Medical Therapy
If surgery is not an option, the best choice for patients is supportive therapy to maintain range of motion and muscle tone. This involves 2 main procedures: (1) immobilization to prevent deforming contractures and (2) massage and exercises to maintain blood flow and free movement. [15]
Surgical Therapy
The goal of surgical nerve repair is axonal growth through a repaired or replaced conduit. If no conduit is present, nerve regeneration fails in favor of neuroma creation. Many different techniques have been developed to facilitate repair of the conduits, including approximation, nerve grafting, alternate conduits, and nerve transfer. [75]
End-to-end closure
End-to-end closure involves the approximation of the transected nerve's free ends. This is the simplest repair procedure and usually has the best prognosis. End-to-end closure is indicated in patients in whom the nerve gap is less than 2 cm in length and/or the nerve can be repaired without tension. This defect is closed most often with epineurial or perineurial/fascicular sutures, which is discussed in Closure of defect. [4, 39, 31, 14]
A study by Fakin et al indicated that in epineurial coaptation of digital nerves in adults, the level of success at long-term follow-up with regard to sensory outcome is related only to the surgeon’s level of experience and not to such factors as the patient’s age, whether or not the patient smokes, the time of immobilization, the mechanism of injury, or anastomosis of a digital artery. The study involved 93 coapted digital nerves, with mean follow-up being 3.5 years. [76]
Nerve grafting
This form of repair is ideally suited for bridging the gap between 2 ends that cannot be easily approximated. For many years, the popularity of short nerve grafts and the resulting poor patient outcomes were responsible for the avoidance of this technique. However, a nerve graft, regardless of length, if performed in a tensionless manner, has been shown to generally have better results than an end-to-end approximation performed under tension. [77, 10, 26, 78]
A retrospective study by Felder et al indicated that in patients with severe ulnar neuropathy, sensory recovery can be enhanced via adjunct treatment with cross-palm nerve grafting, either through allograft or autograft. In the study, cross-palm, side-to-side, tension-free grafting was performed, with the grafts extending from the median to the ulnar nerve. The investigators found that protective sensation returned in 21 out 24 patients (87.5%); diminished light touch sensation was restored in 16 patients (66.7%), and normal range sensation returned in six patients (25.0%). [79]
In general, harvesting a nerve graft to repair a defect creates a secondary defect in a different location (see Table 5). For this reason, good donor nerves provide noncritical sensation, and their innervation pattern loss does not leave a body part unprotected. Nerves that meet this requirement include small cutaneous nerves, which lead to a minimal loss in sensation, and nerves that have been severed concomitantly, as in a polytrauma or amputation. Harvest of the graft can be performed in a variety of ways, but removing the graft in a manner that leaves the remaining proximal end buried, thus minimizing possible complications from neuromas at the donor site, is beneficial. [19, 9]
Table 5. Common Donor Sites (Open Table in a new window)
Graft Donor Site |
Length Obtained |
Sensory Deficit |
Distal posterior interosseous nerve |
15-20 cm |
Dorsal wrist joint |
Lateral antebrachial cutaneous nerve |
15 cm |
Lateral forearm surface |
Medial antebrachial cutaneous |
20 cm |
Medial and anterior surface of forearm |
Superficial radial |
25 cm |
Dorsal radial hand surface |
Lateral femoral cutaneous |
30 cm |
Lateral and thigh |
Anterior femoral cutaneous |
40 cm |
Medial and anterior thigh |
Sural |
40 cm |
Lateral foot surface and a portion of the heel |
Saphenous |
25-40 cm |
Medial foot surface |
Many different types of grafting have been performed, but very few have worked well. One method used a trunk graft, or a section of a large nerve, that bridged the gap completely without any other grafts. This was similar to the cable grafts developed slightly later, in which smaller nerves were harvested and glued together to create a single large graft. Both of these methods met with little success, largely because the grafts were too thick and their centers took too long to become vascularized, which is a requirement to provide the energy needed for degeneration and reinnervation. Trunk grafting is still used occasionally in situations in which other options have been exhausted, but some have suggested that the graft be cut prior to grafting. This form of delay allows the metabolically active degenerative process to occur in a vascularized bed, before the nerve is free grafted; the idea being that this helps prevent the center and distal ends of the graft from becoming fibrotic. [19]
The use of small cutaneous nerves for grafts minimizes the morbidity of the harvest and has allowed for much better results than using an interfascicular graft. Multiple sections of the donor nerve are used to bridge the gap and are attached between similar fascicles, independent of the other graft pieces. This technique attempts to return some semblance of fascicular continuity. Maintaining the donor nerve vasculature in a free graft form is also possible.
Harvesting the dominant pedicle to the graft and attaching it appropriately in the donor site can allow the graft to survive in suboptimal conditions, such as scar beds, or can accelerate the growth in proximal injuries. [19]
Axons have been demonstrated to preferentially innervate endoneurial tubes of similar function. However, that preference is nonspecific for location. Also, the discovery has been made that over time, regenerating nerves disregard an existing fascicular pattern and progress down extrafascicular paths or create a new fascicle. This means that even in situations in which the fascicles match up, the potential for disastrous disorganization upon reinnervation exists. Thus, take extreme care to align and repair the fascicular patterns because a misalignment can result in a defect of reinnervation. Interestingly, this disorganization can be somewhat overcome through sensory reeducation.
A study by Rinker et al indicated that short-gap digital nerve injuries (ie, 5-15 mm) can be effectively repaired with processed nerve allografts (PNAs). The study, which included 24 patients (37 repairs), found that in 92% of repairs, patients achieved sensory recovery scores of S3-S4 on the Medical Research Council Classification scale. [80]
Conduits
Nonneural tissue and synthetic substances have been used as alternatives for nerve grafts for the last century, although with only marginal success until the 1980s. Since that time, some success has been achieved with arteries, veins, and silicon or bioabsorbable conduits. These have been used with a fair bit of success to bridge gaps less than 3 cm, with good-to-excellent sensory recovery. The use of these tubes is believed to create a microenvironment for the various chemical factors that regulate nerve regeneration, thus enhancing the process. [37, 81, 39, 82, 49, 83]
A prospective, randomized study compared the sensory recovery, cost, and complications of digital nerve repair using autogenous vein and polyglycolic acid conduits. The results concluded that although the cost and sensory recovery after autogenous vein conduit was similar to that of the polyglycolic acid conduit, fewer postoperative complications were found after the autogenous vein conduit technique. [84]
A study by Huber et al comparing end-to-end suture with the implantation of a collagen conduit for the repair of digital nerve injury found that greater functional impairment was reported by the conduit patients at follow-up (6-36 mo). With regard to both procedures, sensory function by the C and A-delta fibers was found to have largely recovered, while mechanical detection thresholds increased due to severe A-beta–fiber function loss. [85]
A study by Isaacs et al indicated that for long-gap acute or subacute digital nerve injuries (15-25 mm), repair with PNAs is more effective than with conduits. For study patients, better average static two-point discrimination was achieved with PNA repairs, at 6.1 mm, than for conduit procedures, at 7.5 mm. Moreover, 40% of the PNA surgeries produced normal sensation (as measured using the American Society for Surgery of the Hand scale), as opposed to 18% of the conduit repairs. In addition, more clinical failures (in which patients lacked protective sensation) were associated with long-gap conduits than with conduits used to repair short gaps (5-14 mm). Results for PNAs and conduits were comparable for short-gap repairs in terms of average static two-point discrimination (7.3 vs 7.5 mm, respectively). [86, 87]
Nerve transfers
This form of nerve repair transfers damaged or minor motor pathways and uses them to reinnervate major pathways, with the hope of restoring some function. This is indicated in severe polyneuropathy and is usually performed only if nerve grafts are unfeasible, the injury is extremely proximal compared to essential end organs, or muscle and tendon transfers have been exhausted or are unavailable. This procedure is not used often in the upper extremities and has primarily been described for cranial nerve injuries. [88]
The results of one study conclude that a reconstruction method of very distal nerve transfer of radial nerve branches to palmar nerves at the level of the proximal phalanx is useful in high median nerve lesions and can restore fingertip sensation. However, very distal nerve transfers might be used in addition to nerve grafting in older patients or in patients with chronic lesions of the median nerve at the wrist. [89]
Preoperative Details
Preoperative planning is important and includes the diagnostic tests (described in Diagnostic Procedures) that allow localization of the injury. This is important because the grade of injury plays a major role in deciding whether surgery is indicated. Injuries of first to third degree are likely to heal well on their own, without intervention. However, fourth- and fifth-degree injuries need intervention, and the sooner surgery is performed, the better.
Another consideration that becomes apparent based on the patient's history is the mechanism of injury. Sharp transections, because of their minimal tissue damage, can be operated on immediately without worrying whether neural and other tissue close to the wound will die. This certainty does not extend to injuries with a crush component, and these injuries must be handled differently by waiting a few weeks for the degeneration of neural tissue to reach its maximum levels so that healthy nerve tissue can be reached by dissection and repaired by nerve graft.
The issue of how long to wait, ie, whether to perform an immediately primary closure, wait a week, and perform a delayed primary closure or wait more than 2 weeks and perform a secondary closure, has been debated for some time. In general, better results have been achieved following earlier repair, but the conditions that allow for primary repair are fairly stringent. This is discussed in Indications and is one of the most important factors to consider prior to surgery.
Working with patient issues is also extremely important before surgery. During the history and workup, estimate patient compliance. By nature, repairs of peripheral nerves are delicate and can be destroyed within days of the surgery in a noncompliant patient. [90, 91, 92] Because nerve repair is handled as elective surgery, a noncompliant patient may be a candidate for education prior to surgery. If the patient's dominant hand is injured, he or she may need reeducation for the opposite hand to cope during and after surgery and during recovery. Patients also need to be informed, realistically, of the expected outcome. While the results are improving, very few patients recover normal or close-to-normal function. This plays a big role in patient satisfaction later.
Finally, knowing what kinds of activities patients enjoy, their occupation, and their avocations is important because in some patients, this information may be involved in the type of repair and nerve graft site selection. For instance, harvesting the sural nerve is not wise in construction workers who are on their feet in dangerous situations.
Intraoperative Details
Incision
To repair the nerve under optimal conditions, making a large enough incision to facilitate exposure of the proximal and distal ends of the injured nerve is best. Take care to preserve the vascular attachments when exposing the nerves, if possible. Also, because the entry incision inevitably produces a scar that is detrimental to good nerve function, make the incision away from the portion of the wound maintaining the perfusion of the nerve bed. [10, 19, 93]
Repair
The amount of tension on a site of repair or graft is the single largest determinant of success. A repair site under tension has an increased amount of scar tissue and fibrosis and a reduced cross-sectional area, which blocks axonal growth. This is observed in the postoperative period when an advancing Tinel sign stops at or just distal to the repair site. Increased tension on the nerve stretches it out, decreases the cross-sectional area, and increases the pressure within the nerve. With higher pressure, less blood passes through the intrinsic vessels of the nerve. While the peripheral nerves are fairly resistant to ischemia, if the tension is not relieved, ischemic nerve damage and internal fibrosis can occur. [77, 94, 26, 95]
Since the detrimental effect of tension on the site of union was recognized, various strategies have been proposed to lengthen the nerve or shorten the distance between the ends so that the tension is reduced. The most successful and most commonly used method is nerve grafting. A section of nerve can be harvested and placed between 2 severed ends, allowing union without tension. Because excess graft length is typically easy to obtain, current recommendations include harvesting a donor segment at least 15% longer than the nerve gap site. [96, 78]
Other techniques that can be used in extreme or isolated situations include mobilization, bone shortening, and joint repositioning. Mobilization is fairly useful in patients in whom the injured nerve lies outside the center of rotation of a joint, such as the ulnar nerve at the elbow. By transposing the nerve inside the point of rotation, the amount of needed excursion is reduced and the length of nerve is increased. Bone shortening is an extreme method of gaining nerve length and is indicated only in the upper extremity when a humoral osteotomy is also indicated.
Because of the large amount of excursion possible with nerves, joint repositioning can make available significant nerve length. Extensive studies have been performed on cadavers to determine how many millimeters of nerve length flexing and extending various joints can gain. Large amounts of length can be gained with 90° flexion at the elbow and 40° at the wrist. The increase in nerve length is beneficial for a tensionless repair, but the gradual return to full extension once the nerve has started healing inflicts a series of traction injuries. This reduces the number and effect of regenerating axons; thus, the results are inferior to a tensionless nerve graft that allows for maximum extension. [50]
Closure of defect
Surgeons have several options to close the nerve defect. Epineurial closure involves placing several nonabsorbable sutures in the epineurium of the free nerve ends. Use a fairly small suture, 8-0 to 10-0, so that the amount of tissue displaced within the nerve is minimal, as is scar formation from the presence of a foreign body. Place the sutures such that the nerve ends are approximated, but not under enough tension to strangulate the tissue. Excess tension overcomes the capillary perfusion pressure; thus, the nerve is rendered ischemic. The number of sutures required to obtain closure varies depending on the size of the nerve and the size of the gap. Triangulation closure provides the most accurate alignment. This method of closure is recommended for distal injuries in which the nerve fascicles generally have been sorted into discrete sensory and motor functions. [97, 98, 81, 31, 14]
Perineurial closure is involved with fascicular repair. In this method, the outer epineurium is pulled back, exposing the individual fascicles of axons. Care is taken to approximate fascicles of the same function in end-to-end closure or to connect fascicles of similar function in aimed graft repair. The fascicles are then sutured together with a single 10-0 suture placed through the perineurium. If rotation occurs so that the fascicle is no longer lined up, a second suture may be required. Starting at the deepest part of the wound and working toward the surface in a one-way-up anastomotic technique is a good idea.
This type of repair is recommended for more proximal injuries that are not yet well sorted. A variation on this type of repair is the grouped fascicular, in which a number of fascicles are arranged tightly. In this situation, a few sutures are used to approximate and close the whole group. [10, 99, 100, 97, 101, 4, 31, 14]
Closure of wound
Once the nerve is repaired, maximizing the chances for the repair to heal and be functional is important. This can be aided by attempts to reduce the amount of scar tissue and leave the repaired nerve in a well-vascularized bed, away from the incision. Anything that reduces the number of adhesions and lets the repaired nerve regain its ability to glide improves eventual function. In some cases of repair, in which a large amount of trauma and swelling is present, performing adjacent tissue transfers may be necessary to ensure that the repaired nerve is not under pressure by tightly closed soft tissue. [10]
Postoperative Details
Following surgery, immobilizing the limb is imperative to protect the repair site. Follow basic guidelines for safe splint positioning. This prevents the denervated muscles from remaining in an overstretched position, prevents disfiguring joint contractures, prevents the patient from adapting to the injury, and eventually allows maximum use of the hand. For the first week to 10 days, immobilize the limb completely to prevent disruption of the repaired union. In the second postoperative week, therapy to maintain the range of motion, muscle tone, and blood supply to the area can be started.
Even though the site of repair tolerates movement, the continuing healing process and the sensory deficits warrant a protective splint for several weeks. By the third or fourth week, removing the splint and relying on the patient (after a warning about the dangers of excessive excursion) to slowly increase the amount of movement and function in the affected limb is generally safe. [102, 103, 30, 39]
Follow-up
Following surgery, continuing care for the patient and establishing a therapy routine are important. Continued care and therapy involve 2 main aspects. The continued care aspect is tracking the regenerating axons, using EMG/NCS testing and the Tinel sign, to their successful reinnervation of muscle and sensory end organs. Close follow-up care is essential to detect the arrest of axon regeneration for any reason, especially near the repair, because a second operation may be required to resect scarred or other unfavorable tissue and reconstruct the nerve a second time.
The therapy aspect of follow-up care is essential for functional return. Axon regrowth is only part of the process that must occur for a good functional result because reinnervation of sensory organs has been shown to not correlate with return of function. [104] This finding, when integrated with the improved results in children, suggests that a large central component to nerve repair exists. Several studies have demonstrated that sensory reeducation protocols greatly increase the functional outcome and that the return of function is accompanied by cortical reorganization. [11, 105, 106, 107] In essence, a new part of the brain must figure out what it is like to feel, which is why sensory-rich environments can help speed the process. In addition to the sensory reeducation, hand therapists work with strength and coordination function so that the hand is also functional. [19, 108, 109, 39, 31]
Complications
Complications are a concern in every surgery, although being prepared can help minimize the resulting consequences. Additionally, knowing what kinds of situations increase the risk of complications can help decrease the postsurgery complication rate simply by avoiding high-risk procedures. [110, 9]
Potential complications are as follows:
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Hematoma of large or small vessels
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Failure of sutures or grafted structures
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Traction due to adhesions or repair using joint repositioning
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Fibrosis of the nerve or nerve graft if no profusion occurs for long periods (This is especially common if the repair is placed under tension or in an unvascularized bed.)
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Neuroma formation following incomplete repair
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Entrapment of the nerve following the repair due to excessive scar tissue formation or pressure from associated wounds
Outcome and Prognosis
Factors that affect the results of nerve repairs are varied, and only a very few of them rely on physician proficiency. Despite this, awareness of these factors is beneficial to enable the patient and doctor to have realistic expectations of the outcome. [4, 110, 39, 31, 71]
Timing
Better results have been demonstrated when the repair is performed sooner. Good results can be expected if the repair is performed before the 6-month mark. Muscle neuromuscular junctions are usually absent after 15-18 months of inactivity; thus, sooner reinnervation is better.
Patient age
Young patients tend to achieve much better results than older patients, probably due to the elasticity of the CNS and the increased ability to heal.
A literature review by Dunlop et al did not find strong evidence to support the surgical repair of injured digital nerves in adults as opposed to a strategy of no repair. Protective sensation was recovered by most patients in the groups that did or did not undergo repair. Although static two-point discrimination tended to be better in association with nerve repair versus nonrepair, normal levels of sensibility were attained in less than 25% of the operated nerves. Both groups had similar adverse outcomes. [111]
Condition of the wound
A clean, small, noninfected wound fares much better than a wound full of debris or infection or one that is missing a great deal of tissue.
Level of injury
The chances of regeneration are better for injuries that are more distal. Proximal injuries are less likely to regenerate because the distance required for reinnervation is much greater and the percentage of cells lost in the distal portion of the nerve is greater. Also, if the proximal injury is a traction-type injury, it can pull the cell body out of the anterior horn, resulting in neuron death and no regeneration.
Tension of the repair
Tension tends to increase the fibrotic and scar tissue found within the nerve and the repair site, hindering proper axon regrowth.
Gap size
Gap size is different from the amount of tissue loss. The gap size is simply the distance between ends that must be closed. If the nerve is left in the severed condition, it retracts over time, increasing the gap size due to the elastic properties of the epineurium. When the gap size is larger, more of a bridge must be filled and the prognosis is worse.
Mechanism
The manner in which the nerve was injured is also involved in healing, largely because it affects so many of the other categories. From a surgical point of view, a sharp laceration, such as a knife wound, has a good prognosis, can be closed early, and should do fairly well.
Traction injuries, if mild, undergo demyelination. If the stretch is more severe, the axon and endoneurium can rupture, causing a second- to third-degree injury. These usually have a fairly good prognosis.
A wound caused by a large crush component can destroy long stretches of nerve and surrounding tissue. Usually, waiting and observing how much tissue dies is best so that viable nerve ends can be joined, which results in a much better prognosis.
The worst kinds of wounds are those created by projectiles. The rapid changes in momentum tend to damage a great deal of tissue and can leave debris in the wound. These types of injuries usually result in axonotmesis, although spontaneous recovery is possible.
While the factors affecting prognosis seem rather intuitive, communicating a patient's recovery status can be much more difficult. In an effort to create a standard scale for measuring the outcomes of surgery, British physicians created scales for grading sensory and motor function. [31, 71] These have been and remain widely used in clinical practice. Unfortunately, these grades are very subjective, which makes using this system for comparison between institutions difficult to impossible. Other scales have been introduced, such as the Semmes-Weinstein monofilament testing, but they have not been used widely in the literature as a measure of outcome.
Aside from the difficulty in measuring and grading the regenerative outcome of the surgery, patient satisfaction is an extremely important variable that is very difficult to measure. Even if a good-to-excellent functional result is achieved, the patient may be wholly unsatisfied with the result. Patient satisfaction can be improved through upfront communication early in the process about what to expect.
Future and Controversies
Currently, a large amount of research is investigating the molecular science of nerve growth and the chemical cascades that take place during regeneration. As these mechanisms are elucidated and more is known about the regenerative process, better methods of repair can be determined.
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Hand nerve injury repair. Crushed median nerve at the elbow.
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Hand nerve injury repair. Epineural repair of median nerve.
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Hand nerve injury repair. Partial transection of ulnar nerve in the forearm.
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Hand nerve injury repair. Posttraumatic neuroma.
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Hand nerve injury repair. Excision of posttraumatic neuroma.
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Hand nerve injury repair. Algorithm for the treatment of nerve injuries.