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Thread: ?nurse or wise

  1. #1
    Senior Member jb's Avatar
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    Jan 2002

    ?nurse or wise

    if macrophages and microglia "eat away" debris, then why aren't glial scars and syrinx eaten?

  2. #2
    Your question is interesting. The obvious answer is that macrophages don't "eat" living glial cells and cannot "drink" the fluid in a syringomyelic cyst. But I suspect that there is a deeper underlying question that you are asking, i.e. Why is it that the spinal cord cannot repair itself? This question has a misleading presupposition, that the spinal cord cannot repair itself. I think that much evidence suggest that the injured spinal cord does repair itself and is actually does a very good job. Let me summarize this evidence.

    Recovery is the rule and not the exception in spinal cord injury. Of the million of so people who sustain spinal cord injury every year in the United States, probably 99% recover almost completely. Wait, you are probably saying, there are not a million spinal cord injuries in the United States every year. Indeed, surveys of hospital admissions suggest that only about 10,000 people get spinal cord injury every year in the United States. But there are over a million incidents of whiplash injury or cervical injury leading to transient neurological loss and pain, "stingers" where athletes suffer temporary paralysis and recover, and many cases of trauma to the spinal cord without permanent neurological deficits. The assumption is that none of these injuries cause significant damage to the spinal cord and therefore people recover. Of course, we will never really know because few of these people die shortly afterwards and we do not have an opportunity to examine their spinal cords.

    Laboratory studies indicate that animals have the ability to recover substantially from devastating injuries to the spinal cord. For example, if the spinal cord were hemisected (i.e. half of the spinal cord is cut, on one side), rats will recover virtually normal walking within 10 days. In fact, you can cut as much as 80-90% of the spinal cord, the remaining 10% can support substantial function, including locomotion. In the late 1970's, when scientists observed that rats can recover walking after 90% of their spinal cord was cut, they proposed the "string test": a string is passed underneath the cord and pulled up to ensure that the spinal cord is completely cut. So, it is clear that the spinal cord possesses remarkable abilities to recovery from severe damage.

    Humans have a remarkable ability to recover from spinal cord injury, too. I (and most neurosurgeons) have seen people walk out of the hospital with tumors or injuries that have damaged 80-90% of their spinal cord. A majority of people who have severe spinal cord injury, i.e. coming into hospital with nearly complete loss of voluntary movement and sensation below the injury site, will recover substantial function over several years after the injury. At the present, over 65% of people admitted to hospital with the diagnosis of spinal cord injury have so-called incomplete spinal cord injury (ASIA classification B, C, or D). Most of these people will recover substantial function. Many recover walking. There are many "walking quads".

    Our NASCIS clinical trial which studied the effects of methylprednisolone on recovery after spinal cord injury showed that a person with "incomplete" spinal cord injury that had not been treated with methylprednisolone (MP) will recover an average of 59% of the motor function absent at the time of admission. If they received MP within 8 hours, they recovered on average 75% of what they had lost. People with so-called "complete" spinal cord injuries recover only 8% of the motor function that they had lost, compared to about 21% if they received MP. The recent GM1 clinical trial that was reported in 1999, 17% of patients who were ASIA A on admission and received methylprednisolone recovered enough function to be classified ASIA C by one year. As many people know, even people like Christopher Reeve who has been documented to be a C3 "complete" injury and had minimal or no motor or sensory function below his injury level for the first year after injury has recovered sensation over 3/4 of his body and some voluntary movement of his left index finger and ability to lift his legs voluntarily in a swimming pool. Most of this recovery did not occur until 3-5 years after his injury and he is probably going to continue to recover.

    Recent studies suggest strongly that a syringomyelic cyst develops in the injured spinal cord because cerebrospinal fluid flow has been obstructed in some way. Several clinical trials have shown that decompressing, removal of adhesions between the spinal cord and the arachnoid/dura, and untethering of the spinal cord alone will result in the collapse and disappearance of the cyst in as many as 80% of the patients. Dr. Henry Bohlman from Case Western Reserve University has reported large series of cases (of hundreds of patients) where decompression of compressed spinal cords years after injury can result in the return of substantial motor and sensory function, particularly if the patient has some motor or sensory function below the injury site. This is only true if the person has compression, adhesions, or tethering of the cord. Also, recovery is rare common in people who have "complete" spinal cord injury and have had compression of the cord for more than 3 years.

    One might conclude from the above that decompression of the "complete" spinal cord injury more than three years after injury is ineffective. However, I want to remind people that these results were from cases that were operated on before 1998, before we knew about "learned non-use" and the remarkable effect of weight-supported ambulation training in people with spinal cord injury. Apparently, unused neural circuits in the brain and spinal cord turn themselves off and can be turned back on with intensive training. Anton Wernig and others have reported that 25-75% of people who have never walked after spinal cord injury can significantly improve their locomotion through intensive locomotor training. It is possible that decompression of chronic complete spinal cord injury did not restore function because they did not have intensive training and exercise to reverse "learned non-use".

    An informal poll of our own little community suggests strongly that 60% of people continue to recover motor and sensory function more than one year after injury. Such late recovery may very well be due to spontaneous regeneration. Some recovery in chronic spinal cord injury, however, may well be due to spontaneous regeneration. Even though most scientists still believe the spinal cord cannot regenerate, I think that the evidence for lack of regeneration is very weak for several reasons. First, much of the evidence that the spinal cord cannot regenerate comes from animal studies involving transections of the spinal cord which leave a gap between the two cut ends of the cord. Axons don't like to grow across gaps. Studies of the more realistic contusion model suggest that many axons will grow into the contusion site after injury. Second, it is very difficult to explain the high incidence of late recovery of motor and sensory function in many people with spinal cord injury. We have to engage in all sorts of contorted explanations of why Christopher Reeve is getting movement of his left index finger and ability to move his legs 6 years after injury when the most parsimonious explanation is that he had some spontaneous recovery.

    So, perhaps the more important question to ask is why many people do not recover more function. We should consider several possible reasons. The first is learned non-use. If the circuits in the lower spinal cord have turned off because of non-use, no function will result from spontaneous regeneration. The second is the presence of some obstacle to axonal growth. This includes compression of the cord which causes ischemia of the cord, the presence of a large syringomyelic cyst that reduces the paths for axonal regeneration, or perhaps demyelination or incomplete remyelination of axons at the injury site. The latter may limit recovery in as many as a third of people with spinal cord injury, as evidenced by data showing that as many as a third of people with chronic spinal cord injury show some motor or sensory benefit from 4-aminopyridine, a drug that improves conduction of demyelinated axons. Finally, injuries to their cervical or lumbar spinal cord may have destroyed neurons (gray matter) serving the arms or legs. Incidentally, for such people, regeneration alone may not be sufficient to restore function. Neuronal replacement may be necessary. At the present, the only way to replace neurons is transplantation of cells that can make more neurons. Embryonic stem cells can do that. Some evidence is beginning to suggest that adult stem can also do so.

    In summary, evidence from both animal and human studies indicate that the spinal cord possesses remarkable capabilities to repair itself and restore function. Much of the recovery is probably due to redundancy of spinal tracts that can perform similar function, the plasticity of the spinal cord to adapt to the losses of ascending and descending tracts, and possibly sprouting of axons that survive and pass through the injury site. Some of the recovery, particularly years after injury, may very well be due to spontaneous regeneration. Nevertheless, recovery is limited in many people. This may be due to the presence of compression and the presence of cysts at the injury site, demyelination, or loss of neurons when the injury is in the cervical or lumbosacral cord. The reasons for limited recovery will be different for everybody and our goal must be to develop therapies that can address all the reasons.

  3. #3
    Wow, very well written Wise, I learned a lot from just reading your reply to the post. Thank you. Even though I have been doing intense physical therapy for the last three years and am a t-4 complete and nothing has changed in 22 years, I still refuse to give up.

    "Life is about how you
    respond to not only the
    challenges you're dealt but
    the challenges you seek...If
    you have no goals, no
    mountains to climb, your
    soul dies".~Liz Fordred

  4. #4
    Senior Member
    Join Date
    May 2002
    Thank you Doctor Young. I have a much clearer understanding of my own body. As a walking quad [1976] I continued to improve for years. A botched laminectomy [1980]left me in worse condition, further paralyses left side. I had intense physio and spent countless hours in a heated pool recovering a lot of movement.


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