Correlation between Facial Nerve Axonal Load and Age and its Relevance to Facial Reanimation

Austin Hembd, M.D., Purushottam Nagarkar, M.D., Justin Perez, M.D., Andrew Gassman, M.D., Philip Tolley, B.S., Joan Reisch, Ph.D., Charles L. White, III, M.D, Shai Rozen, M.D.

University of Texas Southwestern Medical Center, Dallas, TX

Methods:

63 fresh, cadaveric heads were dissected to expose the facial nerve. For each hemi-face, two facial nerve samples were taken: one proximal as the nerve exits the stylomastoid foramen, and one distal at the buccal branch (at a point 1cm proximal to the anterior parotid border). Nerve samples were stained using a SMI-31 immunological stain and the number of discrete axons were quantified. Correlation analysis was completed using a Pearson's correlation coefficient.

Figure 1: Example of a transverse section of proximal facial nerve with SMI-31 immunological stain that was used for axon quantification.

Figure 3: Linear relationship between age and axonal load at distal sampling point (1cm proximal to the anterior parotid border along the buccal branch).

Figure 4: Linear relationship between age and axonal load at the proximal sampling point (at the stylomastoid foramen).

Figure 2: The average axonal loads at the proximal and distal sampling points from cadavers age 22-59 (n= 26), age 61-79 (n=53), and age 80-97 (n=33).

Results:

• 36 females and 27 males were dissected with an average age of 71 (age range 22-97). At the proximal (r = -.26; p < .01; n=104) and distal (r= -.45; p <.0001; n=114) sampling points, there was a significant negative correlation between age and axonal load.

• Average axonal loads at the proximal and distal sampling points from cadavers age 22-59 (n= 26), age 61-79 (n=53), and age 80-97 (n=33) are depicted in Figure 2 below.

• The difference of mean axon counts at the distal sampling point was statistically significant between both the youngest and middle-aged cohorts (p=. 02), and the middle-aged and oldest cohorts (p=. 002). The difference of mean axon counts at the proximal sampling point was statistically significant between the youngest and oldest cohorts only (p=. 03).

Introduction:

Two-stage facial reanimation procedures with a cross-facial nerve graft often have unsatisfactory results in the older patient. Although the cause of result variability is likely multifactorial, some studies suggest that increased donor nerve axonal load improves function of a free muscle transfer after a cross-face nerve graft. This study attempts to characterize the relationship between age and facial nerve (donor) axonal counts.

Conclusion:

• As age increases, the axonal counts of the facial nerve at the zygomatic and buccal branches decreases.

• These results propose that decreasing axonal load can be a factor in less reliable outcomes of cross-facial grafting in the aging population. Moreover, this underscores the importance of recruiting more donor axons in attempting to improve facial reanimation in the older patient.

• Whether an intraparotid coaptation in a two-stage reanimation technique may be plausible in an older age group (seventh or eighth decade of life) is difficult to answer. In our opinion, this is not the only solution, as nerve regeneration in this group may be so poor that it is insurmountable by increasing the donor axonal load alone. Yet, this information could possibly be used in patients in the fifth or sixth decade of life and younger to improve outcomes.

References:1. Gousheh, J., Arasteh, E. Treatment of facial paralysis: dynamic reanimation of spontaneous facial expression-apropos of 655 patients. Plast Reconstr Surg 2011;128:693e- 703e. 2. Terzis, J. K., Konofaos, P. Experience with 60 adult patients with facial paralysis secondary to tumor extirpation. Plastic and reconstructive surgery 2012;130:51e-66e. 3. Terzis JK, Wang W, Zhao Y. Effect of axonal load on the functional and aesthetic outcomes of the cross-facial nerve graft procedure for facial reanimation. Plast Reconstr Surg. 2009;124:1499–1512.4. Braam MJ, Nicolai JP. Axonal regeneration rate through cross-face nerve grafts. Microsurgery. 1993;14(9):589-91. 5. Cavallotti C, Cavallotti D, Pescosolido N, Pacella E. Age-related changes in rat optic nerve: morphological studies. Anat Histol Embryol. 2003 Feb;32(1):12-6.6. Cavallotti C, Pacella E, Pescosolido N, Tranquilli-Leali FM, Feher J. Age- related changes in the human optic nerve. Can J Ophthalmol. 2002 Dec;37(7):389-94. 7. Fujii M, Goto N. Nerve fiber analysis of the facial nerve. Ann Otol Rhinol Laryngol. 1989 Sep;98(9):732-6.8. Jacobs JM, Love S. Qualitative and quantitative morphology of human sural nerve at different ages. Brain. 1985 Dec;108 (Pt 4):897-924. 9. Kondo Y, Moriyama H, Hirai S, Qu N, Itoh M. The relationship between Bell's palsy and morphometric aspects of the facial nerve. Eur Arch Otorhinolaryngol. 2012 Jun;269(6):1691-5.10. Lehmann J. Age-related changes in peripheral nerves. Zentralbl Allg Pathol. 1986;131(3):219-27. German. 11. Oka K, Goto N, Nonaka N, Goto J, Tsurumi T. Nerve fiber analysis and age-related changes of the human mandibular nerve. Okajimas Folia Anat Jpn. 2001 May;78(1):39-41. 12. Streppel M, Angelov DN, Guntinas-Lichius O, Hilgers RD, Rosenblatt JD, Stennert E, Neiss WF. Slow axonal regrowth but extreme hyperinnervation of target muscle after suture of the facial nerve in aged rats. Neurobiol Aging. 1998 Jan-Feb;19(1):83-8. 13. Sturrock RR. Loss of neurons from the motor nucleus of the facial nerve in the ageing mouse brain. J Anat. 1988 Oct;160:189-94. 14. Kullman GL, Dyck PJ, Cody DTR. Anatomy of the mastoid portion of the facial nerve. Arch Otolaryngol 1971;93:29-33.15. Snyder-Warwick, A. K., Fattah, A. Y., Zive, L., Halliday, W., Borschel, G. H., Zuker, R. M. The degree of facial movement following microvascular muscle transfer in pediatric facial reanimation depends on donor motor nerve axonal density. Plast Reconstr Surg 2015;135:370e- 381e. 16. MacQuillan AH, Grobbelaar AO. Functional muscle transfer and the variance of reinnervating axonal load: Part I. The facial nerve. Plast Reconstr Surg. 2008;121:1570–1577.17. Hassan, K.M. Histomorphometric Analysis of Nerve Biopsies in the Two- Stage Cross-Face Free Muscle Transfer for Facial Reanimation with Correlation to the Functional Outcome. Egypt, J. Plast. Reconstr. Surg., Vol. 37, No. 1, January: 131-138, 201318. Frey M, Happak W, Girch W, Bittner RE, Gruber H. Histomorphometric studies in patients with facial palsy treated by functional muscle transplantation: New aspects for the surgical concept. Ann Plast Surg. 1991;26:370 –379. 19. Thanos PK, Terzis JK. A histomorphometric analysis of the cross-facial nerve graft in the treatment of facial paralysis. J Reconstr Microsurg. 1996;12:375–382.20. Jacobs JM, Laing JH, Harrison DH. Regeneration through a long nerve graft used in the correction of facial palsy: A qualitative and quantitative study. Brain 1996;119:271–279. 21. Dyck, P. J., Thomas, P. K. Peripheral neuropathy, 4th ed. Philadelphia: Saunders; 2005 22. Klebuc M, Shenaq SM. Donor nerve selection in facial reani-mation surgery. Semin Plast Surg. 2004;18:53–60. 23. Bae YC, Zuker RM, Manktelow RT, Wade S. A comparison of commissure excursion following gracilis muscle transplanta- tion for facial paralysis using a cross-face nerve graft versus the motor nerve to the masseter nerve. Plast Reconstr Surg. 2006;117:2407–2413. 24. Hontanilla B, Marre D, Cabello A. Facial reanimation with gracilis muscle transfer neurotized to cross-facial nerve graft versus masseteric nerve: A comparative study using the FACIAL CLIMA evaluating system. Plast Reconstr Surg. 2013;131:1241–1252. 25. Coombs CJ, Ek EW, Wu T, Cleland H, Leung MK. Masseteric- facial nerve coaptation: An alternative technique for facial nerve reinnervation. J Plast Reconstr Aesthet Surg. 2009;62:1580–1588. 26. Borschel GH, Kawamura DH, Kasukurthi R, Hunter DA, Zuker RM, Woo AS. The motor nerve to the masseter muscle: An anatomic andhistomorphometric study to facilitate its use in facial reanimation. J Plast Reconstr Aesthet Surg. 2012;65:363–366.27. Placheta E, Wood MD, Lafontaine C, et al. Enhancement of facial nerve motoneuron regeneration through cross- face nerve grafts by adding end-to-side sensory axons. Plast Reconstr Surg. 2015;135:460–47128. Hembd A, Nagarkar PA, Saba S, Wan D, Kutz JW, Isaacson B, Gupta S, White CL 3rd, Rohrich RJ, Rozen SM. Facial Nerve Axonal Analysis and Anatomic Localization in Donor Nerve: Optimizing Axonal Load for Cross Facial Nerve Grafting in Facial Reanimation. Plast Reconstr Surg. 2016 Sep 14.29. Placheta, E, Frey, M, Tzou, CH, Pona, I. Histomorphometric Analysis of Facial Nerve Regeneration through Cross-face Nerve Grafts in Facial Reanimation Surgery. American Society for Peripheral Nerve, Paradise Island, Bahamas. 201530. Van Buskirk, C. The seventh nerve complex. Journal of Comparative Neurology 1945;82:303-333.