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Approach to management of nerve gaps in peripheral nerve injuries

Published:January 20, 2022DOI:https://doi.org/10.1016/j.injury.2022.01.031

      Highlights

      • Nerve gaps are broadly categorized into 3 groups depending upon the length of the gap between proximal and distal ends – less than one cm, upto five cm and longer than five cm.
      • A tension-free good nerve coaptation is usually achieved in gaps less than 1 cm and leads to good functional outcome provided the patient is not an elderly and presents within 6 months from time since injury.
      • Repair under tension causes neural ischemia resulting in poor functional outcome, pain and neuroma formation. So, autologous nerve grafting is the procedure of choice for nerve gaps up to 5 cm. Other options are cellular and acellular allografts and nerve conduits.
      • For longer nerve gap (more than 5 cm), autologous vascularized nerve grafts (VNGs) are used and in cases of unavailable proximal stump, nerve transfers and end-to-side neurorrhaphy are the useful options.
      • Electrodiagnostic studies are useful only when done 3–4 weeks after the injury conducted for motor and sensory nerves for both the limbs as to compare the values with that of normal side.
      • Researchers working in the areas of nerve injuries and regeneration are mainly targeting the different phases of the neural regeneration which comprises of two categories: strategies resulting in enhancement of axonal regeneration and process that shorten the denervation time.
      • The major factors to guide the clinical decision are the types of injury, patients’ age and duration of injury, the available options and the surgeon preferences and expertise.

      Abstract

      Peripheral nerve injuries (PNI) are a major clinical problem. In general, PNI results from motor vehicle accidents, lacerations with sharp objects, penetrating trauma (gunshot wounds) and stretching or crushing trauma and fractures. They can result in significant morbidity, including motor and/or sensory loss, which can affect significantly the life of the patient. Currently, the standard surgical technique for complete nerve transection is end-to-end neurorrhaphy. Unfortunately, there is segmental loss of the nerve trunk in some cases where nerve mobilization may permit end-to-end neurorrhaphy if the gap is less than 1 cm. When the nerve gap exceeds 1 cm, autologous nerve grafting is the gold standard of treatment. But in light of limited availability and concerned donor site morbidity, other techniques have been used: vascularized nerve grafts, cellular and acellular allografts, nerve conduits, nerve transfers and end-to-side neurorrhaphy. This review intends to present an overview of the literature on the applications of these techniques in repair of peripheral nerve injuries. This article also focuses on preoperative assessment, surgical timing, available options and future perspectives.

      Abbreviations:

      PNI (Peripheral nerve injuries), NCS (Nerve conduction studies), EMG (Electromyography)

      Keywords

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      References

        • Fowler J.R.
        • Lavasani M.
        • Huard J.
        • Goitz R.J.
        Biologic strategies to improve nerve regeneration after peripheral nerve repair.
        J Reconstr Microsurg. 2015; 31: 243-248
        • Midha R.
        Epidemiology of brachial plexus injuries in a multitrauma population.
        Neurosurgery. 1997; 40: 1182-1188
        • Noble J.
        • Munro C.A.
        • Prasad V.S.
        • Midha R.
        Analysis of upper and lower extremity peripheral nerve injuries in a population of patients with multiple injuries.
        J Trauma. 1998; 45: 116-122
        • Ciaramitaro P.
        • Mondelli M.
        • Logullo F.
        • Grimaldi S.
        • Battiston B.
        • Sard A.
        • et al.
        Traumatic peripheral nerve injuries: epidemiological findings, neuropathic pain and quality of life in 158 patients.
        J Peripher Nerv Syst JPNS. 2010; 15: 120-127
        • Nicholson B.
        • Verma S.
        Comorbidities in chronic neuropathic pain.
        Pain Med Malden Mass. 2004; 5: S9-S27
        • Terzis J.
        • Faibisoff B.
        • Williams B.
        The nerve gap: suture under tension vs. graft.
        Plast Reconstr Surg. 1975; 56: 166-170
        • Millesi H.
        • Meissl G.
        Consequences of tension at the suture site.
        in: Gorio A Millesi H Mingrino S Post-traumatic peripheral nerve regeneration. Raven Press, New York1981: 277
        • Millesi H.
        Forty-two years of peripheral nerve surgery.
        Microsurgery. 1993; 14: 228-233
        • Sachanandani N.F.
        • Pothula A.
        • Tung T.H.
        Nerve gaps.
        Plast Reconstr Surg. 2014; 133: 313-319
        • Chaudhry V.
        • Cornblath D.R.
        Wallerian degeneration in human nerves: serial electrophysiological studies.
        Muscle Nerve. 1992; 15: 687-693
        • Gilliatt R.W.
        • Hjorth R.J.
        Nerve conduction during Wallerian degeneration in the baloon.
        J Neurol Neurosurg Psychiatry. 1972; 35: 335-341
        • Zachary L.S.
        • Dellon A.L.
        • Seiler W.A.
        Relationship of intraneural damage in the rat sciatic nerve to the mechanism of injury.
        J Reconstr Microsurg. 1989; 5: 137-140
        • Ring D.
        • Chin K.
        • Jupiter J.B.
        Radial nerve palsy associated with high-energy humeral shaft fractures.
        J Hand Surg Am. 2004; 29: 144-147
        • Kline D.G.
        Timing for brachial plexus injury: a personal experience.
        Neurosurg Clin N Am. 2009; 20: 24-26
        • Robinson L.R.
        Traumatic injury to peripheral nerves.
        Muscle Nerve. 2000; 23: 863-873
        • Willmott A.D.
        • White C.
        • Dukelow S.P.
        Fibrillation potential onset in peripheral nerve injury.
        Muscle Nerve. 2012; 46: 332-340
        • Toros T.
        • Karabay N.
        • Ozaksar K.
        • Sugun T.S.
        • Kayalar M.
        • Bal E.
        Evaluation of peripheral nerves of the upper limb with ultrasonography: a comparison of ultrasonographic examination and the intra-operative findings.
        J Bone Joint Surg Br. 2009; 91: 762-765
        • Chhabra A.
        • Williams E.H.
        • Wang K.C.
        • Dellon A.L.
        • Carrino J.A.
        MR neurography of neuromas related to nerve injury and entrapment with surgical correlation.
        AJNR Am J Neuroradiol. 2010; 31: 1363-1368
        • Trumble T.E.
        • McCallister W.V.
        Repair of peripheral nerve defects in the upper extremity.
        Hand Clin. 2000; 16: 37-52
        • Lundborg G.
        • Rydevik B.
        Effects of stretching the tibial nerve of the rabbit. A preliminary study of the intraneural circulation and the barrier function of the perineurium.
        J Bone Joint Surg Br. 1973; 55: 390-401
        • Orgel M.G.
        • Terzis J.K.
        Epineurial vs. perineurial repair.
        Plast Reconstr Surg. 1977; 60: 80-91
        • Williams H.B.
        • Jabaley M.E.
        The importance of internal anatomy of the peripheral nerves to nerve repair in the forearm and hand.
        Hand Clin. 1986; 2: 689-707
        • Terzis J.K.
        • Dykes R.W.
        • Hakstian R.W.
        Electrophysiological recordings in peripheral nerve surgery: a review.
        J Hand Surg Am. 1976; 1: 52-66
        • Gaul J.S.
        Electrical fascicle identification as an adjunct to nerve repair.
        Hand Clin. 1986; 2: 709-722
        • Riley D.A.
        • Lang D.H.
        Carbonic anhydrase activity of human peripheral nerves: a possible histochemical aid to nerve repair.
        J Hand Surg Am. 1984; 9: 112-120
        • Carson K.A.
        • Terzis J.K.
        Carbonic anhydrase histochemistry. A potential diagnostic method for peripheral nerve repair.
        Clin Plast Surg. 1985; 12: 227-232
        • Engel J.
        • Ganel A.
        • Melamed R.
        • Rimon S.
        • Farine I.
        Choline acetyltransferase for differentiation between human motor and sensory nerve fibers.
        Ann Plast Surg. 1980; 4: 376-380
        • Szabolcs M.J.
        • Gruben H.
        • Schaden G.E.
        • Freilinger G.
        • Deutinger M.
        • Girsch W.
        Selective fascicular nerve repair: a rapid method for intraoperative motor sensory differentiation by acetylcholinesterase histochemistry.
        Eur J Plast Surg. 2022; 14: 21-25
        • Best T.J.
        • Mackinnon S.E.
        • Evans P.J.
        • Hunter D.
        • Midha R.
        Peripheral nerve revascularization: histomorphometric study of small- and large-caliber grafts.
        J Reconstr Microsurg. 1999; 15: 183-190
        • MacKinnon S.E.
        • Dellon L.E.
        Surgery of the peripheral nerve.
        Thieme, New York1988
        • Moradzadeh A.
        • Borschel G.H.
        • Luciano J.P.
        • Whitlock E.L.
        • Hayashi A.
        • Hunter D.A
        The impact of motor and sensory nerve architecture on nerve regeneration.
        Exp Neurol. 2008; 212: 370-376
        • Brushart T.M.
        • Gerber J.
        • Kessens P.
        • Chen Y.G.
        • Royall R.M.
        Contributions of pathway and neuron to preferential motor reinnervation.
        J Neurosci Off J Soc Neurosci. 1998; 18: 8674-8681
        • Mackinnon S.E.
        • Doolabh V.B.
        • Novak C.B.
        • Trulock E.P.
        Clinical outcome following nerve allograft transplantation.
        Plast Reconstr Surg. 2001; 107: 1419-1429
        • Evans P.J.
        • Mackinnon S.E.
        • Levi A.D.
        • Wade J.A.
        • Hunter D.A.
        • Nakao Y.
        Cold preserved nerve allografts: changes in basement membrane, viability, immunogenicity, and regeneration.
        Muscle Nerve. 1998; 21: 1507-1522
        • Hess J.R.
        • Brenner M.J.
        • Fox I.K.
        • Nichols C.M.
        • Myckatyn T.M.
        • Hunter D.A
        Use of cold-preserved allografts seeded with autologous Schwann cells in the treatment of a long-gap peripheral nerve injury.
        Plast Reconstr Surg. 2007; 119: 246-259
        • Gulati A.K.
        • Cole G.P.
        Nerve graft immunogenicity as a factor determining axonal regeneration in the rat.
        J Neurosurg. 1990; 72: 114-122
        • Hudson T.W.
        • Zawko S.
        • Deister C.
        • Lundy S.
        • Hu C.Y.
        • Lee K.
        Optimized acellular nerve graft is immunologically tolerated and supports regeneration.
        Tissue Eng. 2004; 10: 1641-1651
        • Mackinnon S.E.
        • Hudson A.R.
        • Falk R.E.
        • Kline D.
        • Hunter D.
        Peripheral nerve allograft: an immunological assessment of pretreatment methods.
        Neurosurgery. 1984; 14: 167-171
        • Safa B.
        • Buncke G.
        Autograft substitutes: conduits and processed nerve allografts.
        Hand Clin. 2016; 32: 127-140
        • Pabari A.
        • Lloyd-Hughes H.
        • Seifalian A.M.
        • Mosahebi A.
        Nerve conduits for peripheral nerve surgery.
        Plast Reconstr Surg. 2014; 133: 1420-1430
        • Terzis J.K.
        • Konofaos P.
        Low-dose FK506 after contralateral C7 transfer to the musculocutaneous nerve using two different tubes: a study in rats.
        Ann Plast Surg. 2010; 64: 622-631
        • Kostopoulos E.
        • Konofaos P.
        • Frazer M.
        • Terzis J.K.
        Tubulization techniques in brachial plexus surgery in an animal model for long-nerve defects (40 mm): a pilot study.
        Ann Plast Surg. 2010; 64: 614-621
        • Lundborg G.
        • Rosén B.
        • Dahlin L.
        • Holmberg J.
        • Rosén I.
        Tubular repair of the median or ulnar nerve in the human forearm: a 5-year follow-up.
        J Hand Surg Br. 2004; 29: 100-107
        • Boeckstyns M.E.
        • Sørensen A.I.
        • Viñeta J.F.
        • Rosén B.
        • Navarro X.
        • Archibald S.J.
        Collagen conduit versus microsurgical neurorrhaphy: 2-year follow-up of a prospective, blinded clinical and electrophysiological multicenter randomized, controlled trial.
        J Hand Surg Am. 2013; 38: 2405-2411
        • Merle M.
        • Dellon A.L.
        • Campbell J.N.
        • Chang P.S.
        Complications from silicon-polymer intubulation of nerves.
        Microsurgery. 1989; 10: 130-133
        • Lundborg G.
        • Dahlin L.B.
        • Danielsen N.
        • Gelberman R.H.
        • Longo F.M.
        • Powell H.C.
        Nerve regeneration across an extended gap: a neurobiological view of nerve repair and the possible involvement of neuronotrophic factors.
        J Hand Surg Am. 1982; 7: 580-587
        • Lundborg G.
        • Dahlin L.B.
        • Danielsen N.
        • Gelberman R.H.
        • Longo F.M.
        • Powell H.C.
        In vivo regeneration of cut nerves encased in silicone tubes: growth across a six-millimeter gap.
        J Neuropathol Exp Neurol. 1982; 41: 412-422
        • Lin M.Y.
        • Manzano G.
        • Gupta R.
        Nerve allografts and conduits in peripheral nerve repair.
        Hand Clin. 2013; 29: 331-348
        • Pabari A.
        • SY Yang
        • Seifalian A.M.
        • Mosahebi A.
        Modern surgical management of peripheral nerve gap.
        J Plast Reconstr Aesthet Surg. 2010; 63: 1941-1948
        • Wongtrakul S.
        • Bishop A.T.
        • Friedrich P.F.
        Vascular endothelial growth factor promotion of neoangiogenesis in conventional nerve grafts.
        J Hand Surg Am. 2002; 27: 277-285
        • Lind R.
        • Wood M.B.
        Comparison of the pattern of early revascularization of conventional versus vascularized nerve grafts in the canine.
        J Reconstr Microsurg. 1986; 2: 229-234
        • Penkert G.
        • Bini W.
        • Samii M.
        Revascularization of nerve grafts: an experimental study.
        J Reconstr Microsurg. 1988; 4: 319-332
        • Brooks D.
        The place of nerve-grafting in orthopaedic surgery.
        J Bone Joint Surg Am. 1955; 37: 299-305
        • Seddon H.J.
        Nerve grafting.
        J Bone Joint Surg Br. 1963; 45: 447-461
        • El-Gammal T.A.
        • Fathi N.A.
        Outcomes of surgical treatment of brachial plexus injuries using nerve grafting and nerve transfers.
        J Reconstr Microsurg. 2002; 18: 7-15
        • Brandt K.E.
        • Mackinnon S.E.
        A technique for maximizing biceps recovery in brachial plexus reconstruction.
        J Hand Surg Am. 1993; 18: 726-733
        • Viterbo F.
        • Trindade J.C.
        • Hoshino K.
        • Mazzoni A.
        Two end-to-side neurorrhaphies and nerve graft with removal of the epineural sheath: experimental study in rats.
        Br J Plast Surg. 1994; 47: 75-80
        • Viterbo F.
        • Trindade J.C.
        • Hoshino K.
        • Mazzoni N.A
        End-to-side neurorrhaphy with removal of the epineurial sheath: an experimental study in rats.
        Plast Reconstr Surg. 1994; 94: 1038-1047
        • Viterbo F.
        • Trindade J.C.
        • Hoshino K.
        • Mazzoni N.A
        Latero-terminal neurorrhaphy without removal of the epineural sheath. Experimental study in rats.
        Rev Paul Med. 1992; 110: 267-275
        • Riddoch M.D.
        • Brigadier G.
        Medical research council war memorandum no. 7: aids to the investigation of peripheral nerve injuries.
        2nd ed. Her Majesty's Stationery Office, 1952
        • Bell-Krotoski J.
        • Tomancik E.
        The repeatability of testing with Semmes-Weinstein monofilaments.
        J Hand Surg Am. 1987; 12: 155-161
        • Shooter D.
        Use of two-point discrimination as a nerve repair assessment tool: preliminary report.
        ANZ J Surg. 2005; 75: 866-868
        • Dellon E.S.
        • Mourey R.
        • Dellon A.L.
        Human pressure perception values for constant and moving one- and two-point discrimination.
        Plast Reconstr Surg. 1992; 90: 112-117
        • Konofaos P.
        • Ver Halen J.P.
        Nerve repair by means of tubulization: past, present, future.
        J Reconstr Microsurg. 2013; 29: 149-164
        • Lee S.K.
        • Wolfe S.W.
        Peripheral nerve injury and repair.
        J Am Acad Orthop Surg. 2000; 8: 243-252
        • Terenghi G.
        Peripheral nerve regeneration and neurotrophic factors.
        J Anat. 1999; 194: 1-14
        • Rodríguez F.J.
        • Verdú E.
        • Ceballos D.
        • Navarro X.
        Nerve guides seeded with autologous schwann cells improve nerve regeneration.
        Exp Neurol. 2000; 161: 571-584
        • di Summa P.G.
        • Kingham P.J.
        • Raffoul W.
        • Wiberg M.
        • Terenghi G.
        • Kalbermatten D.F.
        Adipose-derived stem cells enhance peripheral nerve regeneration.
        J Plast Reconstr Aesthet Surg. 2010; 63: 1544-1552
        • Kingham P.J.
        • Kalbermatten D.F.
        • Mahay D.
        • Armstrong SJ
        • Wiberg M.
        • Terenghi G.
        Adipose-derived stem cells differentiate into a Schwann cell phenotype and promote neurite outgrowth in vitro.
        Exp Neurol. 2007; 207: 267-274
        • Dedkov E.I.
        • Kostrominova T.Y.
        • Borisov A.B.
        • et al.
        Survival of Schwann cells in chronically denervated skeletal muscles.
        Acta Neuropathol. 2002; 103: 565-574
        • Walsh S.
        • Biernaskie J.
        • Kemp S.W.
        • Midha R.
        Supplementation of acellular nerve grafts with skin derived precursor cells promotes peripheral nerve regeneration.
        Neuroscience. 2009; 164: 1097-1107
        • Amoh Y.
        • Kanoh M.
        • Niiyama S.
        • Hamada Y.
        • Kawahara K.
        • Sato Y.
        Human hair follicle pluripotent stem (hfPS) cells promote regeneration of peripheral-nerve injury: an advantageous alternative to ES and iPS cells.
        J Cell Biochem. 2009; 107: 1016-1020
        • Schaakxs D.
        • Kalbermatten D.F.
        • Raffoul W.
        • Wiberg M.
        • Kingham P.J.
        Regenerative cell injection in denervated muscle reduces atrophy and enhances recovery following nerve repair.
        Muscle Nerve. 2013; 47: 691-701
        • Tohill M.
        • Mantovani C.
        • Wiberg M.
        • Terenghi G.
        Rat bone marrow mesenchymal stem cells express glial markers and stimulate nerve regeneration.
        Neurosci Lett. 2004; 362: 200-203
        • Tohill M.
        • Terenghi G.
        Stem-cell plasticity and therapy for injuries of the peripheral nervous system.
        Biotechnol Appl Biochem. 2004; 40: 17-24
        • Dezawa M.
        • Takahashi I.
        • Esaki M.
        • Takano M.
        • Sawada H.
        Sciatic nerve regeneration in rats induced by transplantation of in vitro differentiated bone-marrow stromal cells.
        Eur J Neurosci. 2001; 14: 1771-1776
        • Keilhoff G.
        • Goihl A.
        • Langnäse K.
        • Fansa H.
        • Wolf G.
        Transdifferentiation of mesenchymal stem cells into Schwann cell-like myelinating cells.
        Eur J Cell Biol. 2006; 85: 11-24
        • Ladak A.
        • Olson J.
        • Tredget E.E.
        • Gordon T.
        Differentiation of mesenchymal stem cells to support peripheral nerve regeneration in a rat model.
        Exp Neurol. 2011; 228: 242-252