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Fig. 33.3 Diagram of
epineural sleeve repair,
reproduced with
permission from
Siemionow M, Brzezicki
G.Current techniques
and concepts in
peripheral nerve repair.
Int Rev. Neurobiol
2009;87:148
J. R. Brennan et al.
33.3.4 Nerve Grafts
33.3.4.1 Autografts
For the repair of larger nerve gaps across which
tension-free or minimal tension neurorrhaphy is
unavailable, grafts are indicated. Nerve grafts in
particular contain components, namely, Schwann
cells and their extracellular matrix and growth
factors, that make them the ideal scaffold for
regeneration of injured nerve axons. Taken
together, these constitute a microenvironment
that effectively promotes the advancement of
regenerating axons [19].
As compared to primary suture repair, nerve
grafting results in both an increased incidence of
synkinesis and a longer rehabilitation time as
nerve function returns [20]. In synkinesis, aberrant neural regeneration across the graft can
cause multiple muscle groups to contract when
just one is activated. This can be minimized by
the use of multiple neural inputs such that the
upper facial musculature and lower facial musculature are innervated separately. Using a
masseteric- to-buccal coaptation as an adjunct to
the cable nerve graft has been shown to reduce
the incidence of synkinesis and result in a faster
recovery of oral commissure movement [
21]
(Fig.33.4).
There has also been consideration as to the
importance of nerve polarity in orienting these
nerve grafts. Historically, the philosophy has been
to orient the nerve graft in its physiologic orientation such that the proximal end of the graft is
coapted with the proximal end of the defect.
Conversely, many surgeons recommend the opposite so as to minimize the potential for arborized
axons to get lost to misrouting [22]. A systematic
review revealed no signicant differences in functional outcomes or nerve generation between normal and reversed polarity nerve autografts [23].
33 Advances inFacial Nerve Paralysis: Surgical Innovation, Tissue Engineering, andEmerging Technology
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Facial
Masseteric
MAB graft
Fig. 33.4 Diagram of concurrent masseteric nerve transfer and cable graft. MAB represents the medial antebrachial nerve used as the nerve graft
33.3.5 Nerve Reconstruction
andNerve Transfers
In some instances of facial nerve injury, neither
primary suture repair nor graft techniques are
applicable. When the proximal facial nerve stump
is resected or damaged but the distal NMJ and
facial muscles are intact, a nerve substitution
may be indicated. The best outcomes for these
procedures have been reported when they are
performed within 12–18months, although some
studies report success after up to 4 years [24, 25].
After chronic denervation, the neuromuscular
junction undergoes signicant atrophy at the
motor end plate, and the outcomes of nerve transfers are much less successful [5].
33.3.5.1 Hypoglossal-Facial (XII-VII)
The hypoglossal nerve is a valuable option for
nerve substitution of the facial nerve as it is proximal to the extratemporal portion and has a high
population of myelinated motor axons. In addition, hemi-tongue weakness is more tolerable
among patients than weakness of other facial
musculature [26, 27].
Historically, the classic procedure entailed
transection of the entire hypoglossal nerve and
reattachment distally to the facial nerve stump.
Since its advent, there have been several modications in order to minimize tongue dysfunction
and subsequent issues with articulation and mastication. Animal studies have sought to quantify
the percentage of hypoglossal axons required to
preserve acceptable tongue function. A rodent
model demonstrated that at 40% preservation of
the hypoglossal nerve, tongue atrophy is minimized and the facial musculature can be effectively reinnervated [28]. This has led to an early
modication in which there is partial nerve sacrice. Other modications include the jump graft
which utilizes a donor cable graft– either from
the greater auricular or sural nerve– to bridge the
hypoglossal nerve and the distal facial nerve
trunk. Studies demonstrate that the end-to-side
neurorrhaphy used in the jump graft repair is best
facilitated by deliberate transection of some of
the donor nerve axons to facilitate regeneration
[29]. This modication serves to preserve some
tongue function and decrease mass activation of
the hemiface [30].
Finally, the infratemporal facial nerve can be
reected out of the mastoid bone and used for
direct communication between the hypoglossal
nerve and the distal facial trunk. This obviates the
need for an interpositional graft and decreases
axonal loss through an additional coaptation site
[31]. After proximal nerve injuries such as acoustic neuroma with facial nerve sacrice or, indeed,
whenever there is adequate facial nerve available,
this is a very attractive option as it necessitates
just one coaptation between two intact nerves.
As of yet, the outcomes of these various modications have not yet been studied among one
another, and there is some debate as to which one
balances the least morbidity with the best functional results. However, there is a consensus as to
the inferiority of the classic nerve transfer relative
to the three alternative procedures as the former
results in hemiglossal paresis and mass activation
and synkinesis [
5]. The complete sacrice of the
hypoglossal nerve is no longer considered a treatment standard due to the existence of these newer
techniques with signicantly less morbidity.
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33.3.5.2 Masseteric-Facial (V-VII)
The masseteric branch of the trigeminal nerve
has more recently been popularized as an option
for nerve transfer in the setting of facial nerve
injury [32]. The masseteric nerve presents as a
valuable option as it has reliable surgical anatomy, which provides for ease of dissection. There
is minimal-to-no donor site morbidity from sacrice. In addition, the nerve to the masseter is
located in close proximity to the facial nerve,
obviating the need for a cable graft, and has a
high axonal count allowing for quick recovery
and robust input [4, 33] (Fig.33.5).
The success of the masseteric-facial coaptation may lie in the physiologic connectedness of
cranial nerves V and VII.Some studies have indicated that patients who undergo this procedure
may achieve spontaneous movement without the
conscious thought required of hypoglossal nerve
transfers [34]. In a study comparing hemihypoglossal nerve and masseteric nerve transpositions
for rehabilitation of facial paralysis, the latter
was demonstrated to result in better symmetry
and faster onset of movement [35]. Other studies
further suggest that masseteric nerve transfer
minimizes the synkinesis, dysphagia, and dysarthria associated with hypoglossal nerve transfer
and provides a robust axonal volume that allows
for a speedy recovery to function [
36].
A major disadvantage of the masseteric nerve
transfer is the poor resting tone that results.
Outcomes after this operation demonstrate a limited effect on symmetry of the oral commissure at
rest, and this is particularly evident during
dynamic stages such as speech during which the
patient isn’t clenching down [37]. In order to
mitigate this, it is the authors’ preference to combine the masseteric-to-buccal with a hypoglossalto- facial coaptation, either through an end-to-side
or a jump graft. In doing so, the repair is provided
better resting tone from the hypoglossal while
also beneting from the fast, powerful masseteric
input (Fig.33.6).
33.3.5.3 Cross-Facial Nerve Grafting
Cross-facial nerve grafting has been described as
another means of facial nerve repair in which the
source of axons is the contralateral healthy facial
nerve. It is the only donor nerve option that provides mimetic potential. It also allows for recov-
Fig. 33.5 Diagram of masseter-to-facial nerve transfer
anatomy, reproduced with permission from Klebuc
MJ.Facial reanimation using the masseter-to-facial nerve
transfer. Plast Reconstr Surg 2011;127(5):1911
Facial
Masseteric
Hypoglossal
Interposition graft
Fig. 33.6 Diagram of concurrent masseteric nerve transfer and hypoglossal nerve transfer
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401
ery of emotion-based expression in which a
patient is able to produce a smile as a natural
response [38]. Due to the use of contralateral
facial nerve bers, there is no need for neuromuscular retraining or physical therapy to relearn
how to activate these muscles [35].
The disadvantage to the cross-facial nerve
graft procedure is that it requires a long nerve
graft to reach the facial mimetic muscles and thus
consists of a prolonged recovery time and
requires two stages. The ensuing muscle atrophy
and the limited number of axons in the repair are
such that the reinnervation generates less motor
power than hypoglossal nerve transfers [39].
33.3.5.4 Babysitter Procedure
The babysitter procedure is an adaptation that
seeks to address some of the disadvantages of
the cross-facial nerve graft technique. It capitalizes on optimal spontaneous outcomes of the
procedure while mitigating the effects of longer
deinnervation time. In it, a portion of the ipsilateral hypoglossal nerve is utilized rst in a nerve
transfer with the facial nerve trunk.
Simultaneously, a nerve graft – often the sural
nerve – is coapted to a healthy facial nerve
branch to create the cross-
facial nerve graft,
which is delivered, but not connected, to the
paretic side. At a later operation, once the activity of the facial nerve grows across the graft, the
distal end(s) of the cross-facial nerve graft(s) is
coapted to distal branches of the facial nerve [40,
41] (Fig.33.7). The premise is that the hypoglos-
sal nerve is a temporizing measure to prevent
atrophy of the facial musculature while awaiting
reinnervation [
42]. By combining these two
techniques, studies demonstrate that the babysitter procedure can preserve the facial musculature with an immediate, powerful nerve transfer
and thus allows for optimal reanimation and synchronized facial expression in long term once the
facial nerve grafts are attached [5, 43].
Fig. 33.7 Diagram of the babysitter procedure, stage 1
(left) and stage 2 (right), reproduced with permission
from Terzis JK,Tzafetta K. The “babysitter” procedure:
minihypoglossal. To facial nerve transfer and cross-facial
nerve grafting. Plast Reconstr Surg 2009;123(3):872
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33.4 Reanimation
33.4.1 Free Muscle Transfers
In patients who have long-standing facial paralysis, muscle transfers may be pursued. In these
patients, the facial muscles are subject to irreversible atrophy and loss of function at the motor
end plates and thus cannot be simply reinnervated by any of the nerve transfer procedures
described above. Similarly, patients with Möbius
syndrome or developmental palsy in whom the
facial muscles are paralyzed from birth can be
candidates for free muscle transfers as well [4].
Free muscle transfers have emerged as the
premier option for these patients. The most commonly used gracilis free muscle transfer has
been demonstrated to achieve quantiable
improvements in several measures including
static symmetry, dynamic symmetry, and oral
commissure excursion [44]. In addition, there is
the potential for these patients to undergo
movement- associated cortical reorganization
which may allow for the development of spontaneous smiles [5, 45].
The choice of the gracilis is due to its predictable anatomy, appropriate length and contractility, and ease of harvest [43]. The procedure
involves a portion of the gracilis muscle being
exposed and demarcated around a neurovascular
pedicle after which it is split longitudinally for
transplantation. It is inset via a face-lift incision
and secured to the oral commissure. For vascular
supply, the facial artery and vein are used [46].
For nerve supply, there are several options. The
obturator nerve has traditionally been driven by a
cross-facial nerve graft which allows for a coordinated and spontaneous smile (Fig. 33.8).
Alternatively, the masseteric nerve provides a
signicantly more powerful smile with higher
axonal counts [32]. More recently, a combined
approach has coupled the benets of the two neural inputs with a double-powered transfer [47].
Due to the prolonged regeneration time of the
cross-facial nerve graft, the traditional operation
occurs in two parts: in the rst, the cross-facial
nerve graft is placed using a sural nerve donor.
Axonal regeneration is followed clinically using
J. R. Brennan et al.
Gracilis
muscle
Facial
nerve
Sural nerve
graft
Masseter
muscle
Fig. 33.8 Diagram of gracilis muscle free ap and innervation by the ipsilateral masseteric nerve and the contralateral facial nerve through an interpositional sural nerve
graft, reproduced with permission from Biglioli F,
Colombo V, Tarabbia F, etal. Double innervation in freeap surgery for long-standing facial paralysis. J Plast
Reconstr Aesthet Surg 2012;65:1345
flap
Masseter
nerve
Obturator
nerve
Tinel’s sign to determine the timing of the second
stage of surgery. It may take up to a year for the
regenerating axons to reach across the face. In the
second operation, the gracilis muscle is transplanted as a neurovascular muscle free ap [3].
The ap is inset medial to the nasolabial crease
and around the modiolus with an extension into
the lower lip. Then, the vascular anastomosis is
performed followed by the nerve coaptations.
The ap is then afxed to the deep temporalis
fascia or zygomatic periosteum along the vector
of excursion [
42]. The combination of this cross-
facial nerve graft with input from the ipsilateral
masseteric permits for spontaneous, mimetic
smiles that are much more highly powered [45].
There are disadvantages associated with the
gracilis muscle specically. There is the potential
for contour abnormalities and muscle bulk asymmetry that may lead to aesthetic deformities [5].
In addition, poor muscle contraction may lend to
a less powerful repair if the ideal muscle tension
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is not set. Studies have proposed the use of the
sternohyoid muscle as an alternative as a muscle
more comparable in nerve ber makeup and bulk
to the zygomaticus major. Other benets include
its nonessential function and longer recipient
nerve that may provide advantages over gracilis
transposition [48]. Despite this, the gracilis
remains the widely accepted standard for free
muscle transfer in facial reanimation.
33.4.2 Regional Muscle Transfers
As an alternative to the free muscle transfer, the
donor muscle can be transferred regionally such
as the temporalis, the masseter, or the anterior
digastric. The temporalis muscle transfer is the
most frequently used, and the favored, orthodromic approach involves removing the muscle
at its insertion on the coronoid process and reattaching it to the oral commissure [43]. The
advantage of regional muscle transfers is that the
operation is far less complex than the free muscle
transfers as there is no need for microvascular
surgery; the neurovascular supply is pedicled
with the regional muscle transfers [42]. In addition, the functional benet is immediate after surgery without the long rehabilitation time
associated with free aps. Disadvantages of this
operation include the potential for smile vector
asymmetries, diminished excursion relative to a
free ap, and lack of spontaneous smile [49].
33.5 Emerging Research
33.5.1 Advances inNerve
Regeneration
33.5.1.1 Nerve Allografts
There is a great deal of interest in nding alternatives to the use of autografts in the repair of
nerve gap injuries due to secondary sensory or
motor decits incurred [50]. Allografts have
been studied as an alternative, in particular acellular nerve allografts which avoid the need for
long-term immunosuppression [51]. The
RANGER Study has allowed for investigation
into the long-term outcomes of patients who
have utilized human nerve allograft in the reconstruction of the nerve. The data suggest that
these allograft repairs result in high functional
recovery and are a promising alternative to the
traditional autograft repairs [
52].
33.5.1.2 Nonneural Biological Grafts
Nonneural biological grafts have also been studied as an alternative to nerve autografts. These
typically consist of artery segments, vein segments, or skeletal muscle autografts. Vein segments have been studied the most in the literature,
and animal studies have reported outcomes comparable to those of nerve autografts [53, 54]. In
addition, there has been some interest in the use
of multiple-component conduits such as musclevein- combined techniques. Experimental studies
have shown that combined muscle-vein conduits
are rapidly colonized by Schwann cells which
assist in promoting nerve regeneration [55, 56].
These, too, have demonstrated nerve repair outcomes that are nearly equivalent to autograft
reconstruction [49].
33.5.1.3 Articial Nerve Guidance
Conduits
Articial nerve guidance conduits are advantageous as they can circumvent the issues of donor
site morbidity and immunogenicity that are associated with other graft techniques. Research in
nerve conduits has sought to design a support
structure to facilitate the direction and growth of
the injured nerve and provide a barrier through
which the intervening connective tissue could not
cross. There are currently FDA-approved options
for conduits, many of which are constructed out
of type I collagen. There are a number of studies
looking into techniques to control the inner conduit bioactivity in an effort to improve the efciency and outcomes of nerve regeneration [57].
Schwann cells have been used to seed these conduits in order to mimic the native neural environment and promote nerve repair [58]. In addition,
chemical inuences have been studied to reduce
the surrounding inammation that can otherwise
impair tissue healing in the area of the repair.
Researchers have looked at using lentiviral gene
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therapy to elicit a sustained IL-10 expression to
modulate leukocytes in the area of spinal cord
injury [59]. These and other modulators will
likely play important roles in the generation of
articial nerve conduits which effectively promote guided neural regeneration.
33.5.1.4 Motor Nerve Donor Grafts
Typically, autologous nerve grafts are derived
from sensory nerves, despite their role in reconstructing injuries in motor nerves. Research into
Schwann cell gene expression has demonstrated
that cells may express different genes and phenotypes depending on whether they are from sensory or motor nerves. Studies demonstrate that
there is a phenomenon called preferential motor
reinnervation in which a motor axon tends to
regenerate down a motor pathway when given the
option between motor and sensory pathways
[60]. This is thought to be driven by the motor or
sensory phenotype Schwann cells present within
the nerve pathways which assist in inuencing
the regenerating nerves [61]. Similarly, studies in
rats demonstrated preferential nerve regeneration
with the use of motor nerve grafts vs sensory
nerve grafts [62, 63]. There is still an absence of
clinical studies in this area, but the ndings thus
far suggest that motor nerve defects may see optimal regeneration results with the use of dispensable motor nerve grafts.
The motor nerve to the vastus lateralis muscle
is a readily accessible motor nerve during the
harvest of an anterolateral thigh free ap in cases
where advanced parotid malignancies require
nerve grafting and soft tissue coverage. Its
branching pattern is made up of 4–5 branches
that arborize, and it is particularly well-suited for
facial nerve repair or cable grafting [5].
33.5.2 Functional Electrical
Stimulation
Studies into microelectrical system-based devices
use functional electrical stimulation as a means
to apply an electrical current to deinnervated
muscles to stimulate muscle contraction. This
technology is currently in use in several clinical
applications including patients with paralyzed
limbs, impaired respiratory function, and bowel
and bladder dysfunction [64]. Animal studies in
hemiparalysis have utilized this concept to pace
intact neural signals from a healthy orbicularis
oculi muscle with the contralateral, paralyzed
muscle to restore eyeblink [65–67] (Fig. 33.9).
There is also research to suggest that this technology may be translated into applications for other
facial muscle palsies [8, 68].
33.5.3 Bioelectrical Interfaces
A major focus of research efforts targeting facial
nerve injury is the study of neural interfaces that
allow for the recording of a signal from a donor
nerve and the stimulation of a recipient nerve.
External Receiver
• Microcontroller
• Battery
• Telemetry
Skin
Fig. 33.9 Stimulation of paralyzed mimetic musculature using signals captured from the non-paralyzed side to generate symmetric activation, reproduced with permission from McDonnall D and Ward PD [63]
Data
Power
Implant Electronics
• Stimulator
• EMG Amplifier
• Control Logic
• Telemetry
Stimulation
HealthyParalyzed
Recording
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This could be applied in the setting of unilateral
facial nerve injury in which the contralateral,
functional facial nerve is recorded and the input
is used to stimulate the side of the face ipsilateral
to the injury [5]. There are a signicant number
of bioelectrical interfaces currently undergoing
evaluation (Table33.1).
Table 33.1 Comparison of peripheral nerve interfaces currently being studied, reproduced with permission from
Langhals etal. [
Electrode
structure
Interface Records or induces
Advantages – Limited neural
Limitations – Poor resolution
5]
Cuff electrodes
Exposed metal
wires in silicon
with monopolar,
bipolar, or tripolar
conguration
gross nerve
activity from the
surface of the
nerve
trauma,
favorable
biocompatibility
–
Long safety
track record
– Extensive prior
use in humans
of individual
nerve fascicles
Biased toward
–
axons near the
epineurium/
close to cuff
Flat-interface
nerve electrodes
(FINE)
Advanced cuff
electrode–
multiple
electrodes
individually
stimulate or
record nerve
activity
Reshapes
nerve into
atter
footprint to
bring
individual
nerve fascicles
to the
epineurium
surface
Greater
selectivity and
neural
discrimination
than standard
cuff electrodes
–
Poor
resolution of
individual
nerve
fascicles
– Biased
toward
axons near
the
epineurium/
close to cuff
Penetrating nerve
arrays of electrodes
Either individual
wires or
microfabricated
silicon-based
electrodes that are
implanted into the
nerve
May need
pneumatic
insertion tools to
insert electrode
intrafascicularly
into the nerve
Allows interfacing
of multiple nerve
fascicles and
potentially
individual axons
– 6-month life
– Signicant
Cuff electrodes function through the placement of an electrode placed atop the nerve that
is capable of either recording neural inputs from
or translating activity to the nerve. The technology is limited by the fact that the signal in question may not reect individual nerve fascicles
but rather the net activity of the entire nerve.
Regenerative
peripheral nerve
interface (RPNI)
Modication of
regenerative
electrodes–
utilized a
mechanical
intermediary
(muscle) to
maximize interface
stability
Muscle tissue
creates a
mechanical
intermediary
between nerve and
electrode
–
Avoids the
neural trauma
seen with other
interfaces
Muscle tissue
–
amplies
neural signals
10–100x
– Potentially
protects the
nerve from
direct electrical
stimulation
damage
– Potential for
interference
between
nearby
interfaces
– Optimal
applicationspecic
integrated
circuit in
progress
due to
neuralelectrical
interface
instability
trauma and
bleeding
reported with
cortical
implantation
Regenerative
electrodes
Silicon or polymer
with holes in
structure, device
afxed to ends of
divided nerve to
allow nerve
regrowth through
structure
If electrodes are
afxed inside the
channel so that
nerve regrows
through, it allows
interface with
electrodes already
in place
– Flexibility in
size of sieves,
tubes, and
channels allows
regeneration of
nerves and
fascicles
Used when the
–
facial nerve has
been divided or
it is surgically
acceptable to
divide
– Mechanical
mismatch
between
electronics and
soft neural
tissue
– Nerve
transection
required and
scaffold may
impede ber
growth
406
Nerve
& Electrode Sites
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As a result, this technology cannot accurately
capture the neural input to each of the individual
facial muscle groups. An alternative to this is
the use of the at-interface nerve electrode to
reshape the geometry of the nerve such that the
individual fascicles are more supercial and
thus accessible for selective stimulation [69].
The penetrating nerve array of electrodes is
another option which works via intrafascicular
implantation of the electrode into the nerve
which allows for maximal surface area between
the electrode and the neural tissue. It is a major
feature in research in amputated limbs and prostheses [70]. Issues with this technology surround the incompatibility between the rigid
electronic interface and the soft nerve tissue that
results in rapid performance loss over the course
of months [71].
Another technology on the horizon in the
eld of peripheral nerve repair includes the use
of a regenerative peripheral nerve interface that
seeks to mitigate these performance issues.
Muscle tissue is used as a physiologic target into
which the peripheral nerve grows, thus providing a nerve- electrode interface that prevents neuroma formation. Additionally, it facilitates a
major multifold increase in signal clarity [72].
Figure33.10 illustrates an example in which the
muscle and tissue from the small intestine are
used as the interface.
Sprouts
15
SIS
Fig. 33.10 Diagram depicting regenerative peripheral
nerve interface in which the peripheral nerve has grown
into the muscle and small intestine submucosa (SIS). The
unlabeled arrow indicates neural input. Reproduced with
permission from Langhals etal. [5]
mm
Muscle
NMJ
Electrode
33.6 Conclusion
Facial nerve palsy can have a signicantly detrimental impact on a patient’s life insofar as quality, activities of daily living, and self-image.
Efcacious correction of this decit can return a
patient’s ability to eat, blink, and share emotion
and thus has far-reaching clinical implications.
The location of the injury and the time to repair
are critical factors in guiding therapeutic
decision- making. From a wide variety of
approaches in reinnervation and reanimation, a
surgeon can effectively target the underlying neural and/or muscular decit and return symmetry
and motion to a once-paralyzed face. Important
among all these techniques is the need for postoperative neuromuscular training that allows for
return to function in these patients [73, 74].
Together with rehabilitation, these procedures
make up a therapeutic arsenal through which
critical facial nerve function can be returned to
those who have suffered a very damaging
paralysis.
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