Clinical Evaluation

The type and cause of injury is an important historical point to determine, because stretch, blunt trauma, or crush injuries typically produce more diffuse nerve injury than do penetrating injuries. The timing from the trauma to the development of neurological deficits is important. In most cases, the onset of neurological deficits occurs at the time of trauma, and delayed deficits may indicate injury from other complications, such as hemorrhage or edema. The neurological examination is crucial for determining the degree and distribution of deficits. However, in many instances, such as with multiple fractures of the extremity or alteration of consciousness with concomitant closed-head injury, it may be difficult to perform a reliable neurological examination. When possible, the examination should include careful assessment of motor function, including distribution and severity of weakness and atrophy, and of sensory loss, as well as of injury to associated soft tissue and supportive structures.

Electrophysiological Evaluation

Electrophysiological evaluation is a useful adjunctive test, performed in conjunction with the neurological examination, to assess peripheral nerve trauma. Electrophysiological studies generally consist of a combination of nerve conduction studies (NCS) and needle electromyography and are helpful in

Basic NCS are designed to evaluate the function of peripheral sensory and motor axons, striated muscles and the neuromuscular junction. NCSs are performed in two ways: (1) by stimulating a motor or mixed motor-sensory nerve and recording the action potentials of the muscle fibers innervated by the nerve or (2) by stimulating a mixed or pure sensory nerve at one site and recording the sensory nerve action potential at a distal or proximal site along the nerve. The combination of abnormalities in motor and sensory NCS allows identification of the site and pathophysiology of nerve injury.

Motor NCS are often more useful than sensory NCS in identifying the degree and stage of nerve injury. In a normal nerve, supramaximal electrical stimulation of a nerve depolarizes all of the motor axons within the nerve, which subsequently produce action potentials within all muscle fibers innervated by that nerve. This produces a summated compound muscle action potential (CMAP), or M wave, recorded from a muscle innervated by the nerve. When the nerve is stimulated at a proximal and distal site, the CMAP amplitudes and areas of the two sites are similar, inasmuch as all axons within the nerve are similar in size and conduct at a similar rate. In most motor nerves, there is never more than a 20% reduction in amplitude and area between the two sites of stimulation (Fig. 105-2).

Figure 105-2 Normal result of a motor nerve conduction study of the median nerve.

In nerve trauma characterized by neurapraxia or early axonotmesis, the evoked action potential initiated at a site proximal to the injury is unable to propagate through the lesion. Thus, the lesion produces a “conduction block” of the action potential. However, because the axonal segment and supporting structures distal to the injury remain intact, stimulation distal to the lesion produces a normal response. In the most severe cases in which all axons within a nerve are affected, such as with complete nerve transection or a neurapractic lesion involving all motor axons, no response is obtained with proximal stimulation (complete conduction block) (Fig. 105-3). Stimulation distal to the site of nerve injury produces a propagated action potential and a normal CMAP. In cases of incomplete nerve injury, only some axons are affected, and a partial conduction block may occur (Fig. 105-4). Stimulation proximal to the lesion produces action potentials in all the motor axons. Some percentage of these action potentials are propagated by motor axons that are damaged, and these action potentials do not spread through the lesion. There, action potential spread is blocked. Other motor axons in the nerve may be spared by the lesion, and these spread across the lesion to reach the muscle and produce a CMAP. The amplitude and area of the CMAP are a rough guide to the number of axons spared in an acute to subacute lesion. In more superficial nerves, or with near-nerve stimulation with a monopolar needle, the precise site of the nerve injury can be localized to within 2 cm by short-segment incremental stimulation (“inching”) studies.

Figure 105-3 Ulnar motor nerve conduction study with short segmental incremental stimulation technique demonstrates complete focal conduction block at the medial epicondyle.

Figure 105-4 Ulnar nerve conduction study (NCS) demonstrating partial conduction block in the forearm. ADM, abductor digiti minimi.

In neurapractic lesions, the conduction block persists until the underlying process is reversed. However, in lesions characterized by axonotmesis or neurotmesis, subsequent events produce further changes on NCS. Within the first 5 to 7 days after injury, the NCS simulates a focal conduction block that is indistinguishable from a neurapractic lesion, with normal conduction distal to the injury but block of conduction with stimulation proximal to the lesion. However, after 5 to 7 days, wallerian degeneration of the axons in the distal segment of the nerve occurs, leading to inexcitability of the distal nerve. This is manifest on NCS by a low or absent CMAP response with stimulation proximal and distal to the site of the lesion. Therefore, within the first week after injury, NCS is useful in localizing the lesion but not in determining severity or prognosis. However, after approximately 2 weeks, NCS can help the clinician distinguish neurapractic from axonotmetic lesions and better determine severity, pathophysiology, and prognosis, but in the case of axonotmetic lesions, it may be less helpful in precisely localizing the injury.

Sensory NCSs are less helpful in localizing nerve injury because of the wide variation of conduction velocities from different fiber sizes within sensory nerves. As a result, there is more dispersion of the response with distal to proximal stimulation. In nerve injuries, this normal dispersion in sensory nerve action potentials makes it difficult to identify conduction block in sensory axons. Sensory NCSs are useful in attempts to distinguish injury to the brachial plexus from root avulsion. In axonotmetic lesions localized distal to the dorsal root ganglion (e.g., brachial or lumbosacral plexus), sensory fibers undergo wallerian degeneration, which leads to low-amplitude or absence of sensory responses. However, in root lesions in which the dorsal root ganglia remain intact, the sensory NCS responses remain entirely normal despite profound sensory loss. Sensory NCSs are also very important in the study of injuries to pure sensory nerves.

Needle electromyography is used in conjunction with NCS to determine the pathophysiology, localization, and severity of nerve injury. Needle electromyography assesses spontaneous electrical activity arising from muscle fibers and the firing characteristics and structure of voluntary motor unit potentials. Fibrillation potentials are spontaneous action potentials from individual muscle fibers that are separated from the nerve terminal. Fibrillation potentials arise within 2 to 4 weeks after nerve injury and occur in muscles that are nearest the site of nerve injury before more distal muscles.

Each limb motor axon innervates hundreds of muscle fibers, and each limb muscle is innervated by several hundred motor axons. A basic concept of reinnervation that is often not understood requires some explanation. After motor axonal loss and denervation, reinnervation of skeletal muscle may occur in two basic ways. The loss of motor axons to a muscle may be incomplete or complete. If the axonal loss or denervation to a skeletal muscle is incomplete with some intact motor axons remaining, the surviving motor axons give off collateral sprouts from the nerve terminals near the muscle fibers that have lost their innervation. These collateral axonal sprouts from the surviving motor axons begin to reinnervate muscle fibers within a matter of days to weeks. Therefore, after incomplete lesions, reinnervation by collateral sprouting begins quickly. On the other hand, if all of the motor axons to a muscle are severed, reinnervation must occur by regrowth of axonal sprouts from the distal end of the proximal stump down the nerve to the end organ. This form of reinnervation takes much longer. Axonal sprouts grow at 1 mm per day, or 1 inch per month. In the case of complete axonal loss, the time to the beginning of reinnervation is determined primarily by the distance that the axonal sprouts have to travel to reach the end organ, and this takes months to years.

Electromyographic assessment of voluntary motor unit potentials is helpful in identifying whether reinnervation by regrowth or collateral spouting is occurring. In pure neurapractic lesions, the needle examination reveals a reduced number of voluntary motor unit potentials recruited when the patient attempts to produce a more forceful activation of the muscle under examination. There are no fibrillation potentials or change in the amplitude, duration, or structure of the motor unit potentials. In axonotmetic or neurotmetic lesions, the disintegration of the motor axons extends to the nerve terminal at the neuromuscular junction, and the muscle fiber is separated from its innervation. Immediately after the injury, the needle examination reveals reduced recruitment if the lesion is partial or no motor unit activity if the lesion is complete. In partial lesions, the structure of the motor unit potentials should be normal. Fibrillation potentials appear in the denervated muscles after 2 to 3 weeks. In partial or incomplete axonotmetic lesions, the nerve terminals of surviving motor axons begin to produce axonal sprouts 4 days after the injury. These effectively reinnervate some denervated muscle fibers after 3 weeks. At that time, the structure of the surviving motor unit potentials begins to change. There is an increased number of turns or phases on the motor unit potential. As more and more collateral sprouts from a motor neuron reinnervate muscle fibers, the motor unit potentials become more complex, larger in amplitude, and longer in duration.

In the case of reinnervation by regrowth of axons, the earliest motor unit consists of only one or a few muscle fibers, and as a result, the motor unit potential of those motor units is very small. These potentials have been called nascent motor unit potentials. As the reinnervating axons give off more branches that reinnervate more motor fibers, the number of muscle fibers innervated by each motor unit increases, and the amplitude and duration of the motor unit potential increase.

The needle examination is performed on different muscles innervated by different nerves, different components of the plexus, and different nerve roots and anterior horn cells. A systematic approach allows determination of the site of the lesion, the age and severity of the lesion, the type of pathology, and the prognosis for recovery.

In cases with electromyographic evidence of reinnervation, surgical intervention is often delayed or postponed, as described later.

Imaging of Peripheral Nerve Trauma

Historically, the sensitivity of imaging studies for identifying the anatomy of the peripheral nerve in detail was low, and imaging studies had low utility in the evaluation of peripheral nerve trauma. However, as the quality of imaging has improved, these studies are becoming increasingly useful adjunctive measures for assessing peripheral nerve trauma. Imaging studies can provide important information regarding the continuity of a nerve after trauma. Magnetic resonance imaging with short-time inversion recovery sequences can demonstrate denervated skeletal muscle, which is high in extracellular water content and thereby produces increased signal on short-time inversion recovery and T2-weighted images.⁵ The distribution of muscle involvement can be extrapolated to determine which nerve or nerves are affected by trauma. More recently, magnetic resonance neurography has evolved to allow for visualization of large peripheral nerves.^6,7 Indications for magnetic resonance neurography include the need to visualize roots and nerves for entrapments, adhesions, or the effects of trauma.⁸ In some cases, magnetic resonance neurography can identify discontinuity of the nerve and therefore is helpful in determining prognosis of recovery.⁸

Ultrasonography provides less detail of nerve anatomy than does magnetic resonance neurography, but it has been evaluated for its utility in monitoring patients who have undergone direct nerve repair after peripheral nerve injury.⁹ In a group of 11 patients, reliable identification of the nerve was made with ultrasonography, and neuroma formation, scarring with compression of underlying nerve, and partial discontinuity of nerve fascicles could be identified.⁹

In cases of injury to the brachial plexus in which root avulsion may have occurred, myelography and computed tomographic myelography are the imaging modalities of choice.¹⁰ The myelogram may demonstrate several findings to indicate root avulsion, including pseudomeningocele, poor root sleeve filling, and spinal cord edema or atrophy (Fig. 105-5). Although magnetic resonance imaging may also demonstrate findings suggestive of root avulsion, the findings on computed tomographic myelogram were correlated better with such injury at surgery than were the findings on magnetic resonance imaging.¹¹

Figure 105-5 Computed tomographic myelogram demonstrating pseudomeningocele after traumatic root avulsion.

Acute Nerve Transection or Laceration

Acute transection of the nerve is less common than blunt or compressive injury and occurs with clean, sharp lacerations, such as wounds inflicted by glass or knife injuries. Nerve transactions may also occur as a result of fracture of an adjacent bone or as an iatrogenic injury after inadvertent nerve transection during surgical procedures. In a study of 722 surgically treated cases of nerve trauma, approximately 17% were iatrogenic, the majority occurring during orthopedic procedures or minor surgery.¹⁴ The nerve most commonly affected was the spinal accessory nerve (after lymph node biopsy), followed by the common peroneal, radial, and genitofemoral nerves.

In most cases of nerve laceration, neurotmesis or complete transection of the entire axon and surrounding connective tissue structures occurs, producing a distinct separation of the two ends of the nerve. Depending on the length of the nerve separation, potential for regrowth or reinnervation is low. After clean nerve laceration, early surgical repair is usually necessary to align the two ends of the nerve. With lacerations related to blunt injuries, such as chainsaw or propeller blades, a delay of several weeks before surgical intervention may allow for identification and resection of damaged nerve tissue before realignment.¹⁵ In iatrogenic surgically induced nerve lacerations, the outcome after surgical intervention was good in approximately half of the patients, with some improvement in sensory, motor, or pain.

Chronic Nerve Compression

The most common type of focal nerve injury encountered in most clinical practices is focal nerve compression. Although this may occur acutely, such as when transient paresthesias are experienced after compression of the ulnar nerve (the “funny bone”), it more commonly occurs over an extended period of time. Chronic compression most commonly affects the median, ulnar, and peroneal nerves. Compression of the nerve may occur as the result of repeated external force against the nerve, such as repeated compression of the peroneal nerve from leg crossing, or as a result of compression of the nerve within a fixed or enclosed passage or compartment, such as that occurring in carpal tunnel syndrome or ulnar neuropathy in the cubital tunnel. Several factors predispose a nerve to compression injury, such as anatomical location of the nerve at a site that lies in direct contact with an unyielding surface, when the nerve lies in a fixed or fibrous canal or passes through fibrous tissue, or when the nerve crosses an extensor side of a joint.

The pathological changes that occur with chronic or repeated compression include mechanical and vascular changes. One of the first changes is focal demyelination at the site of compression. Experimental studies with tourniquet compression have been performed to produce a model of compressive lesions.¹⁶ In these studies, compression of the myelin with invagination and intussusception of paranodal regions was identified most prominently at the edge of the tourniquet. Over time, focal demyelination is followed by reduction in the axon diameter and, ultimately, axonal degeneration. However, if the cause is removed, reinnervation and remodeling of myelin may lead to recovery of nerve function and resolution of symptoms within weeks to months. In addition to the mechanical changes in the nerve, mechanical compression produces increased intraneural pressure, which in turn produces intraneural venous obstruction and capillary congestion.

The symptoms and findings of nerve compression depend on the severity and chronicity of the injury. Sensory nerves are more susceptible to compression than are motor nerves, and affected patients initially present with paresthesias or sensory loss in the distribution of the nerve. When motor fibers are affected, weakness in muscles distal to the site of compression becomes evident. With axonal loss, muscle atrophy may occur. As expected, when clinical and electrophysiological signs of axonal loss are present, the recovery, even if the inciting cause is removed, is more prolonged and may be less complete.

Stretch Injury

Stretch or traction is the most common mechanism of peripheral nerve injury after trauma and most commonly occurs with severe, violent trauma, such as that occurring in high-speed motor vehicle accidents. Less severe stretch injuries may occur after falls or surgical procedures (such as that occurring in the sciatic nerve after hip arthroplasty). Stretch injury is the most common type of traumatic injury affecting the brachial plexus and is a major cause of increased morbidity after motor vehicle accidents. In contrast to focal compression or laceration of the nerve, stretch injury produces traction and more mechanical strain on the nerves.

As discussed earlier, nerve fibers travel in a plexiform configuration within the fascicles, and supporting connective tissue structures, which assist in maintaining the structure and integrity of the nerve, surround the axons. Although the epineurium protects the nerve fibers from external compression, the perineurial tissue is most important in the protection against stretch injury, because it provides more of the elasticity and resistance than do other structures. Several features of nerves protect them from stretch injury: (1) the undulating course of the nerve fibers within the fascicle, (2) the anatomical course of nerves across flexor aspects of joints (with the exception of the ulnar nerve at the elbow and the sciatic nerve at the hip), and (3) the elasticity of the nerve trunks.¹⁷

When the nerve is stretched, stepwise alterations of nerve anatomy occur (Fig. 105-6). First, the undulations of the epineurial connective tissue disappear, although partial laxity of the nerve fibers remains unaffected. Next, with continued stretching, the nerve fibers become straightened, the cross-sectional area of the nerve is reduced, and the intraneural pressure is increased. Finally, with continued stretch, the nerve fibers become stretched and ultimately may rupture if continued tension is present.^2,17 Experimental studies with rabbit nerves have shown that with mild, gradual stretch to 30% of the initial nerve length, minimal macroscopic changes occurred and the epineurium, perineurium, and endoneurium remained intact; however, the cross-sectional area of the nerve was reduced, and the myelin became swollen. With more severe gradual stretch, epineurium rupture occurred. The mean elongation to the point of limit of elasticity was 56%. No significant difference was seen in the pattern of damage with gradual or sudden stretching.¹⁸

Figure 105-6 Stages of stretch injury to peripheral nerve (see text for description).

The structure of nerve roots differs slightly from that of distal nerves in that nerve roots lack perineurial tissue and are arranged in a nonplexiform manner, which makes roots more vulnerable to injury than nerves. Therefore, when significant traction is produced along the nerve, the root is the region of least resistance, and root avulsion is more common than avulsion of a distal nerve segment.

The severity of clinical features depends on the degree of stretch injury. In mild cases, a mild degree of motor and sensory loss may be present. However, in severe traction injuries, especially with nerve or root avulsion, the neurological deficits are much more severe and often complete. In addition, in most cases, the injury is more extensive, involving multiple nerves or root. In this situation, rupture of fascicles may occur over several centimeters of the nerve, which makes regeneration of the nerve less likely.

Injection Injury

Injection injury is nerve damage resulting from the injection of a pharmacological agent at or adjacent to a nerve. Injection injury is an uncommon cause of peripheral nerve trauma and has most commonly been described in the sciatic nerve after gluteal muscle injections. Injury to the sciatic nerve is most likely to occur in patients with wasting of the glutei muscles and may also be related to fixation of the nerve to the piriformis muscle. Injection injuries have been identified more commonly in infants than adults, probably because of the small size of the overlying musculature.

Patients with injection nerve injury typically develop neurological symptoms immediately or within minutes after the injection.¹⁹ Sharp stabbing or radiating pain in the distribution of the nerve is the initial symptom. Motor and sensory loss is common and occurs to a variable degree, ranging from severe weakness and sensory loss in the distribution of the injured nerve to only mild deficits. Spontaneous recovery is variable. Early reviews suggested that residual deficits persist in the majority of cases, with recovery in only 14%.¹⁹ Experimental studies of injection injury have demonstrated that regeneration of the injured nerve does occur, beginning 2 to 3 weeks after injection.²⁰

A number of mechanisms of nerve injury after injections have been proposed. The most supported mechanism is a direct toxic affect of the offending agent on the nerve. Several factors may be important in the development of nerve injury after injection. First, the nature of the offending agent may affect the degree of nerve injury. When injected intraneurally, many different pharmacological agents, including antibiotics, paraldehyde, and magnesium sulfate, produce significant nerve damage. In one animal study, injections of nine different agents produced a variable degree of pathological changes within the nerve. Meperidine and cephalothin resulted in minimal loss of myelinated and unmyelinated fibers, whereas severe nerve injury occurred after injections of penicillin, diazepam, and chlorpromazine, even when administered in the extrafascicular region.²⁰ Comparison of the degree of injury with dose of several medications indicated that higher doses resulted in more severe injury. Because most active components of medications are contained in a buffered mixture with other agents, it is difficult to determine whether the nerve response was a reaction to the active ingredient or to the buffering agent. Control studies with intrafascicular or extrafascicular saline injection produces no pathological change.²⁰

Second, the site of injection in relation to the nerve anatomy plays an important role in the development of nerve injury. Early studies have shown that injection in the epineurial region produces little no pathological change, although some medications such as paraldehyde may produce circumferential fibrosis. On the other hand, intraneural injections consistently produce inflammatory cell infiltration.^19–21 In addition to direct toxic effect of the infused agent, nerve ischemia caused by thrombosis or spasm of a nutrient artery may occur as a reaction to the toxic effect of the drug infused, or mechanical trauma from the needle may also injure the nerve.^22,23 The effect of the length of the bevel tip on the degree of nerve injury has been studied in mechanical nerve “impalement” and has demonstrated that shorter bevel tips produce more severe damage than do long bevel tips.²²

Treatment of injection injury is largely symptomatic. However, exploratory surgery with nerve irrigation or neurolysis has been proposed.²⁰

Ischemic Nerve Injury

Peripheral nerves are relatively resistant to ischemia, inasmuch as they are supplied by a network of longitudinally arranged arterioles and veins, with feeding arteries entering the nerve at several sites along the nerves. Therefore, pure ischemia of nerve after trauma is unlikely to occur without concomitant nerve compression, stretch, or crush. Experimental studies of ischemia in the nerve are sparse, because ligation of a feeding artery does not produce significant ischemia.^24,25 In a study on rat sciatic nerve, conduction failure occurred after 30 minutes of ischemia and was reversible if the ischemia persisted for less than 1 hour.²⁶ Dyck and associates found a patchy distribution of nerve fiber degeneration that began in a central fascicular location in watershed zones in the mid–upper arm and in the midthigh for the lower extremity after nerve ischemia in humans.²⁷

In many cases of peripheral nerve trauma, direct injury to the nerve from laceration, crush, or stretch produces nerve dysfunction. However, with these mechanisms of injury, interruption of the vascular supply surrounding the nerve may also play a role in the mechanism of nerve injury. Ischemic nerve injuries may occur after thrombosis that follows soft tissue trauma or bone fractures. This seems typically to result from bone and arterial lesions around the distal humerus, distal femur, and proximal tibia, where the arterial blood supply to nerves is more vulnerable because long sections of these nerves are dependent on a single nutrient artery. Embolization or graft thrombosis after aortofemoral bypass or peripheral vascular surgeries may produce ischemic damage to the distal tibial, distal peroneal, sciatic, or femoral nerves.²⁸ Similar complications have been reported after transfemoral intraaortic balloon assist pumps.²⁹ Therapeutic or accidental intra-arterial injection of drugs may result in severe arterial spasm and thrombosis with soft tissue and nerve damage.^23,30 Upper limb ischemia associated with artificial arteriovenous shunts for dialysis has produced ischemic damage to nerves.³¹

Radiation Injury

Radiationinduced nerve injury is a delayed manifestation of radiation therapy. This entity most commonly occurs in the brachial plexus in patients receiving radiation to the breast or axilla, but it may affect the lumbosacral plexus or individual distal nerves coursing through in other fields of radiation. The incidence of development of brachial plexus injury after radiation usually ranges from 1.8% to 5% but has been reported as high as 9%.^32–34 Clinical manifestations of radiation neuropathy include gradually progressive paresthesias and sensory loss, weakness and atrophy, and pain in the distribution of the nerve or nerves affected. Symptom onset occurs 1 month to 18 years after radiation exposure.^34,35 Several factors have been associated with an increased risk of development of brachial plexopathy, including a higher dose of radiation (greater than 5000 cGy), increased number of ports of radiation administration, the use of adjunctive chemotherapy, and the extent of axillary node dissection.^32–34,36 Although some authors have reported more selective involvement of the upper trunk of the brachial plexus, others have shown that the upper, lower, or entire plexus may be involved.^32,36–38

The underlying pathophysiology of radiationinduced injury has not been completely established. Pathological studies have demonstrated loss of myelin, the presence of fibrosis and thickening of the neurolemma sheath, and hyalinization and obliteration of the vasa nervorum to the brachial plexus, which are suggestive of either focal compression of the plexus by fibrosis or chronic nerve ischemia as possible underlying mechanisms.³²

Electrophysiological studies demonstrate abnormal motor and sensory findings and large motor unit potentials with reduced recruitment in the majority of patients. Myokymia is the hallmark clinical feature of radiation neuropathy and is seen as an undulation, wormlike rippling of the muscle. Myokymic discharges, spontaneously recurring bursts of motor unit potentials, are the electrophysiological correlate of myokymia and are found in up to 63% of patients with radiationinduced brachial plexopathies³⁵ (Fig. 105-7). The presence of myokymic discharges is helpful in distinguishing radiationinduced plexopathies from neoplastic plexopathies.^35–37 Neuroimaging studies may show increased or decreased signal and fibrosis in the region of the brachial plexus.³⁹

Figure 105-7 Myokymic discharge in radiationinduced plexopathy.

The course of radiationinduced neuropathy is usually one of steady progression or stabilization in 90% of patients, although cases of improvement have been reported.^36,40,41 There is no treatment established to reverse or improve the nerve injury, although surgical intervention, such as neurolysis or neurolysis with omental grafting, has been performed in some patients with variable improvement in symptoms.^42,43

Cold-Induced Nerve Injury

Cold-induced peripheral nerve injuries are uncommon causes of peripheral nerve trauma in peacetime. However, during wartime, military personnel exposed to prolonged cold, including trench foot, frostbite, and immersion foot syndrome, suffered manifestations of peripheral nerve injury. Early reports of immersion foot syndrome occurring during World War II described military personnel who developed skin abnormalities and sensory disturbances after exposure to immersion in nonfreezing water for prolonged periods of time.

Clinical manifestations of cold-induced peripheral nerve injury begin an average of 6 days after exposure and initially consist of hyperemia and skin edema. With more severe or prolonged exposure, vesicle and blister formation occurs, followed by skin necrosis and loss of tissue. Symptoms may persist for months to years after the initial injury.⁴⁴ Blair and colleagues reviewed the manifestations of cold-induced injuries in 100 patients 4 years after exposure during the Korean War.⁴⁵ The most commonly experienced residual symptoms included (1) neuropathic symptoms (recurrent pain, sensitivity to cold, numbness) and (2) signs of sympathetic overactivity (vascular changes, hyperhidrosis).^44,45 Pain is a prominent symptom; it may be described as aching, sharp, or burning and is aggravated by prolonged standing and cold. Electrophysiological studies in cold-induced peripheral nerve injury have demonstrated decreased sensory nerve action potential with slowed conduction velocity in the affected foot 6 months to 1 year after exposure.^46,47

Several mechanisms of cold-induced nerve injury have been proposed, including primary vascular constriction or venous stasis in the vasa nervorum, vascular occlusion caused by thrombus formation, and cellular changes produced directly by cold.⁴⁴ Early studies in cold-induced peripheral nerve injury demonstrated abnormalities in large myelinated fibers after cold exposure.⁴⁸ More recent experiments on rat sciatic nerves have also demonstrated degeneration of large myelinated fibers, occurring within 48 hours after exposure.⁴⁹ Although the duration of exposure is important in the development of nerve injury, repeated exposure with rewarming plays a crucial role in extending the degree of nerve injury. Experimental studies on rat sciatic nerves demonstrated that the amplitudes of compound nerve fiber action potentials and recovery of nerve blood flow to nerves that were exposed to intermittent cooling and rewarming were significantly reduced in comparison with those of nerves exposed to continuous cold for the same duration.⁵⁰ Furthermore, pathological analysis demonstrated preservation of myelinated and unmyelinated fibers after continuous cold injury but axonal degeneration with intermitted cooling.⁵⁰ These findings suggest that initial insult to the nerve after cold exposure results from factors such as prolonged vascular stasis, endoneurial anoxia, and direct injury. However, rewarming produces further nerve damage, possibly from free radical injury.⁵⁰

Treatment of cold-induced nerve injury is largely symptomatic. Agents previously used include anticoagulants, sympathetic blocking agents, and sympathetic blocks but have not been systematically studied.⁴⁴

Electrical Nerve Injury

Electrical injuries to peripheral nerves are uncommon and usually occur in the context of more severe or diffuse electrical injury of an extremity. In an early study of electrical injuries in 64 patients, 13% of patients developed peripheral nerve complications.⁵¹ The site of nerve injury is correlated with the site of electrical contact. Extensive tissue destruction and burn are often present.⁵¹ The anatomical distribution of nerve injury follows the path that the electrical current takes. Factors that affect the extent of nerve injury include the duration of contact, the voltage of the exposure, and the current density within the tissue.⁵²

Peripheral nerves are very sensitive to electrical forces and have a lower resistance to current flow than blood, muscle, skin, tendon, or bone.⁵³ The pathway of electrical current typically follows the course of neurovascular bundles because of its lower resistance to electrical current. Several mechanisms have been implicated in the pathogenesis of electrical nerve injury. The immediate and acute injuries to motor and sensory fibers are the direct result of the electrical current.⁵⁴ The mechanism of electrical nerve injury is related to the propagating electrical current through the skin and deeper tissues to the nerves. The electrical current results in heating of the tissue and the buildup of electrical charge along the nerve membrane. In most instances, only a few seconds of exposure are necessary for the high-energy electrical trauma to occur. The current is denser at the closer proximity to the contact point; however there is often nonuniform exposure along the electrical field, which makes the pattern of tissue involvement variable. Pathological studies have suggested that permanent changes in the nerve do not extend beyond the area of local destruction.^53,54 Persistent or delayed damage results from thermal or mechanical injury, fibrosis of the perineural tissues, or thrombosis of nutrient blood vessels.⁵³

The clinical manifestations of electrical nerve injury most commonly include sensory disturbances, such as paresthesias, dysesthesias, and sensory loss, which may resolve within hours or days. The nerves most commonly affected are the median and ulnar nerves.^51,53 In addition, sympathetic dysfunction may begin within hours, producing pain, burning sensation, and allodynia in the distribution of the nerve. Months after the injury, other sudomotor autonomic signs may manifest, including muscle atrophy, hair loss, and osteoporosis. Weakness occurs in more severe exposure but may be related to direct skeletal muscle injury, as well as neurogenic injury. Muscle swelling, myonecrosis, and compartment syndromes may also occur.

The evaluation of electrical nerve injury occurs after the patient has been medically stabilized from a cardiovascular and respiratory standpoint. Careful neurological examination is necessary for documenting the degree of weakness and sensory loss. Electrophysiological studies (NCS and needle electromyography) can be a useful adjunct to determining nerve function.

Treatment of electrical nerve injury is predominantly supportive, rehabilitative, and focused on pain management. Early surgical intervention with fasciotomy and escharotomies may be effective for reducing increasing pressure from compartment syndromes. Neurological manifestations may persist for years after exposure, and the degree of recovery is variable.⁵⁵ In one study of more than 2000 patients with electrical injuries over a 20-year period, approximately 8% sustained long-term peripheral nerve manifestations, including pain, sensory loss, and weakness.⁵⁶

Surgical Treatment

The surgical treatment of traumatic nerve injury is dependent on the etiology, type, and pathophysiology of injury and the timing of evaluation in relationship to the injury. In many cases, surgical intervention provides an opportunity for more rapid and significant recovery of function, although one of the most difficult treatment decisions is the determination of the need for surgical intervention and the appropriate timing of surgery. Spinner and Kline (2000) reviewed the management of peripheral nerve injuries.¹⁰ When the decision to surgically intervene is being considered, electrodiagnostic studies can be helpful in the determining how many axons are injured and whether the lesion is neurapractic or axonotmetic. Neurapractic lesions are more likely to recover spontaneously and are generally treated nonsurgically unless they persist longer than expected. In contrast, minimal and protracted recovery is expected with axonotmetic lesions, and therefore surgical intervention may help improve the chance and rapidity of recovery.

Early surgical intervention may be considered immediately after the injury as primary repair or after a short delay of 3 to 4 days as delayed primary repair. Immediate primary repair is usually recommended when there has been a clean laceration of the nerve by a sharp object and where the nerve endings are not injured by crush or stretch. When a clean division of the nerve has occurred, end-to-end suture repair within 72 hours is recommended.¹⁰

In most other situations, it is often necessary to delay surgery by weeks to months. Secondary repairs may be performed as early as 2 to 4 weeks after the injury or 3 to 6 months after the injury. In some cases, surgery may be performed as late secondary repairs 1 to 2 years after the injury. Secondary early surgical repair after 2 to 4 weeks is generally recommended for blunt injuries or injuries with extensive soft tissue damage in which the nerve injury appears to be complete or very severe. In this situation, neuroma and scarring may develop within several weeks after trauma. Delaying surgery by several weeks allows for better determination of neuroma formation and scarring, and resection of the neuroma and scarring may improve recovery. When these scarred nerve stumps are resected, the growth cones of the new nerve endings may grow more rapidly.⁵⁷ However, in many cases, surgery is usually delayed between several weeks and 6 months in order to determine the degree of spontaneous improvement. If the nerves remain in continuity and nerve regeneration is evident clinically or electrophysiologically during this time, surgical intervention is unlikely to be more beneficial than physiological recovery and is not recommended, because approximately 90% of patients in these cases recover.¹⁰ In one series, secondary repair 3 weeks to 3 months after sciatic nerve injury resulted in useful motor recovery in the tibial nerve in 83% of patients and the peroneal nerve in 39%.⁵⁸ Useful recovery was achieved in 71% with thigh lesions and in only 31% with buttock-level lesions. Late surgery 1 to 2 years after the injury has not generally resulted in good recovery of motor function but may be necessary for pain control or to resect a neuroma.

A variety of operative methods can be used to attempt to improve nerve function after nerve trauma^10,59 (Table 105-3). Details of each method are beyond the scope of this chapter, but the neurosurgical literature contains more extensive reviews of this subject.^10,59 One of the simplest procedures is internal neurolysis, which consists of opening the epineurium and separating out the different fascicles under magnification. The surgeon then inspects the individual fascicles and stimulates and records from them to determine which fascicles are intact. After internal neurolysis, the surgeon separates the fascicles within the nerve, and if some fascicles are interrupted or not functional, the surgeon attempts to identify the distal and proximal stumps, match up the fascicles, and suture together the distal and proximal stumps of the matching fascicles. If there is no evidence of viable axons crossing the injured area of the fascicle, the injured segment is resected back to normal-appearing nerve, and an end-to-end repair or graft repair is performed. These procedures risk damage to the blood supply of the nerve and damage to branches of the fascicles either leaving the nerve or passing from one fascicle to another, as well as scar and neuroma formation.

TABLE 105-3 Operative Methods Used to Treat Nerve Injury

Intraoperative electrophysiological monitoring can be useful to determine the precise borders of the nerve injury and determine whether nerve action potentials can be conducted through the injured segment.³ The prognosis after surgical intervention varies according to the procedure performed. Direct suture repair carries the best prognosis, with approximately 79% of patients demonstrating recovery, whereas only 50% experience improvement with graft repair.¹⁰ Furthermore, in brachial plexus injuries, there is a better chance of recovery with upper trunk/lateral cord lesions than with lower trunk/medial cord lesions. Contraindication to surgical intervention include delayed evaluation (more than 1 year), C8-T1 root avulsion, or other comorbid conditions.¹⁰

In more severe cases of nerve rupture, the retracted ends of the nerve are identified and the surgeon must then make an evaluation of the condition of the distal and proximal ends of the nerve to determine whether the two separated ends of the nerve can be approximated without subjecting the nerve to too much tension or stretch. The damaged portions of the nerves are trimmed, and the fascicles of the proximal stump are aligned with fascicles of the distal stump under magnification. Then the proximal and distal stumps are connected either by sutures in the outer epineurium (epineurial repair) or in the interfascicular epineurium (grouped fascicular or fascicular repair) or by using nonsuture techniques. Nonsuture techniques have included wrapping the nerve; gluing the ends together with plasma clot or fibrin glue; or use of the carbon dioxide laser to weld the nerve ends together. Suture line tension must be minimized by mobilization of the nerve, positioning, and postoperative immobilization. If the gap is too large and suture line tension would be too great, then nerve grafting must be considered.

Spinner and Kline (2000) gave some general guidelines based on their experience.¹⁰ They found that injured nerves with a measurable nerve action potential transmitted across the lesion during intraoperative nerve stimulation have a good recovery of function in 90% of cases. Good functional results can be expected in about 70% of end-to-end repairs and in 50% of graft repairs. Characteristics with a better outcome include (1) shorter nerve grafts, (2) early surgical intervention, and (3) young age of patients. Proximal lesions do worse than distal lesions, and lesions in the lower trunk brachial plexus do worse than those in the upper trunk.

If a long segment of nerve is damaged or a long gap is present between the two retracted ends of the nerve, it may not be possible to perform an end-to-end repair of the nerve, and a nerve graft may be necessary to bridge the gap. With this technique, the axonal sprouts must cross two gaps, which slows growth, increases the risk of neuroma formation, and increases the risk that the axonal sprouts will not reach the proper end organ. However, grafts up to 20 cm in length have been used successfully. The survival and success of the graft depend on the quality of the operative bed, the vascular supply of the graft, and the thickness of the graft. Nerve grafts may be autologous (from the same patient), allografts (from another human), xenografts (from another species), or artificial or synthetic.⁶⁰ Autologous nerve grafts from a remote donor site are the most commonly used technique for bridging a nerve gap. Various nerve guides have been used to direct axonal sprouts toward the distal stump, including silicone tubes, collagen-based nerve conduits, and a biodegradable polyglycolic acid-collagen tube filled with laminin-coated collagen fibers.^59,61 Vanderhooft⁶² and Frykman and Gramyk⁶³ reviewed the results of nerve grafting. In combining results from multiple centers, grafting of digital nerves produced good or better results in 50%. Even with a delay between injury and repair of up to 6 months, 90% of patients achieved useful recovery. MacKinnon and Dellon performed grafts by using polyglycolic tubes in carefully selected patients and reported good results in 86%.⁶⁴

Other procedures, such as end-to-side nerve anastomosis have been used.^65,66 The distal segment of the injured nerve is sutured in an end-to-side manner to an adjacent nerve trunk, usually after an epineurial window and sometimes a perineurial window are formed in the donor nerve. The distal degenerated nerve segment attracts collateral sprouts from the healthy intact axons. The collateral sprouts from the donor nerve theoretically reinnervate the distal segment of the injured nerve. In the future, peripheral nerve repair may employ tissue engineering, neurotrophic factors, immunosuppression, and bioimplants.

In cases in which the nerve injury is so severe that primary repair or grafting is impossible, such as root avulsion or proximal nerve injuries, then neurotization or nerve-to-nerve anastomosis may be employed. They are also useful in cases of destruction of a very long segment of nerve or cases of a long time between the injury and repair.⁶⁷ For example, if the musculocutaneous axons to the biceps are destroyed very proximally, a portion of the median nerve can be divided and connected to the musculocutaneous nerve near the point where the musculocutaneous nerve enters the biceps. Nath and MacKinnon reported excellent recovery of biceps strength with this technique in 20 of 22 patients.⁶⁷ Various neural structures such as the cervical plexus, contralateral spinal nerves, or components of the brachial plexus, spinal accessory nerve, phrenic nerve, pectoral nerves, and intercostal nerves have been employed. These nerves are severed, and the ends are connected primarily or by graft to a distal nerve such as the musculocutaneous, radial, or median nerve. The interposing nerve graft is usually taken from the sural nerve. More recently, muscles such as the gracilis have been removed from the lower extremity with particular care to preserve the nerve and vascular supply to the muscle. Then the muscle is transferred to the upper extremity and the nerve connected, usually to one of the intercostal nerves. Such neurotization procedures have resulted in effective elbow flexion in 25% to 50% of cases. A clinically useful outcome of such reinnervation requires training to produce central motor reorganization. As knowledge of the neurotrophic and neurotropic effects of various growth factors expands, it is possible that systemic or local administration of these agents may be used to enhance neuronal survival and promote regeneration.

Symptomatic Treatment

In addition to potential surgical intervention, a multidisciplinary approach to therapy is necessary. Physical therapy should be instituted as early as possible after injury. Physical and occupational therapy are key in preventing contractures or overstretching of muscles and ankylosis of joints and directing rehabilitation. Other considerations include the optimal use of prostheses, splints, or slings. It is extremely important to protect skin, muscles, tendons, and joints from secondary complications while nerve regeneration or recovery is awaited. Splinting in the best physiological position helps prevent stretching or contractures. Active and passive range-of-motion exercises must be performed. There should be careful design and timing of exercise programs.

Neuropathic pain is a major cause of morbidity after nerve trauma and may be as disabling as loss of function. Pharmacological treatment of nerve pain may include anticonvulsants, tricyclic antidepressants, or opioid medications.