GREGORY A. DUMANIAN
INTRODUCTION
Amputation of an upper extremity is a devastating injury from both a functional and psychological standpoint. A major advance in the treatment of upper limb amputees occurred in the past decade with the development of targeted muscle reinnervation (TMR). In this procedure, nerves that had previously controlled the amputated limb are manipulated and transferred to provide signals for a multifunctional myoelectric prosthesis. These procedures have been shown to dramatically improve function after limb loss, and reconstructive plastic surgeons are ideally suited to perform the delicate nerve handling and soft tissue rearrangements required for TMR. This chapter will provide the basis for understanding prosthetic limb control and the level-by-level management of patients with upper limb amputation.
Prosthetic Devices for Upper Limb Amputees
A prosthesis is only as good as the control signals that it receives from the user. Body-powered prostheses utilize shoulder motions for movement. This is problematic, because muscles that are designed for strong movements, such as the latissimus dorsi and the serratus anterior, are required to sensitively activate cables and switches to move the prosthesis in space. Additionally, only one function of the prosthesis can be actuated at a time. Prosthetic hand, wrist, and elbow motions must be performed sequentially, and this slows use of the device to unacceptable levels. It is not surprising that many amputees functionally abandon their prostheses, wearing them only for cosmetic purposes.1
Standard myoelectric prostheses, in comparison, utilize electromyographic (EMG) signals from intact muscles on the limb or shoulder to activate and control prosthetic motion. The muscle activity creates an electric signal that is picked up by sensors and activates motors of the terminal device. For standard myoelectric prostheses, the ease of use depends on the muscles that remain on the amputated limb. For example, in a transradial amputee, native wrist and finger flexors and extensors control the opening and closing of the terminal device, providing a natural pairing of EMG signals and prosthetic movement. For more proximal amputations such as at the transhumeral level, clumsy biceps and triceps muscles are required to open and close the “hand” of the terminal device. The same muscles must also control flexion and extension of the prosthetic elbow. The user must somehow command the device to change from movement of the elbow to movement of the hand, either by muscle co-contraction or by touching a switch. Because this is not intuitive and the hand and elbow movements cannot be performed simultaneously, the device appears jerky and is slow to use. Myoelectric prostheses are heavier, more fragile, and require more daily maintenance than body-powered devices. However, as unilateral upper extremity amputees tend to use the prosthetic limb only as a helper hand, the improved cosmetic appearance of myoelectric devices can make up for their drawbacks and are often preferred.
TARGETED MUSCLE REINNERVATION
In 1995, Kuiken and Childress demonstrated in an animal study a new strategy now called targeted muscle reinnervation for the control of myoelectric prostheses. Rather than using the “wrong” signals from nearby and functionless muscles, the amputated nerve was placed near a denervated muscle in rats. After successful neurotization, the muscle served to amplify the signal of the amputated nerve, and the EMG signal could be detected transcutaneously.2 The downside of this approach is that the amputee requires a surgical procedure and that the intact EMG signal from that muscle is lost for a time until neurotization occurs. The latter tends not to be a problem, given that the muscles “sacrificed” for TMR are not contributing to the function of the limb because the limb is absent. Kuiken and Dumanian reported this procedure in a human shoulder disarticulation patient in 20043 and in transhumeral amputees in 2008.4 The TMR surgical procedure was recently reviewed,5 and this demonstrated improved outcomes in comparison to standard prostheses, with marked improvement (up to 271%, average 198%) in manual dexterity tasks6 and a statistically significant improvement in Assessment of Motor and Process Skills testing (a measure of performance of activities of daily living) when conventionally controlled prostheses were compared with TMR-controlled prostheses. The remarkably smooth coordination of complex tasks has been illustrated in numerous videos.5,7,8 Complications of the procedure have included occasional cellulitis and seroma formation deep to the undermined skin flaps, as well as a transient increase in phantom limb pain.5 Rehabilitation involves socket fitting and optimizing electrode fitting by a skilled prosthetist. Minimal occupational therapy is required because control of the device is more intuitive than with conventionally controlled prostheses.9
Technique
TMR is a technique that transfers the median, radial, ulnar, and/or musculocutaneous nerves in an amputated arm to the small motor nerves of nonfunctional residual limb muscles. These reinnervated target muscles then serve as biological amplifiers of the nerve signals to provide additional EMG control signals and improve control of motorized prostheses. A surgical training video demonstrating key steps in the procedure is available at http://www.ric.org/research/centers/cbm/index.aspx and http://drdumanian.com. Unique features to the procedure that vary based on the level of amputation and individual anatomy are discussed below.
Shoulder Disarticulation Level. TMR at the shoulder level should not be performed unless the surgical team has significant knowledge of upper chest and axillary anatomy.10 Indications for TMR are poor prosthetic function with a standard prosthetic device despite adequate rehabilitation. Patient evaluation begins with a thorough history and physical examination. Patients with brachial plexus injuries are not candidates for the procedure, because the musculocutaneous, median, radial, and ulnar nerves are unable to generate action potentials under direct cortical control. The surgeon must confirm the presence of Tinel signs for these nerves at the end of the residual limb, indicating that the end neuromas are located close to the end of the residual limb. A history of limb avulsion should alert the team that the nerve endings may be proximally located and not able to reach their targets for transfer. Voluntary contractions of the pectoralis, serratus, and latissimus muscles must also be verified by physical examination both to establish that the entire brachial plexus was not avulsed from the spinal cord and to verify with the patient that these muscle contractions will temporarily be lost after the nerve transfer procedure. Relative contraindications to surgery include a lack of muscle targets, a lack of distally located nerve endings, poor local soft tissues, and the inability to tolerate a 4- to 5-hour surgical procedure.

FIGURE 90.1. Elevation of the adipofascial flap and exposure of the sternal and clavicular heads of the pectoralis major. (Note that although this patient has a short residual humerus, no muscle targets in the arm remain and therefore the nerve transfers were performed to the chest muscles.)
Prior to the skin incision, a dilute epinephrine solution (1:200,000) is injected into the subcutaneous tissues to aid in dissection. An infraclavicular approach to the plexus and proximal nerve branches is performed by incising the skin two fingerbreadths below the clavicle and carefully opening the interspace between the sternal and clavicular heads of the pectoralis major. Thin skin flaps are raised and the subcutaneous chest fat is thinned for improved EMG signal detection over an area of approximately 100 cm2 from the medial chest to the anterior axillary line and from the clavicle inferiorly toward the nipple. An adipofascial flap is then elevated (Figure 90.1) for later placement between the pectoral heads to reduce aberrant reinnervation and to separate the muscle bellies from each other, thereby improving EMG signal differentiation.11 Next, the tissue plane between the clavicular and sternal heads of the pectoralis major is dissected. In this space, the motor nerve to the clavicular head is found, entering the muscle in a vertical direction. Occasionally, a second small motor nerve innervates this muscle. The sternal head generally has a medial branch, a middle branch located medial to the pectoralis minor tendon, a lateral branch that travels through the pectoralis minor muscle, and on occasion a far lateral branch that innervates the lateral most fibers of the muscle. All nerve branches to the pectoralis major must be identified so that the muscle is completely denervated by the end of the procedure. The origin of these motor nerves is irrelevant—only their size and location as they reach the muscle is important as they must be close enough to the mobilized median, radial, ulnar, or musculocutaneous nerves for the transfer. Next, either medial or lateral to the pectoralis minor tendon, the brachial plexus and nerves emanating from it are identified (Figure 90.2). The radial nerve is stimulated to make sure there is no triceps remnant to leave intact (which could be used as an intact signal for prosthetic elbow extension). The identity of the nerves is made by their branching pattern off of the brachial plexus. Deep to the plexus, the proximal thoracodorsal nerve is identified as another nerve transfer recipient. The donor nerves are cut back proximally as far as possible to reach normal fascicular architecture, while keeping enough length to avoid tension at the coaptation site. Often, 4 to 6 cm of nerve can be trimmed to reach a more normal appearing nerve. The nerve transfer is performed by dividing the small (1 to 1.5 mm) motor nerve innervating the muscle segment and coapting it directly to the large (1 to 1.5 cm) mixed nerve with 6-0 permanent monofilament suture from epineurium to epineurium (Figure 90.3). The site where a motor nerve enters the muscle is termed as “motor point.” A tacking suture into the nearby muscle epimysium helps stabilize and reduce tension on the coaptation site.

FIGURE 90.2. The branches of the brachial plexus are dissected. Note the large end neuromas, which will be transected along with several centimeters of nerve proximal to the neuroma based on the distance to each nerve’s target motor point.

FIGURE 90.3. The epineurium of the radial nerve is coapted to the epineurium of the thoracodorsal target motor nerve using 6-0 permanent monofilament suture.
Typically, there are four nerves to transfer and there must be four recipients (Figure 90.4). The most common transfers are the musculocutaneous nerve to the motor point of the clavicular head of the pectoralis, the median nerve to the largest motor point innervating the sternal head of the pectoralis, and the radial nerve to the thoracodorsal. In certain cases, the radial nerve is coapted to the long thoracic nerve, or to a nerve innervating the lateral, inferior aspect of the pectoralis major. Ideally, the coaptation occurs directly to the recipient nerve as it enters the muscle (i.e., to the motor point), to minimize the distance required for nerve regeneration. Given the location of the thoracodorsal nerve, there is usually a slightly greater distance from the coaptation site to the latissimus muscle, and as such there may be a longer time period before reinnervation. When available, the best target motor point for the radial nerve is one of the lateral motor nerves to the pectoralis major because they are closer to the target muscle than either the long thoracic or the thoracodorsal nerves are to the serratus and latissimus, respectively. The recipient for the ulnar nerve is generally the motor point found on the lateral and deep aspect of the pectoralis minor. Alternatives for the ulnar nerve include the long thoracic nerve, or the most lateral motor nerve innervating the pectoralis major. If the pectoralis minor is used, it is mobilized laterally and superficially away from the overlying pectoralis major for better signal detection. The sternal and clavicular heads of the pectoralis are routinely separated to provide two targets. The sternal head can be additionally split based on its neurovascular anatomy to create an additional target (Figure 90.4). These segments should be at least 4 to 5 cm in diameter for adequate signal detection. The adipofascial flap is then divided and placed in between the segments to reduce aberrant reinnervation and to physically separate the muscle bellies from each other (Figure 90.5).
The skin is closed over drains after placement of the quilting sutures to reduce the likelihood of seroma formation, and quilting sutures are used to bring the skin down to the chest and pectoralis muscle. The patient may resume wearing his/her original prosthesis when there is adequate wound healing and after postoperative swelling subsides, which typically occurs after 6 weeks. Prosthetic fitting for new control sites will take place after the newly neurotized muscles’ EMG signals have become robust, in approximately 3 to 6 months. If used as a target, the latissimus muscle, being farthest away from the coaptation site, will take the longest to come under cortical control.
Transhumeral Level. The indications to perform TMR at the transhumeral level include poor prosthetic function using standard body-powered, myoelectric, or hybrid systems despite adequate training. Good candidates are young patients with adequate biceps and triceps contraction without plexopathy, a long residual limb, and supple soft tissues. Bilateral amputees are considered for unilateral TMR surgery to enhance their dexterity while retaining the contralateral limb for more robust activities with a body-powered prosthesis. Patients who have suffered avulsions of the limb at the time of injury should be carefully screened to rule out brachial plexopathy, as this is a contraindication to surgery.
Preoperatively, Tinel signs signifying the ends of the median, ulnar, and radial nerve are marked. Tinel’s sign must be appreciated at or distal to the mid-humeral level, rather than high in the axilla, for the nerve transfers to be performed without tension. The patient is asked to contract the biceps and triceps muscles, and the midline of both of the muscles is marked, dividing the medial and lateral heads of the biceps and the long and lateral heads of the triceps, respectively. The typical nerve transfers for a transhumeral level amputee are shown in Figures 90.6A–E. The goal of the anterior incision is to transfer the median nerve to the motor point of the medial head of the biceps, while preserving the innervation of the musculocutaneous nerve to the lateral head of the biceps (Figures 90.6A–C). This will add a “hand-close” signal for the prosthesis, while preserving the “elbow flexion” signal of the native biceps. If the residual limb is long enough and a motor point to the brachialis is present, it can be used as a recipient for the ulnar nerve, adding an additional signal for wrist motion. Before the skin incision is made, a dilute epinephrine solution (1:200,000) is injected into the subcutaneous tissues beneath the planned incisions. The key to the dissection on both the anterior and posterior sides is cleanly opening the space between the muscle bellies and identifying all of the individual motor nerve branches to each muscle. It is important to completely denervate the target muscle to eliminate “cross-talk” from the native innervation and ensure that the only signal controlling the muscle comes from the transferred nerve. After the anterior skin incision is made, a proximally based adipofascial flap is elevated. This maneuver will thin the overlying soft tissues on top of the muscles to improve signal detection, and after placement between the heads of the biceps at the end of the procedure, physically separate the “hand-close” and the “elbow flexion” EMG signals. The neuromatous end of the median nerve is identified and cut back to healthy-looking fascicles. If there is redundancy when the nerve is brought to the motor point of the target muscle, more length may be trimmed. The median nerve is mobilized adjacent to the musculocutaneous nerve and its small motor nerve that enters the medial head of the biceps. For amputees with long residual limbs, a similar dissection is performed to mobilize the ulnar nerve adjacent to the motor point of the brachialis. The epineurium of both nerves is approximated using 6-0 polypropylene suture, and a tacking suture into the adjacent epimysium reduces tension across the coaptation.

FIGURE 90.4. The typical nerve transfers for a patient with a shoulder disarticulation are illustrated. Ideally, the radial nerve should be coapted to one of the motor points of the pectoralis major, if more than one is identified. Alternatively, the thoracodorsal or long thoracic nerves may be used (not shown), although given the increased distance to their target muscles, the time to reinnervation may be longer.

FIGURE 90.5. After the nerve transfers have been performed, the adipofascial flap is placed between the muscle segments to reduce aberrant reinnervation and improve EMG signal differentiation.
On the dorsal aspect of the arm, the skin incision is made between the long and lateral heads of the triceps, and an adipofascial flap is elevated. A schematic of the dorsal nerve transfer is illustrated in Figure 90.6D and E. The radial nerve is dissected and the branches to the long and lateral heads of the triceps are identified (Figure 90.7). The distal radial nerve is coapted to the motor nerve that innervates the lateral head of the triceps, while maintaining the native innervation of the long head of the triceps. This separates the “hand-opening” signal from the “elbow extension” signal of the proximal radial nerve. The adipofascial flap is placed between the heads of the triceps. Drains and a mildly compressing dressing are applied. Therapy can begin several weeks after the nerve transfer procedure.12
Transradial Level. Prosthetic hands with intrinsic thumb movements exist, as does “pattern-recognition” software that permits individual digit movement, but these are not widely available commercially. As such, there is not much to gain with TMR for the median and ulnar nerves in a transradial amputee. With their remaining forearm flexors and extensors, transradial almputees are able to perform intuitive hand-open and hand-close motions. A small free muscle transfer to the end of the residual limb might amplify either the motor aspect of the median or ulnar nerves without damaging the intact innervation of the forearm musculature, but this has yet to be performed clinically. TMR has also been performed in patients with this level of amputation for treatment of painful neuromas, which will be discussed in a later section.
TARGETED MUSCLE REINNERVATION VERSUS TRANSPLANTATION
Compositive tissue allotransplantation (CTA) and TMR have significant potential benefits and drawbacks for upper limb amputees,13 reviewed in Table 90.1. The ideal patient for TMR is an above elbow amputee, who wishes to have better control of his or her prosthetic device and is willing to accept the possibility of a transient increase in phantom limb pain. As mentioned above, TMR is also suited to bilateral amputees who are proficient with their more robust body-powered system, but wish to have TMR for tasks requiring more dexterity. Limb transplantation (Chapter 6) is considered for transradial- or distal-level amputees, with suboptimal prosthetic function whose body image is centered on the replacement of a human limb, and who are willing to accept the lifetime risks of antirejection medication. More proximal-level transplantation is not widely accepted because of the poor results that have been published,16 possibly related to the distance required for nerve regeneration. Interestingly, when we analyzed nerve segments discarded after TMR surgery, we found that the percentage of motor nerves was reduced within and just proximal to the end neuroma, and this percentage steadily increased with increasing distance from the distal end of the nerve. Moreover, the microarchitecture of these nerves in “normal” appearing areas was not normally organized and the organization also improved with distance from the neuroma (Figure 90.8). Although this observation is based on a small sample size, the trend suggests that motor nerves “die back” relatively far proximal to the end neuroma. It is not known if this observation is clinically relevant; however, it is less concerning for TMR surgery, because of the long segments of discarded nerves. It may be more worrisome for limb transplantation, because of the premium on the length of the remaining nerve. With current technology both for prosthetics and for CTA, we expect that proximal amputees (transhumeral level and above) would do better with TMR, and distal amputees (transradial level and below) better with CTA.
NEUROMA MANAGEMENT
Neuromas are significant problems after upper extremity amputations. Large series from areas of conflict document neuromas and stump pain in over one-fourth of upper extremity amputees.19,20 Neuroma pain is described as a localized area of chronic tenderness when pressure is applied, typically with a radiating sensation of discomfort in the area that the nerve had previously innervated. This is in contradistinction to phantom sensations, which are defined as the feeling that a deafferented body part is still present following amputation.21

FIGURE 90.6. The typical nerve transfers for a patient with a transhumeral-level amputation are illustrated. A. The musculocutaneous nerve and the motor points to the medial and lateral heads of the biceps brachii and the brachialis (if present) are dissected. B. The motor points to the medial biceps and brachialis are isolated and transected off of the musculocutaneous nerve. The native innervation to the lateral head of the biceps remains intact for the “elbow flexion” signal. C. The median and ulnar nerves are identified and transected as far proximally so as to be coapted without tension to the motor points of the medial biceps and brachialis for “hand-close” and wrist motion signals, respectively. D. The radial nerve and each of its motor points to the long and lateral heads of the triceps brachii are dissected. E. The distal radial nerve is mobilized and transected as far proximally as needed so as to be coapted to the motor point of the lateral triceps, for a “finger extension” signal. The innervation of the long head of the triceps remains intact, preserving the “elbow extension” signal.
Numerous strategies have been reported to be successful in the management of painful stump neuromas. The simplest method of neuroma excision and traction neurectomy has excellent or satisfactory results in 65% of patients.22 Neuroma excision with burying the nerve end in muscle,23 neuroma translocation away from areas of pressure,24 and the centro-centralization technique of Gorkisch25 have all been documented to have high levels of patient satisfaction and low recurrence rates. These studies are all limited by being small case series. Experimental neuroma work in animal models is hampered by an inability to differentiate a painless neuroma from a symptomatic one.

FIGURE 90.7. On the dorsal aspect of the arm, the radial nerve and braches to the long and lateral heads of the triceps brachii are identified. An adipofascial flap has been elevated for placement between the heads of the triceps muscles after the nerve transfer has been performed, to separate the finger extension from the elbow extension EMG signals.
Despite the mismatch in sizes between the donor mixed nerve and recipient motor nerve, none of the 40 patients who have undergone TMR (with 2 to 5 nerve transfers per case) have been re-explored for a symptomatic neuroma at the nerve coaptation site. We now routinely use the techniques of TMR for symptomatic neuromas in both the forearm and the leg, and preventatively at the time of a major planned amputation. In a transradial amputation, for example, the median nerve can be transferred to the anterior interosseous nerve through a proximal incision, the ulnar nerve can be transferred to a motor nerve innervating the flexor carpi ulnaris, and the radial nerve is transferred to the motor nerve innervating the pronator quadratus. In the lower limb at the time of an above knee amputation, the sciatic nerve can be split into its component tibial and common peroneal divisions26 and coapted to a motor point of the semimembranosis, the long head of the biceps femoris, or the semitendinosis (Figure 90.9).
TARGETED SENSORY REINNERVATION
In several patients, a sensory nerve in the vicinity of the motor nerve transfers has been coapted end-to-side to either the median or ulnar nerve to achieve targeted sensory reinnervation (TSR). Stimulation of the resulting reinnervated skin results in the sensation of the patient’s hand being touched, providing cortical feedback to the “hand” aspect of the brain. All modalities of cutaneous sensation are restored, including pressure, vibration, and thermal. Analysis of these patients has revealed an ability to discriminate between gradations of force28 that matches their uninjured skin. TSR not only improves the utility of the prosthetic device (patients do not drop or crush objects because they are able to sense what degree of force is being applied), but may allow the patient to integrate the prosthesis into the user’s self-image.29 The technology for TSR to be integrated into prosthetic devices, although still in developmental stages, has the potential to complete the restoration of the amputated limb.


FIGURE 90.8. A. Nerve specimens discarded at the time of TMR surgery were sectioned at 0.5 cm intervals into 5 µM slices and stained with myelin basic protein (MBP, green, which stains all myelinated neuronal tissue17) and choline acetyltransferase (ChAT, red, specific for motor nerves18) immunofluorescent markers. B. A 5 µM section of nerve 0.5 cm proximal to the distal end of the nerve. A motor nerve is signified by an inner spot of red (ChAT) staining the fascicle’s center surrounded by a green circular stain (MBP). Note the disorganized architecture and paucity of MBP + ChAT + axons. C. 5 µM section of nerve 4.5 cm proximal to the distal end of the nerve. Note the more organized architecture and presence of MBP + ChAT + axons, suggesting a relative abundance of motor nerves in this segment.

FIGURE 90.9. This patient with a transfemoral-level amputation had a symptomatic sciatic neuroma. At the time of surgery, a large neuroma was identified at the distal aspect of the sciatic nerve. The sciatic nerve was easily separated into its component tibial and common peroneal divisions,27 which were then coapted to the motor points of the semimembranosis and the long head of the biceps femoris, respectively.
CONCLUSION
TMR has been shown to restore intuitive limb control to upper extremity amputees and is appropriate for transhumeral and more proximal-level amputations. As specialists in delicate nerve handling and soft tissue rearrangement, plastic surgeons are well suited to perform this life-altering reconstructive surgery. A surgical training video for TMR can be found at http://www.ric.org/research/centers/cbm/index.aspx and http://drdumanian.com.
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