Disorders of Nerve Roots and Plexuses

Nerve Root Avulsion

As noted earlier, each spinal root is composed of lesser amounts of collagen and is not supported by a dense epineural sheath compared to the mixed spinal nerves they form. This lack of reinforcement results in the spinal roots having approximately one-tenth the tensile strength of their corresponding peripheral nerves. Thus, the nerve root is the weakest link in the nerve root–spinal nerve–plexus complex, leading to root avulsion in the setting of traumatic traction injuries. 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, 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 ( ).

Avulsion at the level of the cervical roots can be total or may 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, infraspinatus, deltoid, and biceps). The second is Dejerine-Klumpke palsy , in which there is weakness and wasting of the intrinsic hand muscles, with a characteristic claw-hand 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 cause of this injury, but the classic paradigm is C5 and C6 root avulsions occurring in newborns during obstetrical procedures. Brachial plexus injuries in the newborn are discussed in Chapter 112 . Dejerine-Klumpke palsy occurs when the limb is elevated beyond 90 degrees and tension falls directly on the lower trunk of the plexus, C8, and T1 roots. Such an injury may occur in a fall from a height in which the outstretched arm grasps an object to arrest the fall, or during obstetrical traction on the extended arm when a newborn is delivered arm first.

Disk Herniation

Beginning in the third or fourth decade of life, cervical and lumbar intervertebral disks are liable to herniate into the spinal canal or intervertebral foramina and impinge on the spinal cord (in the case of cervical disk herniations), nerve roots (in both cervical and lumbosacral regions), or both (at the cervical level where on occasion large central and paracentral disk herniations may produce a myeloradiculopathy) (see Chapter 104 ).

Two factors contribute to this alteration in the intervertebral disks: degenerative change and trauma. An intervertebral disk is composed of a central, gelatinous, nucleus pulposus, and, surrounding, fibrocartilaginous, annulus fibrosus. With age, the fibers of the annulus fibrosus lengthen, weaken, and fray, 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 the nucleus pulposus. 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. 105.3 ). 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. 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 condition termed spondylosis , characterized by osteoarthritic changes in the joints of the spine, the disk per se (desiccation and shrinkage of the normally semisolid, gelatinous nucleus pulposus), and the facet joints. 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 comprising radicular pain, dermatomal sensory loss, weakness in the myotome, and reduction or loss of the deep tendon reflex subserved by the affected root ( and ). Nerve root pain is variably described as knife-like 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. 105.4 ).

Most radiculopathies occur in the lumbosacral region; compressive root lesions in this area account for 62%–90% of all radiculopathies. Cervical radiculopathies are less common, comprising 5%–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 ( and ). 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 (see Fig. 105.3 ).

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, knee flexors, and hip extensors.

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), tibial nerve (tibialis posterior), and the superior gluteal nerve (including gluteus medius). Weakness may be restricted to the extensor hallucis longus, or be more extensive and involve the tibialis anterior, resulting in foot drop.

A positive straight leg–raising test result is a sensitive indicator of L5 or S1 nerve root irritation. The test is deemed positive when the patient complains of pain radiating from the back into the buttock and thigh with leg elevation to less than 60 degrees. The test result is positive in up to 83% of patients with a proven disk herniation at surgery. A less sensitive but highly specific test is the crossed straight leg–raising test when the patient complains of radiating pain on the affected side with elevation of the contralateral leg.

The less common L4 radiculopathy is characterized by pain and paresthesias along the medial aspect of the knee and lower leg. The patellar reflex is diminished, and weakness may be noted in the quadriceps and hip adductors (innervated by the femoral and obturator nerves, respectively). When large herniations occur in the midline at either the L4–L5 or the L5–S1 level, many of the nerve roots running past that level to exit through intervertebral foramina below that level may be compressed, producing the cauda equina syndrome of bilateral radicular pain, paresthesias, weakness, attenuated reflexes below the disk level, and 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. As previously noted, cervical nerve roots emerge above the vertebra that share their 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 and , clinical and radiological evidence of radiculopathy was found to occur most often at C7 (70%), less frequently at C6 (19%–25%), and uncommonly at C8 (4%–10%) and C5 (2%). Radiculopathy involving the T1 root is a clinical rarity ( ).

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 (median nerve). The clinical features of C5 radiculopathies are similar, except that the rhomboids and spinati 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 the flexor carpi radialis and the pronator teres.

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 interosseous branch of the radial nerve), and flexor pollicis longus (anterior interosseous branch of the median nerve).

Variations in cervical root innervation to the brachial plexus can complicate the interpretation of symptoms and signs of suspected cervical radiculopathy. A well-appreciated anatomical variant is the “pre-fixed” brachial plexus, whereby cervical root innervation is caudally displaced by one spinal segment, such that the C4 nerve root offers a greater contribution to the brachial plexus, and the T1 nerve root has less representation. A pre-fixed variant is believed to be present in 22%–40% of dissected plexi and should be considered when there is poor correlation between clinical signs and radiographic findings. For example, in one retrospective study of 31 patients with clinical and electrophysiological evidence supporting a C8 radiculopathy, 16% were attributable to compression of the C7 nerve root at the C6–C7 spinal level ( ).

Diagnosis

Diagnosis is aided by a variety of imaging techniques (e.g., plain radiography, CT myelography, MRI) and EMG testing ( and ) (see Chapter 104 ). Both diagnostic modalities—the imaging approach that reveals anatomical details and the EMG techniques that disclose neurophysiological function—agree in the majority of patients (60%) with a clinical history compatible with cervical or lumbosacral radiculopathy, although only the results of one study will be positive in a significant minority of patients (40%) ( ). 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 post-myelography CT (unenhanced CT reveals little more than the presence of bony changes) and MRI. MRI is equivalent in diagnostic capacity to post-myelography 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 ( ).

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 proximal 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. However, in the specific instance of L5 radiculopathy, 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 attenuation or loss of the superficial peroneal nerve SNAP ( ).

Needle EMG is the most useful electrodiagnostic procedure in the diagnosis of suspected radiculopathy ( and ). A study is considered positive if abnormalities—especially acute changes of denervation including fibrillation potentials and positive sharp waves—are present in two or more muscles that receive innervation from the same root, preferably via different peripheral nerves. No abnormalities should be detected in muscles innervated by the affected root’s rostral and caudal neighbors. Reduced motor unit potential (MUP) recruitment (manifested by decreased numbers of MUPs firing at an increased rate) and MUP abnormalities of reinnervation (high-amplitude, increased duration, polyphasic MUPs) are also sought by the needle electrode but are not as reliable as fibrillation potentials in establishing a definitive diagnosis of radiculopathy. However, the absence of fibrillation potentials does not exclude the diagnosis of radiculopathy. Two main reasons for this exist. First, examination in the first 1–3 weeks after onset of nerve root compromise may be negative because it takes approximately 2 weeks for these potentials to appear. At the early stages in the process of nerve root compression, the only needle electrode examination manifestation of radiculopathy might be reduced MUP recruitment resulting from axon loss, focal demyelination with conduction block, or both. Second, fibrillation potentials disappear as denervated fibers are reinnervated by axons of the same or an adjacent myotome beginning 2–3 months after nerve root compression ( Fig. 105.5 ). 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 ( ).

Polyradiculopathy Associated with Sarcoidosis

Sarcoidosis is a systemic, multiorgan, inflammatory granulomatous disease. Neurological involvement of any kind is rare, observed in approximately 5% of patients, and characterized by granulomatous infiltration of CNS parenchyma, meninges, peripheral nerves and their roots. Predominant involvement of motor and sensory roots has been described ( ), manifesting in the lower extremities with subacute onset of proximal more than distal weakness, sensory loss, and pain in the back or legs. Deep tendon reflexes are often attenuated in keeping with a pure radiculopathy, although concomitant intraparenchymal involvement may occur, leading to upper motor neurons signs with hyperreflexia and extensor plantar responses. More acute onset presentations mimicking the Guillain-Barré syndrome (GBS) also have been described ( ).

Sarcoidosis characteristically presents in late adolescence through middle age, with a higher incidence in African Americans in North America. Establishing the diagnosis of neurosarcoidosis may be challenging. The gold standard of diagnosis is pathological evidence of noncaseating granulomas in involved nervous tissue. When this level of certainty cannot be achieved, clinicians turn to serum, CSF, and radiological testing to help support the diagnosis. Serum angiotensin- converting enzyme (ACE) levels are of limited utility, and do not correlate well with CSF ACE levels ( ). Elevated serum ACE levels should spur further diagnostic investigation, whereas a negative test result should not dissuade the clinician from a potential diagnosis of neurosarcoidosis. CSF analysis typically discloses elevated total protein, hypoglycorrhachia, and a lymphocytic pleocytosis, although not all patients will have all three abnormalities. The most common CSF abnormality is a high protein concentration. MRI may be most helpful in demonstrating increased T2 signal or post-gadolinium enhancement of involved nerve roots, meninges, or brain and spinal cord parenchyma. When neurosarcoidosis is suspected as the initial manifesting symptom of sarcoidosis, a diagnostic work-up to assess for systemic disease should also be pursued. This should include a plain chest x-ray or high-resolution CT to look for hilar lymph node or pulmonary involvement. Consideration should also be given to fluorodeoxyglucose positron emission tomography (FDG-PET) evaluating for pulmonary or extrapulmonary involvement that would subsequently allow for targeted biopsy of a more accessible involved organ ( ).

Formal evaluation of drug therapy in neurosarcoidosis is nonexistent, though convention favors initial treatment with oral or IV corticosteroids. Many patients improve with corticosteroid therapy, though long-term immunosuppression with corticosteroid-sparing agents such as azathioprine, mycophenolate mofetil, and methotrexate may be required. In the spinal column, where granulomatous infiltration may be associated with significant mass effect, decompressive laminectomy may be required.

Tabes Dorsalis

Tabes dorsalis, the most common form of late neurosyphilis, begins as a spirochetal (Treponema pallidum) meningitis (see Chapter 78 ). After 10–20 years of persistent infection, damage to the dorsal roots is severe and extensive, producing a set of characteristic symptoms and signs. Symptoms are lightning pains, ataxia, and bladder disturbance; signs include Argyll Robertson pupils, areflexia, loss of proprioceptive sense, Charcot joints, and trophic ulcers. Lancinating or lightning pains are brief, sharp, or stabbing in quality and 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. Episodes of visceral crisis, 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 ( ). 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 studies disclose 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 may be normal in tabes dorsalis or may show a mild lymphocytic pleocytosis (10–50 cells/μL) and elevated protein concentration (45–75 mg/dL). While up to 25% of patients are found to have nonreactive CSF-Venereal Disease Research Laboratory (VDRL), the serum treponemal tests fluorescent treponemal antibody absorption (FTA-ABS), Treponema pallidum particle agglutination assay (TPPA), and syphilis enzyme immunoassay (EIA)), remain reactive for life in virtually all patients regardless of previous treatment ( ). The preferred treatment is aqueous penicillin G, 2–4 million units IV every 4 hours for 10–14 days, with careful CSF follow-up. CSF examination 6 months after treatment should demonstrate a normal cell count and decreasing protein content. If not, a second course of therapy is indicated. The CSF examination should be repeated every 6 months for 2 years or until the fluid is normal.

Polyradiculoneuropathy in Human Immunodeficiency Virus-Infected Patients

Cytomegalovirus (CMV) polyradiculoneuropathy is a rapidly progressive opportunistic infection that usually occurs late in the course of human immunodeficiency virus (HIV) infection when the CD4 count is very low (<50 cells/mL) and acquired immunodeficiency syndrome (AIDS)-defining infections are present. Uncommonly, it is the initial manifestation of AIDS ( and ). 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 ( and ). 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 ( and ).

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 ( and ). The MRI in CMV polyradiculoneuropathy is usually normal, but adhesive arachnoiditis has been described. The CSF has an elevated protein level, depressed glucose level, polymorphonuclear pleocytosis, and a positive CMV polymerase chain reaction (PCR) ( and ). 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. 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. 105.7 ).

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 alternate, or combination therapy with an antiviral agent such as foscarnet, which, unlike ganciclovir, 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 ( ). Additionally, one must consider acute inflammatory demyelinating polyradiculoneuropathy, syphilitic polyradiculoneuropathy (which often has an accelerated course in the patient with AIDS), herpes simplex virus type 2 and varicella-zoster virus infections. Toxoplasma gondii may also cause myelitis, presenting as a subacute conus medullaris syndrome that simulates the clinical features produced by CMV polyradiculoneuropathy. In the case of T. gondii , MRI may reveal abscess formation.

Lyme Radiculoneuropathy

Lyme disease is caused by the spirochete Borrelia burgdorferi , transmitted by the deer tick Ixodes dammini , and is most prevalent in the American northeast and upper Midwest, where risk of infection is greatest during the spring and summer months. A European form, caused by the spirochetes B. afzelii and B. garinii , is also well recognized in temperate climates of central Europe and Asia. Lyme is a multisystem disease affecting the skin, peripheral 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 ( ). Stage 1 follows within 1 month of the tick bite and is marked by a characteristic rash in 60%–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. Stage 2, the stage of dissemination of the spirochete from the initial lesion, may occur within weeks of the rash, and may result in peripheral nerve, joint, and cardiac abnormalities. 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, myelopathy, psychiatric disturbances, and migratory oligoarthritis.

Nerve root and peripheral nerve abnormalities that characterize stage 2 develop in about 4%–5% of untreated patients ( ). Possible manifestations occurring within weeks after the onset of erythema chronica migrans most commonly include headache with lymphocytic (aseptic) meningitis, cranial neuropathy (especially facial mononeuropathies, bilateral in 25% of cases), and a multifocal radiculoneuropathy or mononeuritis multiplex. With nerve root involvement there may be an associated myelitis at adjacent spinal cord levels, with accompanying long tract signs on examination ( ). The clinical features of nerve root involvement include burning radicular pain with sensory loss, weakness, and hyporeflexia in the territory of the involved roots. Nerve conduction studies provide evidence for an associated primarily axon-loss polyneuropathy. The rare patient with chronic neuroborreliosis , seen in stage 3, may develop a stocking-glove patterned axon-loss polyneuropathy, that may in fact represent confluence of multiple mononeuropathies ( ). In a nonhuman primate model of neuroborreliosis, the spread of B. burgdorferi within the nervous system—leptomeninges, motor and sensory roots, DRG, but not the brain parenchyma—has been demonstrated. In peripheral nerves from such animals, spirochetes were seen in the perineurium ( ).

The diagnosis of Lyme disease can be made on the grounds of history and clinical presentation alone especially when there is evidence of erythema migrans. Serological testing for antibodies against B. burgdorferi (and confirmatory Western blot in those with borderline or positive results) can be beneficial, though neurological manifestations can be seen prior to the appearance of IgM antibodies in the blood as part of the early humeral response. Thus, antibody testing in a patient with suspected exposure within 3–6 weeks of presentation may be negative ( ). CSF analysis may be reserved for those with suspected CNS involvement, and will typically be abnormal with a lymphocytic pleocytosis, elevated protein, and normal glucose.

Treatment of Lyme radiculoneuropathy with IV ceftriaxone (cefotaxime and penicillin G are acceptable alternates) for 2–4 weeks is associated with resolution of symptoms and signs in most patients. Oral doxycycline (100 mg twice daily), has been shown to be equally efficacious in the treatment of European forms of neuroborreliosis, including radiculopathy ( ), while studies comparing IV versus oral antibiotics for the treatment of North American Lyme disease are lacking. After successful treatment, serum antibodies will often remain positive and their presence or absence offers no clinical utility in determining efficacy of treatment.

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 77 ). Primary infection presents as varicella (chickenpox) earlier in life ( ), usually in epidemics among susceptible children. Involvement may occur at any level of the neuraxis but is most commonly seen in the thoracic dermatomes, followed by the face. Zoster, when involving the ophthalmic division of the trigeminal nerve (herpes zoster ophthalmicus), may be accompanied by keratitis, a potential cause of blindness requiring immediate treatment. When isolated to the seventh nerve, it is associated with a facial palsy and ipsilateral external ear or hard palate vesicles known as Ramsay Hunt syndrome ( ). Rarely, the viral episode can present as dermatomal pain without a rash, known as herpes sine herpete .

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

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, numbness, dysesthesias (altered sensation), and/or allodynia (a painful response to normally non-noxious stimulation) typically in a single dermatome ( ). 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 3–5 days ( ). These become pustules by 3–4 days and form crusts by 10 days. In the normal immunocompetent host, lesions resolve in 2–4 weeks, often leaving a region of reduced sensation, scarring, and pigmentation. Pain usually disappears as vesicles fade, but 10%–50% of patients experience persistent severe pain, that when present for more than 30 days after rash onset or following cutaneous healing is termed postherpetic neuralgia (PHN; ). This complication is more likely to develop in the elderly, occurring in 50% of patients over 60 years of age. In half of patients affected with PHN, the pain resolves within 2 months, and 70%–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%–50% of patients. Most often, spread is to distant cutaneous sites, but involvement of the viscera (lung, gastrointestinal tract, and heart) and CNS may occur. A serious complication of herpes zoster ophthalmicus is delayed contralateral hemiparesis caused by cerebral angiitis. The syndrome usually develops 1 week to 6 months after the onset of zoster and occurs in patients of all ages, 50% of whom are immunologically impaired. The mortality rate from cerebrovascular complications is 25%, and only approximately 30% of survivors recover fully.

A complication of cutaneous herpes zoster is segmental motor weakness, which occurs in up to 30% of patients with zoster reactivation ( ). Segmental zoster paresis is about equally divided between the arms and legs, with predominantly proximal muscle weakness reflecting weakness in cervical and lumbar—C5, C6, and C7 or L2, L3, and L4—myotomes, respectively. The diaphragm and abdominal muscles may be affected, and bladder and bowel dysfunction may occur in the setting of lumbosacral zoster ( ). 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 ( ); 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 1–2 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 ( ). 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 ( ). A low-grade viral ganglionitis may contribute to PHN ( ).

The major goals of treatment are to relieve local discomfort, prevent dissemination, and reduce the severity of PHN ( ). 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 ( ). IV acyclovir is the treatment of choice in immunocompromised patients, having been shown to halt disease progression, prevent dissemination, and speed recovery in immunocompromised patients ( and ). In 2017, the US Food and Drug Administration (FDA) approved a non-live recombinant glycoprotein E vaccine for use in the United States to reduce the risk for herpes zoster in older adults (≥60 years). The vaccine requires two intramuscular injections, separated by 2–6 months, and is effective in preventing herpes zoster and reducing risk of post-herpetic neuralgia ( ).

The pain of PHN—described variably as continuous deep aching, burning, sharp, stabbing, and shooting, and triggered by light touch over the affected dermatomes—is often debilitating and difficult to treat ( and ). Singly or in combination, tricyclic antidepressants, 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. IV acyclovir followed by oral valacyclovir was found to reduce the pain of PHN in more than 50% of treated patients ( ).