The injured facial nerve can be regenerated and repaired, which has been acknowledged in basic research and clinical settings. A large amount of clinical data show that the hypoglossal nerve center is superior to other cranial nerves in controlling facial muscle and restoring facial function. Currently, HN-FN end-to-end neurorrhaphy, either directly or via a nerve graft, is the favored procedure because of the functional similarity between the HN and the FN. For example, the cortical representations of the tongue and facial muscle are close to one another[13, 14]. However, speech problems, swallowing dysfunction and atrophy of the tongue muscle are major complications after the operation that seriously affect the quality of life of these patients.
There are several main factors that determine the extent of nerve regeneration after nerve injury: the amount and route of nerve axon regeneration, the rate of nerve regeneration, the retention of target tissue structure and the re-formation of synaptic connections. In other words, in order to attain a good repair result, a sufficient amount of nerve fiber regeneration is needed within an appropriate period of time, that is, before the dominant tissue structure qualitatively changes, enabling proper matching of the target tissue for the formation of synaptic connections. Therefore, ideal facial nerve repair should be a type of treatment that does not affect the basis of facial nerve repair and that promotes recovery of facial nerve function.
Is immediate repair or delayed repair more appropriate after peripheral nerve injury? In experimental studies, Bignotti showed electrophysiological and morphological changes with early suture or delayed suture of the sciatic nerve in rats. The nerve conduction velocity results showed that early suture was more effective. However, Guntinas found that when the facial nerve of rats was taken as the object of observation, delayed repair was better than immediate restoration. Chen showed in a study of hypoglossal-facial nerve anastomosis guinea pigs that early surgical nerve regeneration led to better outcomes because with an earlier anastomosis time, the extent of Schwann cell-mediated myelin degradation is smaller and there is less replacement by fibrous tissue, thus facilitating axonal growth and myelination. Nevertheless, Barrs observed no significant difference between immediate and delayed repair in experiments of facial nerve injury in piglets. Most of the previous studies on nerve damage repair conducted complete injury, while the timing of incomplete repair has been less studied. However, facial nerve injury results in atrophy of certain facial muscles innervated by the facial nerve, nerve fibrosis, degeneration of nuclei in the pons and cerebral motor cortex, and other changes. Therefore, the repair operation should be performed before neurodegeneration occurs.
The optimal timing for nerve anastomosis resulting in maximal facial reanimation has not been precisely determined for patients and is usually influenced by personal clinical experience[17, 18]. It has been suggested that a delay in FN reconstruction may decrease functional recovery, especially when repair is delayed for more than 1 year. However, Kunihiro reported that HN-FN repair can be postponed for as long as 2 years with only a minimal effect on the recovery of facial movement. Recently, some researchers have obtained similar results through animal experiments. Appropriately delayed repair is beneficial to facial nerve repair. Guntinas-Lichius showed that delayed FN repair in rats within a defined denervation period of 14-112 days can result in accelerated and enhanced muscle reinnervation. Spector showed that the number of regenerated nerve fibers after the delayed repair of the facial nerve was greater than that after early facial nerve repair. A study of peroneal nerve injury by other researchers suggested that the nerve repair had no adverse effect on nerve regeneration in one month, but the efficacy of nerve regeneration would be impacted by a longer delay.
In this study, sural nerve grafts were pre-degenerated, the axonal degradation and a large number of Schwann cell proliferation, so that the motor nerve and sensory nerve axons do not affect neural remodeling. It is necessary to hemi-section the hypoglossal nerve because the number and extension of the axonal regeneration determine the recovery of the nerve function. In order to protect the remaining facial nerve axons and/or potential spontaneous regeneration ability, it is also necessary to only open the window to the facial nerve. This kind of PNG bridging for the hemiHN-FN neurorrhaphy can make the damaged facial nerve double repaired by the hypoglossal nerve and the facial nerve itself.
Our study generated results from facial symmetry assessments, electrophysiological examination, retrograde labeling and measurement of axon regeneration in the reconstructed nerve pathway. The optimal surgical time of the side-to-side anastomosis of the hypoglossal nerve and facial nerve was 4 weeks after the facial nerve injury, based on the data 3 months after repair. The control group without anastomosis, in some indexes, had better outcomes than the immediate repair group, the 2-week-delayed repair group, and the 8-week-delayed repair group. One possible reason for this result may be facial nerve regeneration and repair after injury. In addition, in a sense, incomplete injury is a kind of pre-degeneration that promotes the removal of myelin debris produced via Wallerian degeneration, and the nerve regeneration is guaranteed after transplantation. After 2-3 weeks of Wallerian degeneration, most myelin has been cleared, and the greatest effect on nerve regeneration is attained[23-26]. Some delay prior to repair is appropriate in order to minimize the factors hindering nerve regeneration, such as myelin degradation products and low levels of nerve growth inhibitory factor, and maximize the factors promoting nerve regeneration, such as peak levels of neurotrophic factor and an ideal for microenvironment nerve regeneration. Under these circumstances, the time for regenerating axons to reach the target tissue to promote nerve regeneration will be shortened.
It also takes a certain time to make the axon from the hypoglossal nerve into the graft, and then to the regeneration of the facial nerve, which depends on the length of the graft and the extension speed of the axons. The regeneration rate of axons is 1-4 mm/d, and the initial stage of axon regeneration is almost 2 weeks. If the length of the grafts is 10 mm, this time is 3 weeks[27, 28]. Moreover, the facial nerve of all the rats receiving anastomosis likewise underwent a secondary injury, as some nerve fibers were cut off and the formation of fibrous scars reduced the regeneration ability. Additionally, time was needed for the two nerve endpoints to heal. This also explains why the recovery index of some rats in the anastomosis groups was lower than those in the control and non-repair groups.
The findings of this study can provide a more reliable basis for the clinical treatment of incomplete paralysis, leading to diminished or even cured incomplete paralysis, pain relief, and reduced personal, social, psychological, and economic burdens for many patients. Therefore, the key to treating incomplete facial paralysis is determining how to preserve the function of the residual facial nerve to the utmost extent and finding the best time for performing the nerve repair operation.