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More researches are needed to elucidate the exact the endoneurial sheath produce key components that
mechanism of sensory protection and compare its promote growth (e.g. collagen, fibronectins, and laminin)
functional outcomes with mixed protection. Goals for and provide a substrate for reinnervation. [16,41‑43] Impaired
future studies include comparing differences in Schwann reinnervation translates into reduced capacity to generate
cell phenotype and neurotrophic expression between force. [44]
sensory protection and mixed protection. While mixed Recent neurotization experiments using animal models
protection appears more advantageous compared to have been more promising. Wang et al. demonstrated
[24]
sensory protection, the need to sacrifice innervation to that implantation of either a sensory nerve or
a donor muscle to harvest mixed nerve may preclude its preganglionically avulsed sensory nerve could slow
use clinically. muscle atrophy. Compared to unprotected controls, the
Side‑to‑side neurorrhaphy implantation groups demonstrated higher fibrillation
As an extension of end‑to‑side neurorrhaphy, researchers potential, muscle weight, cross sectional area, and protein
have also examined the efficacy of performing side‑to‑side content at one and three months after neurotization.
neurorrhaphy. The technique involves joining the side of In parallel experiments, Ochi et al. [45,46] showed that
an intact donor nerve with the side of an injured nerve joining the isografted dorsal root ganglia to the common
using a nerve “bridge” composed of either synthetic peroneal nerve stump also mitigated muscle atrophy.
conduit or autologous graft. The few basic science Microscopy demonstrated sensory neuron survival and
and clinical studies investigating this technique have growth of fine axonal branches into the muscle. Although
yielded mixed results. Experimentally, Shea et al. the sensory axons did not reinnervate motor endplates,
[34]
demonstrated the benefits of side‑to‑side neurorrhaphy the neurotized group showed functional advantages
using a synthetic collagen bridge to connect a healthy over unprotected controls with higher twitch tension
peroneal nerve with a transected tibial nerve in a and tetanic contraction. Similar to other techniques, the
rodent model. The investigators noted superior muscle protective effect of neurotization is attributed to trophic
preservation (higher muscle weight and less histologic factors derived from or stimulated by the sensory nerve.
evidence of muscle damage) and improved functional Compared to neurorrhaphy, however, the structural and
outcome (gait assessment) in their side‑to‑side nerve functional results of direct muscle neurotization remain
bridge group compared to denervated controls. However, inferior.
no rats in the experimental group showed axonal Clinically, neurotization has limited applicability for
regeneration along the length of the entire conduit. patients with multiple denervated muscles, including
Clinically, Magdi Sherif and Amr showed the potential those with proximal median or ulnar nerve injuries. For
[35]
effectiveness of using autologous nerve graft bridges example, with proximal median nerve transection, over
between median and ulnar nerve fascicles at the wrist ten muscles in the arm may be affected. Each denervated
in patients with high median or ulnar nerve injuries. muscle would require implantation with a separate
However, this was a small case series without rigorous sensory nerve, rendering this approach impractical. Thus,
outcome measures making it difficult to definitively state direct muscle neurotization is only appropriate for a
that this technique is clinically efficacious. selective group of patients.

Although the process of axonal repopulation and
end‑organ reinnervation is similar between end‑to‑side FUTURE DIRECTIONS
and side‑to‑side neurorrhaphy, the efficacy of side‑to‑side
neurorrhaphy is less. Without donor axon, disruption To date, the outcomes of peripheral nerve manipulations
and injury to the recipient nerve, the neurotrophic such as end‑to‑end and end‑to‑side neurorrhaphy have
signals stimulating Schwann cell proliferation and primarily been assessed using histomorphometric analysis.
axonal sprouting through nerve bridges are substantially Inferences about functional recovery have been made
diminished. [33,36,37] As a result, few axons are available using anatomic measurements such as axonal density and
downstream for reinnervation or to provide trophic myelin thickness. However, anatomic proxies for nerve
factors. Thus, compared to other techniques, side‑to‑side regeneration offer little information about functional
[47]
neurorrhaphy is a relatively inefficient technique for recovery. For years, muscle contractile properties,
nerve reconstruction, and it does not result in clinically such as twitch force, tetanic force, peak‑to‑peak tension,
significant functional recovery or offer sufficient and contractile velocity have been used to evaluate the
“protection” from muscle atrophy. degree to which motor axons reestablish their functional
connections with muscle. Further studies measuring
Direct muscle neurotization contractile properties as they relate to sensory protection
Neurotization showed limited success in early human would provide a more direct measure of muscle integrity
studies. [38,39] Poor outcomes are in part due to the failure and nerve regeneration. In addition, when compared with
to form new neuromuscular junctions. Specifically, supra‑physiological measures like tetanic force, functional
[40]
directly implanting a sensory nerve into muscle forces outcomes such as grip strength, ambulation biomechanics,
axonal regeneration to occur outside of native endoneurial and upper extremity performance tests provide clinically
conduits. The endoneurial conduit is important in relevant information about the extent and quality of
regeneration because Schwann cells and basal lamina of muscle reinnervation.

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