III

Chapter

75

Disorders of Nerve Roots and Plexuses

David A. Chad CHAPTER OUTLINE
Disorders of Nerve Roots 1890
Anatomical Features 1890 Traumatic Radiculopathies 1891 Diabetic Polyradiculoneuropathy 1896 Neoplastic Polyradiculoneuropathy (Neoplastic Meningitis) 1898 Infectious Radiculopathy 1898 Acquired Demyelinating Polyradiculoneuropathy 1901 Acquired Disorders of the Dorsal Root Ganglia 1902 Radiculopathies Simulating Motor Neuron Disease 1902 Electrodiagnostic Studies 1904 Radiological Studies 1905 Traumatic Plexopathy 1905 Neurogenic Thoracic Outlet Syndrome 1906 Metastatic and Radiation-Induced Brachial Plexopathy in Patients with Cancer 1906 Idiopathic Brachial Plexopathy 1908

Disorders of the Lumbosacral Plexus 1909

Anatomical Features 1909 Clinical Features 1910 Differential Diagnosis 1911 Structural Lumbosacral Plexopathy 1912 Nonstructural Lumbosacral Plexopathy 1914 Idiopathic Lumbosacral Plexopathy 1914

Disorders of the Brachial Plexus 1903

Anatomical Features 1903 Clinical Features and Diagnosis 1904 Neurological Examination 1904

Disorders of Nerve Roots

The anterior and posterior nerve roots run from the spinal cord to the dorsal root ganglia, where they unite to form the spinal nerve. They are susceptible to diseases specific to their location and to many of the disorders that affect the peripheral nerves in general. Although surrounded by a rigid bony canal, they are delicate structures subject to compression and stretching. Bathed by cerebrospinal fluid (CSF), they may be injured by infectious, inflammatory, and neoplastic processes that involve the leptomeninges. Separated from the blood by an incomplete blood-nerve barrier, the dorsal root ganglion (DRG) neurons may be injured by circulating neurotoxins. In the clinical sphere, it is usually not difficult to recognize that a group of symptoms and signs is caused by a lesion of a nerve root. Radicular pain and paresthesias are accompanied by sensory loss in the dermatome (the area of skin innervated by one nerve root), weakness in the myotome (defined as muscles innervated by the same spinal cord segment and nerve root), and diminished deep tendon reflex activity at a segmental level subserved by the nerve root in question. When many roots are involved by a disease process (polyradiculopathy), however, the clinical picture may resemble a disorder of the peripheral nerves, as in a polyneuropathy, or of the anterior horn cells, as in the progressive muscular atrophy form of amyotrophic lateral sclerosis (ALS). Diagnosis therefore 1890

may become more difficult. Clinicians then turn to laboratory studies for help in arriving at a diagnosis. A disorder of the nerve roots is favored by abnormalities of the CSF (raised protein concentration and pleocytosis), paraspinal muscle needle electromyographic (EMG) examination (presence of positive sharp waves and fibrillation potentials), and spinal cord magnetic resonance imaging (MRI) (compromise or contrast enhancement of the nerve roots per se). The sections that follow cover some anatomical features relevant to an understanding of the pathological conditions that affect the nerve roots, as well as specific nerve root disorders.

Anatomical Features
Each nerve root is attached to the spinal cord by four to eight rootlets that are splayed out in a longitudinal direction (Rankine, 2004). The dorsal roots are attached to the spinal cord at a well-defined posterolateral sulcus. The ventral rootlets are more widely separated and emerge over a greater area. At each spinal cord segment, a pair of dorsal and ventral roots unite just beyond the DRG to form a short mixed spinal nerve that divides into a thin dorsal ramus and a thicker ventral ramus (Fig. 75.1). The dorsal ramus innervates the deep posterior muscles of the neck and trunk (the paraspinal muscles) and the skin overlying these areas. The ventral ramus (the large anterior branch) contributes to the intercostal nerve or
Copyright 2012 Elsevier Inc., Ltd., BV. All rights reserved. DOI: 10.1016/B978-1-4377-0434-1.00100-6


CSF Dura Arachnoid PIA Ligamentum dental Spinal cord Dorsal nerve rootlets Joint

Chapter 75Disorders of Nerve Roots and Plexuses 1891 tomographic (CT) and MRI scans, the fat acts as an excellent natural contrast agent that defines the thecal sac and nerve roots, allowing detection of nerve root compression. The dorsal roots contain sensory fibers that are central processes of the unipolar neurons of the DRG. On reaching the spinal cord, these fibers either synapse with other neurons in the posterior horn or pass directly into the posterior columns. In the ventral root, most fibers are essentially direct extensions of anterior horn motor neurons (alpha, beta, and gamma fibers) or of neurons in the intermediolateral horn (preganglionic sympathetic neurons found in lower cervical and thoracic segments). In addition, ventral roots contain a population of unmyelinated and thinly myelinated axons that come from sensory and sympathetic ganglia (Hildebrand etal., 1997). There are 31 pairs of spinal nerves that run through the intervertebral foramina of the vertebral column: 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, and 1 coccygeal (Fig. 75.2). A feature of clinical relevance is the pattern formed by the lumbar and sacral roots as they leave the spinal cord and make their way to their respective DRG to form spinal nerves. In the adult, the spinal cord is shorter than the spinal column, ending usually between L1 and L2. Therefore, the lumbar and sacral roots descend caudally from the spinal cord to reach the individual intervertebral foramina, forming the cauda equina. The concentration of so many nerve roots in a confined area makes this structure vulnerable to a range of pathological processes.

Dural septum Spinal ganglion Dorsal ramus of nerve Ventral ramus of nerve Ventral nerve rootlets Body of vertebra

Vertebral artery Posterior longitudinal ligament Anterior longitudinal ligament

Fig. 75.1 Relations of dura to bone and roots of nerve shown in an oblique transverse section. On the right, the relations between the emergent nerve and the synovial joint are seen, but the joint between the vertebral bodies is not in the plane of the section. Dorsal and ventral roots meet at the dorsal root ganglion in the intervertebral foramen to form the mixed spinal nerve. The small dorsal ramus is the most proximal branch of the mixed spinal nerve and serves the cervical paraspinal muscles (not shown). The dura becomes continuous with the epineurium of the mixed spinal nerve at the intervertebral foramen. The posterior longitudinal ligament helps contain the intervertebral disk (not shown), preventing protrusion into the spinal canal. CSF, Cerebrospinal fluid.
(Reprinted with permission from Wilkinson, M., 1971. Cervical Spondylosis: Its Early Diagnosis and Treatment. Saunders, Philadelphia.)

Traumatic Radiculopathies 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 rootspinal nerveplexus 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 charac teristic 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

the cervical, brachial, or lumbosacral plexus and thereby supplies the trunk and limb muscles. The nerve roots lie freely in the subarachnoid space, covered by a thin root sheath which is a layer of flattened cells continuous with the pial and arachnoidal coverings of the spinal cord. They lack the epineurial and perineurial coverings found in peripheral nerves. Compared with spinal nerves, the roots have many fewer connective tissue cells in the endoneurium and considerably less collagen. A capillary network derived from the radicular arteries provides the blood supply to the spinal nerve roots (Levin, 2002). Where the nerve roots form the mixed spinal nerve, the pial covering of the root becomes continuous with spinal nerve perineurium, and the nerve takes the dural nerve root sheath through the intervertebral foramen to become continuous with the epineurium of the mixed nerve. At the intervertebral foramen, the root-DRG-spinal nerve complex is securely attached by a fibrous sheath to the transverse process of the vertebral body. In general, the DRG is located in a protected position within the intervertebral foramina, but at the lumbar and sacral levels, the DRG resides proximal to the neural foramina in an intraspinal location (Levin, 2002). There they may be vulnerable to disk herniation and the complications of osteoarthritis and lumbosacral spondylosis. Nerve fibers, together with their meningeal coverings, occupy 35% to 50% of the cross-sectional area of an intervertebral foramen. The remaining space is occupied by loose areolar connective tissue, fat, and blood vessels. On computed

1892 Part IIINeurological Diseases

I II III IV V VI VII TI II III IV V VI VII 6 7 8 9 VIII IX 10 11 12 5 4 3 C1 2 3 4 5 6 7 8

I II III IV V VI VII

C1 2 3 4 5 6 7 8 T1 2 3 4 5 6 7 8 9

injuries in the newborn are discussed in Chapter 80. DejerineKlumpke 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. CLINICAL FEATURES AND DIAGNOSIS At the onset of root avulsion, flaccid paralysis and complete anesthesia develop in the myotomes and dermatomes served by ventral and dorsal roots, respectively. Clinical features supplemented by electrophysiological and radiological studies help determine whether the cause of severe weakness and sensory loss is root avulsion or an extraspinal plexus lesion. For example, C5 root avulsion results in virtually complete paralysis of the rhomboids and spinatus muscles (innervated primarily by C5) and a varying degree of weakness of the deltoid, biceps, brachioradialis, and serratus anterior (which receive additional innervation from C6). A clinical sign of T1 root avulsion is an ipsilateral Horner syndrome caused by damage to preganglionic sympathetic fibers as they traverse the ventral root to their destination in the superior cervical ganglion. Electrophysiological tests include the measurement of a sensory nerve action potential (SNAP) and needle EMG examination of the cervical paraspinal muscles. In the setting of an isolated C5 root avulsion, the SNAP should be preserved despite complete anesthesia in the dermatome, because the peripheral axons and the DRG cell bodies remain intact. Needle EMG of the cervical paraspinal muscles permits separation of damage of the plexus and of ventral root fibers because the posterior primary ramus, which arises just beyond the DRG and proximal to the plexus as the first branch of the spinal nerve, innervates these muscles (see Fig. 75.1). Thus, cervical paraspinal fibrillation potentials support the diag nosis of root avulsion. Paraspinal muscles have also been evaluated radiologically in the setting of root avulsion. Contrast-enhanced MRI studies of the cervical paraspinal muscles showing severe atrophy were accurate in indicating root avulsion injuries, and abnormal enhancement in the multifidus muscle was the most accurate among paraspinal muscle findings (Hayashi etal., 2002). Intraspinal neuroimaging using postmyelographic CT or MRI usually demonstrates an outpouching of the dura filled with contrast or CSF at the level of the avulsed root (Hayashi etal., 1998). This posttraumatic meningocele results from tears in the dura and arachnoid sustained during root avulsion. Advances in MRI technology now provide high-resolution images that can demonstrate root avulsion and obviate the need for CT myelography (Rankine, 2004). In most cases, these tests are helpful in ascertaining whether root avulsion has occurred, but clinical assessment may be challenging, and testing results may be ambiguous. The physical examination may be limited because of severe pain. An absent SNAP indicates sensory axon loss distal to the DRG but does not exclude coexisting root avulsion. Even when this test of sensory function points to avulsion of the dorsal component of the root, the status of the ventral root may remain uncertain if paraspinal fibrillation potentials are not found. There are two reasons for their absence. First, they do not

T1 2

TI II III IV V

VI VII VIII IX X

X XI

10
XI XII

L1 2 3 4 5 XII S1 2 3 LI 4 5 II III IV V

11 12
LI

L1
II

2
III

3
IV

4
V

5 S1 2 3 4 5 Coc.1 Fig. 75.2 Relationship of spinal segments and nerve roots to vertebral bodies and spinous processes in the adult. Cervical roots C1 to C7 (i.e., all except C8) exit through foramina above the vertebral body of the same number. The C8 root passes through the C7-T1 neural foramen, and all thoracic, lumbar, and sacral roots leave the spinal canal below the body of the vertebrae of the same number. The spinal cord is shorter than the spinal column, ending between vertebral bodies L1 and L2. Lumbar and sacral roots form the cauda equina and descend caudally, beside and below the spinal cord, to exit at the intervertebral foramina.
(Reprinted with permission from Haymaker, W., Woodhall, B., 1953. Peripheral Nerve Injuries, second ed. Saunders, Philadelphia.)

Chapter 75Disorders of Nerve Roots and Plexuses 1893

appear for 7 to 10 days after the onset of axonotmesis, and second, even if the timing of the needle EMG is right, they may not be seen because of innervation of the paraspinal muscles from multiple segmental levels. TREATMENT Root avulsion produces a severe neurological deficit that was considered an untreatable injury up until a few decades ago. In the past 30 years, microsurgical techniques and intraoperative electrophysiological studies have improved prospects for recovery for many patients with severe injury to peripheral nerves. The procedures of neurolysis (freeing intact nerve from scar tissue), nerve grafting (bridging ruptured nerves), and neurotization, or nerve transfer (attaching a donor nerve to the ruptured distal stump), have all been employed in the management of root avulsion injuries (Rankine, 2004). After C5 and C6 root avulsion injuries, for example, the plegic elbow flexors may be restored by several procedures that provide for neurotization of the musculocutaneous nerve, including reinnervating the biceps with an ulnar nerve fascicle (Tung etal., 2003) or employing a branch of the accessory nerve using a sural nerve graft (Samil etal., 2003); intercostal and phrenic nerves have also been used (Rankine, 2004). Carlstedt and colleagues (1995) pioneered another approach nerve root repair and reimplantation. They reported on a patient who had an avulsion injury involving C6-T1 in whom they were able to successfully implant two ventral roots (C6 directly and C7 via sural nerve grafts) into the spinal cord through slits in the pia mater. The surgical treatment of patients with avulsion injuries is an area of active ongoing investigation with the promise that if continuity between spinal cord and nerve roots can be restored, subsequent recovery of function may be possible (Fournier etal., 2001). The sometimes intractable pain of cervical root avulsion injuries may be successfully treated with dorsal root entry zone coagulation procedures (Samii etal., 2001).

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

L4 Vertebra Posterior-lateral protrusion of L4-L5 disc L4 Spinal nerve L4-5 Central disk protrusion L5 Vertebra Posterior-lateral protrusion of L5-S1 disc L5 Spinal nerve Lateral protrusion of L5-S1 disk S1 Spinal nerve

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.)

1894 Part IIINeurological Diseases of the cauda equina. Most cervical disk herniations are posterolateral or foraminal. In the cervical and lumbar regions, alteration in the integrity of the disk space is a component of a degenerative con dition 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 etal., 2001). The release of NO by disk cells may contribute to the process of disk degeneration by inducing apoptosis (Kohyama etal., 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). 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
Touch sensation Pain sensation

B
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.)

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 legraising 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

Chapter 75Disorders of Nerve Roots and Plexuses 1895 Both diagnostic modalitiesthe imaging approach that reveals anatomical details and the EMG techniques that disclose neurophysiological functionagree 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 etal., 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 etal., 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 abnormalitiesespecially acute changes of denervation including fibrillation potentials and positive sharp wavesare 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 roots 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

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 legraising 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).

1896 Part IIINeurological Diseases

Normal Acute axon-loss L5 radiculopathy Collateral re-innervation by L4 axon

L4 L5

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 Mini monograph #32: the electrophysiologic examination in patients with radiculopathies. Muscle Nerve 11, 1099-1114.)

Peroneal nerve

Tibialis anterior muscle

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). TREATMENT For cervical disk protrusion and spondylotic radiculopathy, the mainstay of treatment is conservative managementa combination of a period of reduced physical activity with use of a soft cervical collar, physiotherapy, and antiinflammatory and analgesic agents. Most patients improve, even those with mild to moderate motor deficits. Indeed, in some cases, herniated cervical disks have been observed to regress on MRI images, a circumstance that appears more likely to occur if disk material has extruded and becomes exposed to the epidural space (Mochida etal., 1998). Although there appears to be a short-term benefit to surgical decompression of an affected nerve root with regard to pain, weakness, or sensory loss, at 1 year, there is no significant difference between the outcome of surgical or conservative management (physical therapy or hard cervical collar immobilization) (Fouyas etal., 2002). A surgical approach may be warranted, however, in selected cases: (1) if there is unremitting pain despite an adequate trial of conservative management, (2) if there is progressive weakness in the territory of the compromised nerve root, or (3) if there are clinical and radiological signs of an accompanying new onset of myelopathy, although in a group of patients with mild or moderate myelopathy, those managed

surgically had the same outcome (degree of functional disability) as those allocated to conservative treatment (Fouyas etal., 2002). In the lumbosacral region, disk herniation and spondylotic changes respond to conservative management in more than 90% of patients. Bed rest had been recommended as the centerpiece of patient care, but controlled trials have demonstrated that back-strengthening exercises under the direction of a physical therapist, performed within the limits of the patients pain, result in more rapid resolution of pain and return to normal function (Vroomen etal., 1999). Follow-up MRI studies in conservatively managed patients indicate reduction in size or disappearance of herniated nucleus pulposus corresponding to improvement in clinical findings (Komori etal., 1996). Epidural corticosteroid injection may help relieve pain but does not improve neurological function or reduce the need for surgery (Carette etal., 1997). A single intravenous (IV) bolus of methylprednisolone (500mg) given to patients with acute diskogenic sciatica of less than 6 weeks duration provided short-term improvement in leg pain, but the effect was relatively small, with no effect on functional disability, and transitory (3 days) (Finckh etal., 2006). When a patient population with sciatica due to a herniated lumbar disk is followed at regular intervals for more than 10 years, surgically treated patients report more complete relief of leg pain and improved function and satisfaction compared with the nonsurgically treated group. However, improvement in the patients predominant symptom and work or disability outcomes were similar in the two groups (Atlas etal., 2005). Three situations occur in which surgical referral is indicated: (1) in patients presenting with cauda equina syndrome, for which surgery may be required urgently, (2) if the neurolo gical deficit is severe or progressing, or (3) if severe radicular pain con tinues after 4 to 6 weeks of conservative management.

Diabetic Polyradiculoneuropathy
Diabetic neuropathies can be classified anatomically into two major groups: symmetrical polyneuropathies and asymmetrical focal or multifocal disorders. Examples of the latter include

Chapter 75Disorders of Nerve Roots and Plexuses 1897 Laboratory studies disclose elevated fasting blood glucose in the vast majority of patients; when values are normal, they are found in treated diabetics. The erythrocyte sedimentation rate is usually normal, but in a subgroup of patients with diabetic lumbosacral polyradiculoneuropathy, it is elevated, a clue perhaps to an immune-mediated pathogenesis. The typical electrodiagnostic findings comprise features of a sensorimotor axon-loss polyneuropathy (diminished sensory and motor action potentials, normal or slightly prolonged distal latencies, and normal or mildly slowed conduction velocities) with additional needle electrode examination findings of active and chronic denervation changes in paraspinal, pelvic-girdle, and thigh muscles. Taken together, the findings reflect multifocal axonal damage to the nerve roots and lumbosacral plexus (Amato and Barohn, 2001). Although clinical findings may point to unilateral involvement, the electrodiagnostic examination generally discloses bilateral signs. Imaging studies of the thoracic and lumbosacral spinal canal with CT, myelography, and MRI are typically normal but are almost always necessary to exclude a structural abnormality of the nerve roots that may simulate diabetic polyradiculopathy. The CSF protein level is usually increased to an average of 120 mg/dL, but in some patients values exceed 350 mg/dL; pleocytosis is not a feature of this condition. Biopsy of proximal nerve sensory branches reveals axon loss and demyelination; in more severely affected patients, inflammatory cell infiltration and vasculitis is found (Said et al., 1997). Further studies of nerve biopsy specimens indicate that a microscopic vasculitis (involvement of small arterioles, venules, and capillaries) leads to ischemic injury, which in turn causes axonal degeneration and secondary segmental demyelination (Dyck et al., 1999). The presence of a smallvessel vasculitis with distinctive pathological features including transmural polymorphonuclear leukocyte infiltration of postcapillary venules and endothelial deposits of immunoglobulin (Ig)M and activated complement supports an immune-mediated inflammatory pathogenesis for this disorder (Kelkar et al., 2000). Electrophysiological studies have suggested that a demyelinating polyneuropathy indistinguishable from chronic inflammatory demyelinating polyneuropathy (CIDP) occurs frequently in diabetes and may be the cause of a severe motor sensory polyneuropathy, sometimes with features of a plexopathy (Sharma etal., 2002a, 2002b). The natural history of diabetic polyradiculoneuropathy is for improvement to occur in most patients, although the recovery phase is lengthy, ranging between 1 and 18 months with a mean of 6 months. Pain and dysesthesias improve or disappear entirely in 85% of patients; numbness improves or recovers in 50%; and strength is partially or completely restored in 70%. In some patients, episodes recur. Therapy is usually directed toward ameliorating the severe pain of this condition. The tricyclics, especially nortriptyline (with a better side-effect profile than amitriptyline), selective serotonin reuptake inhibitors (e.g., sertraline, nefazodone hydrochloride), anticonvulsants (e.g., gabapentin, carbamazepine), clonazepam, baclofen, clonidine, mexiletine, IV lidocaine, and topical capsaicin may have a role separately or in combination. Histopathological findings indicative of an immune-mediated pathogenesis have led to treatment of selected patients with intravenous immunoglobulin (IVIG) or immunosuppressive treatment or both (Krendel etal., 1995;

the cranial mononeuropathies and the conditions covered in this section: thoracoabdominal and lumbosacral polyradiculoneuropathies. Though treated separately in the following paragraphs, they often coexist in an individual patient. Occasionally, a similar syndrome can occur in the cervical roots. When there is predominant involvement of the thoracic roots, the presenting symptoms are generally pain and paresthesias of rapid onset in the abdominal and chest wall. The trunk pain may be severe, described variably as burning, sharp, aching, and throbbing. It may mimic the pain of acute cardiac or intraabdominal medical emergencies and may simulate disk disease, but the rarity of thoracic disk protrusions and the usual development of a myelopathy help exclude this diagnosis. Findings of diabetic thoracoabdominal polyradiculoneuropathy include heightened sensitivity to light touch over affected regions; patches of sensory loss on the anterior, lateral, or posterior aspects of the trunk; and unilateral abdominal swelling due to localized weakness of the abdominal wall muscles (Longstreth, 1997). Diabetic lumbosacral polyradiculoneuropathy involves the legs, especially the anterior thighs, with pain, dysesthesia, and weakness, reflecting the major involvement of upper lumbar roots. A variety of names have been used to describe it, including diabetic amyotrophy, proximal diabetic neuropathy, diabetic lumbosacral plexopathy, diabetic femoral neuropathy, and Bruns-Garland syndrome. Because it is likely that the brunt of nerve pathology falls on the nerve roots, it can be designated as diabetic polyradiculoneuropathy. Motor, sensory, and autonomic fibers are all affected by the disease process (Dyck etal., 1999). In most patients, onset is fairly abrupt, with symptoms developing over days to a couple of weeks. Early in the course of the condition, the clinical findings are usually unilateral and include weakness of muscles supplied by L2-L4 roots (iliopsoas, quadriceps, and hip adductors), reduced or absent patellar reflex, and mild impairment of sensation over the anterior thigh. As time passes, there may be territorial spread, a term used by Bastron and Thomas in 1981 to describe proximal, distal, or contralateral involvement as the polyradiculoneuropathy evolves. Worsening may occur in a steady or a stepwise fashion, and it may take several weeks to progress from onset to peak of the disease. At its peak, weakness varies in severity and extent from a mildly affected patient with slight unilateral thigh weakness to a profound degree of bilateral leg weakness in the territory of the L2-S2 nerve roots. Upperextremity involvement appears to occur in approximately 15% of patients with diabetic lumbosacral radicular plexopathy as a unilateral or asymmetrical sensorimotor neuropathy that primarily affects hands and forearms. Like the lumbosacral syndrome, EMG findings suggest a multifocal axon-loss process localized to roots, plexus, or peripheral nerve (Katz etal., 2001). Rarely, the process of territorial spread is so extensive that it involves a multiplicity of nerve roots along the entire spinal cord and leads to profound generalized weakness, a condition designated diabetic cachexia. Diabetic polyradiculoneuropathy tends to affect patients in the sixth or seventh decade of life who have noninsulindependent diabetes of several years duration. The syndrome of painful polyradiculoneuropathy, whether referable to thoracic or lumbosacral roots, may be the presenting manifestation of diabetes. In 30% to 50% of patients, the disorder is preceded by substantial weight loss of 30 to 40 pounds.

1898 Part IIINeurological Diseases Younger etal., 1998). Although immunotherapy may be beneficial, spontaneous improvement in some patients with painful proximal diabetic neuropathy with different patterns of inflammatory nerve lesions has been described (Said etal., 1997). A comprehensive and critical review of the literature on the role of immunotherapy of diabetic polyradiculopathy concludes that treatment remains controversial because the natural history is for spontaneous improvement, the side effects of immunotherapy may be significant, and information on efficacy is lacking from controlled clinical trials (Amato and Barohn, 2001). Prospective studies have suggested a role for immunotherapy in the treatment plan of diabetic polyradiculoneuropathy where electrophysiological findings are those of CIDP (Sharma etal., 2002a, 2002b), although the degree of improvement has been shown not to be as robust as in the immunotherapy of idiopathic CIDP (Gorson etal., 2000). The major differential diagnostic considerations are polyradiculoneuropathies related to degenerative disk disease and infectious, inflammatory, and neoplastic processes. These can usually be excluded by history, examination, and routine laboratory investigations including CSF analysis. In our experience, however, the clinical presentation provoking the most anxiety is the frail elderly patient not known to be diabetic who has weight loss and abrupt onset of lower-extremity pain and weakness that progresses over months. In such a patient, the specter of neoplasia looms large, and thorough imaging studies of the nerve roots and plexuses are mandatory.

Fig. 75.6 Cauda equina in leptomeningeal carcinomatosis. Seeding of multiple nerve roots by adenocarcinoma produces a nodular appearance.
(Courtesy Dr. T.W. Smith, Department of Pathology [Neuropathology], University of Massachusetts Medical Center, Worcester, MA.)

Neoplastic Polyradiculoneuropathy (Neoplastic Meningitis)

A wide variety of neoplasms are known to spread to the leptomeninges. These include solid tumors (carcinoma of the breast and lung and melanoma), non-Hodgkin lymphomas, leukemias, and intravascular lymphomatosis (Viali etal., 2000). Although neoplastic polyradiculoneuropathy usually occurs in patients known to have an underlying neoplasm, meningeal symptoms may be the first manifestation of malignancy. Neoplastic meningitis occurs in approximately 5% of all patients with cancer (Chamberlain, 2006). The clinical features of neoplastic polyradiculoneuropathy include radicular pain, dermatomal sensory loss, areflexia, weakness of the lower motor neuron type and bowel/bladder dysfunction (Balm and Hammack, 1996; Mammoser and Groves, 2010). Often the distribution of the sensory and motor deficits is widespread and simulates a severe sensorimotor polyneuropathy. Associated clinical manifestations (e.g., nuchal rigidity, confusion, cranial polyneuropathies) result from infiltration of the meninges. At postmortem examination, the cauda equina shows discrete nodules or focal granularity (Fig. 75.6). Microscopy discloses spinal roots encased by tumor cells, which appear to infiltrate the root. Malignant cells have the capacity to penetrate the pial membrane and invade the spinal nerves (Mammoser and Groves, 2010). It is presumed that disturbed nerve root function results from several mechanisms including nerve fiber compression and ischemia. The most revealing diagnostic procedure is lumbar puncture, which is almost always abnormal, disclosing one or more or the following: mononuclear pleocytosis, reduced CSF glucose, elevated protein, and neoplastic cells (Grossman and Krabak, 1999). Spinal fluid cytological analysis is, however,

persistently negative in up to a third of patients who have compelling evidence of leptomeningeal carcinomatosis (Kim and Glantz, 2001). A sensitive electrophysiological indicator of nerve root involvement is a change in the F wave. In the symptomatic patient with cancer, prolonged F-wave latencies or absent F responses should raise suspicion of leptomeningeal metastases. Postmyelography CT adds strong evidence in support of the diagnosis if it demonstrates multiple nodular defects on the nerve roots, but spinal MRI, especially with gadolinium enhancement, is the initial test of choice in the cancer patient in whom leptomeningeal involvement of the spine is suspected (Gleissner and Chamberlain, 2006). Approximately 50% of patients with neoplastic meningitis and spinal symptoms have abnormalities on these studies. Gadoliniumenhanced MRI of the brain discloses abnormalities, including contrast enhancement of the basilar cisterns or cortical convexities and hydrocephalus. Standard therapy for neoplastic meningitis is essentially palliative; it does, however, afford stabilization and protection from further neurological deterioration (Chamberlain, 2006). A multidisciplinary approach is recommended, with input from medical oncology, neuro-oncology, radiation oncology, and neurosurgery (Mammoser and Groves, 2010). With treatment that includes radiotherapy to sites of symptomatic disease, intrathecal or intraventricular chemotherapy (methotrexate, thiotepa, and cytosine arabinoside), and optimal management of the underlying malignancy, median survivals of 3 to 6 months may be achieved (Chamberlain, 2006; Kim and Glantz, 2001). On occasion, longer-term survival is observed in patients with neoplastic meningitis accompanying breast cancer (13% survival rate at 1 year and 6% at 2 years), melanoma, and lymphoma (Jaeckle, 2006). A complication of aggressive treatment is a necrotizing leukoencephalopathy that becomes symptomatic months after treatment with radiation and intrathecal methotrexate (Grossman and Krabak, 1999).

Infectious Radiculopathy 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

Chapter 75Disorders of Nerve Roots and Plexuses 1899 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). 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 etal., 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

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 etal., 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 (5-165cells/mL). More than 50% have mild protein elevation (45-100mg/dL, with rare instances of values up to 250mg/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 VirusInfected 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).

Fig. 75.7 Cytomegalovirus polyradiculoneuropathy. Numerous mono nuclear 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.)

1900 Part IIINeurological Diseases 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. 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 etal., 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 ageamong persons older than 75 years exceeds 10 cases per 1000 person-yearsand 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 etal., 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

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 etal, 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 parenchymahas 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,

Chapter 75Disorders of Nerve Roots and Plexuses 1901 tating 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 etal., 2000). Intravenous acyclovir followed by oral valacyclovir was found to reduce the pain of PHN in more than 50% of treated patients (Quan etal., 2005).

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 etal, 2008; Merchut and Gruener, 1996; Yaszay etal., 2000). Segmental zoster paresis is about equally divided between the arms and legs, with predominantly proximal muscle weakness reflecting weakness in cervical and lumbarC5, C6, and C7 or L2, L3, and L4myotomes, respectively. The diaphragm and abdominal muscles may be affected, and bladder and bowel dysfunction may occur in the setting of lumbosacral zoster (Gilden etal., 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 etal., 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 etal, 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 etal., 2000). A low-grade viral ganglionitis may contribute to PHN (Quan etal., 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 etal., 2010) and is well tolerated (Simberkoff etal., 2010). The pain of PHNdescribed variably as continuous deep aching, burning, sharp, stabbing, and shooting, and triggered by light touch over the affected dermatomesis often debili-

Acquired Demyelinating Polyradiculoneuropathy

Acquired demyelinating polyradiculoneuropathy has two major clinical forms. One develops acutely and is known as Guillain-Barr syndrome (GBS); the other is chronic, progressive, or relapsing and remitting and is designated CIDP. These disorders are described in detail in Chapter 76 but are mentioned here briefly because pathological changes may be pronounced in the spinal nerve roots, especially the ventral roots. There is a dense mononuclear inflammatory infiltrate of lymphocytes, monocytes, and plasma cells (Fig. 75.8), and segmental demyelination with relative sparing of axons. Neuroimaging with MRI discloses contrast enhancement of lumbosacral roots in both GBS and CIDP (Bertorini etal., 1995; Koller etal., 2005). The predilection for nerve root involvement in these conditions helps explain certain features including CSF and some neurophysiological findings, as well as disturbances in autonomic function that may be especially problematic in patients with GBS. A CSF profile of albuminocytological dissociation is characteristic of this syndrome. A high lumbar CSF protein concentration in the face of a normal cisternal protein level supports the hypothesis that increased CSF protein derives largely from capillaries of the spinal roots. Nerve conduction studies usually disclose slowed motor conduction velocities, dispersed motor responses, and partial conduction block, but

Fig. 75.8 Cauda equina in Guillain-Barr syndrome. A dense mononuclear infiltrate in the connective tissue surrounding the nerve roots is shown (hematoxylin-eosin stain). (Courtesy Dr. T.W. Smith, Department of Pathology
[Neuropathology], University of Massachusetts Medical Center, Worcester, MA.)

1902 Part IIINeurological Diseases additional abnormalities include delayed or unobtainable F-wave responses or H-reflexes, reflecting demyelination in nerve roots (Koller etal., 2005). Indeed, abnormalities of these late responses may be the sole finding in 10% to 20% of patients with GBS in the first few weeks of the illness. The autonomic disturbances that occur in GBS may be due to involvement of preganglionic sympathetic fibers, which travel in the ventral roots en route to the paravertebral sympathetic ganglia. of cancer, however, gives the best chance of helping the neurological disorder before it becomes devastating (Kuntzer et al., 2004). Other causes of DRG neuronopathy include hereditary, toxic, and autoimmune disorders (Kuntzer etal., 2004). Hereditary sensory neuropathies are usually marked by their chronicity, acrodystrophic ulcerations, fractures, bouts of osteomyelitis, and lack of paresthesias. Pyridoxine abuse and cisplatin neurotoxicity are generally easily recognized. Sjgren syndrome may be accompanied by ataxia and kinesthetic sensory loss very similar to subacute sensory neuropathy. The presence of antibodies to extractable nuclear antigens such as anti-Ro (SS-A) and anti-La (SS-B) are suggestive of the diagnosis, but their absence does not exclude Sjgren syndrome. Diagnosis may be established with the demonstration of clusters of inflammatory cells in minor salivary glands (focal sialadenitis) from a biopsy of clinically normal lip mucosa. In some cases of Sjgren sensory neuronopathy, cervical MRI shows cervical cord atrophy with increased T2 signal intensity at the dorsal column, which probably stems from wallerian degeneration of neurons in the dorsal root ganglia (Lin and Chiu, 2008). Improvement from courses of IVIG may occur in some patients when treated early in the course of the illness. Other autoimmune acute ataxic syndromes range from ataxic Guillain-Barr syndrome to Fisher syndrome and Bickerstaff brainstem encephalitis. In these syndromes, serum anti-GQ1B IgG antibody levels are frequently elevated. The disorders may respond to immunotherapy with IVIG and plasma exchange (Kuntzer etal., 2004).

Acquired Disorders of the Dorsal Root Ganglia

DRG may be selectively vulnerable to a variety of malignant and nonmalignant conditions. The resulting neurological disorder is a sensory neuronopathy syndrome whose clinical features are explained by the loss of large- and small-diameter DRG neurons (Bryer and Chad, 1999). Large-cell dropout leads to kinesthetic sensory impairment, poor coordination, loss of manual dexterity, ataxia, and areflexia, whereas smallcell depletion contributes to a hyperalgesic state marked by burning pains and painful paresthesias. The sensory neuronopathies are characterized by nonlength-dependent abnormalities of SNAPs, a global decrease in SNAP amplitudes, and hyperintensities on T2-weighted MRI images of the dorsal spinal cord (Kuntzer etal., 2004; Lin and Chiu, 2008). Clinical and electrophysiological criteria have been proposed to help separate patients with sensory neuronopathy from those with predominantly sensory polyneuropathy (Camdessanche etal., 2009). Favoring the diagnosis of neuronopathy are the following findings: the presence of limb ataxia early in the disease, asymmetrical sensory loss at onset, upper-limb sensory loss, lost or attenuated upper-limb sensory action potentials, and relatively normal motor conduction studies. Perhaps the best known of these uncommon conditions is paraneoplastic subacute sensory neuropathy (or neuronopathy), a disorder developing over weeks to months and characterized by ataxia and hyperalgesia while muscle strength is well preserved (Posner and Dalmau, 1997). Some patients have clinical signs of brainstem and cerebral dysfunction, reflecting a more widespread encephalomyelitis. The neuronopathy may antedate the diagnosis of cancer, usually small-cell lung carcinoma, by months to years. The CSF profile discloses elevated protein concentration and a mild mononuclear cell pleocytosis. Nerve conduction studies reveal widespread loss of sensory potentials. Neuropathological features include inflammation and phagocytosis of the sensory neurons in the DRG. This condition is associated with the presence of specific antineuronal (anti-Hu) antibodies that are complement-fixing polyclonal IgG antibodies that react with the nuclei of the neurons of the CNS and sensory ganglia but not with non-neuronal nuclei. The antigens recognized by the anti-Hu antibodies have been characterized as proteins with molecular weights of 35 to 40 kD. The presence of identical protein antigens in small-cell lung cancer cells and neuronal nuclei supports the view that the pathogenesis of paraneoplastic subacute sensory neuropathy is immunologically mediated, with tumor antigens triggering the production of cross-reactive antibodies. Morphological studies provide evidence for both cytotoxic T cellmediated attack and humoral mechanisms in the pathogenesis of this condition. Response to immunotherapy is disappointing; early diagnosis

Radiculopathies Simulating Motor Neuron Disease

Disorders of the motor roots may lead to clinical features that resemble those encountered in motor neuron disease. Detailed study of such motor neuron syndromes is important because it might provide clues to the pathogenesis of the most common form of motor neuron disease, ALS. Clinicians should consider the possibility of an ALS-mimic syndrome when a patient with clinical features of lower motor neuron involvement is found to have a monoclonal gammopathy (Chad and Harris, 1999). In that instance, investigations must vigorously pursue the possibility that physical findings stem from ventral root involvement rather than anterior horn cell degeneration. An elevated CSF protein level, the presence of a monoclonal gammopathy, along with a demyelinating process identified by nerve conduction studies suggest a potentially treatable lymphoproliferative disease manifesting as motor polyradi culoneuropathy. In some instances of IgM monoclonal gammopathy, there is antibody specificity for the gangliosides GM1, asialo-GM1, and GD1b, among others. In rare instances, immunotherapy that reduces the serum concentrations of IgM gangliosides is associated with improvement in the lower motor neuron syndrome, thereby suggesting a possible pathogenic role of antiganglioside antibodies. The association between lower motor neuron findings and lymphoma has been known for many years and is designated subacute motor neuronopathy, but the site of major pathology is not certain and could be at root and neuronal level. It is characterized by subacute, progressive, painless, often patchy and asymmetrical weakness of the lower motor neuron type, with greater involvement of the arms than the legs. The illness

Chapter 75Disorders of Nerve Roots and Plexuses 1903

often progresses independently of the activity of the under lying lymphoma and tends to follow a relatively benign course, with some patients demonstrating spontaneous improvement. A postradiation lower motor neuron syndrome affecting the lumbosacral region, probably a polyradiculopathy, has been described occurring 4 months to 25 years after radiation therapy for testicular cancer, vertebral metastases, and lymphoma (Hsia etal., 2003). In some patients, MRI shows gadolinium enhancement of the conus medullaris and cauda equina that may mimic a leptomeningeal tumor (Hsia etal., 2003). Neuropathological study in a case of testicular cancer disclosed radiation-induced vasculopathy of proximal spinal roots with preserved motor neurons (Bowen etal., 1996). The course of the disorder is typically one of progression for 1 to 2 years followed by eventual stabilization.

Disorders of the Brachial Plexus

Anatomical Features
The brachial plexus is formed by five spinal nerve ventral rami (C5-T1), each of which carries motor, sensory, and postganglionic sympathetic fibers to the upper limb. It is a large and complex peripheral nervous system structure that contains 100,000 to 160,000 individual nerve fibers (Ferrante and Wilbourn, 2002). These five rami unite above the level of the clavicle to form the three trunks of the brachial plexus (Fig. 75.9): C5 and C6 join to form the upper trunk; T1 and C8 unite to form the lower trunk; and C7, the largest of the five rami, continues as the middle trunk. (To review, a ventral ramusanterior primary ramusderives from a mixed spinal nerve that is formed in turn by the fusion of the posterior dorsal and ventral roots in the intervertebral foramen.)

Roots Trunks Subdivisions Cords

Subclavian nerve

Dorsal scapular nerve

Suprascapular nerve
5 5 6 7 8 1 1 2

Radial nerve

Axillary nerve

Subscapular nerves
Up
A A P P

pe
Mi

r
le

dd

Lo

r we

ra

La

te

Po

st

er
ia l

io

ed

Long thoracic nerve (nerve to serratus anterior)

Medial and lateral anterior thoracic nerves Musculocutaneous nerve Median nerve Ulnar nerve Medial cutaneous nerve of arm Medial cutaneous nerve of forearm Thoracodorsal nerve (Nerve to latissimus dorsi)

Fig. 75.9 Brachial plexus. Components of the plexus have been separated and drawn out of scale. The five ventral rami (C5-T1) unite to form the upper, middle, and lower trunks of the plexus above the clavicle. Beneath the clavicle, each trunk divides into anterior (A) and posterior (P) divisions. Three cords (lateral, posterior, and medial) lie below the pectoralis minor muscle (not shown). Major upper limb nerves originate from the cords.
(Reprinted with permission from Haymaker, W., Woodhall, B. 1953. Peripheral Nerve Injuries, second ed. Saunders, Philadelphia.)

1904 Part IIINeurological Diseases Beneath the clavicle, each trunk divides into an anterior and posterior branch leading to six divisions, which become the three cords of the brachial plexus, the lateral, medial, and posterior. The cords, which lie behind the pectoralis minor, take their names from their relationship to the subclavian artery. The lateral and medial cords carry motor fibers to the ventral muscles of the limb. The lateral cord is formed from anterior divisions of the upper and middle trunks, the medial cord from anterior division of the lower trunk. The posterior cord carries motor fibers to the dorsal muscles of the limb; it is formed from posterior divisions of the upper, middle, and lower trunks. The major named nerves of the upper limb derive from the cords. After contributing a branch to the formation of the median nerve, the lateral cord continues as the musculocutaneous nerve. Similarly, after making its contribution to the median nerve, the medial cord continues as the ulnar nerve. The posterior cord divides into a smaller axillary nerve, which leaves the axilla via the quadrangular space to supply the deltoid and teres minor and the larger radial nerve. Also, from the level of the cords, branches are distributed to the pectoralis major and minor muscles (from the lateral and medial cords, respectively) and to the subscapularis, latissimus dorsi, and teres major muscles (from the posterior cord). In addition to these motor branches, sensory branches also arise at a cord level. The posterior cutaneous nerve of the arm arises from the posterior cord, and the medial cutaneous nerve of the arm and the medial cutaneous nerve of the forearm come from the medial cord. Nerve branches to the serratus anterior, levator scapulae, rhomboids, and supraspinatus and infraspinatus muscles derive from more proximal levels of the plexus. The first three muscles are supplied by branches of the anterior primary rami: the serratus anterior from C5, C6, and C7 (the long thoracic nerve) and the levator scapulae and rhomboids from branches of C5 (the dorsal scapular nerve). The supraspinatus and infraspinatus muscles are supplied by the suprascapular nerve, a branch of the upper trunk of the plexus. side, except that an intact trapezius allows shrugging of the shoulder. The limb is flaccid and areflexic, with complete sensory loss below a line extending from the shoulder diagonally downward and medially to the middle of the upper arm. Lesions of the upper trunk produce weakness and sensory loss in a C5-C6 distribution. Affected muscles include the supraspinati and infraspinati, biceps, brachialis, deltoid, and brachioradialis, so the patient is unable to abduct the arm at the shoulder or flex at the elbow. If a lesion is so proximal that it involves the C5 ramus, the rhomboids and levator are also affected. The arm hangs at the side internally rotated at the shoulder, with the elbow extended and the forearm pronated in a waiters tip posture. The biceps and brachioradialis reflexes are diminished or absent, and sensory loss is found over the lateral aspect of the arm, forearm, and thumb. Lesions of the lower trunk produce weakness, sensory loss, and reflex changes in a C8-T1 distribution. Weakness is present in both median- and ulnar-supplied intrinsic hand muscles and in the medial finger and wrist flexors. The finger flexion reflex is diminished or absent, and there is sensory loss over the medial two fingers, the medial aspect of the hand, and the forearm. Cord lesions are usually found in the setting of trauma. A posterior cord lesion produces weakness in the territory of muscles innervated by both radial and axillary nerves. Sensory loss occurs in the distributions of the posterior cutaneous nerve of the forearm and the radial and axillary nerves. This results in sensory loss over the posterior aspect of the arm, the dorsal surface of the lateral aspect of the hand, and a patch of skin over the lateral aspect of the arm. Lateral cord injuries produce weakness in muscles supplied by the musculocutaneous nerve, as well as weakness in the muscles of the median nerve supplied by the C6 and C7 roots (the pronator teres and flexor carpi radialis muscles). The median and ulnar nerve fibers originating from C8 and T1 segments are spared, and thus there is no intrinsic hand muscle weakness. In medial cord lesions, there is weakness in all ulnar nervesupplied muscles and in the C8 and T1 median nervesupplied muscles.

Clinical Features and Diagnosis

Not surprisingly, disorders of the brachial plexus are determined in large part by its anatomical relationships (Ferrante and Wilbourn, 2002). Because of its location between two highly mobile structures, the neck and the shoulder, it is vulnerable to trauma. And because neighboring tissues such as lymph nodes, blood vessels, and lung parenchyma may themselves be targets of a variety of disease processes, the brachial plexus itself may be secondarily affected as an innocent bystander.

Electrodiagnostic Studies
Nerve conduction studies and needle EMG provide helpful information for confirming the clinical diagnosis of brachial plexopathy, determining the character of the lesion predominantly axon loss, demyelinating, or bothand arriving at a judgment with respect to prognosis for recovery of function. In axon-loss brachial plexopathies, SNAPs and compound motor action potentials (CMAPs) are attenuated or lost depending on the severity of the disease process because the amplitude of these responses correlates directly with the number of conducting fibers. (In preganglionic lesions [at a root level], sensory responses are expected to be spared, and only motor responses will be affected.) As long as at least some fast-conducting fibers are spared, the conduction velocities and distal latencies are unaffected. In the case of demyelinating lesions, however, nerve conduction velocities are typically slowed, motor evoked responses dispersed, and distal latencies prolonged. Most brachial plexus lesions are axon-loss in nature (Ferrante and Wilbourn, 2002). The needle examination is very sensitive for detecting even mild motor fiber loss because fibrillation potentials develop in affected muscles by 3 weeks after the onset of a disease process.

Neurological Examination
Patients with a brachial plexopathy present with a variety of patterns of weakness, reflex change, and sensory loss, depending on whether the whole or a portion of the plexus is disturbed. Most commonly encountered are three patterns resulting from involvement of the entire plexus, the upper trunk, and the lower trunk; less commonly seen are partial plexopathies caused by selective cord lesions. In a panplexopathy, paralysis of muscles supplied by segments C5 through T1 occurs. The arm hangs lifelessly by the

Chapter 75Disorders of Nerve Roots and Plexuses 1905 as a complication of the administration of nerve blocks. The most pronounced of the lesions affecting the brachial plexus are preganglionic, characterized by a nerve root avulsion when rootlets are torn from the spinal cord. Lesions affecting the postganglionic portion of the plexus may be severe because of nerve rupture or of lesser severity if caused by nerve stretch (Giuffre etal., 2010). Direct injury may be either open (gunshot wounds and lacerations) or closed (stretch or traction). The main causes of brachial plexus palsies are traction and heavy impact. Injuries are usually secondary to motorcycle and snowmobile accidents, but sporting accidents in football, bicycling, skiing, and equestrian events are also important. Supraclavicular injuries are more common and more severe and have a worse prognosis than infraclavicular injuries (Midha, 1997). Another form of brachial plexus traction is seen in rucksack paralysis. The straps of a rucksack or backpack pressed to the shoulders may exert heavy pressure in the region of the upper trunk of the brachial plexus and thus lead to weakness in the muscles supplied by the suprascapular and axillary nerves and sensory loss in the C5-C6 distributions.

Ferrante and Wilbourn (2002) note that axon-loss brachial plexus neuropathies fall along a spectrum of severity that may be determined by the results of the electrodiagnostic study. In the context of a minimal lesion affecting both sensory and motor fibers, SNAPs and CMAPs will typically be unaffected, but needle examination will disclose fibrillation potentials because the loss of one motor fiber will result in denervation of hundreds of muscle fibers. With an increase in lesion severity, SNAPs become attenuated while CMAPs are still spared. The most severe lesions compromise sensory responses and affect motor responses. Ferrante and Wilbourn also observed that it is the CMAPs that are most useful for quantifying the amount of loss suffered by a nerve. In contrast, SNAPs may be attenuated, even absent, with only partial lesions; and needle electrode examination, as we have seen, may reveal prominent fibrillation potentials with only mild motor axon loss. The needle examination is helpful in evaluating whether or not recovery from axon-loss lesions is ongoing because features of MUP remodeling (increased duration and complexity of MUPs) indicate the ongoing process of collateral reinnervation, distal-to-proximal reinnervation, or both. In a postganglionic plexopathy, numbness and sensory loss are associated with reduced or absent SNAPs because the lesion is located distal to the DRG. By contrast, in a pure radiculopathy, sensory loss is found in the face of a normal SNAP because the lesion is proximal to the DRG. In certain conditions, preganglionic and postganglionic lesions coexist, so electrodiagnostic studies disclose paraspinal muscle fibrillation and absent SNAPs. This situation is encountered most commonly in patients with trauma that damages both the plexus and avulses nerve roots. It is also found in some peripheral neuropathies such as diabetes and in malignant plexopathies in which tumor not only injures the plexus but also infiltrates the nerve roots by tracking through the intervertebral foramina. Specific EMG changes are covered under individual disorders of the plexus, later in the chapter.

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 patients 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.

Radiological Studies
Plain films of the neck and chest are often very helpful in evaluating arm weakness that is thought to be caused by a disorder of the brachial plexus. The presence of a cervical rib or long transverse process of C7 may provide an explanation for hand weakness and numbness, as seen in thoracic outlet syndrome. A lesion in the pulmonary apex, erosion of the head of the first and second rib, or the transverse processes of C7 and T1 may reveal the cause of a lower brachial plexopathy, as found in cases of Pancoast tumor. High-resolution CT and MRI scanning are also useful in detecting mass lesions of the plexus and may allow early diagnosis and specific therapy (Amrami and Port, 2005). There is an emerging role for magnetic resonance neurography to evaluate brachial plexus lesions (Zhou etal., 2004). CT-guided biopsy can be used to obtain cytological or histological material for precise diagnosis.

Long-Term Management
Once the patients 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

Traumatic Plexopathy
Three general categories of brachial plexus injury exist: (1) direct trauma, (2) secondary injury from damage to structures around the shoulder and neck, such as fractures of the clavicle and first rib, and (3) iatrogenic injury, most commonly seen

1906 Part IIINeurological Diseases 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 lesions 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 freefunctioning muscle transfers (Giuffre etal., 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 etal., 1997). In a large series of more than 1000 patients treated over a 30-year period (Kim etal., 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. median sensory amplitudes, along with a mildly reduced ulnar motor response and reduced ulnar sensory amplitude. The needle electrode examination typically discloses features of chronic axon loss with mild fibrillation potential activity in C8- and T1-innervated muscles. The clinical and electrophysiological findings point to a lesion of the lower trunk of the brachial plexus. Levin and colleagues (1998) have refined our understanding of the precise lesion localization of the neurogenic thoracic syndrome. They compared electrophysiological results between a group of patients with true neurogenic thoracic outlet syndrome and a group with brachial plexopathy stemming from median sternotomy. In the former group, the findings pointed to severe axon loss in the medial antebrachial cutaneous nerve and the abductor pollicis brevis, both sharing T1 root innervation. In the latter, an iatrogenic disorder resulting from rib retraction, the findings indicated axon loss in the ulnar sensory and motor nerves, conforming most to involvement predominantly of C8. These findings suggest that thoracic outlet syndrome and median sternotomy brachial plexopathy are due to damage to the mixed spinal nerve fibers at the level of the anterior primary rami (Levin, 2002)distal to the C8 or T1 nerve roots but proximal to the lower trunk of the brachial plexus. In most patients, a fibrous band extending from the tip of a rudimentary cervical rib to the scalene tubercle of the first rib causes angulation of either the C8 and T1 roots or the lower trunk of the brachial plexus (Fig. 75.10). Surgical division of the fibrous band can be expected to relieve pain and paresthesias and arrest muscle wasting and weakness in the majority of patients; return of muscle bulk and strength, however, is unlikely.

Neurogenic Thoracic Outlet Syndrome

Although it is frequently (mis)diagnosed, neurogenic thoracic outlet syndrome is a rare entity, seen only once or twice a year in busy EMG laboratories. Most patients are women. The mean age at onset is 32 years, but patients as young as 13 and as old as 73 have been reported. Pain is usually the first symptom, with either aching noted on the inner side of the arm or soreness felt diffusely throughout the limb. Tingling sensations accompany pain and are felt along the inner side of the forearm and in the hand. Most patients note slowly progressive wasting and weakness of the hand muscles. The physical examination discloses hand muscle weakness and atrophy, most marked in the lateral part of the thenar eminence. In a smaller number of patients, there is mild atrophy and weakness in the forearm muscles. Sensory loss is present along the inner side of the forearm. Except for the occasional Raynaud-type episode, vascular symptoms and signs are uncommon. In many cases, cervical spine roentgenograms disclose small bilateral cervical ribs or enlarged down-curving C7 transverse processes. When not visualized in anteroposterior radiographs of the cervical spine, they can be seen on oblique views. MRI of the thoracic outlet is a useful diagnostic method, revealing deviation or distortion of nerves or blood vessels and suggesting the presence of vasculonervous compressions (Demondion etal., 2003). Electrodiagnostic studies on the affected side disclose a reduced median motor response with normal

Metastatic and Radiation-Induced Brachial Plexopathy in Patients with Cancer Metastatic Plexopathy
Damage to the brachial plexus in patients with cancer is usually secondary to either metastatic plexopathy or radiationinduced 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.


Scalenus medius Scalenus anticus Brachial plexus Subclavian artery Subclavian vein First rib

Chapter 75Disorders of Nerve Roots and Plexuses 1907

Fig. 75.10 A, Normal relationships of subclavian artery and brachial plexus as they course over the first rib between the scalenus medius and anterior muscles. B, From the end of a short cervical rib arises a fibrous band (arrow), which attaches to the upper surface of the normal first rib. This stretches and angulates chiefly the lower trunk of the brachial plexus, causing neurogenic thoracic outlet syndrome. (Reprinted with permission from

Stewart, J.D., 1993. Focal Peripheral Neuropathies, second ed. Raven Press, New York.)

An important syndrome first described by Pancoast in 1932 is a superior pulmonary sulcus tumor, the vast majority of which are nonsmall-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 etal., 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 anti depressants 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 etal., 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 etal., 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 etal., 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 etal., 2001). The natural history of radiation-induced plexopathy is that of steadily increasing deterioration, although

1908 Part IIINeurological Diseases 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 radiationinduced 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 etal., 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 etal., 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. some individuals, associated findings include relative hypertelorism, occasional cleft palate, and skin folds or creases on the neck or forearm (Hannibal etal., 2009).

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 etal., 2002). Individual fascicular involvement of the musculocutaneous nerve, causing isolated brachialis wasting, has also been reported (Watson etal., 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 etal., 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 etal., 2006).

Idiopathic Brachial Plexopathy

Arm pain and weakness are the cardinal manifestations of idiopathic brachial plexopathy. They occur in all age groups, particularly between the third and seventh decades of life. Men are affected two to three times more often than women; there appears to be a higher incidence among men engaged in vigorous athletic activities such as weight lifting, wrestling, and gymnastics. Although half the cases seem unrelated to any precipitating event, in others the plexopathy follows an upper respiratory tract infection, a flulike illness, an immunization, surgery, or psychological stress, or it occurs postpartum (van Alfen and van Engelen, 2006). A familial form of brachial plexus neuropathy, so-called hereditary neuralgic amyotrophy, is an autosomal dominant disorder causing repeated episodes of intense pain, paralysis, and sensory disturbances in an affected limb (Chance, 2006). Like the idiopathic disorder, there may be similar antecedent triggering events. Onset is at birth or early childhood, with a good prognosis for recovery after each attack. Three point mutations have been found in the gene SEPT9, encoding the septin-9 protein, in 49 pedigrees with hereditary neuralgic amyotrophy linked to chromosome 17q25 (Hannibal etal., 2009; Kuhlenbaumer etal., 2005). In

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

Chapter 75Disorders of Nerve Roots and Plexuses 1909 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 etal., 2002).

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) (CruzMartinez etal., 2002). Sensory studies are abnormal in onethird 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.

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 etal., 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.

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 etal., 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

Disorders of the Lumbosacral Plexus

Anatomical Features
The lumbar plexus is formed within the psoas major muscle by the anterior primary rami of lumbar spinal nerves L1, L2, L3, and L4. It is connected to the sacral plexus in the true

1910 Part IIINeurological Diseases

L1 Iliohypogastric nerve Ilioinguinal nerve Lateral cutaneous nerve of thigh 4 Genitofemoral nerve

L1

Lumbosacral trunk Superior gluteal nerve Inferior gluteal nerve Sciatic nerve 3 4 Inferior hemorrhoidal nerve Dorsal nerve of penis Perineal nerve Pudendal nerve

5 Femoral nerve Obturator nerve Lumbosacral trunk Posterior cutaneous nerve of thigh

Fig. 75.11 A, Lumbar plexus is formed by anterior primary rami of lumbar spinal nerves L1, L2, L3, and L4 (note branches that arise from plexus). B, Sacral plexus is connected to lumbar plexus by the lumbosacral trunk (note branches that arise from plexus in pelvis). (Reprinted with permission from
Haymaker, W., Woodhall, B., 1953. Peripheral Nerve Injuries, second ed. Saunders, Philadelphia.)

pelvis by the anterior division of L4 (Fig. 75.11, A). Branches of the lumbar plexus include the iliohypogastric and ilioinguinal nerves arising from L1 (with a contribution from T12), the lateral femoral cutaneous nerve of the thigh originating from the posterior divisions of L2 and L3, and the genitofemoral nerve arising from the anterior division of L1 and L2. Other branches are the femoral nerve, formed from the posterior divisions of L2, L3, and L4 within the substance of the psoas muscle, and the obturator nerve, formed by the anterior divisions of L2, L3, and L4. The lumbar plexus communicates with the sacral plexus via the anterior division of L4, which joins with L5 to form the lumbosacral trunk at the medial border of the psoas at the ala of the sacrum. The trunk enters the pelvis and joins the sacral plexus in the piriformis fossa. The sacral plexus, derived from the anterior rami of spinal nerves L4, L5, S1, S2, and S3, forms in front of the sacroiliac joint (see Fig. 75.11, B). Like the lumbar plexus, the sacral plexus has anterior and posterior divisions. The anterior division contributes to the tibial portion, and the posterior division contributes to the peroneal portion of the sciatic nerve, which leaves the pelvis through the greater sciatic notch. A number of important branches come from the sacral plexus in the pelvis; the superior and inferior gluteal nerves arise from posterior divisions of the sacral plexus and supply the gluteus medius and minimus muscles and the gluteus maximus, respectively. The posterior cutaneous nerve of the thigh is formed by the anterior divisions of S1, S2, and S3. It passes through the greater sciatic foramen into the buttock. The pudendal nerve originates from the undivided anterior primary rami of spinal nerves S2, S3, and S4 and extends into the gluteal region via the greater sciatic foramen.

Clinical Features 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.

Chapter 75Disorders of Nerve Roots and Plexuses 1911

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.

Box 75-1 Clues to the Nature of a Plexopathy

Structural disorders History or presence of malignancy Hemophilia or treatment with an anticoagulant Pelvic trauma Known atherosclerotic vascular disease and hypertension aneurysm) Pregnancy, labor, delivery Abdominal (pelvic) surgery Nonstructural disorders Diabetes mellitus* Vasculitis Previous pelvic radiation
*Diabetics may develop a polyradiculoneuropathy that simulates a lumbosacral plexopathy.

Suspect lumbosacral plexopathy (by history and physical examination)

Electrodiagnostic studies

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).
Radiculopathy demonstrated* Lumbosacral plexopathy confirmed Polyneuropathy demonstrated

CT scan (ensure patient is not pregnant before performing scan) or MRI

Abnormal CT or MRI scan (structural plexopathy)

Normal CT or MRI scan (nonstructural plexopathy)

Determine precise nature of the lesion with the aid of history, general physical examination, and laboratory studies.

Differential Diagnosis
The differential diagnosis of lumbosacral plexopathy includes spinal root disorders (e.g., lumbosacral radiculopathy, poly radiculoneuropathy, cauda equina syndrome, anterior horn cell disorders) and myopathic conditions. Radiculopathies are usually painful, and the pain follows a predictable radicular distribution. Weakness is usually found in several muscles supplied by the same root, and the EMG usually demonstrates paraspinal muscle involvement. It is sometimes difficult to separate plexopathy from radiculopathy on clinical grounds alone, especially if several roots are involved.

Possibilities include diabetic, vasculitic, radiationinduced, and idiopathic plexopathies (determine exact cause with the help of history, physical examination, and other laboratory studies).

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).

1912 Part IIINeurological Diseases Anterior horn cell disorders give rise to painless progressive weakness with atrophy and fasciculation in the absence of sensory loss. When fully developed, such disorders should not be confused with lumbosacral plexopathy. In rare cases, however, a restricted anterior horn cell disorder (focal spinal muscular atrophy involving one leg) is seen. Absence of pain and sensory loss, normal imaging studies, and absence of diabetes and vasculitis all help point away from a disturbance of the lumbosacral plexus. Myopathies are rarely confused with lumbosacral plexopathy. Myopathies with a focal lower-extremity onset can be distinguished from lumbosacral plexopathy by elevation of muscle enzymes, myopathic features on EMG, and muscle biopsy.

Structural Lumbosacral Plexopathy 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 etal., 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
Fig. 75.13 Hemorrhagic lumbosacral plexopathy. Computed tomo graphic 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.

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 etal., 2006).

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 etal., 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 etal.,

Chapter 75Disorders of Nerve Roots and Plexuses 1913 ceeds, 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.

1997); 13% of patients with aneurysms of the iliac artery will present with features of sciatica (Delgado-Garcia etal., 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.

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 etal., 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

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 etal., 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 twothirds 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 etal., 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 pro-

1914 Part IIINeurological Diseases 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 etal., 2006). 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.

Nonstructural Lumbosacral Plexopathy 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 etal., 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.

Idiopathic Lumbosacral Plexopathy

Because lumbosacral plexopathy may occur in the absence of a recognizable underlying disorder, it can be considered a counterpart of idiopathic brachial plexus neuropathy (van Alfen and van Engelen, 1997). It may begin suddenly with pain, followed by weakness, which progresses for days or sometimes many weeks. In many patients, the condition stabilizes, but in some, the course is chronic progressive or relapsing/remitting. Weakness is found in the distribution of the upper and lower portions of the lumbosacral plexus in 50% of cases; major involvement occurs in the territory of the upper portion in 40% and in the lower portion in only 10% of patients. Most patients recover over a period of months to 2 years, although recovery is often incomplete. The EMG discloses a patchy pattern of denervation in the distribution of part or all of the lumbosacral plexus, but the paraspinal muscles are spared, indicating that the process does not affect the lumbosacral roots. Dyck and colleagues (2001) designated idiopathic lumbosacral plexopathy as nondiabetic lumbosacral radiculoplexus neuropathy and found that it resembles diabetic polyradiculoplexopathy in terms of its clinical presentation (subacute, asymmetrical, and painful with delayed and incomplete recovery) and pathological findings (ischemic injury and microvasculitis) and suggested that it probably has an immune pathogenesis. MRI has been reported to show gadolinium enhancement in the lumbar plexus that disappeared in association with resolution of symptoms and signs of plexopathy following IV gamma globulin treatment (Ishii etal., 2004). Immune-modulating therapy may be beneficial for a subgroup of patients with idiopathic lumbosacral plexopathy (Dyck and Windebank, 2002).

Vasculitis
Vasculitic neuropathy has generally been associated with the pattern of multiple mononeuropathy, but other neuropathic

References
The complete references list is available online at www. expertconsult.com.