I am campaigning to get MS redefined as a biological disease and to get the MS community to move away from the current clinico-radiological definition of MS. Do you agree with me on this?
I can’t tell you how happy I am to read this. The gaslighting that many of us must endure when trying to explain symptoms independent of MRI evidence is not acceptable. From my first relapse on I noticed underlying progression that was dismissed as my MRIs were stable. A year on Copaxone with worsening symptoms and stable MRIs I had a severe spinal relapse, it left only a small lesion but much disability. Rather than getting better I felt I was continuing to decline on Gilenya for another 18 months, including one episode where my leg stopped working with no MRI evidence - pain was worsening also and two neuro physios I had to pay to see privately to try and help myself stay strong (public system under resourced) said my spasticity was worsening and an increase in right side limb weakness as they were working regularly with me over period of 18months.
My wonderful consultant wanted to change me to Ocrevus but as I hadn’t technically failed Gilenya it was messy. I had to be admitted to hospital for review from the whole team. Unfortunately my consultant was away when a bed became available and while in hospital I was under the care of a different consultant and I received nothing but constant gaslighting to the point I was seen by the psyche team who were asking me my opinion on psychosomatic disorder within 60 seconds of meeting me. I queried how they could be so sure my symptoms were of a psychological nature when I had a diagnosed neurological disease that could also account for them.
I am passionate about role of mind-body medicine and minding my mental health - even now I still attend regular sessions with a psychotherapist to help me live with this disease - so it was so difficult to have my symptoms constantly dismissed during this period (my therapist even said the way I was treated by the psych team in hosp and some of the questions asked were totally unethical- she was horrified). It has left me with a huge mistrust of the system as this is not the only time I have experienced gaslighting. One doctor when I moved countries wouldn’t look at any of my old MRIs only the one she’d just done and told me I didn’t have MS at all and it was all in my head.
I am lucky that my main consultant in Ireland is kind and listens to his patients even if he is operating in a system that doesn’t, and I have also found a wonderful consultant here in Germany too (I live between the two countries). I have had to learn to trust my own body and at every stage have fought for what I know my body needs. It hasn’t been easy though and when I chat to others with MS to find we have all experienced gaslighting at some stage (even more so in those of us who are female) it makes me angry that in 2021 many doctors still refuse to listen to their patients’ lived experiences of this disease. Apologies again for a long reply but this topic is something I am very passionate about and I’m one of the lucky ones who has a consultant who acknowledges smouldering MS and listens - many sadly do not.
Absolutely - when I had severe ON in 2003 I was referred to MS clinic, MRI (of only brain, "forgot" to order contrast, if they had done cspine as well they would have found a lesion) did not confirm MS, pitched out and referred to a general neuro for follow-up as. My new near retirement General neuro who also did part time hours at the MS clinic "well dear I was diagnosing MS before the age of MRI, and you have MS, it just hasn't shown up on MRI yet". Another year wait list for MRI got scan of brain and spine and voila. In my case it took a long time for typical lesions to show up in the brain. I still have a very low lesion load but a 4 on the EDSS. Then we had to fight escalating/wait and see model of treatment that was prevalent at that time here in Canada. pretty sure current DMT are treating the effect, not the cause of MS.
Completely agree that MS is a biological disease. I'm slowly losing mobility without any obvious signs on MRI. My neurologist is not interested so please keep campaigning and let us know what we can do to keep the campaign front and centre.
Prof G, can you comment on how much of an add-on effect you think lifestyle changes (mainly exercise) have on brain atrophy? Do you think an intensive exercise program on top of a high-efficacy DMT is enough to normalize brain atrophy?
Depends on what you define as highly effective. Alemtuzumab is the only licensed DMT that 'normalises' brain atrophy rates. AHSCT does so as well, but come at a cost of quite a lot of early brain volume loss from neurotoxicity. The other high efficacy DMTs reduce the rate of BVL, but not into the normal range. Please note alemtuzumab was tested in a relatively early MS population, which may explain why it is so effective on BVL. I don't exercise and lifestyle factors on top of these is sufficient because our current treatments don't seem to target the processes driving smouldering MS.
:( Disappointing to hear but thanks for taking the time to respond. I started alemtuzumab recently (about a year after being diagnosed), and my neurologist also agreed to let me take teriflunomide as a maintenance therapy afterwards. Maybe I should bug him about simvastatin next.
Thanks for this excellent podcast and article. It absolutely makes sense. Last year I developed the MS hug for the first time, but I was told it was not a relapse because my scans were stable. I felt it was likely further demyelination in my spinal cord where I already have a lesion at T4. I also seem to have deteriorated over the last 12 months even though my MR scans show no new lesions. Hoping switching onto Ocrelizumab is going to help.
I completely agree. MRI scans are completely inaccurate with MS. The reading of them is also very subjective, different radiographers have reported differently with my scans and the appearance varies when different strength scanners are used. Neurologists don’t always do MRI scans on the spine, even when it is indicated by the symptoms of a relapse. It was this that meant that I couldn’t get HSCT on the NHS and had to pay privately to have it done abroad. I had RRMS and have now been in remission nearly three years.
Same here. No evidence of new lessions on my MRIs for the past 7 years but my MS is slowly advancing year by year. Currently I'm trying to develop and accept my role as a vegetable, I kinda lost hope.
I'm sure I have a simplistic view of things but if one were to be diagnosed with Systemic lupus erythematosus It is possible to suffer with quite serious Neurological symptoms without there being any lesions visible on MRI but it is a recognised symptom of systemic inflammation and surely if Multiple sclerosis is fundamentally an inflammatory condition then the lack of MRI lesions wouldn't necessarily mean a person wasn't suffering from a relapse I personally have a dual diagnosis of Antiphospholipid syndrome and Multiple sclerosis so have one foot in Rheumatology and the other in Neurology and it is difficult sometimes to know where one begins and the other ends as there is a lot of overlap
The lesions in lupus and APS are typically vascular and have associated MRI findings. Difficult to be labelled as having MS if you have APS. MS is a diagnosis of exclusion.
Similarly to you Jane, I have a diagnosis of both SLE and MS. I do not have APS though. The diagnosis of MS took over 18 months from the discovery of cervical cord and brain lesions (and subsequent new lesions on updated MRI scans) as well as a lumbar puncture. My first Neurologist felt my lesions must be related to my Lupus (which I already had previously been diagnosed with) however, my Rheumatologist was unconvinced and did not feel my presentation fitted "CNS Lupus". After consulting his fellow neurological colleagues and the return of oligoclonal bands from my csf fluid, as well as the fact that my brother also has MS, as does our first cousin, I was referred to a MS Specialist who diagnosed me with MS on our first consultation. I actually have six autoimmune diseases. Fortunately, my Lupus has not attacked my CNS and by and large remains relatively stable.
I do agree with you Professor Giovannoni that the description of smouldering MS better describes the condition in general.
I have been diagnosed with Multiple sclerosis after positive lumber puncture and MRI with lesions from C2 to C6 and also Antiphospholipid syndrome after suffering multiple and life threatening Thrombosis by Prof D'Cruz and team at ST Thomas's hospital
If they are failing ocrelizumab, and have failed alemtuzumab in the past, AHSCT is one option. If they don't want the risks, e.g. infertility, natalizumab or cladribine would be options as well.
Is there any studies on cumulative side effects on pwMS had to change their DMTs? Would you prescribe Cladribine to this patient that Alemtuzumab failed her and Ocrelizumab maybe failing her as well?
Yes, cladribine would be an option. We have loop-hole in the UK guidelines under COVID-19 to prescribe cladribine. Prior to COVID-19 we need to have MRI activity as well.
My understanding of how MRI works is that, certainly with the standard resolution scans, you're really only going to see something that's very big. It's designed to show tumours and haematomas / massive strokes. Regular size lesions are on the very edge of what it can detect and most of us will be having tiny lesions.
Secondly an MRI is a snapshot, almost by definition. So if you're having an annual MRI all that shows is what's happened in the last two or three weeks. If we took the same approach to weather forecasting we could presume it the United Kingdom experiences sub-arctic conditions all year round.
The problem with ocrelizumab, other than that it is an absolute sledgehammer, is it lulls MS-ologists into a false sense of security. Far easier to follow convention and say that MS is an inflammatory condition driven by lesions leading to relapses. Then if we cure the lesions we've cured MS! Everything else is just patients being hypochondriacs.
A lot of neurologists take issue with professor Giovannoni, believing he is making their lives more difficult, rather than empowering us with information and trying to make our lives easier (and actually treat the condition and the underlying reasons for the condition). For this specifically I want to thank you Gavin. As a patient I am supposed to be a "good patient" and take my ocrelizumab without questioning. My neurologist doesn't want me making their life more difficult by asking awkward questions like, "if this stuff is so good why am I getting worse?" etc. They need to realize that their job is to treat their patients, not to treat by numbers.
Thank you for treating us as patients and not numbers. And thank you for your work on trying to get this smouldering concept recognised. That is the only way proper therapy and treatment of the whole disease will emerge.
Absolutely agree! Over the years on Tysabri I have had several episodes lasting many weeks which I believe to be relapses - mainly spinal cord. MRI doesn’t pick them up! I definitely feel I’m worse. I’ve always believed MS smoulders away under the surface.
Yes, via a MS-Selfie case study. I anonymise the details and give an opinion in writing so everyone learns from the case. I only do NHS work and don't see patients privately.
May be repeat the alemtuzumab. When you have breakthrough activity on an IRT it doesn't necessarily mean you are failing that treatment. Another option is AHSCT.
7 years ago I started with symptoms of severe headaches, started losing color and then vision in right eye, balance issues, vertigo. Was in OU medical hospital for 8 days spinal taps mri, CT scan showed nothing. Took 4 months get get eye sight back. I did not get diagnosed till Feb 2020. Not on MS meds my neurologist does not want my immune system compromised. She said because I am 65 years old. She usually takes her patients off meds at 65. I am doing good with diet and exercise. I believe a new protocol needs to be developed for MS dignosis.
I agree with you. Also don't agree with not treating active MS because someone is 65 or older. There are MS DMTs that are not long-term immunosuppressive therapies that can be used safely in older patients, e.g. cladribine, interferon-beta, glatiramer acetate and teriflunomide.
100000% ignored - I am lumped in the CIS group mentioned that experiences PIRA with optic neuritis and one juxtacortical lesion on Tysabri for a year with progressive worsening of symptoms and no MRI changes so zero entertainment of switching DMT or steroid treatment even though I am mounting disability progression.
I can’t tell you how happy I am to read this. The gaslighting that many of us must endure when trying to explain symptoms independent of MRI evidence is not acceptable. From my first relapse on I noticed underlying progression that was dismissed as my MRIs were stable. A year on Copaxone with worsening symptoms and stable MRIs I had a severe spinal relapse, it left only a small lesion but much disability. Rather than getting better I felt I was continuing to decline on Gilenya for another 18 months, including one episode where my leg stopped working with no MRI evidence - pain was worsening also and two neuro physios I had to pay to see privately to try and help myself stay strong (public system under resourced) said my spasticity was worsening and an increase in right side limb weakness as they were working regularly with me over period of 18months.
My wonderful consultant wanted to change me to Ocrevus but as I hadn’t technically failed Gilenya it was messy. I had to be admitted to hospital for review from the whole team. Unfortunately my consultant was away when a bed became available and while in hospital I was under the care of a different consultant and I received nothing but constant gaslighting to the point I was seen by the psyche team who were asking me my opinion on psychosomatic disorder within 60 seconds of meeting me. I queried how they could be so sure my symptoms were of a psychological nature when I had a diagnosed neurological disease that could also account for them.
I am passionate about role of mind-body medicine and minding my mental health - even now I still attend regular sessions with a psychotherapist to help me live with this disease - so it was so difficult to have my symptoms constantly dismissed during this period (my therapist even said the way I was treated by the psych team in hosp and some of the questions asked were totally unethical- she was horrified). It has left me with a huge mistrust of the system as this is not the only time I have experienced gaslighting. One doctor when I moved countries wouldn’t look at any of my old MRIs only the one she’d just done and told me I didn’t have MS at all and it was all in my head.
I am lucky that my main consultant in Ireland is kind and listens to his patients even if he is operating in a system that doesn’t, and I have also found a wonderful consultant here in Germany too (I live between the two countries). I have had to learn to trust my own body and at every stage have fought for what I know my body needs. It hasn’t been easy though and when I chat to others with MS to find we have all experienced gaslighting at some stage (even more so in those of us who are female) it makes me angry that in 2021 many doctors still refuse to listen to their patients’ lived experiences of this disease. Apologies again for a long reply but this topic is something I am very passionate about and I’m one of the lucky ones who has a consultant who acknowledges smouldering MS and listens - many sadly do not.
Absolutely - when I had severe ON in 2003 I was referred to MS clinic, MRI (of only brain, "forgot" to order contrast, if they had done cspine as well they would have found a lesion) did not confirm MS, pitched out and referred to a general neuro for follow-up as. My new near retirement General neuro who also did part time hours at the MS clinic "well dear I was diagnosing MS before the age of MRI, and you have MS, it just hasn't shown up on MRI yet". Another year wait list for MRI got scan of brain and spine and voila. In my case it took a long time for typical lesions to show up in the brain. I still have a very low lesion load but a 4 on the EDSS. Then we had to fight escalating/wait and see model of treatment that was prevalent at that time here in Canada. pretty sure current DMT are treating the effect, not the cause of MS.
~Karen
Completely agree that MS is a biological disease. I'm slowly losing mobility without any obvious signs on MRI. My neurologist is not interested so please keep campaigning and let us know what we can do to keep the campaign front and centre.
Prof G, can you comment on how much of an add-on effect you think lifestyle changes (mainly exercise) have on brain atrophy? Do you think an intensive exercise program on top of a high-efficacy DMT is enough to normalize brain atrophy?
Depends on what you define as highly effective. Alemtuzumab is the only licensed DMT that 'normalises' brain atrophy rates. AHSCT does so as well, but come at a cost of quite a lot of early brain volume loss from neurotoxicity. The other high efficacy DMTs reduce the rate of BVL, but not into the normal range. Please note alemtuzumab was tested in a relatively early MS population, which may explain why it is so effective on BVL. I don't exercise and lifestyle factors on top of these is sufficient because our current treatments don't seem to target the processes driving smouldering MS.
:( Disappointing to hear but thanks for taking the time to respond. I started alemtuzumab recently (about a year after being diagnosed), and my neurologist also agreed to let me take teriflunomide as a maintenance therapy afterwards. Maybe I should bug him about simvastatin next.
I would wait for the results of the MS-STAT-2 trial. Simvastatin at high doses is not necessarily free of side effects.
Thanks for this excellent podcast and article. It absolutely makes sense. Last year I developed the MS hug for the first time, but I was told it was not a relapse because my scans were stable. I felt it was likely further demyelination in my spinal cord where I already have a lesion at T4. I also seem to have deteriorated over the last 12 months even though my MR scans show no new lesions. Hoping switching onto Ocrelizumab is going to help.
I completely agree. MRI scans are completely inaccurate with MS. The reading of them is also very subjective, different radiographers have reported differently with my scans and the appearance varies when different strength scanners are used. Neurologists don’t always do MRI scans on the spine, even when it is indicated by the symptoms of a relapse. It was this that meant that I couldn’t get HSCT on the NHS and had to pay privately to have it done abroad. I had RRMS and have now been in remission nearly three years.
Same here. No evidence of new lessions on my MRIs for the past 7 years but my MS is slowly advancing year by year. Currently I'm trying to develop and accept my role as a vegetable, I kinda lost hope.
I'm sure I have a simplistic view of things but if one were to be diagnosed with Systemic lupus erythematosus It is possible to suffer with quite serious Neurological symptoms without there being any lesions visible on MRI but it is a recognised symptom of systemic inflammation and surely if Multiple sclerosis is fundamentally an inflammatory condition then the lack of MRI lesions wouldn't necessarily mean a person wasn't suffering from a relapse I personally have a dual diagnosis of Antiphospholipid syndrome and Multiple sclerosis so have one foot in Rheumatology and the other in Neurology and it is difficult sometimes to know where one begins and the other ends as there is a lot of overlap
The lesions in lupus and APS are typically vascular and have associated MRI findings. Difficult to be labelled as having MS if you have APS. MS is a diagnosis of exclusion.
Similarly to you Jane, I have a diagnosis of both SLE and MS. I do not have APS though. The diagnosis of MS took over 18 months from the discovery of cervical cord and brain lesions (and subsequent new lesions on updated MRI scans) as well as a lumbar puncture. My first Neurologist felt my lesions must be related to my Lupus (which I already had previously been diagnosed with) however, my Rheumatologist was unconvinced and did not feel my presentation fitted "CNS Lupus". After consulting his fellow neurological colleagues and the return of oligoclonal bands from my csf fluid, as well as the fact that my brother also has MS, as does our first cousin, I was referred to a MS Specialist who diagnosed me with MS on our first consultation. I actually have six autoimmune diseases. Fortunately, my Lupus has not attacked my CNS and by and large remains relatively stable.
I do agree with you Professor Giovannoni that the description of smouldering MS better describes the condition in general.
I have been diagnosed with Multiple sclerosis after positive lumber puncture and MRI with lesions from C2 to C6 and also Antiphospholipid syndrome after suffering multiple and life threatening Thrombosis by Prof D'Cruz and team at ST Thomas's hospital
Glad you are under Prof D'Cruz, he is an excellent specialist in Lupus.
I have met several people online who also have MS and Lupus. I hope you are managing as well as possible. Take good care.
Hi Jen Thank you my care is managed locally but I literally wouldn't have survived without his input
Hi Prof G, thanks for this case study. What would your advice be to this patient, would AHSCT offer the best possible outcome?
If they are failing ocrelizumab, and have failed alemtuzumab in the past, AHSCT is one option. If they don't want the risks, e.g. infertility, natalizumab or cladribine would be options as well.
Is there any studies on cumulative side effects on pwMS had to change their DMTs? Would you prescribe Cladribine to this patient that Alemtuzumab failed her and Ocrelizumab maybe failing her as well?
Yes, cladribine would be an option. We have loop-hole in the UK guidelines under COVID-19 to prescribe cladribine. Prior to COVID-19 we need to have MRI activity as well.
My understanding of how MRI works is that, certainly with the standard resolution scans, you're really only going to see something that's very big. It's designed to show tumours and haematomas / massive strokes. Regular size lesions are on the very edge of what it can detect and most of us will be having tiny lesions.
Secondly an MRI is a snapshot, almost by definition. So if you're having an annual MRI all that shows is what's happened in the last two or three weeks. If we took the same approach to weather forecasting we could presume it the United Kingdom experiences sub-arctic conditions all year round.
The problem with ocrelizumab, other than that it is an absolute sledgehammer, is it lulls MS-ologists into a false sense of security. Far easier to follow convention and say that MS is an inflammatory condition driven by lesions leading to relapses. Then if we cure the lesions we've cured MS! Everything else is just patients being hypochondriacs.
A lot of neurologists take issue with professor Giovannoni, believing he is making their lives more difficult, rather than empowering us with information and trying to make our lives easier (and actually treat the condition and the underlying reasons for the condition). For this specifically I want to thank you Gavin. As a patient I am supposed to be a "good patient" and take my ocrelizumab without questioning. My neurologist doesn't want me making their life more difficult by asking awkward questions like, "if this stuff is so good why am I getting worse?" etc. They need to realize that their job is to treat their patients, not to treat by numbers.
Thank you for treating us as patients and not numbers. And thank you for your work on trying to get this smouldering concept recognised. That is the only way proper therapy and treatment of the whole disease will emerge.
Absolutely agree! Over the years on Tysabri I have had several episodes lasting many weeks which I believe to be relapses - mainly spinal cord. MRI doesn’t pick them up! I definitely feel I’m worse. I’ve always believed MS smoulders away under the surface.
Prof G, is there a way to consult online particular case with you?
Yes, via a MS-Selfie case study. I anonymise the details and give an opinion in writing so everyone learns from the case. I only do NHS work and don't see patients privately.
Prof G - could you pls reinstate my subscription?
There is no need to reinstate it. All content is now free. Being a paid subscriber is now voluntary and altruistic to support MS-Selfie.
Thanks Prof G. Will I still be emailed the MS-Selfie emails? I’ve had an email saying it’s been cancelled
You will still be on the list!
From a patient perspective, what can be done to this patient after she failed Alemtuzumab and Ocrelizumab may not be fully controlling the disease?
May be repeat the alemtuzumab. When you have breakthrough activity on an IRT it doesn't necessarily mean you are failing that treatment. Another option is AHSCT.
7 years ago I started with symptoms of severe headaches, started losing color and then vision in right eye, balance issues, vertigo. Was in OU medical hospital for 8 days spinal taps mri, CT scan showed nothing. Took 4 months get get eye sight back. I did not get diagnosed till Feb 2020. Not on MS meds my neurologist does not want my immune system compromised. She said because I am 65 years old. She usually takes her patients off meds at 65. I am doing good with diet and exercise. I believe a new protocol needs to be developed for MS dignosis.
I agree with you. Also don't agree with not treating active MS because someone is 65 or older. There are MS DMTs that are not long-term immunosuppressive therapies that can be used safely in older patients, e.g. cladribine, interferon-beta, glatiramer acetate and teriflunomide.
100000% ignored - I am lumped in the CIS group mentioned that experiences PIRA with optic neuritis and one juxtacortical lesion on Tysabri for a year with progressive worsening of symptoms and no MRI changes so zero entertainment of switching DMT or steroid treatment even though I am mounting disability progression.