Laryngeal Reinnervation

  • Kenneth R. Feehs
  • Richard W. Thomas
  • Michael I. OrestesEmail author


Laryngeal denervation from recurrent laryngeal nerve injury is a known complication of anterior neck and thyroid surgery resulting in unilateral or bilateral vocal fold paralysis. Laryngeal reinnervation refers to various surgical techniques that restore neural connection to denervated portions of the larynx. These techniques include direct anastomosis or neurorrhaphy, nerve-muscle pedicle transfer, direct implantation of a nerve into muscle, and muscle-nerve-muscle transfer. Laryngeal reinnervation presents multiple advantages over traditional static techniques and has been shown to achieve normal vocalization in unilateral vocal fold paralysis and phasic glottic opening in bilateral vocal fold paralysis. The principal disadvantage of laryngeal reinnervation compared to static techniques is time duration to clinical effect and perceived complexity of the surgery. Reinnervation of the larynx continues to be an active, propitious area of investigation holding significant promise for both current and future patients with vocal fold paralysis.


Recurrent laryngeal nerve Laryngeal reinnervation Vocal fold paralysis Direct neurorrhaphy Nerve-muscle pedicle Direct nerve implantation Ansa cervicalis nerve Hypoglossal nerve Superior laryngeal nerve External branch 



The views expressed in this article are those of the authors and do not reflect the official policy or position of the US Department of the Navy, Department of the Army, Department of Defense, Uniformed Service University, or the US Federal Government.


  1. 1.
    Jeannon JP, Orabi AA, Bruch GA, Abdalsalam HA, Simo R. Diagnosis of recurrent laryngeal nerve palsy after thyroidectomy: a systematic review. Int J Clin Pract. 2009;63(4):624–9.PubMedCrossRefGoogle Scholar
  2. 2.
    Rosato L, Avenia N, Bernante P, De Palma M, Gulino G, Nasi PG, et al. Complications of thyroid surgery: analysis of a multicentric study on 14,934 patients operated on in Italy over 5 years. World J Surg. 2004;28(3):271–6.PubMedCrossRefGoogle Scholar
  3. 3.
    Thomusch O, Machens A, Sekulla C, Ukkat J, Lippert H, Gastinger I, Dralle H. Multivariate analysis of risk factors for postoperative complications in benign goiter surgery: prospective multicenter study in Germany. World J Surg. 2000;24(11):1335–41.PubMedCrossRefGoogle Scholar
  4. 4.
    Hayward NJ, Grodski S, Yeung M, Johnson WR, Serpell J. Recurrent laryngeal nerve injury in thyroid surgery: a review. ANZ J Surg. 2013;83(1–2):15–21.PubMedCrossRefGoogle Scholar
  5. 5.
    Lo CY, Kwok KF, Yuen PW. A prospective evaluation of recurrent laryngeal nerve paralysis during thyroidectomy. Arch Surg. 2000;135(2):204–7.PubMedCrossRefGoogle Scholar
  6. 6.
    Horsley JA. Suture of the recurrent laryngeal nerve with report of a case. Trans South Surg Gynecol Assoc. 1909;22:161–70.Google Scholar
  7. 7.
    Orestes MI, Berke GS. Intralaryngeal anatomy of the recurrent laryngeal nerve. In: Randolph GW, editor. The recurrent and superior laryngeal nerves. Switzerland: Springer International; 2016. p. 53–63.CrossRefGoogle Scholar
  8. 8.
    Paniello RC. Laryngeal reinnervation. Otolaryngol Clin N Am. 2004;37(1):161–81, vii-viii. ReviewCrossRefGoogle Scholar
  9. 9.
    Doyle PJ, Brummett RE, Everts EC. Results of surgical section and repair of the recurrent laryngeal nerve. Laryngoscope. 1967;77(8):1245–54.PubMedCrossRefGoogle Scholar
  10. 10.
    Lahey FH. Suture of the recurrent laryngeal nerve for bilateral abductor paralysis. Ann Surg. 1928;87(4):481–4.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Crumley RL. Laryngeal synkinesis: its significance to the laryngologist. Ann Otol Rhinol Laryngol. 1989;98(2):87–92.PubMedCrossRefGoogle Scholar
  12. 12.
    Siribodhi C, Sundmäker W, Atkins JP, Bonner FJ. Electromyographic studies of laryngeal paralysis and regeneration of laryngeal motor nerves in dogs. Laryngoscope. 1963;73(2):148-64.CrossRefGoogle Scholar
  13. 13.
    Crumley RL. Repair of the recurrent laryngeal nerve. Otolaryngol Clin N Am. 1990;23(3):553–63.Google Scholar
  14. 14.
    Chou FF, Su CY, Jeng SF, Hsu KL, Lu KY. Neurorrhaphy of the recurrent laryngeal nerve. J Am Coll Surg. 2003;197(1):52–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Zheng H, Li Z, Zhou S, Cuan Y, Wen W. Update: laryngeal reinnervation for unilateral vocal cord paralysis with the ansa cervicalis. Laryngoscope. 1996;106(12 Pt 1):1522–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Hast MH. Studies on the extrinsic laryngeal muscles. Arch Otolaryngol. 1968;88(3):273–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Hisa Y, Malmgren LT. Muscle fiber types in the human sternothyroid muscle: a correlated histochemical and ultrastructural morphometric study. In: Baer T, Sasaki C, Harris K, editors. Laryngeal function in phonation and respiration. Boston: College-Hill; 1987. p. 29–44.Google Scholar
  18. 18.
    Talmadge RJ. Myosin heavy chain isoform expression following reduced neuromuscular activity: potential regulatory mechanisms. Muscle Nerve. 2000;23(5):661–79.PubMedCrossRefGoogle Scholar
  19. 19.
    Goding GS Jr. Nerve-muscle pedicle reinnervation of the paralyzed vocal cord. Otolaryngol Clin N Am. 1991;24(5):1239–52.Google Scholar
  20. 20.
    Brondbo K, Jacobsen E, Gjellan M, Refsum H. Recurrent nerve/ansa cervicalis nerve anastomosis: a treatment alternative in unilateral recurrent nerve paralysis. Acta Otolaryngol. 1992;112(2):353–7.PubMedCrossRefGoogle Scholar
  21. 21.
    Zheng H, Li Z, Zhou S, Cuan Y, Wen W, Lan J. Experimental study on reinnervation of vocal cord adductors with the ansa cervicalis. Laryngoscope. 1996;106(12 Pt 1):1516–21.PubMedCrossRefGoogle Scholar
  22. 22.
    Frazier CH. Anastomosis of the recurrent laryngeal nerve with the descendens noni: in cases of recurrent laryngeal paralysis. JAMA. 1924;83(21):1637–41.CrossRefGoogle Scholar
  23. 23.
    Crumley RL, Izdebski K. Voice quality following laryngeal reinnervation by ansa hypoglossi transfer. Laryngoscope. 1986;96(6):611–6.PubMedCrossRefGoogle Scholar
  24. 24.
    Crumley RL. Update: ansa cervicalis to recurrent laryngeal nerve anastomosis for unilateral laryngeal paralysis. Laryngoscope. 1991;101(4 Pt 1):384–7.. discussion 388PubMedCrossRefGoogle Scholar
  25. 25.
    Olson DE, Goding GS, Michael DD. Acoustic and perceptual evaluation of laryngeal reinnervation by ansa cervicalis transfer. Laryngoscope. 1998;108(12):1767–72.PubMedCrossRefGoogle Scholar
  26. 26.
    Wang W, Chen D, Chen S, Li D, Li M, Xia S, Zheng H. Laryngeal reinnervation using ansa cervicalis for thyroid surgery-related unilateral vocal fold paralysis: a long-term outcome analysis of 237 cases. PLoS One. 2011;6(4):e19128.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Miyauchi A, Yokozawa T, Kobayashi K, Hirai K, Matsuzuka F, Kuma K. Opposite ansa cervicalis to recurrent laryngeal nerve anastomosis to restore phonation in patients with advanced thyroid cancer. Eur J Surg. 2001;167(7):540–1.PubMedCrossRefGoogle Scholar
  28. 28.
    Wang W, Chen S, Chen D, Xia S, Qiu X, Liu Y, Zheng H. Contralateral ansa cervicalis-to-recurrent laryngeal nerve anastomosis for unilateral vocal fold paralysis: a long-term outcome analysis of 56 cases. Laryngoscope. 2011;121(5):1027–34.PubMedCrossRefGoogle Scholar
  29. 29.
    Paniello RC, Lee P, Dahm JD. Hypoglossal nerve transfer for laryngeal reinnervation: a preliminary study. Ann Otol Rhinol Laryngol. 1999;108(3):239–44.PubMedCrossRefGoogle Scholar
  30. 30.
    Paniello RC. Laryngeal reinnervation with the hypoglossal nerve: II. Clinical evaluation and early patient experience. Laryngoscope. 2000;110(5 Pt 1):739–48.PubMedCrossRefGoogle Scholar
  31. 31.
    Tucker HM, Harvey J, Ogura JH. Vocal cord remobilization in the canine larynx. Arch Otolaryngol. 1970;92(6):530–3.PubMedCrossRefGoogle Scholar
  32. 32.
    Tucker HM. Human laryngeal reinnervation. Laryngoscope. 1976;86(6):769–79.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Tucker HM. Reinnervation of the unilaterally paralyzed larynx. Ann Otol Rhinol Laryngol. 1977;86(6 Pt 1):789–94.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Applebaum EL, Allen GW, Sisson GA. Human laryngeal reinnervation: the Northwestern experience. Laryngoscope. 1979;89(11):1784–7.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    May M, Beery Q. Muscle-nerve pedicle laryngeal reinnervation. Laryngoscope. 1986;96(11):1196–200.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Tucker HM. Long-term results of nerve-muscle pedicle reinnervation for laryngeal paralysis. Ann Otol Rhinol Laryngol. 1989;98(9):674–6.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Tucker HM, Rusnov M. Laryngeal reinnervation for unilateral vocal cord paralysis: long-term results. Ann Otol Rhinol Laryngol. 1981;90(5 Pt 1):457–9.PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Su WF, Hsu YD, Chen HC, Sheng H. Laryngeal reinnervation by ansa cervicalis nerve implantation for unilateral vocal cord paralysis in humans. J Am Coll Surg. 2007;204(1):64–72.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    El-Kashlan HK, Carroll WR, Hogikyan ND, Chepeha DB, Kileny PR, Esclamado RM. Selective cricothyroid muscle reinnervation by muscle-nerve-muscle neurotization. Arch Otolaryngol Head Neck Surg. 2001;127(10):1211–5.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Chhetri DK, Gerratt BR, Kreiman J, Berke GS. Combined arytenoid adduction and laryngeal reinnervation in the treatment of vocal fold paralysis. Laryngoscope. 1999;109(12):1928–36.PubMedCrossRefGoogle Scholar
  41. 41.
    Crumley RL. Teflon versus thyroplasty versus nerve transfer: a comparison. Ann Otol Rhinol Laryngol. 1990;99(10 Pt 1):759–63.PubMedCrossRefGoogle Scholar
  42. 42.
    Lee SW. Park KN. A long-term comparative prospective study between reinnervation and injection laryngoplasty. Laryngoscope. 2018;128:1893. [Epub ahead of print].CrossRefPubMedGoogle Scholar
  43. 43.
    Paniello RC, Edgar JD, Kallogjeri D, Piccirillo JF. Medialization versus reinnervation for unilateral vocal fold paralysis: a multicenter randomized clinical trial. Laryngoscope. 2011;121(10):2172–9.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Tucker HM. Long-term preservation of voice improvement following surgical medialization and reinnervation for unilateral vocal fold paralysis. J Voice. 1999;13(2):251–6.PubMedCrossRefGoogle Scholar
  45. 45.
    Rosenthal LH, Benninger MS, Deeb RH. Vocal fold immobility: a longitudinal analysis of etiology over 20 years. Laryngoscope. 2007;117(10):1864–70.PubMedCrossRefGoogle Scholar
  46. 46.
    Nguyen M, Junien-Lavillauroy C, Faure C. Anatomical intra-laryngeal anterior branch study of the recurrent (inferior) laryngeal nerve. Surg Radiol Anat. 1989;11(2):123–7.PubMedCrossRefGoogle Scholar
  47. 47.
    Prades JM, Faye MB, Timoshenko AP, Dubois MD, Dupuis-Cuny A, Martin C. Microsurgical anatomy of intralaryngeal distribution of the inferior laryngeal nerve. Surg Radiol Anat. 2006;28(3):271–6.PubMedCrossRefGoogle Scholar
  48. 48.
    E M, Leon X, Orus C, Quer M, Sanudo JR. Variability in nerve patterns of the adductor muscle group supplied by the recurrent laryngeal nerve. Laryngoscope. 2005;115(2):358–62.CrossRefGoogle Scholar
  49. 49.
    Baldissera F, Tredici G, Marini G, Fiori MG, Cantarella G, Ottaviani F, Zanoni R. Innervation of the paralyzed laryngeal muscles by phrenic motoneurons. A quantitative study by light and electron microscopy. Laryngoscope. 1992;102(8):907–16.PubMedCrossRefGoogle Scholar
  50. 50.
    Rice DH. Laryngeal reinnervation. Laryngoscope. 1982;92(9 Pt 1):1049–59.PubMedGoogle Scholar
  51. 51.
    Doyle PJ, Chepeha DB, Westerberg BD, Schwarz DW. Phrenic nerve reinnervation of the cat’s larynx: a new technique with proven success. Ann Otol Rhinol Laryngol. 1993;102(11):837–42.PubMedCrossRefGoogle Scholar
  52. 52.
    Crumley RL. Experiments in laryngeal reinnervation. Laryngoscope. 1982;92(9 Pt 2 Suppl 30):1–27.PubMedCrossRefGoogle Scholar
  53. 53.
    Marie JP, Lerosey Y, Dehesdin D, Jin O, Tadíe M, Andrieu-Guitrancourt J. Experimental reinnervation of a strap muscle with a few roots of the phrenic nerve in rabbits. Ann Otol Rhinol Laryngol. 1999;108(10):1004–11.PubMedCrossRefGoogle Scholar
  54. 54.
    Crumley RL. Phrenic nerve graft for bilateral vocal cord paralysis. Laryngoscope. 1983;93(4):425–8.PubMedCrossRefGoogle Scholar
  55. 55.
    Marie JP. Nerve reconstruction. In: Remacle M, Eckel HE, editors. Surgery of larynx and trachea. Berlin. Heidelberg: Springer-Verlag; 2010. p. 279–94.Google Scholar
  56. 56.
    Woodson GE. Respiratory activity of the cricothyroid muscle in conscious humans. Laryngoscope. 1990;100(1):49-53.CrossRefGoogle Scholar
  57. 57.
    Woodson GE, Murry MP, Schweizer V, Hengesteg A, Chen N, Yeung D. Unilateral cricothyroid contraction and glottic configuration. J Voice. 1998;12(3):335–9.PubMedCrossRefGoogle Scholar
  58. 58.
    Maniglia AJ, Dodds B, Sorensen K, Katirji MB. Rosenbaum ML.Newer technique of laryngeal reinnervation: superior laryngeal nerve (motor branch) as a driver of the posterior cricoarytenoid muscle. Ann Otol Rhinol Laryngol. 1989;98(11):907–9.PubMedCrossRefGoogle Scholar
  59. 59.
    Orestes MI, Chhetri DK, Berke G. Selective reinnervation for bilateral vocal cord paralysis using the superior laryngeal nerve. Laryngoscope. 2015;125(11):2547–50.PubMedCrossRefGoogle Scholar
  60. 60.
    Zheng H, Zhou S, Li Z, Chen S, Zhang S, Huang Y, et al. Reinnervation of the posterior cricoarytenoid muscle by the phrenic nerve for bilateral vocal cord paralysis in humans. Zhonghua Er Bi Yan Hou Ke Za Zhi. 2002;37:210–4. [Article in Chinese].PubMedGoogle Scholar
  61. 61.
    Smith ME, King JD, Elsherif A, Muntz HR, Park AH, Kouretas PC. Should all newborns who undergo patent ductus arteriosus ligation be examined for vocal fold mobility? Laryngoscope. 2009;119(8):1606–9.PubMedCrossRefGoogle Scholar
  62. 62.
    Smith ME, Roy N, Houtz D. Laryngeal reinnervation for paralytic dysphonia in children younger than 10 years. Arch Otolaryngol Head Neck Surg. 2012;138(12):1161–6.PubMedCrossRefGoogle Scholar
  63. 63.
    Carroll TL, Rosen CA. Long-term results of calcium hydroxylapatite for vocal fold augmentation. Laryngoscope. 2011;121(2):313–9.PubMedCrossRefGoogle Scholar
  64. 64.
    Mallur PS, Morrison MP, Postma GN, Amin MR, Rosen CA. Safety and efficacy of carboxymethylcellulose in the treatment of glottic insufficiency. Laryngoscope. 2012;122(2):322–6.PubMedCrossRefGoogle Scholar
  65. 65.
    Patel NJ, Kerschner JE, Merati AL. The use of injectable collagen in the management of pediatric vocal unilateral fold paralysis. Int J Pediatr Otorhinolaryngol. 2003;67(12):1355–60.PubMedCrossRefGoogle Scholar
  66. 66.
    Marcum KK, Wright SC Jr, Kemp ES, Kitse DJ. A novel modification of the ansa to recurrent laryngeal nerve reinnervation procedure for young children. Int J Pediatr Otorhinolaryngol. 2010;74(11):1335–7.PubMedCrossRefGoogle Scholar
  67. 67.
    Sipp JA, Kerschner JE, Braune N, Hartnick CJ. Vocal fold medialization in children: injection laryngoplasty, thyroplasty, or nerve reinnervation? Arch Otolaryngol Head Neck Surg. 2007;133(8):767–71.PubMedCrossRefGoogle Scholar
  68. 68.
    Butskiy O, Mistry B, Chadha NK. Surgical interventions for pediatric unilateral vocal cord paralysis: a systematic review. JAMA Otolaryngol Head Neck Surg. 2015;141(7):654–60.PubMedCrossRefGoogle Scholar
  69. 69.
    Bouhabel S, Hartnick CJ. Current trends in practices in the treatment of pediatric unilateral vocal fold immobility: a survey on injections, thyroplasty and nerve reinnervation. Int J Pediatr Otorhinolaryngol. 2018;109:115–8.PubMedCrossRefGoogle Scholar
  70. 70.
    A S, O’Malley BW Jr, Coleman ME, Alila HW, Flint PW. Reinnervation of motor endplates and increased muscle fiber size after human insulin-like growth factor I gene transfer into the paralyzed larynx. Hum Gene Ther. 1998;9(14):2039–47.CrossRefGoogle Scholar
  71. 71.
    Araki K, Shiotani A, Watabe K, Saito K, Moro K, Ogawa K. Adenoviral GDNF gene transfer enhances neurofunctional recovery after recurrent laryngeal nerve injury. Gene Ther. 2006;13(4):296–303.PubMedCrossRefGoogle Scholar
  72. 72.
    Sakowski SA, Heavener SB, Lunn JS, Fung K, Oh SS, Spratt SK, et al. Neuroprotection using gene therapy to induce vascular endothelial growth factor-A expression. Gene Ther. 2009;16(11):1292–9.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Rubin AD, Hogikyan ND, Oh A, Feldman EL. Potential for promoting recurrent laryngeal nerve regeneration by remote delivery of viral gene therapy. Laryngoscope. 2012;122(2):349–55.PubMedCrossRefGoogle Scholar
  74. 74.
    Araki K, Suzuki H, Uno K, Tomifuji M, Shiotani A. Gene therapy for recurrent laryngeal nerve injury. Genes (Basel). 2018;9(7):E316. Scholar
  75. 75.
    Hydman J, Remahl S, Björck G, Svensson M, Mattsson P. Nimodipine improves reinnervation and neuromuscular function after injury to the recurrent laryngeal nerve in the rat. Ann Otol Rhinol Laryngol. 2007;116(8):623–30.PubMedCrossRefGoogle Scholar
  76. 76.
    Nishimoto K, Kumai Y, Minoda R, Yumoto E. Nimodipine accelerates reinnervation of denervated rat thyroarytenoid muscle following nerve-muscle pedicle implantation. Laryngoscope. 2012;122(3):606–13.PubMedCrossRefGoogle Scholar
  77. 77.
    Gorphe P, Guerout N, Birchall M, Terenghi G, Marie JP. Tacrolimus enhances the recovery of normal laryngeal muscle fibre distribution after reinnervation. J Laryngol Otol. 2012;126(11):1155–8.PubMedCrossRefPubMedCentralGoogle Scholar
  78. 78.
    Park AM, Dhanda Patil R, Paniello RC. Prevention of post-traumatic reinnervation with microtubule inhibitors. Laryngoscope. 2015;125(10):E333–7.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Paniello RC. Vocal fold paralysis: improved adductor recovery by vincristine blockade of posterior cricoarytenoid. Laryngoscope. 2015;125(3):655–60.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Kenneth R. Feehs
    • 1
  • Richard W. Thomas
    • 2
  • Michael I. Orestes
    • 3
    Email author
  1. 1.Department of SurgeryWalter Reed National Military Medical CenterBethesdaUSA
  2. 2.Office of the President, Uniformed Services UniversityBethesdaUSA
  3. 3.Department of Otolaryngology/Head and Neck SurgeryWalter Reed National Military Medical CenterBethesdaUSA

Personalised recommendations