to switch to a stronger drug. But worsening on strong drugs can also occur

Once the damage is triggered by one type of inflammation involving T and B white blood cells, a different type of inflammation will continue to cause damage to the nerves and this damage will take time to become manifest and die out.

This may take 2-3 years. At present we do not have effective treatments to limit this type of inflammation in the brain and so disease can get worse.

Plasma exchange removes antibodies from the circulation but if they are being produced in the brain these wont be touched.

To see it more simply. If you think of the cause of MS to be a match and when the match lights, MS attacks occur.

These matches cause damage and light a fuse which burns slowly and the damage acccumulates as the fuse gets to the dynamite. This will be the slow nerve damage.

Now you can blow the match out so it doesn’t light any more fuses, but thi bit of puff is not enough to blow out the lit fuse and this is going to continue to burn and so damage accumulates despite effective treatment. Therefore the drug can be working even if you feel you are worsening.

This is why it is important to get treatment, and that treatment needs to be effective, as soon as possible to stop those fuses being lit because for every attack you notice there may be 7-10 match strikes without you noticing.

There may be other reason why someone may worsen despite being on MS treatments

About the author

MouseDoctor

75 comments

  • Selma Blair is currently in Chicago undergoing HSCT, so I think you should probably take those comments at face value…

    • People who get HSCT can also worsen. HSCT is a strong bit of puff but in Chicago at the Burth lab this is not the strongest bit of puff you can get. The response was not directed to Ms.Blair but is a general response. It serve to highlight the important of brsi health

      • They can worsen, yes, but most will see a halting of progression, some symptomatic improvements and / or a reduction in the EDSS.

        My point was that Selma is currently there having treatment right now so it’s a bit early to tell if it’s helped or not! Given how my husband was feeling at this stage in the procedure, I’d be willing to bet she’s feeling pretty rough! But then, so would anyone undergoing any kind of transplant.

        She hasn’t tweeted anything of the kind recently. Worth checking your sources (or even just her Twitter) if your using that as your introduction to the topic. She’s posted more on Instagram about her journey than she does on twitter.

    • We’re aware of numerous cases where patients lesions have shrunk or disappeared after HSCT, Gavin. Not in every case, granted, but it can happen.

      Also, it’s likely that hidden inflammation not picked up in an MRI is diminished or eradicated after HSCT for many patients.

      • Allison, just for my own edification as I have been reading up on stem cell replacement therapy as a possibility, is it still trialing in the U.S. or has it been approved at this point?

        • Third phase trials have been completed and the results published – it’s due for FDA approval in 2023 I believe.

          • I guess some countries are more progressive than others! Thank goodness for the good old NHS (at least for some sufferers!), Russia and Mexico.

      • Alison, I think you ought to have very robust scientific evidence before bandying such claims about. “Numerous cases”, “it can happen”, “it’s likely” doesn’t cut it.

        • I’m aware that I’m reporting anecdotal evidence, ‘Anonymous’, but it doesn’t make it less factual. I’m simply reporting back on what patients (I have personally communicate with) have been told by their doctors on analysis of their MRIs post-HSCT. It is what it is.

          Just because these stories aren’t part of a clinical trial (although, of course, some of them ARE), that doesn’t make them any less valid. There is a place for anecdotal evidence too you know.

          What I can tell you about my husband is anecdotal, but it doesn’t alter the fact that he’s living, breathing proof of the benefits of HSCT even for someone of SPMS and EDSS 6.5 with no active inflammation in an MRI prior to treatment.

          Of course trial data is important, but you can’t just sweep these stories under the carpet and pretend they don’t exist!

    • The clearest, most honest statement on progressive MS I’ve ever read.

      As someone with PPMS for whom the phenomenon of relapse has been more than elusive, I thank you for pushing for real treatments for progression.

  • Hi Prof G – I’m aware that my MS is with me every day & is very reactional to lots of factors. I still feel that it must matter to Neuros & Healthcare Professional that we should be advocating for the medicine to help with the symptoms & progression. Why has it taken so long to highlight this area of MS! Although there is no ultimate cure, as HSCT, as noted through various sources, that it doesn’t always work & is dependant on the type of MS you have (where the attacks took place, how many and how aggressive, etc, etc…

    • HSCT has been successfully used to treat ALL forms of MS. Yes, those with highly active, early RRMS tend to see better results and more reversal of symptoms, but that’s not to say that it won’t halt progression in progressive patients and patients with a higher EDSS. My husband was SPMS EDSS 6.5 (he had NO active inflammation visible on a scan) – his EDSS is still the same, but he has had well over twenty symptomatic improvements that have improved his quality of life enormously and, more importantly, after progressing very rapidly in a short time, he’s had no progression at all in the last three years. He was treated on the NHS in London (yes, he slipped through the net and thank goodness he did!) Please check out the HSCT Facebook groups as they are full of stories like this and the true facts of HSCT.

      • Alison, speaking personally, I have “PPMS”, and it would take an awful lot more than anecdotes and Facebook stories (in my experience, people are less than honest on Facebook) to persuade me to go through HSCT. Perhaps it does help some people, but it will harm others on balance.

        • Of course! I wouldn’t for a moment suggest that you should take my anecdotal evidence in isolation. There is plenty of research for outcomes (including HSCT for PPMS) and it’s entirely the responsibility for the individual to do their own due diligence – which is exactly what we did. However, there IS still a place for anecdotal evidence alongside the clinical data – I came across this article a few years ago which sums is up rather well.

          https://www.theguardian.com/healthcare-network/2012/sep/03/in-praise-of-anecdotal-evidence?CMP=share_btn_fb

        • Of course! I wouldn’t for a moment suggest that you should take my anecdotal evidence in isolation. There is plenty of research for outcomes (including HSCT for PPMS) and it’s entirely the responsibility for the individual to do their own due diligence – which is exactly what we did. However, there IS still a place for anecdotal evidence alongside the clinical data – I came across this article a few years ago which sums is up rather well.

          I can’t post the link here, but if you look up “In praise of anecdotal evidence by Dick Vinegar
          Mon 3 Sep 2012” you should find it.

        • Of course! I wouldn’t for a moment suggest that you should take my anecdotal evidence in isolation. There is plenty of research for outcomes (including HSCT for PPMS) and it’s entirely the responsibility for the individual to do their own due diligence. This website seems to be playing up a bit for me today when I try to reply, but hopefully if you search for an article I read in The Guardian a few years ago (“In praise of anecdotal evidence” by Dick Vinegar Mon 3 Sep 2012) you will see where I’m coming from on this – there is most definitely a place for anecdotal evidence alongside clinical data – I think it would be remiss of us to ignore that.

        • Apologies for the duplication of my reply! It didn’t appear to have sent each time. Oh well, at least I’ve made myself clear, albeit in triplicate! Sorry about that! (If admin could delete the duplicates that’d be great!)

  • Prof G, I know all DMDs are there to help & God willing stop progression but as I said before, medicine to support the progression other than steroids or pain relief other, that are available at the mo (mostly make you, spaced out, affect your fatigue, stomach & other nasty side effects). Communicating with your patients all this up to date info, very important for patients to know, options & not be left to Dr Google, would be amazing progress too!

  • Thanks MD for providing this post. Hadn’t picked up on your having done so, before replying to Gavin on July Q&A querying those very things: failing on treatment and progression despite NEDA.
    Those of us with RRMS are so lucky any treatment is available but it isn’t a guarantee and shouldn’t be presented that way!

  • Great post and briliant diagrams that make understanding it much easier – thanks for all the effort in explaining this.

  • Isn’t the obvious answer to the question: “Because you are being treated for something you don’t have”?

  • Hi MD. I asked the original question. Thankyou for a full and complete answer to my question. It’s insightful that selma has gone for HSCT and not Alemtuzumab.

    • The data and Prof Burt are compelling, but alemtuzuab is third line and has the baggage, but would anti-lymphocyte therapy (non myeoablative) be better than alemtuzumab be different (the phase II alemtuzumab data was pretty striking), There is still the risk of secondary autoimmunities with HSCT.

      • Alemtuzumab and HSCT are not comparable. Alemtuzumab is less effective compared to HSCT (70% as effective as HSCT in relapsing MS), AND ineffective for progressive MS, unlike HSCT. HSCT is effective for the majority of all forms of MS; relapsing AND progressive. Alemtuzumab ALSO has the unfavorable side effect of initiating secondary autoimmune disease (30% risk), AND occasional cases of persistent cytopenia which has caused patient deaths. This compares with a 1-2% occurrence of HSCT initiating a secondary autoimmune disease. 30% v 1-2%… Hmm!

        • Mmm in phase ii aletuzumab it was highly effective and as for progressive MS it was not controlled so disagree we can say it has no effect. Alemtuzumab and cytpopenia and mortality and for HSCT the result is….

          • I clicked on the notification especially to see how that sentence finished, Mousedoctor! I was bitterly disappointed!

          • About 0.5-2% mortality, yes it is getting lower all the time, but we need a balanced view. I am sorry we are being overrun by the HSCT brigade.

          • Your top end is considerably higher than was quoted by the team at the London Bridge Open event this morning. They stated 0.7% Mexico is currently 0.26% – Russia is similar.

            I’m sorry you think you’ve been invaded by the ‘HSCT brigade’ – just me, as far as I can tell? I’m sure you’re only teasing – I’ll try not to take offence.

  • I am not convinced there is any drug or procedure (HSCT) that can significantly alter the course of progressive MS, both SPMS and PPMS. At that stage, any inflammation has quieted down and for unknown reasons switched to neurodegeneration. This is not news, of course, but to highlight that we have to look at stopping the different mechanisms of action that cause irreversible axonal damage. Even remyelination will not fully reverse established disability (especially in progressive patients). Axonal regeneration is the only hope, getting rid of the glial scar, etc. Look at the failed Biogen study for Anti Lingo. They’re still clinging on to this failed remyelination drug after it showed no clinical (who cares about optic nerve evoked potentials) benefit. And that trial was in RRMS for ON. What a joke. Until we can focus on regenerating axons, a very tall order, disability will remain. There is one hopeful phase 2 trial (following the ongoing phase 3 trial in ALS) started for MS with Dr. Karussis work in Israel which has shown very successful reversal of disability and slowing down in MS. The company, Brainstorm, has partnered with Mayo clinic and is recruiting progressive MS patients with no MRI lesions in their phase 2. This is the hope in progressive MS

  • I’ve rarely heard of anyone with SPMS or PPMS who improved demonstratively form Lemtrada, Ocrevus or HSCT. As you have brilliantly pointed out here, the sequestered CNS environment is not accessible to Ocrevus or Lemtrada. So, why should we expect much effect? The ongoing damage within the CNS seems, like a runaway train, to buildup and cause further damage and disability.

    • If you were part of the HSCT community, you’d regularly hear about improvements people have had. While it’s less likely to see a reduction in EDSS in progressive MS, people report a multitude of symptomatic improvements which add up to improve their overall quality of life. We aren’t talking placebo effect either – these are sustainable, measurable improvements. In my husband’s case (SPMS EDSS 6.5 and treated on the NHS 3 years ago) he has seen improvements in cognitive function, fatigue, bowel function, bladder function, upper body strength, skin inflammation, insomnia, headaches, balance, numbness in lower limbs, spasms, legs giving way, heartburn, and respiratory issues. His EDSS remains the same. His foot drop hasn’t improved. But that doesn’t mean HSCT hasn’t worked for him (or the others who report similar improvements). In the HSCT community we talk about the main purpose of HSCT being a halting of progression – symptomatic improvements are a bonus. We speak to people on a daily basis who have had HSCT in the UK, Mexico and Russia – probably in the hundreds by now. I don’t know how many you have spoken to, but I bet it’s nowhere near that amount. Your generalisation doesn’t reflect what we see. Most people keep a personal tracker of their symptoms so they can measure any and all improvements, no matter how small. A reversal of EDSS does not tell the whole story.

      • Alison, you need to be careful about reporting bias! The academic community learnt about reporting bias decades ago, which is why we now have to register trials with clinicaltrials.gov and the EMA and report on the result whether they are positive or negative.

        • I couldn’t agree more – we are in contact with non-responders too, so we also see that side of it. I have to say, those accounts are more few and far between – that’s a personal observation. We have forums for veterans of HSCT and for non-responders. There are more than ten times more members in the responders forums than in the non responders forums.

          What I’m saying here, is that we (as AIMS and as part of the HSCT community at large) have a lot more contact with a lot more HSCT recipients (worldwide) than your average neuro who might see a handful of HSCT recipients in their practice. I don’t think you can dismiss anecdotal evidence (whether positive or negative) when it’s on this scale, Gavin.

          • “There are more than ten times more members in the responders forums than in the non responders forums.”

            There could be a multitude of reasons for that. People who are disappointed with results don’t tend to report back as readily, for example. Platforms such as Facebook engender exaggerated positivity and egotistical representations.

            Clinical trials are the best way to remove bias, the huge potential for placebo/nocebo effects.

            Everyone’s body is different, everyone’s disease is different. A heterogenous collection of people who supposedly respond positively to a treatment in some of a variety of ways doesn’t amount to a lot.

            I think people need to be careful about gushing about the potential benefits of treatments for all and sundry. I feel green tea is helpful for various aspects of my PPMS, but I don’t go around recommending it, as it could harm some.

          • The lead up to HSCT can take a considerable time – usually because people are having to pay for it themselves. On average, you’re looking at a year or two. That means that we build up relationships with these people – from the very first query (usually following up on some total misinformation that their neuro has provided) to the point they’re undergoing HSCT, to their going about their lives after HSCT. It isn’t an exaggeration to say that most of these people stay in the existing forums (as WELL as joining the other forums I mentioned). They’ve built up relationships, formed friendships and become part of a community. The forums people come to when they start on their journeys are twenty to thirty times bigger again and very, very active. At no point have I ever said that HSCT works for everyone- it doesn’t, but there is a place for anecdotal evidence (read the article I posted earlier) alongside clinical research. And I think it’s a little disingenuous to liken the feedback on HSCT to your green tea…

            Unless you’re a member of this growing community, I think it’s hard for you to appreciate. But if you really don’t think there is a place for anecdotal evidence then you need to tell that to the neuros who perhaps have 2 patients who have had HSCT and haven’t responded – they cannot then use this as ‘evidence’ not to refer other patients. Our local neurologist has now at least 5 patients who have undergone HSCT – 2 on the NHS and the rest overseas (could be more by now). They are all, in her judgement, doing well. But they’re still only a drop in the ocean.

          • I do not “liken the feedback on HSCT to my green tea”. I am saying that I will not trumpet even something relatively innocuous, no matter how convinced I might be of its benefits to me. Clinical trials are conducted by professionals for good reason. Not least to help stop people being harmed by unsuitable, ineffective treatments through willy-nilly experimentation.

          • Did you actually read my reply? Did you read the article about the value of anecdotal evidence? Anecdotal evidence can not be dismissed when it’s on this scale. Of course clinical trials and peer reviewed research is key, but it’s very naive to dismiss hundreds of testimonials just because they don’t fit your way of thinking. Read the article.

          • Believe me, with the ubiquity of internet testimonials of unknown veracity, it is more important than ever.

          • I think it’s quite arrogant to dismiss anecdotal evidence and when it comes to MS. Of course data is important, but it’s not the be all and end all.

            Do you really believe there’s no value in anecdotal evidence? None at all?

          • Between a clinician and patient yes, there is a role, otherwise, I think we all remember the CCSVI furore of a few years back and the role of internet anecdote and Facebook groups in driving its promotion, leading to millions being wasted in debunking it.
            Now I don’t think HSCT is by any means equivalent but to deny that there are malign agents out there some of whom are touting for business, is naive.

          • No, when it can be verified.
            Verified anecdotal testimony was the spur for our group getting into medicinal cannabis research twenty years ago.

          • I’m sure that the HSCT veterans community would be delighted to help you to verify their testimony. How can we facilitate this?

    • If you look at the literature there is clear evidence of a reduction in EDDSS post alemtuzumab. They suggested protective immunity was the basis. More likely stop disease and the repair mechanisms opperate

  • For the discussion on anecdotal evidence. I guess a researcher could draw up a quanitative survey and conduct a study on pwMS. The survey could ask about experiences of such and such. Then the results collated would be data.

  • Hello to “Anonymous with PPMS”! Here is my anecdote with regard to HSCT.
    I was diagnosed with PPMS in 2009, and was told by the NHS neurologist that there were no treatments for PPMS, only for some symptoms. Initially I accepted what I was told – doctors are experts with their patients best interests at heart, right?
    Then I became so disabled that I had to give up my job and symptoms like swallowing/choking frightened me into searching the internet, where I came across HSCT. Firstly, I read the anecdotes of people (including a few PPMS patients) and followed that by reading as much research information as I could find. I spoke to various HSCT doctors – haematologists. I also spoke to my neurologist, who was vehemently against the very idea. Interestingly my local hematologist was very supportive and reassuring about the procedure, and so in 2014 I became the third Brit to go to Russia for HSCT. To cut a long story short: Jere I am, five years later, and my PPMS has not worsened at all – in fact, I have many symptomatic improvements, including the swallowing problems which prompted me to search for help. I will be forever grateful to the people who shared their “anecdotes” and showed me the way to HSCT and getting my future back.
    You can dismiss my experience as anecdotal, of course, because that is what it is. It also happens to be true, and another little piece in the jigsaw. Best wishes to you!

  • Hey there ‘anonymous’. I’m not angry at all. I’m slightly disappointed and maybe even slightly disgusted at the absolute rubbish that many PWMS are advised by the so called gatekeepers of their health. I’m actually really grateful because, in spite of the poor advice we received from people who claimed to be experts but were nothing of the kind in retrospect, my husband has had his MS halted. And you know what? Even if in five years, or ten years, or whatever he starts to progress again, he’s had a lengthy period of time where MS isn’t ravaging him. It’s kept him out of a wheelchair for the last three years (how can I be sure? Because I live with him 24/7 and could see the weekly new symptoms and the rapid deterioration. Since then? Nothing). So no, I’m probably the opposite of angry. I’m passionate – there’s a big difference.

    • Okay, I understand you better. But I think it doesn’t help when people with a passionate message come across as aggressive, and use block capital shouty text. All the best. 🙂

        • You can call it what you like, sweetheart. As I said – capitalising a single word for emphasis does not a shouty post make…

          If we’re going to comment on style, I had an interesting message from someone following this thread last night (wasn’t going to post it, but you will provoke the situation!)

          “Just read the Mouse Doctor thread. I’d love to comment, but just don’t have the energy! He just annoys me so much; a true condescending t***! He drains my will to live…”

          Maybe you should consider your own tone / style / lexicon?

      • I’m not sure that highlighting a single word in caps (for emphasis – no italics or bold option here) can be construed as ‘block shouty text’, but I guess it’s all in your perception. All the best to you too!

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