MS researchers must all have the game Boggle - a word game in which players try to find as many words as they can from a grid of lettered dice. I’ve lost count of the various acronyms dreamed up by under worked MS researchers: RRMS, SPMS, PIRA, RAW, NEDA, PIRA, EDSS…… the list is endless. Surely the important point is that MS causes unrelenting brain tissue damage (sometimes slowly and sometimes quickly) and the mechanisms need to be understood and treated effectively. Do oncologists spend hours coming up with acronyms for the cancers they treat? (I suspect not). I want to see MS researchers with their white coats on identifying drugs to address the mechanisms and running trials, rather than moving tiles around on a Scrabble board. MS patients don’t give a shit about the latest acronym to describe the mechanisms damaging their brains, they’d rather hear “take these two / three treatments to stop any further damage and go enjoy your life”.
It feels like the whole ethos needs to change. If many neurologists won’t believe their patients who describe their lived experiences of worsening clinical state then why would they go to the effort search for progression even the patient is unaware of? Many centres appear overwhelmed and this generates work for them esp if response to findings means discussion re changing treatment. There seems to be a big gulf between MSologists approach.
That rather negative statement made, this re-working of concepts of worsening disease feels aggressive in approach which I think is exactly what is needed to try and give pwMS the very best chance long term. But it needs backing up with treatment options else you just declare patients on a disabling trajectory without options. HSCT/IRTs need to be much more available.
Yes!! If smouldering MS processes are the core component of this disease and there is the ability to measure and track ‘silent’ MS progression, that causes ongoing brain shrinkage, whether or not it is obvious to the patient or the neurologist - then surely it should be part of routine assessments?
The NHS understandably triages patients based on severity, but what happens when patients present as well for years, but possibly have ongoing brain shrinkage? If time is brain, isn’t it too late to not manage proactively?
I guess this is budget restraints that dictate whether to focus on more ‘hidden’ disease processes?
i refused future MRIs because what does it matter? I was labeled as having PPMS. I dont need to know what the MRI says. I need support until someone gets their act together and figures out remylenation. Until then its all diet and exercise for me and other complementary support that is all out of pocket expense but its what keeps me moving and feeling better.
Interesting... I have a collection of old MRI's that perhaps retrospectively, someone could take a look at and discern hitherto-missed insights. Except that when they were offered, nobody was interested: it's nobody's job to go back and review. Obviously money, resources and a reason for doing it are at the root of it. The MS Community appear wedded to the 6-monthly comparison with the MRI immediately previous and declare NEIDA if no identifiable change. Also, based on current meds available, would the new information suggest any different treatment options?
My first thought reading this Selfie was, 'I want to pay for “Enhanced MRI Analytics”!! Where do I go?!' But then I read on and realised it probably doesn't exist yet... I had undiagnosed MS for decades, had no MRI scans till I gave up on the NHS and went private. But I'd pay to have the recent ones analysed if I could 🤷
Yes, we need to go further! Alphabet soup or Scrabble, whatever your preference, are just fine. Even if my brain can’t remember them all. Those acronyms to me, just like NEIDA describe what is or is not taking place. The point for me being in the smoldering SAW category is there is nothing to do about this, other than treat symptoms, which are getting progressively worse. I can’t even manage to get an MRI because of the cost of anesthesia required due to a cochlear implant. (At my age, that is negligent imo. There are more issues than MS that could be involved.) I have also, as NEIDA, had definite relapses and flares however, I am considered “clinically stable”. Only we know what we’ve lost. Press on, please!🌷
I greatly appreciate the push to move the frontier of treatment here to tackle new biomarkers and relatively harder to observe signs of disease. I am a bit worried SAW suggests extremely high severity and could further stigma against MS, but it's a tradeoff to make sure people take smoldering seriously and don't just discard it because relapses aren't occurring.
With that, I am have some lingering questions on ocrelizumab atrophy data. You have frequently discussed how early damage in MS can damage neuron and prime later atrophy. The majority of these studies are showing atrophy within a couple years years after starting the drug, so why could this not be driven by previously damaged neurons slowly failing? I think the extension studies indicate YoY atrophy reverts right around healthy control range by year 3-5?
The counter argument is drugs like alemtuzumab work immediately to normalize atrophy, but there is also material brain atrophy as part of the treatment itself. The initial toxicity of alem may purge all the weak neurons immediately and leave a healthy control level of atrophy immediately after. However, this doesn't seem obviously preferable to me versus ocrelizumab's slow glide to normal atrophy rates.
Prof G, this is part of a larger, longtime confusion for me. You usually describe smoldering MS as a poorly understood concept or controversial, but seem to define it as "getting worse despite no relapses and no MRI changes". Surely mainstream MS docs don't believe that current DMTs (which work at preventing relapses and MRI activity, but which say on their labels they don't really do much for disability accrual) are stopping MS in its tracks? Like, when I see my neuro and say "last year my legs weren't stiff but this year they are" she doesn't say "no they aren't", she says "I'll give you a prescription for baclofen and if it doesn't help we can talk about it". I mean, no doubt she is a great doc who I really like, but I also don't hear people complain about their doctors being surprised, etc when they slowly get worse?
Is Brain atrophy measurable on standard NHS MRI's? My wife has her annual neurologist appointment in June and this is one of the big questions for me? She goes to Queen Elizabeth in Glasgow for her MRI's. Are they able to review the last 2 year's scans to calculate the annual % of atrophy or would we need to go private for that?
My answer is Yes to “Enhanced MRI Analytics”. I'd go with "Smoldering Associated Worsening" in MS.
This has never been news to me, really. Even back in 1997 or so, I remember the big thing about interferon was that it was able to penetrate the Blood Brain Barrier and that’s why it worked. Then news reports that it didn’t really stop disease progression behind the MRI, a little later. I put that all to the back of my mind, did my injections, and focused on other stuff for the next 25 years.
My awareness or simplistic understanding was that improvement after relapse was largely temporary due to long term effectiveness of naturally occurring remyelination , and that improvement was often a compensating process, where new nerve connections and other adaptations were made. If you hadn’t suffered an attack with a particular set of body functions (whatever they may be), and if new disease activity had stopped, you need only worry about long term return to what had been damaged once, a long time ago (something unscientific like that).
Then you have different doctors motivated by different things. I was told, for example, after moving and seeing a new Doc, after 20 years with MS, that my MRI looked so good that he thought maybe “Do you really have MS?”. He was ready to start the whole diagnosis thing over, and I said good-bye. He was a newbie. I kept my wheelchair for emergencies.
But in 2018 (at 60 yrs.) a pain developed in my leg and foot, and we all thought at first, “Well, you have MS, it must be MS!”. (Keep in mind there have been no new lesions since 2000). I even went on Ocrevus until Covid came along. I went to the leg doc, the leg surgeon, the neuro-rehab MD, the nerve tester guy, and the podiatrist. Increasing pain for 3+ years. But then it improved on its own for no reason but carefulness on my part. I’m left with a slightly crooked leg (PTTD). I suspect it will improve more but not get back to what it was. Was this a relapse? No MRI evidence and the whole thing took too long. Was this progression? No, progression doesn’t remit. I’ll call it long term no pain MS spasticity with flat fleet at childhood with inflamed nerve and increased reflexes, all leading at least in part to PTTD.
So yes, knowing how things have changed and continue to change, for certain, neurologically, to use when listening to Doctors and making diagnoses of other things as I get older, would be very useful, even if there isn’t any DMT for it.
Survey question: Could PIRA be expanded to include these biomarkers instead of just physical worsening?
MS researchers must all have the game Boggle - a word game in which players try to find as many words as they can from a grid of lettered dice. I’ve lost count of the various acronyms dreamed up by under worked MS researchers: RRMS, SPMS, PIRA, RAW, NEDA, PIRA, EDSS…… the list is endless. Surely the important point is that MS causes unrelenting brain tissue damage (sometimes slowly and sometimes quickly) and the mechanisms need to be understood and treated effectively. Do oncologists spend hours coming up with acronyms for the cancers they treat? (I suspect not). I want to see MS researchers with their white coats on identifying drugs to address the mechanisms and running trials, rather than moving tiles around on a Scrabble board. MS patients don’t give a shit about the latest acronym to describe the mechanisms damaging their brains, they’d rather hear “take these two / three treatments to stop any further damage and go enjoy your life”.
It feels like the whole ethos needs to change. If many neurologists won’t believe their patients who describe their lived experiences of worsening clinical state then why would they go to the effort search for progression even the patient is unaware of? Many centres appear overwhelmed and this generates work for them esp if response to findings means discussion re changing treatment. There seems to be a big gulf between MSologists approach.
That rather negative statement made, this re-working of concepts of worsening disease feels aggressive in approach which I think is exactly what is needed to try and give pwMS the very best chance long term. But it needs backing up with treatment options else you just declare patients on a disabling trajectory without options. HSCT/IRTs need to be much more available.
Yes!! If smouldering MS processes are the core component of this disease and there is the ability to measure and track ‘silent’ MS progression, that causes ongoing brain shrinkage, whether or not it is obvious to the patient or the neurologist - then surely it should be part of routine assessments?
The NHS understandably triages patients based on severity, but what happens when patients present as well for years, but possibly have ongoing brain shrinkage? If time is brain, isn’t it too late to not manage proactively?
I guess this is budget restraints that dictate whether to focus on more ‘hidden’ disease processes?
i refused future MRIs because what does it matter? I was labeled as having PPMS. I dont need to know what the MRI says. I need support until someone gets their act together and figures out remylenation. Until then its all diet and exercise for me and other complementary support that is all out of pocket expense but its what keeps me moving and feeling better.
Interesting... I have a collection of old MRI's that perhaps retrospectively, someone could take a look at and discern hitherto-missed insights. Except that when they were offered, nobody was interested: it's nobody's job to go back and review. Obviously money, resources and a reason for doing it are at the root of it. The MS Community appear wedded to the 6-monthly comparison with the MRI immediately previous and declare NEIDA if no identifiable change. Also, based on current meds available, would the new information suggest any different treatment options?
My first thought reading this Selfie was, 'I want to pay for “Enhanced MRI Analytics”!! Where do I go?!' But then I read on and realised it probably doesn't exist yet... I had undiagnosed MS for decades, had no MRI scans till I gave up on the NHS and went private. But I'd pay to have the recent ones analysed if I could 🤷
Yes, we need to go further! Alphabet soup or Scrabble, whatever your preference, are just fine. Even if my brain can’t remember them all. Those acronyms to me, just like NEIDA describe what is or is not taking place. The point for me being in the smoldering SAW category is there is nothing to do about this, other than treat symptoms, which are getting progressively worse. I can’t even manage to get an MRI because of the cost of anesthesia required due to a cochlear implant. (At my age, that is negligent imo. There are more issues than MS that could be involved.) I have also, as NEIDA, had definite relapses and flares however, I am considered “clinically stable”. Only we know what we’ve lost. Press on, please!🌷
I greatly appreciate the push to move the frontier of treatment here to tackle new biomarkers and relatively harder to observe signs of disease. I am a bit worried SAW suggests extremely high severity and could further stigma against MS, but it's a tradeoff to make sure people take smoldering seriously and don't just discard it because relapses aren't occurring.
With that, I am have some lingering questions on ocrelizumab atrophy data. You have frequently discussed how early damage in MS can damage neuron and prime later atrophy. The majority of these studies are showing atrophy within a couple years years after starting the drug, so why could this not be driven by previously damaged neurons slowly failing? I think the extension studies indicate YoY atrophy reverts right around healthy control range by year 3-5?
The counter argument is drugs like alemtuzumab work immediately to normalize atrophy, but there is also material brain atrophy as part of the treatment itself. The initial toxicity of alem may purge all the weak neurons immediately and leave a healthy control level of atrophy immediately after. However, this doesn't seem obviously preferable to me versus ocrelizumab's slow glide to normal atrophy rates.
Prof G, this is part of a larger, longtime confusion for me. You usually describe smoldering MS as a poorly understood concept or controversial, but seem to define it as "getting worse despite no relapses and no MRI changes". Surely mainstream MS docs don't believe that current DMTs (which work at preventing relapses and MRI activity, but which say on their labels they don't really do much for disability accrual) are stopping MS in its tracks? Like, when I see my neuro and say "last year my legs weren't stiff but this year they are" she doesn't say "no they aren't", she says "I'll give you a prescription for baclofen and if it doesn't help we can talk about it". I mean, no doubt she is a great doc who I really like, but I also don't hear people complain about their doctors being surprised, etc when they slowly get worse?
Is Brain atrophy measurable on standard NHS MRI's? My wife has her annual neurologist appointment in June and this is one of the big questions for me? She goes to Queen Elizabeth in Glasgow for her MRI's. Are they able to review the last 2 year's scans to calculate the annual % of atrophy or would we need to go private for that?
I think you didn't need to point out it was fictional, the patients sounds exactly like prof G and no one will use the term SAW.
My answer is Yes to “Enhanced MRI Analytics”. I'd go with "Smoldering Associated Worsening" in MS.
This has never been news to me, really. Even back in 1997 or so, I remember the big thing about interferon was that it was able to penetrate the Blood Brain Barrier and that’s why it worked. Then news reports that it didn’t really stop disease progression behind the MRI, a little later. I put that all to the back of my mind, did my injections, and focused on other stuff for the next 25 years.
My awareness or simplistic understanding was that improvement after relapse was largely temporary due to long term effectiveness of naturally occurring remyelination , and that improvement was often a compensating process, where new nerve connections and other adaptations were made. If you hadn’t suffered an attack with a particular set of body functions (whatever they may be), and if new disease activity had stopped, you need only worry about long term return to what had been damaged once, a long time ago (something unscientific like that).
Then you have different doctors motivated by different things. I was told, for example, after moving and seeing a new Doc, after 20 years with MS, that my MRI looked so good that he thought maybe “Do you really have MS?”. He was ready to start the whole diagnosis thing over, and I said good-bye. He was a newbie. I kept my wheelchair for emergencies.
But in 2018 (at 60 yrs.) a pain developed in my leg and foot, and we all thought at first, “Well, you have MS, it must be MS!”. (Keep in mind there have been no new lesions since 2000). I even went on Ocrevus until Covid came along. I went to the leg doc, the leg surgeon, the neuro-rehab MD, the nerve tester guy, and the podiatrist. Increasing pain for 3+ years. But then it improved on its own for no reason but carefulness on my part. I’m left with a slightly crooked leg (PTTD). I suspect it will improve more but not get back to what it was. Was this a relapse? No MRI evidence and the whole thing took too long. Was this progression? No, progression doesn’t remit. I’ll call it long term no pain MS spasticity with flat fleet at childhood with inflamed nerve and increased reflexes, all leading at least in part to PTTD.
So yes, knowing how things have changed and continue to change, for certain, neurologically, to use when listening to Doctors and making diagnoses of other things as I get older, would be very useful, even if there isn’t any DMT for it.
https://jnnp.bmj.com/content/early/2023/05/01/jnnp-2023-331051