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Thread: Dr. Young: Demyelination Question

  1. #1

    Question Dr. Young: Demyelination Question

    I am very confused about a "which comes first, the chicken or the egg?" issue regarding demyelination and inflammation in SCI (whether traumatic and non-traumatic), specifically in relation to the matter of cures or correctives.

    I have long thought that demyelination is a result of inflammation of the myelin sheath, but I attended a talk recently in which a SCI researcher (Timothy Vollmer, MD) stated that demyelination actually precedes inflammation; that inflammation is the body's secondary response to a primary demyelinating process. Dr. Vollmer's work involves looking for underlying causes of demyelination, since we already understand the role of inflammation; he asserts that cures can only be effected when we arrive at more basic understandings of the relationship between demyelination and inflammation.

    This would make sense, except that if he is correct, I don't understand how it is possible to discern inflammatory diseases (such as MS) from demyelination associated with processes which do not involve disease (e.g., cervical spondylotic myelopathy, the topic of a recent thread in the Care forum).

    I can see how a feedback loop would be inaugurated, whereby demyelination leads to inflammation, which leads to demyelination, which leads to inflammation, and so on - but how is it that demylinating plaques (which I understand to be the end results of inflammation) can be seen on MRI of patients with MS, for example, yet demyelinating processes unrelated to disease (such as CSM) can go undetected on imaging exams?

    Thank you so much for any light you can shed.
    Last edited by Bonnette; 03-18-2011 at 10:13 PM.

  2. #2
    Quote Originally Posted by Bonnette View Post
    I am very confused about a "which comes first, the chicken or the egg?" issue regarding demyelination and inflammation in SCI (whether traumatic and non-traumatic), specifically in relation to the matter of cures or correctives.

    I have long thought that demyelination is a result of inflammation of the myelin sheath, but I attended a talk recently in which a SCI researcher (Timothy Vollmer, MD) stated that demyelination actually precedes inflammation; that inflammation is the body's secondary response to a primary demyelinating process. Dr. Vollmer's work involves looking for underlying causes of demyelination, since we already understand the role of inflammation; he asserts that cures can only be effected when we arrive at more basic understandings of the relationship between demyelination and inflammation.

    This would make sense, except that if he is correct, I don't understand how it is possible to discern inflammatory diseases (such as MS) from demyelination associated with processes which do not involve disease (e.g., cervical spondylotic myelopathy, the topic of a recent thread in the Care forum).

    I can see how a feedback loop would be inaugurated, whereby demyelination leads to inflammation, which leads to demyelination, which leads to inflammation, and so on - but how is it that demylinating plaques (which I understand to be the end results of inflammation) can be seen on MRI of patients with MS, for example, yet demyelinating processes unrelated to disease (such as CSM) can go undetected on imaging exams?

    Thank you so much for any light you can shed.
    Bonnette,

    You are not the only one who is confused. Many scientists and doctors are also confused about the relationship between demyelination and inflammation. So, let us start with what we know and see if we can proceed from knowledge to explain observed phenomena. What we know from many observations in animals and humans are:

    1. Inflammation can cause demyelination. For example, if you inject pro-inflammatory cytokines into the spinal cord of an animals, you can cause demyelination in normal spinal cords.

    2. Demyelination causes inflammation. Myelin breaking down will attract inflammatory cells. These cells include macrophages that cluster around the injury site and form the so-called "plaques".

    3. Compression of the spinal cord causes demyelination. Chronic compression of the spinal cord, i.e. like that associated with cervical spondylotic myelopathy (CSM), causes demyelination.

    The mechanisms by which chronic cord compression causes demyelination are not clear but one possibility is that the compression causes ischemia (loss of blood flow). Ischemic damage to oligodendroglial cells (the cells that myelinate white matter in the spinal cord) causes demyelination. The breakdown products of demyelination attracts macrophages and other inflammatory cells.

    I hope that the above helps.

    Wise.

  3. #3
    Senior Member marycsm77's Avatar
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    Quote Originally Posted by Wise Young View Post
    Bonnette,

    You are not the only one who is confused. Many scientists and doctors are also confused about the relationship between demyelination and inflammation. So, let us start with what we know and see if we can proceed from knowledge to explain observed phenomena. What we know from many observations in animals and humans are:

    1. Inflammation can cause demyelination. For example, if you inject pro-inflammatory cytokines into the spinal cord of an animals, you can cause demyelination in normal spinal cords.

    2. Demyelination causes inflammation. Myelin breaking down will attract inflammatory cells. These cells include macrophages that cluster around the injury site and form the so-called "plaques".

    3. Compression of the spinal cord causes demyelination. Chronic compression of the spinal cord, i.e. like that associated with cervical spondylotic myelopathy (CSM), causes demyelination.

    The mechanisms by which chronic cord compression causes demyelination are not clear but one possibility is that the compression causes ischemia (loss of blood flow). Ischemic damage to oligodendroglial cells (the cells that myelinate white matter in the spinal cord) causes demyelination. The breakdown products of demyelination attracts macrophages and other inflammatory cells.

    I hope that the above helps.

    Wise.
    Dr. Wise,

    If demyelination can show up as plaques on imaging in MS, does demyelination from CSM also show up on imaging? I ask this as a sort of follow up to a question in Care forum that you addressed. I have endurance problems I believe assoiciated with CSM and you had stated that people with CSM often have demyelination. So I am wondering does it show up on imaging? If not, how does one know if they have demyelination?

    Also, does demyelination continue with CSM even if the cord was decompressed?

    thanks
    mary

  4. #4
    marycsm, great questions. I had an inflammation of the spinal cord that attacked myelin at differnt sectins of the spianl cord. I then devoped "tm". I know that groups like the The Myelin Repair Foundation are working on restoring myelin. they 've continually said that progress in being made in their research and that by 2014, they might have a drug or therapy to restore myelin. Hopefully any discovery that restores myelin will help a whole host of conditions.

    keeping on

  5. #5
    Quote Originally Posted by marycsm77 View Post
    Dr. Wise,

    If demyelination can show up as plaques on imaging in MS, does demyelination from CSM also show up on imaging? I ask this as a sort of follow up to a question in Care forum that you addressed. I have endurance problems I believe assoiciated with CSM and you had stated that people with CSM often have demyelination. So I am wondering does it show up on imaging? If not, how does one know if they have demyelination?

    Also, does demyelination continue with CSM even if the cord was decompressed?

    thanks
    mary
    Mary,

    People with cervical spondylosis generally do not show plaques. Plaques are supposed to be relatively unique for multiple sclerosis and related immune-mediated demyelinating diseases.

    Because white matter is mostly membrane or fat, white matter produce less MRI signal than gray matter or water. MRI signals derives mostly from H2O (water). When demyelination occurs from compression, MRI signals increase. Note that MRI signals also increase with edema, gliosis, and inflammation. To enhance these signals, radiologists use what are called T2-weighted MRI to detect what they call "myelopathy".

    There have been several reports of cervical spondylosis associated with multiple sclerosis plaques (Source) but I think that these are more coincidental than causative in one direction or the other. In any case, when myelopathy is associated with cord compression, whether or not multiple sclerosis plaques are present, decompression often improve function.

    Wise.

  6. #6
    Senior Member marycsm77's Avatar
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    Quote Originally Posted by Wise Young View Post
    Mary,

    People with cervical spondylosis generally do not show plaques. Plaques are supposed to be relatively unique for multiple sclerosis and related immune-mediated demyelinating diseases.

    Because white matter is mostly membrane or fat, white matter produce less MRI signal than gray matter or water. MRI signals derives mostly from H2O (water). When demyelination occurs from compression, MRI signals increase. Note that MRI signals also increase with edema, gliosis, and inflammation. To enhance these signals, radiologists use what are called T2-weighted MRI to detect what they call "myelopathy".

    There have been several reports of cervical spondylosis associated with multiple sclerosis plaques (Source) but I think that these are more coincidental than causative in one direction or the other. In any case, when myelopathy is associated with cord compression, whether or not multiple sclerosis plaques are present, decompression often improve function.

    Wise.
    Thanks a lot Dr. Wise. It's weird as i was dx with spondylosis with myelopathy and had my cord decompressed, I continue with gait and endurance problems EVEN THOUGH the pre-surg. MRI doesn't state anything about signal change in the cord, so i was assuming there wasn't. I know the signal change supposedly predicts permanent damage. And although my MRI doesnt state signal changes in the cord, I STILL have deficits, difficulty walking, endurance problems, although somewhat improved since surgery, but nowhere even close to normal, after 14 months post-op.

    thanks again
    mary
    Last edited by marycsm77; 03-21-2011 at 04:12 PM.

  7. #7
    Dr. Young, thank you for this detailed and very helpful information. Clearly, this is a complicated field of investigation - much appreciation for helping us to understand what is involved.

  8. #8
    Senior Member marycsm77's Avatar
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    Quote Originally Posted by Wise Young View Post
    Mary,

    People with cervical spondylosis generally do not show plaques. Plaques are supposed to be relatively unique for multiple sclerosis and related immune-mediated demyelinating diseases.

    Because white matter is mostly membrane or fat, white matter produce less MRI signal than gray matter or water. MRI signals derives mostly from H2O (water). When demyelination occurs from compression, MRI signals increase. Note that MRI signals also increase with edema, gliosis, and inflammation. To enhance these signals, radiologists use what are called T2-weighted MRI to detect what they call "myelopathy".

    There have been several reports of cervical spondylosis associated with multiple sclerosis plaques (Source) but I think that these are more coincidental than causative in one direction or the other. In any case, when myelopathy is associated with cord compression, whether or not multiple sclerosis plaques are present, decompression often improve function.

    Wise.
    Dr. Wise,

    My last question to you about this, thankyou. I have been researching CSM for two years and very difficult to understand after decompression why I still have difficulty walking, limp, endurance. So after all you said about signal changes on MRI:

    Since on my MRI's I clearly had cord compression, however NO increased signal changes were noted. Is is POSSIBLE to still have damage such as I describe above without having signal change? I had signs and symptoms of frank myelopathy for 1 year prior to sugery, and this is only when I became symptomatic. I have no idea how long it went on before signs and symptoms manifested to the point of very bad motor impairment, mostly lower extremities. I guess it is possible, as I am living proof. Just would like to confirm it.


    You see i would like to try the 4AP if i can get it prescribed but under the circumstances don't know if I can.

    Thank you again so much for your time. I think the answer will finally clarify for me what I have been trying to find out for so long.

    thanks again dr. wise.

    mary
    Last edited by marycsm77; 03-21-2011 at 11:47 PM.

  9. #9
    Quote Originally Posted by marycsm77 View Post
    Dr. Wise,

    My last question to you about this, thankyou. I have been researching CSM for two years and very difficult to understand after decompression why I still have difficulty walking, limp, endurance. So after all you said about signal changes on MRI:

    Since on my MRI's I clearly had cord compression, however NO increased signal changes were noted. Is is POSSIBLE to still have damage such as I describe above without having signal change? I had signs and symptoms of frank myelopathy for 1 year prior to sugery, and this is only when I became symptomatic. I have no idea how long it went on before signs and symptoms manifested to the point of very bad motor impairment, mostly lower extremities. I guess it is possible, as I am living proof. Just would like to confirm it.


    You see i would like to try the 4AP if i can get it prescribed but under the circumstances don't know if I can.

    Thank you again so much for your time. I think the answer will finally clarify for me what I have been trying to find out for so long.

    thanks again dr. wise.

    mary
    Mary,

    MRIs only provide limited information about the spinal cord. Because magnetic resonance primarily reflect water content in the spinal cord (i.e. increased water causes increased signal), it is quite good at detecting edema (which is associated with increased water) and demyelination (which is also associated with increased water). Therefore, MRI's tend to show the injury site or demyelinated white matter (often called myelopathy). Places where inflammatory cells infiltrate into the white matter are also easily seen because inflammatory cells have more water content than white matter (which have mostly fatty myelin with low water content).

    In your particular case, compression can damage axons or myelin. You may have lost axons as well as myelin, accounting for your symptoms. The initial increased MRI signals from your spinal cord will subside (i.e. the edema goes away). There may be partial or incomplete remyelination. The spinal cord undergoes atrophy or shrinkage. Several years after decompression, the spinal cord may return to having normal signal levels, albeit 10-20% smaller. So, it is possible to have a relatively "normal" looking spinal cord and have neurological symptoms.

    Wise.

  10. #10
    Senior Member marycsm77's Avatar
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    Quote Originally Posted by Wise Young View Post
    Mary,

    MRIs only provide limited information about the spinal cord. Because magnetic resonance primarily reflect water content in the spinal cord (i.e. increased water causes increased signal), it is quite good at detecting edema (which is associated with increased water) and demyelination (which is also associated with increased water). Therefore, MRI's tend to show the injury site or demyelinated white matter (often called myelopathy). Places where inflammatory cells infiltrate into the white matter are also easily seen because inflammatory cells have more water content than white matter (which have mostly fatty myelin with low water content).

    In your particular case, compression can damage axons or myelin. You may have lost axons as well as myelin, accounting for your symptoms. The initial increased MRI signals from your spinal cord will subside (i.e. the edema goes away). There may be partial or incomplete remyelination. The spinal cord undergoes atrophy or shrinkage. Several years after decompression, the spinal cord may return to having normal signal levels, albeit 10-20% smaller. So, it is possible to have a relatively "normal" looking spinal cord and have neurological symptoms.

    Wise.
    Dr. Wise,

    i went to see my neurosurgeon this morning for a "check up" and relayed to him your thoughts regarding my situation and of course he agrees.

    I can't thank you enough for answering my questions, you are very kind. I think I could speak for many people when I say how difficult and frustrating it is at times to get answers from one's own physicians but to be able to have a question answered by a world renown neuroscientist such as yourself,in the field of SCI is a real privilege. Much appreciation to you and all you do.

    Mary

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