A major argument against early treatment of MS is that ‘I may have benign MS’, therefore treating me with DMTs is unnecessary as MS is not going to affect me very much in the long-term. I agree if you have benign MS then you don’t need treatment. However, the difficulty with making a diagnosis of benign MS early on in the course of the disease as been stressed many times before on this blog. This is why a wait-and-see approach to defining your prognosis, should be an active wait-and-see approach. Not the go away and come back and see me when you have a relapse. Most MS disease activity occurs at a sub-clinical level which is why we need MRI monitor to assess MS disease activity. As more data emerges the more sophisticated MRI and biomarker techniques will be needed, to measure more subtle signs of damage.
The population based natural history study of MS below is probably the best there is in relation to defining benign MS. These pwMS were diagnosed between 1950 and 1964 (the year of my birth) and were followed for up to 50 years. Their chances of having non-progressive disease at the 50 years was 14%; i.e. 1 in 7 pwRRMS had not become progressive by then. Early features that predicted a non-progressive course were complete remission after the first attack, low or moderate initial relapse frequency and possibly a clinical course dominated by sensory symptoms. I suspect if they had MRI back when this study was started then a low lesion load (zero or less than 2 lesions) would also have helped. The important thing to note is that transition to SPMS still continued to occur after forty years of follow-up. MS is truly a life-long disease.
Who makes the decision about risks and benefits that affect you. Should it be the regulators (FDA or EMA), payers (NICE, NHS or insurance companies), national neurological associations, your neurologist, your MS nurse, you or someone else?
Background: MS may have a non-progressive symptomatology for decades; however, it is not clear whether the disease activity may abate completely.
Results: For pwMS with an initial relapsing-remitting course and multiple sclerosis diagnosis according to the Poser criteria (n = 202), the probability of non-progressive disease after 40 years was 22% (standard error 3.0%), and after 50 years it was 14% (standard error 3.2%). For attack onset including pwMS with possible multiple sclerosis, the corresponding probabilities after 40 and 50 years were 35% (standard error 3.3%) and 28% (standard error 3.5%), respectively. At the last follow-up in 2009-10, when pwMS reached the average age of the Swedish population life expectancy, only 13 pwMS from the MS diagnosis cohort, according to the Poser criteria, remained alive and non-progressive. Their annualized attack frequency diminished with time from 0.29 to 0.015. These pwMS had been functioning well socially. Nine pwMS had an Expanded Disability Status Scale score of 0-2.5, and four patients had a score of 3 or 3.5, with deficits dating back to attacks decades ago. Eight pwMS participated in a complete neuropsychological examination, which showed a slight difference (P < 0.01) concerning verbal memory and executive function compared to an age and socially matched reference group, whereas results for five other cognitive domains were within the normal range. Magnetic resonance images fulfilled the Barkhof-Tintoré criteria for multiple sclerosis in 10 of 11 pwMS, with conspicuously few subcortical lesions relative to extensive periventricular lesions and lesions extending from the inferior midline aspect of the corpus callosum.
Conclusions: Prediction of the non-progressive stage was possible with moderate hazard ratios and low sensitivity. Early features that predicted a non-progressive course were complete remission of the onset attack, low or moderate initial relapse frequency and-when the pwMS with possible multiple sclerosis were included-dominating afferent or sensory symptoms. The clinical disease activity had abated in these 13 pwMS, with the caveat that transition to secondary progression continued to occur after four decades, albeit with decreasing risk.
CoI: multiple
How do we know that those people who were still not progressive after 50 years even had/have MS?
We don't they were diagnosed as having MS. As you know the diagnostic criteria are not a 100% and therefore there is a reasonable chance they may not have MS.
The diagnostic criteria are not 100% today – and we have 3T MRI machines today.In the 1950s, there were no MRI machines. The diagnosis must have been awfully hit and miss back then. It would be good to actually have put the people who weren't SPMS after 40 + years into an MRI machine to verify if they actually have changes consistent with MS.
Bizarre — neither of you seem to have read the abstract. The paper addresses this issue."Magnetic resonance images fulfilled the Barkhof-Tintoré criteria for multiple sclerosis in 10 of 11 pwMS,"
This MRI criteria apply to the here and now and to the few survivors, not to the whole cohort. The problem with applying MS MRI criteria in older people is that a lot of them acquire white matter lesions that are vascular and nothing to do with MS. We know that the misdiagnosis of rate of MS is about 5% so most of these people will have MS.
Do you think that the survivors would have been more likely than the rest of the non-progressive cohort to have had MS? In any case, from reading the paper, you'll see that this cohort is half the total number of patients who remained non-progressive at 40 years.Anyway, here's an interesting bit of the paper, which undermines the claim that OCBs drive progression:"During the years 2000–03, CSF was sampled and analysed using isoelectric focusing and cytology in 9 of the 13 patients characterized as non-progressive by 2009–10. Six of these patients had a CSF enriched oligoclonal IgG reaction. All of the patients had essentially normal values for CSF parenchymal damage markers (neurofilament light, glial fibrillary acidic protein and tau protein)"
Until there are better genetic tests or biomarkers that can predict how severe your MS will be, I think that early, aggressive treatment makes the most sense. I advocated to receive alemtuzumab after my first relapse and my neurologist supported my decision. I just felt that preserving my brain from potential damage was worth the risks. This is consistent with the precsutionary principle in my field: "Where there are threats of serious or irreversible damage, lack of full scientific certainty shall not be used as a reason for postponing cost-effective measures to prevent environmental degradation." You can swap out environmental degradation for neurodegeneration and you've got the animating principle behind my treatment philosophy.
Absolutely. Good on you for acting quickly and aggressively. It's heartbreaking to see people with aggressive MS diligently but fruitlessly injecting themselves with Copaxone and other underpowered drugs when there's so much more powerful stuff out there. That's why informative blogs like this one are invaluable.
I think it's about time to have a biomarker to diagnose MS and MS severity. This should be really one of the top 5 on every researcher's agenda. Everything else is just speculation and doesn't help the MSers in their drug decision making & life choices.I am a very cautious MSer but if I had a test to tell me that I might progress quickly than I might have changed my mind regarding side-effects.Also, with a test we would not need to speculate how much/ little benign MS is benign etc. We simply want certainties and not endless 'what ifs'.
We don't have certainties, but we have predictors that give you some idea how well or badly you are going to do in the long-term.
Those graphs are very basic. I don't think any "type" of MS translates well to labels (RR, SP, PP) or crap graphs very well. We are talking biology here, not physics. It's fuzzy and has a lot of grey areas.
These graphs are not mine. But I agree too simplistic and don't capture the trajectory of the disease for most pwMS.
There's a hugely critical component to this that you have raised before on the blog: prompt and accurate diagnosis. Born in 1963 and diagnosed in Nov 2015 I was told by the neurologist that I'd almost certainly had MS for years. I now know the likihood is that I had benign MS with my initial relapse in 2011. Years of living with headaches, low energy, walking slower than everyone else and an unexplained shoulder ache. Even my first relapse was incorrectly diagnosed! Unlike so many PwMS I had many years of being well, but I don't like to dwell too much on how I'd be if I'd received an early diagnosis, most particularly in 2011 when I pretty much had a full recovery. Now (as we know as '63 and '64 babies) I have age to contend with, as well as the disability impact of a lack of diagnosis. In the circumstances, I have be been supremely fortunate to have been given Alemtuzumab, but as an Oldie, I'm not going to retrieve what I've lost.If I'd known, if there had been an early diagnosis – would I have chosen treatment and a strong one at that – as far as I'm able to state retrospectively – most definitely! No diagnosis then no decision as to the options – you don't know you need 'em!
Hi Fi 3.46, how are you doing post alemtuzumab? The retrospectoscope is an incredibly useful medical instrument! What we all wouldn't change if we only knew then…You're 7 years ahead of me in terms of age, but MS wise you've hit reset and had the nearest thing to a cure we know today 🙂 I wish you well and hope things go well for you. Judy x
Lol! I'm no scientist and my IT knowledge and abilities are so naff! So, Judy I've just pinged a post after yours to Luis, having not scrolled back and seen this reply from you!I've my second round of the first course of Alemtuzumab in Nov, but post the initial five infusions I'm doing OK thanks. Think I've said before I do feel blessed to have received Alemtuzumab and when I dwell on that feeling it's makes me all the more keen to see treatments for those such as yourself who are having to deal with being offered nothing – hence my query that I've already sent!I like the 'retrospectoscope' – think I'll adopt it and use it myself.
You'll do great with best treatment and attitude to match! Well done you for researching and standing your ground. Have tried a few things in the past, never quite worked out for one reason or another. Don't worry about me, there's always a plan B, plus I've got loads of fab holidays booked for this year :-)Ps I'm easy to track down online if you look (benefit or peril of blogging as real person)
What I wouldn't do to have 60 years of life without a life altering illness.
I am going with the nuclear aproach early on
This disease is cruel in so many ways, not least the wide-ranging ways it hits each and every person living with it, and that's combined with difficulties in achieving diagnosis, obtaining treatment, lack of treatment for some forms it takes and those PwMS living in countries where there's nothing available for them. Now wonder whether my other post may read like a gripe, or even self-pity, when that wasn't my intention. Wanted simply to highlight the relevance of early and effective diagnosis in regards to benign MS. I return to this Blog so regularly because reading about anything that is,or maybe, of benefit to PwMS lifts my spirits.
Hi Luis 6.03 I read all your posts yesterday re HSCT, thanks for all the links. Will be interesting to see how the study reports when complete. If I had my time again and knew 10 years ago what I do now…. As I've just said to someone else, the retrespectiscope is an incredibly useful medical instrument….
Hope you're seeing some progress with receiving further treatment Judy.Thanks to your book recommendation I've been causing amusement about macrophages being 'big eaters' – so thanks for the unlooked for laughter with family & friends!
Morning Fi 8.13Haha! I frequently return to that book when reading MD posts, not that it's anything like in depth enough but MD brilliant at explaining so I muddle through ;-)Treatment an ongoing saga… won't bore you and the rest of the world here. Have a good weekend 🙂
When I was diagnosed with CIS privately I went to see Dr ???? privately for a second opinion. This was because the neuro who had diagnosed CIS admitted he wasn't that clued up on current MS practice/approaches, etc. I brought my mri scans on disk for him to review. I have to say that I was so disappointed to be turned away being told "don't worry you look fine you feel fine and you're a young female so your prognosis is great… oh and avoid animal fats as they seem to cause inflammation". I came out of his office feeling deep down that a lot about the consultation was not right. Luckily my private insurance covered the £250 or so cost of the 5 minutes I spent with him or I would have been seriously fuming. I was at a stage when I did not know a lot about what was happening to me. I now know a lot more. But yes my point is that this neurologist who I thought would be at the forefront of treatment etc was not at all. I'm not sure I'll ever understand why he just sent me away saying "come back if anything else happens". Such a dismissive consultation. I'm now luckily in very good hands. (I went on to have another relapse and am now on tecfidera which seems to be doing its job).
This saddens me so much and your experience is sadly not an isolated incident. It would be really interesting to see the prescribing habits of major neurological centres, pharma know and have done Freedom of Information requests to find out. My clinical colleagues shudder at the thought.
Only today I was fortunate to see a case presentation with brain scans and I believe a lot of the damage was a consequence of slow diagnosis and failure to treat the disease adequately, (This persons MS journey did not start at Barts) again I suspect risk averse neurologists were at the heart of the problem
"I suspect risk averse neurologists were at the heart of the problem."More accurate term would be "do nothing neurologists"In progressive disease if you do nothing it will progress.
'Is your ms benign?' Current relapse says no.'Who makes the decision about risks and benefits that affect you. Should it be the……' I do, though ideally it would have been a joint effort between myself and a neurologist. Sometimes though ideas that look good in policies, on paper, or in a blog, don't happen that way in reality, and allowing the disease to run it's course becomes a less stressful, more truthful and therefore more tolerable, route.
I assume these longitudinal/cohort type studies tend to be skewed towards the severe rather than the mild. Given the amount of people who fight for 20-30 years for a diagnosis, there must be a proportion of people with community managed MS that never come to the attention of an MS specialist or even a neurologist (and therefore a registry). There is also that incidentally found RIS stuff, which again makes you think there must be bigger cohort of people that “cope” just fine than meets the eye. However… I am emotionally exhausted with the “your symptoms are benign/your borderline hysterical/you seem fine/but make sure you give us a tinkle when your limbs stop working again approach”… It is a bit annoying that the NHS pour gajillions of pounds into things like breast cancer and AAA screening when there is no scientific consensus on the benefits/risks, but it’s ok as it’s politically favourable; yet getting proper support for routine MRI in CIS/early MS (which seems quite well evidenced(?)) feels like you’re asking for the world. I just kind of hope the modern era of cohort studies/registries etc offer you guys enough evidence to get some consensus opinion, which can be carried forward into RCT design/licensing/NICE guidelines etc.
What is benign? Is it when you have MS but have no symptoms whatsoever? Is it when you have had a relapse followed by no other symptoms? Is it when you have a relapse followed by mild symptoms, such as numbness and tingling and no spasticity? Is there a definitive answer? I think it would help us to know.
I found this in ms society website :'Benign' means 'something doesn't cause any harm'. You can only really say you have Benign MS after you've gone 15 years or so without many symptoms and you've got little or no disability.A diagnosis of benign MS doesn't guarantee you'll be free of problems. You might still get things like fatigue or problems with your memory or thinking.MRI scans can still show MS is damaging your brain and spinal cord even if yours seems mild. After many years of your MS appearing to be 'benign' it's possible you might have a relapse.
One question about this "bening ms" blah blah (a commentor above touched on it).For whom is MS really benign? For people with MS who turn out to have not so much a benign ms 10 years later or for neuros who don't have to stress about people with 'benign ms'?i remember well the look on the oncologist's face upon feeling my partner's lump (which he proclaimed to be a sweat gland initially) a few weeks later. the "benign sweatgland" turned out to be an aggressive breast cancer and to this day i'm thankful the weeks' delay did not alter her successful outcome. i also remember well waiting for results on whether it had spread.this all happened very quickly, a matter of weeks. there was no time for doctor shopping or analysing what had happened: one day she was in for what was supposed to be a sweat gland, a few tests and weeks later she was taking a note across the clinic to the hospital,on which the doctor had written 'death imminent' in order for her to be treated the next day (to his credit, after the initial delay, she literally had surgery 1 the next day and began other extensive treatment as soon as her body allowed after). people with "bengin" ms take years, find new neuros, sometimes move on. neuros have the luxury of benign ms and wondering if they should treat everyone hard early if 1 out of 10 will end up having 'benign ms'. do people with ms -those who want aggressive treatment – have the luxury of waiting to see if it's "benign" (aka you might go a bit dimmer faster than the rest us of, but other than that you'll be right mate?')i have been called ranter many times on this blog, a fascinating name and one that i regard as 'so be it' but it saddens me immensely to think that if it wasn't for the cancer experience there is a good chance we would be lost in this ms world (which is, frankly, a nightmare of dogmas opinions and egos). it terrifies me that if i didn't learn along the way how to throw tantrums and make beaurocracies move, if i didn't have the money to afford to pay for things, my partner would likely be receiving what i would consider low level of care. the sheer number of times i read stories of women with ms feeling like they are getting worse but their doctors not listening makes me despair and the number of people with ms that come or get sent to me for help with dealing with beaurocracies makes me want to cry.incidentally, i watched my partner's father die a few days ago from asbestiosis. the disease ravaged him quickly – in the matter of months, and the death was relatively quick – small mercy for everyone involved. his biggest fear before dying was his youngest daughter taking 20 years to get to the point he got to in 6 months.14% benign ms that can only be confirmed 15 years later?that's what the hippocratic oath is about?
There is no such thing as Benign MS; it's all one disease that progresses at different rates in different ways, in different people. Benign is a convenient, and inappropriate label. My MS was diagnosed 20 years ago. I'm still working part time, and currently walking without aid. I've no doubt I would satisfy the 'Benign' label. But then there is the fatigue, the numbness, the lack of feeling in areas of my body, the muscle spasms, the pain and the mechanical assistance required for both bladder and bowel function. How is this benign??
Just as I thought Sarah, no such thing as benign MS. I think you've either got it or not.
Great point This is a "Stable" pwmshttp://www.msdiscovery.org/news/news_synthesis/322-more-meets-eyeThere is a war is my head
"When I was diagnosed with CIS privately I went to see Dr ******* privately for a second opinion. This was because the neuro who had diagnosed CIS admitted he wasn't that clued up on current MS practice/approaches Etc I brought my MRI scans on disk for h** to review. I have to say that I was so disappointed to be turned away being told "don't worry you look fine you feel fine and you're a young female so your prognosis is great… oh and avoid animal fats as they seem to cause inflammation". I came out of h** office feeling deep down that a lot about the consultation was not right. Luckily my private insurance covered the £250 or so cost of the 5 minutes I spent with h** or I would have been seriously fuming. I was at a stage when I did not know a lot about what was happening to me. I now know a lot more. But yes my point is that this neurologist who I thought would be at the forefront of treatment etc was not at all. I'm not sure I'll ever understand why they just sent me away. #ClinicSpeak: do you have benign MS?"