Optimal site for facial nerve transection and neurorrhaphy: a randomized prospective animal study
© Mendez et al. 2015
Received: 22 October 2014
Accepted: 13 May 2015
Published: 24 May 2015
Since the first facial allograft transplantation was performed, several institutions have performed the procedure with the main objectives being restoration of the aesthetic appearance and expressive function of the face. The optimal location to transect the facial nerve during flap harvest in transplantation to preserve facial movement function is currently unknown. There are currently two primary methods to perform facial nerve neurorrhaphy between the donor and recipient-one protocol involves transection and repair of the facial nerve at the main trunk while the another protocol advocates for the neurorrhaphy to be performed distally at the main branches. The purpose of this study is to establish the optimal location for transection and repair of the facial nerve to optimize functional recovery of facial movement.
A prospective randomized controlled trial using a rat model was performed. Two groups of 12 rats underwent facial nerve transection and subsequent repair either at the main trunk of the nerve (group 1) or 2 cm distally, at the main bifurcation (group 2). Primary outcome of nerve functional recovery was measured using a previously validated laser curtain model, which measured amplitude of whisking at 2, 4, and 6 post-operatively. The deflection of the laser curtain sent a digital signal that was interpreted by central computer software.
At week 2 post-nerve surgery, the average amplitude observed for group 1 and 2 was 4.4 and 10.8 degrees, respectively. At week 4, group 1 showed improvement with an average amplitude of 9.7 degrees, while group 2 displayed an average of 10.2 degrees. The week 6 results showed the greatest improvement from baseline for group 1. Group 1 and 2 had average amplitudes of 17.2 and 6.9 degrees, respectively. There was no statistically significant difference between the two groups at 2, 4, and 6 weeks after facial nerve surgery (p > 0.05).
We found no statistical difference between these two locations of nerve repair using identical methods. Therefore, the authors recommend a single versus multiple nerve repair technique. This finding has potential implications for future facial allograft transplantations and at minimum necessitates further study with long-term follow-up data.
Since the first facial allograft transplantation was performed in Amiens, France, in 2005, several institutions have performed the procedure with the main objectives being restoration of the aesthetic appearance and expressive function of the face. An essential component of this procedure involves the neurorrhaphy of the donor facial nerve to the corresponding recipient patient’s facial nerve. The optimal location to transect the facial nerve during flap harvest in transplantation to preserve facial movement function is currently unknown. There are presently two primary methods to perform facial nerve neurorrhaphy between the donor and recipient-one protocol involves transection and repair of the facial nerve at the main trunk while another protocol advocates for the neurorrhaphy to be performed just distally to the main trunk at the main upper and lower branches.
There are several known clinical factors that have an effect on peripheral nerve function recovery after nerve repair including time interval between trauma and repair, type of lesion and repair, and the age of the patient . Furthermore, in order to optimize nerve function, there are certain techniques of nerve repair that have been shown to be vital for outcome. The basic requirement is to appose the cut ends of the nerve in such a fashion as to minimize scar formation and preserve the optimal blood supply . In cases of sharp nerve division with minimal gap, as is the case with facial allograft transplantation, direct end-to-end nerve repair is indicated . Furthermore, tension-free suture repair remains the preferred treatment option as tension will result in scaring and poor regeneration [2, 3].
Despite an abundance of knowledge regarding nerve regeneration physiology and nerve repair techniques, little is known about optimal sites of transection and repair along a peripheral nerve. Some literature has suggested that more proximal peripheral nerve injuries are associated with worse outcomes. In their 2009 study of upper extremity nerve injuries, Lohmeyer et al. found that increasing distance between nerve lesion and fingertip correlated significantly with decreasing fingertip sensibility . The reason for this is complex and not fully understood but it is felt that the more proximal the nerve injury, the lower the chances for the axons to re-innervate adequate terminal receptors and organs because possible misdirection increase . Also, in the time needed to reach the end organ, it is felt that multiple irreversible changes take place, which can negatively affect outcome .
In regards to peripheral nerve recovery, it is also well recognized that the functional outcome following repair of different individual nerves, in otherwise comparable circumstances, are not the same . Although there is no widely accepted explanation, it is felt the intrinsic complexity of the function of the nerve plays a role .
Unfortunately, literature regarding optimal sites for transection and repair specifically of the facial nerve is exceedingly scarce. In their 2006 study, Liu et al. compared lesions of the central nervous system to those of the peripheral nervous system along the facial nerve. The authors found that axonal injuries of central facial motoneurons caused greater nerve damage than injuries along the axons of the peripheral facial nerve . A recent study by Hadlock et al. did attempt to compare injuries along different lengths of the facial nerve . The authors found no significant difference in recovery using similar repair techniques .
The technique of facial nerve transection and subsequent neurrorhaphy between donor and recipient during facial allograft transplantation proposed by the Amiens group specifies transecting the nerve at the main upper and lower bifurcation. That of the Cleveland group specifies transecting and repairing the nerve at the main trunk. There currently exists no literature comparing these two types of transection and repair.
Our objective in completing this study was to directly compare these two methods in an established animal model to better predict the ideal location of facial nerve transection to optimize facial nerve regeneration and functional recovery following repair.
This was a prospective randomized control animal trial conducted at the Surgical Medical Research Institute (SMRI) at the University of Alberta. A previously validated rat facial nerve model was used. Ethics approval was obtained from the Animal Care and Use Committee (ACUC) overseen by the University Animal Policy and Welfare Committee (UAPWC) at the University of Alberta in Edmonton, Alberta [AUP00000785].
24 female Wistar rats (Charles River Laboratories, Canada) weighing 200–220 g were used for this study. Sample size was based on the study by Heaton et al. which employed a similar outcome measure . All rats were housed in pairs in cages at the Health Sciences Laboratory Animal Services (HSLAS) at the University of Alberta. Rats were weighed and handled daily 2 weeks prior to the commencement of the study to reduce animal stress during the study. The 24 rats were block randomized into two groups of 12. Each animal underwent unilateral facial nerve transection and repair at either the main trunk of nerve or at the main upper and lower bifurcation of the nerve. Facial nerve functional outcome assessment was collected at 2, 4, and 6 weeks post-operatively.
Facial nerve functional outcome assessment
The facial nerve functional outcome assessment model we employed in this study was based on the model described and validated by Heaton et al. in their 2008 study . This model employs a head fixation device, body restraint, and bilateral photoelectric sensors to detect precise whisker movements as an objective measure for facial nerve function.
In order to ensure proper head fixation during whisker movement measurement, an implantable head fixation device was required. In conjunction with the biomedical engineering department at the University of Alberta, we designed a unique head implant adequate for our purposes. The implant itself was composed of acrylic and long threaded screws. The exact procedure is described below in section 7 of the materials and methods.
Tracking whisker movement
The laser micrometer itself was comprised of an emitter, which produced a 780 nm wavelength light curtain, and a detector composed of a 28 mm linear array of 4000 charge-coupled devices (CCD scanline). The emitter and detector were separated by a 5 cm vertical distance, producing a laser curtain. Movement detected within the laser curtain sent a digital signal that could then be recorded. The laser micrometers themselves were calibrated to not detect objects less than 1 mm in size to avoid tracing multiple whiskers. Instead the laser curtain detected only the marked whisker.
All subjects underwent both head implantation surgery as well as facial nerve surgery during the same anesthetic. All rats were first anesthetized with 3–4 % isoflurane. Subjects were then maintained under general anesthesia using 1.5 % isoflurane. Hair was then removed from the right side of the face and the top of the head using an electric shaver.
Facial nerve surgery
All facial nerve surgery was completed on the right side of the face on all subjects. A small incision was made just inferior to the right ear bony prominence. Under microscopic visualization, the parotid glad was visualized and everted and retracted out of the surgical field, without removing it completely. Subsequently, distal branches of the facial nerve were identified just inferior to the parotid bed. These were followed proximally until the main trunk of the facial nerve was identified. Once identified, the main trunk and upper and lower bifurcation of the facial nerve were carefully dissected. If the subject was randomized to group 1 (main trunk), a single transection of the main trunk of the facial nerve was made using straight microscopic scissors. If the subject was randomized to group 2 (bifurcation), two nerve transections were completed: one at the upper bifurcation and one at the lower bifurcation of the nerve. These transections were similarly completed using straight microscopic scissors. In both groups, the cut nerve ends were immediately repaired using a direct end-to-end technique. Using 9–0 sutures, four simple interrupted sutures were made within the proximal and distal epineural nerve endings. Care was taken to ensure proper nerve alignment. In group 1 subjects, only one nerve repair was necessary while group 2 subjects underwent two nerve repair techniques in this fashion. The parotid gland was then reflected back into the surgical field. Skin was approximated using 3–0 vicryl sutures.
Head implant surgery
Head fixation and body restraint
Once this was completed, a scented stimulus was introduced and recording started usually for a period of 5 min. The non-operative left side was used as the control for each subject. This procedure was completed for each rat at 2, 4, and 6 weeks post-operatively.
All animals tolerated the surgical procedure very well. They exhibited normal cage behavior and did not lose weight. Three animals had problems with suture break down post-operatively. This occurred in all 3 animals within 5 days of the surgical procedure. For these animals, we re-anesthetized them with isoflurane and were able to re-approximate the incision edges with 3–0 vicryl sutures. No animals had to be removed from the study.
Post-operative whisking amplitudes at week 2, 4, and 6
Week 2 amplitude (degrees)
Week 4 amplitude (degrees)
Week 6 amplitude (degrees)
MAIN TRUNK (group 1) Right side (operated)
MAIN TRUNK (group 1) Left side (control)
MAIN BIFURCATION (group 2) Right side (operated)
MAIN BIFURCATION (group 2) Left side (control)
Since 2005, facial allograft transplantation has rapidly started becoming a more commonly employed surgical procedure, indicated for individuals disfigured from trauma, burns, and birth defects among other entities. As the procedure has become more commonly employed, knowing the exact location of where to transect and repair the facial nerve has become that much more vital.
The most significant study attempting to answer the question of the location to transect and repair the facial nerve for optimal functional outcome was published by Hadlock et al. in 2010 . The authors studied a variety of different types of facial nerve injuries and injury locations in the rat model. When comparing proximal facial nerve lesions of the main trunk to peripheral facial nerve lesions of distal branches, the authors found no statistically significant difference in whisking amplitude .
In our study, we specifically compared the two locations employed by the Cleveland and Amiens groups to transect and repair the facial nerve in facial allograft transplantation (main trunk and main nerve bifurcation, respectively). Our literature search found that these two methods had never been compared in a randomized study. Similar to Hadlock et al., we found that there was no statistically significant difference between injuries at the main trunk and more distal injuries, which in our study was specifically at the main bifurcation of the nerve. However, we did find a non-statistically significant improvement in whisking amplitude for group 1 (main trunk) as compared to group 2. The whisking amplitude of group 1 was consistently greater at week 6 postoperatively. Although the whisking amplitude difference is relatively small, it does raise the possibility that a greater follow-up time may reveal a larger, statistically significant difference between the two groups. This notion is further supported by the observation that the whisking amplitude difference between the two groups consistently became greater the further out from nerve surgery.
However, given that our study showed only a minimal, non-statistically significant difference in whisking amplitude between the two groups, it seems logical with the given evidence to favor the Cleveland facial nerve protocol. The Cleveland protocol, as previously mentioned, entails only a single nerve transection and repair (group 1), minimizing operative time.
Overall, facial nerve functional recovery remained fairly limited in both groups. This may be due to several reasons, including peripheral misrouting of axons and reduction of brainstem synaptic connection with facial motoneurons. A potential limitation of our study was our follow up time. A more protracted follow-up time may have elucidated a more significant difference between the two groups.
Our study has important findings to guide future facial allograft transplantations. Given the minimal difference in whisking amplitude between the two groups, single nerve repair is more advisable as it has the added benefit of less required operative time and potential cost savings.
Our study directly compared, in a rat model, the transection and subsequent neurorrhaphy of the facial nerve at two distinct locations commonly used during facial allograft transplantation; the main trunk (group 1) and main bifurcation (group 2). We found no statistical difference between these two locations of nerve repair using identical methods. Therefore, the authors recommend the protocol outlined by the Cleveland group, which requires only single nerve repair as opposed to that described by the Amiens group. This finding has potential implications for future facial allograft transplantations and at minimum necessitates further study with long-term follow-up data.
- Post R, de Boer KS, Malessy MJ. Outcome following nerve repair of high isolated clean sharp injuries of the ulnar nerve. PLoS One. 2012;7(10):e47928. doi:10.1371/journal.pone.0047928.View ArticlePubMedPubMed CentralGoogle Scholar
- Fawcett JWKR. Peripheral nerve regenration. Annu Rev Neurosci. 1990;13:43.View ArticlePubMedGoogle Scholar
- Griffin JW, Hogan MV, Chhabra AB, Deal DN. Peripheral nerve repair and reconstruction. J Bone Joint Surg Am. 2013;95(23):2144–51. doi:10.2106/JBJS.L.00704.View ArticlePubMedGoogle Scholar
- Lohmeyer JA, Sommer B, Siemers F, Mailander P. Nerve injuries of the upper extremity-expected outcome and clinical examination. Plast Surg Nurs. 2009;29(2):88–93. doi:10.1097/01.PSN.0000356867.18220.73. quiz 94–5.View ArticlePubMedGoogle Scholar
- Liu PH, Yang LH, Wang TY, Wang YJ, Tseng GF. Proximity of lesioning determines response of facial motoneurons to peripheral axotomy. J Neurotrauma. 2006;23(12):1857–73. doi:10.1089/neu.2006.23.1857.View ArticlePubMedGoogle Scholar
- Hadlock TA, Kowaleski J, Lo D, Mackinnon SE, Heaton JT. Rodent facial nerve recovery after selected lesions and repair techniques. Plast Reconstr Surg. 2010;125(1):99–109. doi:10.1097/PRS.0b013e3181c2a5ea.View ArticlePubMedPubMed CentralGoogle Scholar
- Heaton JT, Kowaleski JM, Bermejo R, Zeigler HP, Ahlgren DJ, Hadlock TA. A system for studying facial nerve function in rats through simultaneous bilateral monitoring of eyelid and whisker movements. J Neurosci Methods. 2008;171(2):197–206. doi:10.1016/j.jneumeth.2008.02.023.View ArticlePubMedPubMed CentralGoogle Scholar
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.