RESEARCH ARTICLE


Advances of Peripheral Nerve Repair Techniques to Improve Hand Function: A Systematic Review of Literature



Mafi P1, Hindocha S*, 2, 3, Dhital M4, Saleh M5
1 Hull York Medical School, John Hughlings Jackson Building, University of York, Heslington, York, YO10 5DD, UK
2 Manchester Interdisciplinary Biocentre, University of Manchester, 131 Princess Street, M17DN, UK
3 Department of Plastic Surgery, Whiston General Hospital, Liverpool, L355DR, UK
4 University of Nottingham, University Park, Nottingham, NG7 2RD. UK
5 Shams University, Khalifa El-Maamon St, Abbasiya Sq, Cairo. 11566. Egypt


Article Metrics

CrossRef Citations:
0
Total Statistics:

Full-Text HTML Views: 2963
Abstract HTML Views: 968
PDF Downloads: 245
Total Views/Downloads: 4176
Unique Statistics:

Full-Text HTML Views: 737
Abstract HTML Views: 513
PDF Downloads: 176
Total Views/Downloads: 1426



© Mafi et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Department of Plastic Surgery, Whiston Hospital, Warrington Road, L355DR, UK; Tel: 01244366265; Fax: 01244366265; E-mail: hindocha2001@yahoo.com


Abstract

Concepts of neuronal damage and repair date back to ancient times. The research in this topic has been growing ever since and numerous nerve repair techniques have evolved throughout the years. Due to our greater understanding of nerve injuries and repair we now distinguish between central and peripheral nervous system. In this review, we have chosen to concentrate on peripheral nerve injuries and in particular those involving the hand. There are no reviews bringing together and summarizing the latest research evidence concerning the most up-to-date techniques used to improve hand function. Therefore, by identifying and evaluating all the published literature in this field, we have summarized all the available information about the advances in peripheral nerve techniques used to improve hand function. The most important ones are the use of resorbable poly[(R)-3-hydroxybutyrate] (PHB), epineural end-to-end suturing, graft repair, nerve transfer, side to side neurorrhaphy and end to side neurorrhaphy between median, radial and ulnar nerves, nerve transplant, nerve repair, external neurolysis and epineural sutures, adjacent neurotization without nerve suturing, Agee endoscopic operation, tourniquet induced anesthesia, toe transfer and meticulous intrinsic repair, free auto nerve grafting, use of distal based neurocutaneous flaps and tubulization. At the same time we found that the patient’s age, tension of repair, time of repair, level of injury and scar formation following surgery affect the prognosis. Despite the thorough findings of this systematic review we suggest that further research in this field is needed.

Keywords: Advances of nerve technique, hand function, neural regeneration, nerve repair techniques, peripheral nerve injury, peripheral nerve repair.



INTRODUCTION

A Brief History

The understanding of peripheral nerve injuries dates back to the nineteenth century [1, 2]. World War I and World War II brought about invaluable experiences in terms of classification of nerve injuries and surgical interventions, at the same time, sieving out unreliable techniques and leading to the modern era of direct nerve repair [1]. However, concepts of neuronal damage and repair date back to ancient times. Wound closure and apposition of nerve ends was originally described by Paul of Aegina sometime during the 7thcentury [3]. Neuronal degeneration were discovered and explained in Augustus Waller’s article in 1850s [4, 5]. In 1864 Nelaton described secondary nerve repair and primary epineurial nerve suturing was explained by Hueter (1871, 1873) [6]. Techniques used to optimize suturing and regeneration of nerves where described in early 1880s by Mikulicz (1882) and Loebke (1884) describing sutures and bone shortening to reduce nerve tension, respectively [7]. Nerve grafting was described by Albert in 1876 for the first time [7]. Refining of these techniques and further experiences came later from treating war injuries, as described earlier [1].

Nerve Injuries and Degeneration

Several different classification of nerve injuries exist. According to Seddon [8] nerve injuries can be referred to as neuropraxia, axonotmesis and neurotmesis according to the disruption of the internal structure and consequently in order of worsening prognosis. Neuropraxia is a reversible condition when the electrical signal fails to travel through a nerve segment, when there is no anatomical disruption in the affected neuron [9]. There is minor damage to the axon and hence the prognosis is good [8]. Axonotmesis is when there is complete interruption of the axon in the affected neuron [9]. Neurotmesis describes the complete derangement of axons and supporting connective tissue and has the worst prognosis in these three types of nerve injury described by Seddon [8]. Sunderland [10] classified nerve injuries into first, second, third, fourth and fifth degree nerve injury in order of severity of the injury. Lorei and Hershman [11] divide neural traumas into chronic injuries or entrapment neuropathies, caused by repetitive trauma or compression, and acute injuries, which is caused by direct trauma leading to immediate onset of symptoms. Distal degeneration of neurons following traumatic injury has been termed Wallerian degeneration since Waller [5] described posttraumatic changes in peripheral nerves in 1850. It is important to note that endoneurium, the Schwann sheath and blood vessels remain intact [12] despite the occurrence of wallerian degeneration. Proximal changes in the neuron, however, have been termed axonal degeneration [12].

Nerve Repair

The purpose of nerve repair is the precise apposition of the two sides of transected nerve using a minimum number of sutures while dissecting nerve ends just to the extent necessary to achieve appropriate alignment with minimal tension [12]. Best return of function is possible if and only if the motor and sensory parts of a nerve are accurately and correctly connected. Deutinger et al., [13] clearly states that for reestablishing the sensory function a nerve, particularly in median nerve injuries, intra-operative sensory motor differentiation is helpful. Intraoperative motor-sensory differentiation is currently possible with electrophysiological, immunohistochemical, histochemical and anatomical methods [12].

Branching and fascicular formation are observed in peripheral nerves [12]. In 1945 Sunderland [14] observed branching of musculocutaneous nerve every few millimeters. Following this observation numerous surgeons become pessimistic about the probability of successful nerve grafting and intraneural dissection since the assumption was made that this pattern of branching occurs at every level in the arm and forearm [12]. Jabaley, Wallace and Heckler [15] in 1980 showed in their dissection of median, radial and ulnar nerves that there are no adjacent fibers branching off the main nerve trunks for a considerable distance. Despite there being connections, it does not make fascicular repair, intrafasciular grafting or intraneural neurolysis impossible [12]. Having sound knowledge of the internal neural anatomy regarding nerve repair has been emphasized by Williams and Jabaley [16] in1986.

Several methods can be applied to bridge a nerve gap. These include direct repair, neurotization, nerve transfer, nerve allografts, various tubes and conduits, grafting, and tissue expansion [12, 17, 18]. Nerve transfer can be explained as a procedure to reinnervate a motor or sensory area by transferring another nerve [12]. Neurotization is the direct placing into an end target muscle of a proximal motor nerve stump [12]. There are three types of nerve repair, nevertheless neither has proved to have a comparative advantage over the others [12]. Each of these techniques has some advantages and disadvantages.

Epineurial Repair

The conventional technique for suturing lacerated nerves is the so-called epineurial repair [12]. Daniel and Terzis [19] list several advantages of this technique which include short execution time, minimal magnification, technical ease, not invading the intraneural contents, being applicable to both primary and secondary neural repairs and the placement of sutures only in the outer investing sheath. Tension from natural retraction despite no loss of nerve tissue, compromising the accurate alignment of fascicles, sutured epineurium and cut axonal interphase being in the same plane, controversial outcome, the need for many sutures in order to achieve structural integrity of the repaired nerve rank among the most significant disadvantages [19].

Perineurial (Fascicular or Funicular) Repair

This technique was initially described by Langley and Hashimoto [20] in1917 and its superiority over epineurial repair is still questioned. This could be due to the controversial findings of researchers. Perineurial repair tends to be favoured over funicaular suture by Bora [21], Goto [22], Grabb et al., [23], Wise et al., [24] Yamamoto [25] and Brushart, Tarlov and Mesulam [26] while Sunderland [27] and Young, Wray and Weeks [28] find no difference between the two techniques.

Taking into account the morphological and neurophysiological aspects of fascicular nerve repair, it proves to be more beneficial in terms of stabilizing and neuronal pathways when the fibers are well localized at the nerve terminals [29]. The technique of choice for the majority of the acute nerve lacerations, however, is suturing the outer epineurium as it is a faster and simpler method which requires little disruption of the internal structure of the nerve, argues Orgel [30]. Jabaley [31] in the “Current concepts of nerve repair” explains the indications for perineural and epineural repair. He states that the technique is contraindicated in multifascicled nerves but is the treatment of choice in nerve grafting and in nerves with less than five fascicles [31]. According to Langley and Hashimoto [20] the advantages of funicular repair are better recovery of motor and sensory end-organs, greater regeneration of axons entering distal nerves, coaptation of perineurial tubes allowing for more desirable alignment of fascicles and better myelination of the stumps. Nonetheless, the drawbacks are described by Sunderland [27] as greater fibrosis at the site of suture, increased injury to vessels at the nerve ends, extended operative duration, possibility of compromising the vascular supply of isolated fasciculi, discontinuity of fasciculi on a one-to-one basis and the inability to approximate small funiculi. Furthermore, Madden and Peacock [32] point out to the possibility of precisely matching the ends of transected nerves by identifying sensory and motor fascicles in both distal and proximal stumps.

Group Fascicular Repair

Group fascicular repair is feasible if a nerve is lacerated where branches in the transected nerve are well formed and readily identifiable in the main trunk [12]. In this case, motor and sensory fascicles can be matched correctly and motor-sensory cross-innervation can be avoided. Nevertheless, this technique is currently not very practical due to the long operative process, despite the existence of numerous histochemical staining techniques aiding the differentiation between motor and sensory axons [33-35]. Indications for group fascicular repair at different levels in the upper limbs are reported by Jabaley [16, 31].

Nerve Grafting

Nerve grafting dates back to Philipeaux and Vulpian in 1817 [3]. During the early 1970s Millesi recommended nerve grafting for any nerve gap larger than 2 cm and achieved great results in ulnar, median and radial nerve lesions [36-40]. Some of his most significant techniques in interfascicular nerve grafting include: 1) Grafts to bridge the gap should be cut slightly longer than the lesion itself 2) connective tissue between groups of fascicles should be dissected rather than every individual fascicle. 3) preserve only the healthy tissue and if in doubt, resect 4) dissection of fascicles should be both at the distal and proximal ends in relation to the lesion in a normal tissue. 5) In matching the stumps a drawing of the cut surface can prove helpful.6) five to 6 autografts are needed for the median nerve and four to five for ulnar and radial nerves [40].

Nerve Transfer

Another method to bridge a nerve gap is by nerve transfer. This is similar to that of tendon transfer [12]. In this procedure spare motor units are surgically re-organized in order to reestablish a vital missing function and have the potential to restore sensibility [12]. Nerve transfer is done to convert a high-nerve injury to a low nerve injury, avoid nerve grafting and to preserve muscle structure [12].

Purpose of Our Review

There is not sufficient information about the advances in repairing peripheral nerves and how these can be beneficial in terms of improving hand function. Therefore, finding the correct indications for applying different nerve repair techniques can be a challenge. There are no articles bringing together and summarizing the advances in peripheral nerve techniques. The purpose of this study is to summarize all the available information regarding the advances in peripheral nerve techniques which help to improve hand function by identifying and evaluating all the published literature in this field. The studies reporting different surgical methods and management of peripheral nerve injuries were searched mainly using PubMed, Medline, EMBASE, CINAHL (EBSCO), ZETOC, and AMED. This systematic review is intended to provide a good basis for identification and selection of peripheral nerve repair techniques which have proven to be helpful in improving hand function.

MATERIALS AND METHOD

The studies referencing different nerve repair techniques were searched using the electronic databases Medline, CINAHL (EBSCO), ZETOC, PubMed, EMBASE, AMED, PREMEDLINE In-Process & Non-Indexed Citations (OvidSP), ASSIA (CSA Illumina), Conference Proceedings Citation Index: Science (ISI) on Web of Knowledge, PsycINFO (OvidSP), Science Citation Index (ISI) on Web of Knowledge, Social Sciences Citation Index (ISI) on Web of Knowledge and Cochrane Library (Wiley). To cite relevant articles the following keywords were used: peripheral nerve injury, peripheral nerve repair, neural regeneration, hand function, nerve repair techniques. The inclusion criteria were based on 1)Identification of nerve repair techniques 2)describing nerve injuries and regeneration 3)nerves of the forearm and hand 4)commented on improvement or deterioration of hand function. Studies were excluded which 1) did not comment on nerve repair techniques of any kind 2) did not involve peripheral nerves 3) identified nerve repair techniques only applicable to non-human species 4) did not involve the hand 5)were not available for free viewing. A total of 187 articles were reviewed. 24 articles were identified as relevant according to the inclusion criteria. These studies were summarized and the relevant information is presented in this review.

RESULTS

Out of 187articles reviewed, 24 studies were identified as relevant according to the inclusion criteria. Subsequently, these were reviewed carefully and the results summarized in Table 1. Aberg et al., [41] compare the effectiveness of resorbable poly[(R)-3-hydroxybutyrate] (PHB) against epineural end-to-end suturing for nerve injuries at wrist/forearm. The overall conclusion of this study is that PHB is a safe alternative for end-to-end suturing, however it is important to note that most methods applied reported no statistically significant difference between the treatment and control groups [41]. Furthermore there was great variability observed for the evaluating techniques [41]. Cherqui et al., [42] evaluate the surgical treatment of lipofibrohamartoma of the median nerve and state that graft repair following resection of the tumour may be the best treatment [42]. They report that the outcome may be even better for pediatric patients [42]. Ducic et al., [43] transferred the radial sensory nerve to the ulnar digital nerve of the thumb and the radial digital nerve of the index finger in 2 case reports of patients with proximal median nerve injury [43]. In this radial sensory neurotization of the thumb and index finger they report faster return of sensation with digital nerve transfers of the dorsal radial sensory nerves compared with conventional median nerve repairs [43]. Yuksel et al., [44] report on two extreme cases of peripheral nerve injuries with no chance for direct repair. A side-to-side neurorrhaphy between the median and ulnar nerves, and an end-to-side neurorrhaphy between the median, radial and ulnar nerves was performed. In this report, the two surgical procedures, referred to as alternative nerve repair techniques by Yuksel et al., [44], are considered to be reasonable treatments for challenging peripheral nerve lesions after both patients regained their protective sensation and returned to work. A study by Lenz-Scharf et al., [45] involving 17 children with upper extremity nerve lesions showed results after nerve transplantation within a timeframe of six weeks. The subjects were treated with sural nerve transplant to median or ulnar nerves and observed for 2.9 years on average [45]. Lenz-Scharf et al., [45] reported good to excellent results. They argue that nerve regeneration at the proximal end of the lesion is best within 6 weeks as Wallerian degeneration is complete and nerve grafting should be done within this period [45]. However, it is important to note that complete restoration of muscle motor units did not occur in the examined cases [45].

Table 1.

Summary of the Relevant Studies


Study/Year Type of Study Number of Patients Follow Up Period Number of Patients Method/Technique Outcome
Aberg et al./2009 [41] a prospective, assessor-blinded, randomised clinical study 12 18 months 12 Resorbable poly[(R)-3-hydroxybutyrate] (PHB) and epineural end-to-end suturing. PHB is a safe alternative for end-to-end suturing
Cherqui et al./2009 [42] Case report 1 1 year 1 Tumour resection and graft repair of median nerve: Maybe the best surgical treatment of lipofibrohamartoma.
Ducic et al./2006 [43] Case report 2 14 months 2 Radial nerve transfer in patients with proximal median nerve injury. Faster return of sensation with digital nerve transfers of the dorsal radial sensory nerves compared with conventional median nerve repairs.
Yuksel et al./2004 [44] Case report 2 9 and 14 months 2 Side to side neurorrhaphy and end to side neurorrhaphy between median, radial and ulnar nerves. Patients regained their protective sensation and returned to work.
Lenz-Scharf et al./2004 [45] Longitudinal observational study 17 2.9 years 17 Sural nerve transplant to median or ulnar nerves. Good to excellent results, but it is important to note that complete restoration of muscle motor units did not occur in the examined cases
Battiston and Lanzetta/1999 [46] Longitudinal observational study 7 1 - 3.5 years 7 Connection was made between anterior interosseous nerve and the superficial sensory palmar branch of the median nerve with the motor and sensory components of the ulnar nerve at Guyon's canal. Good sensory and motor recovery was observed in all but one of the cases.
Wang Y. Zhu S. Zhang B./1997 [47] Longitudinal observational study 20 2 – 7 years 20 Median and ulnar nerve repair by transferring the pronator quadratus branch of anterior interosseous nerve. The muscle strength returned in different degrees ranging from M2 to M5.
Barrios and de Pablos/1991 [48] 15-year retrospective study 33 2 years 33 Interfascicular grafting, decompressive external neurolysis and epineural sutures. Majority regained satisfactory sensory and motor function.
Faivre et al./2003 [49] Longitudinal observational study 8 8 years 8 Adjacent and spontaneous neurotization after distal digital replantation without nerve suturing. Children are excellent candidates for replantation of distal extremities.
Schafer et al./1996 [50] prospective randomised study, 101 9 months 101 Epineural neurolysis versus Agee endoscopic operation: Epineural neurolysis is not necessary, because when Agee endoscopic operation is performed the results are better.
Bjorkman et al./2004 [51] Prospective clinical study 20 25min before – 60 min after anaesthesia 20 Tourniquet induced anesthesia after deafferentation Rapid improvement in tactile discrimination, grip strength and sensibility of the contralateral hand
Study/year Type of study Number of patients Follow up period Number of patients Method/Technique Outcome
Vilkki/1995 [52] Longitudinal observational study 18 microsurgical toe transfers 1.5 – 6 years 18 microsurgical toe transfers Microsurgical 3-jointed second toe transfer and meticulous intrinsic repair: Most patients regained ability to pinch
Sanmartin et al./2004 [53] retrospective cohort study 105 139 days (mean) 105 Review results of 105 cases of ring avulsion injuries and Primary nerve repair. Good sensory recovery is not achieved by primary neuronal repair in most cases
Xu, J et al./2000 [54] Prospective study 47 47 Free auto nerve grafting in median and ulnar nerve repair. Had no obvious effects in long-term improvement of the hand function. scar formation and inadequate blood supply responsible for poor outcome following nerve grafting
Haase and Chung/2002 [55] Case report 2 6 months and 1 year 22 Primary nerve repair by nerve transfer For these types of injuries, this method is better than the conventional primary neurorrhaphy.
Song et al./2009 [56] Longitudinal observational study 187 2 months – 3 years 187 Distal based neurocutaneous flaps Less invasive and results in sensory recovery, two point discrimination and improvement in hand function after cutaneous nerve ending anastomosis.
Rosen et al./2000 [57] Longitudinal cohort 19 4 years 19 Median and ulnar nerve repair No significant improvement in two point discrimination
Stevanovic et al./1991 [58] 17 thumbs 17 thumbs Nerve grafting in avulsion injuries Both key pinch and grip strength were less than normal.
Goldberg et al./2007 [59] 67 digital nerves Not applicable 67 digital nerves Digital nerve repair Number of suture strands crossing the repair site determine the nerve repair strength.
Braga-Silva et al./2008 [60] non-randomised retrospective study 44 1 year 44 Use of bone marrow mononuclear cells in addition to Tube-reconnection (tubular repair of median and ulnar nerves) Better recovery in patients with filled tubes was observed.
Mondelli et al./2004 [61] 3 year prospective study 282 6 months 282 Review the results of surgical decompression of carpal tunnel syndrome. Elderly patients showed less improvement in all modalities
Deutinger et al./1993 [62] Longitudinal observational study 22 1 – 11 years 22 Motor-sensory differentiation in ulnar and median nerve repair Better sensibility recovery.
Lohmeyer et al./2009 [63] a prospective cohort study and literature review 14 12 months 14 Tubulization: Interpositional grafting of a hollow collagen I conduit. This is an alternative method to autologous nerve grafting.
Pfeiffer/1993 [64] Direct nerve repair vs nerve-grafting Direct nerve repair should be used in avulsion injuries of the thumb to prevent neuroma formation. Nerve-grafting is not recommended

Battiston and Lanzetta [46] present the clinical outcome of 7 patients with ulnar nerve lesion at the elbow in which a distal connection was made between anterior interosseous nerve and the superficial sensory palmar branch of the median nerve with the motor and sensory components of the ulnar nerve at Guyon's canal. The patients were followed up from 1 to 3.5 years and the results were graded using the Highet-Zachary scale [46]. In all but one of the cases good sensory and motor recovery was observed. Only one of the cases did not achieve good motor recovery, however protective sensation returned in this subject [46]. Wang, Zhu and Zhang [47] explain the clinical applications and anatomical basis for the repair of thenar branch of the median nerve and deep branch of ulnar nerve by transferring the pronator quadratus branch of anterior interosseous nerve. This technique was used in 20 ulnar nerve injuries and 17 of these were followed up from 2 to 7 years. The muscle strength returned in different degrees ranging from M2 to M5 [47]. Barrios and de Pablos [48] review the results of surgically treated ulnar, median and radial nerve injuries in 33 children.18 patients were treated with interfascicular grafting, 14 with decompressive external neurolysis and 5 with epineural sutures [48]. In 84% of the children useful sensory function was restored and 67% regained satisfactory motor function [48]. Interestingly, the median nerve showed the best ability for recovery in terms of motor and sensory function regardless of the type of injury [48]. At the same time, radial nerve proved to have a worse prognosis in terms of regaining motor function in lesions affecting the continuity of the nerve trunk [48]. Barrios and de Pablos state that the worsening prognosis was related to a time period of longer than 1 year from nerve damage to surgery [48].

Faivre et al., [49] review the functional results following distal replantation without nerve suturing in a cohort of 8 children. All children regained discriminatory sensation through the adjacent and spontaneous neurotization after distal digital replantation [49]. Thus they report that children are excellent candidates for replantation of distal extremities even without nerve suturing [49]. Schäfer et al., [50]. Compare the open surgical epineural neurolysis of the median nerve in carpal tunnel syndrome with agee endoscopic operation and report that the endoscopic group were able to return to work significantly earlier and had reduced postoperative pain compared to the surgical group. They conclude that the epineural neurolysis is not necessary [50]. Bjorkman et al., [51] investigate the improvement of hand function following tourniquet induced anaesthesia after deafferentation.

Table 1 demonstrates the studies reviewed in this systematic review. The authors, type of study, number of patients involved, techniques and outcome of the studies have been summarized.

Interestingly they report that this resulted in significant and rapid improvement in tactile discrimination, grip strength and sensibility of the contralateral hand [51]. Thus they conclude that this technique may have potential clinical application [51]. Vilkki [52] reports significant improvement of hand function in congenitally adactylous hand after microsurgical 3-jointed second toe transfer and meticulous intrinsic repair. Abundant nerve supply was found to be important in normal growth of the transferred nerve [52]. 14 out of the 17 patients regained the ability to pinch [52]. Sanmartin et al., [53]. Review the results of 105 cases of ring avulsion injuries and conclude that good sensory recovery is not achieved by primary neuronal repair in most cases.

Free auto nerve grafting in median and ulnar nerve repair had no obvious effects in long-term improvement of the hand function following severe electrical injury of the wrist [54]. In this study Xu, Li and Chen [54] report that the 2 out of the 47 cases repaired by compound tissue grafting of sural nerve and deep facia carried by small saphenous veins demonstrated uncertain results. However, 3 cases of proximal neuronal anastomosis showed fairly good results. They conclude 2 factors to be responsible for the poor outcome following nerve grafting: scar formation and inadequate blood supply [54].

Haase and Chung [55] investigate the primary repair of 2 cases of high ulnar nerve injuries and report a consistent poor outcome due to the distance between the innervated muscles and the site of injury. In these procedures the distal branch of anterior interosseous nerve was transferred to the distal motor branch of the ulnar nerve which was reported to be a much better method than the conventional primary neurorrhaphy for this type of injuries [55]. Song et al., [56]. Valuate the application of distal based neurocutaneous flaps in repair of hand wounds. This simple procedure is less invasive, has a high survival rate and results in sensory function recovery of the hand [56]. They also report recovery in hand function and two point discrimination after cutaneous nerve ending anastomosis [56].

Rosen et al., [57] assess the functional outcome of median and ulnar nerve repair in a study of 19 patients and report that there was no significant improvement in two point discrimination over time. However, they suggest the use of alternative or complementary test instruments for measuring the tactile gnosis [57]. Furthermore, most changes occurred during the first year and later it was mainly the motor function that improved [57]. Stevanovic et al., [58] use nerve grafts to bridge gaps in avulsion injuries of the thumb. They state that the cold ischaemia time and patient’s age had no significant effect on the function or survival of the transplanted thumb [58]. However, the grip strength was always less than normal and key pinch was 60% of normal [58]. Moreover, when a venous backflow was established and continued for at least 20 minutes the transplanted thumb always survived without complications [58].

Goldberg et al., [59] determine the number of suture strands crossing the repair site in a cadaver as the most significant variable that would influence the nerve repair strength. Braga-Silva et al., [60] investigate the effect on recovery of late tubular repair of human median and ulnar nerves using a silicon tube filled with autologous bone marrow mononuclear cells from iliac crest aspiration. The effects of pain as well as the motor and sensory recovery were assessed after 1 year and the tube filled with mononuclear cells showed better recovery than the empty tubes [60]. Hence they claim this method to be better in term of neuronal regeneration when using conventional tubular reconnection [60]. Mondelli et al., [61]. Review the results of surgical decompression of carpal tunnel syndrome and report that elderly patients showed less improvement in all modalities compared to the 20-54 year group, probably due to lower repair capacity and greater preoperative damage. Deutinger et al., [62]. Report better sensibility recovery after motor-sensory differentiation in median and ulnar nerve repair. Lohmeyer et al., [63] repaired 15 digital nerve lesions in 14 patients using interpositional grafting of a hollow collagen I conduit and state that this tubulization technique to be an alternative to autologous nerve grafting since it successfully bridges short nerve gaps. In a review of treatment possibilities of thumb avulsion injuries Pfeiffer [64] recommends direct nerve repair over use of nerve-grafting in order to prevent neuroma formation.

DISCUSSION

In this systematic review we looked at various nerve repair techniques currently used for different types of nerve injuries to improve hand function. These include the use of resorbable poly[(R)-3-hydroxybutyrate] (PHB) [41], epineural end-to-end suturing [41], graft repair [42, 48, 58, 64], nerve transfer [43-55], side to side neurorrhaphy and end to side neurorrhaphy between median, radial and ulnar nerves [44], nerve transplant [45], nerve repair [47, 53, 57, 59, 62, 64], external neurolysis and epineural sutures [48], adjacent neurotization without nerve suturing [49], Agee endoscopic operation [50], tourniquet induced anesthesia [51], toe transfer and meticulous intrinsic repair [52], free auto nerve grafting [54], use of distal based neurocutaneous flaps [56] and tubulization [60-63].

There are, however, a number of factors that influence the functional outcome and recovery. Sunderland [10] argues that if enough axons can be directed to their end-organs and if the muscle is maintained in good condition through therapy then the affected muscle, even after a year of denervation, is able to regain almost 100% function. Therefore, functional deficits observed in muscles are due to a lack of adequate re-innervated muscle fibers, fiber mixing or persisting trans-synaptic neuronal changes which prevent the normal activity pattern [65].

Patient’s Age

In peripheral nerve repair the functional results are inversely proportional to the patients age, holding all other variables constant [12]. For patients up to 20 years of age the regained two point discrimination value calculated in millimeters for ulnar and median nerve repairs has been found to be the same as the patient’s age [66]. Onne [66] noted that in this type of nerve repair there was variable but generally poor recovery for patients between 20 and 31 and for those above 31 poor results were recorded. Digital nerve repairs, on the other hand, showed good functional recovery up to the age of 50 years [66]. Young, Wray, and Weeks [28] reported that patients older than 40 achieved no two point discrimination but protective sensation after digital nerve repairs. However, they reported useful two point discrimination in 80% of patients below 20 years of age [28]. Lundborg and Rosén [67] found that patients under 10 showed best results in term of regaining sensibility following transected median or ulnar nerves at the wrist level. Moreover, they observed a marked decline in recovery up to the age of 18 and a plateau thereafter [67]. Cherqui et al., [42] argue that the result of nerve graft after tumour resection in lipofibrohamartoma of the median nerve may be better in pediatric patients. Mondelli et al., [61] also report that elderly patients showed less recovery than the 20-54 year group. They argue that this might be due to lower repair capacity and greater preoperative damage [61]. Faivre et al., [49] state that children are excellent candidates for replantation of distal extremities even without nerve suturing. Contradicting outcomes have been reported by Sunderland [10], who claims that there is no correlation between the patient’s age and functional outcome. Venkatramani et al., [68] support this statement and suggest that the patient’s age should not be a criterion for denying treating and good results are expected if the procedure is done within 6 months.

Time of Repair

There is some degree of disagreement concerning the optimal timing for suturing transected nerves. Sunderland [10] and Ducker [69] recommend nerve repair within the first 10 days of injury whereas Kleinert and Griffin [70] and Holmes and Young [71] believe that the nerve repair should be at the time of maximal axoplasmic synthesis. Cabaud et al., [72] support early treatment to minimize scarring in endoneurial space and benefit from early axonal sprouting. Seddon [8], however, states that fibrosis at 3 weeks offers a mechanical advantage for nerve suturing. Lenz-Scharf et al., [45] argue that nerve regeneration is best within 6 weeks at the proximal end of the lesion as Wallerian degeneration is complete. Barrios and de Pablos state that the worsening prognosis was related to a time period of longer than 1 year from nerve damage to surgery [48]. Rosen et al., [57] report that most functional recovery occurred within the first year of median and ulnar nerve repair and later it was mainly the motor function that improved.

Other Factors

The level at which the injury has occurred can also affect the outcome. The more proximal the injury, the worse the prognosis in terms of motor and sensory return [10, 73]. Moreover, more complete and rapid regain of function occurs in more proximally innervated muscles [12]. Another factor affecting the outcome is the tension of the repair. While the elasticity of the nerve tissue can prove helpful in bridging nerve gaps, Millesi [36] argues that human nervous tissue has an elongation capacity of 20% beyond which the conductivity is compromised. Xu, Li and Chen [54] assume 2 factors to be responsible for the poor outcome following nerve grafting: scar formation and inadequate blood supply.

Barrios and de Pablos [48] found that the median nerve had the best recovery but the radial nerve had the worst prognosis in term of motor recovery in lesions affecting the continuity of the nerve trunk. Sanmartin et al., [53] conclude that good sensory recovery is not achieved by primary neuronal repair in most cases in a review of 105 ring avulsion injuries. Similarly, Haase and Chung [55] report consistently poor outcome in primary repair of 2 cases of high ulnar nerve injuries. Rosen et al., [57] also report was no significant improvement in two point discrimination over time in 19 patients with ulnar and median nerve repair. Goldberg et al., [59] determine the number of suture strands crossing the repair site in a cadaver as the most significant variable that would influence the nerve repair strength.

CONCLUSION

In this systematic review we have summarized the advances in nerve repair techniques which have been used to improve hand function. The most important ones are the use of resorbable poly[(R)-3-hydroxybutyrate] (PHB) 41, epineural end-to-end suturing [41], graft repair [42, 48, 58, 64], nerve transfer [43, 55], side to side neurorrhaphy and end to side neurorrhaphy between median, radial and ulnar nerves [44], nerve transplant [45], nerve repair [47, 53, 57, 59, 62, 64], external neurolysis and epineural sutures [48], adjacent neurotization without nerve suturing [49], Agee endoscopic operation [50], tourniquet induced anesthesia [51], toe transfer and meticulous intrinsic repair [52], free auto nerve grafting [54], use of distal based neurocutaneous flaps [56] and tubulization [60, 63]. The results have been summarized in Table 1. We also identified factors that may affect the prognosis following surgery. Among the most significant are patient’s age [10, 12, 28, 42, 49, 61, 66-68], time of repair [8, 10, 45, 48, 57, 69-72], level of injury [10, 12, 73], tension of repair [44], and scar formation following surgery [54]. Despite the thorough findings of this systematic review, we suggest that further research in this field is needed.

CONFLICT OF INTEREST

None declared.

ACKNOWLEDGEMENT

None declared.

REFERENCES

[1] Terzis JK, Sun DD, Thanos PK. Historical and basic science review: past, present, and future of nerve repair J Reconstr Microsurg 1997; 13(3 ): 215-5.
[2] Naff NJ, Ecklund JM. History of peripheral nerve surgery techniques Neurosurg Clin N Am 2001; 12(1 ): 197-209.
[3] Mackinnon S, Dellon AL. Surgery of the peripheral nerve NY: Thieme Medical 1988.
[4] Stoll G, Jander S, Myers RR. Degeneration and regeneration of the peripheral nervous system: from Augustus Waller's observations to neuroinflammation J Peripher Nerv Syst 2002; 7(1 ): 13-27.
[5] Waller A. Experiments on the section of the glossopharyngeal and hypoglossal nerves of the frog, and observations of the alterations produced thereby in the structure of their primitive fibers Philosoph Trans R Soc Lond (Biol) 1850; 140: 423-0.
[6] Millesi H. Microsurgery of peripheral nerves Hand 1973; 5(2 ): 57-60.
[7] Christine BN. Peripheral Nerve Injuries 2011.
[8] Seddon HJ. Three types of nerve injury Brain 1943; 66: 237.
[9] Mosby's medical dictionary. 8th. Makti City : Elsevier Health Sciences 2009.(8):
[10] Sunderland S. Nerves and nerve injuries. 2nd. Edinburgh, NY: Churchill and Livingstone 1978; pp. 69-141.
[11] Lorei MP, Hershman EB. Peripheral nerve injuries in athletes. Treatment and prevention Sports Med 1993; 16(2 ): 130-47.
[12] Karol AG. Peripheral nerves and Tendon Transfers Selected Reading in Plastic Surgery 2003; 9: 23.
[13] Deutinger M, Girsch W, Burggasser G, et al. Peripheral nerve repair in the hand with and without motor sensory differentiation J Hand Surg Am 1993; 18(3 ): 426-32.
[14] Sunderland S. The intraneural topography of the radial median and ulnar nerves Brain 1945; 68: 243-99.
[15] 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(1 ): 1-18.
[16] Williams HB, Jabaley ME. The importance of internal anatomy of the peripheral nerves to nerve repair in the forearm and hand Hand Clin 1986; 2(4 ): 689-707.
[17] Manders EK, Saggers GC, Diaz-Alonso P. Elongation of peripheral nerve and viscera containing smooth muscle Clin Plast Surg 1987; 14(3 ): 551-62.
[18] Mackinnon SE. Surgical management of the peripheral nerve gap Clin Plast Surg 1989; 16(3 ): 587-603.
[19] Daniel RK, Terzis JK. Reconstructive microsurgery. Boston: Little Brown and Company 1977.
[20] Langley JN, Hashimoto M. On the suture of separate nerve bundles in a nerve trunk and on internal nerve plexuses J Physiol 1917; 51(4-5 ): 318-46.
[21] Bora FW Jr. Peripheral nerve repair in cats. The fascicular stitch J Bone Joint Surg Am 1967; 49(4 ): 659-6.
[22] Goto Y. Experimental study of nerve autografting by funicular sxuture Nihon Geka Hokan 1967; 36(4 ): 478-94.
[23] Grabb WC, Bement SL, Koepke GH, Green RA. Comparison of methods of peripheral nerve suturing in monkeys Plast Reconstr Surg 1970; 46(1 ): 31-8.
[24] Wise AJ, Topuzlu C, Davis P, et al. A comparative analysis of macro and microsurgical neurorrhaphy techniques Am J Surg 1969; 117: 556.
[25] Yamamoto K. A comparative analysis of the process of nerve regeneration following funicular and epineurial suture for peripheral nerve repair (author's transl) Nihon Geka Hokan 1974; 43(4 ): 276-301.
[26] Brushart TM, Tarlov EC, Mesulam MM. Specificity of muscle reinnervation after epineurial and individual fascicular suture of the rat sciatic nerve J Hand Surg Am 1983; 8(3 ): 248-53.
[27] Sunderland S. The pros and cons of funicular nerve repair J Hand Surg 1979; 4: 201.
[28] Young L, Wray RC, Weeks PM. A randomized prospective comparison of fascicular and epineural digital nerve repairs Plast Reconstr Surg 1981; 68(1 ): 89-93.
[29] Orgel MG, Terzis JK. Epineurial vs perineurial repair: An ultrastructural and electrophysiological study of nerve regeneration Plast Reconstr Surg 1977; 60: 80.
[30] Orgel MG. Epineurial versus perineurial repair of peripheral nerves Clin Plast Surg 1984; 11(1 ): 101-4.
[31] Jabaley ME. Current concepts of nerve repair Clin Plast Surg 1981; 8(1 ): 33-44.
[32] Madden JW, Peacock EE Jr. Some thoughts on repair of peripheral nerves South Med J 1971; 64(1 ): 17-21.
[33] Gruber H. Identification of motor and sensory funiculi in cut nerves and their selective reunion Br J Plast Surg 1976; 29(1 ): 70-3.
[34] 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(5 ): 376-80.
[35] Riley DA, Lang DH. Carbonic anhydrase activity of human peripheral nerves a possible histochemical aid to nerve repair J Hand Surg Am 1984; 9A(1 ): 112-20.
[36] Millesi H, Meissl G, Berger A. The interfascicular nerve-grafting of the median and ulnar nerves J Bone Joint Surg Am 1972; 54(4 ): 727-50.
[37] Millesi H, Meissl G, Berger A. Further experience with interfascicular grafting of the median ulnar and radial nerves J Bone Joint Surg Am 1976; 58(2 ): 209-18.
[38] Berger A, Millesi H. Nerve grafting Clin Orthop Relat Res 1978; (133): 49-55.
[39] Millesi H, Michon J. Treatment of nerve lesions by fascicular free nerve Grafts In: Moberg E, Ed. Traumatic nerve lesions of upper limbs. Edinburgh: Churchill Livingstone 1975.
[40] Millesi H. Fascicular Nerve Repair and Interfascicular Nerve Grafting Reconstructive Microsurgery 1977; 00: 430-2.
[41] Aberg M, Ljungberg C, Edin E, et al. Clinical evaluation of a resorbable wrap-around implant as an alternative to nerve repair a prospective, assessor-blinded, randomised clinical study of sensory motor and functional recovery after peripheral nerve repair J Plast Reconstr Aesthet Surg 2009; 62(11 ): 1503-9.
[42] Cherqui A, Sulaiman WA, Kline DG. Resection and nerve grafting of a lipofibrohamartoma of the median nerve case report Neurosurgery 2009; 65(Suppl 4): A229-35.
[43] Ducic I, Dellon AL, Bogue DP. Radial sensory neurotization of the thumb and index finger for prehension after proximal median and ulnar nerve injuries J Reconstr Microsurg 2006; 22(2 ): 73-8.
[44] Yuksel F, Peker F, Celikoz B. Two applications of end-to-side nerve neurorrhaphy in severe upper-extremity nerve injuries Microsurgery 2004; 24(5 ): 363-8.
[45] Lenz-Scharf O, Fansa H, Galazky I, Schneider W. Secondary nerve reconstruction in the upper extremity in children--results with respect to number of motor units Handchir Mikrochir Plast Chir 2004; 36(1 ): 19-24.
[46] Battiston B, Lanzetta M. Reconstruction of high ulnar nerve lesions by distal double median to ulnar nerve transfer J Hand Surg Am 1999; 24(6 ): 1185-91.
[47] Wang Y, Zhu S, Zhang B. Anatomical study and clinical application of transfer of pronator quadratus branch of anterior interosseous nerve in the repair of thenar branch of median nerve and deep branch of ulnar nerve Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 1997; 11(6 ): 335-7.
[48] Barrios C, de PJ. Surgical management of nerve injuries of the upper extremity in children a 15-year survey J Pediatr Orthop 1991; 11(5 ): 641-5.
[49] Faivre S, Lim A, Dautel G, Duteille F, Merle M. Adjacent and spontaneous neurotization after distal digital replantation in children Plast Reconstr Surg 2003; 111(1 ): 59-65.
[50] Schafer W, Sander KE, Walter A, Weitbrecht WU. Agee endoscopic operation of carpal tunnel syndrome in comparison with open surgical technique Handchir Mikrochir Plast Chir 1996; 28(3 ): 143-6.
[51] Bjorkman A, Rosen B, van WD, Larsson EM, Lundborg G. Acute improvement of contralateral hand function after deafferentation Neuroreport 2004; 15(12 ): 1861-5.
[52] Vilkki SK. Advances in microsurgical reconstruction of the congenitally adactylous hand Clin Orthop Relat Res 1995; (314 ): 45-58.
[53] Sanmartin M, Fernandes F, Lajoie AS, Gupta A. Analysis of prognostic factors in ring avulsion injuries J Hand Surg Am 2004; 29(6 ): 1028-37.
[54] Xu J, Li Q, Chen S. Analysis of the long-term results of late hand function reconstruction in patients with severe electrical injury of the wrists Zhonghua Shao Shang Za Zhi 2000; 16(6 ): 328-0.
[55] Haase SC, Chung KC. Anterior interosseous nerve transfer to the motor branch of the ulnar nerve for high ulnar nerve injuries Ann Plast Surg 2002; 49(3 ): 285-90.
[56] Song Y, Zhang F, Liu H. Application of new type distal based neurocutaneous flap in repair of limb wound Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2009; 23(12 ): 1435-9.
[57] Rosen B, Dahlin LB, Lundborg G. Assessment of functional outcome after nerve repair in a longitudinal cohort Scand J Plast Reconstr Surg Hand Surg 2000; 34(1 ): 71-8.
[58] Stevanovic MV, Vucetic C, Bumbasirevic M, Vuckovic C. Avulsion injuries of the thumb Plast Reconstr Surg 1991; 87(6 ): 1099-4.
[59] Goldberg SH, Jobin CM, Hayes AG, Gardner T, Rosenwasser MP, Strauch RJ. Biomechanics and histology of intact and repaired digital nerves an in vitro study J Hand Surg Am 2007; 32(4 ): 474-82.
[60] Braga-Silva J, Gehlen D, Padoin AV, Machado DC, Garicochea B, Costa da CJ. Can local supply of bone marrow mononuclear cells improve the outcome from late tubular repair of human median and ulnar nerves? J Hand Surg Eur Vol 2008; 33(4 ): 488-93.
[61] Mondelli M, Padua L, Reale F. Carpal tunnel syndrome in elderly patients: results of surgical decompression J Peripher Nerv Syst 2004; 9(3 ): 168-76.
[62] Deutinger M, Girsch W, Burggasser G. Clinical application of motorsensory differentiated nerve repair Microsurgery 1993; 14(5 ): 297-303.
[63] Lohmeyer JA, Siemers F, Machens HG, Mailander P. The clinical use of artificial nerve conduits for digital nerve repair a prospective cohort study and literature review J Reconstr Microsurg 2009; 25(1 ): 55-61.
[64] Pfeiffer KM. Combined dorsal injuries of the thumb A review of treatment possibilities Handchir Mikrochir Plast Chir 1993; 25(2 ): 80-4.
[65] Sunderland S. Factors influencing the course of regeneration and the quality of the recovery after nerve suture Brain 1952; 75(1 ): 19-54.
[66] Onne L. Recovery of sensibility and sudomotor activity in the hand after nerve suture Acta Chir Scand Suppl 1962; 300(Suppl ): 1-69.
[67] Lundborg G, Rosen B. Sensory relearning after nerve repair Lancet 2001; 358(9284 ): 809-10.
[68] Venkatramani H, Bhardwaj P, Faruquee SR, Sabapathy SR. Functional outcome of nerve transfer for restoration of shoulder and elbow function in upper brachial plexus injury J Brachial Plex Peripher Nerve Inj 2008; 3: 15-0.
[69] Ducker TB, Kempe LG, Hayes GJ. The metabolic background for peripheral nerve surgery J Neurosurg 1969; 30(3 ): 270-80.
[70] Kleinert HE, Griffin JM. Technique of nerve anastomosis Orthop Clin North Am 1973; 4(4 ): 907-15.
[71] Holmes W, Young JZ. Nerve regeneration after immediate and delayed suture J Anat 1942; 77(Pt 1 ): 63-96.
[72] Cabaud HE, Rodkey WG, Nemeth TJ. Progressive ultrastructural changes after peripheral nerve transection and repair J Hand Surg Am 1982; 7(4 ): 353-65.
[73] Gutmann E, Guttmann L. factors affecting recovery of sensory function after nerve lesion J Neurol Psychiatry 1942; 5(3-4 ): 117-29.