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Thread: Study of the effects of "chronic scar" on axonal growth in spinal cord injury

  1. #31
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    Quote Originally Posted by Wise Young
    Given the above comments, you are probably wondering I am not more critical of Spetzler's removal of your AVM nidus. I was involved in and participated in the some of the pioneering studies of interventional neuroradiological treatments of spinal cord AVM's by Alejandro Berenstein at NYU Medical Center in the early 1980's. I have seen many cases of AVM that have been successfully treated with embolization as opposed to surgical removal. However, in the hands of a skillful neurosurgeon, it is possible to remove a superficial AVM without compromising the spinal cord. I believe that surgical removal of an spinal cord AVM is most successful in patients who have a superficial AVM without significant loss of function. However, there are no systematic comparisons of embolization and surgical removal. In your case, you had many embolizations that were apparently ineffective before you opted for surgical removal.

    Wise.
    Thanks a lot Wise. I just quote parts of your answer here. I have read about your work with AVM’s, good job. But, just to make sure there are no misunderstandings here I don’t blame any doctors for my problems, quite the opposite in fact, all of them did put up good efforts to fix my complicated situation with this intramedullary located AVM. You see this whole thing started with me getting worse by more and more loss of motor and sensation etc. Here at home we have a couple of leading European radiologist and they tried to fix my problems. They only managed to glue off one of the major feeding arteries, the other smaller ones they could not do anything with due to risk of navigation and the risk of gluing off parts of necessary arteries for blood supply to the cord. Anyway, the neurosurgery professor that handled my case here did not want to give that easily, he sent papers and films first to Professor Luc Picard in Nancy France but the reply from him was negative. Then the professor here sent the same materials to Professor Pierre Lasjaunias and his team in Paris France. They accepted me and I went there for additional attempts for emolization but when I woke up from anaesthesia they told me they could not do anything due to the same risk as the radiologist here at home told me. The team in France also advised me strongly to not have any surgery to have the nidus removed. Well I got home and the professor here at home was actually a bit surprised they advised me not to have surgery, this in light of I was rapidly getting worse. Luckily the professor here knew Bob Spetzler and the same papers and films were sent to him in Phoenix. He replied just after five days with suggested procedures to remove the nidus and help me. I went to AZ and he also told me they would first try to embolize but if not he would do a laminectomy, open the cord and cut out the nidus and associated feeders and veins. He and Volker Sonntag (another great surgeon) did so. This resulted in that my negative path was curtailed and the negative trend stopped. They managed to remove the entire AVM and I never got worse after this, in fact I believe I got a little bit better a time after but it is hard to determine, but one thing is for sure, they managed to stop the negative trend which sooner or later would have left me complete paralyzed. So thanks to all of them. The fact that I didn’t get any worse after this surgery also to me indicates they did a good job. Due to the report says the cord looks normal now should also indicate I was lucky all in all due to the circumstances. But above that, I remember that Spetzler said to me after the surgery he could see some damage in there. I guess the cord is a very fragile thing and that just small damages to it can result in a lot of problems like BBS, loss of functions and additional pain. Well, again, I consider myself lucky anyway due to the complexity of this AVM and that doctors could get rid of it.

    As for Carlos Lima and his teams procedure I have read some about it and are also very sceptical to this, if not I would have gone there long time ago. I have just posted some news about patients going there here on this website of yours but have never bothered to go into discussions as for this procedure due to the things the procedure involves. To me it seems like they are making an additional SCI and then try to fix the old injury plus this new damage, it does not seem to be a logical way to fix things at all to me.

    Above that I just wanted to ask those above posted questions to you as for my situation as for the scar issues in discussion in this thread. Thanks for explanations. Neither do I believe that the scar will be a big hindrance for me (don't know if it really exist at all) due to the post surgical reports as for me having future therapies but more the problems as to fix things as you highlighted in your bullet items in your answer post above here in this thread… My comments as for “how can future treatments be carried out if we don’t know what to treat” was also more directed to MR and such equipment as for how to for example how to know where to inject cells and biological matter into an injured cord if we can’t decide where the injury is? I expect it will be several injections if the course of future therapies will involve injections are to do multiple injections in and around the expected injury site.
    Last edited by Leif; 10-11-2006 at 11:24 AM.

  2. #32
    Quote Originally Posted by Leif
    Cripply. Since the cord is very complex and consists of several 100 millions of axons and there are probably some 20.000 inter neurons in each vertebral segment and we also know that plasticity occur in the spinal cord why is it so important that axon has to be at the right spot in the 3D configuration of the cord. The cord is built by a variety of neural networks (se image below), could not that result in that some signals could find other ways than originally designed and still work as for future therapies? I think it could.
    I said 3D would be important unless basic science advances enough so that the axon can make the right connections without.
    Random connections result in unwanted recovery. For example, if I touch my hip, I feel it in my foot. Sometimes I want to move my R leg and my L leg moves instead. I am speculating that those examples are the result of connections made in the proximity.

  3. #33
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    Cripply. I understand, but maybe the brain will take care of this x-wiring for future terapies. It happens during stroke in the brain. Other parts learn to speak again. But. sure, more basic research is required as well, but som could be tested in humans now I feel.

  4. #34
    Leif, recovery needs to happen in an acceptable timeframe. If we have to wait for the brain to figure out things we are going to despair. The CNS is notoriously slow to recover. That´s why I think more basic science knowledge is needed to know what makes an axon recognize a target with a very specific function, and be able to direct those connections.

  5. #35
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    Quote Originally Posted by Cripply
    Leif, recovery needs to happen in an acceptable timeframe. If we have to wait for the brain to figure out things we are going to despair. The CNS is notoriously slow to recover. That´s why I think more basic science knowledge is needed to know what makes an axon recognize a target with a very specific function, and be able to direct those connections.
    Thanks Crip’ I agree with some here but what is an acceptable timeframe if we could collect all the know-how right now for instance. Timeframes does not necessarily happen to be true either as such, things can occur in random order, re; the network image above. Above that, one of my concerns regarding fixing a cord is how to get blood supply to the fixed site, this is just me thinking tough, but if a procedure creating new neurons and so on for a grey matter injury will be successful does not this site also need those fine capillaries to supply nutrition’s and the things that goes whit the vascular system. I would think regardless if a person has a bruise, a hemi section or a cut the capillary system will be as important as the biological implants, likewise injured. Say a neuron replacement procedure for example, a CNS cell can only survive for a couple of minutes, how can cell implants or what ever fix in a lesion in an injured cord accelerate or hold back for that matter when it comes to angiogenesis. Will new blood vessels grow like crazy just like that to give the necessary nutrition’s and oxygen to the implanted bio matter in an injury site? Who, none discuss this, only cells and anti and inhibitor stuff and the bioelectrical grid, but this grid needs fuel to survive and if blood capillaries vessels are not there how can cells and bio matter survive? Just a thought here Cripply.

    On the other hand, Say if we could gather all the scientific know-how into a single project (human trial network) and use all the SCI research in the world. Would you deny a trial on humans? I doubt it. The job is partly to have this done based upon western sound research, I’m not discriminating other places here now because some will be a major player, maybe in the future (Link). Thanks for discussing.

    As for more basic research, much more of course.

  6. #36
    Leif, I totally agree with you. I think human trials should happen now, as all progress in science is sequential, one discovery built on the back of the previous discovery. Even tiny discovery counts. Sometimes incidental observations are made during trials that lead to yet further discovery.
    The issue of angiogenesis (building the blood supply to the tissue) somehow does not concern me that much. First off, stem cells, which are in some aspects not dissimilar to tumor cells, I believe have the capability to promote the growth of their own blood supply. Second, the science on vascularization and the prevention thereof is very advanced, thanks to cancer and cardiovascular researchers. Folkmann was a pioneer. Many studies have been done on the revascularization of ischemic limbs, using drugs and other approaches.

    The issue of whether the scar is fibrotic or glial, in my opinion, is a bit moot. The fibrotic scar might have more tensile strength and present more of a barrier, but the issue is that the "scar" is an area that must be circumvented, and its hostile elements overcome, in order for the axons to attach to their respective targets. The length to which said axons must travel is also a factor, as attractive factors and paracrine influences will not exert their action through extended distances.

    In my opinion, if you align an axon to its target close enough, in the right 3D orientation, and with no intervening "scar", whether this be made of collagen, glial cells, or marmalade, the axon will reconnect. I further believe that sometimes stem cell injection works not because of the cells, but because the puncture at the scar produces a hole, which compared to the axon diameter is huge, through which substances can migrate.

  7. #37
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    Much agree but still above the cells capability to create their own blood supply it depends on the cells, the cells as for regeneration up to now do not have this characteristics due to they are “pushed” meaning are derived to be specialized as for to do the job and not create “weed” or cancer but to do what researchers want ‘em to do, namely to deal with the wire connections as I see it. Angiogenesis, just me thinking this tough because it seems logical, say if one has a hole in the cord will to me be like who came first, the hen or thee egg although now both has the possibility to die, here particularly the niches, signals which many and much of those has not been discovered can play a role but capillaries in the cord grow slow and say cell implants are instant and thereby need a friendly environment as you say. So how can implanted neurons for example survive without blood supply to be there first? I’m not a doc so thanks for commenting but still something has to be there firsts, and then especially blood from the body system, cells themselves do lure this angiogenesis to take place sure, but that is in a normal situation over time. I understand that for capillaries like those has been made by researchers and also used in clinics, still? In a cord? How? I don’t buy just for and example to inject some cells and then all this will happen.

    The scar, if a major obstacle, it’s just bio matter and should in my opinion be easier to deal with than say replacing neurons, I don’t know although I always like to discuss tings like that. Guess we have to create an atlas as for what is going on now.

    As I understands for the axons regardless if we apply marmalade, some of them as I have understood die back not just over and a few segments below a injury site, but could die all the way from a muscle up to the injury site, from there they die back to the brains neuron synapses and vice versa depending on sensation or motor signals. Not an easy task to fix I guess, but still many believe it is achievable regardless of open up new tracts or for them fibres to get new pathways. Don’t know. Still, I believe if they can fix a partial damage in animal model and like now some say that the understanding of the cord is pretty much here - severe injuries can be fixes the same way, - building a small or a big house is done the same way.

    Glad you mentioned tumour cells; many believe that this know-how as for putting money into this research will benefit all of us dealing whit damaged cells.

    Hope we don’t make coup of the whole scare tissue discussion here now Crip’ lol, thanks.

  8. #38
    Quote Originally Posted by Princess "Leia"
    Wise,

    So basically I have a fibrous scar that is tethering my cord causing some of my pain. Is that correct?

    Pam
    Pam, I believe so. Most of the "scar" that you have is probably superficial to your spinal cord. You know how amazing I think you are, walking all over Washington DC with me on the Rally.

    Wise.

  9. #39
    Quote Originally Posted by Cripply
    I said 3D would be important unless basic science advances enough so that the axon can make the right connections without.
    Random connections result in unwanted recovery. For example, if I touch my hip, I feel it in my foot. Sometimes I want to move my R leg and my L leg moves instead. I am speculating that those examples are the result of connections made in the proximity.
    Cripply,

    What you describe, i.e. some of the incorrect sensory connections, is very common. Many people may develop unusual connections in the spinal cord below the injury site. For example, a majority of people with cervical spinal cord injury develop a tendency for the thumb to twitch when their legs are touched, suggesting that axons have grown between the parts of the spinal cord that receive sensation from the legs and the parts of the spinal cord that control movement of the hands.

    The above is both good news and not such good news. It is good news because it suggests strongly that there are reconnections going on in the spinal cord below the injury site. It is not good news because some of the reconnections are inappropriate. It is strong evidence of the plasticity of the spinal cord and that it is constantly trying to regrow and reconnect, even years after injury. Many of the unusual connections develop years after injury.

    We must learn how to harness the plasticity of the spinal cord to restore function, how to direct the reconnections that are going on so that they provide function. Part of the goal of spinal cord injury therapies is to get the reconnections to occur not only below the injury site but across the injury site. This is one of the reasons why I am quite confident that there will be therapies that will help restore function in chronic spinal cord injury.

    Wise.

  10. #40
    Quote Originally Posted by Wise Young
    Pam, I believe so. Most of the "scar" that you have is probably superficial to your spinal cord. You know how amazing I think you are, walking all over Washington DC with me on the Rally.

    Wise.
    That day Wise I was very motivated by our most important mission(CRPA), on major medications and at days end payed very dearly for pushing myself way to hard. It was worth it all! By the way, do you recall meeting Congressman Mark Foley with me that same afternoon?

    Pam

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