Semin Neurol
DOI: 10.1055/s-0044-1791665
Review Article

An Updated Evaluation of the Management of Nerve Gaps: Autografts, Allografts, and Nerve Transfers

Anna Rose Johnson
1   Division of Plastic and Reconstructive Surgery, Washington University School of Medicine, St. Louis, Missouri
,
Abdullah Said
1   Division of Plastic and Reconstructive Surgery, Washington University School of Medicine, St. Louis, Missouri
,
Jesus Acevedo
1   Division of Plastic and Reconstructive Surgery, Washington University School of Medicine, St. Louis, Missouri
,
Ruby Taylor
1   Division of Plastic and Reconstructive Surgery, Washington University School of Medicine, St. Louis, Missouri
,
Kitty Wu
2   Division of Hand and Microvascular Surgery, Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota
,
Wilson Z. Ray
3   Department of Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri
,
J. Megan Patterson
4   Department of Orthopedic Surgery, University of North Carolina, Chapel Hill, North Carolina
,
Susan E. Mackinnon
1   Division of Plastic and Reconstructive Surgery, Washington University School of Medicine, St. Louis, Missouri
› Author Affiliations

Abstract

Within the past decade, there have been multiple innovations in the field of nerve surgery. In this review, we highlight critical changes and innovations that have helped advance the field and present opportunities for further study. This includes the modification and clarification of the classification schema for nerve injuries which informs prognosis and treatment, and a refined understanding and application of electrodiagnostic studies to guide patient selection. We provide indications for operative intervention based on this nerve injury classification and propose strategies best contoured for varying injury presentations at differing time points. Lastly, we discuss new developments in surgical techniques and approaches based on these advancements.



Publication History

Article published online:
11 October 2024

© 2024. Thieme. All rights reserved.

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  • References

  • 1 Ray WZ, Mackinnon SE. Management of nerve gaps: autografts, allografts, nerve transfers, and end-to-side neurorrhaphy. Exp Neurol 2010; 223 (01) 77-85
  • 2 Naff NJ, Ecklund JM. History of peripheral nerve surgery techniques. Neurosurg Clin N Am 2001; 12 (01) 197-209 , x
  • 3 Jabaley ME, Wallace WH, Heckler FR. Internal topography of major nerves of the forearm and hand: a current view. J Hand Surg Am 1980; 5 (01) 1-18
  • 4 Kobayashi J, Mackinnon SE, Watanabe O. et al. The effect of duration of muscle denervation on functional recovery in the rat model. Muscle Nerve 1997; 20 (07) 858-866
  • 5 Mackinnon SE, O'Brien JP, Dellon AL, McLean AR, Hudson AR, Hunter DA. An assessment of the effects of internal neurolysis on a chronically compressed rat sciatic nerve. Plast Reconstr Surg 1988; 81 (02) 251-258
  • 6 Nath RK, Mackinnon SE, Shenaq SM. New nerve transfers following peripheral nerve injuries. Operative Techniques in Plastic and Reconstructive Surgery 1997; 4 (01) 2-11
  • 7 Gilbert A, Pivato G, Kheiralla T. Long-term results of primary repair of brachial plexus lesions in children. Microsurgery 2006; 26 (04) 334-342
  • 8 Saheb-Al-Zamani M, Yan Y, Farber SJ. et al. Limited regeneration in long acellular nerve allografts is associated with increased Schwann cell senescence. Exp Neurol 2013; 247: 165-177
  • 9 Poppler LH, Ee X, Schellhardt L. et al. Axonal growth arrests after an increased accumulation of Schwann cells expressing senescence markers and stromal cells in acellular nerve allografts. Tissue Eng Part A 2016; 22 (13-14): 949-961
  • 10 Sunderland S. A classification of peripheral nerve injuries producing loss of function. Brain 1951; 74 (04) 491-516
  • 11 Sunderland SS. Nerve Injuries and Their Repair: A Critical Appraisal. Churchill Livingstone; 1991
  • 12 Mackinnon SE, Dellon L. Surgery of the Peripheral Nerve. 1st ed. Thieme; 1988
  • 13 Hill EJR, Patterson JMM, Yee A, Crock LW, Mackinnon SE. What is operative? Conceptualizing neuralgia: neuroma, compression neuropathy, painful hyperalgesia, and phantom nerve pain. J Hand Surg Glob Online 2022; 5 (01) 126-132
  • 14 Peters BR, Pripotnev S, Chi D, Mackinnon SE. Complete foot drop with normal electrodiagnostic studies: Sunderland “zero” ischemic conduction block of the common peroneal nerve. Ann Plast Surg 2022; 88 (04) 425-428
  • 15 Mackinnon SE, Yee A, Barbour JR. et al. Nerve Surgery. 2015th ed. Thieme Verlag; 2015. DOI: 10.1055/b-003-106416
  • 16 Dengler J, Dolen U, Patterson JMM. et al. supercharge end-to-side anterior interosseous-to-ulnar motor nerve transfer restores intrinsic function in cubital tunnel syndrome. Plast Reconstr Surg 2020; 146 (04) 808-818
  • 17 Chi D, Ha AY, Alotaibi F. et al. A surgical framework for the management of incomplete axillary nerve injuries. J Reconstr Microsurg 2023; 39 (08) 616-626
  • 18 Varagur K, Jacobson L, Teixeira R, Patterson JMM, Skolnick GB, Mackinnon SE. Following a surgical paradigm shift through the adoption of nerve transfers among board-eligible and practicing plastic surgeons. Hand (N Y) 2023; DOI: 10.1177/15589447231167582.
  • 19 Chi D, Tandon D, Evans AG. et al. Brachial Gunshot Wounds: Injury Patterns and Considerations for Managing the Abnormal Neurological Examination. Hand (N Y) 2024; DOI: 10.1177/15589447231221170.
  • 20 Pripotnev S, Bucelli RC, Patterson JMM, Yee A, Pet MA, Mackinnon S. Interpreting electrodiagnostic studies for the management of nerve injury. J Hand Surg Am 2022; 47 (09) 881-889
  • 21 Mackinnon SE, Yee A. Interpreting Electrodiagnostic Studies for the Management of Nerve Injuries;. 2022 . Accessed April 25, 2024 at: https://www.youtube.com/watch?v=pxB5aOqCDU4
  • 22 Hydén H. Protein Metabolism in the Nerve Cell During Growth and Function. Kungl. Boktryckeriet; 1943
  • 23 Zuo KJ, Shafa G, Antonyshyn K, Chan K, Gordon T, Borschel GH. A single session of brief electrical stimulation enhances axon regeneration through nerve autografts. Exp Neurol 2020; 323: 113074
  • 24 Nix WA, Hopf HC. Electrical stimulation of regenerating nerve and its effect on motor recovery. Brain Res 1983; 272 (01) 21-25
  • 25 Al-Majed AA, Neumann CM, Brushart TM, Gordon T. Brief electrical stimulation promotes the speed and accuracy of motor axonal regeneration. J Neurosci 2000; 20 (07) 2602-2608
  • 26 Senger JL, Chan KM, Macandili H. et al. Conditioning electrical stimulation promotes functional nerve regeneration. Exp Neurol 2019; 315: 60-71
  • 27 Juckett L, Saffari TM, Ormseth B, Senger JL, Moore AM. The effect of electrical stimulation on nerve regeneration following peripheral nerve injury. Biomolecules 2022; 12 (12) 1856
  • 28 Chu XL, Song XZ, Li Q. et al. Basic mechanisms of peripheral nerve injury and treatment via electrical stimulation. Neural Regen Res 2022; 17 (10) 2185-2193
  • 29 Therapeutic strategies for peripheral nerve injuries: FK506 and electrostimulation. Plast Aesthet Res 2023; 10 (00) null-null
  • 30 Power HA, Morhart MJ, Olson JL, Chan KM. Postsurgical electrical stimulation enhances recovery following surgery for severe cubital tunnel syndrome: a double-blind randomized controlled trial. Neurosurgery 2020; 86 (06) 769-777
  • 31 Wong JN, Olson JL, Morhart MJ, Chan KM. Electrical stimulation enhances sensory recovery: a randomized controlled trial. Ann Neurol 2015; 77 (06) 996-1006
  • 32 Barber B, Seikaly H, Ming Chan K. et al. Intraoperative Brief Electrical Stimulation of the Spinal Accessory Nerve (BEST SPIN) for prevention of shoulder dysfunction after oncologic neck dissection: a double-blinded, randomized controlled trial. J Otolaryngol Head Neck Surg 2018; 47 (01) 7
  • 33 Roh J, Schellhardt L, Keane GC. et al. Short-duration, pulsatile, electrical stimulation therapy accelerates axon regeneration and recovery following tibial nerve injury and repair in rats. Plast Reconstr Surg 2022; 149 (04) 681e-690e
  • 34 Sayanagi J, Acevedo-Cintrón JA, Pan D. et al. Brief electrical stimulation accelerates axon regeneration and promotes recovery following nerve transection and repair in mice. J Bone Joint Surg Am 2021; 103 (20) e80
  • 35 Millesi H. The nerve gap. Theory and clinical practice. Hand Clin 1986; 2 (04) 651-663
  • 36 Teijink SBJ, Pesser N, Goeteyn J. et al. General overview and diagnostic (imaging) techniques for neurogenic thoracic outlet syndrome. Diagnostics (Basel) 2023; 13 (09) 1625
  • 37 McCarthy JE, Attaluri P, Nicksic P. On the physiology of the sensory-collapse test. J Hand Surg Am 2024; 49 (06) 603-606
  • 38 Abdo H, Calvo-Enrique L, Lopez JM. et al. Specialized cutaneous Schwann cells initiate pain sensation. Science 2019; 365 (6454) 695-699
  • 39 Öztürk N, Erin N, Tüzüner S. Changes in tissue substance P levels in patients with carpal tunnel syndrome. Neurosurgery 2010; 67 (06) 1655-1660 , discussion 1660–1661
  • 40 George SC, Boyce DE. An evidence-based structured review to assess the results of common peroneal nerve repair. Plast Reconstr Surg 2014; 134 (02) 302e-311e
  • 41 Pripotnev S, Pinni SL, Zhou S, Skolnick G, Mackinnon SE. The medial antebrachial cutaneous nerve is a low-morbidity alternative to the standard sural nerve autograft. Hand (N Y) 2024; DOI: 10.1177/15589447231218459.
  • 42 Dorsi MJ, Chen L, Murinson BB, Pogatzki-Zahn EM, Meyer RA, Belzberg AJ. The tibial neuroma transposition (TNT) model of neuroma pain and hyperalgesia. Pain 2008; 134 (03) 320-334
  • 43 Kotani T, Toshima Y, Matsuda H, Suzuki T, Ishizaki Y. [Postoperative results of nerve transposition in brachial plexus injury]. Seikei Geka 1971; 22 (11) 963-966
  • 44 Tuttle H. Exposure of the brachial plexus with nerve transplation. JAMA 1913; •••: 15-17
  • 45 Brandt KE, Mackinnon SE. A technique for maximizing biceps recovery in brachial plexus reconstruction. J Hand Surg Am 1993; 18 (04) 726-733
  • 46 El-Gammal TA, Fathi NA. Outcomes of surgical treatment of brachial plexus injuries using nerve grafting and nerve transfers. J Reconstr Microsurg 2002; 18 (01) 7-15
  • 47 Samardzic M, Grujicic D, Rasulic L, Bacetic D. Transfer of the medial pectoral nerve: myth or reality?. Neurosurgery 2002; 50 (06) 1277-1282
  • 48 Waikakul S, Wongtragul S, Vanadurongwan V. Restoration of elbow flexion in brachial plexus avulsion injury: comparing spinal accessory nerve transfer with intercostal nerve transfer. J Hand Surg Am 1999; 24 (03) 571-577
  • 49 Balas EA, Boren SA. Managing clinical knowledge for health care improvement. Yearb Med Inform 2000; 09 (01) 65-70
  • 50 Weber R, Mackinnon SE. Upper extremity nerve transfers. In: Peripheral Nerve Surgery: Practical Applications in the Upper Extremity. 1st ed. Churchill Livingstone. Elsevier.; 2006
  • 51 Novak CB, Mackinnon SE. Distal anterior interosseous nerve transfer to the deep motor branch of the ulnar nerve for reconstruction of high ulnar nerve injuries. J Reconstr Microsurg 2002; 18 (06) 459-464
  • 52 Viterbo F, Trindade JC, Hoshino K, Mazzoni Neto A. End-to-side neurorrhaphy with removal of the epineurial sheath: an experimental study in rats. Plast Reconstr Surg 1994; 94 (07) 1038-1047
  • 53 Amr SM, Moharram AN. Repair of brachial plexus lesions by end-to-side side-to-side grafting neurorrhaphy: experience based on 11 cases. Microsurgery 2005; 25 (02) 126-146
  • 54 Lundborg G, Zhao Q, Kanje M, Danielsen N, Kerns JM. Can sensory and motor collateral sprouting be induced from intact peripheral nerve by end-to-side anastomosis?. J Hand Surg [Br] 1994; 19 (03) 277-282
  • 55 Luo Y, Wang T, Fang H. [Preliminary investigation of treatment of ulnar nerve defect by end-to-side neurorrhaphy]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 1997; 11 (06) 338-339
  • 56 Tham SK, Morrison WA. Motor collateral sprouting through an end-to-side nerve repair. J Hand Surg Am 1998; 23 (05) 844-851
  • 57 Yan JG, Matloub HS, Sanger JR, Zhang LL, Riley DA, Jaradeh SS. A modified end-to-side method for peripheral nerve repair: large epineurial window helicoid technique versus small epineurial window standard end-to-side technique. J Hand Surg Am 2002; 27 (03) 484-492
  • 58 Zhao JZ, Chen ZW, Chen TY. Nerve regeneration after terminolateral neurorrhaphy: experimental study in rats. J Reconstr Microsurg 1997; 13 (01) 31-37
  • 59 Hayashi A, Pannucci C, Moradzadeh A. et al. Axotomy or compression is required for axonal sprouting following end-to-side neurorrhaphy. Exp Neurol 2008; 211 (02) 539-550
  • 60 Hayashi A, Yanai A, Komuro Y, Nishida M, Inoue M, Seki T. Collateral sprouting occurs following end-to-side neurorrhaphy. Plast Reconstr Surg 2004; 114 (01) 129-137
  • 61 Matsumoto M, Hirata H, Nishiyama M, Morita A, Sasaki H, Uchida A. Schwann cells can induce collateral sprouting from intact axons: experimental study of end-to-side neurorrhaphy using a Y-chamber model. J Reconstr Microsurg 1999; 15 (04) 281-286
  • 62 Brenner MJ, Dvali L, Hunter DA, Myckatyn TM, Mackinnon SE. Motor neuron regeneration through end-to-side repairs is a function of donor nerve axotomy. Plast Reconstr Surg 2007; 120 (01) 215-223
  • 63 Dvali LT, Myckatyn TM. End-to-side nerve repair: review of the literature and clinical indications. Hand Clin 2008; 24 (04) 455-460 , vii
  • 64 Felder JM, Hill EJR, Power HA, Hasak J, Mackinnon SE. Cross-palm nerve grafts to enhance sensory recovery in severe ulnar neuropathy. Hand (N Y) 2020; 15 (04) 526-533
  • 65 May M, Schaitkin BM. The Facial Nerve. Thieme; 2000
  • 66 May M, Sobol SM, Mester SJ. Hypoglossal-facial nerve interpositional-jump graft for facial reanimation without tongue atrophy. Otolaryngol Head Neck Surg 1991; 104 (06) 818-825
  • 67 Domeshek LF, Novak CB, Patterson JMM. et al. Nerve transfers - a paradigm shift in the reconstructive ladder. Plast Reconstr Surg Glob Open 2019; 7 (06) e2290
  • 68 Baltzer H, Woo A, Oh C, Moran SL. Comparison of ulnar intrinsic function following supercharge end-to-side anterior interosseous-to-ulnar motor nerve transfer: a matched cohort study of proximal ulnar nerve injury patients. Plast Reconstr Surg 2016; 138 (06) 1264-1272
  • 69 Koriem E, El-Mahy MM, Atiyya AN, Diab RA. Comparison between supercharged ulnar nerve repair by anterior interosseous nerve transfer and isolated ulnar nerve repair in proximal ulnar nerve injuries. J Hand Surg Am 2020; 45 (02) 104-110
  • 70 Peters BR, Jacobson L, Pripotnev S, Mackinnon SE. Abductor digiti minimi and anterior interosseous to ulnar motor nerve transfer: the super turbocharge end-to-side transfer. Plast Reconstr Surg 2023; 151 (04) 815-820
  • 71 Hahn J, Cooper C, Flood S, Weymouth M, van Zyl N. Rehabilitation of supinator nerve to posterior interosseous nerve transfer in individuals with tetraplegia. Arch Phys Med Rehabil 2016; 97 (06) S160-S168
  • 72 Bazarek S, Sten M, Nin D, Brown JM. Supinator to posterior interosseous nerve transfer for restoration of finger extension. Oper Neurosurg (Hagerstown) 2021; 21 (05) E408-E413
  • 73 Anderson PN, Turmaine M. Peripheral nerve regeneration through grafts of living and freeze-dried CNS tissue. Neuropathol Appl Neurobiol 1986; 12 (04) 389-399
  • 74 Campbell JB, Bassett AL, Boehler J. Frozen-irradiated homografts shielded with microfilter sheaths in peripheral nerve surgery. J Trauma 1963; 3: 303-311
  • 75 Evans PJ, Mackinnon SE, Best TJ. et al. Regeneration across preserved peripheral nerve grafts. Muscle Nerve 1995; 18 (10) 1128-1138
  • 76 Hiles RW. Freeze dried irradiated nerve homograft: a preliminary report. Hand 1972; 4 (01) 79-84
  • 77 Lawson GM, Glasby MA. A comparison of immediate and delayed nerve repair using autologous freeze-thawed muscle grafts in a large animal model. The simple injury. J Hand Surg [Br] 1995; 20 (05) 663-700
  • 78 Marmor L. The repair of peripheral nerves by irradiated homografts. Clin Orthop Relat Res 1964; 34 (34) 161-169
  • 79 Martini AK. [The lyophilized homologous nerve graft for the prevention of neuroma formation (animal experiment study)]. Handchir Mikrochir Plast Chir 1985; 17 (05) 266-269
  • 80 Singh R, Lange SA. Experience with homologous lyophilised nerve grafts in the treatment of peripheral nerve injuries. Acta Neurochir (Wien) 1975; 32 (1-2): 125-130
  • 81 Wilhelm K. [Briding of nerve defects using lyophilized homologous grafts]. Handchirurgie 1972; 4 (01) 25-30
  • 82 Wilhelm K, Ross A. [Homeoplastic nerve transplantation with lyophilized nerve]. Arch Orthop Unfallchir 1972; 72 (02) 156-167
  • 83 Gulati AK. Immune response and neurotrophic factor interactions in peripheral nerve transplants. Acta Haematol 1998; 99 (03) 171-174
  • 84 Gulati AK, Cole GP. Nerve graft immunogenicity as a factor determining axonal regeneration in the rat. J Neurosurg 1990; 72 (01) 114-122
  • 85 Lassner F, Schaller E, Steinhoff G, Wonigeit K, Walter GF, Berger A. Cellular mechanisms of rejection and regeneration in peripheral nerve allografts. Transplantation 1989; 48 (03) 386-392
  • 86 Mackinnon S, Hudson A, Falk R, Bilbao J, Kline D, Hunter D. Nerve allograft response: a quantitative immunological study. Neurosurgery 1982; 10 (01) 61-69
  • 87 Pollard JD, Gye RS, McLeod JG. An assessment of immunosuppressive agents in experimental peripheral nerve transplantation. Surg Gynecol Obstet 1971; 132 (05) 839-845
  • 88 Trumble TE, Shon FG. The physiology of nerve transplantation. Hand Clin 2000; 16 (01) 105-122
  • 89 Yu LT, Rostami A, Silvers WK, Larossa D, Hickey WF. Expression of major histocompatibility complex antigens on inflammatory peripheral nerve lesions. J Neuroimmunol 1990; 30 (2-3): 121-128
  • 90 Feng FY, Ogden MA, Myckatyn TM. et al. FK506 rescues peripheral nerve allografts in acute rejection. J Neurotrauma 2001; 18 (02) 217-229
  • 91 Gold BG, Katoh K, Storm-Dickerson T. The immunosuppressant FK506 increases the rate of axonal regeneration in rat sciatic nerve. J Neurosci 1995; 15 (11) 7509-7516
  • 92 Mackinnon SE, Doolabh VB, Novak CB, Trulock EP. Clinical outcome following nerve allograft transplantation. Plast Reconstr Surg 2001; 107 (06) 1419-1429
  • 93 Cabaud HE, Rodkey WG, McCarroll Jr HR, Mutz SB, Niebauer JJ. Epineurial and perineurial fascicular nerve repairs: a critical comparison. J Hand Surg Am 1976; 1 (02) 131-137
  • 94 Lans J, Eberlin KR, Evans PJ, Mercer D, Greenberg JA, Styron JF. A systematic review and meta-analysis of nerve gap repair: comparative effectiveness of allografts, autografts, and conduits. Plast Reconstr Surg 2023; 151 (05) 814e-827e
  • 95 Safa B, Jain S, Desai MJ. et al. Peripheral nerve repair throughout the body with processed nerve allografts: results from a large multicenter study. Microsurgery 2020; 40 (05) 527-537
  • 96 Limited recovery following acellular nerve allograft reconstruction in major peripheral nerve injuries. Accessed April 22, 2024 at: https://www.oaepublish.com/articles/2347-9264.2023.89
  • 97 Best TJ, Mackinnon SE, Midha R, Hunter DA, Evans PJ. Revascularization of peripheral nerve autografts and allografts. Plast Reconstr Surg 1999; 104 (01) 152-160
  • 98 Pan D, Mackinnon SE, Wood MD. Advances in the repair of segmental nerve injuries and trends in reconstruction. Muscle Nerve 2020; 61 (06) 726-739
  • 99 Leckenby JI, Furrer C, Haug L, Juon Personeni B, Vögelin E. A retrospective case series reporting the outcomes of advance nerve allografts in the treatment of peripheral nerve injuries. Plast Reconstr Surg 2020; 145 (02) 368e-381e
  • 100 Peters BR, Wood MD, Hunter DA, Mackinnon SE. Acellular nerve allografts in major peripheral nerve repairs: an analysis of cases presenting with limited recovery. Hand (N Y) 2023; 18 (02) 236-243
  • 101 Levi ADO, Evans PJ, Mackinnon SE, Bunge RP. Cold storage of peripheral nerves: an in vitro assay of cell viability and function. Glia 1994; 10 (02) 121-131
  • 102 Oud T, Beelen A, Eijffinger E, Nollet F. Sensory re-education after nerve injury of the upper limb: a systematic review. Clin Rehabil 2007; 21 (06) 483-494
  • 103 Beaulieu JY, Blustajn J, Teboul F. et al. Cerebral plasticity in crossed C7 grafts of the brachial plexus: an fMRI study. Microsurgery 2006; 26 (04) 303-310
  • 104 Malessy MJA, Bakker D, Dekker AJ, Van Duk JG, Thomeer RTWM. Functional magnetic resonance imaging and control over the biceps muscle after intercostal-musculocutaneous nerve transfer. J Neurosurg 2003; 98 (02) 261-268