Upper Extremity Targeted Muscle Reinnervation

Residual limb and phantom limb pain can affect as many as 80% of individuals after amputation and can drastically affect a patient’s quality of life and ability to wear a prosthetic device. Targeted muscle reinnervation (TMR) is a novel nerve transfer technique developed to increase the number of available electromyography (EMG) signals available for myoelectric prosthetic control. This initial indication has been expanded as later studies have also shown a reduction in opioid usage and increased prosthetic wear, even in highly comorbid patients, secondary to reduced phantom and residual limb pain. In this article we review the relevant anatomy and discuss TMR nerve transfer options available for patients with amputations at varying levels including partial hand, trans-radial, trans-humeral and shoulder disarticulation.

Introduction

In the United States, there are 1.5-1.7 million amputees with an expected 50-100,000 new amputations each year. Although trauma is the most common cause of upper extremity amputation, other causes include vascular disease, infection, tumors, and diabetes mellitus. ^, Amputations have a significant impact on a people’s overall well-being including emotional and psychological distress, diminished function, and chronic pain. As high as eighty percent of patients with major limb amputations experience residual or phantom limb pain and 25 percent have chronic pain secondary to symptomatic neuromas.

Targeted muscle reinnervation was developed and described by Dumanian and colleagues to allow for more intuitive control of upper limb prostheses. Prior to the development of targeted muscle reinnervation (TMR) techniques, myoelectric upper limb prostheses were operated using 2 surface electrodes, each controlled by a separate, innervated muscle group. The user activated various prosthetic joints through co-contraction of these muscles, with linear control of the joints based on the signals from these 2 muscle groups. With TMR, the transected nerves are rerouted to motor nerve targets innervating specific muscle units within the residual limb. These coaptations allow for the creation of up to 6 distinct myoelectric signals, enabling more intuitive and simultaneous control of multiple prosthetic joints. ^, Although, TMR was created for improved function, it was additionally noted that TMR decreased phantom limb pain and pain from residual limb symptomatic neuromas, resulting in widespread use for pain management even in patients who may never utilize a myoelectric prosthesis

Concepts in TMR

Fundamentally, TMR consists of an end-to-end nerve transfer that involves a donor nerve and a recipient nerve. Any sensory, motor, or mixed motor-sensory nerve can serve as the donor nerve, depending on the reason for TMR. The recipient nerve is a motor nerve which innervates an expendable, nonessential muscle target. The premise of the nerve transfer is to provide a suitable environment for axonal regeneration and organized nerve growth. For myoelectric control, the process of reinnervating specific target muscles creates new end effectors for these neural signals, amplifying them and enabling interaction with a myoelectric prosthetic via surface electrodes. The donor nerve is any motor or mixed motor-sensory nerve responsible for motion of one of the amputated joints and the recipient nerve is a motor branch to a superficial muscle which can be easily detected by surface electrode. For pain, the nerve transfer provides a physiologically suitable environment for more organized nerve regeneration which can prevent neuroma formation and pain, by directing the regeneration of an amputated sensory or mixed motor-sensory nerve into a local motor branch and associated muscle.

Indications

TMR is indicated in patients who: (1) are undergoing an amputation, (2) have a prior history of amputation complicated by chronic pain, neuroma, phantom limb pain, and/or (3) utilize a myoelectric prosthetic.

Contraindications

The benefits of TMR should be weighed carefully. TMR is contraindicated in the setting of infection, active oncologic treatment, poor soft tissue, and medical instability. TMR is not recommended in patients with preganglionic brachial plexus injury, spinal cord injury, generalized peripheral neuropathy, and multilevel nerve injuries as these conditions may preclude nerve regeneration. TMR may not be suitable in patients with comorbidities such as diabetes, peripheral vascular disease, etc.; however, new literature suggests that these highly co-morbid patients may also benefit from improved function and decreased pain.

Relevant Anatomy

In upper extremity TMR, the major peripheral nerves (musculocutaneous, radial, median, and ulnar) are coapted to specific targeted motor nerve branches. Understanding and knowing the anatomical course of the nerve involved is imperative in performing TMR successfully and efficiently.

The musculocutaneous nerve (C5-C7) arises from the lateral cord of the brachial plexus. The nerve courses from the inferior border of the pectoralis minor and enters the anterior compartment of the upper arm as it pierces the coracobrachialis approximately 5.6 cm from the coracoid process. The nerve then continues between the biceps and the brachialis. The motor branches to the biceps and brachialis muscles exit from the musculocutaneous nerve at 11.9 cm and 17.0 cm, respectively, from the coracoid process. The nerve continues distal to the elbow and pieces the deep fascia lateral to the biceps brachii tendon. The musculocutaneous nerve terminates in the forearm as the lateral antebrachial cutaneous nerve.

The median nerve (C5-T1) arises from the lateral and medial cords in the axilla and descends anterior to the coracobrachialis and medial to the biceps. The nerve then courses under the bicipital aponeurosis at the elbow and continues distally in the forearm between the superficial and deep heads of the pronator teres. In the upper arm, the median nerve does provide sympathetic innervation to the brachial artery but does not give off any motor branches. A variant of the median nerve with motor branches to the coracobrachialis, brachialis, and biceps has been described in the setting of an absent musculocutaneous nerve. The nerve continues in the forearm between the flexor digitorum superficialis (FDS) and flexor digitorum profundus (FDP). The proper median nerve gives off motor branches to the pronator teres, palmaris longus, flexor digitorum superficial, and flexor carpi radialis (FCR). The anterior interosseous nerve (AIN) branches off the median nerve approximately 5 cm distal to the medial epicondyle. The AIN innervates the index and middle FDP, flexor pollicis longus (FPL), and pronator quadratus. The palmar cutaneous branch of the median nerve (PCBMN) is the last branch before the nerve enters the carpal tunnel. Distal to the carpal tunnel, the median nerve gives off a sensory branch which divides into the palmar digital nerves, motor branches to the 1st and 2nd lumbricals, and the motor recurrent branch. The motor recurrent branch innervates the opponens pollicis, abductor pollicis brevis, and flexor pollicis brevis. ^,

The ulnar nerve (C8-T1) arises from the medial cord of the brachial plexus. The nerve proceeds medial to the axillary artery. The ulnar nerve passes from the anterior compartment to the posterior compartment through the medial intermuscular septum (Arcade of Struthers) approximately 9.6 cm proximal to the medial epicondyle. At the level of the elbow, the nerve gives off proprioceptive articular branches. In the forearm, the nerve travels deep to the flexor carpi ulnaris (FCU). In the proximal forearm, the ulnar nerve gives of motor branches to the FCU and medial half of the flexor digitorum profundus (FDP). Numerous variations have been noted of the motor branches of the FCU. The average number of motor branches is 2.9 and arise at a mean distance of 1.9 cm distal to the medial epicondyle. Branches to the FDP typically arise from the radial aspect of the nerve at an average of 5 cm from the medial epicondyle. ^, As the nerve continues distally, the dorsal cutaneous branch of the ulnar nerve exits approximately 5 cm proximal to the wrist before the ulnar nerve, along with the ulnar artery, enters the hand through Guyon’s canal. The nerve divides and terminates into the superficial sensory branch and deep palmar motor branch.

The radial nerve (C5-T1) arises from the posterior cord along with the axillary nerve. Before exiting into the posterior compartment through the triangular space, the radial nerve gives of a branch to the long head of the triceps. It then descends along the upper arm in the spiral groove. Within the groove, the radial nerve gives off 4 branches: inferior lateral cutaneous nerve, posterior cutaneous nerve, branch to the lateral head of the triceps, and branch to the medial head of the triceps and anconeus. The radial nerve exits from the spiral groove 10 cm proximal to the lateral epicondyle. It then pierces the lateral intermuscular septum to enter the anterior compartment no less than 7.5 cm from the distal humerus articular surface. As the nerve courses between the brachialis and brachioradialis it continues to give motor branches to the brachialis, brachioradialis, and wrist extensors. At the radiocapitellar joint, the radial nerve divides into the posterior interosseous nerve (PIN) and superficial branch of radial sensory nerve (SBRN). The posterior interosseous nerve, along with the posterior interosseous artery, travels between the brachioradialis and ECRL in the forearm and pierces through the supinator. As the nerve travels between the superficial and deep compartments of the dorsal forearm, the PIN gives off branches to the digit extensors (EDC, EIP, EDM), ECU, APL, EPL, and EPB. The PIN terminates at the floor of the fourth dorsal extensor compartment. The SBRN runs along the underside of the brachioradialis. About 8 cm proximal to the radial styloid, the SBRN becomes superficial and innervates the dorsal radial hand.

Preoperative Evaluation

Patients may undergo TMR either acutely at the time of the initial amputation (primary) or at a later stage (secondary). Those considered for TMR should undergo a comprehensive evaluation, beginning with a detailed history and physical examination. Key information to gather includes the timing, location, and cause of the amputation. The physical examination should assess the viability and condition of remaining muscles, the length of the residual limb, the quality of surrounding soft tissues, and sites of nerve pain (positive Tinel sign). Additional diagnostic testing may be necessary, including radiographs of the affected extremity to assess the length and bony anatomy.

Prior to proceeding, patients should be optimized. Patients with poor vasculature should undergo vascular studies and wound healing evaluation. Patients with a traumatic amputation or amputation with associated nerve injury may need further evaluation with NCS-EMG to identify viable donors and targets. Special consideration should be given to the oncologic population. Chemotherapy and local radiation may compromise healing. Care should be coordinated with the primary oncology team. ^,

Surgical planning should also include bony procedures and osteotomies as well as soft tissue coverage. For example, an angular osteotomy or shoulder arthrodesis may be considered for patients with a trans-humeral amputation or elbow disarticulation to improve prothesis fitting and function. Coverage with regional and free flaps should be coordinated with appropriate surgical teams.

In patients undergoing TMR for pain, there should be careful assessment of previous treatment, limb function, type of pain (neuroma, centralized, phantom limb pain, etc.), and location of pain. An ultrasound guided lidocaine injection at the site of the neuroma or affected nerve may be helpful preoperatively with pain scores recorded pre- and postinjection. ^,

Surgical Technique

Anesthesia options include general anesthesia with limited paralysis or monitored anesthesia with regional block depending on level of amputation. Special equipment needed for the procedure include loupe magnification, microsurgical instruments, nerve stimulator, fibrin glue, and vessel loops. The level of amputation, prior surgical debridement, and scarring may lead to great variability in the available donor and recipient target nerves. Surgical planning, intraoperative flexibility, and knowledge of the anatomy is key in performing the procedure. Table 1 shows possible nerve transfers for various amputation levels.

Table 1

Demonstrates the Donors and Recipients at Varying Amputation Levels

Amputation Level	Donor Nerve	Target Nerve Option
Hand (digit, metacarpal, carpal level)	Digital nerves	Interossei
		Lumbricals
		Recurrent motor branch of median
		Motor branch of ulnar
	SBRN	1st dorsal interossei
		Pronator quadratus
Trans-Radial
	Median	FDS
		PL
		FCR
		BR
	Ulnar	FCU
		FPL
		FDP (ulnar)
		PL
	SBRN	AIN
		ECRB
		FDP
Trans-Humeral
	Musculocutaneous	Biceps (long head)
	Radial (proximal)	Triceps (long head)
	Radial (distal)	Triceps (lateral head)
		Triceps (long head)
		Brachioradialis
		Brachialis
	Median	Biceps (short head)
		Biceps (long head)
		Brachialis
	Ulnar	Brachialis
		Deltoid
		Triceps (medial head)
Shoulder disarticulation
	Median	Pectoralis Major (sternal head)
		Pectoralis major (clavicular head)
	Musculocutaneous	Pectoralis Major (clavicular head)
		Deltoid
	Ulnar	Pectoralis Minor
		Pectoralis Major
		Deltoid
		Latissimus Dorsi
	Radial	Thoracodorsal nerve
		Serratus anterior
		Deltoid
		Teres major