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Eftekari et al. Plast Aesthet Res 2022;9:43 https://dx.doi.org/10.20517/2347-9264.2022.33 Page 5 of 13

The simple neuroma excision with nerve retraction or manual burial into muscle relies on creating a safe
and privileged environment to shield the inevitable future neuroma from external stimuli. Although this
approach is used as standard therapy to reduce the risk of symptomatic neuroma formation, it does not
address the pathologic formation of a neuroma which is likely why the reoperation rates with this technique
remain as high as 65% .
[17]

TARGETED MUSCLE REINNERVATION
Targeted muscle reinnervation (TMR) was originally developed in 2002 as a method to augment the
interface of myoelectric prosthetics but was soon expanded for the treatment of symptomatic
neuromas [20,21] . The basis of this surgical approach is to introduce an autologous denervated target, in the
form of skeletal muscle, that has a high propensity for reinnervation in order to guide the newly transected
nerve into growing and establishing a connection with this target. TMR is considered a nerve transfer
because it transects a healthy motor nerve near the neuroma site to create the denervated skeletal muscle
target for the residual nerve to reinnervate [Figure 3] . The mixed nerve’s motor neurons then grow into
[22]
[2]
the denervated skeletal muscle and form new synapses, halting the growth of the neurons . By providing a
target for the transected nerve to reinnervate, TMR provides the regenerating nerve “somewhere to go and
something to do”, a term coined by Souza et al. . In doing so, TMR harnesses the physiology of a
[23]
regenerating nerve and works to prevent the pathologic formation of a future neuroma.

The surgical approach of TMR involves isolation of the symptomatic neuroma and proximal transection of
the involved nerve to resect the neuroma. The transected nerve is dissected away from surrounding tissue
and sharply cut to expose all of the nerve’s fascicles, preserving as much length as possible . Next, an
[22]
electric nerve stimulator is utilized to locate and isolate motor nerves that are innervating healthy skeletal
muscle adjacent to the site of the residual nerve . Muscles are specifically sought out that are functionally
[22]
not required or redundant to preserve the utility of an amputated limb . Once the motor nerve is identified
[18]
with a nerve stimulator, the motor nerve is transected near its entry into the muscle, thereby creating a
denervated muscle target . The residual nerve is then transferred to the motor nerve’s muscle entry site
[22]
[22]
and epineurial anastomosis is performed . Ideally, a small region of skeletal muscle around this site is also
dissected away and folded over the anastomosis to suture to the nerve epineurium in order to optimize
reinnervation of the muscle [Figure 4] . Although the TMR procedure results in a newly transected pure
[22]
motor nerve in order to create a target for the mixed nerve, this transected pure motor nerve has not been
[20]
shown to produce a clinically symptomatic neuroma .
Preclinical trials of TMR include an animal study involving five rabbits with neuromas, each undergoing
TMR procedures on their median, ulnar, and radial nerves onto motor nerves of their rectus abdominis
muscles . Ten weeks following surgery, histologic analysis of all of the anastomosis sites showed partially
[24]
regenerated nerves without the formation of a new neuroma, while electromyography showed partial
reinnervation of the rectus abdominis muscles in a segmental fashion . The histologic analysis also showed
[24]
decreased myelination of the nerves and increased fascicle diameter, both of which are considered favorable
[24]
characteristics following neuroma resection . Thus, this investigation was able to show successful
reinnervation of skeletal muscles using mixed nerves and prevention of neuroma formation using the TMR
approach .
[24]
Following these preclinical trials, Dumanian et al. compared TMR to standard simple neuroma excision
with muscle burial in 28 patients . Patients were blinded and followed postoperatively over a 1-year period.
[20]
Results revealed an overall significant improvement in patients’ phantom limb pain and a trend for
improvement in a patient’s residual limb pain . Although the TMR approach may provide a more
[20]