Anatomy and Physiology

A few basic principles underlie the anatomy of the peripheral nervous system. Each peripheral nerve is composed of fibers from more than one spinal nerve root; correspondingly, each spinal nerve contributes fibers to more than one peripheral nerve. Consequently, whereas spinal nerve lesions manifest in the clinical picture of radiculopathies with dermatomal sensory disturbances and mild to moderate weakness of muscles supplied by the spinal nerve, peripheral nerve lesions manifest in more precise borders of sensory disturbances acutely and more severe atrophy and paresis of muscles supplied solely by the peripheral nerve as time elapses.

The microscopic anatomy of the peripheral nerve comprises nerve fibers, fascicles, connective tissue (epi-, peri-, and endoneurium), blood vessels, lymphatics, and nervi nervorum (Fig. 32.1). Although the fascicular pattern may change as the nerve courses more distally, the general structure of the nerve remains constant. After a peripheral nerve is injured, a coordinated sequence of events occurs to remove the damaged tissue and ultimately initiates the regenerative process. When the nerve is disrupted, the severed ends retract owing to the elasticity of the endoneurium. Trauma to the vasa nervorum leads to robust inflammation triggering fibroblasts to proliferate to form the basis for a dense scar at the injury site: in the most severe cases, the nerve ends become markedly disorganized, with fibroblasts, macrophages, capillaries, Schwann cells, and collagen fibers within which the regenerating axons form disorganized masses known as neuromas. The degree of damage sustained by the proximal segment and neuronal cell body depends on the distance of the zone of injury from the cell body. The nucleus migrates to the periphery of the cell and select cytoplasmic elements (e.g., Nissl granules, endoplasmic reticulum) undergo chromatolysis. Cell survival relies upon the Schwann cells and trophic molecules present in the immediate environment.

FIGURE 32.1 Microscopic anatomy of the peripheral nerve.

Conversely, the distal portion of the axon undergoes Wallerian degeneration within hours after injury; this granular disintegration of the cytoskeleton and axoplasm occurs over several days to weeks, yielding empty endoneurial tubes. Early after injury, until the distal axons are totally degenerated, motor conductivity and sensory nerve potentials still can be observed in the distal segment; therefore, electrodiagnostic studies, used to predict severity of the lesion and to guide treatment recommendations, should not be performed within the first several weeks after injury.

When a peripheral nerve is injured, the accompanying muscle is denervated. Denervation leads to a series of structural changes and atrophy of the muscle if neural regeneration does not occur. Atrophy is seen as a mean 70% reduction in the cross-sectional area after 2 months.³ Sodium channels regress toward embryonic forms with altered biochemical properties, and acetylcholine receptors redistribute to cover the entire muscle surface. This supersensitivity to acetylcholine manifests clinically as spontaneous uncoordinated muscle activity, otherwise known as fibrillation. Death of muscle fibers generally does not occur, but when it does, dropout occurs between 6 and 12 months after denervation.

Pertinent History of Injury

Pertinent history regarding the timing and location of the motor and sensory disturbances is critical for an accurate assessment of the acute nerve injury. For instance, an immediate neurological deficit coincident with the injury implies direct involvement of the peripheral nerve at the site of injury. In contrast, a delayed neurological deficit implies consequent involvement of the peripheral nerve, as with reduction of fractures, injections, or tourniquet application. If the motor and sensory disturbance progressively worsens, an enlarging adjacent lesion compromising the nerve (such as a hematoma, pseudoaneurysm, or pressure from a cast or splint) must be considered and urgently addressed. Additionally, with time, a bony callus can form causing a progressive neurological deficit such as in tardy ulnar palsy.

The description of the mechanism of injury can also yield information about the severity of injury to the nerve and guide treatment. For instance, if the injury involved low/no impact such as a fall from a standing position, neurapraxia will be the likely result. In contrast, if there is high impact as in extreme sports or high-speed motor vehicle accidents, then the likely injury is axonotmesis or neuronotmesis. This classification of nerve injury described by Seddon and associates in 1943⁴ and expanded by Sunderland and colleagues in 1951⁵ (Fig. 32.2) remains useful today, although most injuries occur along the continuum of pure grades.

FIGURE 32.2 Seddon and Sunderland classifications of nerve injuries.

Nerve injuries can also be classified as preganglionic or postganglionic, with profound surgical implications (Fig. 32.3). A preganglionic injury implies injury proximal to the dorsal root ganglion with permanent paralysis of the muscles innervated by the avulsed roots, complete sensory loss of the corresponding dermatomes, and most importantly, the preclusion of spontaneous recovery. A postganglionic injury potentially retains function of the cell body within the ventral horn of the spinal cord and these neurons may regenerate axons in the appropriate conditions. Acute nerve injuries can be classified as open or closed. Open injuries include sharp lacerations and missile wounds whereas closed injuries include traction or compressive injuries. Current guidelines recommend early repair (days) of clean, sharp nerve lacerations, and the delayed (weeks) repair of ragged or dirty nerve lacerations. Missile wounds with vascular injury should be explored acutely. Early intervention is generally not recommended in closed injuries because of the potential for neurapraxic injury. Spontaneous regeneration, when it occurs, generally yields superior functional outcomes when compared to iatrogenic repair or reconstruction. Consideration of the clinical implications of these issues led to an algorithm for the surgical management of peripheral nerve and brachial plexus injuries⁶ (Fig. 32.4).

FIGURE 32.3 Pre- and postganglionic nerve injury.

FIGURE 32.4 Algorithm for surgical management of peripheral nerve and brachial plexus injuries.

(Modified from Dubuisson A, Kline DG. Indications for peripheral nerve and brachial plexus surgery. Neurol Clin 1992;10(4):935-951.)

Directed Physical Examination

The directed physical examination can be divided arbitrarily into several parts (Box 32.1). Inspection and observation initiate the examination. The presence of bruises, abrasions, and obvious lacerations can lead the examiner to the site of nerve injury: for example, road rash over the shoulder implies an upper brachial plexus injury, whereas road rash in the axilla extending along the chest wall implies a lower brachial plexus injury. Likewise, Horner’s sign (ptosis, meiosis, anhydrosis) is indicative of a potential proximal T1/lower trunk brachial plexus lesion. Significant swelling can imply musculoskeletal injury such as a ruptured muscle/tendon in addition to the nerve injury in the absence of motor function. As described earlier, the observation of fasciculations and atrophy with time are also consistent with peripheral nerve injury.

An assessment of the relevant vasculature is a critical part of the directed physical examination because of the adjacent course of nerves and vessels. For example, the cords of the brachial plexus surround the axillary artery, and the median nerve courses adjacent to the brachial artery. Injury to the vessel can indicate simultaneous injury to the nerve, and the integrity of both should be assessed in the acute situation.

The motor examination should be conducted in the context of range of motion. If the range of motion is acutely compromised, musculoskeletal injury should be considered and motor power can be difficult to assess. To assess nerve function, there is no substitute for a thorough motor examination; the complete description of the motor examination lies outside the scope of this chapter but can be found in Aids to the Examination of the Peripheral Nervous System,⁷ among other texts.⁸ The importance of a thorough assessment of relevant muscles cannot be overemphasized because the standard cursory trauma examination can be misleading. Muscles in the distribution of noninjured nerves can simulate the motor function of the injured nerve to the inexperienced examiner: abduction of the fingers (ulnar nerve) can be mistaken for extension of the fingers (radial nerve), leading to the incorrect conclusion that the radial nerve is intact. A systematic examination of all muscles supplied by the relevant nerve(s) can preclude such errors.

The testing of sensory function is important but is often difficult and can be misleading. Observations should be made in the autonomous zones where the overlap in the innervation from adjacent nerves is minimal.

The presence of Tinel’s sign can be indicative of a regenerating nerve, but whether the regeneration will be adequate to confer functional movement cannot be ascertained. Tinel’s sign indicates an ectopic mechanosensitivity and can be used to assess the growth of a nerve; the expected progression is 1 mm per day distally in accordance with the extending axon. Failure of Tinel’s sign to progress at the expected rate would suggest the need for surgical exploration.

Ancillary Studies

Electrodiagnostic studies (EDS) can aid in defining the site of injury and the potential for reinnervation of affected musculature. Baseline EDS are best performed 3 or more weeks after injury for reasons described earlier. Serial EDS can document clinically significant regeneration. Lack of innervation of paraspinal muscles implies a proximal injury. Sensory nerve action potentials (SNAPs) and somatosensory evoked potentials (SSEPs) are also useful in determining the site of injury; presence of a normal SNAP in the absence of SSEPs implies a preganglionic injury.

Radiographic studies may include long bone, cervical spine, and chest radiographs, which can reveal associated fractures, and in the case of brachial plexus injury, can demonstrate an elevated hemidiaphragm (phrenic nerve injury). Postmyelogram computed tomography (CT) and magnetic resonance imaging (MRI) can be used to detect pseudomeningoceles (Fig. 32.5), which are often associated with preganglionic injuries. The present resolution provided by standard imaging techniques is yet unable to demonstrate direct evidence of the site and severity of nerve injury.

FIGURE 32.5 Postmyelogram computed tomography scan demonstrating pseudomeningocele (arrows).

Surgical Options

Neurolysis is the removal of scar tissue from around the nerve (external neurolysis) or between fascicles (internal neurolysis) if the nerve is injured asymmetrically. Dissection is started with proximal and distal uninjured nerve ends toward the involved injured segment. Intraoperative EDS can determine if the injured segment can conduct electric signal. The presence of nerve action potentials (NAPs) across an involved segment implies that neurolysis alone is adequate for neural recovery (Fig. 32.6).⁹

FIGURE 32.6 Nerve action potential electrodiagnostic tracing.

(From Spinner RJ, Kline DG. Surgery for peripheral nerve and brachial plexus injuries or other nerve lesions. Muscle Nerve 2000;23(5):680-695.)

Direct (end-to-end) repair is possible only if a short nerve gap exists after resection of the nonfunctioning neural segment. Direct repair is preferred over indirect (graft) repair because of better functional results. Tension across the repair must be avoided to reduce the risk of failure of regeneration. Reducing tension across the repair can be achieved with proximal and distal mobilization of the nerve and optimal position of the surrounding soft tissues/bony elements to shorten the nerve gap distance. Direct repair is performed by coapting the ends with sutures if the repair crosses tissue planes, or by approximating the ends with tissue-fibrin glue if the repair lies within a tissue plane.

Graft (indirect repair) is needed when the gap that exists after resection of the nonfunctioning neural segment is too large for direct approximation without tension (Fig. 32.7). The length of the graft should be the length of the gap plus 10%. Autograft is usually used and derived from sural nerve, medial antebrachial cutaneous nerve, or superficial radial nerve because these small-caliber grafts achieve better results (faster revascularization) than larger-caliber grafts.¹⁰ Coaptation of the ends of the graft to the proximal and distal stumps is similar to that used for the direct repair. Artificial grafts are under active investigation but are not yet routinely used for repair of major nerves.

FIGURE 32.7 Graft repair of an injured brachial plexus.

Nerve transfers/neurotization have augmented the surgical arena for the treatment of peripheral nerve injuries, particularly of brachial plexus injuries, especially in the context of avulsion (preganglionic) injury.^11,12 Nerve transfers have changed the outlook for the “unrepairable” injuries to “reconstructable” injuries by coapting a proximal functional nerve donor with a distal denervated nerve to reinnervate the latter with healthy donor axons. Popularized nerve transfer techniques include neurotization of the spinal accessory to the suprascapular nerve^13–16 or radial branch to axillary nerve^17,18 to achieve shoulder abduction and intercostal,^19–21 medial pectoral,^22,23 phrenic,^24,25 or ulnar fascicular nerve transfer to the musculocutaneous nerve (Fig. 32.8)^26,27 for elbow flexion. Recovery of the translated function appears to rely upon cortical plasticity.²⁸

FIGURE 32.8 Transfer of ulnar nerve fascicle to musculocutaneous nerve.

Postoperative Care

After nerve repair/reconstruction, appropriate joints can be immobilized for 3 to 6 weeks to allow the nerve suture lines to heal. Afterward, physical/occupational therapy is recommended for range of motion (prevent contractures) as well as for maintaining strength in the unaffected muscles and the affected muscles when reinnervation occurs. Patients should be informed that recovery is a long process, which may last several years. The treatment of pain with Neurontin/Lyrica, certain tricyclic antidepressants, and other agents, or later by neurosurgeons employing dorsal root entry zone (DREZ) procedures can aid in recovery. Documenting recovery following peripheral nerve repair/reconstruction relies upon clinical and electophysiological examinations. Additional augmentation of function via muscle/tendon transfers may be considered for those who are motivated to request other treatment options to maximize the functional outcome.

Outcomes After Nerve Surgery

Outcomes for functional repair of sharp lacerations of the median and radial nerves have been reported to be as high as 91% in contrast to 73% for ulnar nerves; similarly, for graft repair, functional outcomes were better for the median (68%) and radial nerves (67%) than for ulnar nerves (56%).²⁹ Outcomes for ulnar fascicular transfer to the musculocutaneous branch to biceps has been reported at 75% for antigravity elbow flexion with an average time for reinnervation at 5 months.²⁷