Barts-MS rose-tinted-odometer: ★★ (Purple Haze Friday #7D7098; looking forward to the weekend)
It is quite amazing how large and extensive the focal inflammatory lesion blindspot or scotoma is in the field of MS. I was on a call with a few American neurologists last week and they were saying how anti-CD20 therapy has transformed their MS practice. One neurologist claimed that 4 out of 5 of their patients were now going onto ocrelizumab or ofatumumab. He even said that ofatumumab will become the new Copaxone; i.e. no blood monitoring and very safe. Do you agree? When I reminded this neurologist of the end-organ damage data, i.e. brain volume loss, and the progression independent of relapse data in relation to anti-CD20 therapies he dismissed me saying that these patients were free of relapses and their MRI’s were quiet so he had done his job.
And herein lies the problem, the wider MS community including MS experts are not prepared to look beyond relapses and MRI activity; for them this is MS. In other words, if you render people relapse and MRI activity free then you have treated their MS. However, if you scratch the surface this is clearly not the case. If relapses were MS then they would predict long term outcome, but they don’t except when you are on therapy. According to the Prentice criteria that define a surrogate endpoint for relapses to be MS they need to predict outcome regardless of treatment. This is why relapses cannot be MS; relapses and their MRI equivalent (focal lesions) simply represent the immune system’s response to what is causing the disease or the real MS.
The data set below from the MS-Base register supports this proposition; i.e. off-therapy relapses do not predict long-term outcome, unlike on-therapy relapses. This point is so fundamental to understanding the real MS that most people can’t get their heads around it.
So what does this mean to you if you have MS? It means that if you have no evident inflammatory disease activity (NEIDA), and are relapse-free and MRI-activity free, it doesn’t mean your MS is necessarily under control. In other words, you could still be losing brain volume at double the rate of what is expected for your age and you could still be worsening. This is why we mustn’t be lulled into a sense of false security that we have cracked MS with our current therapies, in particular with the anti-CD20 therapies. We really need to go beyond NEIDA and target smouldering MS with new add-on strategies.
I hope all this makes sense? I have asked you before, would you rather be NEIDA or NEIDA and NEO-EOD (no evident ongoing end-organ damage)? The challenge for the MS community is to shift our focus to the latter target.
Jokubaitis et al. Predictors of long-term disability accrual in relapse-onset multiple sclerosis. Ann Neurol. 2016 Jul;80(1):89-100.
Objective: To identify predictors of 10-year Expanded Disability Status Scale (EDSS) change after treatment initiation in patients with relapse-onset multiple sclerosis.
Methods: Using data obtained from MSBase, we defined baseline as the date of first injectable therapy initiation. Patients need only have remained on injectable therapy for 1 day and were monitored on any approved disease-modifying therapy, or no therapy thereafter. Median EDSS score changes over a 10-year period were determined. Predictors of EDSS change were then assessed using median quantile regression analysis. Sensitivity analyses were further performed.
Results: We identified 2,466 patients followed up for at least 10 years reporting post-baseline disability scores. Patients were treated an average 83% of their follow-up time. EDSS scores increased by a median 1 point (interquartile range = 0-2) at 10 years post-baseline. Annualized relapse rate was highly predictive of increases in median EDSS over 10 years (coeff = 1.14, p = 1.9 × 10(-22) ). On-therapy relapses carried greater burden than off-therapy relapses. Cumulative treatment exposure was independently associated with lower EDSS at 10 years (coeff = -0.86, p = 1.3 × 10(-9) ). Furthermore, pregnancies were also independently associated with lower EDSS scores over the 10-year observation period (coeff = -0.36, p = 0.009).
Interpretation: We provide evidence of long-term treatment benefit in a large registry cohort, and provide evidence of long-term protective effects of pregnancy against disability accrual. We demonstrate that high annualized relapse rate, particularly on-treatment relapse, is an indicator of poor prognosis. Ann Neurol 2016;80:89-100.
General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust and are not meant to be interpreted as personal clinical advice.
Of course, I’d definitely rather know that the ‘real’ MS is being tackled. But how does an NHS patient do something about a neurologist who is just as you describe? Generally, in my experience it is a case of ‘take your DMT’ and if your MRI is stable all is well. See you in a few months. Brain volume loss? That’s not possible to measure (apparently). It can vary with how much water you have drunk! Clinical tests? What do you need them for? Bye!
How do you break through a system that is set up this way? Even asking an ‘unusual’ question sets you up as a trouble maker or difficult patient who should know their place.
Sorry. Just my experience. Really would be delighted to know how to shift the status quo but now with two minute phone appointments it seems even less likely. 🙁
Your neuro has opinions and they do not all co-incide with ProfGs opinions, mine don’t alwaysalign either and sometimes we have to try stuff for ourselves…I think we have to look at the Swedish data and see what happens when you go on a highly effective DMT from the start…then it is very, veryy clear that disability is slowed. Some places are doing a trial to say does early effective treatment work better than standard platform agents…..Why?…..I think we know the answer but it is still a priority question for the MS Society….I am happy that BartsMS can’t participate because they have moved forward and you can see this by the prescriptions….but I think we are an outlier……See this data and you know where some of the luddites work, move and you could be going somewhere worse.
This is part of the idea of “Raising the Bar” initiative
My experience is very similar. I was lucky to get alemtuzamub a few months after my diagnosis. Shortly after round 2 I started to have trouble with leg pain, but it wasn’t classed as a relapse as my MRIs have been stable. My neurologist first blamed my underactive thyroid for my symptoms and this year seemed to deny I was in decline and told me that the drug had done its job. I’m trying to understand why I have new, persistent pain in spite of NEDA. I have had to give up my job 3.5 years after diagnosis. I asked if I had moved to a secondary progressive phase as I can only understand it as accumulation of disability (I have a heavy lesion load but had few symptoms until my big relapse that led to diagnosis). No MS is not
bi-phasic, he said, and I get this, but what is it, then? Neither he, nor the MS nurses are interested, and I am left managing my own disease with meds to deal with symptoms that I really don’t want to take.
Prof G,
I posted this on the June Q&A:
“If NFL is really an inflammatory biomarker, what can be used to measure the success (or not) of treatments to address smouldering MS / neurodegeneration eg on trials such as Sizomus?
At my annual appointment last week with my MS neuro, I mentioned smouldering MS and he said that he didn’t agree with the idea of smouldering MS. That was the end of that discussion as tome was pressing. Are there other theories for the cause of neurodegeneration not caused by relapses (PIRA)?”
My neuro is also a leading MSologist (U.K.), but was very dismissive of the idea that smouldering MS existed / caused progressive disease. This is annoying to me as I’ve had an induction therapy and years later notice slow worsening. I can think back 5, 7, 10 years and know there are things I can’t do as well as I did then. My neuro didn’t offer any treatment – my MRIs show no lesions or active inflammation (so Siponimod not an option). He was very lukewarm about treatments being trialled for progressive MS (Sizomus, Simvastatin and the upcoming Octopus trial).
Once again, it’s an uphill battle for people with the disease. IRTs and anti-CD20 drugs are gaining popularity, and many neuros are sitting back and thinking job done!
Can any aspects of smouldering MS be shown on MRIs eg SELs or hot microglia? Could annual calculations of brain shrinkage not show (eventually) that even the most effective anti-inflammatories aren’t tackling all the MS processes e.g. the processes which continue to destroy brain tissue? How does the MS Progressive Alliance fit with all this? Does this alliance acknowledge the existence of smouldering MS?
Can it be used to measure…I would say yes and no.
How leading is leading…are they leading you down the garden path:-)….However, they didnt offer treatment because the agents available have not been shown to tackle what you described. Lukewarm about sizomus (so not from London), statins (so not from London)…octupus (what is it…I havent heard what they actually intend to do except have multi arm studies…on top of a DMT why not, not on top of DMT….asking for trouble. As you say SELS and imaging. You would have to be an ostrich to think that current anti-inflammatories deal with all the processess of MS.
The progressive alliance is its own beast…it has been going for a decade…but it has not lead to trials yet…They had a trial task force but has it re-invented the wheel. I think the alliance so acknowledge the existence of MS, but we didnt get funded to look at them:-(
‘sizomus (so not from London), statins (so not from London)…octupus (what is it…I havent heard what they actually intend to do’
as someone with SPMS which if any of the trials/treatments you mention (+ siponimod, cladribine, chariot) would you advise trying to participate in/take? Especially if your neuro not in same mindset as ‘London’?
Octupus and statins chariot are nationwide trials and the idea of octupus would to offer every one something…this is why it may be a bottomless pit….but if you are interested in statin study just go to the the STAT2 website and say you are interested. https://www.ucl.ac.uk/ion/centres/queen-square-multiple-sclerosis-centre/ms-clinical-trials/about-ms-stat2. If you eligible for the trials please volunteer, you may get a second opinion
Thanks MD. I was on the active drug on previous stat trial now take q high dose and don’t want to risk having placebo, if that might happen
This is the problem.
It doesn’t matter whether we as a community accept the existence of smouldering MS or not. We don’t have any say in our treatment – not in the real world. In the real world we are ushered into the offices of our holy MS neurologist specialist who has deigned to treat us and has miraculously lifted us from the grasp of this dreaded condition. His / her word is law, he / she is in charge, practically a deity. How dare we challenge the facts and knowledge (not opinions, oh no – this is surely knowledge…) of one so grand and glorious when they have graciously lowered themselves to the level of treating us mere mortals…
Of course their time is short – as it must be – surely it would be better if they didn’t need to see us at all. What – you’re on a CD20 treatment? Wonderful we can reduce you to an annual check up. By all means contact your MS nurse if you have any symptoms, so we can ignore your communications and pretend all is well. For we have CURED MS. Look – no relapses. No MRI lesions. MS is CURED. All bow before the almighty neurologists.
You need a wheelchair now? No – surely not – it cannot be – you’re a hypochondriac, MS is CURED
etc etc etc ad nauseum.
I’ve already met the opposition to ProfG. I live on a desert island off the coast of North Africa, we have ONE neurologist at the local hospital and he doesn’t like ProfG one bit. Apparently ProfG is all about his own ego – the Mourinho to Montalban’s Messi. Montalban runs CEMCAT the MS centre in Barcelona – where I used to go when I lived up there… the problem is… both my neuro here and Montalban aren’t particular fans of the idea of smouldering MS.
Coincidentally they have lots of patients in wheelchairs…
And in the end this is about brain, not personalities. I don’t care if ProfG is Mourinho, he can be Sam Allardyce for all I care – what matters is MS is eating my brain / our brains, despite CD20 therapy. And whether they believe smouldering MS exists (because of the evidence) or they believe the earth is flat I don’t care, I just want it treated…
But it’s an important question.
High up in their ivory towers, how do we mere patients – little more than ambulant cretins (for all the agency they give us) – how can we make them hear our voices? They may not like ProfG. I’ve never met him, maybe I wouldn’t like him either. But it doesn’t matter, this isn’t about personalities, it’s about brain. Time is brain. MS is smouldering. How do we make them see this?
Apart from heavy guns up-front such as alemtuzumab or HSCT, which may reduce the chances of getting smouldering disease or at least slow it down more than other therapies, there is little we can do for the processes that drive it at present. This is why we need combination therapy trials.
“This is why we need combination therapy trials.”
[polite tone] hasn’t this aim been around for ages?
Here’s a post from the blog from Jan 2014 (Deflames):
“End-organ damage in MS; can we prevent it? We are putting in a grant application to test a new class of neuroprotective agent in early MS as an add-on therapy to existing DMTs.”
I’m not blaming you / Barts, but what are the MS centres of excellence at Cambridge, Oxford, Bristol, Edinburgh doing? What about the US, Dutch, Italian, German, French MS research centres? Problem is known (preventing neurodegeneration), no solutions delivered! I might turn up to the next ACTRIMS / ECTRIMS meeting with 10,000 custard pies. Someone needs a kick up the ass. Too many awards and praise when people with MS continue to worsen.
My neuro called you an extremist. I warmed to you more. MS an extreme disease – all functions potentially affected and EDSS 10 is death. We need people like you – the Bin Laden of MS research. Keep up the crusade.
Can we quantify smouldering damage? How much damage (EDSS?) is the smouldering causing on average in 10 years, for 30yo, 40yo and 50yo? Any image features we can spot the smouldering across 5-10 years of MRI follow ups? How does the smouldering damage compare to the real relapsing damages on average for 10 years?
“This is annoying to me as I’ve had an induction therapy and years later notice slow worsening. ”
What induction therapy did you have..?
I completely agree that atrophy is important here. However, it’s not clear to me your data comparing ocrelizimab with alemtuzumab/HSCT is fair.
Alemtuzumab/HSCT cause massive immediate brain atrophy to patients during treatment. Post this, their year-by-year atrophy rates look good. However, if you look at the incremental atrophy experienced by ocrelizimab pateints in a given year, alemtuzumab/HSCT aren’t actually on-net better for something like a decade.
One potential scenario is that previous MS damage is primed to atrophy and a “lost cause”. With ocrelizimab, this damage slowly atrophy over many years until eventually reverting to health rates. With alemtuzumab/HSCT, the toxicity of the drugs kills off the damage immediately PLUS some healthy brain, and you immediately go to health rates with the remaining tissue.
I don’t think it’s clear if the scenario above is true or your view, but it’s worth acknowledging the relatively low risk of ocrelizimab makes it appealing given this uncertainty.
One potential scenario is that previous MS damage is primed to atrophy….this is the smouldering lesion the embers left after the napalm bomb has dropped
You shouldn’t equate alemtuzumab and HSCT. Alemtuzumab causes pseudoatrophy, i.e. in line with its anti-inflammatory effects, but is not neurotoxic. In comparison, AHSCT is much more neurotoxic and patients lose much more BVL in year one than what is expected. The data I have seen on ocrelizumab and brain volume loss doesn’t hint at any normalisation.
“With ocrelizimab, this damage slowly atrophy over many years until eventually reverting to health rates. ”
No..this does not happen w/ocrevus…But yes brain atrophy is why myeloablative hsct is avoided and
non-myeloablative hsct is used in order to kill off b and t cells in cns…but avoid excess
brain atrophy.
I definitely want to be NEIDA and NEO-EOD (no evident ongoing end-organ damage). Your blogs have helped me enormously to understand why, although I am relapse-free and no new lesions on MRI’S, I have had new symptoms for past 17 months.
Because one lesion has shrunk slightly, my Consultant Neurologist hasn’t seen me for 3 years (despite repeated requests on my part and recently on my GP’s part).
I think smouldering MS and end organ damage are CRUCIAL to our understanding of MS. Thankyou for taking up the fight Prof G 👏👏👏.
Sadly we don’t have any treatments for smouldering MS, but this where we should be looking for the next generation of MS treatments.
Isn’t ppms the real “smoldering” ms…and no wonder there are no
treatments because everyone has avoided ppms in all trials forever..
even the harvard ebv drug trial is just rr.
The phase 2 trial of the BTK inhibitor was originally tested only in relapsing remitting multiple sclerosis. Now phase 3 trials of BTK inhibitors are being conducted in progressive ms and relapsing remitting ms…
The btk inhibitor trials started at the same time in regards to the phase 3 trials. So if we get a positive result of the tenofovir alafenamide trial in rrms a trial ( currently being done by Harvard ) that compound could be not too far away from a trial in progressive ms.
The problem you describe is very real – and both neurologists (ms-specialists) I have dealt with so far are unable to look past MRIs.
I went off DMTs (because of chronic lymphopenia and infections). My MRIs showed no changes after 8 months without DMTs, so my neurologist sees no reason whatsoever to start a new DMT.
I had to insist to have a new DMT prescribed (doing all the research on the various DMTs myself).
I feel I’m practically self-medicating, doing the research, and making decisions based solely on my own research. That’s not okay, but it’s reality.
As other comments, of course would want to be free of the smouldering. It sounds as though the balance of power amongst stakeholders/interested parties needs to be shifted! It’s such a big topic and would need such time and energy to achieve…how to go about it? Thank you for doing all you do and championing the cause 🙂
Perhaps you are not influencing MSologists at the rate that you like, which is frustrating as they hold the keys to the treatment of so many patients. However, your efforts are not in vain. In the last couple of weeks i think i have convinced my nuerologist to switch me to alemtuzumab, having spent a miserable year on ocrelizumab following my initial diagnosis. Without this blog, i would have probably have followed my current course. No guarantees it will work of course, but hopefully i will be giving myself a better chance. So thank you from me and dont give up the fight
Hey Anon, why was it a “miserable” year on Ocrevi for you? How long have you had MS? Best wishes, CK
Hey CK, officially diagnosed July 2021. First CIS event was in 2015, which i had largely forgotten about but obvious the disease was present at that point. For the last year, i have basically felt ‘ill’ the majority of the time and continue to accumulate sensory symptoms, the latest of which has been a tremor in my hands. Its not directly attributable to ocrevus of course, but i have continue to experience mild sensory relapses whilst on the drug. They have not been disabling and i am still fully functional. However, the exacerbation of symptoms has been clear cut. I am being scanned next week so we will see what the damage is but as we know MRI does not present the whole story. I think i had high hopes that Ocrevus would keep things in check which seems to have been the case for many, at least in terms of relapses and MRI activity. Dont let me put you off….there are plenty of success stories and the treatment is still a quantum leap from the ones being offered to patients 15 years ago! Hopefully we will be still running around when the next jump is made
Hey Anon,
July 2021 – you’re from the future 😮 Sorry you have to forgive me (it’s a Friday). I’m on Ocrevus now but felt the walking/balance getting worse since I started so just wanted to compare experiences. I’m glad you got Alemtuzumab and I’ll keep my fingers crossed that you are jumping around for many more years to come.
Best wishes and I hope you have a lovely weekend. Enjoy the Sunday 29C <3 <3
CK
CK – i have heard that to on a couple of ocrevus facebook groups i am a member of. The majority of feedback is positive but there are a few cases of ‘walking getting worse’. I havent found a decent theory as to why this may be yet. Difficult to know what is ocrevus related and what is just MS but there was enough cases to suggest this was more than just the balance of probability. Jeepers….shame i wasnt diagnosed in July 2021 or i would be kicking this thing before it even starts! have a great weekend and best of luck with your own journey
Sometimes I think that with my awful slow, early onset PPMS, which has stuck to the same areas of my body to a great degree over 2 decades, I have the smouldering without the (distinct) relapses. Would people like me not be good study subjects?
I was diagnosed in january 2014. Edss 0
Despite using rebif and tecfidera I became edss 7.5 in 2016.
In 2017 I started Natalizumab and got some functions back. Handfunction, transfers, eyesight, bladder control and I can stand straight up again.
In 2019 I switched to Ocrelizumab with the same benefits as Natalizumab.
Since 2017 I am NEIDA. But all my MRI’s show atrophy, also in the spinal chord.
Fysically I feel okay but I know that my head is playing tricks with me. For me it is important that I know this so that I can trick the trickster. In other words I have built in some tools to not forget stuff!
Around me there are other pwwMS who just keep focussing on there disability, but I see them getting worse mentally each time I see them. Ignorance is a bless? Maybe.
So being NEIDA? Absolute!!!
Being NEO-EOD? Yes please
Where can I sign in…?
Professor G,
I believe, to your point about the real MS, I just came upon this article this morning 6/11/21, which you likely have seen. I’m not as internet savvy as you, so here it is for you to comment or not as you wish.
Cortical Involvement Determines Impairment 30yrs. After CIS
Lukas Haider( lead author), et. al., including Alan Thompson and Fred Barkhof
Brain, awab 033,https://doi.org/10.1093/brain/awab033 published 21, April 2021.
Clifford Reed
Thanks for sharing this Clifford. I’m no expert, just a pwSPMS and regular reader here. Long term follow up studies are fascinating I always think and this one way back to 1987 years before beta interferon! Cortical involvement (lesions and grey matter atrophy) and also cervical cord atrophy (for t25ftw) really show up here as key indicators. Maybe we all should have routine brain volume assessments…
On reading the abstract I thought it pretty amazing that none of the 63 had been lost to follow up! But I see there were 132 at the start so about half were unavailable for MRI at 30 years. Of these 29 had died, 16 due to MS 🙁
However frustrated we might all get now, things are light years better than they were 30 years ago 🙂
Have a good weekend all 😊
I know this topic is a “Hot Button” Issue for you. I don’t doubt it’s importance.
But I think that the real problem is not that people are not taking it seriously enough, but rather that we are expecting the wrong people to find solutions where they might not exist.
Mixing up the roles between Academia, Researchers, Drug Companies, MS non-profits, Medical policy makers, Clinicians, Social Media champions, just makes for more confusion. While a certain amount of cross boundary collaboration is productive and even necessary, too much makes for chaos.
People do not understand their own role or even what other people are doing so that they can provide a catalyst for the desired change. There is a lot of wasted energy and competition where there could be economy and turbocharged productivity.
It has become my non educated opinion that MS drives many (Most?) of it’s sufferers into accelerated aging. This can be seen not only in the BVL loss but in many in other parametric measures. Many of these have been studied in the past and reported in publications.
You could I suppose rage against the end users. Those who prescribe the DMTs are easy targets. You can’t really blame the MSers. (OK. Maybe a bit if they can read this blog and understand the between the lines messages.) But the MS clinicians are are in a jam too. They are the experts. But so little is known about what the best treatment is and it is continuously changing. The drug companies are trying to make money.
The insurance companies and government agencies are trying to save money. The academic organizations are trying to do their academic thing. The grad students and post-docs are trying to get degrees or publish papers.
There is a lot of opportunity for confusion and misinformation. If everyone knew what the best treatment of the day was for the specific patient it would be a lot easier.
But the plain fact of the matter is that there is no great solution for the BVL and aging symptoms of MSers known at present. There is not even good agreement between the imaging providers on how to make these measurements in a consistent standard protocol.
So this points to the known sensible approach that you have presented before.
Reduce comorbidities. Smoking, Diet, Exercise, Sleep, Social/Mental Health.
Get on the best DMT if it applies, as soon as possible, and stick to it until the next best thing comes up.
Try to avoid pitfalls along the way. Don’t get on treatments are are substandard. Manage your symptoms.
Everybody ages. We all do so at different rates. No one knows how much time they have. Make the best use of it as you can. Medicine will not likely give you a long extension. If you are lucky, you might just buy a little more time to love those around you and make the world a better place.
For those in a position to do so, challenge for the needed tools and research.
Lets standardize BVL metrics. Lets standardize NfL metrics. Lets standardize non-invasive OCB.
Lets collect useful clinical level feedback in a way where it can be compared internationally in registries.
Engineering systems with poor feedback are unstable or non-functional.
Let’s see what works. Let’s expose what doesn’t.
Drive research that has promise. Don’t mix up R&D with production.
Everybody has a role to play. We can overlap. We can share ideas.
But don’t expect the Architect to be on the job site laying mortar. Don’t expect the brick mason to file for the building permits. Don’t expect the bank financier to review the engineering drawings.
So without really meaning to I have gotten on a rant myself.
But my main point is don’t beat up on yourself. You are doing a great work. If you get exhausted take a break. Do something fun. Come back tomorrow or in a week or so and carry on charging at those windmills.
👍
Well said!
Sunny weekend ahead c.28C on Sunday. No doubt Prof G has invited Mouse Doctor round for an afternoon barbecue. As they sit on their sun loungers sipping fine wine and real ale, they might want to have a quick read of the following:
https://link.springer.com/content/pdf/10.1007/s40265-021-01526-w.pdf
Have a nice weekend
Thanks. Some gardening and #BackTo21 exercise as a weekend warrior. A BBQ sounds like a good idea. I now only drink good/fine wine; at my age life is too short to drink wine you don’t enjoy. I am particularly into the new crop of experimental wines that are coming out of the Western Cape.
You could invite the top 20 UK MSologists to the barbecue but you might end up with boxes of sausages left over😊
As my first boss (abrasive guy) used to say “I’m not here to make friends”.
Keep chipping away with the smouldering MS theory. In the kingdom of the blind the one eyed man is king.
Thanks I have read it already, this lab has been documenting the failures in MS for the past few decades and picks up a few that I have missed. The title doesnt allow it to report on any successes so there is no balance.
However, it re-inforces what I have said over, and over and over and over again…If the trial design/patient population is not responsive you will struggle to show an effect. I have no control over this…..so not sure why it will spoil the BBQs and Footie over the weekend….I would say add-on to platform DMT is not the clinical experiment you want to do if you want to maximize the chance of success and likewise most importantly pick agents that get into the brain if you want target events in the brain. This bit of rocket science continues to be ignored:-(……It doesn’t give me any pleasure either…Some of the choices were turkeys even before it was Christmas.
P.S. You’ll be pleasedbe to know that not at drop of real-ale has passed these lips during the pandemic, so have a a nice weekend and hope you enjoy your tipple……but be careful I hear bile has a choking risk:-)
The team are about to publish an extra chapter on the work of Professor David Baker. I’ve seen the draft. The section on successes is very short and I want to watch the England game so won’t get through the section on near misses (long read).😁
Are you following the back to 21 [stone] challenge?
I should cut back on my bile consumption. An effective neuroprotectant will get me back on the straight and narrow.
Sticks and stones:-)
effective Neuroprotectant…read chapter 4…it’s there, oh and try chapter 6 as well:-)
“I was on a call with a few American neurologists last week and they were saying how anti-CD20 therapy has transformed their MS practice.”
Yes..because in u.s. and canada alemtuz is not widely used for whatever reason…and hsct is only done in trials
which have been running non-stop in u.s. for 20 years…so anti-CD 20 is all they know.
Most neurologists entered the profession when MS was another terminal neuro degenerative condition about which you could do nothing. Compared with that, NEIDA is a good target. Most neurologists learned palliative care and immunology must have come as a shock. Show them how to be a 21st century neurologist. Eventually the younger ones will follow and the older ones will retire. Also, ‘purple haze’ is a Sativa which will do nothing for exasperation. An Indica will do far more for exasperation.
“the profession when MS was another terminal neuro degenerative condition about which you could do nothing.”
It still is for ppms…..unless your ppms has mri lesions…
Can you give us some MSers some practical advice regarding ANYTHING we can do the lessen the rate that MS is smouldering in the background? I am on Ocrevus which is the highest efficacy drug I am eligible to be on in the UK at the present time. It is exasperating at times to read posts like this…it literally feels like there is nothing I can do. Can you give some glimmer of hope…however tenious it may seem to you…some of us really need to feel like we have some sort of control, even if it is barely there?!
🙂 apparently I cant give advice
I’m assuming you can’t give advice for legal reasons? Instead could a blog post perhaps be created detailing theories and early studies suggesting things that may have the ability to affect the rate of smouldering MS…including things that MSers are able to start practicing themselves, rather than medications that are not/and will not be available to the majority for some time?
I am not a neuro and I don’t have insurance
I can offer you some suggestions based on my own reading.
The most effective add-on neuroprotective therapy is almost certainly exercise. However, I think you do have to go beyond the rather conservative official recommendation of 150 minutes a week. I would suggest a minimum of seven hours of high-intensity exercise a week if you want to make a serious dent in MS.
Prof G has suggested before that there is a strong case from basic science for a ketogenic diet and intermittent fasting being beneficial. I personally do 16:8 intermittent fasting.
In terms of supplements, you can take 5000 IU vitamin D (obvious recommendation), 1200 mg alpha-lipoic acid (in a single dose, without food), and 500 mg coenzyme Q10. There are more you might want to consider, but these are the basics.
If you can, start taking a sodium channel blocker drug. There have been two positive phase II sodium channel blocker trials. These are already used for treating pain so you might be able to get a doctor to prescribe them if you say you have MS-related pain.
Finally, there is a drug called Ibudilast which has two high-quality (multi-center, hundreds of participants) phase II trials indicating benefit for brain atrophy at a dose of 100 mg/day. Ibudilast has been used for stroke and asthma in Asia for decades and has a well-know, excellent safety profile. I have personally never experienced any side effect other than slight, transient nausea. It is an OTC drug in Japan and it is very easy to order online from Japanese pharmacies. However, 100 mg/day is a high dose, so be warned that this will set you back several hundred dollars a month.
Hope this helps.
I love your belt and braces approach to neuroprotection. Like you I do exercise, Alpha Lipoic Acid (my neuro said the data looked good for having a neuroprotective effect), Keto and intermittent fasting.
Phase 2 data on Ibudilast looked promising (but a bit confusing re the difference between SPMS and PPMS).
As ever the world of neurology never ceases to amaze me. Should we cut back on exercising?
https://www.bbc.co.uk/news/health-57431412
Agree re lipoic acid, expect.anotjer study will happen
How do you all deal with the burn from ALA? It’s nigh unbearable even at 600mg for me.
Sorry, can’t advise, as I’ve experienced no adverse effects from taking 1200mg of ALA each day..
I think ibudilast had been granted ‘fast track’ status over 5 years ago and it’s still in phase 2 trails.
The pace of change in MS is shocking even for already approved drugs, all be it for other conditions.
You suggest to fake pain to get Sodium channel blockers?????
OMG, were not talking about M&M’s or Smarties!!!
Come on people, self medicating? The neuro’s and all other doctors didnt’t go to doctorschool for more then a decade for nothing!
Unbelievable
“The neuro’s and all other doctors didnt’t go to doctorschool for more then a decade for nothing!”
With regard to the former, I wonder what they are taught ie the cause of most neurological disease are still not known (MND, Parkinson’s, Huntington’s, MS….) and treatments don’t really exist for MND and Huntington’s. There are no treatments for the neurodegenerative processes driving MS. Imagine you’re a patient with PPMS with no signs of active inflammation and you are accumulating disability. The neuro can’t offer you anything (maybe a trial). If there are signs from early stage trials of drugs which might help with neuroprotection (eg ALA, Ibudilast, Metformin) what is there to loose? Progressive MS is a slow death sentence (EDSS 10 is death from MS), so a patient has the option of doing nothing or trying something ie something not approved but which shows some promise of having some positive effect.
“OMG, were not talking about M&M’s or Smarties!!!”
In terms of their effect on disease…you might as well be.
“Can you give us some MSers some practical advice regarding ANYTHING we can do the lessen the rate that MS is smouldering in the background?”
It’s been said many times here…..alemtuzumab or hsct.
Do you think this could change if we get a potent drug against progressive ms ?
Your maven colleague Prof Georg ebers
Said in 2013 that relapses are not a good prognostic factor to reach disability milestones (edsss 3,6 ,8, 10) in
natural history studies
But they predict disability if they happen in the first 2 years after diagnosis
Ie: those with more relapses in the first 2 years progress faster
So a bit different opinion
“But they predict disability if they happen in the first 2 years after diagnosis
Ie: those with more relapses in the first 2 years progress faster
So a bit different opinion”
This is well known from natural history studies…total recovery from first relapse is a
good sign…but no disability in first 5 years…gives 50% chance to go 30 years with none.
Obrigado
😉
Relapses are a bit important after all
“Relapses are a bit important after all”
They are important factor but they aren’t the disease…
because people recover from them.
The real disease is brain loss from inflammation and
neurodegeneration.