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Creating new connections.

As reported in the prestigious Journal of the American Medical Association (JAMA), U.S. scientists have for the first time rerouted nerves from above the spinal-cord-injury (SCI) site to restore some function in paralyzed areas. Specifically, Drs. Charles Frazier and Charles Mills, University of Pennsylvania, successfully rerouted nerves to restore bladder function in a 27-year-old man who had sustained a lumbarlevel (L2) injury after a gas tank exploded near him.

Although the patient had regained some function since injury, his bladder remained paralyzed, and he had "absolute incontinence." Eight months after injury, he underwent surgery in which a functional L1 nerve above the injury site "was divided extradurally at its exit from the spinal canal and brought within the dural sac," then sutured end-to-end to sacral-level S3 and S4 nerve roots. Eight months later, the patient had regained some bladder control.

In previous PN articles, I discussed the creation of function-restoring neuronal connections such as the aforementioned. I assumed such procedures were at the cutting-edge of twenty-first century science. Amazingly, the surgery described above was carried out in 1912!

When I came across the article (JAMA 59, 1912), I realized with dismay that function-restoring surgeries in some form have been available for nearly a century--but relegated to the therapeutic dustbin until recently. Given such glacial progress, it is understandable why many people with SCI are frustrated with science's slow pace in producing real-world therapies.

This article will briefly review the slow emergence of these procedures since this 1912 publication.

Carrying Out a Concept

Another rerouting surgery was completed in 1951 by Dr. L.W. Freeman, Indiana University (J Neurosurg 18, 1961). In this case, Freeman connected intercostal nerves (those leading from the spinal cord around each rib to the sternum) to sacral-nerve roots below the injury site in a 33-year-old prisoner who sustained a thoracic (T8-9) injury from police gunshot five months earlier. Retaining their central spinal-cord connections, intercostal nerves were freed, routed through the spinal canal, and connected to sacral-nerve roots or implanted into the conus medullaris (i.e., the spinal cord's conical tip). Although the patient believed new leg and bladder phenomena were attributed to the surgery, he died four months later. Post-mortem analyses indicated the continuity of intercostal nerve axons into the sacral roots and spinal cord.

Based on Freeman's work, Dr. Hiroyasu Makino et al. (Japan) also routed intercostal nerves to paralyzed areas in eight patients who sustained paraplegia at least a year before surgery (Neurol Mediochir [Tokyo] 6, 1964). In four, one pair of intercostal nerves was inserted in the conus medullaris and another pair connected to L4 nerve roots. In the other four, two pairs of intercostal nerves were connected to L3 and L4-nerve roots. Because results were reported relatively soon after the surgeries, only one patient at that early stage had demonstrated significant improvement, including some ambulatory ability.

Reported in 1980, Drs. Carl-Axel Carlsson and Torsten Sundin (Sweden) connected thoracic T12-nerve roots to the S2 and S3-nerve roots in two men, age 23 and 43, with L1 injuries from accidents 10 and 14 days earlier (Spine5[1], 1980). About a year later, they had regained some bladder function, and one regained erectile ability.

More recently; Dr. Shaocheng Zhang (China) rerouted peripheral nerves to restore function in hundreds of patients (PN, April 2002). Restored function depended upon the specific areas the target nerves serve (e.g., leg muscles, bladder, bowel, etc). Like Freeman and Makino, Zhang often rerouted intercostal nerves; if they were not long enough to reach the target site, intervening sural-nerve segments (from the calf) were attached. In one of Zhang's studies using this procedure, 18 of 23 subjects regained some ambulatory function and were able to walk with crutches of other assistive technology (Surgical Technology International XI, 2003). Another study demonstrated that an intercostal-sural nerve bridge restored some bladder-and-bowel function in the majority of 30 subjects.

Dr. Giorgio Brunelli (Italy) has restored function by redirecting the wrist's ulnar nerve and connecting it to nerves that control leg function. After this procedure, a patient with a complete spinal-cord transection could stand and walk short distances. In another procedure carried out in a woman with a complete thoracic transection, the peroneal nerve (to the leg) was used as a bridge directly flora the spinal cord above the injury site to the nerves of the gluteus and quadriceps muscles. After two years, she was able to walk 30-40 meters with a walker (PN, August 2004).

Dr. Marc Tadie and colleagues (France) have rerouted lumbar nerve roots from below the injury site to the spinal cord above the injury site, creating a functional neuronal pathway from brain to paralysis-affected leg muscles. This rerouting took place in a man who had sustained a complete T9 injury at age 52 three years earlier in an auto accident (J Neurotrauma 19[2], 2002). Three 6-cm-long nerve segments from the patient were implanted on each side of the cord at the T7-8 level immediately above the injury site. The opposite ends were sutured to L2-4 nerve roots, which had been detached from the point where they exit the cord. Eight months after surgery, the patient was able to initiate some contraction of adductor and quadriceps leg muscles, activity which was electrophysiologically confirmed.

Finally, Dr. A Livshits et al. (Russia and Israel) connected intercostal nerves above the injury site to nerve roots below the injury site in 11 patients with complete L1-injuries (Spinal Cord 42[4], 2004). Specifically, intercostal nerves were transferred through a vertebral canal created under deep spinal muscles and then connected end-to-end to S2-3 nerve roots. Some bladder function was restored in all patients.

Conclusion

Although I usually see much promise and potential on the SCI horizon, I was dismayed to learn that function-restoring, nerve-rerouting surgeries have existed in some form for nearly a century. I have personally observed such surgeries and the dramatic improvements accruing from them. Overall, I strongly believe such procedures can restore significant life-enhancing function in many with SCI.

Given its key role in developing new therapies, I'm troubled that the National Institutes of Health (NIH) with its nearly $30-billion research budget seemingly cannot duplicate century-old results while a growing number of foreign scientists are able to do so. As a former senior NIH official, I believe this is partially the result of NIH's approach to funding the most scientifically meritorious of laissez-faire submitted grant applications. Although the process sounds good, it is based on a questionable assumption that funding the best science automatically translates into the greatest potential for spinning off new therapies. In fact, the result is usually that the development of real-world therapies becomes secondary to scientific agendas.

Although I'm in awe watching surgeons connect nerves I can barely see, this nerve-rerouting approach represents theoretically a simple concept. Perhaps this is an example of NIH overly emphasizing sophisticated science agendas at the expense of nonglamorous, but much more promising, surgical approaches.

Contact: LauranceJohnston@msn.com.
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Title Annotation:healing options
Author:Johnston, S. Laurance
Publication:PN - Paraplegia News
Date:Dec 1, 2005
Words:1155
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