Case study: is it too late to treat my MS?
I haven't ever been on DMTs, does it make sense to go on them now?
Case study
I recently discovered your newsletter MS Selfie and it has drastically changed how I think about my MS diagnosis and journey. One passage hit me particularly hard.
“In almost every MS clinic I do I see the difference between pwMS who have either had a delay in getting a diagnosis, or a delay in getting access to effective therapy, compared to those pwMS with early access to optimal therapies with no evident inflammatory disease activity (NEIDA). A large number of the latter pwMS are leading near-normal lives, whereas the former have to live with the consequences of end-organ damage. Bladder, bowel and sexual dysfunction, cognitive problems, anxiety, depression, fatigue, and all the rest that goes with a failing nervous system. I am stressing the hidden problems because they are invisible to others but cause so many problems for individuals with MS.”
I was diagnosed when I was 22 (1996) with relapsing-remitting MS. My first symptoms were L'Hermitte's sign and optic neuritis. On MRI I had two lesions on my brain and one on my spinal cord. I was never prescribed disease-modifying therapies (DMTs) and usually had one major flareup (involving significant fatigue, feeling of heaviness in my arms and legs, some numbness in my feet) per year when I would spend 6 weeks resting and getting back to baseline.
I completed my University studies and worked as a researcher. I also had three children. Throughout that time, I never had any motor symptoms or loss of function, so my experience has been invisible to others. I've struggled with depression, anxiety, fatigue and what I now know to be brain fog (over the years I, and others, explained these as being overwhelmed and exhausted by my lifestyle, first as a student, then as a mother with young, challenging children). I stopped working outside the home around 2014 to work at home as a mother, as I couldn't do both effectively.
In 2012 (between my second and third kids), I realized my fatigue (generally and in my legs) was increasing and I was having to make adjustments in my everyday life as I couldn't walk very far anymore without getting too tired. With the guidance of a naturopath (and less interest from my neurologist), I changed my diet and ate a very clean anti-inflammatory diet for 2 years, and in a less strict, but similar, way since. This diet made me feel much better from a depression and fatigue perspective and I didn't have any major attacks for 8 years but have had smaller flare-ups where I would feel very tired and have heavy arms and legs for 3-7 days that would go away with rest.
Coming out of a very stressful 4 year period I've realized that my anxiety has been steadily increasing and my brain fog has worsened: I experience difficulty focusing, losing track of what I'm doing constantly, losing things, uncontrollable rumination, difficulty consolidating knowledge, etc. I decided to do some cognitive testing in the fall of 2021 which found very high scores on all measures except for processing speed. The psychiatrist I saw. who specializes in doing these tests for pwMS, said he had never seen someone with MS score so highly, but that the deficits in my processing speed can definitely explain the impacts I'm having on my working memory and executive functioning. I'm also noticing intermittent mild bladder symptoms (urgency, some leaking) and mild bowel issues. I have no sexual dysfunction. Finally, I've had more significant attacks last January and now I am taking longer to resolve. I had a recent MRI in August 2021, with no further activity noted and brain volume consistent with my age.
I am also experiencing some perimenopausal symptoms (mood lability pre-menstrually), so it's possible that some of these symptoms I'm attributing to MS (anxiety, depression, brain fog, etc) could be exacerbated by hormonal imbalances.
When I read your description of how you see patients at your clinic who haven't been put on DMTs, it sounded very familiar: the constellation of mild and invisible symptoms that, while they don't severely impact my functioning, make me feel like everything is a struggle and that I'm deteriorating slowly.
My question is this: if I haven't ever been on DMTs, does it make sense to go on them now? I brought some of your thoughts to my neurologist who said that we've learned more about how to treat people with MS and obviously I was not treated early with DMTs 25 years ago. She said that we don't have data to show us what to do for someone like me - reported worsening of symptoms with no visible activity on MRI and no reduction of scores on in-office testing (usual balance, power, coordination tests I've done for 25 years). She said that she "can't look me in the eye and tell me it's going to help" and that I have to consider the side effects/burden of being on the DMTs. She also said that they recommend people go off the DMTs at age 60 to avoid problems with reduced immunity, so, I have 13 years. She will put me on them if I want, but I'm having trouble making the decision about what to do. Do you ever see patients like me that you've put on DMTs this late in a case of mild RRMS that is worsening in a diffuse way? Would you put me on DMTs now? And, should I try to find another neurologist who has a more holistic/nuanced approach.
Prof G’s opinion
I was diagnosed when I was 22 (1996) with relapsing-remitting MS.
In 1996 interferon-beta-1b (Betaseron) was only available in the US for the treatment of MS. So if you live outside of the US you would not have been offered treatment or possibly participation in a clinical trial.
My first symptoms were L'Hermitte's sign and optic neuritis. On MRI I had two lesions on my brain and one on my spinal cord. I was never prescribed disease-modifying therapies (DMTs) and usually had one major flareup (involving significant fatigue, feeling of heaviness in my arms and legs, some numbness in my feet) per year when I would spend 6 weeks resting and getting back to baseline.
L'Hermitte's sign is indicative of spinal cord involvement and would be considered a poor prognostic sign. With a history of regular relapses/flare-ups, most neurologists would have at least offered you a DMT. Back in the early naughties, the aim was to reduce the frequency and severity of relapses.
I completed my University studies and worked as a researcher. I also had three children. Throughout that time, I never had any motor symptoms or loss of function, so my experience has been invisible to others. I've struggled with depression, anxiety, fatigue and what I now know to be brain fog (over the years I, and others, explained these as being overwhelmed and exhausted by my lifestyle, first as a student, then as a mother with young, challenging children). I stopped working outside the home around 2014 to work at home as a mother, as I couldn't do both effectively.
You have a lot of hidden symptoms suggestive of sickness behaviour, i.e. the response of the body to inflammation. I suspect that despite not having overt motor symptoms or loss of function your MS was active. Having a University degree, working and having a family provide you with cognitive reserve and social resilience, which are associated with better MS outcomes. Not everyone with MS has these advantages.
In 2012 (between my second and third kids), I realized my fatigue (generally and in my legs) was increasing and I was having to make adjustments in my everyday life as I couldn't walk very far anymore without getting too tired. With the guidance of a naturopath (and less interest from my neurologist), I changed my diet and ate a very clean anti-inflammatory diet for 2 years, and in a less strict, but similar, way since. This diet made me feel much better from a depression and fatigue perspective and I didn't have any major attacks for 8 years but have had smaller flare-ups where I would feel very tired and have heavy arms and legs for 3-7 days that would go away with rest.
Again the persistent fatigue could have indicated that you had ongoing inflammatory disease activity and would possibly have been eligible for a DMT. Your observation that diet helped control your disease is interesting. There are observational studies supporting your own experience with diet and there are many theoretical reasons why diet may help suppress inflammation and help. However, I am not sure the evidence supporting one diet over another is robust enough to prescribe one specific diet for pwMS. I cover the issue of MS and diet in an earlier Newsletter; ‘Which is the best MS diet?’ (25-Aug-2021).
Coming out of a very stressful 4 year period I've realized that my anxiety has been steadily increasing and my brain fog has worsened: I experience difficulty focusing, losing track of what I'm doing constantly, losing things, uncontrollable rumination, difficulty consolidating knowledge, etc. I decided to do some cognitive testing in the fall of 2021 which found very high scores on all measures except for processing speed. The psychiatrist I saw. who specializes in doing these tests for pwMS, said he had never seen someone with MS score so highly, but that the deficits in my processing speed can definitely explain the impacts I'm having on my working memory and executive functioning.
I would be interested to know how these cognitive scores compared to your premorbid function. PwMS who have a large amount of cognitive reserve manage to keep their cognitive functioning in the normal range, which for them is often much lower than what they started out with. Again reserve capacity is what acts as a buffer from overt worsening. Yes, you are correct deficits in processing speed are typical MS-related cognitive problems.
I'm also noticing intermittent mild bladder symptoms (urgency, some leaking) and mild bowel issues. I have no sexual dysfunction.
These symptoms are telling me that you are losing reserve; the bladder is one of the first pathways to report out based on the length and extent of the pathway that controls bladder function. I assume the leaking is due to urgency and not stress incontinence. If it is stress incontinence it may be related to pelvic floor issues, which are a common problem in women who have had children. If in doubt you may need to have an examination and possibly urodynamic studies done. Please don’t accept being incontinent there are treatments for all types of incontinence.
Finally, I've had more significant attacks last January and now I am taking longer to resolve. I had a recent MRI in August 2021, with no further activity noted and brain volume consistent with my age.
If you are having relapses your MS is active regardless of what the MRI shows. I have discussed this in an earlier Newsletter; ‘Am I having a relapse?’ (5-Jan-2022). If you were my patient I would be doing a detailed neurological examination to look for worsening and if in doubt I would offer you a lumbar puncture and spinal fluid analysis for neurofilament levels.
I am also experiencing some perimenopausal symptoms (mood lability pre-menstrually), so it's possible that some of these symptoms I'm attributing to MS (anxiety, depression, brain fog, etc) could be exacerbated by hormonal imbalances.
Yes and no. It sounds as if you are having regular periods, which means you still have functioning ovaries. If your periods are irregular you can ask your family doctor for a trial of HRT. I have discussed HRT and its potential as a DMT in a previous Newsletter; ‘Is it MS or is it the menopause?’ (5-Aug-2021).
When I read your description of how you see patients at your clinic who haven't been put on DMTs, it sounded very familiar: the constellation of mild and invisible symptoms that, while they don't severely impact my functioning, make me feel like everything is a struggle and that I'm deteriorating slowly.
Yes, I agree with your interpretation. I suspect you have both active MS with relapses and gradual worsening due to smouldering MS. I assume you have read my numerous Newsletters on ‘do you have smouldering MS’ and ‘why you are getting worse’?
My question is this: if I haven't ever been on DMTs, does it make sense to go on them now? I brought some of your thoughts to my neurologist who said that we've learned more about how to treat people with MS and obviously I was not treated early with DMTs 25 years ago. She said that we don't have data to show us what to do for someone like me - reported worsening of symptoms with no visible activity on MRI and no reduction of scores on in-office testing (usual balance, power, coordination tests I've done for 25 years). She said that she "can't look me in the eye and tell me it's going to help" and that I have to consider the side effects/burden of being on the DMTs. She also said that they recommend people go off the DMTs at age 60 to avoid problems with reduced immunity, so, I have 13 years. She will put me on them if I want, but I'm having trouble making the decision about what to do. Do you ever see patients like me that you've put on DMTs this late in a case of mild RRMS that is worsening in a diffuse way? Would you put me on DMTs now? And, should I try to find another neurologist who has a more holistic/nuanced.
The question is if you have active MS we would at least offer you a DMT and as you seem to be getting worse we would offer you the option of volunteering to participate in a trial. You would potentially be a good candidate for our SIZOMUS trial targeting smouldering MS in the brain and spinal cord. Please note the terms offer and volunteer; it would be your choice.
We are of the opinion that it is never too late to treat and modify the course of MS and this even extends to people who are in wheelchairs. This is why we are doing the #OHAND and #CHARIOTMS studies to preserve upper limb function in people with more advanced MS. From your description above you seem to have a lot of neurological function to preserve.
It sounds as if you understand the holistic management of MS and so there is a lot outside of just treating MS that needs to be taken into account when managing MS. Diet, exercise, sleep, infections, comorbidities, social determinants, etc. All these issues need to be taken into account and addressed.
I hope this answers your questions and helps other people understand what the issues are in individuals with quite complex problems. As with all case studies without seeing and examining the patient and reviewing the MRI studies and ordering additional investigations the advice is only really generic and not personalised.
Subscriptions and donations
I am using the paid subscriptions to administer the MS-Selfie Newsletter and associated MS-Selfie microsite that is currently in development. If you are an active paying subscriber thank you, your contribution is much appreciated. At the request of several readers, I have now added the option of making a one-off donation as well. Funds from subscriptions and donations are being used to pay a professional medical writer to curate, rewrite and transfer the contents of the Newsletter onto a companion MS-Selfie microsite, which is being designed and maintained by a freelance web designer.
Thank you.
General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust. The advice is intended as general advice and should not be interpreted as being personal clinical advice. If you have problems please tell your own healthcare professional who will be able to help you.
Email:
I was really interested to read your most recent case study, particularly with reference to perimenopausal symptoms. What drew my attention in your response was about having irregular periods and that being a definition of whether it’s possible to have HRT – as per the NICE guidelines section 1.2.1 that defines perimenopause/menopause diagnosis. https://www.nice.org.uk/guidance/ng23/chapter/Recommendations#diagnosis-of-perimenopause-and-menopause
From reading around the topic is about changes in periods that may not be just regularity and can be changed in heaviness/lightness, which can be indicative of changes in hormonal levels due to peri/menopause. Also, taking birth control can mask period regularity (I wasn’t sure if the lady was taking hormonal birth control or not) so changes in how heavy/light a period is can be an early sign of hormonal changes.
I found a podcast on recognizing perimenopause in people with existing health conditions and given the overlap in symptoms with MS I wanted to share it with you in case you found it of interest too.
https://www.nhmenopausesociety.org/resources/podcast-episode-6-recognising-the-perimenopause-and-menopause-in-patients-with-existing-health-conditions-with-dr-sarah-ball/
From a personal perspective, being on relatively low-dose HRT has been transformative for me over the last 9 months – in terms of cognitive function, anxiety, sleep etc – all of which were labile in line with the menstrual cycle but have since settled hugely. I’m obviously fortunate to not have MS and have a decent amount of cognitive reserve, but it’s been life-changing to have more settled hormones, improved QoL and hopefully have long-term health benefits too.
I hate to sound evangelical on this, but given perimenopause can start in the mid-30s (menopause range is 40-58, perimenopause symptoms start 4-8 years before menopause) it would be incredibly interesting to know the additive benefit of HRT to DMTs for women with MS (esp on QoL which we know most DMTs struggle to show a significant benefit) and also if asking women about their periods and any menstrual-cycle issues should be a routine part of MS consultations and be on a checklist of some sort.
Twitter DM:
Good afternoon! I’ve just read your recent selfie. They are fantastic and your time and effort spent education and supporting the MS community is amazing. I know that personally I’ve hugely appreciated your advice. But as someone who has been a GP for 18 years specialising in Women’s health I have to take issue with your comment that irregular periods are required for a woman to be in the peri menopause. This is absolutely incorrect and many women will continue to have regular cycles despite being symptomatically low in oestrogen. Blood levels of hormones or infrequent periods are not required to start HRT- just typical symptoms and being the right kind of age (over 40) so she ticks all those boxes and sounds highly appropriate for HRT trial to me. Would you consider letting her know? I honestly think regardless of decisions about her MS she would benefit from HRT for many of the symptoms she mentions.