People with MS who have lesions in the posterior fossa have a poorer prognosis. However, there are things that can be done for each of the problems that arise from posterior fossa involvement.
Thank you, and yes, it is very helpful! I was diagnosed 40 years ago in 1981, with RRMS, and have now been in SPMS for several years. My MS is considered inactive, but I have many lesions both on the brain and on the brain stem and spine. I do have gait issues, vertigo occasionally and have experienced most of the symptoms listed at one time or another, as well as others. I refuse to give up, and I stay active, walking, gardening, volunteering with the Master Gardeners and the Humane Society. I am not on any DMT currently, and I see my Neurologist up to 4 times a year for check-ups.
I’ve read this article and it describes my MS to a tee! At time of official diagnosis my MRI showed many lesions on my spine, whole brain and brain stem with one of the most significant appearing as a ‘chunk’ penetrating into my cerebellum! I have experienced almost all of the symptoms listed! I was started on Ocrevus as my first line treatment and it has been amazing for me! I went through an horrendous time for 18 months suffering from up to five seizures a day but after just over two years on this amazing drug things have calmed right down and I live with relatively little disability with my main symptoms being extreme fatigue and cognitive impairment. I actually view myself as a bit of a medical miracle and I do think the amount of exercise I have done over the years and still to this day has help to keep the disability at bay? I still manage to swim 2km a day (most days)-it’s my therapy!
Yes, ocrelizumab and the other anti-CD20 therapies are remarkably effective treatments at suppressing inflammatory disease activity and they do this with a very good short-term safety profile.
I think this painting it a bit too positively given the world in 2021. Pre-Covid I would have agreed (main reason I chose it, literally on the eve before the pandemic) but the vaccination issue really make me question that assessment...
I think it’s all relative and all depends on how badly your MS was/is affecting your life? For me personally my life wasn’t worth living prior to this drug-whilst in hospital I couldn’t stand up, let alone walk, completely deaf in one ear, couldn’t speak, absolute agony, couldn’t see properly and then 18 months of up to five hour long seizures per day with total exhaustion between those seizures! Don’t get me wrong I am scared to death of catching Covid especially knowing I’ve had complete vaccine failure after two doses of AZ but i try to keep myself as safe as possible from the virus and positivity for me is a huge part of my fight of this disease! So for me there was no other option than Ocrevus because my disease is so aggressive so I’m really trying to make the best of a bad situation! I hope you figure out what is the best way to deal with your own personal situation in these difficult times!
I find it refreshing to receive accurate and relatively detailed information. Your selfie newsletter has only been a recent discovery and I’ve poured over its contents. Thank you for being a breath of fresh air/clarity on this confusing journey.
I am one of those people who had difficulty getting diagnosed. Early diagnosis in 2008 was Fibromyalgia although I never felt that was accurate. Treatment was minimal.
I presented at emergency with arm numbness, trigeminal neuralgia and vision problems in 2014. This resulted in an MRI showing one lesion and a Neuro appointment. MS was not mentioned and no follow up given. At minimum I feel this was missed CIS. Between 2014 and 2018 I experienced ongoing bladder issues, Lhermitte’s, Uhtoff’s, TN, fatigue, gait issues and sensory issues in limbs etc.
MS diagnosis happened 01/2019 at the age of 64. In 2018 a new family doctor clued in to the relatively singular sign of Lhermitte’s and ordered an MRI. This showed 17 white matter lesions as well as one on the pons, and cerebellum. A 2021 MRI confirmed lesions in the CS at C3,4,and 5. These were not considered new but visible due to better imaging. My first med was Rebif (Mar. 2019)and later a switch to Tecfidera(Feb. 2020). I am radiology stable but I clinically show intermittent symptoms - milder TN lasting 4-5 weeks, greater fatigue, ataxia, and numbness in new areas such as lower legs and feet. I find Tecfidera close to intolerable with near daily reactions that sometimes escalate to full body flushing and bowel issues. I’ve hung in there for over a year. Recently I was denied a switch to a more efficacious med (fingolimod) due to my age, now 64. I am focussed on a better diet and doing functional PT for exercise. I am not risk adverse but feel I have been set aside due to age and supposedly lower disease burden. Six months ago it was suggested to me that I stop DMT altogether. Let’s wait and see what happens on an MRI scheduled after 6 months. I said no. I would prefer to be actively preventing future events.
I’m clearly on the escalation model, complicated by a late start, and being 66!!!
Perhaps it's time to challenge the drugs decision. I started on fingolimod age 65, am now 71 and have moved to cladribine. I think it depends on the approach of the neurologist. Mine has said that his philosophy is to treat according to patient needs as presented to him. I know I'm fortunate. If you're in England, you have the right to a second opinion/change of team.
I was offered Avonex - once a week injection of the same drug as Rebif but only 30 mcg. I felt awful on Rebif. l was also offered daily Copaxone. Three injection a week version is not available to me due to drug coverage problems. These drugs are lower efficacy and may serve a purpose in treatment. However they don’t seem to follow this mantra - ‘diagnose early, treat early, treat effectively’, especially treat effectively considering that I haven’t been MRI stable that long. Thanks for the advice.
I wasn't dx'd until i was in my 50's. I am now 63. I have been having symptoms since i was in my early 30's. As horrible as it souinds, i often wonder where i would if i had been Dx'd in my 30's and began treatment back then. I am now secondary progressive with active disease and seem to show new lesions every MRI that is done. Last one of Brain in Oct 2020 showed 130 plus 4 on brain stem... My doc does not understand how i am still functioning. I wonder myself some days. Best of luck to you as a fellow late MS er
Wow. You seem to have some resilience for sure. I’m trying to see the missed opportunities as the past and just part of my story, but I do sometimes think the same thoughts. What if….. Right now I’m focussed on getting a better quality of life in whatever way I can. Good luck.
sadly, it seems that even now, in 2022, there is still difficulty getting an accurate Dx. I relate so much to your story. It took some 30 years to receive a proper Dx. I too was told I had fibro, arthritis, neuropathy, etc and that I was just plain depressed. Yes, I am depressed. after 30 years, I got lost on my way to the grocery store that I had been going to at least once a week for the prior 5 years at the time. When my doc heard the story, they sent me for CT. Even with numerous lesions showing on that scan, they refused to send me for MRI. I was Dx'd with anxiety and TIA. I switched providers 2 years later when my Medicare kicked in and finally got that MRI. After additional testing.. evoked potentials, EEG, blood work to rule out things like Lyme, the neurologist told me MS.. I was stunned. I was 57 years old. since then I have recently had a neuro question my Dx! IDK what other disease causes all of these symptoms including the 100+ lesions I have in my brain and on my brain stem and cervical spine but I am now feeling like I am back to square one. It really amazes me that they still have so many issues Dx'ing MS. Especially when things are very obvious like they tend to be with a lot of us. Best of luck to you in your search for a better DMT for you.
Amazing insights for us PwMS, thank you so very much Prof for your time and efforts to break this down into logical bite size chunks for us all to read. (Not the fault of the neurologists) but in a clearly stretched system with most of us having just a 5 min phone chat once a year with our neurologists, information, reassurance and understanding is minimal - your provision is like a huge blanket of care. I can’t thank you enough
Scary stuff but so very helpful. My various neurologists never explained this and only through your posts have I been informed. I have damage in very expensive real estate!
👋Good afternoon Professor G! from 🇦🇺 Yes, knowing how MS can affect the function of different parts of the brain and spinal cord will help understand MS. For some individual’s Knowledge and education is medicine💯
Thank you for taking the time to care for PwMS thoughts…. light + peace 😊🦋🌿🌻
Prof G, What is your thought on non lesional neurodegeneration of the cerebellum in PwMS and how to advocate for ourselves as patients with our neuros who do not recognize PIRA or smoldering MS without new or enhancing lesions even with progressive symptoms and worsening neuro exam?
It is hard to measure cerebellar atrophy, but you can do it indirectly by monitoring the size of the fourth ventricle that sits in front of the cerebellum in the brainstem. This can often be seen to get larger in association with worsening cerebellar function clinically.
The problem is if you are a DMT what do we do about this phenomenon? We don't have data that switching DMTs makes any difference at this stage. For example, if you have smouldering cerebellar atrophy on fingolimod does it slow down if you switch to ocrelizumab, natalizumab, alemtuzumab or have AHSCT? We simply don't have data to support these switches nor do we have data that switching from fingolinod to siponimod makes a difference either.
Thanks for the reply, I know the data is sparse, but from my perspective being on Tysabri and developing the regional atrophy (bad enough to spur concerns for paraneoplastic workup) as well as having progressive weakness, numbness, tremors, vertigo and vision symptoms, would it make sense to at least consider a switch to ocrevus and see what happens from a functional perspective?
Why ocrelizumab and not alemtuzumab or oral cladribine? An IRT may be more appropriate here particularly cladribine that can penetrate the CNS and hopefully deal with the so-called intrathecal B-cells that may be making pathogenic antibodies.
I am classified as CIS currently, optic neuritis, one small juxtacortical lesion, and cerebellum atrophy. CSF negative but taken after start of 5 Tysabri infusions and a relapse necessitating a hospital stay and steroids in which the brain mri then first showed the non lesional regional atrophy and neuro was concerned for paraneoplastic disease. Mavenclad and Lemtrada are not approved for CIS, so given my rapid worsening of symptoms and neuro exam I advocated a switch to at least see if it stops or slows the worsening but was shut down due to no new enhancing lesions.
I worry about early ppms with the continuing progression and atrophy - I am a clinical radiological paradox - and they don’t know what to do with me 🤷🏻♀️
I got every symptom on this list in my first relapse and they (Canada, MS Clinic) STILL took forever to get me (f 34 at the time) on a highly effective DMT (Lemtrada, on my insistence). They forced me to fail through 2 front-line meds first, due to the two-tiered "fail up" system (and/or likely neuro not paying attention enough that things were not good, simply because I hold myself together well when in crisis--which some weirdos seem to take for the opposite, despite being told (by a surgeon) that I have one hell of a pain tolerance/constitution.
EDSS score 3+ on first onset, diagnosed in 1 "convincing" MRI (that I paid privately for in public healthcare to go around the PCP/GPs and ER docs (who wouldn't refer to neuro and) who couldn't get a clue what central vertigo looked like--even *I* knew I probably had MS). An ENT was the only clue-holder apparently (once I could coordinate walk again, I asked for a referral), because at least an ENT has sufficient training to rule out peripheral, and in central, vertigo. He did, less than 5 minutes. Immediately ordered public MRI (learned he'd wrote "MS-Brain" as scan type when copies requested) and urged me to consider also private-pay MRI for faster scan. Thought about it for 3 days then leapt. Best $900 I ever spent.
Baseline MRI 10+ lesions, small one in cerebellum (neuro claimed he couldn't see, I requested copies on CD + written report, so I know it's there) plus C-spine lesions (he also claimed we're barely there, meanwhile radiologists still admit to easily being able to see, if I bring it up first as me already knowing). I always suspected a tiny brain stem lesion due to the symptom severity ( but we have crappy old MRI machines here). Meanwhile, neuro played mostly dumb, despite letting me choose Lem after rapid-failing crappy 1st-line DMTs only later to reveal that is just his horrible bedside manner (let's not worry the emotional females attitude--this female is an aspie with more testicular fortitude than he has and I don't even have a pair lol). Glad I went nuclear w Lemtrada, been 4-5 years without progression *fingers crossed*...
Oops, meant to write, *every symptom but 2 (no hearing loss and no hallucination)*. Granted, it wasn't super-epic (I could walk, within a couple of weeks, once I figured out how to coordinate movement again and "tell my legs" to move (walking was no longer automated, had to cling to walls and practice in front of the mirror to relearn, couldn't remain sitting upright if I closed my eyes). I also preyed to the porcelain god and slept on the bathroom floor for a couple months, going back to the ER again and again for fluids and stronger antiemetics that did nothing, betahistine (did nothing of course), gravol, odansetron, maxeran (lost 10-15lbs). Didn’t yet have a regular GP (just walk-in clinics, because I had just moved, so that's how I ended up in diagnosis limbo and requesting referral to ENT to skirt the lousy GPs and ER docs--it worked!). Brain lesions get a referral to neuro really fast lol.
You note in the preamble that there are "things that can be done for each of the problems" and reference further on "specialised and targeted neurorehabilitation" for specific issues. Could you share some examples so that I might have a better discussion with my neurologist? Thank you.
I so appreciate these posts of yours; it definitely helps me to know more about this confounding disease.
Thank you so much for your excellent help in navigating this disease. I look forward to your newsletter. There are so many things that I have been unaware of and can now ask better questions during my check-ups.
You are not wrong! This post has already helped me understand why my long term symptoms occur (vertigo, unsteadiness). I know I have lesions in my cerebellum. Thanks Prof G! I’m waiting for an appt with my neurologist who I have not seen in a long while. I’ll be posing some questions!
Wondering if you have any experience with Tysabri causing cerebellum atrophy? 4 months into treatment I started having worsening cerebellar symptoms and exam with non lesional atrophy on MRI. It progressed so much and so quickly I stopped the Tysabri. Since stopping the Tysabri 11 weeks ago my cerebellar symptoms are starting to slowly abate. My ocular tremor is less severe, my extremity tremors are getting better, I’m experiencing less disequilibrium and heel to shin and antigravity tremors are improving unless overheated as well. I really attribute this to stopping the Tysabri since my symptoms got so much worse 3-4 infusions in but there is no research to support this with the exception of GCN related cerebellum atrophy and I have always been JCV negative. I am curious about your thoughts and experiences.
This is unlikely to be natalizumab related. Atrophy tends to occur 12, 18 or 24+ months after the event so the damage caused by MS probably predated the star of the natalizumab.
Thank you for your response, I have no cerebellum lesions though… and my cerebellar symptoms seem to be getting better off the Tysabri, would that be possible?
Yes and no. Recovery of function is complex and can take years to happen.
With regard to the cerebellum Stephen Waxman and colleagues described MS cerebellar dysfunction being due to abnormal ion channels and the observation that this could be reversible. Over the years I have seen reversible cerebellar ataxia and eye movement problems that I think could be due to this acquired channelopathy.
Shields SD, Cheng X, Gasser A, Saab CY, Tyrrell L, Eastman EM, Iwata M, Zwinger PJ, Black JA, Dib-Hajj SD, Waxman SG. A channelopathy contributes to cerebellar dysfunction in a model of multiple sclerosis. Ann Neurol. 2012 Feb;71(2):186-94.
Just re-reading a number of your newsletters before seeing my neurologist this week and so getting some questions ready! I'm concerned about getting the full picture from my MRI scans as over the past few years after regular MRI scans ( 2x yearly as on Tysabri) All I've heard about the results of the MRI scans are that they are stable ( good news) but I'm now wanting to know how many lesions are present and where they are located.
As you point out that posterior fossa lesions are of some concern I am interested to hear if I have any there as recently I've experienced vertigo ( sudden onset and severe for a few days and then much reduced, more like dizziness) which has never happened before. Also have long term hearing loss (high frequencies in particular but also find it difficult to distinguish clearly what people are saying even though I can hear them speak) and some mild tinnitus. Also in the same time frame there has been an unusual UTI (streptococcus haemolyticus) which was rather stubborn followed soon after by an ear infection. Infections were treated by GP but MS nurses informed.
I'm 62 and have been on Tysabri for nearly 4 years (JCV negative) with no evidence of new relapses as yet.
You need to make sure your attacks of vertigo are not something else; they sound more like Ménière's disease rather than MS. The clue is associated tinnitus and hearing loss.
I’ve just gone back to look at my diagnosis letter in 2014 to see if it mentions where my initial lesions were and it says ‘left superior and middle cerebellar punduncles’ so I’m assuming this is the area featured in your newsletter. I feel even more grateful for having Lem first line now as had no idea of my prognosis although was hit full on with the cognitive problems initially and still have residual language and memory problems - now I know why! Thank you Prof, fascinating stuff
PS. There’s a really compelling documentary about a young woman who experienced a significant stroke called ‘my beautiful broken brain’. I really recommend it to anyone that’s experienced cognitive damage, language, memory or that claustrophobic feeling of being trapped inside your brain on a different time and space to everyone else - this documentary will really resonate. X
Thank you, and yes, it is very helpful! I was diagnosed 40 years ago in 1981, with RRMS, and have now been in SPMS for several years. My MS is considered inactive, but I have many lesions both on the brain and on the brain stem and spine. I do have gait issues, vertigo occasionally and have experienced most of the symptoms listed at one time or another, as well as others. I refuse to give up, and I stay active, walking, gardening, volunteering with the Master Gardeners and the Humane Society. I am not on any DMT currently, and I see my Neurologist up to 4 times a year for check-ups.
I’ve read this article and it describes my MS to a tee! At time of official diagnosis my MRI showed many lesions on my spine, whole brain and brain stem with one of the most significant appearing as a ‘chunk’ penetrating into my cerebellum! I have experienced almost all of the symptoms listed! I was started on Ocrevus as my first line treatment and it has been amazing for me! I went through an horrendous time for 18 months suffering from up to five seizures a day but after just over two years on this amazing drug things have calmed right down and I live with relatively little disability with my main symptoms being extreme fatigue and cognitive impairment. I actually view myself as a bit of a medical miracle and I do think the amount of exercise I have done over the years and still to this day has help to keep the disability at bay? I still manage to swim 2km a day (most days)-it’s my therapy!
Yes, ocrelizumab and the other anti-CD20 therapies are remarkably effective treatments at suppressing inflammatory disease activity and they do this with a very good short-term safety profile.
Let’s hope that the long term safety profile measure up just as well!? 🙏🏼
And the long term? Bad or unknown?
I think this painting it a bit too positively given the world in 2021. Pre-Covid I would have agreed (main reason I chose it, literally on the eve before the pandemic) but the vaccination issue really make me question that assessment...
I think it’s all relative and all depends on how badly your MS was/is affecting your life? For me personally my life wasn’t worth living prior to this drug-whilst in hospital I couldn’t stand up, let alone walk, completely deaf in one ear, couldn’t speak, absolute agony, couldn’t see properly and then 18 months of up to five hour long seizures per day with total exhaustion between those seizures! Don’t get me wrong I am scared to death of catching Covid especially knowing I’ve had complete vaccine failure after two doses of AZ but i try to keep myself as safe as possible from the virus and positivity for me is a huge part of my fight of this disease! So for me there was no other option than Ocrevus because my disease is so aggressive so I’m really trying to make the best of a bad situation! I hope you figure out what is the best way to deal with your own personal situation in these difficult times!
I find it refreshing to receive accurate and relatively detailed information. Your selfie newsletter has only been a recent discovery and I’ve poured over its contents. Thank you for being a breath of fresh air/clarity on this confusing journey.
I am one of those people who had difficulty getting diagnosed. Early diagnosis in 2008 was Fibromyalgia although I never felt that was accurate. Treatment was minimal.
I presented at emergency with arm numbness, trigeminal neuralgia and vision problems in 2014. This resulted in an MRI showing one lesion and a Neuro appointment. MS was not mentioned and no follow up given. At minimum I feel this was missed CIS. Between 2014 and 2018 I experienced ongoing bladder issues, Lhermitte’s, Uhtoff’s, TN, fatigue, gait issues and sensory issues in limbs etc.
MS diagnosis happened 01/2019 at the age of 64. In 2018 a new family doctor clued in to the relatively singular sign of Lhermitte’s and ordered an MRI. This showed 17 white matter lesions as well as one on the pons, and cerebellum. A 2021 MRI confirmed lesions in the CS at C3,4,and 5. These were not considered new but visible due to better imaging. My first med was Rebif (Mar. 2019)and later a switch to Tecfidera(Feb. 2020). I am radiology stable but I clinically show intermittent symptoms - milder TN lasting 4-5 weeks, greater fatigue, ataxia, and numbness in new areas such as lower legs and feet. I find Tecfidera close to intolerable with near daily reactions that sometimes escalate to full body flushing and bowel issues. I’ve hung in there for over a year. Recently I was denied a switch to a more efficacious med (fingolimod) due to my age, now 64. I am focussed on a better diet and doing functional PT for exercise. I am not risk adverse but feel I have been set aside due to age and supposedly lower disease burden. Six months ago it was suggested to me that I stop DMT altogether. Let’s wait and see what happens on an MRI scheduled after 6 months. I said no. I would prefer to be actively preventing future events.
I’m clearly on the escalation model, complicated by a late start, and being 66!!!
Perhaps it's time to challenge the drugs decision. I started on fingolimod age 65, am now 71 and have moved to cladribine. I think it depends on the approach of the neurologist. Mine has said that his philosophy is to treat according to patient needs as presented to him. I know I'm fortunate. If you're in England, you have the right to a second opinion/change of team.
I was offered Avonex - once a week injection of the same drug as Rebif but only 30 mcg. I felt awful on Rebif. l was also offered daily Copaxone. Three injection a week version is not available to me due to drug coverage problems. These drugs are lower efficacy and may serve a purpose in treatment. However they don’t seem to follow this mantra - ‘diagnose early, treat early, treat effectively’, especially treat effectively considering that I haven’t been MRI stable that long. Thanks for the advice.
I wasn't dx'd until i was in my 50's. I am now 63. I have been having symptoms since i was in my early 30's. As horrible as it souinds, i often wonder where i would if i had been Dx'd in my 30's and began treatment back then. I am now secondary progressive with active disease and seem to show new lesions every MRI that is done. Last one of Brain in Oct 2020 showed 130 plus 4 on brain stem... My doc does not understand how i am still functioning. I wonder myself some days. Best of luck to you as a fellow late MS er
Wow. You seem to have some resilience for sure. I’m trying to see the missed opportunities as the past and just part of my story, but I do sometimes think the same thoughts. What if….. Right now I’m focussed on getting a better quality of life in whatever way I can. Good luck.
TY, you too!
sadly, it seems that even now, in 2022, there is still difficulty getting an accurate Dx. I relate so much to your story. It took some 30 years to receive a proper Dx. I too was told I had fibro, arthritis, neuropathy, etc and that I was just plain depressed. Yes, I am depressed. after 30 years, I got lost on my way to the grocery store that I had been going to at least once a week for the prior 5 years at the time. When my doc heard the story, they sent me for CT. Even with numerous lesions showing on that scan, they refused to send me for MRI. I was Dx'd with anxiety and TIA. I switched providers 2 years later when my Medicare kicked in and finally got that MRI. After additional testing.. evoked potentials, EEG, blood work to rule out things like Lyme, the neurologist told me MS.. I was stunned. I was 57 years old. since then I have recently had a neuro question my Dx! IDK what other disease causes all of these symptoms including the 100+ lesions I have in my brain and on my brain stem and cervical spine but I am now feeling like I am back to square one. It really amazes me that they still have so many issues Dx'ing MS. Especially when things are very obvious like they tend to be with a lot of us. Best of luck to you in your search for a better DMT for you.
Amazing insights for us PwMS, thank you so very much Prof for your time and efforts to break this down into logical bite size chunks for us all to read. (Not the fault of the neurologists) but in a clearly stretched system with most of us having just a 5 min phone chat once a year with our neurologists, information, reassurance and understanding is minimal - your provision is like a huge blanket of care. I can’t thank you enough
Scary stuff but so very helpful. My various neurologists never explained this and only through your posts have I been informed. I have damage in very expensive real estate!
Isn't it maddening that Doctors don't explain these things to us?
No, your assumption is correct. Please continue. And thank you.
Great thanks prof. G. It's vital to understand processes in the brain being PwMS!
👋Good afternoon Professor G! from 🇦🇺 Yes, knowing how MS can affect the function of different parts of the brain and spinal cord will help understand MS. For some individual’s Knowledge and education is medicine💯
Thank you for taking the time to care for PwMS thoughts…. light + peace 😊🦋🌿🌻
Prof G, What is your thought on non lesional neurodegeneration of the cerebellum in PwMS and how to advocate for ourselves as patients with our neuros who do not recognize PIRA or smoldering MS without new or enhancing lesions even with progressive symptoms and worsening neuro exam?
It is hard to measure cerebellar atrophy, but you can do it indirectly by monitoring the size of the fourth ventricle that sits in front of the cerebellum in the brainstem. This can often be seen to get larger in association with worsening cerebellar function clinically.
The problem is if you are a DMT what do we do about this phenomenon? We don't have data that switching DMTs makes any difference at this stage. For example, if you have smouldering cerebellar atrophy on fingolimod does it slow down if you switch to ocrelizumab, natalizumab, alemtuzumab or have AHSCT? We simply don't have data to support these switches nor do we have data that switching from fingolinod to siponimod makes a difference either.
Thanks for the reply, I know the data is sparse, but from my perspective being on Tysabri and developing the regional atrophy (bad enough to spur concerns for paraneoplastic workup) as well as having progressive weakness, numbness, tremors, vertigo and vision symptoms, would it make sense to at least consider a switch to ocrevus and see what happens from a functional perspective?
Why ocrelizumab and not alemtuzumab or oral cladribine? An IRT may be more appropriate here particularly cladribine that can penetrate the CNS and hopefully deal with the so-called intrathecal B-cells that may be making pathogenic antibodies.
I am classified as CIS currently, optic neuritis, one small juxtacortical lesion, and cerebellum atrophy. CSF negative but taken after start of 5 Tysabri infusions and a relapse necessitating a hospital stay and steroids in which the brain mri then first showed the non lesional regional atrophy and neuro was concerned for paraneoplastic disease. Mavenclad and Lemtrada are not approved for CIS, so given my rapid worsening of symptoms and neuro exam I advocated a switch to at least see if it stops or slows the worsening but was shut down due to no new enhancing lesions.
I worry about early ppms with the continuing progression and atrophy - I am a clinical radiological paradox - and they don’t know what to do with me 🤷🏻♀️
You may find this case study helpful:
https://gavingiovannoni.substack.com/p/case-study-are-undefined-treatment
I got every symptom on this list in my first relapse and they (Canada, MS Clinic) STILL took forever to get me (f 34 at the time) on a highly effective DMT (Lemtrada, on my insistence). They forced me to fail through 2 front-line meds first, due to the two-tiered "fail up" system (and/or likely neuro not paying attention enough that things were not good, simply because I hold myself together well when in crisis--which some weirdos seem to take for the opposite, despite being told (by a surgeon) that I have one hell of a pain tolerance/constitution.
EDSS score 3+ on first onset, diagnosed in 1 "convincing" MRI (that I paid privately for in public healthcare to go around the PCP/GPs and ER docs (who wouldn't refer to neuro and) who couldn't get a clue what central vertigo looked like--even *I* knew I probably had MS). An ENT was the only clue-holder apparently (once I could coordinate walk again, I asked for a referral), because at least an ENT has sufficient training to rule out peripheral, and in central, vertigo. He did, less than 5 minutes. Immediately ordered public MRI (learned he'd wrote "MS-Brain" as scan type when copies requested) and urged me to consider also private-pay MRI for faster scan. Thought about it for 3 days then leapt. Best $900 I ever spent.
Baseline MRI 10+ lesions, small one in cerebellum (neuro claimed he couldn't see, I requested copies on CD + written report, so I know it's there) plus C-spine lesions (he also claimed we're barely there, meanwhile radiologists still admit to easily being able to see, if I bring it up first as me already knowing). I always suspected a tiny brain stem lesion due to the symptom severity ( but we have crappy old MRI machines here). Meanwhile, neuro played mostly dumb, despite letting me choose Lem after rapid-failing crappy 1st-line DMTs only later to reveal that is just his horrible bedside manner (let's not worry the emotional females attitude--this female is an aspie with more testicular fortitude than he has and I don't even have a pair lol). Glad I went nuclear w Lemtrada, been 4-5 years without progression *fingers crossed*...
Oops, meant to write, *every symptom but 2 (no hearing loss and no hallucination)*. Granted, it wasn't super-epic (I could walk, within a couple of weeks, once I figured out how to coordinate movement again and "tell my legs" to move (walking was no longer automated, had to cling to walls and practice in front of the mirror to relearn, couldn't remain sitting upright if I closed my eyes). I also preyed to the porcelain god and slept on the bathroom floor for a couple months, going back to the ER again and again for fluids and stronger antiemetics that did nothing, betahistine (did nothing of course), gravol, odansetron, maxeran (lost 10-15lbs). Didn’t yet have a regular GP (just walk-in clinics, because I had just moved, so that's how I ended up in diagnosis limbo and requesting referral to ENT to skirt the lousy GPs and ER docs--it worked!). Brain lesions get a referral to neuro really fast lol.
You note in the preamble that there are "things that can be done for each of the problems" and reference further on "specialised and targeted neurorehabilitation" for specific issues. Could you share some examples so that I might have a better discussion with my neurologist? Thank you.
I so appreciate these posts of yours; it definitely helps me to know more about this confounding disease.
Thank you so much for your excellent help in navigating this disease. I look forward to your newsletter. There are so many things that I have been unaware of and can now ask better questions during my check-ups.
You are not wrong! This post has already helped me understand why my long term symptoms occur (vertigo, unsteadiness). I know I have lesions in my cerebellum. Thanks Prof G! I’m waiting for an appt with my neurologist who I have not seen in a long while. I’ll be posing some questions!
Wondering if you have any experience with Tysabri causing cerebellum atrophy? 4 months into treatment I started having worsening cerebellar symptoms and exam with non lesional atrophy on MRI. It progressed so much and so quickly I stopped the Tysabri. Since stopping the Tysabri 11 weeks ago my cerebellar symptoms are starting to slowly abate. My ocular tremor is less severe, my extremity tremors are getting better, I’m experiencing less disequilibrium and heel to shin and antigravity tremors are improving unless overheated as well. I really attribute this to stopping the Tysabri since my symptoms got so much worse 3-4 infusions in but there is no research to support this with the exception of GCN related cerebellum atrophy and I have always been JCV negative. I am curious about your thoughts and experiences.
This is unlikely to be natalizumab related. Atrophy tends to occur 12, 18 or 24+ months after the event so the damage caused by MS probably predated the star of the natalizumab.
Thank you for your response, I have no cerebellum lesions though… and my cerebellar symptoms seem to be getting better off the Tysabri, would that be possible?
Yes and no. Recovery of function is complex and can take years to happen.
With regard to the cerebellum Stephen Waxman and colleagues described MS cerebellar dysfunction being due to abnormal ion channels and the observation that this could be reversible. Over the years I have seen reversible cerebellar ataxia and eye movement problems that I think could be due to this acquired channelopathy.
Shields SD, Cheng X, Gasser A, Saab CY, Tyrrell L, Eastman EM, Iwata M, Zwinger PJ, Black JA, Dib-Hajj SD, Waxman SG. A channelopathy contributes to cerebellar dysfunction in a model of multiple sclerosis. Ann Neurol. 2012 Feb;71(2):186-94.
Just re-reading a number of your newsletters before seeing my neurologist this week and so getting some questions ready! I'm concerned about getting the full picture from my MRI scans as over the past few years after regular MRI scans ( 2x yearly as on Tysabri) All I've heard about the results of the MRI scans are that they are stable ( good news) but I'm now wanting to know how many lesions are present and where they are located.
As you point out that posterior fossa lesions are of some concern I am interested to hear if I have any there as recently I've experienced vertigo ( sudden onset and severe for a few days and then much reduced, more like dizziness) which has never happened before. Also have long term hearing loss (high frequencies in particular but also find it difficult to distinguish clearly what people are saying even though I can hear them speak) and some mild tinnitus. Also in the same time frame there has been an unusual UTI (streptococcus haemolyticus) which was rather stubborn followed soon after by an ear infection. Infections were treated by GP but MS nurses informed.
I'm 62 and have been on Tysabri for nearly 4 years (JCV negative) with no evidence of new relapses as yet.
You need to make sure your attacks of vertigo are not something else; they sound more like Ménière's disease rather than MS. The clue is associated tinnitus and hearing loss.
https://www.nhs.uk/conditions/menieres-disease/
Thanks, will follow up on that.
I’ve just gone back to look at my diagnosis letter in 2014 to see if it mentions where my initial lesions were and it says ‘left superior and middle cerebellar punduncles’ so I’m assuming this is the area featured in your newsletter. I feel even more grateful for having Lem first line now as had no idea of my prognosis although was hit full on with the cognitive problems initially and still have residual language and memory problems - now I know why! Thank you Prof, fascinating stuff
Yes, the cerebellar peduncles are part of the posterior foss and connect the cerebellum to the brainstem.
Sorry my spelling 😂 I’ll remember it as pedantic uncles!
PS. There’s a really compelling documentary about a young woman who experienced a significant stroke called ‘my beautiful broken brain’. I really recommend it to anyone that’s experienced cognitive damage, language, memory or that claustrophobic feeling of being trapped inside your brain on a different time and space to everyone else - this documentary will really resonate. X