Cauda Equina Injuries

[Wise Young]

I recently received the following enquiry via email and thought that I should try to answer this question on the Cure Forum so that people can pitch in with their views and questions.

I recently attended Dr. Young's July conference at Rugers. I would like to thank him for his work on developing cures for spinal cord injury.

I left the conference very confused about my problem. My problems is cauda equina syndrome, which I suppose doesn't qualify as a spinal cord injury.
Will the same therapies be used to treat cauda equina syndrome as spinal cord injury. It seems that cauda equina may be even more complex than spinal cord injury.

Until recently, I had been hopefull that a treatment may be coming in the not too distant future. However, I am left wondering if I am stuck with the bowel, bladder and sexula dysfunction.

Cauda equina injuries typically involve the spinal roots that are present below L1 vertebral level. Strictly speaking, the cauda equina is not spinal cord and many of the obstacles to regeneration are not present in the cauda equina. On the other hand, regeneration of the sensory pathways will require regeneration of sensory axons in the spinal cord.

To illustrate, I have drawn a picture of the injury to sensory and motor axons in the spinal roots. In the case of the sensory axons, the cell bodies are in the dorsal root ganglia and the injury occurs between the dorsal root ganglion and the spinal cord. Thus, the axons must regrow into the spinal cord and then all the way to the brain. This will take a long time (years) and will probably be impeded by the growth inhibitors that are present in the spinal cord. The regrowth of sensory axons into the spinal can be facilitated in two ways, administration of chondroitinase at the dorsal root entry zone so that the axons will enter the spinal cord and blockade of axonal growth inhibitors with Nogo blockers or Nogo receptor blockers to allow the axons to grow in the spinal cord.

Some motor recovery should occur after cauda equina injuries. The reason is that axons should regenerate in the peripheral nerve. Spinal root is peripheral nerve and the axons should regrow. If the injury is too close to the spinal cord and the motoneurons, there may be damage to the motoneurons. However, where motoneurons survive, their axons should be able to regenerate. If they are not doing so, it may be because of scar tissue formation in the peripheral nerve and possibly tethering of the roots.

Now, from a practical point of view, there are relatively few scientists working on animal cauda equina models and no clinical trials that I know of being carried out in the field. This needs to change. I will do what I can to help attract interest and to get research going in the United States and China.

Wise.

[Buck503]

So even if there was a therapy to fix my spinal cord injury, it still
wouldn't help because of the peripheral nerve damage.

Cool.

[SS77]

so it will take longer to heal if you're injury is L1 or will there will be no cure?

[Lindox]

There are numerous cauda equina studies in dogs. Not that any have been all that remarkable in returning function..but at least there are animal researchers interested.

[Wise Young]

Originally Posted by SS77

so it will take longer to heal if you're injury is L1 or will there will be no cure?

SS77,

Please, I did not say that it will take longer to heal and there will be no cure. Motor function is more likely to come back. While there is no cure at the present, I believe that a cure for cauda equina will be easier to achieve than for spinal cord injury.

The person who posted asked about bowel, bladder, and sexual function. I suspect that he already recovered a lot of motor function and that he is now looking for recovery of his bowel, bladder, and sexual function.

As many here already know, there is a lot of excitment about doing a ventral root bridge to restore bladder function. After all, what is the difference between a peripheral nerve bridge and repairing the cauda equina injury?

I suspect that this is probably going on already in China (note: I will post of course if I see such work going on). It is just sad that we don't have many neurosurgeons or other surgeons in the United States that are interested in doing such work.

Wise.

[Dennis888]

Dr. Young,

I have a L2 cauda equina injury. Initially both of my legs were paralyzed but my right leg has largely recovered its motor function. My bowel, bladder, and sexual function have also largely recovered.

But my problem is that my left leg's motor function still has not recovered after 3 years. So now I can only use the walker to hop around on my right leg. The left leg is still paralyzed. Is there any hope that my left leg can also recover its motor function? I understand that the sensory function will be much more difficult to recover.

Thanks.

Dennis

[SS77]

Originally Posted by Wise Young

SS77,

Please, I did not say that it will take longer to heal and there will be no cure. Motor function is more likely to come back. While there is no cure at the present, I believe that a cure for cauda equina will be easier to achieve than for spinal cord injury.

The person who posted asked about bowel, bladder, and sexual function. I suspect that he already recovered a lot of motor function and that he is now looking for recovery of his bowel, bladder, and sexual function.

As many here already know, there is a lot of excitment about doing a ventral root bridge to restore bladder function. After all, what is the difference between a peripheral nerve bridge and repairing the cauda equina injury?

I suspect that this is probably going on already in China (note: I will post of course if I see such work going on). It is just sad that we don't have many neurosurgeons or other surgeons in the United States that are interested in doing such work.

Wise.

Thanks DR Wise for clearing this up for me.I've recover a little since my injury but the pain will just not go way at all all meds have failed.Yep I sure hope United States will start some thing soon.

[cljanney]

Originally Posted by Wise Young

(edit)...Now, from a practical point of view, there are relatively few scientists working on animal cauda equina models and no clinical trials that I know of being carried out in the field. This needs to change. I will do what I can to help attract interest and to get research going in the United States and China.

Wise.

Dr Young,

Would the work that Prof. Geoffrey Raisman is doing in the UK with OECs and ongoing plans to begin human clinical trials re-implanting avulsed Brachial Plexus Nerves back into the Spinal Cord be similar in theory for repair of Cauda Equina Injuries, if successful? It seems to me that the injuries are similar enough in nature that Cauda Equina Injuries would most likely benefit if the upcoming trials, that will attempt to repair Brachial Plexus Avulsions, are successful.

Just curious of your thoughts.

I imagine the distances needed to be covered for both regenerating motor and sensory axons (not to mention possible irreversible muscle atrophy, muscle plate degeneration, etc.) may pose more difficult challenges than just getting the axons to "bridge the gap" and enter and exit the spinal cord and peripheral nerves. With these degenerative obstacles in mind, it seems quiet obvious why addressing the acute injury first is the most sensible path to take.

Christopher



http://www.nature.com/nrn/journal/v8...n2099_BX1.html

Clinical demonstration of the effectiveness of adult OEC autografts would be an important stimulus to research in this area, and would open the door to treating a wide variety of currently incurable injuries of the brain, spinal cord and cranial and spinal nerves. Arising from the rat experiments, one possibility we are exploring is a trial of OECs in brachial plexus avulsion, a situation where the prognosis is clear, surgical procedures are already in practice, and sufficient numbers of cells are available for transplantation.

http://www.ion.ucl.ac.uk/research/hb...epair_unit.htm

As of November 2006, we are planning, in collaboration with our surgical colleagues, to carry out a preliminary safety study of the effects of transplanting olfactory ensheathing cells. The timing of this study is not fixed, but we hope it will start some time in 2007. The study will involve around 10 patients who are part of the routine practice of the National Hospital for Neurology and Neurosurgery and who will be treated within a few days of accidents causing avulsion of the brachial plexus. We do not yet have the technology to tackle other types of injury. The brachial plexus study will take up to 18 months. Where we go from there will depend on the follow-up results of this study showing safety and feasibility.

[Wise Young]

One of the exciting possibility for OEG cells is their potential for allowing sensory axonal growth into the spinal cord. Several animal studies suggesting that when OEG cells are transplanted into the dorsal root entry zone, they may faciitate sensory axonal growth into the spinal cord. If you look at the figure that I drew, a cauda equina injury damages the sensory axons between the dorsal root ganglion and the spinal cord. Now, entry of the axons into the spinal cord injury is no guarantee that it will grow up the dorsal column all the way to the brainstem. On the other hand, the sensory axon may well synapse on some interneurons that may send their axons to the thalamus. It is true that most such interneurons carry pain and thermal sensations and so there is a need to see what happens but I think that this is a worthwhile clinical trial to do.

I would not be so discouraged by the muscle atrophy problem for several reasons. First, even though the muscles may be severely atrophic, they can revive if innervated and stimulated. Several years ago, I came back to these forums all aglow from having seen a talk in Italy that reported that very strong electrical stimulation will renew muscles that have been denervated by peripheral nerve injuries. This is the worst case exampole. Second, if we can transplant cells, we can transplant muscle. This is something we can do very well. Muscles have the capability of expansion. I don't doubt that if we are able to get the nerves to regrow, we will be able to put muscles there for the nerves to innervate. Third, cauda equina injuries are seldom all or none. Because there are many roots, the injury just damaged some of the them and not others. One may be able to selective bridging of some ventral roots to others. After all, if Xiao can reinnervate the bladder by bridging from a lumbar ventral root, they should be able to fix the cauda equina injury.

The problem is that we have few or no surgeons in the United States that are doing this kind of surgery or even thinking about it. That is why I told Dr. Xiao and Dr. Zhang that they need to training other doctors to do these procedures. Even if these guys were to operate on 300 cases years, over the coming ten years, the two of them will only be able to operate on at most 6000 patients. They would be much more effective if they each trained 100 doctors and each ofthe doctors trained 100 doctors.

Wise.

Originally Posted by cljanney

Dr Young,

Would the work that Prof. Geoffrey Raisman is doing in the UK with OECs and ongoing plans to begin human clinical trials re-implanting avulsed Brachial Plexus Nerves back into the Spinal Cord be similar in theory for repair of Cauda Equina Injuries, if successful? It seems to me that the injuries are similar enough in nature that Cauda Equina Injuries would most likely benefit if the upcoming trials, that will attempt to repair Brachial Plexus Avulsions, are successful.

Just curious of your thoughts.

I imagine the distances needed to be covered for both regenerating motor and sensory axons (not to mention possible irreversible muscle atrophy, muscle plate degeneration, etc.) may pose more difficult challenges than just getting the axons to "bridge the gap" and enter and exit the spinal cord and peripheral nerves. With these degenerative obstacles in mind, it seems quiet obvious why addressing the acute injury first is the most sensible path to take.

Christopher



http://www.nature.com/nrn/journal/v8...n2099_BX1.html


http://www.ion.ucl.ac.uk/research/hb...epair_unit.htm

[Lindox]

Originally Posted by Wise Young

One of the exciting possibility for OEG cells is their potential for allowing sensory axonal growth into the spinal cord. Several animal studies suggesting that when OEG cells are transplanted into the dorsal root entry zone, they may faciitate sensory axonal growth into the spinal cord. If you look at the figure that I drew, a cauda equina injury damages the sensory axons between the dorsal root ganglion and the spinal cord. Now, entry of the axons into the spinal cord injury is no guarantee that it will grow up the dorsal column all the way to the brainstem. On the other hand, the sensory axon may well synapse on some interneurons that may send their axons to the thalamus. It is true that most such interneurons carry pain and thermal sensations and so there is a need to see what happens but I think that this is a worthwhile clinical trial to do.

I would not be so discouraged by the muscle atrophy problem for several reasons. First, even though the muscles may be severely atrophic, they can revive if innervated and stimulated. Several years ago, I came back to these forums all aglow from having seen a talk in Italy that reported that very strong electrical stimulation will renew muscles that have been denervated by peripheral nerve injuries. This is the worst case exampole. Second, if we can transplant cells, we can transplant muscle. This is something we can do very well. Muscles have the capability of expansion. I don't doubt that if we are able to get the nerves to regrow, we will be able to put muscles there for the nerves to innervate. Third, cauda equina injuries are seldom all or none. Because there are many roots, the injury just damaged some of the them and not others. One may be able to selective bridging of some ventral roots to others. After all, if Xiao can reinnervate the bladder by bridging from a lumbar ventral root, they should be able to fix the cauda equina injury.

The problem is that we have few or no surgeons in the United States that are doing this kind of surgery or even thinking about it. That is why I told Dr. Xiao and Dr. Zhang that they need to training other doctors to do these procedures. Even if these guys were to operate on 300 cases years, over the coming ten years, the two of them will only be able to operate on at most 6000 patients. They would be much more effective if they each trained 100 doctors and each ofthe doctors trained 100 doctors.

Wise.

I am going to print this post and put it in my scrapbook. This is a glimpse of a brilliant mind..and of a 25 year old Dr. Wise. It is powerful and dynamic.
With a pinch of youthful optimism. It is the type of thinking that does bring Utopia into reality.