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Commentary  |  Open Access  |  27 Dec 2023

Limited recovery following acellular nerve allograft reconstruction in major peripheral nerve injuries

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Plast Aesthet Res 2023;10:70.
10.20517/2347-9264.2023.89 |  © The Author(s) 2023.
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Abstract

Recent studies suggest that acellular nerve allografts (ANA) have similar efficacy as nerve autografts in certain applications of nerve surgery. However, multiple studies also demonstrate the limitations of nerve allografts, resulting in poor patient outcomes. This submission discusses a recent case series of patients who failed allograft use with subsequent histologic analyses of these allografts. Recommendations on the treatment of nerve gaps are presented, drawing from our current understanding of allograft and autograft utility in reconstruction. Factors taken into account include recipient critical nerve function, existent nerve gap, and nerve diameter.

Keywords

Nerve reconstruction, peripheral nerve, acellular nerve allograft, nerve autograft

The increasing use of acellular nerve allografts, nerve conduits, and nerve wraps in nerve reconstruction provides a potential new alternative to nerve repair and nerve autograft. Recent studies, most supported by industry, suggest that outcomes may be comparable between autografts and acellular nerve allografts (ANA)[1,2]. However, a large study from Switzerland showed that ANA reconstruction resulted in poorer outcomes when used to reconstruct longer length motor nerve injuries. Specific details regarding individual use cases are often uncaptured in large cohorts, and more nuance is required to accurately interpret and implement these findings into clinical practice.

In a study by Peters et al., a special cohort of patients offered the rare clinical opportunity where the failed allograft was close enough to the nerve end-target to justify a simultaneous acellular nerve allograft excision and autograft reconstruction[3]. Histologic analyses in these patients demonstrated the presence of myelinated axons proximal to the allograft and a paucity of regenerating axons through the allograft[3]. Figure 1 includes a gross image with corresponding histologic sections demonstrating the presence of myelinated axons proximal to, within, and distal to the ANA. For proximal nerve injuries, the time and distance to end target are usually too long and are thereby prohibitive of autograft reconstruction. The failed ANA is then frequently left in place as the senescent axons traveling through the allograft have dwindled and are thus useful for pain control while distal nerve transfers are performed[4,5].

Limited recovery following acellular nerve allograft reconstruction in major peripheral nerve injuries

Figure 1. Patient 1 with intraoperative findings demonstrating a large proximal neuroma of the median nerve and an 8-cm nerve gap present upon resection of the allograft. The arrows demonstrate the location of the histological sections. Note the abundance of myelinated axons in the median nerve proximal to the coaptation site of the proximal median nerve and the allograft. Note the decrease of myelinated axons across the allograft, as myelinated axons are visible within the midgraft, but only a few myelinated axons present within the distal nerve.

Nerve autografts have been considered the gold standard, with the cellular and extracellular components serving as a biologic scaffold to guide axonal regeneration. However, there are limits to autograft efficacy as dictated by nerve gap length and diameter. For example, 6 cm appears to be a useful approximate ceiling for what outcomes may be expected in reconstructing motor nerve gaps, as demonstrated in a study assessing outcomes from common peroneal nerve decompression and reconstruction[6-8]. However, in another study, gaps greater than 5 cm were associated with 10% meaningful motor recovery and 52.9% meaningful sensory recovery[9]. Additionally, large diameter nerve gaps represent a greater challenge to revascularization demand for autografts and acellular nerve allografts. Increasing nerve diameter increases central necrosis during the period of nerve recovery. In a study by Leckenby et al., ANA nerve diameters greater than 3 mm were inhibitory to axonal growth[9]. Autografts revascularize via longitudinal inosculation, while acellular nerve allografts require the reconstitution of entirely vascular networks de novo[10,11]. Hence, even with matched diameters, allografts have been demonstrated to take several times longer than autografts to revascularize[12].

Fortunately, for shorter or smaller-diameter nerve gaps, acellular nerve allografts and nerve conduits may return function to some degree since only 25%-30% of nerve fibers are necessary, given the compensatory expansion of motor and sensory units[13,14]. However, when critical functions are being restored, it would be reasonable to utilize “gold standard” autografts to maximize functional recovery. In one of the few studies not funded by industry, meaningful motor recovery after ANA declined notably with diameters exceeding 2 mm and lengths of 2 cm[9]. Utilizing an off-the-shelf allograft is less time-consuming than harvesting an autograft, but in keeping with the principles of reconstructive surgery, the solution must match the demands and functional importance of the defect. For example, cortical bone allografts certainly have their place in skeletal reconstruction; however, when bone gap distance and weight-bearing criteria are considered, vascularized bone flaps may be the suitable treatment[15,16]. Therefore, in modern nerve surgery, it remains the practice of the senior author to treat critical motor and sensory nerves with nerve autograft. By contrast, acellular nerve allografts are utilized for noncritical or small-diameter sensory nerves and to prevent neuroma formation by utilizing the dwindling regeneration that occurs over a long distance[17].

DECLARATIONS

Authors’ contributions

Made substantial contributions to manuscript conception, manuscript development, and manuscript editing: Chi D, Johnson AR, Mackinnon SE

Availability of data and materials

Not applicable.

Financial support and sponsorship

None.

Conflicts of interest

All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Copyright

© The Author(s) 2023.

REFERENCES

1. 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;151:814e-27e.

2. 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;40:527-37.

3. 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 2023;18:236-43.

4. Mackinnon SE, Yee A, Barbour JR. Nerve surgery.Available from: http://www.kubalibri.cz/files/229---Nerve-Surgery.pdf [Last accessed on 28 Dec 2023].

5. 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;247:165-77.

6. George SC, Boyce DE. An evidence-based structured review to assess the results of common peroneal nerve repair. Plast Reconstr Surg 2014;134:302e-11e.

7. 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;88:425-8.

8. Carlson TL, Wallace RD, Konofaos P. Cadaveric nerve allograft: single center's experience in a variety of peripheral nerve injuries. Ann Plast Surg 2018;80:S328-32.

9. Leckenby JI, Furrer C, Haug L, Juon Personeni B, Vögelin E. A retrospective case series reporting the outcomes of avance nerve allografts in the treatment of peripheral nerve injuries. Plast Reconstr Surg 2020;145:368e-81e.

10. Best TJ, Mackinnon SE, Midha R, Hunter DA, Evans PJ. Revascularization of peripheral nerve autografts and allografts. Plast Reconstr Surg 1999;104:152-60.

11. Pan D, Mackinnon SE, Wood MD. Advances in the repair of segmental nerve injuries and trends in reconstruction. Muscle Nerve 2020;61:726-39.

12. Farber SJ, Hoben GM, Hunter DA, et al. Vascularization is delayed in long nerve constructs compared with nerve grafts. Muscle Nerve 2016;54:319-21.

13. Gordon T, Yang JF, Ayer K, Stein RB, Tyreman N. Recovery potential of muscle after partial denervation: a comparison between rats and humans. Brain Res Bull 1993;30:477-82.

14. Upton AR, McComas AJ. The double crush in nerve entrapment syndromes. Lancet 1973;302:359-62.

15. Asaad M, Houdek MT, Huang TCT, Rose PS, Moran SL. Vascularized bone flap options for complex thoracic spinal reconstruction. Plast Reconstr Surg 2022;149:515e-25e.

16. Kazmers NH, Thibaudeau S, Levin LS. A scapholunate ligament-sparing technique utilizing the medial femoral condyle corticocancellous free flap to reconstruct scaphoid nonunions with proximal pole avascular necrosis. J Hand Surg Am 2016;41:e309-15.

17. Boyd KU, Nimigan AS, Mackinnon SE. Nerve reconstruction in the hand and upper extremity. Clin Plast Surg 2011;38:643-60.

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OAE Style

Chi D, Johnson AR, Mackinnon SE. Limited recovery following acellular nerve allograft reconstruction in major peripheral nerve injuries. Plast Aesthet Res 2023;10:70. http://dx.doi.org/10.20517/2347-9264.2023.89

AMA Style

Chi D, Johnson AR, Mackinnon SE. Limited recovery following acellular nerve allograft reconstruction in major peripheral nerve injuries. Plastic and Aesthetic Research. 2023; 10: 70. http://dx.doi.org/10.20517/2347-9264.2023.89

Chicago/Turabian Style

Chi, David, Anna Rose Johnson, Susan E. Mackinnon. 2023. "Limited recovery following acellular nerve allograft reconstruction in major peripheral nerve injuries" Plastic and Aesthetic Research. 10: 70. http://dx.doi.org/10.20517/2347-9264.2023.89

ACS Style

Chi, D.; Johnson AR.; Mackinnon SE. Limited recovery following acellular nerve allograft reconstruction in major peripheral nerve injuries. Plast. Aesthet. Res. 2023, 10, 70. http://dx.doi.org/10.20517/2347-9264.2023.89

About This Article

Special Issue

This article belongs to the Special Issue Advancing Peripheral Nerve Repair
© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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