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Thread: Regenerative therapy for mid-thoracic injury

  1. #1

    Regenerative therapy for mid-thoracic injury

    Dr.Young,

    You have previously posted that for a person with a mid-thoracic injury, a regeneration therapy would most likely be enough to produce substantial recovery. Could you please advise me of what you think is one of the more promising regeneration therapies, and which are being looked at to start clinical trials soon? Lastly, would a bone marrow or OEG transplant constitute a regeneration therapy? Thanks in advance.

  2. #2
    Quote Originally Posted by zokarkan
    Dr.Young,

    You have previously posted that for a person with a mid-thoracic injury, a regeneration therapy would most likely be enough to produce substantial recovery. Could you please advise me of what you think is one of the more promising regeneration therapies, and which are being looked at to start clinical trials soon? Lastly, would a bone marrow or OEG transplant constitute a regeneration therapy? Thanks in advance.
    zokarkan this is such a good question .i was fixing to post similar post was trying to figure out how to phase my question..thanks you and hope we both here something soon

  3. #3
    Senior Member Schmeky's Avatar
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    This has been discussed several times in the past. I have taken the liberty to re-post. I hope Dr. Y doesn't object.


    Diagnosis and Treatment of Thoracic Spinal Cord Injury
    By Wise Young, Ph.D., M.D.
    W. M. Keck Center for Collaborative Neuroscience
    Rutgers University, Piscataway, New Jersey
    http:sciwire.com, last updated 23 July 2005

    Many people have been asking for an article about diagnosis and treatment of thoracic spinal cord injury. The following is a short description of upper and mid-thoracic spinal cord injury, emphasizing the anatomy, the neurology, treatment, recovery, and long-term changes, and hope for recovery and therapies.

    Anatomy

    The thoracic spinal cord is situated in the T1-T9 thoracic spinal canal. The thoracic vertebral segments form the chest wall and have ribs. The thoracic segments are the best protected of all the vertebral segments because of the ribs. It takes enormous forces to fracture the thoracic spinal vertebral bodies. Traumatic injuries of the upper thoracic spinal cord are relatively rare, accounting for only 10-15% of spinal cord injuries (compared to 40% due to cervical, 35% due to thoracolumbar injuries, and 5% due to lumbosacral injuries). Thoracic spinal cord injuries occur as a result of high-speed motor vehicular accidents, tumors that have compressed the spinal cord, and ischemic injuries of the spinal cord. When traumatic injuries of the thoracic spinal cord occur, they generally are severe and often result in complete loss of neurological function below the injury site.

    Details of the anatomy are worthwhile noting. The C1 roots exit the spinal column just above the C1 vertebral body, that there is a C8 spinal segment but no C8 vertebral segment. The C8 root therefore exits the vertebral column between C7 and T1. The T1 root exits the spinal column below T1. The thoracic spinal roots form the intercostal nerves (nerves that run on the underside of the ribs). Although many clinicians say and believe mistakenly that the thoracic segments do not have a significant motor component and that all they control are the intercostal muscles for breathing, this is not true. As it turns out, the thoracic segments control muscles that attach to the ribs (which include the abdominal muscles, as well as most of the back muscles).

    Neurology

    Injury to the thoracic spinal cord causes paraplegia, or loss of motor and sensory function in the lower half of the body. Because the thoracic cord is situated some distance from the brain and lumbar cord, sensory and motor axons have a long ways to regenerate before they can restore function. Nevertheless, substantial sensory and motor recovery occurs in a majority of people with mid-thoracic injuries, even those with initially "complete" spinal cord injury. For example, recovery of 4-6 dermatomes of sensory function and upper trunk/abdominal muscles is common. Diagnosis of spinal cord injury usually is based on sensory examination. The axillary (armpit) region is T2, the nipples T4, the bottom of the rib cage is T8, the umbilicus (belly button) is T10, and the suprapubic region is T12.

    The cervical segments innervate superficial trunk muscles such as the scapula and the latissimus dorsi. Multiple overlapping thoracic segments innervate most deeper trunk muscles. Injury to the thoracic spinal cord will cause partial paralysis of deeper trunk muscles such as the cervicis (T1-5), splenius (T3-T6), erector spinae and iliocostalis (T6-12), spinalis (T1-9), semispinalis, transversospinal, and segmental (T1-12) muscles. The thoracic segments and upper lumbar segments innervate the abdominal muscles including the rectus abdominus (T4-L3), external oblique (T6-L3), transverse abdominis (T9-L3), and internal oblique (T12-L3). The posterior oblique (T6-10) and the anterior oblique (T4-8) muscles attach to the lower and upper thoracic ribs respectively. In general, muscles above the belly button are innervated by T5-T11 while muscles below the belly button are innervated by T12 and L1.

    Causes of Injury

    Decompression of the thoracic spinal cord often requires surgery because traction alone often cannot reposition the thoracic vertebral segments. Because surgery on the thoracic spinal column usually requires the opening of the thoracic cavity, decompression of thoracic spinal cord injury may be delayed by many hours, days, or even weeks after injury. Continued compression of the spinal cord contributes to the damage. In my opinion, delays in decompressing the spinal cord contribute to neurological loss in thoracic spinal cord injuries. Compression of the spinal cord causes ischemia or loss of blood flow to the spinal cord. Pressure on the spinal cord exceeding blood pressure will reduce or stop blood flow to the spinal cord. Continued compression for many hours, days, or even weeks is likely to cause further damage to the spinal cord.

    The thoracic spinal cord is vulnerable to ischemic injuries. In humans, the artery of Adamkiewicz is a major source of blood to the thoracic spinal cord and usually enters the spinal cord at T6. Compromise of this artery by traumatic aortic aneurysms, for example, can cause an infarct of the thoracic spinal cord. Arteriovenous malformations (AVM) often occur in the thoracic spinal cord. AVM's cause ischemia by "stealing" blood from the capillaries and increasing venous pressure. Finally, tumors of the spinal cord often occur in the thoracic spinal cord and they compress the cord, reducing blood flow. Ischemic injuries to the spinal cord may outnumber traumatic spinal cord injuries.

    Treatment

    The first goal of treating thoracic spinal cord injury is protection of the spinal cord. This includes treatment with high-dose methylprednisolone if the treatment can be started within 8 hours after injury. If there is continuing compression of the spinal cord, the spinal cord should be decompressed. It may be necessary to open the thoracic cavity to approach the thoracic spinal column from the front. In the United States, such surgery usually involve a thoracic surgeon as well as a spinal surgeon, and the surgery may be delayed until the patient is stable and major surgery can be scheduled. In lower thoracic spinal cord injuries, it is often possible to straighten out and stabilize the spinal column from the back, using posterior rods and screws. Care must be taken to evaluate the screws and whether or not they impinge on the spinal cord and roots.

    Thoracic spinal cord injury disconnects the lower thoracic and lumbosacral spinal cord from the brain. While paraplegia (paralysis of the lower limbs) is the most obvious outcome of spinal cord injury, loss of sacral functions including bowel and bladder function are the most troublesome and a major cause of death before the 1970's. With the advent of antibiotics and intermittent catheterization, as well as better emergency care, most people with thoracic spinal cord injuries today survive their injuries and can live close to normal lifespan. Because the injury does not involve the lumbar and sacral spinal cord, lumbosacral reflexes are usually preserved and spasticity is frequently present. Thus, people with thoracic spinal cord injuries are good candidates for regenerative therapies aimed regrowing descending motor axons from the injury site to the lumbosacral segments or ascending sensory axons from the injury site to the brain.

    Recovery

    Most clinicians tend to be quite pessimistic about recovery from thoracic spinal cord injury. Part of this may be because most people with thoracic spinal cord injury were involved in severe high-speed motor vehicular accidents and prolonged compressions of the spinal cord. In the past, many clinicians often did not even decompress thoracic spinal cords. This has changed in recent years as many studies, particularly the work of Bohlman, et al. at Case Western University, have reported that decompressing thoracic spinal cords even up to 3 years after injury may result in some functional improvement in patients. Up to 80% of the patients got better from such decompressive surgery and only 10% got worse. Most had reduction of pain after the surgery.

    Part of the pessimism associated with thoracic spinal cord injury derives from inadequate neurological examination of patients with thoracic spinal cord injuries. Many clinicians examine only the legs and not the trunk or abdominal muscles or thoracic sensory levels. In my experience, most people with thoracic spinal cord injuries regain 4 or more dermatomes below the initial injury level. For example, a person with a T4 injury (sensory level at the nipples) often regains back the T8 (bottom of the rib cage) or even T10 (umbilicus) dermatomes. Likewise, they often get back upper abdominal muscles representing T5-11. Although many patients with T2-T5 injuries show improved trunk control over several years after injury and many can even stand with bilateral knee-ankle-foot orthoses and a walker, suggesting that they have regained some hip control, these are often not credited as recovery of function. Individuals with T6-T12 injuries often recover lower abdominal muscles and may be able to ambulate short distances. Some with T9-T12 injuries become household walkers (Source).

    Long-term Changes

    White matter (myelinated axons) normally occupies over 90% of the thoracic spinal cord. About half of the axons are ascending sensory fibers from dorsal root ganglia sensory neurons situated just outside the spinal cord and the remainder come from neurons in the lower spinal cord. The rest are descending motor axons that come from brain, brainstem, and cervical spinal cord. Thoracic spinal cord injury interrupts most of these axons. The parts of axons that have been separated from their cell bodies will die. The neurons from which the axons come do not die and the neurons that they contact usually survive. Nevertheless, there is often substantial atrophy of the spinal cord at and around the injury site. This is natural and not something to be worried about.

    Routine MRI and x-rays of the spinal cord and spine are important for people with thoracic spinal cord injury. In children, thoracic spinal cord injuries frequently lead to scoliosis. In older patients, there are progressive changes in the vertebral bodies that may need to be surgically corrected to prevent deformities or compression of the cord. Particularly if the spinal cord is not decompressed, adhesive scars may form between the spinal cord and the surrounding arachnoid/dura mater at the injury site. Such adhesions may interrupt cerebrospinal fluid flow between the upper and lower spinal cord. In such cases, syringomyelic cysts may develop. These are enlargements of the central canal in the spinal cord, usually a thin and barely detectable canal in the middle of the cord. Due to shunting of cerebrospinal fluid into central canal, the canal enlarges and may compress the cord.

    Reasons for Hope

    As pointed out above, people with thoracic spinal cord injury are good candidates for regenerative therapies in clinical trials. A number of recent clinical trials have chosen to focus on people with upper and midthoracic spinal cord injuries. For example, the Proneuron trial that transplanted activated macrophages and the Purdue trial that applied alternating electrical currents chose to focus on patients with thoracic spinal cord injuries. Many clinical investigators focus on thoracic spinal cord injuries for the following reasons. First, because of the pessimism surrounding recovery from thoracic spinal cord injury, any recovery of the lower limbs would be generally perceived as being a positive effect of therapy. Second, because the thoracic spinal cord is considered to be less crucial to body functions, any complications that might cause ascent of lesion level would not be as devastating. Third, the lumbosacral spinal cord is intact and therefore should be available to receive connections from regenerating axons from above.

    People with thoracic spinal cord injuries have much reason to be hopeful. They will probably be among the first to benefit from experimental regenerative therapies of the spinal cord. Because their lumbosacral spinal cords are intact, they should have some atrophy and should not have as much muscle atrophy. Regenerative therapies alone should be sufficient to restore substantial function in many people with thoracic spinal cord injury. The regeneration distances for descending axons to travel from the thoracic spinal cord to the lumbosacral cord are shorter than from the cervical spinal cord. Many will recover trunk function and even proximal hip function without experimental therapies and hence can more easily engage in weight-supported ambulation training, swimming, and other exercises that can maintain bone and muscle.

    Summary

    Thoracic spinal cord injuries represent only 10-15% of people with spinal cord injuries. Because the ribs protect the thoracic segments, most thoracic spinal cord injuries are a result of high-speed motor vehicular accidents, aggravated by continued compression of the spinal cord. Perhaps because most thoracic spinal cord injuries are severe and frequently are not decompressed until late, clinicians tend to be pessimistic about the outcome of thoracic spinal cord injuries. However, most people with upper thoracic spinal cord injury do recover at least 4 dermatomes, improved trunk control, and upper abdomen muscles after the injury. Some with mid-thoracic injuries may recover proximal muscles of the legs. Because the lumbosacral spinal cord remains intact, most people with thoracic spinal cord injuries retain reflexes and spasticity in the lower limbs. Clinical trials of regenerative and other cell transplant therapies often focus on patients with thoracic spinal cord injuries because an ascent of lesion level typically is not as devastating as for cervical levels. Thus, people with thoracic spinal cord injury are likely to be amongst the first to benefit from experimental regenerative therapies of the spinal cord.

  4. #4
    Schmeky,

    Thanks for re-posting this, but I have already seen this before. I wanted Dr.Young to answer the questions I asked, which he has most likely done alot of times, because I wanted his answers to them.

  5. #5
    yeah i have this printed out to show new doctors along with some questions and all that we are questioning on here is highlihted thanks alot david again...

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