Keywords
targeted muscle reinnervation - nerve transfers - painful neuromas - myoelectric prosthesis
Introduction
Targeted muscle reinnervation (TMR) was developed based on the principle of “giving
a nerve somewhere to go and something to do,” which results in direct nerve-to-nerve
healing.[1] Coaptation of severed peripheral nerves to freshly divided motor nerve branches
enables the fascicles of the proximal nerve to grow into the motor end plates and
reinnervate the target muscle rather than forming a symptomatic neuroma.[2]
[3]
[4] The injured/transected peripheral nerves retain their upper nerve innervation from
the motor cortex, necessitating the absence of upper motor nerve injury for effective
TMR. This reinnervated muscle also acts as a bioamplifier that can be detected on
an electromyogram. Thus, as first performed by Souza et al in 2014, TMR was originally
intended to improve myoelectric prosthesis control for amputees.[4] The “secret” of TMR is that the donor motor nerve does not become a symptomatic
neuroma and the TMR nerve transfers “steal” the end receptors in the target muscle.
While divided motor nerves form neuromas, there are no case reports in the literature
of a symptomatic motor nerve neuroma.
Chronic neuroma pain is often described as a sharp, electric, burning pain associated
with minor stimuli (e.g., light touch, pressure, temperature changes) or no stimulation.[5] The neuromas can develop due to a nerve injury following trauma, amputation, or
surgery as the injured mixed (motor and sensory) or sensory nerve sprouts in a chaotic
manner to find a distal nerve or end organ in an attempt to heal.[6]
[7]
[8] With amputation, however, there are multiple severed nerves without any distal target
organ to reinnervate, resulting in uncontrolled proliferation of axons and connective
tissue, forming a neuroma.[9] Approximately 25 to 71% of these neuromas are symptomatic.[10]
[11]
[12]
[13]
[14] The symptomatic neuromas are the primary cause of postamputation pain, including
residual limb pain (RLP) and phantom limb pain (PLP; pain or unpleasant sensation
referred to the missing limb; possibly due to the interaction between neuroma and
multiple levels of the central nervous system [CNS]; correlated with cortical reorganization
and gray matter changes).[13]
[15]
[16]
[17]
[18]
[19]
[20]
[21]
[22]
[23] The symptomatic neuromas not only affect patients' quality of life but also their
functional abilities and independence as the neuroma pain can be exacerbated by prosthesis
use, making it difficult or even intolerable to wear.[11]
[24]
[25]
[26] There are approximately 2 million amputees living in the United States, and this
population will increase to 3.6 million by 2050 with approximately 185,000 major limb
amputations being performed each year.[26]
[27] Considering that at least 25% of the amputee population will develop chronic RLP
and/or PLP due to symptomatic neuromas, chronic neuropathic pain is a significant
public health issue.[11]
[13]
[14]
Evidence
Myoelectric Prostheses Control
The original case series from Kuiken et al (2004, 2007) demonstrated the benefits
of TMR for myoelectric prosthesis control in the proximal upper extremity amputee.[2]
[3] Since those studies were reported, more have followed that support the benefits
of TMR for myoelectric prosthesis control following upper extremity amputation.[4]
[28]
[29]
[30] TMR facilitates intuitive prosthesis control and allows two prosthetic joints to
be moved simultaneously. In addition, it enables control sites for multiple prosthetic
functions (hand open/close, elbow flexion/extension, wrist flexion/extension, and
wrist prono-supination).[31] After a decade of performing TMR for prosthetic control, it was observed that TMR
may also treat chronic postamputation (both neuropathic and phantom) pain.[10]
Phantom Limb Pain and Neuroma Pain
While PLP is distinct from symptomatic neuroma pain, these pain sources are not always
mutually exclusive, and, currently, there is no widely accepted standard to treat
phantom limb or neuroma pain. However, various surgical strategies (e.g., neuroma
excision and burying into nearby muscle, bone, nerve, back on itself; regenerative
peripheral nerve interfaces [RPNIs]) and nonsurgical strategies (e.g., pharmacologic
therapy, psychological and behavioral strategies, and interventional/minimally invasive
procedures) exist to treat PLP and/or symptomatic neuroma pain.[5]
[26]
[32]
[33]
[34]
[35]
[36]
[37]
[38]
[39]
[40]
[41]
[42]
[43]
[44]
[45]
[46]
[47]
[48]
[49]
[50] A recent meta-analysis reports that surgical procedures resulted in a substantial
decrease in neuropathic pain in 77% of the patients, without significant differences
between surgical techniques (“excision and transposition, excision only, excision
and repair, neurolysis and coverage, and excision and cap”).[51] While neuromodulators, specifically gabapentin, have been shown to have positive
effects in preventing postamputation PLP in pediatric patients,[52] benefits to medical and pharmacological treatments in treating PLP are still inconclusive.[50]
[53]
[54]
While there may not be a “gold standard,” recent studies demonstrate the promising
role of TMR in both the prevention and treatment of phantom limb and neuroma pain.
A prospective, single-blind, randomized control trial study comparing TMR to standard
surgical strategies (neuroma excision and muscle burying) in 28 amputees (total of
30 limbs) with chronic neuroma-related RLP and PLP demonstrated that there was a trend
in a greater reduction in numerical rating scale (NRS) with worst PLP and RLP at 1-year
follow-up in the TMR group versus standard; however, the percentage of patients reporting
no pain or mild pain at 1.5-year follow-up was significantly higher in TMR group than
in standard treatment group for both RLP (67% vs. 27%) and PLP (72% vs. 40%).[1] Similar to these results, a prospective case series on 33 amputees who underwent
TMR for neuroma pain after being ineligible for randomization, or refusal to be randomized,
reported improvement in limb function and a significant decrease in the numeric pain
score on 11-point NRS by 1 year after TMR for both RLP (from 6.4 ± 2.6 to 3.6 ± 2.2;
mean difference of −2.7) and PLP (6.0 ± 3.1 to 3.6 ± 2.9; mean difference −2.4).[55] The positive impact of TMR in treating neuropathic and PLP, as supported in the
studies above, may be due to its effects on peripheral nerve regeneration, which has
been reflected in histology studies showing the restoration of axon count, size, and
myelination after TMR in a rabbit amputation model, electromyography studies showing
synaptic inputs to reinnervated muscles, and MRI studies suggesting the role of TMR
in reversing pathological cortical reorganization associated with PLP.[56]
[57]
[58]
[59]
[60]
[61]
[62]
TMR can be used at the time of amputation for the prevention of symptomatic neuromas
and PLP (acute TMR) or in an established amputee for the treatment of chronic neuroma
pain (delayed TMR).[63] Numerous studies to date have shown a reduction in neuroma pain without the formation
of new neuromas and enhancement of myoelectric prosthesis use after acute TMR and
delayed TMR.[3]
[4]
[10]
[34]
[64]
[65]
[66]
[67]
[68]
[69] A recent cohort study comparing 100 patients undergoing below-knee amputation (BKA)
with acute TMR versus 100 patients undergoing BKA and traction neurectomy and muscle
implantation demonstrated significantly less RLP and PLP in the TMR cohort.[70]
The benefits of TMR can be extended to nonamputees with symptomatic neuromas or unreconstructable
nerve injuries with multiple studies showing improved pain, function, and quality
of life outcomes in these patients treated with TMR.[71]
[72]
[73]
[74]
[75] In addition, successful reinnervation following TMR was observed in 96% (94/98)
of transferred nerves,[6] suggesting the potential usage of TMR as a first-line surgical treatment option
for symptomatic neuroma pain amputees and nonamputees alike. While sacrificing a motor
branch in a nonamputee may be questionable, however, TMR involves the use of only
redundant motor branches to minimize downgrading of motor function following nerve
transfer. Evidence to support this concept includes a 15-patient case series of nonamputees
treated with TMR for symptomatic neuromas, no patients had postoperative motor weakness
of their donor nerve.[75] The ability of TMR to give transected nerve endings “somewhere to go and something
to do,” and potentially improve organized peripheral nerve regeneration, is the main
concept behind its efficacy in treating mixed and sensory peripheral neuromas in amputees
and nonamputees.[1]
[76]
Preoperative Considerations
Preoperative Considerations
Anesthesia (Authors' Preference)
Procedures are performed under regional anesthesia for distal amputations, and under
general anesthesia for more proximal procedures. Long-acting muscle relaxants and
local anesthetics are avoided to permit motor nerve identification with nerve stimulators.
Regional anesthesia is a good consideration for patients in the supine position who
have significant comorbidities. Tourniquet time for upper and lower extremity TMR
should be less than 45 minutes to allow for reliable intraoperative stimulation of
motor nerves.[76]
Surgical Techniques (Authors' Preference)
Prior to the operation, the locations of the painful neuromas (if present) are marked,
as they are often heralded by Tinel's signs. The essential operative steps of TMR
are (1) symptomatic neuroma identification and excision when feasible, (2) preparation
of neuroma stump to healthy fascicles, (3) recipient motor nerve identification with
a nerve stimulator, and (4) tension-free coaptation. Recipient motor nerves are redundant
branches of local muscles. The motor nerve must be redundant to not lead to appreciable loss of function when transected to serve as a recipient for
the donor nerve ending. Typically, the donor nerve is coapted as close as possible
to the target muscle to reduce time to reinnervation.[77] The coaptation is performed under loupe magnification with 6–0 or 7–0 polypropylene
epineural sutures. Size mismatch is common and not of concern.
Acute Targeted Muscle Reinnervation
Acute Targeted Muscle Reinnervation
Given the high-level evidence of TMR for both improved myoelectric prosthetic use
and RLP/PLP reduction, acute TMR (commonly defined as within 14 days/2 weeks of major
limb amputation) is now performed routinely.[1]
[34]
[67]
[68]
[70]
[76]
[78] In fact, data suggest that TMR performed at the time of amputation provides greater
RLP and PLP relief than no TMR performed acutely.[34] Complicating considerations include the potential loss of muscle bulk and prosthetic
padding with TMR nerve transfers and the finding that up to 25% of major limb amputees
without any nerve interventions have painless limbs without phantoms.[13] Acute TMR risks overtreatment of the amputee but does so to provide improved comfort
for the 25% of amputees that develop severe pain and phantoms. Acute TMR should be
considered when (1) the nerves have not been avulsed proximally, (2) there are redundant
motor targets, (3) there is well-vascularized soft tissue to close, and (4) patients
can tolerate the additional time in the operating room with anesthesia (see
[
Table 1
]
for a summary of surgical approaches and nerve transfers for TMR in the acute setting).[68]
[70]
[76]
[79]
[80]
Table 1
The surgical approach to the acute amputee is described with corresponding sensory and motor target nerves for coaptation
and surgical tips for a successful operation
|
Amputation type
|
Incision/Dissection
|
Sensory/Mixed nerves
|
Target motor nerves
|
Prosthetic function
|
Notes
|
|
Shoulder disarticulation
|
Transverse, 2 cm inferior to clavicle split pectoralis heads and develop space can
transect pectoralis minor if significant scar present
|
Median
|
Split sternal head
|
Hand function
|
Most variable of TMR patterns presence/absence of humeral head indicates pectoralis
position long thoracic can be coapted to if listed targets absent/nonfunctional MCN
and MN prioritized for elbow flexion and grasping
|
|
Ulnar
|
|
Musculocutaneous
|
Clavicular head
|
Elbow flexion
|
|
Radial
|
Thoracodorsal
|
Extensors
|
|
Transhumeral
|
Anterior, biceps raphe retract short head medially posterior, triceps raphe begin
blunt dissection cephalad
|
Median
|
Short head biceps
|
Hand function
|
Mark biceps and triceps raphe preop adipofasical flap used to increase spatial differentiation
preserve native innervation to long head of biceps and triceps for elbow function
|
|
Ulnar
|
Brachialis
|
|
Distal radial
|
Lateral head triceps
|
Hand open
|
|
Transradial
|
Large volar and dorsal fish-mouth incisions planned to prevent closure directly over
terminal residuum
|
Median
|
Brahioradialis, FDS/FDP
|
Hand function
|
Minimum of 5 cm radius and/or ulnar for prosthetic variable transfer pattern depends
on indication for amputation
|
|
Ulnar
|
FCU
|
|
Sensory branches radial
|
Pronator quadratus, FDS/FDP, ECR
|
RLP/PLP prevention
|
|
AKA
|
Posterior, vertical 10 cm mid-axis
Bluntly dissect hamstring musculature medial thigh at level of Hunter's canal
|
Tibial
|
Semimembranosus
|
Plantarflexion
|
See cadaveric study for detailed motor entry points (Agnew et al 2012) intuitive powered
prosthetics for stair climbing rely on TMR
|
|
Common peroneal
|
Long head biceps femoris
|
Dorsiflexion
|
|
Posterior cutaneous nerve of thigh
|
Short head biceps femoris
|
Plantar sensation
|
|
Saphenous
|
Vastus lateralis
|
RLP/PLP prevention
|
|
BKA
|
Within the operative field, supine
|
Tibial
|
Soleus, FDL
|
RLP/PLP prevention[a]
|
See cadaveric study for detailed motor entry points (Fracol et al 2018)[83]
|
|
Deep peroneal
|
Tibialis anterior
|
RLP/PLP prevention[a]
|
|
Common peroneal
|
Peroneus longus
|
RLP/PLP prevention[a]
|
Abbreviations: AKA, above-knee amputation; BKA, below-knee amputation; ECR, extensor
carpi radialis; FCU, flexor carpi ulnaris; FDL, flexor digitorum longus; FDS/FDP,
flexor digitorum superficialis/profundus; MCN, musculocutaneous nerve; MN, median
nerve; TMR, targeted muscle reinnervation.
a Prosthetics employing these myoelectric signals currently only exist in the laboratory
setting.
Shoulder Disarticulation
The approach to TMR in the setting of shoulder disarticulation is among the most difficult
to perform given multiple factors. The first is that a damaged or compromised surrounding
soft tissue envelope is very common, requiring a thorough preoperative evaluation.
This evaluation assesses both the soft tissues that the prosthesis will rest on and
the remaining musculature for potential motor targets. Volitional control of the pectoralis
major and minor muscles and latissimus dorsi is required since these are the common
motor targets at this level. Second, the presence or absence of a humeral head should
be evaluated with plain radiographs. Absence indicates that the pectoralis major and
its neurovascular bundle should be expected to have shifted 4 to 6 cm medially, while
the presence of the humeral head may indicate a residual triceps with radial nerve
(RN) innervation that may deserve preservation for an elbow extension signal.[78]
[81] A review of 26 consecutive TMR patients displays the complexity and variability
in the pattern of nerve transfers for the shoulder disarticulation level.[10] In comparison from the same study, all 16 transhumeral patients received the same
pattern of nerve transfers, to be discussed below, indicating reliable anatomy, whereas
10 shoulder disarticulation patients received 7 different transfer combinations.[10]
Dissection begins with a transverse incision 2 cm below the clavicle and continues
to identify and develop the potential space between the sternal head (SH) and clavicular
head (CH) of the pectoralis major, which is often marked by a stripe of fibrofatty
tissue. The CH overlaps the SH, and so the fibrous cleft is angled superiorly as the
dissection deepens. The motor nerve to the CH accompanies the vascular pedicle and
is located at the junction of the middle and lateral thirds of the clavicle. The motor
nerves to the pectoralis can be described as a medial clump, a middle grouping, and
a lateral fascicle that goes through the pectoralis minor to the lateral/inferior
border of the muscle. It is crucial to locate all native motor nerves to the pectoralis
major such that complete denervation can be achieved prior to nerve transfers. The
brachial plexus cords are next identified deeper in the fibrofatty tissue between
the SH and CH either medial or lateral to the pectoralis minor. In cases of secondary
fibrosis from trauma, the pectoralis minor tendinous insertion on the coracoid process
can be released. If more length is needed, the nerves can be mobilized to lie medial
to the pectoralis minor. Depending on the patient, correct identification of cords
can be quite challenging, however, postoperative myoelectric mapping solves this issue.
Spatial differentiation and successful neurotization are the two primary goals. Ideally,
the musculocutaneous nerve (MCN) is coapted to the motor nerve to the CH, median nerve
(MN) and ulnar nerve (UN) coapted to split segments of the SH, and RN to the thoracodorsal
nerve.[78]
[81]
In the setting of delayed shoulder TMR for prosthesis optimization ([Fig. 1] and [Video 1]), it is recommended to surgically thin the skin overlying the pectoralis major to
assist with signal recognition, although newer pattern recognition technologies may
obviate the need for thinning. A rich subdermal plexus prevents skin flap necrosis
or poor healing. The MCN and MN represent the two most important nerve transfers as
they allow for elbow flexion of the device and hand closing. For this reason, the
MCN is transferred to the CH as this achieves the most robust, reproducible myoelectric
signal for the surface electrodes.[78]
[81]
Fig. 1 Example of delayed shoulder TMR for myoelectric prosthesis control. The patient is
a 42-year-old male with a previous right upper extremity trauma complicated by infection
requiring shoulder disarticulation who presented with no pain but poor myoelectric
prosthetic control. Of note, a pedicled latissimus muscle flap was previously required
for soft tissue coverage and preop findings were as follows: triceps 0/5, deltoid
1 to 2/5, remnant proximal biceps 2/5, latissimus muscle flap 2/5 (retained voluntary
contracture). (A) demonstrates the planned incision two finger-breadths below the clavicle medial
to sternal notch then laterally and inferiorly along deltopectoral groove. (B, C) demonstrate the nerves dissected and ready for transfer to motor targets with [Video 1] displaying the target motor nerve being stimulated. (D) demonstrates the coaptations performed with 7–0 prolene in end-to-end epineural
fashion: (1) MCN to the motor branch of the clavicular head of pec major (elbow flexion),
(2) median nerve to lateral pectoral nerve (medial and upper sternal head of pec major
muscle; hand close), (3) radial nerve to medial pectoral nerve (lower lateral pec
major sternal head; elbow extension and finger/thumb extension), (4) ulnar nerve to
thoracodorsal nerve (not shown in the figure). (E) A medially based, pedicled adipofascial flap was raised and inset (F) between the clavicular and sternal heads of the pec major to buffer signaling of
elbow flexion (MCN to clavicular head) and elbow extension (radial to sternal head)
for the surface electrodes. MCN, musculocutaneous nerve; TMR, targeted muscle reinnervation.
Video 1 Delayed shoulder TMR for prosthesis optimization. TMR, targeted muscle reinnervation.
Transhumeral
The goals of acute TMR in the transhumeral patient are to preserve native elbow flexion
and extension signals via the MCN innervation of the long head of the biceps and RN
innervation of the long head of the triceps, respectively, while creating novel “hand
open” and “hand close” signals. Before anesthesia, preoperative Tinel's signs can
often help identify end neuromas of the MN, UN, and RN. The biceps and triceps muscle
bellies are also marked by an absence of a hand and humeral condyles can make locating
intraoperative landmarks challenging. Positioning typically begins supine with an
arm board for the anterior nerve transfers, and the patient is flipped to the prone
position for a posterior approach.[78]
[81] Alternatively, transhumeral TMR can be performed in the lateral decubitus position
to avoid a position change. For neuroma control only, all transhumeral TMR nerve transfers
can be performed supine through a single anterior incision.[82]
The longitudinal anterior incision is made along the midportion of the biceps. A proximally
based adipofascial flap is created approximately 6 cm wide and dissected proximally
until the tendinous origin of the long head of the biceps is visualized. The fibrous
septum between the heads of the biceps is identified carefully. Blunt dissection in
this septum reveals the motor nerves emanating from MCN to innervate the biceps muscle
bellies. Proximally, the MCN branches to innervate the two heads, while distally it
continues to innervate the brachialis (MCN-Br) and form the lateral antebrachial cutaneous
(LABC) nerve. The motor branches to the two biceps heads enter the muscle approximately
one-third the length of the humerus and enter the brachialis approximately two-thirds
along its length. After identification of these entry points, dissection proceeds
to identify the MN and UN. This is facilitated by transposing the short head medially
and bluntly dissecting between the short head and the intermuscular septum (IMS).
The MN will be identified adjacent to the brachial artery and anterior to the IMS
and is transferred to the short head of the biceps while preserving the native MCN
innervation of the long head. The UN will be identified posterior to the IMS and transferred
to a motor branch to the brachialis. It must be noted that proximal branching of the
MCN to the short head can be variable in number—all MN motor branches need to be identified
and divided as they travel into the short head. The previously elevated adipofascial
flap is inserted into the raphe to assist with spatial differentiation of the myoelectric
signals and the incision is closed.[78]
[81]
The posterior incision is also made along the previously marked midportion of the
triceps muscle belly and proceeds analogously to the anterior approach with the development
of an adipofascial flap. The muscle bellies are then bluntly dissected beginning cephalad
near the inferior margin of the deltoid. Medial retraction of the long head typically
reveals the RN. The branch to the long head is typically quite proximal and not encountered
during dissection while multiple branches can be easily visualized innervating the
lateral head in this space. The distal RN branch is then divided and coapted to the
newly divided motor nerve of the lateral head; the adipofascial flap is inserted analogous
to the anterior approach and the incision is closed.[78]
[81]
Transradial
Preoperative assessment must evaluate remaining forearm bony structures and nerve
function. A minimum of 5 cm of residual radius and/or ulna is required to correctly
fit a prosthesis, and nerve damage proximal to the elbow will decrease the chance
of successful nerve transfers. The patient is positioned supine with an arm board
and tourniquet. Typically, for a primary transradial amputation that is more proximal
to the elbow, a large volar and dorsal fish-mouth-shaped incision is used. Full-thickness
skin flaps are elevated on the volar and dorsal surface with the incisions carefully
planned for closure to not occur over the terminal residuum.
For distal forearm or wrist-level amputations, TMR nerve transfers can be performed
through a single proximal volar forearm incision.[69] To access the donor motor nerves and their recipients, an incision is made proximal
to the elbow flexion crease and ulnar to the brachioradialis (BR) that extends in
a curvilinear fashion along the volar mobile wad to the midportion of the distal remaining
forearm.[69] Dissecting ulnar to the radial vessels, the MN is found in between the pronator
teres and the FCR, and the motor branches to the palmaris longus (PL; targets) are
found along the superficial surface of the flexor digitorum superficialis (FDS) deep
to the PL. Alternatively, if the patient does not have a PL, the MN can be coapted
to a local motor branch to the FCR or the anterior interosseous nerve (AIN). The MN
may be transferred to the BR or FDS or flexor digitorum profundus (FDP) if needed,
however, the motor branch to FDS is recommended to be spared as it is useful for finger
flexion/grasp control.[69]
The UN is transferred to a branch of the flexor carpi ulnaris (FCU) located proximally
within 5 to 7 cm of the medial epicondyle. First, the UN is found in the interval
between the proximal two heads of the FCU. Motor branches to FCU are locally identified
and selected to receive the UN transfer.[69] The UN can also possibly be transferred to a brachialis motor branch proximal to
the elbow.
After dissecting through the volar forearm fascia, dissection radial to the radial
vessels will help to identify the radial sensory nerve (RSN). The RSN can be transferred
to the FCR motor branch. An alternative transfer is the RSN to the BR-motor branch
through a separate proximal anterolateral incision used to expose the interval between
the brachialis and BR.[69] In this interval, several motor branches to the BR are found which can be coapted
to the RSN.
In very distal transradial or wrist-level amputees, the sensory branches of the RN
(SRN) can be transferred to the AIN to the pronator quadratus, if it remains, or the
FDS, FDP or extensor carpi radialis longus. Myodesis and myoplasty are then performed
to reestablish physiologic tension on the muscles and provide soft tissue coverage
of the residual limb.[77]
[78]
Above-Knee Amputation
TMR in the setting of an above-knee amputation (AKA) requires two incisions for the
transfer of the sciatic nerve (SN) and the femoral nerve (FN). The longitudinal 10-cm
incision is made along the proximal third of the posterior thigh with subsequent blunt
dissection revealing the hamstring musculature and SN. The SN is typically found caudal
to the gluteus maximus and deep and medial to the biceps femoris. The SN is further
bluntly dissected into its common peroneal and tibial components. The motor nerves
of the semitendinosus, semimembranosus, and biceps femoris are then identified as
the recipient motor nerves. Cadaveric studies guide the dissection with expected semimembranosus
motor nerve entry approximately 0 to 50% along the length of the total thigh and long
head of the biceps femoris 20 to 40%.[83] Some motor nerves leave the SN from under the gluteal muscles to innervate the proximal
hamstrings. These nerves are typically 2 mm in diameter. The SN proper can be expected
to give two to three motor nerve branches to each. The tibial division is transferred
to the semitendinosus/semimembranosus while the common peroneal nerve is transferred
to the long head of the biceps femoris. For neuroma prevention, the posterior cutaneous
nerve of the thigh can be transferred to a smaller, more distal biceps femoris motor
branch.[83]
With the patient flipped to the supine position, a 10-cm incision paralleling and
medial to the sartorius muscle is made to identify the femoral nerve in the proximal
thigh. Multiple saphenous sensory nerve branches can be identified exiting immediately
out of the femoral triangle, but more commonly, deeper, paralleling the femoral artery.
Multiple motor branches to the sartorius and the quadriceps are available with this
incision. Alternatively, the second incision can be made more medially over Hunter's
canal to identify and transfer the saphenous nerve to the motor nerve of the vastus
medialis.[78]
[84]
[85]
Below-knee Amputation
Acute TMR in the setting of a BKA is performed in the supine position. The number
of nerves transferred for acute BKA-TMR is debatable, some transfer all nerves, while
others just treat the tibial (TN) and superficial peroneal nerves (SPN). The TN is
typically transferred to a deep compartment motor nerve such as the flexor digitorum
longus (FDL) or the soleus. The deep peroneal nerve (DPN) is preferably transferred
to a tibialis anterior motor nerve, or extensor digitorum longus (EDL). The SPN is
transferred to a peroneus longus motor nerve. Cadaveric studies also guide this dissection
with lengths reported as measured from the lateral femoral condyle to the lateral
malleolus. The FDL can be expected to have approximately six motor entry points along
30 to 90% of the leg length, and the soleus has a reliable motor entry point at 30
to 40% of the leg length. The tibialis anterior has a reliable motor entry point at
30 to 70% of the leg length, and the EDL can be expected to have approximately three
motor entry points along 20 to 80% of the leg length. Finally, the peroneus longus
can be expected to have five to six motor entry points along 20 to 70% of the leg
length. The medial and lateral sural nerves can be coapted to motor nerves to the
gastrocnemius to reduce the probability of neuroma formation, although this can often
result in extensive posterior skin flap dissection.[78]
[83] An alternative to performing acute TMR from within the wound is to flip the patient
to the prone position and to perform TMR in the posterior knee as is done for established
BKA amputees ([Fig. 2] and [Video 2]).[7]
[83]
Fig. 2 Example of delayed BKA-TMR performed via a prone and supine approach. The patient
is a 45-year-old man status post-right traumatic BKA 4 years prior who presented with
symptomatic neuromas and phantom limb pain. Nerve transfers were first performed in
prone positioning through the popliteal fossa. (A) displays the patient in the prone position with a planned incision using the fibular
head as a guide. (B) displays the TN dissected with vessel loops around motor nerve targets. (C) displays the CPN dissected out with LSN. (D) displays the coapted nerve transfers (1) TN to the motor branch of FHL, (2) CPN
to the motor branch of soleus, (3) MSN to the motor branch medial gastrocnemius, and
(4) LSN to the motor branch lateral gastrocnemius. (E) Displays the patient now positioned supine with motor and sensory nerve targets
dissected. [Video 2] displays the nerve stimulator on the motor targets. (F, G) Display the coapted nerve transfers (5) SN to motor branch vastus medialis, (6)
MFCN to motor branch to sartorius. BKA, below-knee amputation; CPN, common peroneal
nerve; FHL, flexor hallucis longus; LSN, lateral sural nerve; MFCN, medial femoral
cutaneous nerve; MSN, medial sural nerve; SN, saphenous nerve; TMR, targeted muscle
reinnervation; TN, tibial nerve.
Video 2 Below-knee amputation.
Concerns regarding potential postoperative complications following TMR at the time
of BKA exist. Complications of BKAs include infection, delayed healing, heterotopic
ossification, PLP, and neuroma pain.[86] A 2022 multicenter study investigating risks of acute TMR in the setting of BKA
found that TMR at the time of BKA is not associated with statistically significant
increased risks of major or minor complications.[87] Another study published in 2023 of 100 highly comorbid patients treated with acute
TMR at the time of BKA found similarly no increased risk of postoperative complications
specific to TMR.[88] However, authors have advocated for the use of separate incisions (outside of the
zone of injury) during acute TMR for BKAs to decrease the risk of wound healing complications
for at-risk patients.[76]
Delayed Targeted Muscle Reinnervation
Delayed Targeted Muscle Reinnervation
Delayed TMR can be simply defined as TMR nerve transfers performed greater than 14
days following extremity amputation or peripheral nerve injury (see
[
Table 2
]
, a summary of surgical approaches and nerve transfers for TMR in the delayed setting).
Table 2
The surgical approach to the delayed amputee is described with corresponding sensory and motor target nerves for coaptation
and surgical tips for a successful operation
|
Amputation type
|
Incision/Dissection
|
Sensory/Mixed nerves
|
Target motor nerves
|
Prosthetic function
|
Notes
|
|
AKA
|
Single posterior incision 6–8 cm inferior limit of incision is 50% thigh length (reference
contralateral)
|
Common peroneal
|
Long head biceps femoris
|
Dorsiflexion
|
Posterior cutaneous nerve of thigh transferred to most proximal motor branch to reduce
tension on neurorrhaphy
|
|
Tibial
|
Semitendinosus
|
Plantarflexion
|
|
Posterior cutaneous nerve of thigh
|
Short head biceps femoris, semitendinosus
|
RLP/PLP prevention
|
|
Saphenous
|
Vastus lateralis
|
RLP/PLP prevention
|
|
Lateral femoral cutaneous
|
Vastus lateralis, rectus femoris
|
RLP/PLP prevention
|
|
BKA[a]
|
Anterolateral incision 30–60% leg length
|
Deep peroneal
|
Tibialis anterior
|
RLP/PLP prevention[b]
|
Very proximal BKA should use single-incision approach through single posterior midline
Single-incision approach increases the chances of anterior and lateral compartment
atrophy—proximal transfer of common peroneal
|
|
Superficial peroneal
|
Extensor digitorum longus
|
|
Posterior midline incision 10–40% leg length
|
Lateral sural
|
Lateral gastrocnemius
|
|
Medial sural
|
Soleus or medial gastrocnemius
|
|
Tibial
|
Soleus
|
|
Partial hand
|
Guided by amputation features and Tinel's sign
|
Ulnar/radial digital, common digital
|
Redundant intrinsic
|
Pain control only
|
Deep targets for median and ulnar-derived neuromas are the respective lumbricals/interossei
|
|
Median nerve-derived
|
RMBMN adductor pollicis
|
|
Ulnar nerve-derived
|
Palmaris brevis hypothenar branches
|
Abbreviations: AKA, above-knee amputation; BKA, below-knee amputation; PLP, phantom
limb pain; RLP, residual limb pain.
a This describes the two-incision approach to mitigate soft tissue atrophy over the
residual stump.
b Prosthetics employing these myoelectric signals currently only exist in the laboratory
setting.
Below-Knee Amputation
While delayed TMR at the AKA level is very similar to acute TMR, strategies for successful
nerve transfer differ between acute and chronic TMR for the BKA patient. For delayed
TMR, there is a desire not to dissect the distal stump as swelling and delayed wound
healing are often problematic. Instead, the tibial and sural nerve transfers are performed
in the proximal posterior leg. The TN is transferred to the motor branch to the soleus
muscle. The two sural nerves (from the tibial and peroneal nerves, respectively) are
transferred to the motor nerve of the FHL, or a nearby redundant motor nerve that
is found intramuscularly. To maintain muscle bulk, the medial gastrocnemius is often
left unperturbed, but can also be a target if necessary. Treatment of the CPN presents
a challenge that is debated. One simple solution is to transfer the entire CPN to
the motor nerve of the lateral gastrocnemius, which risks substantial atrophy of the
anterior compartment musculature. Another solution is to perform TMR in the lateral
decubitus position to perform the peroneal nerve transfers to muscles in the anterolateral
compartment. The saphenous nerve is treated in the thigh at Hunter's canal with a
transfer to the motor nerve of the vastus medialis ([Fig. 2] and [Video 2]).[89]
[90]
To compare these two approaches, the single-incision approach is easier with shorter
operating time, but the effort to preserve the proximal motor fascicle to the anterior
and lateral compartments is required for CPN transfer to minimize the denervation
and atrophy of these muscle compartments.[90] The double incision approach is useful in identifying more distal motor targets
for nerve transfer of DPN and SPN and preserving muscle bulk for prosthesis wear.[90] Hence, the latter approach is more commonly performed to prevent the atrophy of
the residual soft tissue. A study on TMR performed in 22 patients with BKA (18 primary,
4 secondary) reported that none of the patients developed a symptomatic neuroma for
a follow-up period of 18 months after the TMR surgery.[91]
Transradial
Delayed transradial TMR can be performed through a single proximal volar forearm incision
outside the zone of injury, as described above in the acute transradial TMR section.
All donor and target nerves are exposed from one volar incision that extends from
the elbow flexion crease to the mid-aspect of the forearm residual limb along the
medial border of the BR. Similar transfers of MN to PL (or FCR, AIN, or FDP), UN to
FCU, and RSN to FDS, FDP, or ECRL.[69]
[77]
Partial Hand Amputation
Painful neuromas can also develop after partial hand or finger amputations, with an
incidence of 7% forming after isolated digit amputations.[92]
[93] Case reports have demonstrated significant improvement in chronic neuroma pain in
partial hand amputation patients treated with TMR.[94] Specifically, Daugherty et al 2019 presented that for ulnar/radial digital and common
digital nerve painful neuromas, freshened proximal nerve endings can be successfully
transferred to redundant intrinsic muscle motor nerves.[94] Cadaveric studies then demonstrated that TMR after finger or partial hand amputation
is surgically feasible due to the redundant motor nerve branches to the intrinsic
hand muscles. For MN-derived neuromas, superficial targets include the recurrent motor
branch to the thumb, nerves to lumbricals 1/2/3, and deep targets include the adductor
pollicis branches, and first and second interossei branches. For the UN-derived neuromas,
targets include the hypothenar muscle branches, the third and fourth palmar and dorsal
interossei, as well as lumbricals 3 and 4.[95]
[96] Exact TMR nerve transfers will vary depending on the specifics of the partial hand
amputation ([Fig. 3] and [Video 3]).
Fig. 3 Example of delayed hand TMR. The patient is a 62-year-old female who suffered an
avulsion amputation of the right thumb with failed replantation at an outside hospital,
now status post multiple debridements and skin grafting with a symptomatic neuroma
of the digital nerve to the thumb. (A, B) Displays the markings for the simultaneous open carpal tunnel release to easily
access the thenar motor branch of the median nerve and the skin flaps that will be
raised. Her first metacarpal was also noted to be prominent and painful, so this was
also debrided (circular region). (C) Displays the dissected common digital nerve to thumb after distal transection to
healthy fascicles and thenar motor branch (vessel loop). [Video 3] demonstrates the thenar motor branch being stimulated. (D) Displays approximation of the common digital nerve to thumb and thenar motor branch
just prior to coaptation. TMR, targeted muscle reinnervation.
Video 3 Delayed hand thenar.
Chronic Neuroma Pain in the Nonamputee
Chronic Neuroma Pain in the Nonamputee
TMR can be applied to treat localized chronic neuroma pain in nonamputees when other
surgical interventions, such as neuroma excision and/or nerve reconstruction, have
been unsuccessful or are unfeasible. A retrospective review in 2021 of 15 nonamputees
who underwent TMR to redundant motor nerves for refractory neuroma pain demonstrated
significant improvement in pain and quality of life.[75] Here, we describe more detailed TMR techniques for common neuromas found in the
nonamputee patient population ([
Table 3
]
, a summary of surgical approaches and nerve transfers for TMR in the nonamputee).
Table 3
The surgical approach to specific neuromas in nonamputees is described with corresponding
sensory and motor nerves for coaptation
|
Neuroma
|
Incision location
|
Target motor nerves
|
Notes
|
|
Superficial radial
|
9-cm incision with distal edge
4–5 cm proximal to radial styloid
|
Brachioradialis
Extensor carpi radialis brevis
|
Preceding trauma/wrist surgery
|
|
Medial antebrachial cutaneous
|
10 cm V-shape with apex over medial epicondyle
|
Flexor carpi ulnaris
|
Prior brachioplasty, ulnar nerve decompression, elbow surgery
|
|
Lateral antebrachial cutaneous
|
8 cm volar midline
|
Flexor carpi radialis
|
Prior elbow surgery
|
|
At the level of the wrist
|
6 cm incision proximal to carpal tunnel
|
Terminal AIN
|
Can accept dUSN, distal LABC, distal branches of the SRN, and the PCB of the median
nerve
|
|
Saphenous
|
6–8 cm incision 10 cm cephalad to femoral condyle
|
Vastus medialis
|
Biceps femoris and gracilis are alternative targets
|
|
Medial sural
|
Superficial posterior 10–20% leg length
|
Medial/lateral gastrocnemius
|
Redundant innervation results in an insignificant change in function
|
|
Lateral sural
|
Lateral gastrocnemius
|
|
Deep peroneal
|
Anterior 50–70% leg length
|
Extensor digitorum longus
|
Avoid tibialis anterior in the nonamputee—risk of foot drop
|
|
Superficial peroneal
|
Lateral 20–40% leg length
|
Peroneus longus
|
Redundant innervation results in insignificant change in function
|
Abbreviations: dUSN, dorsal sensory ulnar nerve; LABC, lateral antebrachial cutaneous;
SRN, superficial branch of radial nerve; PCB, palmar cutaneous branch.
Upper Extremity
Some of the common upper extremity painful neuromas treated with TMR include SRN neuroma,
medial antebrachial cutaneous (MABC) neuroma, and LABC neuroma.
The SRN neuroma can form due to chronic compression, trauma, or wrist surgery. To
locate an SRN neuroma, an incision is made over the neuroma to begin the dissection.
RN neuromas may coexist with neuromatous changes of the lateral antebrachial cutaneous
nerve (LABCN). Recipients for the RN transfer include the motor nerve to the pronator
quadratus, ECRL, extensor carpi radialis brevis, and BR.[69]
[97]
[98] In the latter transfer, an incision is made proximal to the elbow flexion crease
to locate this motor nerve.
The MABC neuroma can arise following UN decompression, elbow surgery, or brachioplasty.
To approach the neuroma, a curvilinear incision is made along the course of pronator
teres toward the medial epicondyle and then toward the biceps. After the neuroma excision,
the MABCN can be transferred to a motor branch innervating the FCU or to a brachialis
motor branch proximal to the elbow.[69]
Finally, TMR for LABC neuroma involves making an 8-cm incision along the volar midline
just distal to the antecubital fossa to identify the neuroma, and the transected LABCN
can be transferred to a motor nerve supplying FCR.[89] A recent cadaveric study described the utility of using the terminal AIN as a recipient
for TMR to treat symptomatic sensory neuromas around the wrist for more distal LABC
neuromas.[99]
Saphenous
TMR is also considered for patients with unreconstructable saphenous neuromas which
can develop in the medial calf after saphenous vein harvest, trauma, or vein ablation.
Potential targets for an isolated saphenous nerve neuroma depend on the location of
the nerve injury. While motor units to medial gastrocnemius and medial soleus muscles
could potentially serve as targets, the performance of TMR at the level of Hunter's
canal is less complex due to predictable anatomy, less possibility for various nerve
branches, and larger nerve caliber.[83]
[89]
[90]
[100] When neurogenic pain occurs closer to the patella after a knee procedure, the medial
approach just to the saphenous nerve at Hunter's canal may not denervate an accessory
saphenous nerve branch that emerges proximal to this level. In these instances, diagnostic
nerve blocks may help distinguish if there is an accessory saphenous nerve. Accessory
saphenous nerve TMR is performed with an incision medial to the sartorius muscle as
described in the section for TMR for the FN in AKAs.
Sural
Sural neuromas can form after trauma, sural nerve harvest, or during exposure to foot
and ankle surgery. While reconstruction using allografts has been performed in the
past to restore sensation, the unpredictable relief of pain has led to the authors
abandoning this approach and only performing TMR for a painful sural nerve(s). To
approach the sural neuroma, a longitudinal incision is made over the Tinel's sign
over the sural nerve while the patient is in the prone position. The sural nerve is
characterized by its unique anatomical structure because it arises when the medial
and lateral sural cutaneous nerves merge at the level of the distal third of the calf.
Hence, we recommend starting the dissection from distal to proximal via a series of
stairstep incisions with gentle traction on the nerve to track both medial and lateral
sural cutaneous nerves. Upon making multiple incisions up to the proximal calf, a
longitudinal incision is then made in the midline below the popliteal crease. The
one or two sural nerves are then transected to allow for a tension-free coaptation
of the newly divided motor nerve to the lateral gastrocnemius. A case report on a
patient who developed sural nerve neuroma following the sural nerve graft for facial
reanimation showed that the patient was pain-free with normal ambulation at a 6-month
follow-up after TMR surgery.[101]
Nonextremity Painful Neuromas
Nonextremity Painful Neuromas
Abdominal Wall
TMR has recently been used to treat painful abdominal wall neuromas that can arise
after abdominal incisions including laparoscopy. As for extremity neuromas, diagnostic
nerve blocks are helpful in confirming the neurogenic origin of pain ([Table 4]).[102]
Table 4
Recently reported neuromas are described below for successful coaptation, each with
growing bodies of literature
|
Neuroma
|
Incision location
|
Target motor nerves
|
Notes
|
|
Occipital
|
Longitudinal over the area of greatest tenderness
|
Erector spinae
|
Occipital nerve is traced to areas of inflamed nerve, coapted to motor branch to E.
spinae
|
|
Breast
|
Concurrent or same incision as mastectomy
|
Redundant external intercostal, serratus or pectoralis
|
Long dissection time to locate anterior/lateral intercostal cutaneous nerves
|
|
Intercostal
|
8-cm incision over Tinel' sign
|
Internal oblique
|
Allograft can be used if neuroma excision limits the length
Medial or lateral to semilunar line changes dissection
|
|
Ilioinguinal
|
2-cm incision over Tinel aimed at ASIS
|
Internal oblique and transversus abdominis
|
Motor nerve branches from ilioinguinal nerve before arises from internal oblique
|
Abbreviation: ASIS, anterior superior iliac spine.
Groin—Ilioinguinal Neuroma
Chronic abdominal wall and groin pain can occur from symptomatic neuromas following
surgery, massive weight loss, or abdominal wall trauma. Painful inguinal neuromas
can arise after mesh inguinal hernia repair in an estimated 5% of patients.[103]
[104] A recent retrospective review demonstrated significant improvement in pain following
TMR to treat painful ilioinguinal neuromas.[102] The reported technique is as follows: the inguinal incision of approximately one
finger-breadth is made over the Tinel's sign and toward the anterior superior iliac
spine. After identifying the neuroma-in-continuity of the ilioinguinal nerve below
the external oblique facia, the nerve is dissected laterally to expose healthy fascicles.
Then, the nerve stimulator is used to identify the 0.5 mm motor branch to the internal
oblique muscle and transversus abdominis, which are typically supplied by the ilioinguinal
nerve before they arise through the internal oblique muscle. This motor nerve innervates
the local internal oblique muscle and is transected distally and coapted to the freshly
excised donor ilioinguinal nerve ending.[102]
Intercostal Neuroma
To locate an intercostal neuroma, an 8-cm incision is made over the preoperatively
marked Tinel's sign lateral or medial to the semilunar line based on physical exam
and previous incisions. If making an incision lateral to the semilunar line, the intercostal
nerve can be found by using a handheld nerve stimulator to identify the location of
the nerve through the muscle tissues. Typically, the painful nerve can be identified
by the patient in the preoperative holding area and the surgeon just needs to explore
deep into the area of tenderness. For the neuroma medial to the semilunar line, the
intercostal nerve arising between layers of posterior rectus fascia can be identified
by making an incision through the anterior rectus fascia either in transverse or oblique
fashion and mobilizing the rectus muscle medially. Upon identifying and resecting
the neuroma, an interposition nerve allograft is placed.[92] Neuromas lateral to the semilunar line are neurolyzed, as often the nerves can be
compressed as they travel from under or through the internal oblique fascia. A small
motor nerve to the transversus abdominis is located with a nerve stimulator, and a
TMR nerve transfer is performed. A retrospective study on 20 patients who underwent
TMR (8 procedures), allograft nerve reconstruction (18 procedures), or both (2 procedures)
demonstrated that 90% of the patients experienced a reduction in abdominal wall neuropathic
pain postoperatively, with 2 patients reporting complete resolution of pain after
undergoing TMR following unsuccessful nerve allograft reconstruction.[102] This retrospective study on the use of TMR in patients with abdominal wall neuromas
suggests that TMR is safe and effective in reducing abdominal neuroma pain.
Breast
Recently, TMR has been proposed as a novel surgical approach to prevent postmastectomy
pain syndrome (PMPS), which affects approximately 25 to 60% of patients following
mastectomy.[105]
[106]
[107] PMPS can result from symptomatic neuroma formation following mastectomy if iatrogenic
injury occurs to the cutaneous intercostal nerves that provide cutaneous sensation
to the breast and nipple–areolar complex.[108]
[109]
[110]
[111] The first step of breast TMR involves identifying all of the transected intercostal
nerve branches after mastectomy. If any of the lateral cutaneous intercostal nerve
branches are severed, they can be reliably found arising from the second through sixth
intercostal spaces along the midaxillary line.[105] The transected anterior cutaneous nerve branches, if present, can be located lateral
to the sternal border.[105] Upon identifying all the injured or transected nerves, these nerves are dissected
proximally within the external intercostal muscle to increase the length of the nerve
endings.[105] The nearby motor units with redundant neural input (e.g., motor units innervating
adjacent intercostal muscles, serratus anterior muscle, pectoralis muscles) are identified
and divided to serve as recipients for the donor transected intercostal nerves.[105] A multi-institutional case–control study on patients who underwent TMR at the time
of mastectomy reported that TMR resulted in improvement in pain-related outcomes,
with higher BREAST-Q physical well-being: chest scale score of 77.5 in breast surgical
patients who underwent TMR in comparison to 71 in published data among patients who
underwent mastectomy alone.[105]
[112] The study showed that after excluding the outliers, the score becomes 83.3, nearing
the score of 93 in ones without a history of breast cancer or surgery.[105]
[112] While this study is limited by the small sample size (N = 11 with 30 nerve coaptations) and a lack of a control group, the positive findings
suggest the safety of using TMR as a prophylactic intervention against PMPS among
breast surgical patients.[105]
Occipital Neuromas
Occipital nerve neuromas can be present after neurosurgical incisions of the cranium
and after unsuccessful neurolysis or neurotomy of the occipital nerve. The refractory
patient still in pain is explored in the prone position under general anesthesia.
Invariably, a motor nerve to the erector spinae can be found emanating off the occipital
nerve proper. After neuroma excision, TMR of the occipital nerve is performed on this
small motor branch ([Fig. 4] and [Video 4]).[89]
Fig. 4 Example of acute TMR of the GON performed immediately following an oncologic resection
in a middle-aged woman. (A) Demonstrates the lipomatous tumor resected by surgical oncology with (B) GON dissected and skeletonized (arrow) with the retractor assisting with visualization
of the deeper motor compartments of the posterior neck for target motor nerve branches
to accept the coaptation. [Video 4] displays the dissection and demonstrates checkpoint stimulation of the target motor
nerve to semispinalis capitis. (C) Closure of the muscle compartments after TMR. GON, greater occipital nerve; TMR,
targeted muscle reinnervation.
Video 4 Occipital nerve neuromas.
Osseointegration
TMR combined with osseointegrated implants, or “bionic reconstruction,” is an evolving
technology.[113]
[114] Preliminary case reports have demonstrated improved daily function with TMR performed
prior to osseointegrated percutaneous implant placement and improved neuroma and PLP
in upper extremity amputees.[114]
[115] Ongoing research is better elucidating the promise of effective osseointegrated
extremity implants that can provide bidirectional motor and sensory feedback to optimize
limb function in amputees.[114]
Regenerative Peripheral Nerve Interfaces
RPNI involves placing free muscle grafts over proximal transected peripheral nerve
endings to serve as denervated muscle targets. The transected peripheral nerve ending
then reinnervates the muscle graft. This technique has been shown, similarly to TMR,
to improve myoelectric prosthesis control and to treat and prevent neuroma pain and
PLP.[32]
[40]
[41]
[116]
[117] A benefit to RPNI is that it does not require a donor branch target, but a disadvantage
is the small, devascularized muscle target. Although debated in the literature, a
recent consensus group article stated that RPNI and TMR should be seen as “complementary”
and not inferior or superior.[76] Techniques employing both TMR and RPNI have been described, which utilize free muscle
grafts (RPNI) to cover TMR nerve transfers which may have a size mismatch at the coaptation
site.[118]
[119]
[120] The superiority of TMR compared with TMR and RPNI remains unknown.[76]
Conclusion
In summary, TMR is an effective procedure to improve myoelectric prosthesis control
and prevent and treat neuroma pain that is relatively simple to perform. Since its
inception for shoulder disarticulation prosthesis control, TMR has been adapted across
all major limb segments, the thoracoabdominal wall, breast, and occiput for those
suffering from neuromas. The procedural techniques will continue to co-evolve with
prosthetics as technology and osseointegration continue to advance for the direct
benefit of amputees.
