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Thread: Spinal Cord Injury Site "Scar Tissue"

  1. #71
    Quote Originally Posted by Geoman View Post
    Wise, appoligies for crossing over forums, but I just had a query regarding the reduced pain following untethering surgery in your response above. Firstly, I assume you're referring to neuropathic (central) pain. I'm a T10 complete from a trauma 6 year ago and suffer pretty bad NP. I've tried all of the typical medications and the only relief I'm getting at the moment is Fentynal patches. I while ago I had an MRI for a trial stimulator implant (which was unsuccessful), and the MRI showed a small cavity which at first was thought to be a syrinx, but my original surgeon reviewed it and convinced me it that the cavity was present immediately following my injury. My question is, if the MRI doesn't necessarily detect tethering, is there anything we can do to determine if the untethering procedure is likely to help with NP apart from the trial and error of surgery itself.

    Thanks,
    Clayton
    Clayton,

    Dr. Yansheng Liu probably has more experience operating on chronic spinal cord injury than anybody I know. He says that every case is different and he tells his patients that he cannot predict which cases will improve. The goal of his surgery is to relieve all constrictions, remove adhesions between the spinal cord and surrounding tissues, and restore cerebrospinal fluid flow. Thankfully, none of his patients have gotten worse from the surgery.

    Dr. Liu and Dr. Zhu have agreed to organize all the untethering cases that their team has done over the years and I have agreed to help them write it up. We will try to do this as soon as possible. We also discussed the control group in the phase III study and agreed that it should consist of untethering surgery without injection of cells into the spinal cord. This is only possible if we have evidence that the surgery alone has some benefit.

    When the MRI shows a constriction or compression of the spinal cord, that usually means tethering. Normally, there should be cerebrospinal fluid all around the spinal cord. If the spinal cord is not constricted or compressed but still consistently touching one side, this suggests tethering. Ever since they found that opening up the dura of subacute spinal cord injury cases improves recovery in patients classified as ASIA A, they have been exposing many spinal cords.

    But, in answer to your question, while MRI's can show evidence of tethering, it sometimes does not show anything suspicious and then surgery reveals tethering or vice versa. There are no guarantees that the untethering will reduce neuropathic pain or will restore function. I don't know what the percentages of recovery are in his series. I guess that when we compile the data, we will find out.

    Wise.,

  2. #72
    Thanks again Wise.

    Clayton
    "Wheelie Wanna Walk!"

  3. #73
    Senior Member alan's Avatar
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    Quote Originally Posted by Wise Young View Post
    Alan,

    I just came back from China and have been reviewing data from the Kunming group. Over the years, they have done over 300 untethering surgeries of the spinal cord and I hope that we can get that study published. What you describe sounds very much like tethering of the spinal cord. I also know from having observed cases of chronic spinal cord injury that MRI's often cannot show tethering. They have one case of a woman who had a very severe spinal cord injury and nothing improved her recovery for two years until they did an untethering surgery. Now, her pain is mostly gone and she is recovering motor function.

    Wise.
    You've written before that tethering is often not visible on MRI, and I said that to the doctor when I saw him, but he still was against surgery.
    Alan

    Proofread carefully to see if you any words out.

  4. #74
    Dr. Young, when you have time, could you describe what a glial scar looks like in an injured spinal cord of a human. Is it a thin membrane? Clear, opaic, brown? Is it thick and hard like the scar on skin? Does it completely surround the spinal cord? Can it be cut/sliced and then unwrapped by a surgeon? Could the scar be weakened and thined out by using some sort of abrasive (thinking of something like sandpaper)?

    Maybe Jerry Silver could comment on these same questions in relationship to the mice/rats spinal cords that have been seen his lab. Jerry did mention that the glial scar does get smaller (thinner?) as the years go by for chronic SCI.

    Bless you both for your lifetimes of hard work and sacrifices to help SCI's eventually get out of these chairs and recover function.
    Last edited by 6 Shooter; 01-18-2013 at 04:17 PM.

  5. #75
    Quote Originally Posted by alan View Post
    You've written before that tethering is often not visible on MRI, and I said that to the doctor when I saw him, but he still was against surgery.
    Alan, I know. Neurosurgeons are conservative. I am not sure why but I think that very few of them have exposed a chronically injured spinal cord and, if they do, it must be for a good reason. Otherwise, if a patient gets worse after surgery, he will be blamed for doing an unnecessary surgery.

    Wise.

  6. #76
    Quote Originally Posted by 6 Shooter View Post
    Dr. Young, when you have time, could you describe what a glial scar looks like in an injured spinal cord of a human. Is it a thin membrane? Clear, opaic, brown? Is it thick and hard like the scar on skin? Does it completely surround the spinal cord? Can it be cut/sliced and then unwrapped by a surgeon? Could the scar be weakened and thined out by using some sort of abrasive (thinking of something like sandpaper)?

    Maybe Jerry Silver could comment on these same questions in relationship to the mice/rats spinal cords that have been seen his lab. Jerry did mention that the glial scar does get smaller (thinner?) as the years go by for chronic SCI.

    Bless you both for your lifetimes of hard work and sacrifices to help SCI's eventually get out of these chairs and recover function.
    6 Shooter,

    Very few people have seen a "glial scar" in human. Richard Bunge probably looked at more chronically injured human spinal cords than any other scientist before he died. I remember looking at some of the spinal cords once when I visited him at the Miami Project. I remember seeing a lot of macrophages in a spinal cord of a woman who died more than 20 years after injury. He also showed me axons with bulbous terminals at the injury edge, suggesting that the axons are still trying to grow and are showing signs of what Jerry Silver has called "frustrated axons". There were glial cells around and within the lesion site.

    I have looked at many (hundreds) of contused rat spinal cords. In almost all of the spinal cords (6-14 weeks after contusion), gliosis (increased GFAP staining) around the injury site and a loose matrix of GFAP positive cells within the injury site. If a true cavity were present (usually lined with ependymal cells) at the injury site, there is usually a astrocytic lining at the borders of the cavity. However, these are relatively rare. We see them only in 20% or so of the spinal cords and there is almost always a rim of white matter around the cavity through which axons should be able to grow.

    In very severely injured human spinal cords, there may be little tissue left at the injury site. Usually, these spinal cords have been crushed and have not been decompressed for long periods. The injury site is severely atrophied and much scar tissue outside of the spinal cord constrict the cord. In these cases, if the "scar" constricting the spinal cord is removed, the spinal cord expands. Scar outside of the spinal cord may tether the cord. These are usually wispy and barely visible at surgery, easily removed by just sweeping the surface of the cord with an instrument or even cotton swab.

    I have seen the histology of the injury site from human spinal cords shown by Carlos Lima at a meeting Vancouver about a decade ago. He and his colleagues had cut out the injury site and did histology on the tissue that they removed. He showed pictures of tissue that had thousands of silver-stained axons in the sections. That really shocked me. I don't remember seeing any GFAP stained section and did not see anything that looks like a glial scar/barrier.

    In my opinion, there is simply not enough evidence from human spinal cords that would justify the surgical of "glial scar" inside the spinal cord. Yes, there is evidence of gliosis but many studies have already shown that gliosis alone does not present physical barrier to axon growth. More important, I am not sure that the surgery to remove the "glial scar" would actually result in formation of a true glial scar, i.e. meningeal fibroblasts invading into the cut site and astrocytes walling off these fibroblasts.

    The presence of terminal axonal bulbs at the injury edges, seen by Richard Bunge and colleagues at the Miami project, does suggest that CSPG is present and the axons are stopping their growth and forming the terminal bulbs. This justifies, for example, the use of chondroitinase or CSPG receptor blocker, to see such treatments would facilitate axon growth. But, I have not seen evidence of a physical glial scar that would warrant surgical removal of the injury site.

    There are some who says that since axons are not growing across the injury site, why not just remove the injury site and put something more conducive to axon growth at the injury site. While they usually use the excuse of "glial scar" to say that lesion site should be removed, what they really want is to show that their biomaterial is better than the injury site for supporting axon growth. Since the Kunming group showed that intradural decompression improves locomotor recovery in patients with subacute spinal cord injury, we have been thinking that the cavity left behind after removing necrotic tissue would be an excellent place to put biomaterial.

    I recently heard the presentation of a scientist who believes wants to put a biomaterial into the spinal cord. We have been evaluating different biomaterials that can be put into the cavity of subacute injured spinal cord. These include the self-assembling peptide (SAP), different hydrogels, and other materials that may contain growth factors. In the coming year, we are hoping to initiate a multicenter phase III trial to confirm that subdural decompression and intensive locomotor training restore locomotor function in patients with ASIA A complete spinal cord injuries. I am hoping that we can then initiate trials of various biomaterials placed into the cavity.

    Wise.

  7. #77
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    Wise are u also testing these biomaterials in lumbosacral models?

  8. #78
    Quote Originally Posted by Jawaid View Post
    Wise are u also testing these biomaterials in lumbosacral models?
    No. Our goal is to replace motoneurons in the lumbosacral spinal cord. Wise.

  9. #79
    Jack, I moved your post to http://sci.rutgers.edu/forum/showthread.php?t=214227 for further discussion. Wise.

  10. #80
    Senior Member alan's Avatar
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    Quote Originally Posted by Wise Young View Post
    Alan, I know. Neurosurgeons are conservative. I am not sure why but I think that very few of them have exposed a chronically injured spinal cord and, if they do, it must be for a good reason. Otherwise, if a patient gets worse after surgery, he will be blamed for doing an unnecessary surgery.

    Wise.
    Yes, that does happen.

    Of course, if Dr.Long's diagnosis of ongoing scar tissue growth between my two little, stable syrinxes is correct, untethering wouldn't collapse that, anyway. It appears that the word for me here is "screwed."
    Alan

    Proofread carefully to see if you any words out.

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