Barts-MS rose-tinted-odometer: ★ (seeing orange; halfway between red and yellow)
Do you want to know how badly damaged your MS brain is or would you prefer to put your head in the sand and ignore it? This is a dilemma facing a large number of you. Do you ask your neurologist if you have exaggerated or accelerated brain atrophy? Do you ask to have cognitive screening to see how good or bad your cognition is?
Another metric that is likely to enter clinical practice in the future is a metric to assess how well your brain’s functional network is working. The brain is like multiple computers working together in parallel. The brains’ computers or functional domains work together in harmony as a functional network. If you acquire enough lesions and damage the functional network the brain stops working as well and efficiently as it should. This manifests as cognitive fatigue and cognitive problems. It takes so much more mental effort to get the brain’s damaged functional network to perform well, which is why it causes fatigue.
The study below shows that in pwMS with damage to the brain measured using both structure (loss of volume) and function (loss of connectivity) do poorly; i.e. they were more likely to become secondary progressive over the next 6 years. Are you surprised by these results? It is amazing how accurate these MRI metrics were in being able to predict who would become progressive or not.
The message from this and other studies is simple, MS damage begets MS damage. This is why we have to diagnose and treat MS as early as possible and if necessary as effectively as possible. Once damage accumulates it is irreversible and when it is detected it represents a sick brain, which then continues to be shredded by the processes that drive smouldering MS.
Rocca et al. Network Damage Predicts Clinical Worsening in Multiple Sclerosis: A 6.4-Year Study. Neurol Neuroimmunol Neuroinflamm. 2021 May 21;8(4):e1006.
Objective: In multiple sclerosis (MS), clinical impairment is likely due to both structural damage and abnormal brain function. We assessed the added value of integrating structural and functional network MRI measures to predict 6.4-year MS clinical disability deterioration.
Methods: Baseline 3D T1-weighted and resting-state functional MRI scans were obtained from 233 patients with MS and 77 healthy controls. Patients underwent a neurologic evaluation at baseline and at 6.4-year median follow-up (interquartile range = 5.06-7.51 years). At follow-up, patients were classified as clinically stable/worsened according to disability changes. In relapsing-remitting (RR) MS, secondary progressive (SP) MS conversion was evaluated. Global brain volumetry was obtained. Furthermore, independent component analysis identified the main functional connectivity (FC) and gray matter (GM) network patterns.
Results: At follow-up, 105/233 (45%) patients were clinically worsened; 26/157 (16%) patients with RRMS evolved to SPMS. The treatment-adjusted random forest model identified normalized GM and brain volumes, decreased FC between default-mode networks, increased FC of the left precentral gyrus in the sensorimotor network (SMN), and GM atrophy in the fronto-parietal network (false discovery rate [FDR]-corrected p = range 0.01-0.09) as predictors of clinical worsening (out-of-bag [OOB] accuracy = 0.74). An expected contribution of baseline disability was also present (FDR-p = 0.01). Baseline disability, normalized GM volume, and GM atrophy in the SMN (FDR-p = range 0.01-0.09) were independently associated with SPMS conversion (OOB accuracy = 0.84). At receiver operating characteristic analysis, including network MRI variables improved disability worsening (p = 0.05) and SPMS conversion (p = 0.02) prediction.
Conclusions: Integration of MRI network measures helped determining the relative contributions of global/local GM damage and functional reorganization to clinical deterioration in MS.
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.
Prof – is there a correlation between brain lesions and atrophy? i.e. would you expect someone with a high lesion load to have accelerated atrophy? and what of spinal cord disease. Yes, cord lesions are worse in terms of their disabling impact but is there some comfort to these patients in that at least their brains are being spared to a degree? in response to your question, the only time i would want to know is if there was something i could do about it. For instance, if there was still scope to move up the treatment ladder. If i’d had HSCT and disease was stable but my brain was being pruned, not sure that knowing would help me. It would just add worry, depression, sadness. There are occasions with MS where ignorance is bliss
I can share my own MS experience, which may help answer your question. I had aggressive attack with low lesion load but included a significant lesion only several mm in size but in a very significant place; the brain stem. Over past decade, atrophy is observable and disproportionate to age and asymmetrical and in different areas of my prior lesions. % of atrophy and rate is not available. I want to know every speck on my mri (Perhaps as a way to have control over my MS and also as validation for my daily difficulties when I generally “look so good”). But I find it less insightful than my hopes. Correlating lesion to specific deficit isn’t straightforward . I haven’t had a functional MRI, but my motivation would be validation, and what good is that really? Will a functional mri support my claim of disability? (Snicker snort ha ). Cognitive testing revealed slow processing speed but my educational level and fund of knowledge makes this deficit also less “visible”. I am not ignorant to my deficits caused by MS, but unfortunately as much as I struggle I find much of the world is ignorant because fatigue, poor endurance can not be quantified with current mri measurements. And what has to be viewed on a functional MRI to demonstrate a Pwms, “who looks so good” is impaired by disease? Although I couldn’t get my neuro to agree I had transitioned to spms, would the functional mri tell us anything I have not already manifested clinically? I will hope that the functional mri will benefit those more recently diagnosed pms, and lead To earlier treatment.
“Do you want to know how badly damaged your MS brain is or would you prefer to put your head in the sand and ignore it?”
My grandfather always used the phrase “don’t worry about the things you can’t control”. So apt for MS. Your questions like this imply there is something an MSer can do. But we are in a difficult position as we are faced with risk averse neuros and no treatments to halt worsening MS or to promote repair. What would you do Prof G if you had had MS for ten or fifteen years ie the treat early option was no longer an option?
My second question: is there something promising on the horizon (that poor Black Swan still seems to be locked in its cage)? You’ve done a number of posts about the C word in the last couple of weeks. However, the C always goes back to the treat early with highly effective therapies (HSCT or Alemtuzumab) approach. What about the C for those who have already missed the treat early window?
I second Sid’s question. I saw your response to one of the ‘cure’ posts that considered a cure would be found in less than 5-7 years. Was this down to new treatments on the horizon or simply reaching agreement on what could be considered a cure using the treatments that we already have at an early stage in the process? i’m sure everyone would love a post on this. It would certainly be hugely beneficial to those early in their treatment course who are considering the nuclear option of HSCT and may make them think twice
“Cancer patients aren’t treated like this – they trust their doctor to propose the best treatment strategy to stop the spread of the cancer etc. A massive cultural shift is needed in the field of neurology.”
So true problem is so many diseases have no treatment…ALS..PSP..as a result neurologists
adopt a default say-do-nothing approach.
“Progressive supranuclear palsy (PSP) is a rare brain disorder that causes problems with movement, walking and balance, and eye movement. It results from damage to nerve cells in the brain that control thinking and body movement. As a result of these complications, the average life expectancy for someone with PSP is around 6 or 7 years from when their symptoms start. But it can be much longer, as the timespan varies from person to person.”
How else to explain their denial
of hsct..totally unavailable in u.s. and canada. So never even mentioned
to patients..or they say “too risky” “it doesn’t work”
I want to know.
And I want you to do something about it.
Is constantly telling someone your brain is shredding the best approach?
Telling people this doesn’t change the facts. We know
If your wanting patients to push their neurologists for more effective DMTs do you not think the system is broken and should patients (with no knowledge of neurology) but pushing this. When the guidelines probably won’t change.
Alerting patients is critical, not in spite the system being broken but because of it. I’d rather not find out in a few years when it’s too late. Step one of taking ownership is to know whether one is under-treated.
Yes I understand that. However we’re constantly being told we don’t have access first line to the treatments that can potentially stop or effectively slow down the smouldering MS that is ‘shredding’ the brain.
Educating patients yes. But constantly reminding them there brain is ‘shredding’ surely cannot be the most pragmatic approach.
Has any neurologist ever said to their patient there brain is shredding in person? Doubt it or is it just reserved for this blog.
Their neuro who cannot provide treatments such as HSCT, Lemtrada or Mavenclad first line as their hands are tied by the sounds of it.
It’s great that the people behind this blog push for highly effective treatments first hand. But if the patients have todo the bidding somethings wrong.
The term shredding is not for this blog only. It was lifted from the script of the West Wing https://westwingwiki.com/2014/04/season-2-episode-14-war-home/:
ABBEY: Do you get that your own immune system is shredding your brain? And I can’t tell you why. [tearfully] Do you have any idea how good a doctor I am and that I can’t tell you why?
BARTLET: I’ve had one episode in two years.
ABBEY: [tearfully] Yes, but relapsing-remitting M.S. can turn into secondary-progressive M.S. oftentimes ten years after the initial diagnosis which is exactly where we’ll be in two years! Do you know what that’s going to look like when it happens?
He looks away.
BARTLET: [quietly] I know what it’s going to…
ABBEY: Fatigue… an inability to get through the day…
BARTLET: Look…
ABBEY: …memory lapses… loss of cognitive function… failure to reason… failure to think clearly. And I can’t tell you if it’s going to happen. I don’t know if it’s going to get better I don’t know if it’s going to get worse. But we had a deal. And that deal is how you justified keeping it a secret from the world. It’s how you justified it to God.
[hurt] It’s how you justified it to me.
“BARTLET: I’ve had one episode in two years.”
Exactly what all the diet people say to prove they cured their ms with X..Y..Z diet.
“Mr. Sorkin asked his research staff to find an affliction that did not put Mr. Bartlet in a wheelchair, could go undetected for years at a time, and that could be in remission and undetectable in checkups because there was no laboratory test for it. The search turned up multiple sclerosis, an ailment that Mr. Sorkin said he knew little about. Putting the spotlight on multiple sclerosis also tapped television’s great potential to educate, even though Mr. Sorkin said that was not his intent.”
John, we have always tried to tell it as it is, i.e. we don’t pull our punches. As some people don’t like this I bought some rose-tinted glasses a few years ago and now label all my posts with a Barts-MS rose-tinted-odometer, which rates the posts from zero to 5-stars depending on how negative or upsetting the posts may be for pwMS. If you put the term shredder in the blog’s search engine you see posts for 8+ years ago.
Our blog byline is “A BLOG FOR PEOPLE AFFECTED BY MULTIPLE SCLEROSIS. INTERPRETING GOOD, BAD AND OTHER RESEARCH NEWS”, which is what we try to do.
I know you do. I want to know all the facts myself, I’m not one to bury my head in the sand believe me, I want to tackle it head on.
My point is people don’t have access to the highest efficacy treatments.
Therefore telling them there brain is shredding while they cannot get access to the treatments maybe slightly harsh on some and depressing.
I think you guys do a great job and who can argue with your knowledge.
John,
“If your wanting patients to push their neurologists for more effective DMTs do you not think the system is broken.”
I think this is a fundamental point. MS is a life shortening disease (an average of c.8 years off the average life span). It can also be a very disabling disease. Yet a newly diagnosed patient trying to get their head around the diagnosis is expected to research the pros and cons of different treatments strategies, identify a treatment eg HSCT, and then argue the case with their risk averse neuro who is happy to stick them on Copaxone and wait and see. Cancer patients aren’t treated like this – they trust their doctor to propose the best treatment strategy to stop the spread of the cancer etc. A massive cultural shift is needed in the field of neurology. Think of the job satisfaction a neuro could get by offering a cure to a patient, eg young MSer, rather than just patting them on the head and sending them on their way with a box of Copaxone, an appointment with the MS nurse and a lifetime of worsening disability to look forward to. I expect that when the young medics sign up for neurology training they are required to leave their heart and feelings at the reception desk and can collect them on the day they retire.
Hi Sid
I agree people with MS should push for the high efficacy treatments. Other diseases arnt approached like this, unfortunately MS is and it’s great this blog pushes for that.
But it’s not like a patient can ask for the most effective treatment first line as the neurologists simply cannot provide them is my point. Maybe once damage is done. Which is shocking, out dated and pretty immoral.
My point is can patients change the guideline. I’m not sure
The pharmaceutical companies, and the billions in profits they make each year, surely have some culpability in this debate.
Plus, in the US, if you read most health insurance policies, they “require” the use of lower efficacy DMTs, before they will pay for the higher efficacy drugs, which ultimately costs the drug companies, and system as a whole, more money in the long run. One has to assume this is not by chance, but rather by design. So while we suffer, these assholes just continue to make money of our pain and suffering. Not to mention all the side effects and secondary autoimmunity. Dam shame!!
And to answer Prof. G question…..yes, I want to know everything. Knowledge is power.
I think you have brought up an interesting point in the treatment of MS. The patient is expected to understand and decide what DMT they should be on. I’m not saying that patients should not be educated in their disease but this seems to be beyond most patients scope of understanding especially if they are not from a science background. What other disease puts the burden of treatment options on the patient? I am dumbfounded that patients have to push their drs. to prescribe them the most effective treatments. This is backwards thinking.
This doesn’t say anything about neuroplasticity.
Due to neuroplasticity and a lot of real hard work I got some body functions back.
Can neuroplasticity do something for the issue adressed in this topic?
“Can neuroplasticity do something for the issue adressed in this topic?”
Well this is how people recover from relapses. But once the extra brain reserve is gone
it doesn’t work well. They use this to get stroke recovery too,,but stroke is one time event…
MS is like having mini-stroke every day of your life.
I prefer to know all the details, after all I’m living with it. I have found that my functionality & fatigue are a pretty good barometer of what a hot mess I am over the years. Might as well face the enemy head on & figure out the workarounds
I prefer to know the facts.
Of course we should know.
Would you not tell a cancer patient if their disease is progressing, even if it can’t be treated.
If I knew I had atrophy despite no symptoms and NEDA I’d be looking to switch treatments.
If I knew I had atrophy despite the best available treatment I’d have reason to be more vocal with policymakers asking for changes to guidelines.
If I knew I had atrophy despite no available treatments I’d have reason to be more vocal about research and clinical trials and access to unapproved treatments.
If I knew I had no atrophy in addition to no symptoms and NEDA I’d be more calm and confident making future life choices without fear of imminent disability.
Would you not tell a cancer patient their disease has spread, even if you can’t treat it?
MS is a bad disease to get, even today. Not sure why doctors continue to sugar coat that to patients, and then they’re frustrated when patients “choose” lower efficacy options. You can’t ask patients for input without all the facts.
Should we tell MS patients if their very bad disease is getting worse? Why are we still even asking this question in neurology?
We push for “high efficacy treatment” and after many, many years we get reforumalted/repurposed drugs that provide merely “modest benefit”, which now leave us susceptible to virus generally, and poor (if any) responses to vaccines. shredded, and screwed again. guess my glasses are tinted very dark indeed.
Telling us our brains are shredding I feel is useful. Useful in the sense it scares the crap out of me… enough to have persisted with my neurologist in trying to get Cladribine and… she has just given me the green light. I wouldn’t normally fit the prerequisites for this drug but I wrote a long email with my case and asked for their support. I have clinical worsening but no mri evidence of new activity which was the obstacle for me. My case was discussed recently at the weekly Neuro team meeting and they agreed to let me have it. It’s a great birthday present!
Please don’t give up fighting for what you believe you need! It took me several months but I got there.
Yes please, i’d just like to know either way. I dont like to be coddled.
Asking this question to pwMS on TheMS Blog, you are likely to receive 1 sided answer. I know many well-educated individuals would rather rely on their neuros for a decision of DMT, and forget about the disease while they can. And it really should be this way, if the field of MS fully understood their DMTs.
Patient evolvement is really a risk-sharing thing so neuros are less responsible for riskier decisions. I wish the day when neuros don’t have to ask their patients to share risk to make better decisions come sooner.
Hats off to anyone who manages to ignore their ms, you’d have to be pretty determined to achieve that.
I have considered a private scan because I would very much like to know what state my brain is in but then what? Take it to a neurologist so I can be cured?
If you have SPMS there is absolutely zilch point ….I don’t even bother to see a consultant as some people with SPMS seem to want to do annually. Complete waste of their time and my time .
There were no medications available when I was diagnosed in 1965 other than 3 weeks of ACTH gel….which seemed to work for me and I had no episodes or any symptoms for nearly 50 years . I now apparently have SPMS .
However if you are being newly diagnosed or on DMT s then that is a completely different discussion.