Nerve Root Avulsion

The spinal roots have approximately one-tenth the tensile strength of the peripheral nerves because of lesser amounts of collagen and the absence of epineurial and perineurial sheaths in the roots. Therefore, the nerve roots are the weak link in the nerve root–spinal nerve–plexus complex, and nerve root avulsion from the spinal cord typically results from a severe traction injury affecting the upper limb. Ventral roots are more vulnerable to avulsion than dorsal roots, a consequence of the dorsal roots having the interposed DRG and a thicker dural sheath. In most cases, root avulsion occurs in the cervical region. Lumbosacral nerve root avulsions are rare, with only 35 cases reported between 1955 and 1996, and when they occur are generally associated with fractures of the sacroiliac joint with diastasis of the symphysis pubis or fractures of the pubic rami (Chin and Chew, 1997).

Avulsion at the level of the cervical roots can be total, as for a motorcyclist injury, or can result in two clinical syndromes of partial avulsion. One is Erb-Duchenne palsy, in which the arm hangs at the side internally rotated and extended at the elbow because of paralysis of C5- and C6-innervated muscles (the supraspinatus and infraspinatus, deltoid, biceps). The second is Dejerine-Klumpke palsy, in which there is weakness and wasting of the intrinsic hand muscles, with a characteristic clawhand deformity due to paralysis of C8- and T1-innervated muscles. Injuries responsible for Erb-Duchenne palsy are those that cause a sudden and severe increase in the angle between the neck and shoulder, generating stresses that are readily transmitted in the direct line along the upper portion of the brachial plexus to the C5 and C6 roots. Today, motorcycle accidents are the most common causes of this injury, but the C5 and C6 root avulsions classically occurred in the newborn during obstetrical procedures. Brachial plexus injuries in the newborn are discussed in Chapter 80. Dejerine-Klumpke palsy occurs when the limb is elevated beyond 90 degrees and tension falls directly on the lower trunk of the plexus, C8, and T1 roots. Such an injury may occur in a fall from a height in which the outstretched arm grasps an object to arrest the fall, leading to severe stretching of the C7, C8, and T1 roots, or during obstetrical traction on the extended arm when delivering the baby arm first.

Disk Herniation

Beginning in the third or fourth decade of life, cervical and lumbar intervertebral disks are liable to herniate into the spinal canal or intervertebral foramina and impinge on the spinal cord (in the case of cervical disk herniations), nerve roots (in both cervical and lumbosacral regions), or both (at the cervical level where on occasion large central and paracentral disk herniations may produce a myeloradiculopathy) (see Chapter 73).

Two factors contribute to this alteration in the intervertebral disks: degenerative change and trauma. The fibers of the annulus fibrosus that surround the nucleus pulposus lengthen, weaken, and fray with age and use, thereby allowing the disk to bulge posteriorly. In the setting of such changes, relatively minor trauma leads to further tearing of annular fibers and ultimately to herniation of disk material. This “soft-disk” herniation occurs mainly during the third and fourth decades of life when the nucleus is still gelatinous. In fact, although disk herniations may be preceded by unaccustomed strain or direct injury, in many instances there is no history of clinically significant trauma preceding the onset of radiculopathy.

Reinforcing the annulus fibrosus posteriorly is the posterior longitudinal ligament, which in the lumbar region is dense and strong centrally and less well developed in its lateral portion. Because of this anatomical feature, the direction of lumbar disk herniations tends to be posterolateral, compressing the nerve roots in the lateral recess of the spinal canal. Less commonly, more lateral (foraminal) herniations compress the nerve root against the vertebral pedicle in the intervertebral foramen (Fig. 75.3). On occasion, the degenerative process may be particularly severe. This leads to large rents in the annulus and posterior longitudinal ligament, thereby permitting disk material to herniate into the spinal canal as a free fragment with the potentially damaging capacity to migrate superiorly or inferiorly and compress two or more nerve roots of the cauda equina. Most cervical disk herniations are posterolateral or foraminal.

Fig. 75.3 Dorsal view of lower lumbar spine and sacrum, showing the different types of herniations and how different roots and the cauda equina can be compressed.

(Reprinted with permission from Stewart, J.D., 1993. Focal Peripheral Neuropathies, second ed. Raven Press, New York.)

In the cervical and lumbar regions, alteration in the integrity of the disk space is a component of a degenerative condition termed spondylosis, characterized by osteoarthritic changes in the joints of the spine, the disk per se (desiccation and shrinkage of the normally semisolid, gelatinous nucleus pulposus), and the facet joints. Immunohistochemical examination of herniated cervical disks points to an inflammatory process associated with neovascularization and increased expression of matrix metalloproteinase and inducible nitric oxide (NO) synthetase (Furusawa et al., 2001). The release of NO by disk cells may contribute to the process of disk degeneration by inducing apoptosis (Kohyama et al., 2000). Because it spawns osteophyte formation, spondylosis leads to compromise of the spinal cord in the spinal canal and the nerve roots in the intervertebral foramina. Restriction in the dimensions of these bony canals may be exacerbated by thickening and hypertrophy of the ligamentum flavum, which is especially detrimental in patients with congenital cervical or lumbar canal stenosis.

In the cervical region, nerve root compression in patients older than 50 years is often due to disk herniation superimposed on chronic spondylotic changes. Isolated “soft” cervical disk herniation tends to occur in younger people in the setting of neck trauma. In the lumbosacral region, isolated acute disk herniation is a common cause of radiculopathy in the younger patient (<40 years), whereas bony root entrapment with or without superimposed disk herniation is the more typical cause of lumbosacral radiculopathy in the patient older than 50.

Clinical Features

Root compression from disk herniation gives rise to a distinctive clinical syndrome that in its fully developed form comprises radicular pain, dermatomal sensory loss, weakness in the myotome, and reduction or loss of the deep tendon reflex subserved by the affected root (Carette and Fehlings, 2005). Nerve root pain is variably described as knifelike or aching and is widely distributed, projecting to the sclerotome (defined as deep structures such as muscles and bones innervated by the root). Typically, root pain is aggravated by coughing, sneezing, and straining at stool (actions that require a Valsalva maneuver and raise intraspinal pressure). Accompanying the pain are paresthesias referred to the specific dermatome, especially to the distal regions of the dermatomes; indeed, these sensations strongly suggest that the pain has its origins in compressed nerve roots rather than spondylotic facet joints. Sensory loss caused by the compromise of a single root may be difficult to ascertain because of the overlapping territories of adjacent roots, although loss of pain is usually more easily demonstrated than loss of light touch sensation (Fig. 75.4).

Fig. 75.4 The zones of radicular touch and pain sensation. The area for touch sensation (dark orange) supplied by one single root is wider than the area of pain sensation (light orange). Areas of pain sensation do not overlap or at most overlap incompletely, whereas areas of touch sensation of a single root are completely overlapped by those of the adjacent roots (A). Accordingly, monoradicular lesions (B) produce a hypalgesic or analgesic zone, while touch sensation remains intact or only minimally impaired. Only after two roots are involved is an anesthetic zone present.

(Reprinted with permission from Mumenthaler, M., Schliack, H., 1991. Peripheral Nerve Lesions. Diagnosis and Therapy. Thieme, New York.)

Most radiculopathies occur in the lumbosacral region; compressive root lesions in this area account for 62% to 90% of all radiculopathies. Cervical radiculopathies are less common, comprising 5% to 36% of all radiculopathies encountered.

In the lumbosacral region, 95% of disk herniations occur at the L4-L5 or L5-S1 levels; L3-L4 and higher lumbar disk herniations are uncommon (Deyo and Weinstein, 2001). Knowing that the L4 root exits beneath the pedicle of L4 through the L4-L5 foramen and that L5 exits through the L5-S1 foramen, one might predict that disk herniation at these levels would generally compress the L4 and L5 roots, respectively (see Fig. 75.3). In perhaps only 10% of cases of the disk herniating far laterally into the foramen is there compression of the exiting nerve root. More commonly, the posterolateral disk herniation compresses the nerve root passing through the foramen below that disk, so L4-L5 and L5-S1 herniations usually produce L5 and S1 radiculopathies, respectively.

In an S1 radiculopathy, pain radiates to the buttock and down the back of the leg (classic sciatica), often extending below the knee; paresthesias are generally felt in the lateral ankle and foot. The ankle jerk is generally diminished or lost, and weakness may be detected in the plantar flexors and gluteus maximus.

In an L5 radiculopathy, the distribution of pain is similar, but paresthesias are felt on the dorsum of the foot and the outer portion of the calf. The ankle reflex is typically normal, but there may be reduction of the medial hamstring reflex. Weakness may be found in L5-innervated muscles served by the peroneal nerve, including the extensor hallucis longus, tibialis anterior and peronei, as well as the tibialis posterior (served by the tibial nerve) and the gluteus medius (innervated by the superior gluteal nerve). Weakness may be restricted to the extensor hallucis longus. A positive straight leg–raising test result is a sensitive indicator of L5 or S1 nerve root irritation. The test is deemed positive when the patient complains of pain radiating from the back into the buttock and thigh with leg elevation to less than 60 degrees. The test result is positive in 95% of patients with a proven disk herniation at surgery. A less sensitive but highly specific test is the crossed straight leg–raising test when the patient complains of radiating pain on the affected side with elevation of the contralateral leg.

The less common L4 radiculopathy is characterized by pain and paresthesias along the medial aspect of the knee and lower leg. The patellar reflex is diminished, and weakness may be noted in the quadriceps and hip adductors (innervated by the femoral and obturator nerves, respectively). When large herniations occur in the midline at either the L4-L5 or the L5-S1 level, many of the nerve roots running past that level to exit through intervertebral foramina below that level may be compressed, producing the cauda equina syndrome of bilateral radicular pain, paresthesias, weakness, and attenuated reflexes below the disk level, as well as urinary retention. This is a surgical emergency requiring urgent decompression.

In the cervical region, it is likely that the greater mobility at levels C5-C6 and C6-C7 promotes the development of cervical disk degeneration with annulus fraying and subsequent disk protrusion. Cervical nerve roots emerge above the vertebra that shares the same numerical designation. Therefore C7 exits between C6 and C7, and spondylotic changes with or without additional acute disk herniation would be expected to compress the C7 nerve root. Similarly, disk protrusion at C5-C6 and C7-T1 would compress the C6 and C8 roots, respectively. In the classic study of Yoss and associates in 1957, clinical and radiological evidence of radiculopathy was found to occur most often at C7 (70%), less frequently at C6 (19%-25%), uncommonly at C8 (4%-10%) and C5 (2%). Radiculopathy involving the T1 root is a clinical rarity (Levin, 1999).

Involvement of C6 is associated with pain at the tip of the shoulder radiating into the upper part of the arm, lateral side of the forearm, and thumb. Paresthesias are felt in the thumb and index finger. The brachioradialis and biceps reflexes are attenuated or lost. Weakness may occur in the muscles of the C6 myotome supplied by several different nerves, including the biceps (musculocutaneous nerve), deltoid (axillary nerve), and pronator teres (anterior interosseous branch of the median nerve). The clinical features of C5 radiculopathies are similar, except that the rhomboids and spinatus muscles are more likely to be weak.

When the C7 root is compressed, pain radiates in a wide distribution to include the shoulder, chest, forearm, and hand. Paresthesias involve the dorsal surface of the middle finger. The triceps reflex is usually reduced or absent. A varying degree of weakness usually involves one or more muscles of the C7 myotome, especially the triceps and the flexor carpi radialis. Less common C8 root involvement presents a similar clinical picture with regard to pain. Paresthesias, however, are experienced in the fourth and fifth digits, and weakness may affect the intrinsic muscles of the hand, including finger abductor and adductor muscles (ulnar nerve), thumb abductor and opponens muscles (median nerve), finger extensor muscles (posterior interosseus branch of the radial nerve), and flexor pollicis longus (anterior interosseus branch of the median nerve).

Diagnosis

Diagnosis is aided by a variety of imaging techniques (e.g., plain radiography, myelography, CT myelography, MRI) and EMG testing (Carette and Fehlings, 2005) (see Chapter 73). Both diagnostic modalities—the imaging approach that reveals anatomical details and the EMG techniques that disclose neurophysiological function—agree in the majority of patients (60%) with a clinical history compatible with cervical or lumbosacral radiculopathy, although only the results of one study will be positive in a significant minority of patients (40%) (Nardin et al., 1999). Although plain radiography is unhelpful in the identification of a herniated disk per se, in both the cervical and the lumbar area, it reveals spondylotic changes when present. It also may be useful for identifying less common disorders that produce radicular symptoms and signs: bony metastases, infection, fracture, and spondylolisthesis, for example.

In the cervical region, the best methods for assessing the relationship between neural structures (spinal cord and nerve root) and their fibro-osseous surroundings (disk, spinal canal, and foramen) are postmyelography CT (unenhanced CT reveals little more than the presence of bony changes) and MRI. MRI is equivalent in diagnostic capacity to postmyelography CT and therefore is preferred. In the lumbosacral region, CT is an effective method for evaluating disk disease, but when available, MRI is considered the superior imaging study. Its excellent resolution, multiplanar imaging, the ability to see the entire lumbar spine including the conus, and the absence of ionizing radiation make it highly sensitive in detecting structural radicular disorders (Ashkan et al., 2002).

A variety of neurophysiological tests are used to assess patients with disk herniation: motor and sensory nerve conduction studies, late responses, somatosensory evoked potentials, nerve root stimulation, and needle electrode examination. Sensory conduction studies are useful in the evaluation of a patient suspected of radiculopathy because SNAPs are typically normal (because the lesion is rostral to the DRG in the intervertebral foramina) even in the face of clinical sensory loss, in contrast to the situation in plexopathy and peripheral nerve trunk lesions, where SNAPs are attenuated or absent. In the specific instance of L5 radiculopathy, however, because the L5 DRG may reside proximal to the neural foramen, if intraspinal pathology is severe enough, compression of the L5 DRG may lead to loss of the superficial peroneal nerve SNAP (Levin, 1998).

Needle EMG is the most useful electrodiagnostic procedure in the diagnosis of suspected radiculopathy (Wilbourn and Aminoff, 1998). A study is considered positive if abnormalities—especially acute changes of denervation including fibrillation potentials and positive sharp waves—are present in two or more muscles that receive innervation from the same root, preferably via different peripheral nerves. No abnormalities should be detected in muscles innervated by the affected root’s rostral and caudal neighbors. Reduced motor unit potential (MUP) recruitment (manifested by decreased numbers of MUPs firing at an increased rate) and MUP abnormalities of reinnervation (high-amplitude, increased duration, polyphasic MUPs) are also sought by the needle electrode but are not as reliable as fibrillation potentials in establishing a definitive diagnosis of radiculopathy. Absence of fibrillation potentials does not, however, exclude the diagnosis of radiculopathy. Two main reasons for this exist. First, examination in the first 1 to 3 weeks after onset of nerve root compromise may be negative because it takes approximately 2 weeks for these potentials to appear. At the early stages in the process of nerve root compression, the only needle electrode examination manifestation of radiculopathy might be reduced MUP recruitment resulting from either axon loss, conduction block, or both. Second, fibrillation potentials disappear as denervated fibers are reinnervated by axons of the same or an adjacent myotome beginning 2 to 3 months after nerve root compression (Fig. 75.5). Thus in the later phases of nerve root compression, the only needle EMG changes indicative of radiculopathy might be chronic neurogenic changes of reduced recruitment and MUP remodeling. The distribution of fibrillation potentials is relatively stereotyped for C5, C7, and C8 radiculopathies, whereas C6 radiculopathy has the most variable presentation. In about half of patients, the findings are similar to C5 radiculopathy, whereas in the other half, findings are identical to C7 radiculopathy (Levin et al., 1996). A patient with the uncommon disk compression of T1 was found to have isolated fibrillation potential activity of the abductor pollicis brevis (Levin, 1999).

Fig. 75.5 Diagram illustrating how muscle fibers denervated by a radiculopathy are reinnervated by collateral sprouting despite persisting root compression.

(Reprinted with permission from Wilbourn, A.J., Aminoff, M.J., 1988. AAEE Minimonograph #32: the electrophysiologic examination in patients with radiculopathies. Muscle Nerve 11, 1099–1114.)

Tabes Dorsalis

Tabes dorsalis, the most common form of late neurosyphilis, begins as a spirochetal (Treponema pallidum) meningitis (see Chapter 53C). After 10 to 20 years of persistent infection, damage to the dorsal roots is severe and extensive, producing a set of characteristic symptoms and signs. Symptoms are lightning pains, ataxia, and bladder disturbance; signs are Argyll Robertson pupils, areflexia, loss of proprioceptive sense, Charcot joints, and trophic ulcers. Lancinating or lightning pains are brief, sharp, and stabbing; they are more apt to occur in the legs than elsewhere. Sensory disturbances such as coldness, numbness, and tingling also occur and are associated with impairment of light touch, pain, and thermal sensation. Sudden visceral crises, characterized by the abrupt onset of epigastric pain that spreads around the body or up over the chest, occur in some 20% of patients.

Most of the features of tabes dorsalis can be explained by lesions of the dorsal roots, dorsal root ganglia, and posterior columns (Gilad et al., 2007). Ataxia is due to the destruction of proprioceptive fibers, insensitivity to pain follows partial loss of small myelinated and unmyelinated fibers, and bladder hypotonia with overflow incontinence, constipation, and impotence is the result of sacral root damage. Pathological study discloses thinning and grayness of the posterior roots, especially in the lumbosacral region, and the spinal cord shows degeneration of the posterior columns. A mild reduction of neurons in the DRG occurs, and there is little change in the peripheral nerves. Inflammation may occur all along the posterior root.

The CSF is abnormal in active cases. Opening pressure is elevated in 10% of patients, and 50% have a mononuclear pleocytosis (5-165 cells/mL). More than 50% have mild protein elevation (45-100 mg/dL, with rare instances of values up to 250 mg/dL), and 72% have positive CSF serology. In all cases of neurosyphilis, antibodies specific for T. pallidum are found, and the preferred treatment is aqueous penicillin G, 2 to 4 million units IV every 4 hours for 10 to 14 days, with careful CSF follow-up. CSF examination 6 months after treatment should demonstrate a normal cell count and decreasing protein content. If not, a second course of therapy is indicated. The CSF examination should be repeated every 6 months for 2 years or until the fluid is normal.

Polyradiculoneuropathy in Human Immunodeficiency Virus–Infected Patients

Cytomegalovirus (CMV) polyradiculoneuropathy is a rapidly progressive opportunistic infection that usually occurs late in the course of human immunodeficiency virus (HIV) infection when the CD4 count is very low (<200 cells/mL) and acquired immunodeficiency syndrome (AIDS)-defining infections are present. Uncommonly, it is the initial manifestation of AIDS (Anders and Goebel, 1998). Patients often have evidence of systemic CMV infection (retinitis, gastroenteritis). The presentation is marked by rapid onset of pain and paresthesias in the legs and perineal region, associated with urinary retention and progressive ascending weakness of the lower extremities (Robinson-Papp and Simpson, 2009). Examination discloses a severe cauda equina syndrome, the combination of flaccid paraparesis, absent lower-limb deep tendon reflexes, reduced or absent sphincter tone, and variable loss of light touch, vibration, and joint position sense. The upper extremities and cranial nerves may be involved in advanced cases (Robinson-Papp and Simpson, 2009).

A gadolinium-enhanced MRI of the lumbosacral spine is necessary to exclude a compressive lesion of the cauda equina and is generally the first study performed (Robinson-Papp and Simpson, 2009). The CSF has an elevated protein level, depressed glucose level, polymorphonuclear pleocytosis, and a positive CMV polymerase chain reaction (PCR) (Anders and Goebel, 1998). CMV may be isolated from CSF cultures. The needle EMG discloses widespread fibrillation potentials in lower-extremity muscles, and sensory conduction studies may reveal an associated distal sensory neuropathy that is common in the late stages of HIV infection. MRI of the lumbosacral region is usually normal, but adhesive arachnoiditis has been described. The pathological features are marked inflammation and extensive necrosis of dorsal and ventral roots. Cytomegalic inclusions may be found in the nucleus and cytoplasm of endothelial and Schwann cells (Fig. 75.7).

Fig. 75.7 Cytomegalovirus polyradiculoneuropathy. Numerous mononuclear inflammatory cells are apparent, and the presence of myelin ovoids (arrows) reflects axon loss (hematoxylin-eosin stain, ×100). Inset, Cytomegalic cell with intranuclear inclusion (hematoxylin-eosin stain, ×150).

(Courtesy Dr. T.W. Smith, Department of Pathology [Neuropathology], University of Massachusetts Medical Center, Worcester, MA.)

Untreated CMV polyradiculoneuropathy is rapidly fatal within approximately 6 weeks of onset. The antiviral nucleoside analog, ganciclovir, may benefit some patients if treatment is instituted early; improvement occurs over weeks to months. Viral resistance to ganciclovir is suggested by persistent pleocytosis and depressed CSF glucose and should prompt consideration of an alternate antiviral agent such as foscarnet; unlike ganciclovir, it does not require intracellular phosphorylation for its effect.

Other causes of rapidly progressive lumbosacral polyradiculoneuropathy in the HIV-infected patient are meningeal lymphomatosis, Mycobacterium tuberculosis, and axonal polyradiculoneuritis associated with HIV infection per se (Corral et al., 1997). Additionally, one must consider acute inflammatory demyelinating polyradiculoneuropathy. Syphilis has an accelerated course in the patient with AIDS, and syphilitic polyradiculoneuropathy may present with rapidly progressive pain, paraparesis, muscle wasting, and hyporeflexia. In addition to markedly elevated CSF protein level, hypoglycorrhachia, and brisk pleocytosis, the CSF and serum Venereal Disease Research Laboratories (VDRL) serology results are positive. Intravenous penicillin leads to prompt improvement. Other considerations include herpes simplex virus type 2 and varicella-zoster virus infections that involve the lumbosacral nerve roots and the spinal cord, producing a radiculomyelitis. Toxoplasma gondii may also cause myelitis, presenting as a subacute conus medullaris syndrome that simulates the clinical features produced by CMV polyradiculoneuropathy. In the case of T. gondii, MRI may reveal abscess formation.

Lyme Radiculoneuropathy

Lyme disease is caused by the spirochete, Borrelia burgdorferi, transmitted by the deer tick, Ixodes dammini, and is most prevalent in the American northeast and upper Midwest. It is a multisystem disease affecting the skin, peripheral nervous system, central nervous system (CNS; referred to as neuroborreliosis), musculoskeletal system, and heart. To help bring order to the understanding of this illness, it may be divided into three clinical stages (Bratton et al, 2008). Stage 1 follows within 1 month of the tick bite and is marked by a characteristic rash in 60% to 80% of patients, designated erythema chronica migrans (oval or annular shape with a clear center in the area of the bite), and influenza-like symptoms of fatigue, fever, headache, stiff neck, myalgias, and arthralgias. In stage 2, the stage of dissemination of the spirochete from the initial lesion and occurring within weeks of the rash, peripheral nerve, joint, and cardiac abnormalities may appear. Stage 3, caused by late or persistent infection, may occur up to 2 years after the tick bite and is characterized by chronic neurological syndromes, among them neuropathy, encephalopathy, myelopathy, and psychiatric disturbances and migratory oligoarthritis.

Nerve root and peripheral nerve abnormalities that characterize stage 2 develop in about 15% of untreated patients in the United States (Steere, 2001). Possible manifestations occurring within weeks after the onset of erythema chronica migrans include headache with lymphocytic (aseptic) meningitis, cranial neuropathy (especially facial mononeuropathies, bilateral in 25% of cases), multifocal radiculoneuropathy, radiculoplexopathy, mononeuritis multiplex, myelitis, subtle encephalopathy, and cerebellar ataxia (Steere, 2001). The clinical features of nerve root involvement include burning radicular pain with sensory loss and hyporeflexia in the territory of the involved roots. Nerve conduction studies provide evidence for an associated primarily axon-loss polyneuropathy. Chronic neuroborreliosis, seen in stage 3, occurs in some 5% of untreated patients and is characterized by an axon-loss polyneuropathy that manifests as radicular pain or distal paresthesias (Steere, 2001). In a nonhuman primate model of neuroborreliosis, spread of B. burgdorferi within the nervous system—leptomeninges, motor and sensory roots, DRG, but not the brain parenchyma—has been demonstrated. In peripheral nerves from such animals, spirochetes were seen in the perineurium (Steere, 2001). Treatment of Lyme radiculoneuropathy with IV ceftriaxone (cefotaxime and penicillin G are acceptable alternates) for 2 to 4 weeks is associated with resolution of symptoms and signs in most patients.

Herpes Zoster

Herpes zoster, also known as shingles, is a common painful vesicular eruption occurring in a segmental or radicular (dermatomal) distribution and due to reactivation of latent varicella-zoster virus in DRG (see Chapter 53B). Primary infection presents as varicella (chickenpox) earlier in life, usually in epidemics among susceptible children (Gnann and Whitley, 2002). Involvement may occur at any level of the neuraxis but is most commonly seen in the thoracic dermatomes, followed by the face. Zoster may present in a division of the trigeminal nerve (e.g., herpes zoster ophthalmicus), where it is often accompanied by keratitis (a potential cause of blindness requiring immediate treatment), in the maxillary and mandibular nerves, and in the seventh nerve, where it is associated with a facial palsy and ipsilateral external ear or hard palate vesicles known as Ramsay Hunt syndrome (Gilden et al., 2000). Rarely, the viral episode can present as dermatomal pain without a rash, known as herpes sine herpete.

Zoster occurs during the lifetime of 10% to 20% of all people, with an incidence in the general population of approximately 3 to 5 per 1000 per year. The incidence is low in young people and increases with age—among persons older than 75 years exceeds 10 cases per 1000 person-years—and when immunocompetence is compromised. For example, the incidence among HIV-positive individuals was 15-fold greater than that of a control group (Gnann and Whitley, 2002).

During primary infection, the virus colonizes the DRG and remains latent for many decades until it is reactivated, either spontaneously or when virus-specific cell-mediated immunity declines secondary to specific conditions (e.g., lymphoproliferative disorders, treatment with immunosuppressive drugs, organ transplant recipients, seropositivity for HIV) or normal aging, and travels down sensory nerves. Pathological changes, which are characterized by lymphocytic infiltration and variable hemorrhage, are found in the skin, DRG, and spinal roots. Involvement of the ventral roots and on occasion the spinal cord explains the development of motor signs in some patients (see later discussion).

Herpes zoster is characterized by sharp or burning radicular pain associated with itching and dysesthesias (altered sensation), sometimes accompanied by fever, malaise, and rash. In affected dermatomes, sensation is decreased, yet there is allodynia (painful response to normally non-noxious stimulation) (Gilden et al., 2000). The cutaneous eruption, unilateral and respecting the midline, begins as an erythematous maculopapular rash and progresses to grouped clear vesicles that continue to form for 3 to 5 days (Gnann and Whitley, 2002). These become pustules by 3 to 4 days and form crusts by 10 days. In the normal immunocompetent host, lesions resolve in 2 to 4 weeks, often leaving a region of reduced sensation, scarring, and pigmentation. Pain usually disappears as vesicles fade, but 8% to 70% of patients experience persisting severe pain termed postherpetic neuralgia (PHN), defined as “pain that persists more than 30 days after the onset of rash or after cutaneous healing” (Gnann and Whitley, 2002). This complication is more likely to develop in the elderly, occurring in 50% of patients older than 60 years. In half of patients affected with PHN, the pain resolves within 2 months, and 70% to 80% of patients are pain free by 1 year. Rarely, pain persists for years.

In the immunologically normal host, dissemination of the virus is rare, occurring in fewer than 2% of patients. In the immunocompromised patient, however, dissemination occurs in 13% to 50% of patients. Most often, spread is to distant cutaneous sites, but involvement of the viscera (lung, gastrointestinal tract, and heart) and CNS may occur. A serious complication of herpes zoster ophthalmicus is delayed contralateral hemiparesis caused by cerebral angiitis. The syndrome usually develops 1 week to 6 months after the onset of zoster and occurs in patients of all ages, 50% of whom are immunologically impaired. The mortality rate from cerebrovascular complications is 25%, and only approximately 30% of survivors recover fully.

A complication of cutaneous herpes zoster is segmental motor weakness, which occurs in up to 30% of patients with zoster reactivation (Bahadir et al, 2008; Merchut and Gruener, 1996; Yaszay et al., 2000). Segmental zoster paresis is about equally divided between the arms and legs, with predominantly proximal muscle weakness reflecting weakness in cervical and lumbar—C5, C6, and C7 or L2, L3, and L4—myotomes, respectively. The diaphragm and abdominal muscles may be affected, and bladder and bowel dysfunction may occur in the setting of lumbosacral zoster (Gilden et al., 2000). The interval between skin eruption and paralysis is approximately 2 weeks, with a range of 1 day to 5 weeks and a rare instance reported of delayed (4.5 months) onset of diaphragmatic paralysis. Weakness peaks within hours or days and generally follows the dermatomal distribution of zoster eruptions (Yaszay et al., 2000); spread to muscles served by unaffected segments is very uncommon (<3% of cases). The prognosis for recovery is good, with nearly complete return of function in two-thirds of patients over the course of 1 to 2 years, 55% showing full recovery, and another 30% showing significant improvement. One in five patients is left with severe and permanent residua.

Prognosis for recovery in patients with diaphragmatic paralysis is not as good as it is with segmental paresis involving the limb muscles, probably owing to the challenge of axonal regeneration along the long course of the phrenic nerve (Bahadir et al, 2008). The histopathological correlate of herpes zoster is inflammation and neuronal loss in the DRG that correspond to the affected segmental levels. In the case of segmental zoster paresis, there is lymphocytic inflammation and vasculitis involving adjacent motor roots and the spinal cord gray matter, with resulting motor fiber degeneration (Gilden et al., 2000). A low-grade viral ganglionitis may contribute to PHN (Quan et al., 2005).

The major goals of treatment are to relieve local discomfort, prevent dissemination, and reduce the severity of PHN (Sandy, 2005). Acyclovir, valacyclovir, and famciclovir are indicated for the immunocompetent patient older than 50 years with herpes zoster and should be started within 48 hours of the viral episode to receive the most benefit from therapy. These drugs reduce the duration of viral shedding, limit the duration of new lesion formation, and accelerate healing and pain resolution. They are all safe and well-tolerated, but because of superior pharmacokinetic profiles and simpler dosing regimen, the latter two are preferred to acyclovir (Gnann and Whitley, 2002). Treatment with acyclovir speeds recovery in HIV-positive patients (Robinson-Papp and Simpson, 2009). The U.S. Food and Drug Administration (FDA) has approved a vaccine for use in the United States to reduce the risk for herpes zoster in older adults (≥60 years) without compromised immune systems (Mitka, 2006). The vaccine is effective in preventing herpes zoster and decreasing the incidence of complications (Adams et al., 2010) and is well tolerated (Simberkoff et al., 2010).

The pain of PHN—described variably as continuous deep aching, burning, sharp, stabbing, and shooting, and triggered by light touch over the affected dermatomes—is often debilitating and difficult to treat (Watson, 2000). Singly or in combination, tricyclics (amitriptyline or desipramine), selective serotonin reuptake inhibitors (sertraline or nefazodone hydrochloride), anticonvulsants (carbamazepine and gabapentin), oral opioids (oxycodone), and topical capsaicin cream or lidocaine patches are helpful for about 50% of patients. For intractable cases, intrathecally administered methylprednisolone and lidocaine has been shown to provide relief without adverse effects of arachnoiditis or neurotoxicity in more than 90% of patients treated (Kotani et al., 2000). Intravenous acyclovir followed by oral valacyclovir was found to reduce the pain of PHN in more than 50% of treated patients (Quan et al., 2005).

Early Management

The consequences of brachial plexus injury are weakness and sensory loss referable to a part or the whole of the plexus. The ultimate objective in management is to restore as much neurological function as possible with the hope of returning the limb to its preinjury status, but one must first ensure that the cardiovascular and respiratory systems are stable. In open injuries, there may be damage to great vessels in the neck and injury to the lung, in which case immediate operative intervention is necessary to save the patient’s life. At the time of this early acute intervention, it is important to assess to what degree the various elements of the plexus have been injured. As far as possible, disrupted elements should be tagged for later repair. It may be difficult to suture damaged fascicles, and the formation of scar may prevent successful nerve regeneration. Most researchers agree that nerve resection, grafting, and anastomosis are all very difficult in the acute situation because nerve continuity may be difficult to assess. If portions of a plexus have been sharply transected, however, primary repair should be carried out.

Long-Term Management

Once the patient’s general condition has stabilized, a careful assessment of motor and sensory function should be made. At this stage, an important issue is whether there has been root avulsion. This is a critical determination with implications for management because the outlook for return of motor and sensory function in territories supplied by avulsed roots is currently not good, although promising results of surgical repair have recently been noted. Root avulsion and its management are discussed in the section on Disorders of Nerve Roots, earlier in this chapter. If the plexus elements are in continuity and the nerve fibers have received a neuropraxic injury with minimal axonotmesis, return of normal strength and sensation is expected. In the face of axonotmesis, the main factor limiting return of function is the distance the regenerating axon sprouts must traverse before making contact with end organs. Unless the muscles and sensory receptors are reinnervated within about 1 year, a good functional result is unlikely. Thus, recovery of proximal muscle strength from upper portions of the plexus is more likely than recovery of hand function when lower elements have been damaged.

Often, surgery must be performed to provide an exact intraoperative definition of the lesion’s extent (see Chapter 50D). Intraoperative motor evoked potentials are helpful in assessing the functional state of anterior motor roots and motor fibers. Depending on the findings, innovative microsurgical techniques are available to provide an array of options: direct nerve repair, nerve grafting, nerve transfers, and free-functioning muscle transfers (Giuffre et al., 2010). Primary nerve reconstruction combined with joint fusion and tendon transfers provides a worthwhile return of function to many patients. The joint and tendon surgeries are best performed as secondary operations after a period of physiotherapy. Intensive physiotherapy and use of orthoses are often necessary to help restore maximum function. In general, the outcome after nerve grafting is relatively good for recovery of elbow flexors and extensors and for those of the shoulder girdle, but it is very poor for forearm and hand intrinsic muscles. Quality-of-life surveys after brachial plexus surgery indicate that 78% of patients report at least moderate satisfaction (Choi et al., 1997). In a large series of more than 1000 patients treated over a 30-year period (Kim et al., 2003), results of repair by suture and grafts were best for injuries located at the C5, C6, and C7 levels, the upper and middle trunk, the lateral cord to the musculocutaneous nerve, and the median and posterior cords to the axillary and radial nerves. Results were poor for injuries at the C8 and T1 levels and for lower trunk and medial cord lesions, and the chance of recovery was reduced with delays of more than 6 months in undertaking repair.

Metastatic Plexopathy

Damage to the brachial plexus in patients with cancer is usually secondary to either metastatic plexopathy or radiation-induced injury (Jaeckle, 2010). Lung and breast carcinoma are the tumors that most commonly metastasize to the brachial plexus; lymphoma, sarcoma, melanoma, and a variety of other types are less common. Tumor metastases spread via lymphatics, and the area most commonly involved is adjacent to the lateral group of axillary lymph nodes.

The hallmark of metastatic plexopathy is pain, which is often severe. It is generally located in the shoulder girdle and radiates to the elbow, medial portion of the forearm, and fourth and fifth digits of the hand. In many patients, the neurological examination discloses signs referable to the lower plexus and its divisions; more than half of patients have Horner syndrome, whereas few have lymphedema of the affected limb. The predilection for involvement of the C8 and T1 spinal nerves and the lower trunk can be explained by the fact that the lateral group of axillary lymph nodes that drain the commonly located sites (breast and lung) are in close contact with the divisions of the lower trunk; the upper trunk and its divisions are remarkably free of lymph nodes. Some patients have signs indicating involvement of the entire plexus. In most of these patients, however, cervical CT myelography or MRI discloses epidural deposits that explain the upper plexus (C5 and C6 root) signs.

An important syndrome first described by Pancoast in 1932 is a superior pulmonary sulcus tumor, the vast majority of which are non–small-cell bronchogenic carcinomas (Arcasoy and Jett, 1997). The tumor arises near the pleural surface of the apex of the lung and grows into the paravertebral space and posterior chest wall, invading the C8 and T1 extraspinal nerves, the sympathetic chain and stellate ganglion, the necks of the first three ribs, and the transverse processes and borders of the vertebral bodies of C7 through T3. The tumor may eventually invade the spinal canal and compress the spinal cord. Clinical features include a number of symptoms and signs: severe shoulder pain radiating to the head and neck, axilla, chest, and arm; pain and paresthesias of the medial aspect of the arm and the fourth and fifth digits; and weakness with atrophy of intrinsic hand muscles.

On occasion, metastatic brachial plexopathy may be difficult to distinguish from radiation plexopathy (see the following section on Radiation-Induced Plexopathy). Imaging studies are usually informative. In patients with metastases, MRI can identify a mass adjacent to the brachial plexus and reveal whether the tumor has encroached on the epidural space. Magnetic resonance neurography is a novel noninvasive means of helping to exclude tumor in patients presenting with brachial plexopathy who have undergone radiation therapy to the brachial plexus (Du et al., 2010). Results of the treatment of metastatic plexopathy are disappointing. Radiotherapy to the involved field and chemotherapy of the underlying tumor are the mainstays of treatment. Radiotherapy may relieve pain in 50% of patients but has little effect on return of muscle strength. A variety of procedures have been implemented to ameliorate the severe pain of this condition, including opioid analgesics and nonopioid adjuvant analgesics such as antidepressants and antiepileptic drugs, including an emerging role for levetiracetam (Dunteman, 2005), transcutaneous stimulation, paravertebral sympathetic blockade, and dorsal rhizotomies.

In the patient with Pancoast tumor, preoperative radiotherapy followed by extended surgical resection is the most common treatment, with an overall 5-year survival rate of 20% to 35% (Arcasoy and Jett, 1997).

Radiation-Induced Plexopathy

Radiation-induced plexopathy is unlikely to occur if the dose is less than 6000 cGy. If more than 6000 cGy is given, the interval between the end of radiation therapy and the onset of symptoms and signs of radiation plexopathy ranges from 3 months to 26 years, with a mean interval of approximately 6 years. The brachial plexus is more vulnerable to large fraction size, and thus small doses per fraction are recommended (Johansson et al., 2000); cytotoxic therapy also adds to the damaging effect of radiotherapy. Limb paresthesias and swelling are common complaints. Although the pain of radiation plexopathy is usually less intense than that of metastatic plexopathy, it may nonetheless be problematic (severe and persistent), requiring opioids and chemical sympathectomy (Fathers et al., 2002). Weakness is usually most prominent in muscles innervated by branches of the upper trunk, but involvement of the entire limb from damage to the upper and lower portions of the plexus has also been described. Indeed, in a group of women with radiation plexopathy following treatment for carcinoma of the breast, progressive weakness resulted in loss of hand function in 90% of patients (Fathers et al., 2002). Dropcho (2010) points out that breast carcinoma is the tumor most often associated with radiation plexopathy, accounting for 40% to 75% of patients, followed by lung carcinoma and then by lymphoma.

The relative resistance of the lower trunk of the brachial plexus to radiation injury is perhaps explained by the protective effect of the clavicle and the relatively shorter course of the lower trunk and its divisions through the radiation port. The pathogenesis of radiation damage is thought to involve two factors: (1) radiation-induced endoneurial and perineurial fibrosis with obliteration of blood vessels, triggered by small-vessel or microvascular endothelial injury, and (2) direct radiation-induced damage to myelin sheaths and axons. Radiation-induced arteritis of large vessels was found in a patient with delayed onset (21 years) of brachial plexopathy following radiation therapy for breast carcinoma, who underwent arteriography for acrocyanosis in the affected limb (Rubin et al., 2001). The natural history of radiation-induced plexopathy is that of steadily increasing deterioration, although at times a plateau may be reached after 4 to 9 years of progression.

Unfortunately, treatment options are not very satisfactory. Surgical treatment using neurolysis has been reported to relieve pain in some patients, but there is little information on long-term outcome, and surgery may cause significant deterioration in motor and sensory function (Dropcho, 2010). A diagnostic dilemma arises when symptoms and signs of brachial plexopathy develop in a patient who is known to have had cancer and radiation in the region of the brachial plexus. A painful lower-trunk lesion with Horner syndrome strongly suggests metastatic plexopathy, whereas a relatively painless upper-trunk lesion with lymphedema favors radiation-induced plexopathy. MRI does not always discriminate between metastatic and radiation because it may reveal an appearance of high signal intensity on T2-weighted images and contrast enhancement in cases of both radiation fibrosis and tumor infiltration (Wouter van Es et al., 1997), although radiation fibrosis is favored by finding thickening and diffuse enlargement of the brachial plexus without a focal mass (Wittenberg and Adkins, 2000). Magnetic resonance neurography may be useful to exclude tumor (Du et al., 2010) and fluorodeoxyglucose positron emission tomography (FDG-PET) scanning may be useful for identifying metastatic breast cancer in or near the brachial plexus, not clearly imaged by CT or MRI (Dropcho, 2010). In the early and middle stages of radiation plexopathy, nerve conduction studies disclose features of demyelinating conduction block, but as time passes, there is conversion to axon loss (Ferrante and Wilbourn, 2002). Needle EMG is helpful in separating radiation-induced plexopathy from neoplastic plexopathy by the presence of myokymic discharges in the former. These are spontaneously occurring grouped action potentials (triplets or multiplets) followed by a period of silence, with subsequent repetition of a grouped discharge of identical potentials in a semirhythmic manner. They appear to result from spontaneous activity in single axons induced by local membrane abnormalities. They have not been reported in cases of tumor plexopathy.

Clinical Features

The illness begins with abrupt onset of intense pain, described as sharp, stabbing, throbbing, or aching and located in a variety of sites that include the shoulder, scapular area, trapezius ridge, upper arm, forearm, and hand. The pain may last from hours to many weeks, and then it gradually abates. Lessening of pain is associated with the appearance of weakness. This may have been present during the painful period but was not appreciated because the pain prevented the patient from moving the limb. Weakness may progress for 2 to 3 weeks after the onset of pain. Although pain subsides in most patients, it may continue for several weeks after weakness has reached its peak, and rarely, it recurs episodically for a year or more (van Alfen and van Engelen, 2006).

On examination, roughly half of patients have weakness in muscles of the shoulder girdle, a third have weakness referable to both upper and lower parts of the plexus, and about 15% have evidence of lower plexus involvement alone. Most plexopathies are incomplete, because there is sparing of one or more muscles in the same root distribution. The patient may hold the arm in a characteristic posture, with flexion at the elbow and adduction at the shoulder, perhaps to reduce mechanical tension on the plexus.

Recognition is growing that the typical syndrome of brachial plexopathy need not always be associated with lesions of trunks or cords but can be caused by discrete lesions of individual peripheral nerves, including the suprascapular, axillary, musculocutaneous, long thoracic, median, and anterior interosseous. It can also involve cranial nerves VII and X, and the phrenic nerves (Cruz-Martinez et al., 2002). Individual fascicular involvement of the musculocutaneous nerve, causing isolated brachialis wasting, has also been reported (Watson et al., 2001). Thus, the term brachial plexus neuropathy may be appropriate. Sensory loss, found in two-thirds of patients and most commonly over the outer surface of the upper arm and the radial surface of the forearm, is usually less marked than the motor deficit, although the spectrum of brachial plexus neuropathy includes patients with isolated clinical and electrophysiological sensory deficits (Seror, 2004). One-third of cases are bilateral, but many fewer are symmetrical. In a small number of patients, unilateral or bilateral diaphragmatic paralysis occurs (Lahrmann et al., 1999), and the combination of acute shoulder pain with respiratory symptoms should suggest the diagnosis of brachial plexus neuropathy. In a small subset of patients, neuralgic amyotrophy presents with isolated phrenic neuropathy (sometimes bilateral) with no abnormalities on clinical or electrodiagnostic examinations of the limbs (Tsao et al., 2006).

Diagnosis

The major differential diagnostic consideration in a patient with acute arm pain and weakness is cervical radiculopathy related to cervical disease. In this condition, however, pain is usually persistent, neck stiffness is invariable, and it is unusual for radicular pain to subside as weakness increases. Nonetheless, an upper trunk brachial plexopathy can simulate a C5 or C6 radiculopathy. The cervical paraspinal needle EMG done several weeks after the onset of pain should be normal in brachial plexus neuropathy but show increased insertional activity and fibrillation potentials in cervical radiculopathy. Another differential diagnostic consideration is neoplastic plexopathy, discussed earlier in this chapter. This entity is usually unremittingly painful, and neurological findings are most often referable to lower plexus elements. A third consideration might be a focal presentation of motor neuron disease, but pain is not a feature of this disease and sensation is always spared.

Electrodiagnostic testing is helpful in confirming the diagnosis and ruling out other conditions. Findings suggest axonal lesions of peripheral nerves occurring singly (mononeuritis) or in various combinations (mononeuritis multiplex) (Cruz-Martinez et al., 2002). Sensory studies are abnormal in one-third of patients; the most common abnormality is reduced amplitude of one or more sensory action potentials of the median, ulnar, and radial nerves and the lateral and medial antebrachial cutaneous nerves. Van Alfen and colleagues (2009) found sensory abnormalities in less than 20% of nerves studied, even when the nerve was clinically affected, suggesting that the pathology may be in the nerve roots. Needle EMG is helpful because it shows absence of fibrillation potentials in the cervical paraspinal muscles, thereby pointing to a pathological process distal to the DRG. Needle EMG is also helpful in sorting out the problems of localization, identifying lesions localized to the brachial plexus, individual peripheral nerves, or peripheral nerve branches. Finally, in a small number of patients, needle EMG is abnormal on the asymptomatic side as well as the symptomatic side, indicating that brachial plexus neuropathy can sometimes be subclinical. MRI of the brachial plexus is important in excluding structural lesions that might simulate this disorder and should be performed where there is failure to recover function (van Alfen and van Engelen, 2006). The MRI appearance in idiopathic brachial plexopathy reveals findings of diffuse high T2 signal intensity abnormality and fatty atrophy of involved muscles (Gaskin and Helms, 2006). There are additional laboratory findings of interest (van Alfen and van Engelen, 2006). Among the group of patients with severe bilateral brachial plexus neuropathy with phrenic nerve involvement, elevated liver enzymes are found, possibly reflecting an antecedent subclinical hepatitis. In 25% of patients, antiganglioside antibodies are found, and CSF protein elevations with oligoclonal bands are also noted in some patients, reflecting the likelihood of an immune pathogenesis for this condition.

Pathophysiology and Etiology

The pathophysiology and pathogenesis of the disorder are unclear. An abrupt onset might suggest an ischemic mechanism, and prior history of a viral syndrome or an immunization raises the possibility of an immune-mediated disorder. Complement-dependent antibody-mediated demyelination may have participated in the peripheral nerve damage and nerve biopsy findings in four cases of brachial plexus neuropathy that revealed florid multifocal mononuclear infiltrates, suggesting a cell-mediated component as well (Suarez et al., 1996). In some cases, rapid recovery bespeaks demyelination and remyelination; in others, a long recovery period is more in keeping with axonal degeneration followed by axonal regeneration. Indeed, a biopsy of a cutaneous radial branch in a severe case of plexopathy showed profound axonal degeneration. In most patients, electrophysiological abnormalities are restricted to the affected limb, while in a small number of cases there is evidence of a more generalized polyneuropathy. Nerve biopsy studies of patients with autosomal dominant attacks of brachial plexus neuropathy during symptomatic phases disclosed prominent perivascular inflammatory infiltrates with vessel wall disruption, suggesting that the hereditary disorder has an immune pathogenesis possibly caused by genetic abnormalities of immune regulation (Klein et al., 2002).

Treatment and Prognosis

In the acute stage of the disorder, long-acting nonsteroidal antiinflammatory drugs (NSAIDs) and opioid analgesics are required to control pain (van Alfen, 2007). Evidence from one open-label retrospective series suggests that oral prednisone given in the first month after the onset can shorten the duration of the initial pain and leads to earlier recovery in some patients (van Alfen et al., 2009). Arm and neck movements often aggravate pain, so immobilization of the arm in a sling is helpful. With the onset of paralysis, range-of-motion exercises help prevent contractures. Following the phase of acute pain, van Alfen (2007) reported two additional categories of pain. The first, experienced by nearly 80% of patients, is a shooting or radiating neuropathic pain, believed to originate from the heightened mechanical sensitivity of damaged nerves of the plexus and lasting for weeks to months. This pain may respond to gabapentin and tricyclic medications. A second type of pain that develops in many is a musculoskeletal-type pain localized to the origin or insertion of the paretic or compensating muscles, especially in the periscapular, cervical, and occipital regions. This pain requires physical therapy modalities. Up to 30% of patients who have experienced neuralgic amyotrophy will have long-standing pain for an average follow-up of 6 years (van Alfen, 2007). Accordingly, pain management becomes the mainstay of therapy for these individuals and requires a multidisciplinary approach that blends pharmacotherapy with physical and occupational modalities.

The natural history of brachial plexus neuropathy is benign; improvement occurs in the vast majority of patients, even in those with considerable muscle atrophy. Thirty-six percent have recovered by the end of 1 year, 75% by the end of 2 years, and 89% by the end of 3 years. Although some patients think they have made a full functional recovery, careful examination may disclose mild neurological abnormalities such as isolated winging of the scapula, slight proximal or distal weakness, mild sensory loss, or reduced reflex activity. In two-thirds of patients, onset of improvement is noted in the first month after symptoms begin. Those who continue to be bothered by pain and lack any signs of improvement within the first 3 months of the illness take a longer time to recover.

Neurological Examination

Lumbar plexopathy produces weakness, sensory loss, and reflex changes in segments L2 through L4, whereas sacral plexopathy leads to similar abnormalities in segments L5 through S3. Characteristic findings in lumbar plexopathy include weakness and sensory loss in both obturator- and femoral-innervated territories. Weakness of hip flexion, knee extension, and hip adduction, with sensory loss over the anteromedial aspect of the thigh, occurs; the knee jerk is absent or depressed. This combination of hip flexor and adductor weakness marks the disorder as either a plexopathy or radiculopathy. More precise localization depends on laboratory studies, including needle EMG, CT, and MRI.

Findings in sacral plexopathy include weakness and sensory loss in the territories of the gluteal (motor only), peroneal, and tibial nerves. Leg weakness is typically extensive and involves the hip extensors and abductors, knee flexors, and ankle plantar flexors and dorsiflexors. Sensory loss is found over the posterior aspect of the thigh, the anterolateral and posterior aspects of the leg below the knee, and the dorsolateral and plantar surfaces of the foot. Vasomotor and trophic changes may also be found in these areas. The ankle jerk is reduced or absent. Weakness of the gluteal muscles points to involvement of sacral plexus fibers proximal to the piriformis muscle in the true pelvis or to a more proximal sacral root level. As in lumbar plexopathy, accurate diagnosis often depends on electrodiagnostic studies and neuroimaging procedures.

Electrodiagnostic Studies

Electrodiagnostic studies are performed for several reasons. First, the EMG is helpful in identifying a motor-sensory syndrome as a plexopathy and not a radiculopathy. The diagnosis of plexopathy is confirmed if the EMG discloses denervation (fibrillation potentials and positive sharp waves) and reduced recruitment (reduced numbers of motor units, firing rapidly) in muscles innervated by at least two lumbosacral segmental levels and involving at least two different peripheral nerves. An isolated plexopathy should not be associated with EMG abnormalities in paraspinal muscles. As will be seen, however, a number of pathological processes including diabetes, radiation-induced changes, inflammation, vasculitis, and neoplasia may all involve the roots in addition to the plexus and produce a radiculoplexopathy. Second, EMG findings help determine whether a lumbosacral plexopathy is associated with a polyneuropathy. In the presence of the latter, signs of denervation and reinnervation are found bilaterally, especially in the distal muscles. Third, EMG findings may strongly suggest a particular type of plexopathy; for example, myokymic discharges point to the diagnosis of radiation plexopathy.

Routine nerve conduction studies may help establish the diagnosis of plexopathy. Reduced SNAP amplitude (sural and superficial peroneal) indicates loss of axons distal to the DRG of S1 and L5, respectively. Prolongation in F-wave latency with normal motor nerve conduction studies distally suggests a proximal lesion, either at a root or plexus level.

Neuroimaging Studies

Bone destruction found in plain radiographs of lumbar and sacral vertebrae and the pelvis provides evidence for a structural plexopathy. Intravenous pyelography (IVP) may demonstrate distortion of a ureter or the bladder. Barium enema may disclose displacement of the bowel. CT scanning of the abdomen and pelvis from a rostral point at the level of L1-L2 to a caudal point below the level of the symphysis pubis allows the regional anatomy of the entire lumbosacral plexus to be scrutinized (see Chapter 33A).

The resolution of modern CT and MRI scanners allows identification of individual plexus components. The administration of contrast is usually required to demonstrate the extent of structural abnormalities of the lumbosacral plexus, but it may not differentiate benign and malignant neoplasms, inflammatory masses, and hematoma. A normal MRI makes a structural plexopathy very unlikely. Clues to the nature of a plexopathy are given in Box 75.1. An approach to evaluation of a plexopathy is summarized in (Fig. 75.12).

Fig. 75.12 Approach to evaluation of lumbosacral plexopathy. Electrophysiological identification of radiculopathy may require spinal computed tomographic myelography or magnetic resonance imaging for confirmation and precise diagnosis. *Radiculopathy is associated with plexopathy in diabetes, vasculitis, radiation, and malignancy. ^†Polyneuropathy may accompany plexopathies due to diabetes, vasculitis, and certain malignancies (paraneoplastic neuropathies).

Hematoma

Patients with hemophilia and those receiving anticoagulants can develop hemorrhage in the iliopsoas muscle complex. It is important to recall that major components of the lumbar plexus, the femoral and obturator nerves, course from their origins in the lumbar paravertebral regions to their destinations in the thigh under cover of a tight layer of fascia. Over the iliac muscle, it is referred to as the fascia iliaca, and it becomes progressively thicker as it passes down behind the inguinal ligament; at this site, it forms a dense and indistensible funnel enclosing the lower portions of iliacus and psoas.

Two major anatomical syndromes are associated with iliopsoas hematoma. In the first, the femoral nerve is the sole affected portion of the lumbar plexus. The hematoma arises in the iliacus and causes distention of the dense overlying fascia above the inguinal ligament. In the second syndrome, hemorrhage arises in the psoas muscle or begins in the iliacus muscle and extends into the psoas. In this case, other components of the plexus, the obturator and lateral femoral cutaneous nerves, are involved.

Pain, often severe, is usually the first manifestation of a retroperitoneal hematoma. The pain is present in the groin and radiates to the anterior thigh and lumbar region. It is associated with gradually increasing paresthesias and weakness. When the femoral nerve is involved, weakness and sensory loss occur in its territory; when other components of the plexus are involved, changes are more extensive and conform to the territories supplied by the involved branches of the plexus. If the hemorrhage is large, a mass may develop in the lower abdominal quadrant and be associated with systemic signs like tachycardia, hypotension, and a falling hematocrit (Parmer et al., 2006). It typically arises from the lateral wall of the pelvis and can be seen in a CT scan to obscure the normal concavity of the inner aspect of the wing of the ilium (Fig. 75.13). Because of iliacus muscle spasm, the patient usually lies in a characteristic posture with the hip flexed and laterally rotated because hip extension aggravates the pain. Several days after the onset of the hematoma, a bruise may appear in the inguinal area or anterior thigh. In some patients, especially those with relatively small hematomas and mild neurological deficits, recovery may be satisfactory with conservative measures including reversing anticoagulation, although 10% to 15% of patients show no improvement. Accordingly, some centers explore the abdomen through a limited retroperitoneal incision after reversing the coagulopathy; a complete iliacus fasciotomy is performed and the hematoma is evacuated, thus relieving compression on the femoral nerve and enhancing the prospects for full recovery (Parmer et al., 2006).

Fig. 75.13 Hemorrhagic lumbosacral plexopathy. Computed tomographic scan at L5-S1 level shows enlargement of iliacus muscles, especially on left side, owing to iliacus hematoma (large arrow). Small arrows indicate plexal elements. This large hematoma compresses the femoral and obturator nerves and the lumbosacral trunk.

Abscess

Psoas abscess was more common when tuberculosis was prevalent, but neurological complications such as lumbar plexopathy and femoral neuropathy were rare. This phenomenon was explained by the slow distention of the psoas sheath and by the fact that the abscess ruptured through the psoas fascia before the femoral nerve could be damaged by raised intrapsoas compartment pressure. Similarly, acute nontuberculous psoas abscess rarely produces nerve compression, presumably because the psoas fascia is distensible. Femoral neuropathy, however, does occur with iliacus muscle abscess because the fascia iliaca is relatively indistensible. Rarely, lumbar plexopathy is a complication of pelvic hydatidosis caused by the tapeworm, Echinococcus granulosus (Serradilla et al., 2002).

Aneurysm

Back and abdominal pain are often early manifestations of abdominal aortic aneurysms. Knowledge of abdominal and pelvic regional anatomy helps explain the radiating characteristics of these pains. An expanding abdominal aortic aneurysm may compress the iliohypogastric or ilioinguinal nerve, leading to pain radiating into the lower abdomen and inguinal areas. Pressure on the genitofemoral nerve produces pain in the inguinal area, testicle, and anterior thigh. Compression of nerve trunks L5 through S2, which lie directly posterior to the hypogastric artery, may give rise to sciatica (Shields et al., 1997); 13% of patients with aneurysms of the iliac artery will present with features of sciatica (Delgado-Garcia et al., 1999).

Hemorrhage from an abdominal aortic aneurysm may produce prominent neurological problems because of the retroperitoneal location of the hemorrhage or false aneurysm formation. In the case of an abdominal aortic aneurysm, a large retroperitoneal hematoma may injure the femoral and obturator nerves and even branches of the sacral plexus. Rupture of a hypogastric or common iliac artery aneurysm extends into the pelvis, compressing the L5 through S2 nerve trunk.

Early recognition of an aneurysm is important because the mortality rate for operation on unruptured aneurysms is 5% to 7%, whereas that for ruptured aneurysms is 35% to 40%. Unexplained back pain, leg pain, or pain radiating in the distribution of cutaneous nerves coming from the lumbar plexus should raise the suspicion of an aneurysm of the aorta or its major branches. A pulsatile mass felt while palpating the abdomen or, rarely, on rectal examination strongly suggests the presence of an aneurysm. Lumbosacral radiographs show a curvilinear calcific density, and abdominal sonography or CT scanning can confirm an aneurysm.

Trauma

Because of the relatively protected position of the lumbosacral plexus, traumatic lesions are uncommon. However, fracture of the pelvis, acetabulum, or femur or surgery on the proximal femur and hip joint may injure the lumbosacral plexus. Sacral fractures or sacroiliac joint separation accounts for most cases (68%) of traumatic lumbosacral plexopathy, while acetabular and femoral fractures are much less frequently implicated (14% and 9%, respectively) (Kutsy et al., 2000). The latter, however, are more likely to cause injury to proximal nerves originating from the plexus. The mechanism of posttraumatic paresis in lumbosacral plexopathies may involve a number of factors, including nerve crush caused by fractured bone fragments; retroperitoneal hemorrhage; and traction as a result of hyperextension, hyperflexion, or rotation around the hip joint. Conservative measures appear to be the most appropriate way to manage posttraumatic injuries. More than two-thirds of patients show good or moderate recovery of paresis after 18 months of follow-up after injury.

Pregnancy

The lumbosacral trunk may be compressed by the fetal head during the second stage of labor. This tends to occur in prolonged labor with midforceps rotation in a small primigravida mother carrying a relatively large baby. A day or so after delivery when the patient gets out of bed, she notes difficulty walking because of foot dorsiflexor weakness. Examination discloses weakness in dorsiflexion and inversion, with reduced sensation over the lateral aspect of the leg and dorsal surface of the foot. Nerve conduction studies disclose attenuation or absence of the superficial peroneal SNAP on the affected side, and needle EMG reveals denervation in muscles innervated by L5 below the knee (Katirji et al., 2002). The primary pathology is predominantly demyelination, and the prognosis for complete recovery within 5 months is very good. In subsequent pregnancies, a trial of labor can be allowed so long as there is no evidence of disproportion or malpresentation. If labor proceeds, forceps should be used with great caution. Midforceps use in a woman with a previous obstetrical lumbosacral trunk palsy invites danger. It is prudent to perform cesarean section if the trial of labor is unsuccessful or if the infant is large.

Femoral neuropathy may occur in a thin patient during cesarean section in cases managed with self-retaining retractors (Alsever, 1996). In the thin abdominal wall, a deep lateral insertion of retractor blades exerts pressure on the psoas and may injure the femoral nerve. After surgery, the patient notes weakness and numbness in the territory of the femoral nerve. Recovery is usually rapid and full. The obturator nerve may be compressed by the fetal head or forceps near the pelvic brim. Patients note pain in the groin and anterior thigh as well as weakness and sensory loss in the territory of this nerve.

Neoplasia

The lumbosacral plexus may be damaged by tumors that invade the plexus either by direct extension from intraabdominal neoplasm or by metastases. Most tumors involve the plexus by direct extension (73%), whereas metastases account for only a fourth of cases. The primary tumors most frequently encountered are colorectal, cervical, and breast, as well as sarcoma and lymphoma (Jaeckle, 2010). Three clinical syndromes occur: upper plexopathy with findings referable to the L1-L4 segments (31%); lower plexopathy with changes in the L4-S1 segments (51%); and panplexopathy with abnormalities in the L1-S3 distribution (18%). Neoplastic plexopathy typically has an insidious onset over weeks to months. Severe and unrelenting pain is a prominent early manifestation and is aching or cramping in quality; it typically radiates from the low back to the lower extremities. Weeks to months after pain begins, numbness, paresthesias, weakness, and leg edema develop. Incontinence or impotence occurs in fewer than 10% of patients. The most commonly encountered tumors are colorectal in upper plexopathy, sarcomas in lower plexopathy, and genitourinary in panplexopathies. The majority of neoplastic plexopathies are unilateral, although bilateral plexopathies, caused usually by breast cancer, occur in approximately 25% of patients. The prognosis in lumbosacral plexopathy due to neoplasm is poor, with a median survival of 5.5 months.

Three special syndromes do not fit easily into upper, lower, or panplexopathy categories. In the first, there are paresthesias or pain in the lower abdominal quadrant or groin, with little or no motor abnormality. These patients are found to have a tumor next to L1 leading to involvement of the ilioinguinal, iliohypogastric, or genitofemoral nerves. A second group has numbness over the dorsomedial portion of the foot and sole, with weakness of knee flexion, ankle dorsiflexion, and inversion. These patients have a lesion at the level of the sacral ala, with involvement of the lumbosacral trunk. A third group present with perineal sensory loss and sphincter weakness and have neoplastic involvement of the coccygeal plexus, caused usually by rectal tumors.

Neuroimaging with CT or MRI usually establishes the diagnosis of neoplastic plexopathy, but MRI is probably more sensitive (Taylor et al., 1997). Because pelvic neoplasms may extend into the epidural space, most often below the conus medullaris, MRI of the lumbosacral spine is indicated in most patients. On occasion, a plexus neoplasm is difficult to discern by the best neuroimaging procedures. Two main explanations for this phenomenon exist. First, patients who have received previous radiotherapy may have developed tissue fibrosis that cannot be distinguished from recurrent tumor. Second, some tumors track along the plexus roots and do not produce an identifiable mass. In these instances, ancillary imaging tests (high-resolution MRI, bone scan, plain films, IVP), a biopsy of the plexus, or both may be required to determine the etiology. Prostate cancer may cause a lumbosacral radiculoplexopathy when tumor advances into the lumbosacral plexus by perineurial spread, a process that may evolve for up to 8 years, is associated with prominent urinary dysfunction, and leads to an MRI appearance of asymmetrical nerve enlargement but otherwise normal pelvic and abdominal imaging (Ladha et al., 2006).

Radiation Plexopathy

Radiation plexopathy usually produces slowly progressive painless weakness (Jaeckle, 2010). Dropcho (2010) points out that the radiation injury to the plexus most commonly occurs after treatment of pelvic tumors, testicular tumors, or tumors involving paraaortic lymph nodes. Pain develops in approximately half of patients with radiation plexopathy but is usually not early or severe (Dropcho, 2010). Most patients with radiation plexopathy eventually develop bilateral weakness, which is often asymmetrical and affects any muscles innervated by L2 through S1 but typically has an L5-S1 predominance (Dropcho, 2010). In most patients, leg reflexes are absent, and superficial sensation is impaired. Symptoms referable to bowel or urinary tract are usually the result of proctitis or bladder fibrosis. The latent interval between radiation and the onset of neurological manifestations is between 1 and 31 years (median 5 years), although very short latencies of less than 6 months have also been reported. An acute presentation of lumbosacral plexopathy 10 weeks following completion of radiation therapy for cervical cancer has also been observed (Abu-Rustum et al., 1999). No consistent relationship is evident between the duration of the symptom-free interval and the amount of radiation.

In most patients, radiation plexopathy is gradually progressive and results in significant or severe disability. CT and MRI of the abdomen and pelvis are typically normal and are useful in detecting lumbosacral plexus metastases (Dropcho, 2010). EMG discloses paraspinal fibrillation potentials in 50% of patients, suggesting that radiation damages the nerve roots in addition to the plexus; hence, a more appropriate designation is radiation radiculoplexopathy. In almost 60% of patients, the EMG discloses myokymic discharges, a feature that is only rarely seen in neoplastic plexopathy.

Vasculitis

Vasculitic neuropathy has generally been associated with the pattern of multiple mononeuropathy, but other neuropathic syndromes have also been described, including painful lumbosacral plexopathy. The portions of the peripheral nervous system most susceptible to vasculitis-induced ischemia are the segments of peripheral nerve located at the midhumerus and midfemur levels, regions of nerve that appear to be watershed zones between vascular territories of the vasa nervorum. Proximal nerve trunks and nerve roots may also be vulnerable to the vasculitic process.

When a lumbosacral plexopathy syndrome occurs in a patient known to have a vasculitis such as polyarteritis nodosa or rheumatoid arthritis, vasculitic plexopathy is an obvious diagnosis. The clinical diagnosis is more difficult in the setting of a seemingly idiopathic polyneuropathy or plexopathy because the process may be monosystemic and restricted to the peripheral nervous system. In such a case, a nerve biopsy may be required to establish the correct diagnosis.