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Relapses, Remissions and Biomarkers
There is continual discussion and confusion about what constitutes a relapse or a remission. I'm going to try to discuss it a little more thoroughly, but everyone needs to know that the definitons are a little vague on purpose. This is because everyone's disease course is different. Some people or some relapses will slide outside the norm.
If you think about it, in RRMS a person is always either in relapse or remission. The difference is the behavior of the symptoms. Most of the official definitions go something like this:
RELAPSE
A Relapse (or Attack or Flair up) is a sudden appearance of new symptoms OR a definite worsening of old symptoms. It may be a combination of new symptoms and worsening old symptoms. These symptoms come on typically over hours to several days. They occasionally appear quite suddenly and may look like a stroke. They may or may not be accompanied by new signs on physical exam indicating a new area of damage in the brain/spinal cord. A relapse "can" include something that is found on physical exam that was not noticed by the patient, like a problems with eye movements, or a newly positive Babinski sign, or reflexes that become pathologically brisk.
A new or worsened symptom must last at least 24 hours. This is where a lot of people become confused. Again there is no hard and fast rule here that I have read. A symptom doesn't have to be continuously present (every minute of the day) but it should be noticed in the same spot several times in that 24 hours.
People with an early and very mild course may be entirely without symptoms at all most of the time. If they become overheated or extremely fatigued they will notice the appearance of symptoms they have had before. If these symptoms last only a day or so, then the sources that I have read would refer to this apearance of symptoms as a "pseudo-exacerbation" or a false relapse. For people with more constant symptoms, I would regard the small variations talked about earlier also as pseudo-exacerbations.
Symptoms (usually paresthesias) that move around and change in location from moment to moment or which are different every day are not characteristic of MS. They are more characteristic of a systemic or metabolic problem with all of the nerves. Remember that, in MS, the symptoms are a result of specific areas of actual damage to the nerve fibers in specific locations. Thus, you would expect to feel the effects of this damage in the "same" spot on the body over and over or constantly.
A relapse must follow a period of symptom stability of at least a month. This period of stability is a remission. If less time has passed since the last "relapse" then the neurologist may consider it part of the earlier relapse which is evoloving over an unusually long time. The relapse cannot immediately follow a course of steroids. This is because some people will improve during steroids only to have their symptoms "rebound" after stopping the steroids.
A relapse may last a very short time. By definition this may be a short as a day. If it is that short, it becomes difficult to be sure unless the symptom is completely new and fairly severe. A relapse may last several days, weeks or even months. In my reading I have seen references to relapses lasting as long as 6 months. Is that the longest? It probably is not, but I don't know how a longer "relapse" would be viewed by the experts.
REMISSION
A remission is a period of at least 30 days during which a person is symptom-free or during which the intensity of the symptoms that they do have is stable. They will not be acquiring new symptoms. The little variations of symptoms that are present (due to heat or fatigue, etc) was discussed above. The 30 days to define a remission cannot count the month or so immediately following a course of steroids. This is vague, because the length of time steroids may calm the inflammation of active demyelination can vary from person to person and from attack to attack.
The Baseline
Many people have a baseline of ongoing symptoms. Sometimes these will be quiet (less severe) for a while, and then there will be days when they are worse. This could be due to fatigue or heat exposure. These variations seem to be a part of a person's baseline. Whether they are called true relapses is up to the interpretation of the doctor or the esperience of the patient. I have not heard any hard and fast discussion of them. It makes most sense to me to think of these as "normal variations" of a person's disease. Over time, the symptoms that a person deals with on an ongoing basis will change as some lesion in the CNS heal and others appear. Thus, a person's "baseline" will evolve over time. This is a gray area that seems to be very individual.
"Defining" a actual Remission
I have found nothing in my reading that encourages doctors in the clinical setting to define a remission by lack of enhancing activity on an MRI or by absence of a "biomarker." All the definitions of remission are based on a person's "clinical" status. Remember, in medicine the term "clinical" refers to the "symptoms" a person has and the "signs" the doctor finds on their physical exam.
The Search for Biomarkers
We desperately need to find a simple test the will confirm the existence of MS and, ideally, tell us when the disease is most active. To date none have been found.
Research studies DO try to define activity and remission using markers of some type, such as MRI imaging or blood tests. BUT, at the present time, there are no good "biomarkers" for MS. A biomarker is usually a specific substance that can be found in the blood (less commonly the urine or CSF) that points reliably to the presence of a disease or the activity of a disease. The search for a reliable biomarker is going on furiously in the research into MS. There are many studies that have focused on one thing or another hoping to establish a reliable biomarker. Currently, even though some studies have claimed to have identified one, the studies done to confirm its reliablility have still not identified any one test as truly useful.
The most common "biomarker" seen in the literature is the "anti-MBP" and the "anti-MOG" antibodies. These are antibodies against Myelin Basic Protein and against Myelin Oligodendrocyte Glycoprotein. There was great excitement about these two antibodies in the early 2000's (2001 to about 2004). BUT, they were felt to be useful in predicting which patients with an incomplete presentation of MS (people with CIS - a Clinically Isolated Syndrome) would ultimately convert to clinically definite MS. HOWEVER, In January, 2007, a study published in the New England Journal of Medicine showed pretty conclusively that these antibodies alone or together was not useful for this prediction of who would progress!
Rena's Situation
Nowhere in my reading have I seen that these antibodies, or any other substance, can be used reliably to "prove" remission (as Rena's "neurologist seems to be claiming). Besides this, no one in the MS literature is encouraging any doctor to try to "establish" remssion based on lab or imaging data. Rena's neuro is creating a "protocol" that is not based on any science that I have come across. I have seen the articles that she seems to be relying on, but she is taking them out of context and is applying their information inappropriately. This is very poor science and, in my mind, not conforming to the "Standard Of Practice" in the field. In my mind, Rena's neuro is close to committing malpractice. I would very much like to see exactly where she is getting her hard-and-fast data and who else in the entire worldwide field of MS research is supportive of the practice of withholding DMD's based on laboratory and MRI results.
Well, that is my rant for today.
Carry on...
Quix
If you think about it, in RRMS a person is always either in relapse or remission. The difference is the behavior of the symptoms. Most of the official definitions go something like this:
RELAPSE
A Relapse (or Attack or Flair up) is a sudden appearance of new symptoms OR a definite worsening of old symptoms. It may be a combination of new symptoms and worsening old symptoms. These symptoms come on typically over hours to several days. They occasionally appear quite suddenly and may look like a stroke. They may or may not be accompanied by new signs on physical exam indicating a new area of damage in the brain/spinal cord. A relapse "can" include something that is found on physical exam that was not noticed by the patient, like a problems with eye movements, or a newly positive Babinski sign, or reflexes that become pathologically brisk.
A new or worsened symptom must last at least 24 hours. This is where a lot of people become confused. Again there is no hard and fast rule here that I have read. A symptom doesn't have to be continuously present (every minute of the day) but it should be noticed in the same spot several times in that 24 hours.
People with an early and very mild course may be entirely without symptoms at all most of the time. If they become overheated or extremely fatigued they will notice the appearance of symptoms they have had before. If these symptoms last only a day or so, then the sources that I have read would refer to this apearance of symptoms as a "pseudo-exacerbation" or a false relapse. For people with more constant symptoms, I would regard the small variations talked about earlier also as pseudo-exacerbations.
Symptoms (usually paresthesias) that move around and change in location from moment to moment or which are different every day are not characteristic of MS. They are more characteristic of a systemic or metabolic problem with all of the nerves. Remember that, in MS, the symptoms are a result of specific areas of actual damage to the nerve fibers in specific locations. Thus, you would expect to feel the effects of this damage in the "same" spot on the body over and over or constantly.
A relapse must follow a period of symptom stability of at least a month. This period of stability is a remission. If less time has passed since the last "relapse" then the neurologist may consider it part of the earlier relapse which is evoloving over an unusually long time. The relapse cannot immediately follow a course of steroids. This is because some people will improve during steroids only to have their symptoms "rebound" after stopping the steroids.
A relapse may last a very short time. By definition this may be a short as a day. If it is that short, it becomes difficult to be sure unless the symptom is completely new and fairly severe. A relapse may last several days, weeks or even months. In my reading I have seen references to relapses lasting as long as 6 months. Is that the longest? It probably is not, but I don't know how a longer "relapse" would be viewed by the experts.
REMISSION
A remission is a period of at least 30 days during which a person is symptom-free or during which the intensity of the symptoms that they do have is stable. They will not be acquiring new symptoms. The little variations of symptoms that are present (due to heat or fatigue, etc) was discussed above. The 30 days to define a remission cannot count the month or so immediately following a course of steroids. This is vague, because the length of time steroids may calm the inflammation of active demyelination can vary from person to person and from attack to attack.
The Baseline
Many people have a baseline of ongoing symptoms. Sometimes these will be quiet (less severe) for a while, and then there will be days when they are worse. This could be due to fatigue or heat exposure. These variations seem to be a part of a person's baseline. Whether they are called true relapses is up to the interpretation of the doctor or the esperience of the patient. I have not heard any hard and fast discussion of them. It makes most sense to me to think of these as "normal variations" of a person's disease. Over time, the symptoms that a person deals with on an ongoing basis will change as some lesion in the CNS heal and others appear. Thus, a person's "baseline" will evolve over time. This is a gray area that seems to be very individual.
"Defining" a actual Remission
I have found nothing in my reading that encourages doctors in the clinical setting to define a remission by lack of enhancing activity on an MRI or by absence of a "biomarker." All the definitions of remission are based on a person's "clinical" status. Remember, in medicine the term "clinical" refers to the "symptoms" a person has and the "signs" the doctor finds on their physical exam.
The Search for Biomarkers
We desperately need to find a simple test the will confirm the existence of MS and, ideally, tell us when the disease is most active. To date none have been found.
Research studies DO try to define activity and remission using markers of some type, such as MRI imaging or blood tests. BUT, at the present time, there are no good "biomarkers" for MS. A biomarker is usually a specific substance that can be found in the blood (less commonly the urine or CSF) that points reliably to the presence of a disease or the activity of a disease. The search for a reliable biomarker is going on furiously in the research into MS. There are many studies that have focused on one thing or another hoping to establish a reliable biomarker. Currently, even though some studies have claimed to have identified one, the studies done to confirm its reliablility have still not identified any one test as truly useful.
The most common "biomarker" seen in the literature is the "anti-MBP" and the "anti-MOG" antibodies. These are antibodies against Myelin Basic Protein and against Myelin Oligodendrocyte Glycoprotein. There was great excitement about these two antibodies in the early 2000's (2001 to about 2004). BUT, they were felt to be useful in predicting which patients with an incomplete presentation of MS (people with CIS - a Clinically Isolated Syndrome) would ultimately convert to clinically definite MS. HOWEVER, In January, 2007, a study published in the New England Journal of Medicine showed pretty conclusively that these antibodies alone or together was not useful for this prediction of who would progress!
Rena's Situation
Nowhere in my reading have I seen that these antibodies, or any other substance, can be used reliably to "prove" remission (as Rena's "neurologist seems to be claiming). Besides this, no one in the MS literature is encouraging any doctor to try to "establish" remssion based on lab or imaging data. Rena's neuro is creating a "protocol" that is not based on any science that I have come across. I have seen the articles that she seems to be relying on, but she is taking them out of context and is applying their information inappropriately. This is very poor science and, in my mind, not conforming to the "Standard Of Practice" in the field. In my mind, Rena's neuro is close to committing malpractice. I would very much like to see exactly where she is getting her hard-and-fast data and who else in the entire worldwide field of MS research is supportive of the practice of withholding DMD's based on laboratory and MRI results.
Well, that is my rant for today.
Carry on...
Quix
Thank you so much for the information Quix. As I have said so many times before, you offer such valuable information. Thanks for taking the time to post your information.
Mike
Mike
The information I've gained from you has been extremely helpful.
Have you ever considered writing a book? You offer so much, as an MD with MS. This unique perspective can only be offered through someone with MS and with a doctorate in medicine.
I wish you would consider. For example, within just a short time today, I've learned several things that I didn't know about from research on the Internet and the books that I've already purchased. I wished I would have known this information about relapses and remissions--it would have saved confusion as to what to be concerned about to make sure it was mentioned to my neuro. I didn't know that the symptoms didn't have to constantly throughout the day.
This is just one thing that I've learned about today!!!!!!!!!! There have been countless other things about LP's, MRI's, medicines . . .
I hope I didn't embarrass you, but I hope you really do consider. There's no reference book I can think of by an MD with MS that has gone through h*** and back to get a diagnosis. The book would be invaluable to people in limbo or with MS.
I'm reposting this response on a seperate thread to get your attention!!!!
Deb
Have you ever considered writing a book? You offer so much, as an MD with MS. This unique perspective can only be offered through someone with MS and with a doctorate in medicine.
I wish you would consider. For example, within just a short time today, I've learned several things that I didn't know about from research on the Internet and the books that I've already purchased. I wished I would have known this information about relapses and remissions--it would have saved confusion as to what to be concerned about to make sure it was mentioned to my neuro. I didn't know that the symptoms didn't have to constantly throughout the day.
This is just one thing that I've learned about today!!!!!!!!!! There have been countless other things about LP's, MRI's, medicines . . .
I hope I didn't embarrass you, but I hope you really do consider. There's no reference book I can think of by an MD with MS that has gone through h*** and back to get a diagnosis. The book would be invaluable to people in limbo or with MS.
I'm reposting this response on a seperate thread to get your attention!!!!
Deb
Thank you Thank you Thank you
I have been trying to puzzle this out and you made it incredibly clear. My neuro is ok but is a man of few words - I have to push for answers. He is gentle and thoughtful in his care, just a poor explainer.
My symptoms are stable since I have four rounds of montly steroids. I'll be curious to see if I am in a period of remission or if things will rebound.
Thanks for this clarification. You rock!
I have been trying to puzzle this out and you made it incredibly clear. My neuro is ok but is a man of few words - I have to push for answers. He is gentle and thoughtful in his care, just a poor explainer.
My symptoms are stable since I have four rounds of montly steroids. I'll be curious to see if I am in a period of remission or if things will rebound.
Thanks for this clarification. You rock!
Hey girl...just wanted to share this with you...it was taken from the Canadian College of Physician's and Surgeons...
“The 2007 NPS confirms that the dire shortage of family physicians and certain other specialists is a significant and ongoing issue for patients in all provinces and territories,” states CMA President, Dr. Brian Day. “Some areas are worse off than others. Health workforce planning must be addressed to improve access to health care for patients no matter where they live.”
It is a chronic problem in our country and at least they realize it but will they actually do something about it...who knows???
Rena
“The 2007 NPS confirms that the dire shortage of family physicians and certain other specialists is a significant and ongoing issue for patients in all provinces and territories,” states CMA President, Dr. Brian Day. “Some areas are worse off than others. Health workforce planning must be addressed to improve access to health care for patients no matter where they live.”
It is a chronic problem in our country and at least they realize it but will they actually do something about it...who knows???
Rena
Bravo! Thanks for the helpful post--it should definitely go on the health pages.
I have been struggling with this topic--reading about it and pestering my neuro. I had pretty much come to the general conclusions you list above, but it's useful to have it all spelled out so systematically and clearly. I feel like I am slowly coming to see that I have had what probably were relapses over time, although I still struggle with seeing remissions (but I do have a few symptoms that definitely have disappeared or were worse for a while and then not so much).
The info about the search for biomarkers is especially interesting because it really highlights the fact that there is no way to have an objective definition of a relapse without one.
I have been struggling with this topic--reading about it and pestering my neuro. I had pretty much come to the general conclusions you list above, but it's useful to have it all spelled out so systematically and clearly. I feel like I am slowly coming to see that I have had what probably were relapses over time, although I still struggle with seeing remissions (but I do have a few symptoms that definitely have disappeared or were worse for a while and then not so much).
The info about the search for biomarkers is especially interesting because it really highlights the fact that there is no way to have an objective definition of a relapse without one.
Hi Hon...yeah, they have basically said that their workload is too heavy now and if they take on someone with MS the workload will be increased so much they won't be able to give me the "care" that I require.
I would imagine that they would refuse anyone if their workload is too heavy now and if they take on anyone with a chronic illness it would be the same as me. I don't think that I am being discriminated on, I think that, like I said, anyone with a chronic illness is an extra load on all the doctors that they can't handle. Believe me, I have thought of this as well but it really has not been put forward in that manner. I appreciate you thinking of me though and I hope that this new doctor will be able to help me.
I would imagine that they would refuse anyone if their workload is too heavy now and if they take on anyone with a chronic illness it would be the same as me. I don't think that I am being discriminated on, I think that, like I said, anyone with a chronic illness is an extra load on all the doctors that they can't handle. Believe me, I have thought of this as well but it really has not been put forward in that manner. I appreciate you thinking of me though and I hope that this new doctor will be able to help me.
Hi Rena, so good to hear you will be meeting a new physician soon. I hope this opens some new doors for you.
Something I am confused about is that you say you aren't sure if this new doctor will consider taking you on because of your diagnosis. In past posts you have talked about GP's refusing to take on new patients specifically with MS. I know there are many GP's not generally not taking new patients because of workloads, but I was not aware that patients with particular illnesses were being refused to be seen by a particular physician because of the patient's dx.
MS is a disability and therefore, is protected under the Alberta human rights act. Medical services are included among those services for which the Act applies.
Have you been blatantly refused the services of a physician BECAUSE of your MS? This sounds like discrimination. The illegal kind.
db1
Something I am confused about is that you say you aren't sure if this new doctor will consider taking you on because of your diagnosis. In past posts you have talked about GP's refusing to take on new patients specifically with MS. I know there are many GP's not generally not taking new patients because of workloads, but I was not aware that patients with particular illnesses were being refused to be seen by a particular physician because of the patient's dx.
MS is a disability and therefore, is protected under the Alberta human rights act. Medical services are included among those services for which the Act applies.
Have you been blatantly refused the services of a physician BECAUSE of your MS? This sounds like discrimination. The illegal kind.
db1
Very interesting post Quix! Thank you! My course has not run any kind of pattern that has clear remissions apparently since the longest one I have experienced since last May has been 2 1/2 weeks.
No wonder the doctors I have seen so far seam so quick to discount MS. This last neuro I have seen had said I am a complicated case, this cycle thing probably only adds to it.
Thanks for all your hard work for trying to keep us all on track and pointed in the right direction!! You are such a Godsend to me!
Kristin
No wonder the doctors I have seen so far seam so quick to discount MS. This last neuro I have seen had said I am a complicated case, this cycle thing probably only adds to it.
Thanks for all your hard work for trying to keep us all on track and pointed in the right direction!! You are such a Godsend to me!
Kristin
I can't argue with you on this one Quix and I appreciate that you don't mind voicing your opinions on my situation.
I have made an appointment with a dr. for my hubby for next Monday night. This is a new dr. and we heard about him from a friend. I asked the receptionist if this dr. might consider seeing someone with an MS diagnosis and she said to come on in and talk to the dr. and he would let me know. So I am going to do that and see what I come up with. I don't by any means want to scare the poor fellow but I dare say one of my first questions will be "if I needed to be referred to a Neurologist, who would you send me to?"
If his answer is the same neuro's I have already seen, you will see me running and screaming in the other direction.
I hope that he will agree to see me...my options are quickly running out and I don't know what I will do if they do!
I will let you know what happens and in the meantime, I think that this discussion would be very useful to add to the outline...I certainly don't want anyone to find themselves in the same predicament as I and this information would be very valuable to all.
Thank you for spending your precious time writing up this information, you are invaluable to us all as usual! :)
Rena
I have made an appointment with a dr. for my hubby for next Monday night. This is a new dr. and we heard about him from a friend. I asked the receptionist if this dr. might consider seeing someone with an MS diagnosis and she said to come on in and talk to the dr. and he would let me know. So I am going to do that and see what I come up with. I don't by any means want to scare the poor fellow but I dare say one of my first questions will be "if I needed to be referred to a Neurologist, who would you send me to?"
If his answer is the same neuro's I have already seen, you will see me running and screaming in the other direction.
I hope that he will agree to see me...my options are quickly running out and I don't know what I will do if they do!
I will let you know what happens and in the meantime, I think that this discussion would be very useful to add to the outline...I certainly don't want anyone to find themselves in the same predicament as I and this information would be very valuable to all.
Thank you for spending your precious time writing up this information, you are invaluable to us all as usual! :)
Rena
Amy, when I wrote this, I didn't have anyone special in mind, certainly not you. I just see people trying to sort out the patterns and had never put all of these statements together in one post before. I'm just throwing this out to see if it helps people.
If people find this discussion useful, then we might consider adding to the outline.
Quix
If people find this discussion useful, then we might consider adding to the outline.
Quix
Thank you for this information. It does seem to be a gray area, open to definitions and the individual interpretation of neuros. Like many here, my own symptoms are now hard to categorize.
A while back I asked my neuro, and he said I may have established a new baseline. Quix's explanation of this is what I had surmised, and it ain't good. However, it also could be worse.
ess
A while back I asked my neuro, and he said I may have established a new baseline. Quix's explanation of this is what I had surmised, and it ain't good. However, it also could be worse.
ess
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