1) Dr. Giorgio Brunelli (Italy)

2) Dr. Shaocheng Zhang (China)

3) Dr. A Livshits (Russia & Israel)

4) Dr. Chuan-Guo Xiao (China)

5) Dr. Marc Tadie (France)

6) Dr. Carl-Axel Carlsson (Sweden)

7) Dr. Hiroyasu Makino (Japan)

8) Dr. L. W. Freeman (USA)

9) Dr. A. Chiasserini (France)

10) Drs. Charles Frazier & Charles Mills (USA)

11) Dr. Basil Kilvington (Australia)

Peripheral-nerve rerouting represents an surgical procedure that has considerable documented potential for restoring significant function after SCI. Often with this procedure, peripheral nerves (i.e., those outside of the spinal cord and brain) emanating from the cord above the injury site are surgically rerouted and connected to those below the injury site. This reestablishes a functional neuronal connection from the brain to previously dormant muscle or sensory systems.

In spite of intimidating neuroanatomical terminology, peripheral-nerve rerouting is conceptually relatively easy to understand. For example, visualize a house in which the power to the back bedroom is lost (i.e., area below the injury) due to a burned-out master electrical cable (i.e. the spinal cord injury). Instead of fixing the master cable, you disconnect the wire that powers the living-room television (i.e., a nerve to the rib or wrist region), perhaps attach an extension cord, tunnel it through the walls, and splice it directly to the bedroom wiring, circumventing the damaged section of master cable.

Amazingly, as discussed below, these function-restoring surgeries have been around in some form for nearly a century - but relegated to the therapeutic dustbin until recently.

1) Dr. Giorgio Brunelli (Brescia, Italy) has surgically rerouted peripheral nerves to bypass the injury site, reestablishing a functional neuronal connection from the brain to previously dormant body areas. For example, he has restored some function by redirecting the wrist’s ulnar nerve and connecting it to nerves that control leg functioning below the injury site. After this procedure, a patient with a complete spinal-cord transection could stand up and walk short distances. In another procedure carried out in a woman with a complete thoracic transection, the peroneal nerve (a nerve to the leg) was used as a bridge directly from 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. (Photo: Dr. Giorgio Brunelli & Nobel Laureate Dr. Rita Levi-Montalcini)

Because the second procedure represents a direct peripheral-nerve to spinal-cord connection, it challenged traditional beliefs on how neurons control muscle function. Specifically, upper motor neurons (nerves within the spinal cord) and lower motor neurons (nerves that leave the cord to connect to muscles) use different neurotransmitters. Hence, theoretically, the muscle should not be triggered due to neurotransmitter incompatibility. However, Brunelli has recently shown that target muscles are genetically reprogrammed, producing receptors that are responsive to the neurotransmitters released by the upper motor neurons that have grown to the muscles through the peripheral nerve bridge. 

2) Dr. Shaocheng Zhang (Shanghai, China), through a variety of procedural permutations, has rerouted peripheral nerves to restore function in hundreds of patients with SCI. Restored function depends upon the specific functions that the target nerves serve (e.g., leg muscle function, bladder and bowel control, sensation, etc). For example, the rerouted nerve could be connected to a nerve that controls urination, or it could be reconnected to nerve that controls upper leg muscles. Many possible rerouting arrangements exist. Zhang commonly reroutes one of the intercostal nerves that lead from the spinal cord around each rib to the sternum. If the intercostal nerve is not long enough to reach the target nerve site below the injury level, a sural nerve segment is attached to the intercostal nerve (Click on thumbnail).

If the injury site is above the thoracic area where the intercostal nerves originate, other peripheral nerves can be selected. For example, in several cases, Zhang has rerouted the ulnar nerve.

In addition to the intercostal and ulnar nerves, peripheral-nerve-rerouting options can restore function for virtually any level of injury. For example, in high-level injuries, functional peripheral nerves above the injury site (e.g., cervical plexus nerve branches originating from the higher cervical regions) can be connected to nearby dysfunctional nerves below the injury site (e.g., brachial plexus nerves originating from the lower cervical regions), potentially restoring respiratory ability to a previously ventilator-dependent quadriplegic.

Zhang et al have reported the results of 23 patients who had an intercostal nerve surgically rerouted to nerve roots below the injury site (Surgical Technology International XI, 2003). Specifically, two to four intercostal nerves were transferred to the vertebral canal through a submuscle tunnel and connected to lumbar nerve roots. If the selected intercostal nerve was of insufficient length to reach the specific lumbar region, a sural nerve segment was attached. The 23 patients included 19 males and 4 females, ranged in age from 19 to 45, were traumatically injured between the thoracic T9-12 levels, and had sustained their injuries 6 to 30 months before surgery.  Of the 23 patients, 18 regained some ambulatory function and were able to walk with crutches or other assistive technology.

Zhang and colleagues have also used an intercostal-sural nerve bridge to restore some bladder and bowel function. Specifically, two intercoastal nerves above the injury site were transferred to the vertebral canal through a submuscular tunnel. A sural nerve segment was sutured to the intercostal nerves and then to the S2-4 nerve roots. Of the 30 patients studied, 19 were male and 11 female, ages ranged from 19 to 46, and 17 and 13 traumatically injured in the T9-11 and T12-L2 level, respectively.  Significant bowel and bladder function was restored in the majority of patients.

Zhang’s various nerve-rerouting surgeries are listed below. Although the neuroanatomical terminology can be intimidating, the fundamental concept is theoretically simple: a functioning nerve from above the injury site is rerouted and connected to a paralysis-affected nerve.

C1-4 Injuries:

A) The accessory nerve arising from a cranial nerve is connected to the paralysis-affected phrenic nerve, restoring some respiration.

B) The facial nerve’s cervical branches are connected to the paralysis-affected phrenic nerve, restoring some respiration.

C5-8 Injuries:

A) The accessory nerve is connected to the paralysis-affected musculocutaneous nerve, restoring some bicep function.

B) To restore some hand function, the accessory nerve is connected the paralysis-affected median nerve, and a still-functioning cervical plexus nerve branch is connected to a paralysis-affected brachial plexus branch.

C) Again to restore some hand function, a connection is made between a pectoral nerve below the injury site to the paralysis-affected ulnar and radial nerves.

T2-7 Injuries:

A) The arm’s functional ulnar nerve is rerouted below the injury site to paralysis-affected femoral and ilioinguinal nerves, restoring some ambulation and pelvic-area sensation.

B) The arm’s ulnar nerve is attached to paralysis-affected femoral and obturator nerves, restoring some leg-muscle function.

T8-11 Injuries:

A) Rib-associated intercostal nerves are rerouted and connected to the paralysis-affected femoral cutaneous and ilioinguinal nerves, restoring some leg and sexual sensation.

B) Intercostal nerves are rerouted and connected to paralysis-affected lumbar nerve roots, restoring some walking ability.

C) Intercostal nerves are rerouted and connected to paralysis-affected sacral nerve roots, restoring some bowel-and-bladder function.

Cauda Equina Injuries:

A) Intercostal nerves are rerouted and connected to the paralysis-affected pudendal nerve, restoring some bowel-and-bladder function.

B) Still-functioning gluteal nerves are connected to the nearby, paralysis-affected pudendal nerve, restoring some bowel-and-bladder function.

C) The leg’s saphenous nerve is connected to the tibial nerve, restoring some sensation to the foot.

D) The leg’s sural nerve is connected to tibia nerve, restoring some sensation to the foot’s plantar region and toes.

3) Dr. A Livshits et al (Moscow, Russia) have connected intercostal nerves above the spinal cord injury site to nerve roots below the injury site in 11 patients with complete L1 injuries (Spinal Cord 42(4), 2004). All patients were male, ranged in age from 18-47 years, and sustained their injuries 1-4 years before surgery.  Specifically, intercostal nerves from the 11th and 12^th rib were transferred through a vertebral canal created under deep spinal muscles. These nerves were then connected end-to-end to S2-3 nerve roots that had been cut in their proximal portion. (Thumbnail illustration from Spinal Cord 42(4), 2004)

Various bladder-function assessments were carried out 10-12 months after surgery, including bladder capacity, urine volume, residual urine, detrusor tone, voiding pressure, and force of detursor contraction. Restoration of reflex voiding occurred in all patients.

4) Dr. Chuan-Guo Xiao and colleagues (Wuhan, China & New York, USA) have rerouted nerves below the injury site, restoring the patient’s ability to control urination through skin stimulation (J Urol, 170, 2003; & European Urology 49, 2006). As illustrated, the lumbar-level L5 ventral nerve root is usually connected to the sacral-level S3 (or S2) ventral nerve root. (The ventral and dorsal roots contain nerves that leave and enter the spinal cord, respectively). After rerouting, by scratching, gently squeezing, or electro-stimulation of the skin associated with the L5 dermatome, a voiding response is initiated. Basically, these actions trigger a sensory signal that enters the cord via the L5-dorsal root, in turn, stimulating nerves that leave the cord through the L5-ventral roots now connected to the bladder-controlling S3-ventral nerve root. Provided this area of rerouting is undamaged, the procedure is suitable for all levels of injury. Because this procedure does not restore bladder sensation, patients need to consciously initiate the triggering procedures for urination.

In his 2003 article, Xiao reported the results of treating 15 patients with complete, ASIA-A injuries with this procedure. Injuries ranged from C4 to T12; in other words, all were well above the nerve-rerouting area. The time between injury and surgery averaged 6.8 years, and average follow-up was three years. Of the 15 patients, 10 recovered bladder-storage and emptying function starting about a year after surgery (the time for regenerating neurons to reach their target site), residual urine decreased from 332 to 31 milliliters, and urinary-tract infections became negligible. In addition, two patients partially recovered, requiring electrical stimulation to initiate voiding, and, although decreasing residual urine, still retaining over 100 milliliters. Of the three remaining patients, one was lost to follow-up, and two did not accrue benefits, apparently due to poor rerouting connections.

Before surgery, six of the 12 patients who eventually recovered bladder control had elevated serum creatine levels, an indicator of kidney problems. A year and half after the procedure, their creatine levels returned to normal. In addition, patients who regained bladder control also regained bowel control. Overall, by the end of 2004, 81 of 92 treated patients regained bladder function one year after surgery.

5) Dr. Marc Tadie and colleagues (Le Kremlin Bicetre Cedex, 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 was undertaken in man who sustained a clinically complete T9 injury at age 52 three years earlier in an automobile accident (J Neurotrauma 19(2) 2002; Thumbnail illustration from this reference).  

Specifically, three 6-cm long, autologous nerve segments were implanted on each side of the cord at the T7-8 level immediately above the injury site. The segments were inserted 5 mm into the cord to allow contact with ventral horn motor neurons but with care to avoid injury of the main ascending and descending neuronal tracks.  The segments were sutured and glued to the spinal cord. The opposite ends were sutured to L2-4 ventral nerve roots (i.e., containing the motor neurons exiting the cord), which had been detached from the point that they exit the cord. The graft-root connection was covered with a silastic tube.

Eight months after surgery, the patient was able to initiate some contraction of adductor and quadriceps leg muscles. This ability was confirmed by various electrophysiological assessments.

6) Drs. Carl-Axel Carlsson and Torsten Sundin (Göteborg & Lund, Sweden) rerouted thoracic nerve roots above the injury site to sacral nerves below the injury site in two men with L1 injuries (Spine 5(1), 1980). The patients, age 23 and 43, were acutely injured from accidents 10 and 14 days earlier. Specifically, T12-nerve roots were connected to the S2 and S3 ventral and dorsal nerve roots that had been cut as close as possible to the cord. The connection was made using a Silastic filter without sutures. This rerouting theoretically created a functional connection between the brain and bladder.

Approximately a year later, both patients, “could feel the urge to void, could initiate micturition voluntarily, and could empty their bladders satisfactorily.” In one patient, some psychogenic and tactile erectile function was regained. Unlike previously discussed rerouting procedures, the observed functional recovery occurred in a post-injury phase when some recovery is not uncommon.

In a early case study, Carlsson and Sundin restored bladder function in a four-year old girl with paraplegia due to a lumbar-level myelomeningocele (i.e., a spinal bifida birth defect in which the cord and membranes protrude from the back) (Rev Surg 24(1), 1966). The myelomeningocele was surgically excised in a fashion in which no neuronal connection remained between the cord above the lesion and nerve roots below the lesion. A pair of T10 or T11 ventral nerves roots were cut close to where they exited the dura and connected end-to-end to S1 and S2 ventral roots using a Millipore microfilter. Eight-months later, the girl was able to voluntarily urinate.

7) Dr. Hiroyasu Makino (Japan): Based on Dr. Freeman’s operative techniques discussed below, Makino et al routed freed intercostal nerves above the injury site to areas below the injury site in eight patients with paraplegic injuries sustained at least a year before surgery (Neurol. Mediochir (Tokyo), 6, 1964). In four patients, one pair of T10 or T11 intercostal nerves was inserted in the conus medullaris (i.e., the spinal cord’s conical tip) and another pair connected to L4 nerve roots. In four other patients, two pairs of intercostal nerves were connected to L3 and L4 nerve roots.

At the time of this brief, the follow-up period to assess patient functional improvement was relatively limited. As a result, only one patient, who had sustained a L1-L2 injury 13 months before surgery, demonstrated significant improvement, including the ability to walk with the assistance of parallel bars. 

8) Dr. L. W. Freeman (Indiana, USA):  Moving back further in time to 1951, Freeman connected intercostal nerves above the injury site to sacral nerve roots below the injury site (J Neurosurg 18, 1961). This surgical procedure was carried out in a 33-year-old male injured near the T8-9 level from police gunshot five months earlier. In exchange for volunteering for this experimental procedure, he was granted amnesty.   

Specifically, retaining their central connections to the spinal cord, the 8^th and 10^th intercostal nerves were freed laterally and sectioned. The nerves were routed through the spinal canal and connected to either 1) the distal ends of severed sacral nerve roots or 2) implanted into the conus medullaris. 

Although the patient related new phenomena in his legs and bladder to the procedure, he died four months later. After autopsy, histological analysis indicated the continuity of intercostal nerve axons into both the sacral roots and spinal cord.   

9) Dr. A. Chiasserini (France) even earlier in time, connected functional intercostal to cauda equine nerves in four males with paraplegia from traumatic injury (J Chir 46, 1935; also discussed in Vorstman, et al, Urology 30(2), 1987). Patient age ranged from 21-29, and the time since injury from 1-15 months. Procedurally, two intercostal nerves (again, nerves that lead from the spinal cord around each rib to the sternum) were dissected out and connected to cauda equine nerve roots (the roots descending from the lower cord). Although one patient died postoperatively of pulmonary edema, the other three all regained bladder function.  

10) Drs. Charles Frazier & Charles Mills (Pennsylvania, USA): Although we tend to think of the creation of new function-restoring, neuronal connections at the forefront of knowledge, amazingly, such connections were used nearly a century ago to restore bladder function in a 27-year-old man (JAMA 59, 1912; click on thumbnail).  The patient sustained a L2 injury when a gas tank exploded near him. Although he regained some function over time, his “bladder continued paralyzed,” and he had “absolute incontinence.”

Again, a functional neuronal connection was made from above the injury site to paralyzed nerve roots below the injury site. Specifically, eight months after injury, the patient under went surgery in which a functional L1 nerve above the injury site 1) “was divided extradurally at its exit from the spinal canal and brought within the dural sac” and 2) then sutured end-to-end to S3 and S4 nerve roots. Eight months after the operation, the patient regained some bladder control.

11) Dr. Basil Kilvington (Melbourne, Australia): In 1906, Kilvington attempted to restore bladder function in three dogs connecting sacral and lumbar nerve roots (Br Med J April 27, 1907). Based on these animal experiments, which had marginal results, as well as research using cadavers, he attempted this crossover surgery in a 40-year-old man, who six years previously had sustained a T11-12 injury after falling from a tree. Ten days after performing a laminectomy on a patient, Kilvington went in again to connect the nerve roots; unfortunately due to the dense scar formation accruing from the initial surgery, he was unable to continue.

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