Evaluation and Approach

A thorough understanding of the nerve injury is imperative following a clinical diagnosis. This is because subsequent management strategies are strongly based on the type of insult sustained. We now know that a regenerative cascade of events begins immediately after a nerve injury. When the neural elements are disrupted, each axon forms several filopodia, which steadily and slowly advance toward the distal nerve stump in an attempt to bridge the gap. The recovery time is dependent on the regeneration rate, which averages 1 mm/day. ⁸ When endoneurial tubes are intact (pure axonotmesis injury), there is an excellent chance of an uninhibited regenerative process culminating in satisfactory reinnervation. However, when there is a partial or complete internal rupture, the advancing and regenerating axons become tangled in disrupted internal architecture and scar tissue, often resulting in a neuroma-in-continuity. The recovery in axonotmesis largely depends on the ability of the regenerating axons to bridge the gap and establish functional continuity without being impeded by the scarring process. Neuropraxia recovers spontaneously, and neurotmesis requires surgery. In complex clinical scenarios, multiple levels and types of injuries can coexist, giving rise to a therapeutic challenge.

The timing of intervention for nerve repair is largely dependent on the type of nerve injury sustained, condition of the wound, and vascular supply of the nerve bed. ^{9,​ 10} Early surgery is indicated when there is a laceration with concurrent neurological deficit, where the possibility of a nerve transection is quite high. These types of injuries are typically caused by knife wounds, lacerations from glass, or razor blade. Spinner and Kline recommended action with end-to-end repair within 72 hours in such scenarios of sharp lacerating injuries. ¹⁰ On the other hand, a bluntly transected nerve is best managed at 3 to 4 weeks so that the neuromas and scarred portions of the nerve are more obvious at the time of repair. These portions are resected and then the nerve is reapproximated with or without grafts. If such an injury is identified during an early exploration, the contused and ragged ends of the nerve are tacked to the adjacent fascial or muscular planes to minimize retraction and to aid an elective end-to-end repair. Delayed exploration with possible repair is indicated in traction injuries, partial nerve defects, infected wounds, and poor patient’s status. These are typically performed at 3 to 4 months to allow time for spontaneous recovery or complete evaluation of the nerve function with serial clinical and electrophysiological assessments. ¹¹ When there is no nerve tissue loss and ends can be approximated without undue tension, an end-to-end repair should be attempted. In case of injuries resulting in defects less than 3 cm, autografting or tubulization techniques are attempted, whereas in larger defects nerve grafting with autografts (rarely allografts) is recommended. ¹² Nerve transfer repairs are especially indicated in brachial plexus injuries, proximal intraforaminal injuries, spinal cord root avulsion injuries, and in cases with delayed presentation and redo brachial plexus injuries. They are covered in detail in other chapters.

9.3 General Principles of Nerve Repair

The general principle of nerve repair is based on the following: a thorough knowledge of the gross anatomy of the limbs and peripheral nerves; clinical evaluation including a detailed history and a complete physical examination; electrophysiological studies; and relevant imaging. Following determination of the type of nerve injury and formulation of a surgical plan, patients should be adequately informed about the surgical procedure and expected outcome. Proper positioning of the limb, padding of pressure points and draping to allow full exposure of the nerve, and assessment of distal muscle function are crucial. Microsurgical techniques should be used for nerve repair, including the use of microsurgical instruments and an operating microscope or magnifying loupes. A short-acting muscle relaxant is typically used because intraoperative stimulation may be required to test for muscle contraction from nerve stimulation during surgery. The injured nerve should be exposed well proximal and distal to injury, in addition to the injury zone, in a thorough and meticulous manner. As mentioned earlier, the damaged nerve must be resected until a normal fascicular pattern is observed, as the repair will fail unless healthy tissues are approximated. Bleeding occurring from the sectioned surface of the stump can be controlled by using a piece of Gelfoam or muscle, whereas arterial bleeding is controlled using fine-tipped bipolar electrocautery visualized using a microscope. To summarize, a technically perfect nerve repair must consist of four parts: (1) complete debridement to healthy nerve tissue, (2) nerve approximation without tension, (3) end-on alignment of fascicles, and (4) atraumatic and secure mechanical coaptation of nerve ends. ¹³

9.4 Neurolysis

Neurolysis has paramount importance in surgical repair of nerve injuries. In this context, the authors are referring to external neurolysis which essentially involves dissection outside the epineurium to release it from points of compression or tethering due to scarring, particularly in cases of delayed exploration. This will enable sufficient mobilization of the nerve, which is a critical step prior to any form of coaptation. Sufficient exposure of the injured segment, both proximal and distal, is mandatory prior to neurolysis. Dissection is preferably performed toward the injury site from a normal segment of the nerve. Adequate neurolysis is believed to act in concert with a healthy vascularized bed to improve nerve vascularity, thus enhancing the results of nerve repair.

9.5 Direct Repair

This type of repair is attempted when the severed ends can be approximated without tension and when the gap is minimal. A better outcome is observed when the nerves are exclusively motor or sensory and also when the amount of intraneural connective tissue is relatively less. ¹⁴ Several technical principles should be strictly followed in every case of direct nerve repair. The importance of adequate visualization of relevant neural, vascular, and musculoskeletal structures during surgical exposure cannot be overemphasized. External neurolysis should be performed without causing neural damage, as mentioned earlier. The repair should be achieved with minimal tension. Numerous authors have reported that excessive tension is detrimental to nerve vascularity and functional outcome. ^{15,​ 16,​ 17} Due to the elastic nature of nerves, some degree of tension is expected in every repair. The amount of acceptable tension is, however, not properly defined. De Medinaceli and colleagues reported that failure to hold an end-to-end repair with single 9–0 suture is a sign of excessive tension. ¹⁸ Whenever there is excess tension at repair site, nerve grafting is preferred.

9.5.1 End-to-End Repair

This is one of the most widely used techniques for direct nerve repair. Numerous authors have described different techniques to achieve an end-to-end repair.

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  Epineural repair: This technique is commonly used when there is a sharp injury to the proximal portion of the nerves without nerve loss and also in cases of partial injuries with good fascicle alignment. It is highly effective for monofascicular and diffusely grouped polyfascicular nerve repairs. ¹⁹ The primary goal is to achieve continuity of the nerve stumps without tension, along with proper alignment of the fascicles. The correct fascicle positioning is confirmed by aligning the longitudinal blood vessels in the epineurium. ²⁰ The coaptation is performed using 8–0 or 9–0 nylon sutures under magnification. To begin with, two orienting epineural sutures are taken 180 degrees apart to avoid rotational displacement during mobilization. It is important to avoid injury to the perineurium; however, a small amount of internal epineurium should be taken in the suture for appropriate fascicular coaptation. Following placement of the first suture, its tail is held using an instrument such as a fine hemostat, to facilitate the rotation of the nerve for coaptation on the opposite side. Additional interrupted sutures may be placed 90 degrees away from the initial sutures for added strength. Minimal number of sutures (usually four) for accurate coaptation are preferred to reduce the scarring process. ^{19,​ 20,​ 21} Many surgeons will augment repair using fibrin glue to further minimize the number of microsutures.

  
  
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  Grouped fascicular repair: This technique is used in mixed motor and sensory nerves where the fascicles serving specific functions are well formed and easily recognized (e.g., ulnar nerve at wrist, radial nerve above elbow before giving rise to posterior interosseous nerve, and superficial sensory radial nerve). Contrary to epineural repair, grouped fascicular repair is a more accurate but technically demanding method of coaptation. Resection of the damaged nerve ends is imperative to precisely delineate fascicular anatomy. The external epineurium is reflected back to organize the fascicles. Fascicular coaptation is achieved with placement of sutures in the interfascicular epineurium and perineurium with 8–0 to 10–0 nylon sutures. As mentioned earlier, not more than two to three sutures per group are preferred to reduce scarring. ²² It is imperative to keep the tension at the repair site to the utmost minimum as the interfascicular epineurium is not as tough as the external epineurium. Excessive tension could also contribute to malalignment of the fascicles and increased scarring.

  
  
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  Fascicular repair: This technique is used in a clean lacerating injury, where the motor and sensory fascicles can be easily identified, in the partially damaged nerve. This involves coaptation of the individual fascicles for optimal alignment, and hence this is a more technically difficult repair. Following dissection of the interfascicular epineurium, the fascicles are identified using the spiral bands of Fontana in the perineurium. These bands are instrumental in maintaining proper fascicular structure and elastic properties of the perineurium. ²³ If there is protrusion of the intrafascicular material in the perineural edge, it should be carefully trimmed prior to suturing. The external epineurium is stripped for lengths approximately twice the cross-sectional diameter of the nerve. Care should be taken to preserve the surrounding paraneurial tissue as it contains blood vessels, and this can be used to cover the repair site. Fascicular coaptation is achieved under high magnification by placement of sutures, usually two to three 10–0 or 11–0 nylon sutures 120 to 180 degrees apart, in the perineurium. It is important to avoid injury to the endoneurium during suture placement. Excessive tension produces lateral protrusion of the interfascicular contents and disappearance of spiral bands of Fontana. ²³ Should this occur during repair, the surgeon should reassess the tension at the repair site. Unlike epineural repair, both grouped fascicular and fascicular coaptation provides better alignment of the fascicles, thereby reducing misdirection of axons ( ▶ Fig. 9.1). Nevertheless, the additional dissection and increased sutures involved in this technique could potentially lead to increased scarring and disruption of blood supply. ^{20,​ 21} Studies have found no significant difference in functional outcome when individual or grouped fascicular repair techniques were used compared to simple epineural repair. ^{24,​ 25,​ 26}

  
  
  
  

  

  
  

  Fig. 9.1 Intraoperative photograph showing matching fascicles during nerve repair to enhance functional recovery.

9.5.2 End-to-Side Repair

End-to-side or terminolateral neurorrhaphy involves connecting the distal stump of a transected nerve, referred to as the acceptor nerve, to the side of an intact adjacent or neighboring nerve, referred to as the donor nerve. This technique is particularly useful in sensory nerve transfers and facial nerve reanimation. The advantage of this technique is that there is no length limitation and also that there is recovery of injured nerve without compromising the function of donor nerve. The mechanism of functional recovery in the acceptor nerve is not entirely clear. Rovak et al opined that nerve fibers invade from the donor axons damaged during nerve preparation for coaptation. ²⁷ Zhang et al, based on double-labelling studies, found that collateral sprouting occurs from the undamaged donor nerve. ²⁸

Since its introduction by Viterbo et al in 1992, many studies on end-to-side repair have shown that outcomes range from poor to modest but rarely excellent. However, Mennen demonstrated good sensory or motor recovery in a large cohort of 50 patients with various peripheral nerve injuries. Excellent results were seen in facial reanimation procedures, where end-to-side facial to hypoglossal nerve anastomosis was performed with an interpositional jump graft. ^{29,​ 30} This technique was also used with good results for the repair of dysesthesia after removal of the sural nerve, as well as to connect the phrenic nerve to the brachial plexus. End-to-side repair has been used to link the nerve gap after ulnar nerve injury, with median nerve as donor nerve, in addition to phrenic and spinal accessory nerve neurotization, and coaptations of palmar digital nerves and select cases of brachial plexus trauma. Viterbo and Ripari reported good outcome when they tried to restore lower limb sensation in paraplegics, thereby reducing the chances of formation of pressure sores, by linking the intercostal nerves above the site of injury and sciatic nerve in an end-to-side fashion using sural nerve graft. ³¹ However, Bertelli and Ghizoni reported poor results using this technique to repair radial nerve, C5 or C6 root rupture, and common peroneal nerve lesion. ³² It now appears that end-to-side repair would be ideal only in specific and limited clinical scenarios.

With microscopic magnification, following adequate mobilization of the recipient nerve, a small epineural window is created matching the size of recipient nerve end. As with other techniques, any terminal neuromas on the recipient nerve stump should be excised and healthy fascicles be properly visualized prior to coaptation, which is achieved with two to three microsutures placed 180 degrees apart through the epineurium.

9.6 Nerve Grafting

Nerve grafting is recommended whenever a direct repair is likely to result in excessive tension at the repair site. ³³ In the past, nerve stretching, bone shortening, extremity positioning, and stump mobilization were some of the procedures used to shorten the bridging gaps, most of which are now obsolete. In current clinical practice, the ideal choice to circumvent such a scenario is to use a nerve graft. Tubulization techniques may be used for smaller gaps (<3 cm), but larger defects need nerve grafts. ^{34,​ 35} Split repair is a technique which is used when there is partial injury to the nerves with damage to only a portion of the fascicles with relative sparing of the rest. In these conditions, the healthy fascicles are dissected from the injured ones and nerve action potential (NAP) recording is used. Usually, the NAP is recordable from the healthy fascicles and absent in the injured ones. The injured fascicles are then resected till normal fascicular anatomy is visualized and then coapted with a graft using an interfascicular technique. ¹⁰

9.6.1 Autografts

Although many options exist for bridging the gap, an autograft is used whenever possible. Several technical principles influence the success of nerve grafting. The proximal and distal nerve stumps are meticulously inspected, and any damaged portion or neuroma is resected. The epineurium is cut in a longitudinal fashion, and the fascicles are closely inspected under magnification. All fibrotic tissue amid these fascicles is removed using sharp dissection. The surgeon must make sure that the proximal and distal nerve stumps are tension-free even when the extremity is moved along its full range. The harvested graft should be kept moist and handled carefully to prevent injury. To avoid fascicular malalignment, the interfascicular tissue is retracted and the fascicles are defined in groups akin to fingers. The sensory or motor components should be matched as accurately as possible ( ▶ Fig. 9.2). However, this is practically feasible in only distal nerves. The number and length of the graft depend on the cross-sectional area and the bridging gap, respectively. In general, the graft length should be 10 to 20% longer than the gap, to provide room for retraction and shrinkage. The cross-sectional area of the graft is preferably smaller than the recipient nerve. Smaller diameter grafts are associated with better results as larger grafts have compromised vascularity in their core, thus leading to necrosis and greater scar formation. The small-diameter nerves obtain nourishment from their surface. ³⁶ Owing to this, it would be ideal to use multiple small diameter nerves for grafting major nerves ( ▶ Fig. 9.3). Sutures are taken through the epineurium in the host stump 180 degrees apart, to the interfascicular epineurium and perineurium of the isolated fascicles, spreading the cross section of the graft in a fish mouth pattern. Fibrin glue may be used to reinforce the repair. The surgeon must revisit all repair sites at the end of the procedure, as they can get distracted when repair is performed elsewhere. It is important to place the repair on a healthy vascularized bed to promote healing and reduce scarring.

The functional outcome is believed to be inversely proportional to the length of the graft, with poorer results with the use of longer grafts. Though seemingly true, this has to be viewed in a different light. Longer grafts are used when there is a greater nerve tissue loss, which in turn is usually seen in extensive and more proximal injuries. This is also associated with loss of neurons in the spinal cord or dorsal ganglia, which would substantially contribute to the negative outcome. Hence, the use of longer grafts is associated with more severe injuries and greater reinnervation time.

Siemionow et al described the single fascicle method of nerve repair. In experimental models, they could demonstrate faster regeneration and better functional outcome when single fascicle repair was performed on rat sciatic nerve covering 25 to 59% of the cross-sectional area of the nerve. They believed that this technique reduced foreign body reaction, intraneural fibrosis, and donor-site morbidity by reducing the amount of graft material required. ³⁷ Clinical application, however, has not been reported.

The commonly used donor nerve grafts are sural nerve, medial antebrachial cutaneous nerve above and below elbow, lateral antebrachial cutaneous nerve below elbow, superficial sensory radial nerve, dorsal cutaneous branch of ulnar nerve, and lateral femoral cutaneous nerve of thigh. The graft choice depends on site of nerve injury and surgeon’s preference. Whenever possible, the graft should be harvested from the same limb so that the surgery can be performed under regional anesthesia and an additional incision can be avoided ( ▶ Fig. 9.4). However, most often, sufficient graft length is not available from the injury site, leading to incision and exploration of the different region, thus increasing morbidity, operative time, and chances of wound complications. Moreover, harvesting of a nerve adjacent to the injured nerve would result in clinically unacceptable sensory loss.

The sural nerve is one of the most commonly used donor nerve grafts. It supplies cutaneous sensation to the posterior and lateral aspect of the lower one-third of the leg and also lateral aspect of the foot and heel. It can be easily harvested from the posterolateral lower leg. The sural nerve has a diameter of 2.5 to 4 mm proximally and 2 to 3 mm distally with around 9 to 14 fascicles fed by robust nutrient artery and veins. This contributes to the faster graft revascularization and better healing. The sural nerve can easily provide 30 to 50 cm of graft, making it the first choice when repairing large gaps. It is harvested with the patient in supine position with the lower extremity internally rotated and flexed at the hip, flexed at the knee, and dorsiflexed at the ankle. A longitudinal incision or multiple-step incisions may be used to obtain the nerve. The morbidity associated with this procedure includes calf tenderness, numbness along the lateral aspect of the foot, neuroma formation, and intolerable pain. In a study, 6.1% had clinically symptomatic neuromas and 9.1% were found to be dissatisfied with the numbness in the foot. ³⁸

9.6.2 Allografts

Allografts from cadaveric donors have been used rarely when the bridging gap is exceedingly high so that available autografts would not suffice. ³⁹ With allografts, surgeons have an unlimited length of nerve tissue available for grafting. They provide guidance and viable donor Schwann’s cells (SCs) to regenerating host axons. Allograft nerve is not as immunogenic as skin or muscle, but certainly requires immunosuppressive therapies to prevent rejection. Without such therapies posttransplantation, the donor nerves blood–nerve barrier is broken down, graft is revascularized, and infiltration of immune cells occurs, ultimately leading to graft rejection. ⁴⁰ However, Midha et al reported that the immunogenicity of allografts steadily decreased over time as the process of SC exchange from donor to host proceeds. ^{41,​ 42} The following are the strategies available today to prevent graft rejection:

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  MHC matching: MHC matching leads to better results, similar to any organ transplantation. Mackinnon et al, in a study of seven patients, demonstrated a return of sensory and motor function in six patients when ABO blood type matched donor allografts were used. Despite being covered with immunosuppressive medications, one of these patients experienced rejection. ³⁹

  
  
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  Nerve allograft preparation: Several methods of allograft preparation are reported in literature. Irradiation and freeze drying techniques were used initially in the 1960s. Subsequently, cryopreservation (10% dimethyl sulfoxide at -196°C in liquid nitrogen) and lyophilization techniques were used. In cold storage technique, allografts were harvested within 24 hours of death and were stored in university of Wisconsin cold storage solution at 5°C for 1 week. This decreased the antigenic load and hence the chances of rejection. Moreover, the doses of immunosuppressive agents could be reduced following cold storage. ⁴³

  
  
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  Immunosuppression: Most of the data for immunosuppressive strategies come from experimental models. Cyclosporine, which is a calcineurin inhibitor, was one of the first drugs to be tried with nerve allografts. It worked by blocking the transcription of interleukin-2, which played a significant role in the inflammatory cascade of rejection. Subsequently, tacrolimus (FK-506, also a calcineurin inhibitor) was found to be better than cyclosporine in terms of functional recovery and axonal regeneration. The graft pretreatment in cold storage substantially reduced the therapeutic doses of these drugs, thereby bringing down the undesirable side effects. ⁴³ Unlike cyclosporine, tacrolimus can rescue grafts within 10 days of onset of rejection. ⁴⁴

When decellularized allografts are used, immunosuppressive medications are not required as they are devoid of living SCs. These allografts act like a scaffold provided by the extracellular matrix for axon regeneration. ^{45,​ 46,​ 47} In a study by Karabekmez et al, 10 sensory nerve gaps in seven patients were reconstructed with AxoGen nerve allografts (decellularized allograft), the lengths of which ranged between 5 and 30 mm. Five patients achieved excellent results, and the other five patients had good results. ⁴⁷ AxoGen allografts are thought to have better results when compared to type 1 collagen conduits. ⁴⁸ Despite the lack of living SCs, several uncontrolled studies have reported good results with decellularized grafts. ^{47,​ 49} The authors do not advise use of decellularized allograft or tube repairs for gaps exceeding 3 cm (see Chapter 9.7).

9.7 Nerve Tubes

Despite being the gold standard in bridging the gap in peripheral nerve injuries, autologous nerve grafts come with several disadvantages such as donor-site neurological deficit, need for additional incisions and chances of wound complications, neuroma formation and neuropathic pain, limited availability, and so on. Only 40 to 50% of autologous nerve grafting show useful degree of functional recovery. ⁵⁰ These issues have paved the way to the study and use of nonnerve grafts as a conduit for axonal regeneration. A tube works by encasing the distal and proximal nerve ends, guiding axons sprouting from the regenerating nerve end, protecting them from fibrous tissue, and providing a path for diffusion of neurotropic and neurotrophic factors from the injured nerve stump. ⁵¹

An ideal conduit should be biodegradable and nontoxic to axons, produce minimal foreign body reaction and scarring, semipermeable, have an internal structure similar to the architecture of the nerve fascicle, provide protective environment to the nerve regeneration, and be easy to manipulate. ^{52,​ 53,​ 54} Some biomaterials used for tubulization are prone to swelling in vivo, which, if excessive, may block the tunnel and prevent nerve regeneration through it. Therefore, the tube diameter should exceed the nerve diameter by 20%. Conduits are expected to be resorbed gradually with the completion of axonal regeneration. Should this happen too fast, there will be focal inflammation and swelling. On the other hand, if it is too slow, it can cause compression of the regenerated nerve and chronic immune rejection. ⁵⁵

Technique: The healthy nerve stumps are inserted into the tube. Following this, a nonabsorbable microsuture is placed in a “U” fashion—outside to inside of the tube, then through the epineurium 1 to 2 mm behind the stump edge, then again from inside to the outside of the tube to tie a knot after pulling the stump into the lumen ( ▶ Fig. 9.5). The interior of the lumen is then filled with saline, using a small-gauge needle and syringe, to flush out any air bubbles. Fibrin glue is used to reinforce the ends. At present, tubulization techniques are indicated only for shorter nerve gaps (<3 cm). ^{35,​ 56}

Related posts:

Clinical Aspects of Traumatic Peripheral Nerve Lesions in the Lower Limb Nerve Injuries: Anatomy, Pathophysiology, and Classification Thoracic Outlet Syndrome Malignant Peripheral Nerve Sheath Tumors Ultrasound in Peripheral Nerve Surgery Nerve Anatomy of the Upper Limbs

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