Wednesday, 26 March 2014

ClinicSpeak: Under-reporting of relapses

Am I so wrong to be promoting ZeTo? #ClinicSpeak #MSBlog #MSResearch

Are you reporting all your relapses? If you don't it could have consequences.  #ClinicSpeak #MSBlog #MSResearch

“The problem of not reporting and documenting relapses is a serious issue for MSers living in the UK. I saw a patient in outpatients yesterday who has had MS for just over 6 years. He was diagnosed as having CIS after presenting with the MS hug (tight constriction band around the chest) and loss of feeling from waist down and weakness in the legs. When he presented he had an abnormal brain MRI and a positive spinal fluid analysis. Anywhere else in the world he would have been put on therapy; in the UK 2008 we weren’t allowed to treat CIS. Over the next 6 years he went onto have mild attacks; patches of sensory loss and tingling in the arms and legs. Although he was seen at clinic on an annual basis these symptoms were dismissed as possibly being due to minor relapses and because they were not documented his diagnosis remained that of CIS. Tragically not repeat MRI studies were done to see what level of activity he had. He was referred to me in mid-February with progressive weakness in the legs since December of last year. He is now using a walking stick. The weakness came on quite suddenly over a few weeks suggesting this was possibly a relapse; but since then he has progressed. He was treated with a course of steroids before Christmas, but this made little difference to his functioning. He has bladder problems, chronic constipation and sexual dysfunction. He is depressed and is anxious about losing his job; he is having increasingly difficulty at work mainly due to memory problems. He tells me he forgets to complete tasks. His latest MRI show a massive lesion load, gross brain atrophy and four gadolinium-enhancing lesions. Although he has focal inflammation on his MRI and a recent history of a disabling relapse I suspect he probably has entered the secondary progressive phase of the disease. To diagnose SPMS you really need to have a history of progressive MS for at least 6 months. When you speak to him about his cognitive problems these have been getting worse for at least 2 years. I have given him the benefit of the doubt and have offered him a DMT with a recommendation for going onto a highly-active treatment (natalizumab).”

"Please note that this gentleman has only had one documented relapse in the last 12 months. The other relapse that 'qualifies' him for treatment was subjective; i.e. a sensory attack with numbness and pins and needles in the feet associated with unsteadiness of gait in June or July of last year. During this relapse he had some difficulties going up and down stairs; he needed a handrail for support. Some of my colleagues would not have classified this as a relapse as he was not examined during the attack and hence it was not documented. Some would say that it was not a disabling attack as he was still able to function normally through it, nor did he require steroids or a hospital admission. This is not just semantics; in the UK we need two documented disabling relapses in a 12 month period to be deemed eligible for natalizumab and we need an active MRI scan as well. It is my policy to give the patient the benefit of the doubt and any relapse that affects normal activities of daily living is disabling. For a Londoner using the underground everyday, not being able to walk down the escalators is disabling."

“I can only wonder what would have happened if this young gentleman (he is only 32 years of age) was started on treatment at the CIS stage and had his MS actively monitored with relatively frequent MRI studies? Would we have prevented him from developing cognitive impairment? Would he be fully mobile? Would we have prevented his brain from shrinking? Would he have normally bladder and bowel function? Would his sex life be normal? Would he be depressed and anxious?"

" I sincerely hope by suppressing the inflammation in his brain and spinal cord his nervous system has enough reserve capacity to recover some function. I am not sure about this; my experience to date with highly-effective treatments in this phase of the disease is that although we suppress relapses and MRI activity progression continues for a few years before plateauing out. I have rarely seen much recovery when there is so much end-organ damage on MRI (atrophy). The plateauing-out observation is a relatively new observation of mine and at present is still anecdotal and needs to be confirmed in prospective follow-up series. I have referred to the hypothesis underlying this observation as the therapeutic lag-effect. I have posted on the therapeutic lag effect in the past. It is not well accepted by my colleagues; some are however supporting my attempts to look for it in existing data sets and to include it in their thinking about progressive MS trial design.”



“The following is a recent slide presentation of mine in which I promote early, highly-effective, therapy in MS. It explains why treat-2-target of NEDA is the rational extension of this approach and why we need a zero-tolerance approach.”



CoImultiple ; please note the specific details of the brief case scenario above have been change to make sure the individual patient is unidentifiable.

24 comments:

  1. This case illustrates that a objective test is needed for diagnosing ms. This should be a top priority in MS research. I wish him the best of luck.

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    1. Re: "objective test is needed for diagnosing ms"

      Yes, but this case also illustrates why education of MSers is so important. If he knew how important it was to have his relapses documented and if he knew about MS being an iceberg he would have been diagnosed and treated earlier. Education, education, education. People in many circles criticize me for running this blog, but if one MSer benefits from early diagnosis and treatment and I would have achieved a lot. In 2014 therapeutic nihilism should be extinct; sadly this case illustrates that it is not and is alive and kicking.

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    2. Yes I agree. But when you start having these isuues and no one is sure what the problem is, the importance of reporting relapses may not be apparent. In my case I had an extreme ADEM attack and 3 years later was diagnosed with ms. In the beginning I new nothing about MS and it took a long time to understand. Unless you have a good doctor at the onset, the patient is not going to know enough to report relapses. A positive objective test (if one was available) would get the patient into the hands of a specialist quicker.

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    3. Prof G, who is criticising you for running this blog? Do you think that certain powers are trying to crush your spirit and make you abandon this blog? Why would they do that? What's in it for them?

      There is envy, prof G. You put your neck on the line and they're just jealous. You're a celebrity neurologist who we all know of and they are not. You earned the respect, Prof G.

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    4. As I read this story, I thought this is exactly why you started the blog. It's got to be frustrating to see patients who likely could have been helped with the right treatment options. Even if the patient was in denial or was uneducated, an annual MRI would have picked up his ongoing disease activity 5 years before this. Makes no sense that he couldn't get that.

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  2. Poor fella. What an appalling case of health neglect whereby due to the fact our health administration is wilfully sabotaging the lives of young MSers by ignoring realities concerning the disease, an enormous group of sufferers is falling by the wayside.

    This is the worst time to get MS. There are treatments that may cure MS on the market but an entire generation is prevented access to them because of demented reasoning. These drugs will inevitably get licences but it will be too late for us. So near yet so far.

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  3. This is tragic. How can we get more active in the campaigning arena? On this and so many other related topics, BPA etc? Any suggestions?

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  4. This is not only tragic, it shows a blatant disregard and contempt of human rights for every person with MS in the UK. I am sick and tired of reading and hearing about treatment denied to myself and fellow MSers. Treatment that can not only prevent future personal disability but will save - what's left of - the NHS millions in future costs. To reiterate what Bouncy wrote above; how can we be more active in campaigning for treatment? Who do we lobby? Where do we start?

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    1. Re: " I am sick and tired of reading and hearing about treatment denied to myself and fellow MSers."

      This case is tragic in that the neurologist monitoring this patient did not change the diagnosis from CIS to MS and did not use subjective (non-confirmed) relapses to guide therapeutic decisions. In the UK non-MS neurologists still have some doubts about the efficacy of DMTs and have yet to buy into the early treatment rapid escalation paradigm. This patient was also not educated about MS and what to look for in relation to relapses. This could have been overlooked or maybe this patient was in denial and didn't want to report the relapses and get a diagnosis of MS. The wisdom of hindsight is easy.

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  5. Please say something more about what "so much end-organ damage on MRI" means
    How much is "so much" and how do you judge?

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    1. Re: ".... so much end-organ damage on MRI" means How much is "so much" and how do you judge? "

      End-organ damage refers to the number of black holes on the so called T1 images coupled with gross shrinkage or atrophy of the brain. Both of these indicate loss of neurones and axons or nerve processes. When you see this on MRI with someone who has cognitive impairment and physical disability it is not good news. It indicates that the brain (end-organ) is severely damaged. The great tragedy in this case is that we have treatments that reduce black hole formation and reduce the rate of brain atrophy. However, these treatments work better early in the beginning of the disease before there is significant end-organ damage.

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  6. I am glad my original neurologist offered me the chance to go the treatment route for which you seem to advocate. Copaxone was not working for me, and after 2 flares in 8 months on it, I was offered Tysabri which has allowed me to resume much of my pre-MS life. As I read this blog, I often wonder how lucky I am to be relatively stable MS wise for the past 6 years. I count myself as another anecdotal case supporting your call for early treatment with the most effective drugs at our disposal.

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  7. I don't know the proper place for info updates - so I will post here for your review

    Biogen Idec Inc Receives License For Novel Mouse Model From Myelin Repair Foundation

    Monday, 1 Jul 2013 08:00am EDT

    Biogen Idec Inc announced that The Myelin Repair Foundation has granted a non-exclusive sublicense to Biogen Idec for the use of MRF's technologies to generate a novel mouse model for all demyelinating diseases, including multiple sclerosis (MS). Biogen Idec, an independent biotechnology company with a strong focus on multiple sclerosis therapies, will use the MRF technology in its in-house drug discovery programs. The Myelin Repair Foundation and Biogen Idec will collaborate to improve the licensed technologies to enhance discovery of myelin repair therapeutics and speed clinical development.
    http://www.reuters.com/finance/stocks/BIIB.O/key-developments/article/2785765

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    1. I am not sure why this made the news, it means nothing.

      Someone at the Myelin Repair Foundation has made a transgenic/knockout mouse and Biogen has had to pay for the privilege of using it. We could have done the same, except we gave our mice, which were in the public domain to them.

      So rather than saying this will speed up finding drugs you could simply have made a press release to a university/MRF is profiteering or commercialising the mouse they made.

      If you publish you have a duty to make these mice available as a condition of publication.

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  8. Prof G why natalizumab and not fingolimod or alemtuzumab? Did you check this persons JCV status? Surely if they were JCV positive you woundn't start natalizumab?

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    1. Re "why natalizumab and not fingolimod or alemtuzumab? Did you check this persons JCV status? Surely if they were JCV positive you woundn't start natalizumab?"

      In the UK fingolimod is a 2nd-line therapy and you have to fail an injectable before being eligible. Although alemtuzumab is licensed as a 1st-line therapy in the EU it has not been NICED (approved in the UK) yet. Natalizumab is the only licensed option available for RES (rapidly-evolving severe) MS as a 1st-line therapy. The JCV+ status is an issue but with out another licensed option this is difficult. The risk of PML only really kicks in after 12 months so this will give us breathing space to consider other options. In the past (pre-natalizumab) mitoxantrone would have been an option, but its side effect profile excludes it; i.e. the risk of leukaemia and its the fact that you can only give a short course.

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  9. Tysabri risk for PML in the first year is still very minimal. If one believes time is brain, even one year to halt disease progression with the most effective drug would be worthwhile. What's more, many like me would choose to take the risk regardless of JCV test results. Even with a positive result (bad), the odds of dieing from PML are still better than the odds of a middle aged breast cancer patient who opts for chemo after a mastectomy (best statistical option for longest lifespan according to actuarial charts). Chemo therapy kills approximately 1 in 200. If after a year, Tysabri had stabilized the patient and even allowed some recovery, would you understand them opting to continue Tysabri? That was my choice. My wife and I said, "Give us 5 good years over 30 crappy ones." When I had been on Tysabri for 5 years, we talked about it again and said we want to renew the deal. I'm always going to take the good years over more crappy ones.

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  10. This makes me so angry. I keep hearing similar stories time and time again. This blog is a brilliant source of information as is the internet as a whole. As someone diagnosed with a CIS and subsequently sent on my way I took the matter into my own hands and did my own research.

    12 months on, 3 changes in neurologists, 2 complaints and a letter to the PCP later and I am finally on DMD's. What makes me livid about all of this is the PCT came back advising I was entitled to DMD's all along as I'm high risk. Furious doesn't quite cut it as I've faced opposition all the way during a time I was feeling scared and vulnerable and could have done without the aggro.

    I am the only person to be on DMD's for a CIS.in my area and frankly I find it shameful. I imagine I'm a patient from hell but I would encourage everyone to get informed and be your own advocate.

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  11. What about the difficulty of deciding what is and what is not a relapse? I consider myself well informed and well looked after by my MS team, but it seems to me there is a fine line between 'flutters', come and go or ongoing sensory stuff and true relapses. When I've discussed symptoms with the MS nurses, it's clear to me there's a grey area. There's lots of 'it could be..., let's wait and see if it goes of its own accord' and so on. The uncertainty I feel is despite the information and education about MS I have received and despite the fact that the MS team is considered leaders in their field..... so what about all the MSers who don't have this level of support?

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  12. Anon (EDITED) 15:17 pm Said

    Ok time to speak up.

    I am equally a 32 years old Londoner with MS. CIS event 5 years ago.

    Striking similarities. But they end here.

    The doctor who diagnosed me (Dr. X EDITED) sent me home without giving me a diagnosis. He said: let's keep an eye on you. I had an MRI done 2 weeks later at my own expense: white spots and inflammation.I stormed his office in the same day. He was angry and made me wait outside for 4 hours. He then allowed me in and said: I know you have MS but did not want to worry you.

    Another relapse 4 month later and Copaxone 3 months after that.

    I had meanwhile visited another Neuro, who equally hangs her Diploma in her office [EDITED]. She said that I was luck as my relapses have been very mild and should stick to Copaxone.

    She then said that the only guy back in 2009 willing to give Tysabri in London was Geovannoni.

    Then I found this blog, "fired" Dr. X and hired Dr. Geovannoni.(NOT EDITED It's Giovannoni) I asked for the most aggressive available treatment and he kindly obliged by putting me on Tysabri.

    Now 32, still a happy patient of Dr. G and was told last month that I have No Evidence of Disease Activity (4 magic letters!).

    I have taken a pilot's license last year (for fun) and a motorbike license last week (for fun as well). Hopping to run a 10K for the MS Society this summer.


    Yes, early aggressive treatment works.

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    1. Dear Anon 15:17
      Sorry I cut off the bottom but you obviously do not get the whole comment in Blogger comments and it was a cut and paste. MD2 thought it best to remove some locations before posting.

      Now that I see the stuff cut off this is great news

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  13. Thank you for this blog! I was diagnosed CIS in Jan 2017 its now July and I'm getting the hugs, fatigue, numbness in hands etc etc...

    Will be contacting my consultant in the morning. Last time we spoke he had led me to believe that this was purely an isolated incident.

    I'm really hoping I get some treatment if I do actually have MS! I am 34 with a 1½ year old boy an 6 month old girl. I'm also going in to my final year at uni in Oct.

    Really stressful times!

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