Anda di halaman 1dari 8

2144

C OPYRIGHT 2013
BY

T HE J OURNAL

OF

B ONE

AND J OINT

S URGERY, I NCORPORATED

Current Concepts Review

Peripheral Nerve Repair and Reconstruction


Justin W. Grifn, MD, MaCalus V. Hogan, MD, A. Bobby Chhabra, MD, and D. Nicole Deal, MD
Investigation performed at the Department of Orthopaedic Surgery, University of Virginia Health System, Charlottesville, Virginia

When possible, direct repair remains the current standard of care for the repair of peripheral nerve lacerations. In large nerve gaps, in which direct repair is not possible, grafting remains the most viable option. Nerve scaffolds include autologous conduits, articial nonbioabsorbable conduits, and bioabsorbable conduits and are options for repair of digital nerve gaps that are <3 cm in length. Experimental studies suggest that the use of allografts may be an option for repairing larger sensory nerve gaps without associated donor-site morbidity.

Nerve injuries result in approximately $150 billion spent in annual health-care dollars in the United States1. Most patients are young males, with the radial nerve in the upper extremity and the peroneal nerve in the lower extremity most commonly injured2. Selecting the proper treatment continues to pose a challenging problem with a wide variability in approach and outcome. Direct tensionless end-to-end repair, when possible, achieves the most predictable outcomes. In nerve injuries when the nerve ends cannot be approximated without tension, nerve grafts represent the most commonly used method of reconstruction. The development of nerve conduits to enhance nerve repair remains an important research area and future clinical developments in the area of nerve regeneration and repair potentially could improve patient outcomes. Anatomy Nerves are surrounded by the epineurium, perineurium, and endoneurium, each with a vital function. The epineurium serves to wrap the nerve in a supportive barrier against outside stresses. The perineurium lies beneath the epineurium as a thin sheet of at cells with tight junctions to regulate diffusion surrounding individual fascicles and has a high tensile strength. The endoneurium has a loose collagenous matrix surrounding individual nerve bers3 (Fig. 1).

One important clinical aspect of nerve anatomy is that individual fasciculi do not run in a straight line, but instead form plexuses along a nerve ber. An increased number of fascicles increases the strength of the nerve and concomitantly increases the complexity of repair as the fascicle location varies over short distances. It has been suggested that matching these fascicles could improve outcomes. Kato et al. noted excellent results with fascicular orientation using electrical stimulation to help ensure sensory and motor fascicular alignment4. Although time-consuming, matching recently cut nerve endings in terms of motor and sensory function has been described5. Despite these efforts, certain nerves possess greater variability in cross-sectional arrangement along their length3,6,7. Classication Nerve injuries are described with use of the Seddon classication terms8. Three degrees of injury were initially described. Neurapraxia is often the result of a compressive or crush injury to the nerve where conduction is blocked due to myelin damage, resulting in a focal conduction block without Wallerian degeneration as the axon itself remains intact with recovery generally evident in three to six weeks when myelin continuity is restored. The complete interruption of axons is termed axonotmesis. Neurotmesis is the complete physiologic transection of axons

Disclosure: One or more of the authors received payments or services, either directly or indirectly (i.e., via his or her institution), from a third party in support of an aspect of this work. In addition, one or more of the authors, or his or her institution, has had a nancial relationship, in the thirty-six months prior to submission of this work, with an entity in the biomedical arena that could be perceived to inuence or have the potential to inuence what is written in this work. No author has had any other relationships, or has engaged in any other activities, that could be perceived to inuence or have the potential to inuence what is written in this work. The complete Disclosures of Potential Conicts of Interest submitted by authors are always provided with the online version of the article.

J Bone Joint Surg Am. 2013;95:2144-51

http://dx.doi.org/10.2106/JBJS.L.00704

2145
TH E JO U R NA L O F B O N E & JO I N T SU RG E RY J B J S . O RG V O L U M E 95-A N U M B E R 23 D E C E M B E R 4, 2 013
d d d

P E R I P H E R A L N E R V E R E PA I R

AND

RECONSTRUCTION

Fig. 1

Illustration of a cross-sectional anatomy of the peripheral nerve. (Reprinted from Lundborg G. Nerve Injury and Repair. New York: Churchill Livingstone; 1988, p 33, with permission from Elsevier.)

as well as all supporting tissue. Neurotmesis results in changes within the nerve cell body and degeneration with a variable recovery course. The Sunderland classication describes ve degrees of injury based on histology, and allows a better prediction of outcomes following injury6. First-degree injury is equivalent to neurapraxia with no loss in axon integrity. Second-degree injury describes axonal injury within an intact endoneurial tube allowing regrowth within the endoneurial tube. In third-degree injury the endoneurial tube is damaged and the resultant reinnervation is not identical to the original and may result in intrafascicular brotic block, growth of axons into unfamiliar endoneurial tubes, and swelling. In fourth-degree injury, only the epineurium remains intact and fascicular damage occurs in addition to endoneurial damage. Interfascicular regrowth, disorganization, and brous block occur that often necessitate surgical excision and reconstruction. Fifth-degree injury damages the nerve trunk and is equivalent to neurotmesis by the Seddon classication. Pathophysiology of Nerve Degeneration and Regeneration Nerve Degeneration Axonal degeneration follows a sequence of events with the zone of injury extending both proximally and distally. Proximal to the site of injury, traumatic degeneration occurs, traveling to the level of the intact node of Ranvier, or, in some cases, further proximal. The swollen cell body begins production of elements essential to axonal repair and growth9. Distal to the site of injury, Wallerian, or secondary, degeneration occurs within twenty-four to forty-eight hours

following injury and begins with axonal breakdown. Wallerian degeneration is antegrade degeneration in which the part of the axon separated from the neurons cell body degenerates distal to the injury10. Affected Schwann cells throughout the distal segment begin to catabolize the myelin. This distal degeneration, combined with macrophages recruited to the area, leads to phagocytosis of axonal and myelin debris. These events ultimately result in myelin tube collapse9. Nerve Regeneration From the proximal stump, axonal sprouting begins within twenty-four hours after injury. The growth cone protrudes from the axonal sprout elongating down the path of the intact basal lamina and within the regenerative promoting environment. With an intact endoneurial tube, such as in axonotmesis, the regenerating sprouting axon has a direct path to the end organ. This is a slow migration process occurring at approximately 1 mm per day11. The growth cone is under the inuence of neurotrophic and neurite-promoting factors, also referred to as neurotrophins12. Nerve growth factor is an essential neurotrophic factor and one of great interest in nerve injury and the development of future options for peripheral nerve repair13-15. Nerve growth factor plays an important role in the growth, maintenance, and survival of target neurons and supports peripheral nerve regeneration in a rat model. Glial nerve growth factor, ciliary neurotrophic factor, and a number of other growth factors play a critical role in the nerve regeneration process13. Also aiding in the axonal elongation and growth process are a number of neurite-promoting factors and matrix-specic

2146
TH E JO U R NA L O F B O N E & JO I N T SU RG E RY J B J S . O RG V O L U M E 95-A N U M B E R 23 D E C E M B E R 4, 2 013
d d d

P E R I P H E R A L N E R V E R E PA I R

AND

RECONSTRUCTION

substances, which serve as building blocks for nerve development10. A complete understanding of neurotrophins is beyond the scope of this review, but it is clear that these factors play a crucial role in neuron cell survival, neurite outgrowth, cell differentiation, and cell migration, and promote controlled neurogenesis. Reinnervation After nerve injury, muscle atrophy occurs at the motor end plate, followed by brosis. If reinnervation does occur, both old and new motor end plates will be activated. Although the muscle is atrophied and brotic, it can remain viable for up to eighteen months16; however, if reinnervation does not occur within one year, the chance of functional recovery diminishes17. Patient age is the most important factor to consider in evaluating the success of nerve recovery following repair18 while the level of injury also plays a role, with distal injuries having better recovery results than proximal injuries19,20. Clinical Evaluation Evaluation of the patient with peripheral nerve injury begins with determination of the mechanism of injury. Crush injuries can produce a variety of nerve injuries but often lead to neurapraxia. Penetrating injuries can lead to partial or full nerve transection, gunshot-related nerve decits tend to be due to neurotmesis and the degree of injury depends on the velocity of the weapon involved, and fracture-related injuries must be correlated with their mechanism. High-energy blunt trauma can lead to a variety of injury patterns requiring further examination to determine regeneration potential. Twisting, traction, and crush-type injuries can result in nerve entrapments and tension-type stress on the nerve, leading to neurotmesis and axonotmesis20,21. Neurophysiologic Studies When considering the need for surgical intervention, closed fractures with nerve injury often result in nerve recovery in a greater majority of patients without operative intervention and should be followed expectantly22. The standard of care in decision-making in peripheral nerve surgery has been the use of serial neurophysiologic studies over months combined with serial physical examinations. The degree of muscle degeneration that occurs after nerve injury cannot be determined until Wallerian degeneration is complete. This process may take up to four weeks. Although early studies can help to localize injuries, the typical waiting period to allow a baseline to be obtained is approximately six weeks. Electrodiagnostic studies may differentiate acute injury from chronic injury. They may also assist in determining the type of nerve ber affected. When obtained serially over time, they may map nerve recovery23. Nerve conduction studies are generally used initially as a screening test and the addition of electromyography (EMG) provides valuable information in the form of reduced action potentials23. Clinical or electrodiagnostic evidence of progressive recovery of sensorimotor function indicates an injury with a neurapraxic or axonotmetic component, which warrants

further observation because spontaneous recovery normally occurs within the rst few months11. Imaging Ultrasound and magnetic resonance imaging (MRI) remain the most used imaging studies for peripheral nerve injury. Ultrasound is inexpensive and safe and has recently become more commonly utilized in the diagnosis of nerve injury. One prospective study24 utilized high-resolution ultrasound to evaluate twenty-six patients with documented motor or sensory peripheral nerve decits that were due to either trauma or entrapment. Of those twenty-six patients, nineteen underwent operative exploration and ultrasound diagnoses were then correlated with neurological examination and intraoperative ndings. Ultrasound provided reliable visualization of nerve injury in all patients and ndings such as axonal swelling, neuroma formation, and partial laceration had high correlation with intraoperative ndings24. However, ultrasound use in the setting of extensive edema and/or obesity can be challenging and can limit diagnostic accuracy. MRI can provide useful information for diagnosis and surgical planning. Grant et al.25 showed that MRI can provide resolution of fascicular patterns and can demonstrate nerve edema. In addition, their study of sciatic nerve injury in a rat model showed that high-resolution MRI can differentiate neurotmesis from high-grade axonotmesis. However, a clinical study evaluated short T1 inversion recovery (STIR) MRI compared with EMG and found that MRI was less sensitive than EMG, with 11% of cases of nerve injury not recognized on MRI being conrmed on EMG26. Timing of Repair Operative exploration should occur in a timely fashion in open injuries. A transected nerve should be repaired within two to three days postinjury to decrease brosis, to minimize tension due to retraction, and to maximize biologic regrowth19,27. The surgeon must consider reduction attempts when nerve palsy is accompanied by a fracture. However, peripheral nerve injury by examination is not considered a reason for exploration immediately without other indication11. Much of the research on the timing of exploration has focused on one of the most common peripheral injuries, the radial nerve in humeral shaft fractures. B ostman et al.28 retrospectively examined seventy-ve patients with radial nerve palsy, sixteen with decit after manipulation and fty-nine with initial palsy. Early exploration and internal xation were performed in thirty-seven patients. Thirty-eight patients were watched expectantly. Of those thirty-eight patients observed, twenty-six (68%) experienced spontaneous recovery and twelve (32%) underwent delayed nerve exploration. B ostman et al. concluded that early exploration was not advisable. Of those patients who underwent initial exploration, twenty-seven (73%) of thirty-seven had recovery of radial nerve function compared with thirty-three (87%) of thirty-eight who were managed nonoperatively. Ring et al.29 retrospectively reviewed twenty-four patients with humeral shaft fractures. Eleven of the twenty-four humeral shaft fractures were open. Fourteen of the

2147
TH E JO U R NA L O F B O N E & JO I N T SU RG E RY J B J S . O RG V O L U M E 95-A N U M B E R 23 D E C E M B E R 4, 2 013
d d d

P E R I P H E R A L N E R V E R E PA I R

AND

RECONSTRUCTION

twenty-four patients were explored at the time of presentation, and three patients in this group had closed fractures. Ring et al. found that all eight of the patients with intact explored nerves and nine of the ten patients with unexplored nerves with an initial decit recovered fully within a six-month period. Five of the six patients in the transection group underwent repair and none showed functional recovery. Signs of nerve recovery did not appear until approximately seven weeks. Direct Nerve Repair Direct nerve repair is indicated in cases of sharp nerve division with minimal gap. The ideal setting for direct repair is an injury zone with good blood supply and soft-tissue coverage. The proper alignment of nerve ends is critical to optimize nerve recovery, and gaps of >2.5 cm at the site of injury will commonly necessitate nerve grafting. Tension-free suture repair remains the preferred treatment option for nerve injury. If this is not possible because of either gap formation or poor quality of tissue for repair, alternative methods should be utilized30. Simple direct repair entails suturing the nerve together in a tension-free fashion (Fig. 2). End-to-side repair may be favorable when the proximal aspect of the injured nerve is not salvageable. The distal portion of the injured nerve can be sutured to an adjacent nerve with subsequent collateral sprouting31. Yu et al. evaluated end-to-side neurorrhaphy in the ulnar nerve as the donor and in the musculocutaneous nerve as the recipient and noted collateral sprouting of intact axons of the ulnar nerve with limited functional reinnervation32. The development of novel microsurgical techniques and instrumentation led some to promote grouped fascicular repair.

This technique is similar to epineural repair, but in addition the perineural sheaths of individual fascicles are repaired under microscopic magnication. This approach attempts more accurate approximation of regenerating axons but requires more dissection and potential soft-tissue disruption. In nerves with dened motor and sensory topography, such as median or ulnar nerves in the forearm and the sciatic nerve in the thigh, such repair is often used11. With both epineural and fascicular repair, most surgeons advocate the use of 8-0 or 9-0 monolament suture in adult patients. Direct muscular neurotization involves placing the proximal nerve stump into the muscle belly. This technique is not preferred as functional recovery is weakest with this treatment, but it remains an option when direct repair and/or reconstruction are not possible27. Fibrin glue can be considered as an adjunct or alternative to epineurial repair and is viewed by many as quick and easy to use33,34. Multiple studies have shown that brin glue is equivalent to suture repair and may improve resistance to gapping34. Use of Conduits A tensionless repair has been cited as one major factor to the successful recovery of sensorimotor function35. When tensionless direct repair cannot be achieved, interposed autologous nerve grafting is the gold standard for segmental defects27,36. However, autologous grafting carries with it donor-site morbidity, requirement for two anastomotic sites, increased operative time, and elevated costs, thereby justifying the ongoing search for options37. Potential advantages of nerve conduits include absorbability, lack of donor-site morbidity, and lack of axonal escape.

Fig. 2

Photograph showing a median nerve laceration in forearm repaired by direct end-to-end repair.

2148
TH E JO U R NA L O F B O N E & JO I N T SU RG E RY J B J S . O RG V O L U M E 95-A N U M B E R 23 D E C E M B E R 4, 2 013
d d d

P E R I P H E R A L N E R V E R E PA I R

AND

RECONSTRUCTION

TABLE I Options for Bridging Nerve Gaps Nerve Autografts Allografts Biological conduits Vein Artery Synthetic conduits Collagen Polyglycolic acid Caprolactone

randomized study compared autogenous vein nerve conduits with synthetic polyglycolic acid conduits for digital nerve gaps of 4 to 25 mm. Forty-two patients with seventy-six repairs were enrolled in the study, with thirty-seven patients with sixty-eight repairs undergoing repair with either polyglycolic acid conduits or autogenous vein nerve conduits (thirty-six with synthetic polyglycolic acid, and thirty-two with vein conduits). The authors analyzed sensory recovery at six and twelve months after repair, the time and cost of repair, and the complication prole between the two treatment groups and found equivalent results with similar cost proles and sensory recovery outcomes41. Collagen Conduits Type-I collagen and Type-IV collagen remain the most commonly used nerve conduit design, with Type-I collagen being most biocompatible42. Figure 3 demonstrates a commonly available collagen conduit used to bridge a nerve laceration. Animal studies with collagen conduits have demonstrated equivalent efcacy when compared with autograft; however, clinical studies are lacking43,44. To date, only case series have been published with no documented Level-I studies available. Bushnell et al.43 reported a Level-IV case series of twelve digital nerve gaps from 10 to 12 mm over a two-year period. Outcomes in this study were measured with use of American Society for Surgery of the Hand (ASSH) guidelines with static 2-point discrimination, Disabilities of the Arm, Shoulder and Hand (DASH) scores, and Semmes-Weinstein testing. In their study of twelve patients, three of whom were excluded, of the remaining nine patients, four (44%) had excellent results, four (44%) had good results, and one (11%) had fair results with an average DASH score of 10 points. Five patients had full sensory recovery, two patients had diminished sensory recovery, one patient had diminished protective sensation, and one patient had loss of sensation. Lohmeyer et al.45 performed a prospective cohort study with collagen conduits to repair twelve digital

Nerve scaffolds include autologous grafts, articial nonbioabsorbable conduits, and bioabsorbable conduits (Table I). Three main types of bioabsorbable conduits are currently approved by the U.S. Food and Drug Administration (FDA) for use. With variations in tubes currently available, it is helpful to review the evidence surrounding the selection of tubes. Most regard the upper limit of nerve conduit length to be 3 cm38. In a rabbit peroneal nerve study, Strauch et al. compared results of using vein conduits from 1 to 6 cm with deteriorating results at a length of >3 cm39. Autogenous Conduits Veins are the most common type of autogenous conduit used for reconstruction of nerve defects, and are often referred to as autogenous or autologous vein nerve conduits. Chiu and Strauch conducted a prospective study of twenty-two patients with defects of 3 cm, nding that autogenous vein nerve conduits produced results as good as those of sural nerve digital grafts40. Rinker and Liau41 in their recently published prospective

Fig. 3

Photograph showing a collagen conduit used to bridge traumatic nerve laceration.

2149
TH E JO U R NA L O F B O N E & JO I N T SU RG E RY J B J S . O RG V O L U M E 95-A N U M B E R 23 D E C E M B E R 4, 2 013
d d d

P E R I P H E R A L N E R V E R E PA I R

AND

RECONSTRUCTION

nerves with an average 12.7-mm gap. At the one-year followup, of the twelve patients, four (33%) had excellent sensory recovery, ve (42%) had good sensory recovery, one (8%) exhibited poor sensory recovery, and two (17%) had no sensory recovery. However, grading of outcomes using 2-point discrimination remains nonstandardized and no studies have examined motor recovery with collagen tubes42. Polyglycolic Acid Conduits The polyglycolic acid conduit is regarded as more exible, and the porous nature allows oxygen to diffuse in and aid in regeneration with conduit resorption occurring in six months42. In a prospective case series of fteen patients undergoing secondary nerve reconstructions of digital nerve gaps measuring approximately 17 mm with polyglycolic acid tubes, Mackinnon and Dellon 46 found that ve patients (33%) had excellent sensory recovery, eight patients (53%) had good recovery, and two patients (14%) had poor or no recovery. Sensory data were gathered with use of the British Medical Research Council sensory nerve grading scale with moving and static 2-point discrimination. Although that study was an early Level-IV study, Mackinnon and Dellon concluded that polyglycolic acid tubes could produce results equivalent to the classic nerve graft without donor-site morbidity with gaps up to 3 cm. In a cohort study, Battiston et al.47 examined the utility of polyglycolic acid tubes compared with biologically constructed muscle-vein conduits reporting equivalent results. Thirty patients were treated for digital nerve injuries. Of these patients, muscle-vein combined conduits were used in thirteen patients and polyglycolic acid conduits were used in seventeen patients. The authors compared outcomes with use of the MackinnonDellon modication of the British Medical Research Council scale. Results showed no notable differences between the two groups with respect to evaluation testing used, although the polyglycolic acid group achieved S4 sensation (excellent sensibility) in 12% (two of seventeen) compared with 38% (ve of thirteen) of the vein conduit group. The evidence must be weighed with the fact that certain patients underwent immediate repair while others were delayed. Weber et al.48 compared polyglycolic acid conduits with primary repair or autograft for digital nerve injuries in a LevelII study. Ninety-eight patients with 136 digital nerve repairs were prospectively randomized to either a group undergoing direct end-to-end repair or utilizing a nerve graft or a group undergoing repair with a polyglycolic acid conduit. The authors reported that conduits were superior in gaps of 4 mm or >8 mm. That study provided evidence that polyglycolic acid nerve conduits produce equivalent results to nerve repairs or autologous grafts for short or moderate digital nerve gaps. Caprolactone Conduits Poly(DL-lactide-e-caprolactone) was rst demonstrated in rat models to bridge 10-mm sciatic nerve gaps; these guides were reported to degrade completely in one year. Poly(DL-lactide-ecaprolactone) is another bioabsorbable conduit that may be used to bridge nerve gaps49. Bertleff et al.50 performed a multicenter,

blinded, randomized controlled trial of thirty patients with thirty-four nerve injuries using caprolactone Neurolac nerve tubes (Polyganics, Groningen, the Netherlands) compared with primary repair for digital nerve lacerations in gaps of 6 to 8 mm. Moving and static 2-point discrimination was 7 to 10 mm for both the experimental and control groups38. Relative indications for nerve tubes based on the above studies include nerve gaps of <3 cm in length when tension would result from primary repair coupled with patient or surgeon preference to avoid harvesting an autologous nerve graft. Longer nerve gaps may lead to decreased sensory recovery48. In a recent study, Shin et al.51 evaluated sciatic nerve motor recovery in a rat model with a 10-mm defect using autograft, caprolactone, collagen, and polyglycolic acid conduits. They found that caprolactone conduit and autograft repairs were equivalent in motor function as measured by action potentials, muscle weight, histomorphometry, and isometric force. Grafting For larger nerve gaps in which primary repair would cause tension, autografting remains the standard of care, especially for the recovery of motor function. Recent advances in allografting technique and biomaterials continue to produce interesting prospects for the future of peripheral nerve repair. Use of Autograft In patients with larger nerve gaps, use of autograft remains the most reliable repair technique. Sensory donor nerves are most often used, with the sural nerve being the most commonly harvested. Autografting methods include single-stranded, cable, and vascularized, and in all cases the graft is left 10% to 20% longer than the gap for ensuring a tension-free repair. Although no large clinical studies exist comparing these techniques, the most commonly used is cable grafts with multiple small diameter nerve grafts sewn between fascicles parallel to one another to match the diameter of the severed nerve52. Use of Allograft Like autograft, nerve allograft provides a framework for nerve regeneration but with the potential for shorter operative time, abundant supply, and lack of donor site morbidity. A recent multicenter retrospective study53 evaluated seventy-six nerve repairs performed at various centers in a relatively heterogeneous group (forty-nine sensory, eighteen mixed, and nine motor) using a processed human nerve allograft. Subgroup analysis was performed to determine the inuence of nerve type, gap length, patient age, time to repair, age of injury, and mechanism of injury on outcomes. Brooks et al. reported meaningful recovery in 87.3% of subjects across subgroups using both qualitative and quantitative outcome measures with no response to treatment in eight of the subjects. There were no graft-related adverse effects. Additionally, they showed functional recovery in nerve gaps up to 50 mm53. Immunogenicity has historically been a concern with allografts. Although graft Schwann cells display major histocompatibilty complexes that incite T-cell response, host Schwann

2150
TH E JO U R NA L O F B O N E & JO I N T SU RG E RY J B J S . O RG V O L U M E 95-A N U M B E R 23 D E C E M B E R 4, 2 013
d d d

P E R I P H E R A L N E R V E R E PA I R

AND

RECONSTRUCTION

cell proliferation and irradiation of the graft improve regeneration and histologic outcome in animal models54. Karabekmez et al.55 retrospectively studied short-term sensory recovery after decellularized cadaveric nerve transplantation in seven patients with ten nerve gaps, eight digital and two ulnar sensory. They examined 2-point discrimination and found that all patients recovered 10 mm or better static 2-point discrimination with ve good results and ve excellent results with no cases of infection or rejection. Although larger randomized studies are needed, for small gaps up to 3 cm, allograft outcomes may be comparable with that of conduits in sensory outcome43,48. Ray et al.56 reported success in a mouse model with cold preservation for four weeks to decrease immunogenicity. Whereas most studies have focused on sensory recovery, a recent study design compared motor recovery of autograft to allograft and collagen conduit in rat sciatic nerve gap lesions and found autograft superior to allograft at sixteen weeks postoperatively in terms of isometric strength recovery57. Allograft and autograft were superior (p < 0.05) to collagen conduit. Although headway has been made, more development is needed prior to recommending allograft use over autograft for longer nerve gaps. Evaluating Recovery and Outcomes Rehabilitation after nerve injury may include adjacent joint motion and motor and sensory training including biofeedback or re-sensitization focusing on central nervous system reeducation19. Most studies to date have graded the success of nerve repair using the British Medical Research Councils system or its modied versions for the evaluation of motor and sensory return. Physical examination allows grading of sensory recovery from S0 to S5 and motor from M0 to M5. Subjective patient-perceived outcome measures are also helpful in terms of assessing perceived disability, pain, and functional outcome58,59. One recent retrospective review suggested that high DASH scores may be predictive of greater long-term disability59. Injury severity, patient age, site of repair relative to target muscle, and time of repair remain the best predictors of outcome following nerve injury20,31. However, a

standardized, validated method to assess neural recovery following repair has not been established. Most nerve injuries result in some level of nerve decit and the development of a standardized evaluation tool is made more difcult by the variety of factors known to play a role in the recovery process including the level of injury, age of patient, comorbidities, timing of repair, and type of nerve injured. Summary Peripheral nerve injury often results in substantial disability. Patient factors including age, degree of injury, and type of nerve involved often predict the outcome. Although tensionfree direct repair remains the standard of care in easily approximated nerve ends, the armamentarium of the peripheral nerve surgeon has increased in the past decade. Conduits, grafting, and biologic agents can improve recovery when primary repair is not possible. Nerve and tendon transfers provide additional means of dealing with peripheral nerve injuries in the right situation. Future advances in bioengineering, allografts, and operative technique will lead to improved options. n

Justin W. Grifn, MD A. Bobby Chhabra, MD D. Nicole Deal, MD Department of Orthopaedic Surgery, University of Virginia Health System, 400 Ray C. Hunt Drive, Suite 330, P.O. Box 800159, Charlottesville, VA 22908-0159 MaCalus V. Hogan, MD Division of Foot and Ankle Surgery, Department of Orthopaedic Surgery, Universiy of Pittsburgh School of Medicine, UPMC Shadyside Hospital, 5200 Centre Avenue, Suite 415, Pittsburgh, PA 15232

References
1. Taylor CA, Braza D, Rice JB, Dillingham T. The incidence of peripheral nerve injury in extremity trauma. Am J Phys Med Rehabil. 2008 May;87(5): 381-5. 2. Noble J, Munro CA, Prasad VS, Midha R. Analysis of upper and lower extremity peripheral nerve injuries in a population of patients with multiple injuries. J Trauma. 1998 Jul;45(1):116-22. 3. Sunderland S. The anatomic foundation of peripheral nerve repair techniques. Orthop Clin North Am. 1981 Apr;12(2):245-66. 4. Kato H, Minami A, Kobayashi M, Takahara M, Ogino T. Functional results of low median and ulnar nerve repair with intraneural fascicular dissection and electrical fascicular orientation. J Hand Surg Am. 1998 May;23(3):471-82. 5. Ganel A, Farine I, Aharonson Z, Horoszowski H, Melamed R, Rimon S. Intraoperative nerve fascicle identication using choline acetyltransferase: a preliminary report. Clin Orthop Relat Res. 1982 May;(165):228-32. 6. Sunderland S. A classication of peripheral nerve injuries producing loss of function. Brain. 1951 Dec;74(4):491-516. 7. Sunderland S, Roche AF. Axon-myelin relationships in peripheral nerve bres. Acta Anat (Basel). 1958;33(1-2):1-37. 8. Seddon HJ. A Classication of Nerve Injuries. Br Med J. 1942 Aug 29;2(4260):237-9. 9. Stoll G, Grifn JW, Li CY, Trapp BD. Wallerian degeneration in the peripheral nervous system: participation of both Schwann cells and macrophages in myelin degradation. J Neurocytol. 1989 Oct;18(5):671-83. 10. Lee SK, Wolfe SW. Peripheral nerve injury and repair. J Am Acad Orthop Surg. 2000 Jul-Aug;8(4):243-52. 11. Mohler LR, Hanel DP. Closed fractures complicated by peripheral nerve injury. J Am Acad Orthop Surg. 2006 Jan;14(1):32-7. 12. Gordon T. The physiology of neural injury and regeneration: The role of neurotrophic factors. J Commun Disord. 2010 Jul-Aug;43(4):265-73. Epub 2010 Apr 8. 13. Gordon T. The role of neurotrophic factors in nerve regeneration. Neurosurg Focus. 2009 Feb;26(2):E3. 14. Muir D. The potentiation of peripheral nerve sheaths in regeneration and repair. Exp Neurol. 2010 May;223(1):102-11. Epub 2009 Jun 6. 15. de Ruiter GC, Malessy MJ, Yaszemski MJ, Windebank AJ, Spinner RJ. Designing ideal conduits for peripheral nerve repair. Neurosurg Focus. 2009 Feb;26(2):E5.

2151
TH E JO U R NA L O F B O N E & JO I N T SU RG E RY J B J S . O RG V O L U M E 95-A N U M B E R 23 D E C E M B E R 4, 2 013
d d d

P E R I P H E R A L N E R V E R E PA I R

AND

RECONSTRUCTION

16. Atkins S, Smith KG, Loescher AR, Boissonade FM, OKane S, Ferguson MW, Robinson PP. Scarring impedes regeneration at sites of peripheral nerve repair. Neuroreport. 2006 Aug 21;17(12):1245-9. 17. Roganovic Z, Pavlicevic G. Difference in recovery potential of peripheral nerves after graft repairs. Neurosurgery. 2006 Sep;59(3):621-33, discussion:621-33. 18. Apel PJ, Garrett JP, Sierpinski P, Ma J, Atala A, Smith TL, Koman LA, Van Dyke ME. Peripheral nerve regeneration using a keratin-based scaffold: long-term functional and histological outcomes in a mouse model. J Hand Surg Am. 2008 Nov;33(9):1541-7. 19. Lundborg G, Ros en B. Hand function after nerve repair. Acta Physiol (Oxf). 2007 Feb;189(2):207-17. 20. Isaacs J. Treatment of acute peripheral nerve injuries: current concepts. J Hand Surg Am. 2010 Mar;35(3):491-7, quiz:498. Epub 2010 Feb 6. 21. Shah SR, Bindra R, Grifn JW. Irreducible dislocation of the thumb interphalangeal joint with digital nerve interposition: case report. J Hand Surg Am. 2010 Mar;35(3):422-4. 22. Bishop J, Ring D. Management of radial nerve palsy associated with humeral shaft fracture: a decision analysis model. J Hand Surg Am. 2009 Jul-Aug;34(6):991: e1. Epub 2009 Apr 10. 23. Strandberg EJ, Mozaffar T, Gupta R. The role of neurodiagnostic studies in nerve injuries and other orthopedic disorders. J Hand Surg Am. 2007 Oct;32(8): 1280-90. 24. Toros T, Karabay N, Ozaksar K, Sugun TS, Kayalar M, Bal E. Evaluation of peripheral nerves of the upper limb with ultrasonography: a comparison of ultrasonographic examination and the intra-operative ndings. J Bone Joint Surg Br. 2009 Jun;91(6):762-5. 25. Grant GA, Britz GW, Goodkin R, Jarvik JG, Maravilla K, Kliot M. The utility of magnetic resonance imaging in evaluating peripheral nerve disorders. Muscle Nerve. 2002 Mar;25(3):314-31. 26. McDonald CM, Carter GT, Fritz RC, Anderson MW, Abresch RT, Kilmer DD. Magnetic resonance imaging of denervated muscle: comparison to electromyography. Muscle Nerve. 2000 Sep;23(9):1431-4. 27. Dahlin LB. Techniques of peripheral nerve repair. Scand J Surg. 2008;97(4):310-6. 28. B ostman O, Bakalim G, Vainionp aa S, Wilppula E, P ati al a H, Rokkanen P. Radial palsy in shaft fracture of the humerus. Acta Orthop Scand. 1986 Aug;57(4):316-9. 29. Ring D, Chin K, Jupiter JB. Radial nerve palsy associated with high-energy humeral shaft fractures. J Hand Surg Am. 2004 Jan;29(1):144-7. 30. Al-Qattan MM. End-to-side nerve repair. J Hand Surg Am. 2002 Jul;27(4):739, author reply:739-40. 31. Lundborg G. A 25-year perspective of peripheral nerve surgery: evolving neuroscientic concepts and clinical signicance. J Hand Surg Am. 2000 May;25(3):391414. 32. Yu Q, Lin ZK, Ding J, Wang T, Chi YL, Gao WY. Functional motor nerve regeneration without motor-sensory specicity following end-to-side neurorrhaphy: an experimental study. J Hand Surg Am. 2011 Dec;36(12):2010-6. 33. Whitlock EL, Kasukurthi R, Yan Y, Tung TH, Hunter DA, Mackinnon SE. Fibrin glue mitigates the learning curve of microneurosurgical repair. Microsurgery. 2010;30(3):218-22. 34. Ornelas L, Padilla L, Di Silvio M, Schalch P, Esperante S, Infante RL, Bustamante JC, Avalos P, Varela D, L opez M. Fibrin glue: an alternative technique for nerve coaptationPart II. Nerve regeneration and histomorphometric assessment. J Reconstr Microsurg. 2006 Feb;22(2):123-8. 35. Sunderland S. Factors inuencing the course of regeneration and the quality of the recovery after nerve suture. Brain. 1952 Mar;75(1):19-54. 36. Dahlin L, Lundborg G. The use of silicone tubing in the late repair of the median and ulnar nerves in the forearm. J Hand Surg Br. 2001 Aug;26(4):393-4. 37. Lundborg G, Ros en B. The two-point discrimination testtime for a re-appraisal? J Hand Surg Br. 2004 Oct;29(5):418-22. 38. Deal DN, Grifn JW, Hogan MV. Nerve conduits for nerve repair or reconstruction. J Am Acad Orthop Surg. 2012 Feb;20(2):63-8. 39. Strauch B, Ferder M, Lovelle-Allen S, Moore K, Kim DJ, Llena J. Determining the maximal length of a vein conduit used as an interposition graft for nerve regeneration. J Reconstr Microsurg. 1996 Nov;12(8):521-7.

40. Chiu DT, Strauch B. A prospective clinical evaluation of autogenous vein grafts used as a nerve conduit for distal sensory nerve defects of 3 cm or less. Plast Reconstr Surg. 1990 Nov;86(5):928-34. 41. Rinker B, Liau JY. A prospective randomized study comparing woven polyglycolic acid and autogenous vein conduits for reconstruction of digital nerve gaps. J Hand Surg Am. 2011 May;36(5):775-81. Epub 2011 Apr 12. 42. Meek MF, Coert JH. US Food and Drug Administration/Conformit Europeapproved absorbable nerve conduits for clinical repair of peripheral and cranial nerves. Ann Plast Surg. 2008 Apr;60(4):466-72. 43. Bushnell BD, McWilliams AD, Whitener GB, Messer TM. Early clinical experience with collagen nerve tubes in digital nerve repair. J Hand Surg Am. 2008 Sep;33(7):1081-7. 44. Waitayawinyu T, Parisi DM, Miller B, Luria S, Morton HJ, Chin SH, Trumble TE. A comparison of polyglycolic acid versus type 1 collagen bioabsorbable nerve conduits in a rat model: an alternative to autografting. J Hand Surg Am. 2007 Dec;32(10):1521-9. 45. Lohmeyer JA, Siemers F, Machens HG, Mail ander P. The clinical use of articial nerve conduits for digital nerve repair: a prospective cohort study and literature review. J Reconstr Microsurg. 2009 Jan;25(1):55-61. Epub 2008 Nov 26. 46. Mackinnon SE, Dellon AL. Clinical nerve reconstruction with a bioabsorbable polyglycolic acid tube. Plast Reconstr Surg. 1990 Mar;85(3):419-24. 47. Battiston B, Geuna S, Ferrero M, Tos P. Nerve repair by means of tubulization: literature review and personal clinical experience comparing biological and synthetic conduits for sensory nerve repair. Microsurgery. 2005;25(4):258-67. 48. Weber RA, Breidenbach WC, Brown RE, Jabaley ME, Mass DP. A randomized prospective study of polyglycolic acid conduits for digital nerve reconstruction in humans. Plast Reconstr Surg. 2000 Oct;106(5):1036-45; discussion 1046-8. 49. Jiang X, Lim SH, Mao HQ, Chew SY. Current applications and future perspectives of articial nerve conduits. Exp Neurol. 2010 May;223(1):86-101. Epub 2009 Sep 19. 50. Bertleff MJ, Meek MF, Nicolai JP. A prospective clinical evaluation of biodegradable Neurolac nerve guides for sensory nerve repair in the hand. J Hand Surg Am. 2005 May;30(3):513-8. 51. Shin RH, Friedrich PF, Crum BA, Bishop AT, Shin AY. Treatment of a segmental nerve defect in the rat with use of bioabsorbable synthetic nerve conduits: a comparison of commercially available conduits. J Bone Joint Surg Am. 2009 Sep;91(9):2194-204. 52. Nichols CM, Brenner MJ, Fox IK, Tung TH, Hunter DA, Rickman SR, Mackinnon SE. Effects of motor versus sensory nerve grafts on peripheral nerve regeneration. Exp Neurol. 2004 Dec;190(2):347-55. 53. Brooks DN, Weber RV, Chao JD, Rinker BD, Zoldos J, Robichaux MR, Ruggeri SB, Anderson KA, Bonatz EE, Wisotsky SM, Cho MS, Wilson C, Cooper EO, Ingari JV, Safa B, Parrett BM, Buncke GM. Processed nerve allografts for peripheral nerve reconstruction: a multicenter study of utilization and outcomes in sensory, mixed, and motor nerve reconstructions. Microsurgery. 2012 Jan;32(1):1-14. Epub 2011 Nov 28. 54. Brenner MJ, Lowe JB 3rd, Fox IK, Mackinnon SE, Hunter DA, Darcy MD, Duncan JR, Wood P, Mohanakumar T. Effects of Schwann cells and donor antigen on longnerve allograft regeneration. Microsurgery. 2005;25(1):61-70. 55. Karabekmez FE, Duymaz A, Moran SL. Early clinical outcomes with the use of decellularized nerve allograft for repair of sensory defects within the hand. Hand (N Y). 2009 Sep;4(3):245-9. Epub 2009 May 2. 56. Ray WZ, Kale SS, Kasukurthi R, Papp EM, Johnson PJ, Santosa KB, Yan Y, Hunter DA, Mackinnon SE, Tung TH. Effect of cold nerve allograft preservation on antigen presentation and rejection. J Neurosurg. 2011 Jan;114(1):256-62. Epub 2010 Jun 18. 57. Giusti G, Willems WF, Kremer T, Friedrich PF, Bishop AT, Shin AY. Return of motor function after segmental nerve loss in a rat model: comparison of autogenous nerve graft, collagen conduit, and processed allograft (AxoGen). J Bone Joint Surg Am. 2012 Mar 7;94(5):410-7. 58. Novak CB, Anastakis DJ, Beaton DE, Mackinnon SE, Katz J. Relationships among pain disability, pain intensity, illness intrusiveness, and upper extremity disability in patients with traumatic peripheral nerve injury. J Hand Surg Am. 2010 Oct;35(10):1633-9. 59. Novak CB, Anastakis DJ, Beaton DE, Katz J. Patient-reported outcome after peripheral nerve injury. J Hand Surg Am. 2009 Feb;34(2):281-7.