ClinicSpeak: poor recovery from relapses predict progression

Are you a good, or bad, recoverer from relapses? #ClinicSpeak #MSBlog #MSResearch

“The study below shows that if you have a poor recovery from relapses you are much more likely to enter the clinically-apparent progressive phase of the disease sooner; in fact in this study it was ~22 years sooner (8.3 years vs. 30.2 years). These results are important for several reasons:

  1. Firstly, it is clear that recovery from relapse is determined by the amount of functional reserve. If you have spare capacity in the affected, and compensatory, neuronal pathways you are more likely to make a good, or complete, recovery from relapses. Functional reserve is dictated by how long you have had MS and the lesion load in the affected pathway. The more damage you have, the less reserve you have, the more likely you will have poor recovery. This is why we say ‘treat early and effectively’; ‘time is brain’ (and spinal cord).
  2. Age is another factor; the younger you are the more likely you are to recover function. This is simple biology; ageing affects the regenerative capacity of all tissues. This helps explain why age is the best predictor of the onset of the clinically-apparent secondary progressive phase of MS. Please note I use this term clinically-apparent as there is evidence that the pathological substrate that underpins progressive MS is there from the beginning. This is why we are actively promoting the concept that early effective treatment is in fact a treatment strategy that is targeting progressive MS. It is better to prevent the onset of progressive MS than to try and treat it.
  3. DMTs reduce the severity of attacks and hence result in better recovery from relapses. It is now clear that DMTs, in particular highly-effective DMTs, not only reduce the attack frequency, but also reduce attack severity (need for steroids and/or hospital admission). This is why DMTs delay the onset of clinically-apparent SPMS; despite some commentators saying the opposite there is now data to support this position.
  4. Another factor that is lesions location. Brainstem, cerebellar, or spinal cord relapses were associated with a poor recovery from the initial relapse. I have discussed this topic before. I suspect that sensory relapses are more likely to be due to smaller, less damaging, lesions. Why? Sensory, or so called afferent, systems (vision, hearing, cutaneous sensation) are more likely to cause symptoms from small lesions as these symptoms are optimised to sense the environment. In comparison, motor or efferent systems (coordination, power) are more likely to cause symptoms when affected by larger more damaging lesions. This is why we take lesions in motor, or efferent, systems more seriously.
  5. Genetic factors may also play a role. In the animal model of MS, or EAE, some strains of mice recover more quickly than others and the best recoverers become progressive more slowly. Those strains who do badly and recovery less well are more likely to become progressive sooner. As yet we haven’t convincingly defined genetic factors in people with MS that predict recovery, but I am sure there are several to be found.
How is the relevant to you, a person with MS? I think it is highly relevant. If you have non-recovery from early relapses this is a poor prognostic sign and hence you may want to choose one of the big guns (highly effective therapies) from the beginning. If you have active MS you almost certainly want to be on a DMT to prevent new lesions from forming and to become attack free. In essence you want to have NEDA (no evident disease activity) and preferably no ongoing end-organ damage (normalised brain atrophy rates). I am sure some of you may agree with me on this, whilst others will disagree. I think preventing end-organ damage is a no-brainer.”

“Please note, one way of acquiring disability is non-recovery from relapses, and not only the gradual progression we see in the clinically apparent progressive phase of  the disease (SPMS & PPMS). Non-recovery from relapses is more common than we realise. I simply don’t understand why someone with MS would take the chance of having relapses, when they can reduce  their chances with effective DMTs (licensed or unlicensed). I stress unlicensed DMTs, because in resource poor settings people with MS still have affordable options.” 

Epub: Novotna et al. Poor early relapse recovery affects onset of progressive disease course in multiple sclerosis. Neurology. 2015 J. pii: 10.1212/WNL.0000000000001856.

OBJECTIVE: To evaluate the relationship between early relapse recovery and onset of progressive multiple sclerosis (MS).

METHODS: We studied a population-based cohort (105 patients with relapsing-remitting MS, 86 with bout-onset progressive MS) and a clinic-based cohort (415 patients with bout-onset progressive MS), excluding patients with primary progressive MS. Bout-onset progressive MS includes patients with single-attack progressive and secondary progressive MS. “Good recovery” (as opposed to “poor recovery”) was assigned if the peak deficit of the relapse improved completely or almost completely (patient-reported and examination-confirmed outcome measured ≥6 months post relapse). Impact of initial relapse recovery and first 5-year average relapse recovery on cumulative incidence of progressive MS was studied accounting for patients yet to develop progressive MS in the population-based cohort . Impact of initial relapse recovery on time to progressive MS onset was also studied in the clinic-based cohort with already-established progressive MS (t test).

RESULTS: In the population-based cohort, 153 patients (80.1%) had on average good recovery from first 5-year relapses, whereas 30 patients (15.7%) had on average poor recovery. Half of the good recoverers developed progressive MS by 30.2 years after MS onset, whereas half of the poor recoverers developed progressive MS by 8.3 years after MS onset (p = 0.001). In the clinic-based cohort, good recovery from the first relapse alone was also associated with a delay in progressive disease onset (p < 0.001). A brainstem, cerebellar, or spinal cord syndrome (p = 0.001) or a fulminant relapse (p < 0.0001) was associated with a poor recovery from the initial relapse.

CONCLUSIONS: Patients with MS with poor recovery from early relapses will develop progressive disease course earlier than those with good recovery.

CoI: multiple

32 thoughts on “ClinicSpeak: poor recovery from relapses predict progression”

  1. I'm not sure if I should feel slightly happy or slightly anxious on reading this. I've had RRMS for 30 plus years and until the very bad last relapse earlier this year have always had a quick recovery. I'm now on a 'highly effective' DMT and mostly recovered from this relapse in 4 months. By no means completely and now coming up to 6 months after the relapse ended, I fear I may be stuck with with some remaining problems, albeit quite mild apparently (though cognitive and painful sensory deficits combined with fatigue doesn't feel mild to me).I do all I can in terms of diet and exercise (I'm now interval sprinting again after really bad central balance problems that meant I couldn't walk much) and keeping my brain active but in the back of my mind, I really worry that I'm on 'borrowed time'.

  2. what about length of relapse or what people call not significant events? Ie vague tingling numbnes or pain? Where do these classify

  3. These are probably associated with MRI activity remember there are often more than ten lesional events on brain mri for every relapse each lesion doing that little bit of damage so NEDA is the way.Is this a stuck record and are we preaching to the converted…..however for some the idea needs to be punched in and i think many of them we call neuros.

    1. some signs are also the consequence of damage that arise during recovery when nerve finction returns

    2. some signs are also the consequence of damage that arise during recovery when nerve finction returns

    3. If there is inflammation around you can get conduction block of the nerve so you don't transmit signals…this may mean you dont feel anything but then the inflammation subsides and starts to transmit but this could be a nerve trasmitting pain, pins and needles or it could cause muscle stiffness for example

    4. I was also told this about the ten lesions to One eventWhat if there is nothing on mri but many issues symptom wise? Where does this leave someone with partial intermittent recovery?Would this suggest ppms due to lower lesion loadOr lesions not large enough to see

  4. These are probably associated with MRI activity remember there are often more than ten lesional events on brain mri for every relapse each lesion doing that little bit of damage so NEDA is the way.Is this a stuck record and are we preaching to the converted…..however for some the idea needs to be punched in and i think many of them we call neuros.

  5. Prof G – what are exactly the unlicensed drugs you're talking about that can still be used by MSers in poorer countries? Simvastatin? What else?I'm asking cos I am thing about going back to a poor country where I was born due to dire financial situation here in the west where I can barely afford housing etc. due to my MS. But the problem is that once I go back there won't be any meds for MS except maybe cortisone.So what else could I take when expensive meds are not an option?

    1. Re: "…unlicensed drugs…"Please send essential off-label drug list on the top left of the web version of the blog:MethotrexateAzathioprineMitoxantroneCladribineCyclophosphamideRituximabLeflunomide

    2. thanks G but they still seem expensive.are there any other off-label drugs like simva, or vit D or something. I don't think I can get rituximab cheaply – I could get some beta blockers or epilepsy drugs but cladribine??

  6. My neuro has told me that to be eligible for a DMT you need to have 2 clear relapses within a 2 year period. I have had 3, 2008, 2011 and 2014. I am told I need to have 2 within an exact 2 year period. My only medication is vitamin D which I buy myself. I have printed posts like this off before to discuss with my neuro but he says it is all about weighing the risks up between relapses versus problems/side effects from the DMDs. I feel after reading this I want a DMD – maybe it is time I see new neuro.

    1. "I feel after reading this I want a DMD – maybe it is time I see new neuro."That is of course an option, sounds like the one you have is a fingers crossed and hope for the best merchant, which I don't think is acceptable any more IMO.

    2. Dear anon, I feel for you, that is truly alarming that your neuro says this. I'm so fed up hearing about "touchie-feely" neurologists giving this kind of advice. Really it's all well and good to be speaking of weighing up risks when it's not your health at stake. If you can switch neurologists to one that advocates DMTs. I'm assuming you are in the UK so see if your GP can help with this, if necessary find the funds to see a neurologist privately ( not sure these days but years ago, you didn't need to go through your GP for this, though better if you can) for an initial consultation (not exactly difficult to find a neuro with private and NHS lists but really research to find a good one) then switch back to the NHS, if it isn't something you can afford long term.

    3. "My neuro has told me that to be eligible for a DMT you need to have 2 clear relapses within a 2 year period."I guess it all has to be brought into context. What did these relapses consist of? If the we're for example a weird tingling sensation that lasted a few weeks and there is no other supporting evidence that these are MS related, I think your neuro might be giving you good advice.If you have been diagnosed with MS and your doc won't prescribe a DMD, you need to find a new doctor.If you listen to Team G you should be put on Lemtrada immediately. The reality is you need a detailed analysis by a trained neurologist who specializes in MS.

    4. "If you listen to Team G you should be put on Lemtrada immediately."Not true but it's essential to have as many options as possible plus all the information to make an informed choice.

    5. Wow, your neurologist should honestly have their license revoked. You should be on a DMT ASAP if you don't want to end up with serious disability. Please look at all the posts on this blog for a million reasons why this is important.A neurologist is a (hopefully) expert advisor to guide your decision making, but in the end, it's your body and brain that is at risk. The side effect of doing nothing is almost certain dementia and brain damage; the side effects of most DMT's are minor issues or a tiny probability of a serious side effect like PML.My neurologist when I first got diagnosed told me to take 6 months to "deal" with it, and then we could talk about possibly trying a weak dinosaur DMT like Copaxone. I did some research, said f–k that, and asked to get on Tecfidera immediately. She acted like I was playing Russian roulette, so I switched neurologists and never looked back.It was probably the best decision I ever made — two years later, I have zero side effects AND zero progression.

  7. Prof G – What about leg stiffness/numbness as a symptom? What kind of lesions may be responsible for that? A big one or a smaller one? The same question but as applied to dizziness/vertigo – by what is it caused?

  8. After regularly reading your blog, I can't imagine a case where a less effective drug is a good choice. I'm NEDA on glaterimer, but I still don't want that next lesion or attack. Like the poster above, however, my neuro thinks those highly effective drugs are simply too dangerous for me.

  9. Thank you for raising more awareness of this. As the first anon post says, more neurologists should read and understand this. The scenario you describe is exactly what I've always had -very little recovery from relapses and lots of disability. I also have a progressive component going on at the same time. And spinal, cerebellum and brain stem lesions! My first ms neurologist was all at sea with it, but luckily I now have a neurologist who was able to identify this scenario quickly. I would want everyone with the same set of presenting symptoms as me to receive the correct diagnosis as soon as possible.

    1. Dear AlisandeI can not comment as I am not a Neurologist and whilst I appreciate you want answers, I am not sure we can give specific advice on individual cases as we cannot give consultations. Furthermore, our neurologists are on holiday and may or may not have access to the internet and then I cannot say they will respond. If you get no response you can try again in a couple of weeks

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