Saturday, 24 March 2012

What is a relapse?

In response to a previous comment.

"This is a very good question and is something neurologists have been grappling with for decades."

What is a relapse?

A relapse is defined as an episode of neurological symptoms that happens at least 30 days after any previous episode began, lasts at least 24 hours and is not attributable to another cause and occurs in the absence of an infection or fever.

In clinical trials the definition is more stringent and has to be accompanied by either new clinical signs, i.e. changes in the neurological examination,  or an increase in the disability (EDSS) score. This is why you may hear the term "protocol defined relapse"; the "protocol" refers to the definition of a relapse that is used in that particular trial. To confuse things two clinical trials may use slightly different definitions of a relapse, which makes it hard to compare results from different trials. 

Can relapses result in the appearance of old symptoms?

Yes. A relapse can result in the appearance of new symptoms, that you have not experienced before, or the recurrence or worsening of symptoms that have occurred in the past. 

"What about intermittent symptoms?"

It is important not to confuse intermittent symptoms from a previous relapse with a new relapse. Intermittent symptoms occur when a damaged nerve pathway recovers, but the recovery is incomplete. The partially recovered nerves then become susceptible to heat and/or fatigue, which results in symptoms coming and going. For example, if you have previously had an episode of loss of vision or pins and needles you may find when you exercise, or get tired, or experience hot weather, your vision blurs or the pins and needles return. In this situation the symptoms usually resolve on rest or cooling and rarely last more than a few hours. This is not a relapse. 

What causes a relapse?

A relapse is caused by an area of inflammation and demyelination (loss of the nerve's insulation) in a particular pathway in the brain an spinal cord. The pathological and MRI correlate of this is the so called MS lesion or MS plaque.

Are there other names for a relapse?

Yes. Relapses are also referred to as attacks, exacerbations, flare-ups, acute episodes or clinical events.


16 comments:

  1. Thanks for this, I’m most grateful.

    There are two reasons for my interest in this topic. Firstly how, and if, I can fit my own ‘RRMS’ experience into these definitions. Secondly how clinical trials define and use this information as a basis for assessing a treatment’s effectiveness.

    For me:
    ‘A relapse is defined as an episode of neurological symptoms that happens at least 30 days after any previous episode began’

    So if a symptom goes away and another one surfaces two weeks later this is classed as a single ‘episode of neurological symptoms’. (If this is true, I’ve learnt something today!). Unfortunately this definition would also mean I spend my life in one continuous ‘neurological episode’…


    For trials:
    ‘(This) is something neurologists have been grappling with for decades’

    I like the honesty of this statement but is a bit disconcerting to find that these trials each use different definitions of a relapse ‘which makes it hard to compare results from different trials’. If treatments cannot be assessed in this way then it’s all apples and oranges again. How can this be ‘good science’?

    I noted recently on the ‘Bad-Science’ thread (14-03-12 - john) that the patients in the FREEDOMS placebo group had less relapses than the group taking beta interferon in the alemtuzumab trail. Is this because of different criteria? Is this because beta interferon is a less effective treatment than we are led to believe? Is there any way of knowing the answer?


    For me again:
    I had a miserable, side-effect ridden 18 months on Rebif and I am trying to find a way to assess the way forward. A large part of this is deciding whether I have ‘relapses’ or intermittent symptoms from a previous relapse which come and go for a few weeks at a time (rather than just a few hours).

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  2. The time periods of 30 days and 24 hours may come from long experience but cannot be justified by something inherent in MS.
    In that way they are arbitrary, always subsequent to revision and unable to hold the weight of a meaningful conclusion.

    Equally arbitrary is the differentiation process between intermittent symptoms and relapses. Why couldn't someone experience two distinct episodes of vertigo consecutively? I wonder if this is the formal way of counting less relapses in the clinical trials.

    And what about the severity of a relapse? Is there a scale to measure it? How can one tell that a feeling is worth being called a symptom? This is crucial as far as fatigue, depression and cognitive problems are concerned.

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  3. Re: "So if a symptom goes away and another one surfaces two weeks later this is classed as a single ‘episode of neurological symptoms’. (If this is true, I’ve learnt something today!). Unfortunately this definition would also mean I spend my life in one continuous ‘neurological episode'"

    We think of these relapses and being polysymptomatic, i.e. due to lesions in different pathways. This is not surprising as it is well know that lesions come in bursts. All this means is that two or more lesions in a particular burst of activity causes symptoms. The majority of lesions detected on MRI do not cause overt symptoms.

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  4. Hi Gavin mouses I understand this is an old thread
    But with regards to a relapse
    What do you make of symptoms as in starting on
    day 1 lhermittes
    Day 10 hand tinhaling
    Day 30 foot tingling
    Day 45 foot burning
    Day 50 muscle aches

    Would this all be one relapse as each symptom has preceded the previous one by less then 30 days?

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    1. Re: "What do you make of symptoms as in starting on day 1 lhermittes, Day 10 hand tinhaling, Day 30 foot tingling, Day 45 foot burning, Day 50 muscle aches."

      All these symptoms could be explained by one expanding lesion in the spinal cord. I would need examine someone like this to see if the signs were consistent with one lesion. If that was the case it would one relapse; i.e. one lesion. If there was any doubt an MRI may be necessary. However, I would only do an MRI if it was going to change the management; for example starting or switching a DMT or to exclude another diagnosis.

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  5. Any answers from you good people

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  6. You boys are all surely able to comment though?

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  7. Hi thanks Gavin
    The neuro exam currently is completely normal and the mri of brain is normal too, it is of course early stages so maybe as you have stated before, it's lucky one of the first lesions have shown up
    They are calling it a CIS at present and doing follow up mri in May
    It took me private referrals to get this as gp said lhermittes has nothing to do with Ms!
    Thanks again for your help

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  8. Sorry to use your extensive knowledge for my own benefit but it genuinely is appreciated
    Am i right in thinking also, because the lhermittes has subsided and the way it has presented, this does not sound like the progressive variant? 30yr old man

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    Replies
    1. I am sorry to say that our neuros can not give personal advice on the blog. I hope you understand.

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  9. Hi mouse
    No problem I didn't realise and appreciate the info already given, thanks and thanks for the blog in general, it's a frightening place right now and having some contact with people on the front line is always appreciated

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    1. I realise this is not what you want to hear and I hope you get useful information. ProfG won't want to appear rude and this is why he has yet to respond. If your GP is not sure if lhermittes can be a problem in MS, then time for your GP to go for a refresher course.

      It sounds like you are now in the hands of an MS specialist they should have the best information to tell you. It may not be MS but it may be and maybe your scan in May could show MS, it may not.
      ProfG at present doesn't do private and unless the NHS starts to do online consultations then we (I'm not a neuro) can't talk about individual issues.If you want to know details please ask generalised questions such that they can be addressed to anyone rather than a personal consultation, as this way it is easier for the neuros to respond..

      If you are considered to be CIS then your neuro is suggesting the issues are due to the same lesion and the fact that your scans are clear is a good thing. Remember that there is a load of rubbish on the internet and try get your infor from reputable sources e.g. MS Socieities and not the media

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  10. Re. 'A relapse is defined as an episode of neurological symptoms that happens at least 30 days after any previous episode began, lasts at least 24 hours and is not attributable to another cause and occurs in the absence of an infection or fever '.

    Hmm I don't know about this. I and other MSers have had very nasty pseudo relapses. Relapse occuring at the same time as infection. This pseudo relapse has caused me lasting damage and new lesions. So for me the line is blurred for a relapse and pseudo relapse. They both cause lasting damage. I'm pretty much on the ball now and do my own UTI tests at home with dipstick test kit, then head on to the GP or GP at the hospital Out of Hours service to get antibiotics if shows infection. But thats view.

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  11. Can someone help me? I was diagnosed last year, and just recently my symptoms have come up again- numbness all over my body. Mri showed it was not a relapse, but one week on and I am still numb?? Is this still a pseudo relapse??

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  12. For how long on average would you expect a cervical lesion to continue to spread? Do they normally spread vertically or horizontally or is it the luck of the draw?

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