PAIN IN THE NECK, SHOULDER, AND ARMGeneral Considerations

It is useful to distinguish three major categories of painful disease of the neck and armsthat originating in the cervical spine, in the brachial plexus, and in the shoulder. Although the distribution of pain from each of these sources may overlap, the patient can usually indicate its site of origin. Pain arising from the cervical part of the spine is felt in the neck or back of the head and is projected to the shoulder and upper arm; it is evoked or enhanced by certain movements or positions of the neck and is accompanied by limitation of motion of the neck and by tenderness to palpation over the cervical spine.

Pain of brachial plexus origin is experienced in the supraclavicular region, or in the axilla and around the shoulder; it may be worsened by certain maneuvers and positions of the arm and neck (extreme rotation). A palpable abnormality above the clavicle may disclose the cause of the plexopathy (aneurysm of the subclavian artery, tumor, cervical rib).

The combination of circulatory abnormalities and signs referable to the medial cord of the brachial plexus is characteristic of the thoracic outlet syndrome, described further on. Pain localized to the shoulder region, worsened by motion, and associated with tenderness and limitation of movement, especially internal and external rotation and abduction, points to a tendonitis, subacromial bursitis, or tear of the rotator cuff, which is made up of the tendons of the muscles surrounding the shoulder joint. The term bursitis is often used loosely to designate these disorders. Shoulder pain, like spine and plexus pain, may radiate vaguely into the arm and rarely into the hand, but sensorimotor and reflex changeswhich always indicate disease of nerve roots, plexus, or nervesare absent. Shoulder pain of this type is very common in middle and late adult life.

It may arise spontaneously or after unusual or vigorous use of the arm. Local tenderness over the greater tuberosity of the humerus is characteristic. Plain radiographs of the shoulder may be normal or show a calcium deposit in the supraspinatus tendon or subacromial bursa. MRI is able to demonstrate more subtle abnormalities, such as muscle and tendon tears of the rotator cuff or a labral tear of the joint capsule. In most patients the pain subsides gradually with immobilization and analgesics followedby a program of increasing shoulder mobilization. If it does not, the injection of small amounts of corticosteroids into the bursa, or the site of major pain indicated by passive shoulder movement in the case of rotator cuff injuries, is often temporarily effective and allows the patient to mobilize the shoulder. The problem of the frozen shoulder is addressed further on.

Osteoarthritis and osteophytic spur formation of the cervical spine may cause pain that radiates into the back of the head, shoulders, and arm on one or both sides. Coincident compression of nerve roots is manifest by paresthesia, sensory loss, weakness and atrophy, and tendon reflex changes in the arms and hands. Should bony ridges form in the spinal canal, as described in detail in Chap. 44, the spinal cord may be compressed, with resulting spastic weakness, ataxia, and loss of vibratory and position sense in the legs (cervical spondylosis). The bony changes are evident on plain films but are better seen by CT and MRI. There may be difficulty in distinguishing cervical spondylosis with root and spinal cord compression from a disc (see further on) or from a primary neurologic disease (syringomyelia, amyotrophic lateral sclerosis, or tumor) with an unrelated cervical osteoarthritis. Here the MRI is of particular value in revealing compression of the spinal cord, but this study is prone to overinterpretation when a bony ridge barely comes into contact with the cord but does not deform it (see Cervical Spondylosis with Myelopathy in Chap. 44).

Spinal rheumatoid arthritis may be restricted to the cervical apophysial (facet) joints and the atlantoaxial articulation. The usual manifestations are pain, stiffness, and limitation of motion in the neck and pain in the back of the head. In contrast to ankylosing spondylitis, rheumatoid arthritis is rarely confined to the spine. Because of evident disease of other joints, the diagnosis is relatively easy to make, but significant involvement of the cervical spine may be overlooked. In the advanced stages, one or several of the vertebrae may become displaced anteriorly, or a synovitis of the atlantoaxial joint may damage the transverse ligament of the atlas, resulting in forward displacement of the atlas on the axis, i.e., atlantoaxial subluxation.

In either instance, serious and even life-threatening compression of the spinal cord may occur gradually or suddenly. Cautiously performed lateral radiographs in flexion and extension are useful in visualizing atlantoaxial dislocation or subluxation of the lower segments. Occipital headache and neck pain related to degenerative changes in the upper cervical facets is discussed with other cranial pains in Third Occipital Nerve Headache (so-called third occipital nerve pain) in Chap. 10.

Traumatic and Whiplash Injury Injury to ligaments and muscles as a result of forcible extension and flexion of the neck can create a number of difficult clinical problems. The injury ranges from a minor sprain of muscles and ligaments to severe tearing of these structures, to avulsion of muscle and tendon from vertebral body, and even to vertebral and intervertebral disc damage. The latter lesions can be seen with MRI and, if severe, can result in root or spinal cord compression or, occasionally, in cartilaginous embolization of the spinal cord (see Fibrocartilaginous Embolism in Chap. 44). If there is preexisting cervical osteoarthritis, there may be considerable pain, and in extreme cases, cord compression.

However, the more ubiquitous and milder degrees of whiplash injury without the above described structural injuries are so often complicated by psychologic and compensation factors leading to prolonged disability that the syndrome has become a vexing problem without clear medical definition and occupies a disproportionate amount of time on the part of physicians, compensation boards, and courts (see LaRocca for a review and the book by Malleson for an interesting discussion of the sociology and psychology of this subject). We have no doubt that authentic traumatic neck injuries exist, even at times from minor trauma, but we are in accord with the above-mentioned authors that the high frequency of this putative injury is sustained by societal and legal structures.

Cervical Disc Herniation (See Table 11-1)

A common cause of neck, shoulder, and arm pain is disc herniation in the lower cervical region; the process is comparable to disc herniation in the lumbar region but gives rise, of course, to a different set of symptoms (Table 11-1).The problem appears most often without a clear and immediate cause, but it may develop after trauma, which may be major or minor (from sudden hyperextension of the neck, falls, diving accidents, forceful manipulations). The roots most commonly involved are the seventh (in 70 percent of cases) and the sixth (in 20 percent of cases); fifth- and eighth-root compression makes up the remaining 10 percent (Yoss et al). When the protruded disc lies between the sixth and seventh vertebrae, there is involvement of the seventh cervical root as outlined in Table 11-1. The pain is then in the region of the shoulder blade, or spine of the scapula, and posterolateral upper arm; it may project to the elbow and dorsal forearm, index and middle fingers, or all the fingers. Occasionally discomfort is felt in the pectoral or axillary region.

Tenderness is most pronounced over the medial aspect of the shoulder blade opposite the third to fourth thoracic spinous processes and in the supraclavicular area and triceps region. Paresthesia and sensory loss are most evident in the index and middle fingers. Weakness involves the extensors of the forearm and sometimes of the wrist; occasionally the handgrip is weak as well; the triceps may beweak and the triceps reflex is usually diminished or absent; the biceps and supinator reflexes are preserved. With a laterally situated disc herniation between the fifth and sixth cervical vertebrae, the symptoms and signs are referred to the sixth cervical root. The full syndrome is characterized by pain at the trapezius ridge and tip of the shoulder, with radiation into the anterior-upper part of the arm, radial forearm, often the thumb, and sometimes the index finger as well. There may also be paresthesia and sensory impairment in the same regions; tenderness in the area above the spine of the scapula and in the supraclavicular and biceps regions; weakness in flexion of the forearm (biceps) and in contraction of the deltoid when sustaining arm abduction; and diminished or absent biceps and supinator reflexes (the triceps reflex is retained or sometimes has the appearance of being slightly exaggerated because of flaccidity of the biceps).

The fifth cervical root syndrome, produced by disc herniation between the fourth and fifth vertebral bodies, is characterized by pain in the shoulder and trapezius region and by supra- and infraspinatus weakness, manifest by an inability to abduct the arm and rotate it externally with the shoulder adducted (weakness of the supra- and infraspinatus muscles). There may be a slight degree of weakness of the biceps and a corresponding reduction in the reflex, but these are inconsistent findings. A small patch of diminished sensation commonly overlies the deltoid muscle. Compression of the eighth cervical root at (C7-T1 disc) may mimic an ulnar nerve palsy. The pain is along the medial side of the forearm and the sensory loss is in the distribution of the medial cutaneous nerve of the forearm and of the ulnar nerve in the hand. The weakness largely involves the intrinsic muscles supplied by the ulnar nerve (see Ulnar Nerve in Chap. 46). The reflexes may be unaffected but the triceps jerk is often slightly reduced.

These syndromes are usually incomplete in that only one or several of the typical findings are present. Particularly noteworthy is the occurrence, in laterally placed cervical disc rupture, of isolated weakness without pain, especially with discs at the fifth and sixth levels. Friis and coworkers have described the distribution of pain in 250 cases of herniated disc or spondylotic nerve root compression in the cervical region. Virtually every patient, irrespective of the particular root(s) involved, showed a limitation in the range of motion of the neck and aggravation of pain with movement (particularly hyperextension). Coughing, sneezing, and downward pressure on the head in the hyperextended position usually exacerbated the pain, and traction (even manual) tended to relieve it. Nerve conduction studies, F responses, and EMG are helpful in confirming the level of root compression and distinguishing pain of radicular origin from that originating in the brachial plexus or in individual nerves of the arm (see Brachial Neuritis in Chap. 46).

Unlike herniated lumbar discs, cervical ones, if large and centrally situated, result in compression of the spinal cord (Fig. 11-7). The centrally situated disc is often painless, and the cord syndrome may simulate multiple sclerosis or a degenerative neurologic disease. Bilateral hand numbness, paresthesia, or similar altered sensation is common. Failure to consider a protruded cervical disc in patients with obscure symptoms in the legs, including stiffness and falling, is a common error. A vague sensory change can often be detected on the thorax, the rostral margin of which is several dermatomes below the level of compression. The diagnosis and the level of disc protrusion can be confirmed by MRI or by CT myelography (Fig. 11-7).

Management of Herniated Cervical Disc

Conservative measures should be instituted before turning to surgical removal of the disc unless there are signs of a rapidly or subacutely progressing myelopathy (i.e., leg and arm weakness, hyperreflexia in the legs, gait ataxia, sphincteric dysfunction). Treatment In the case of cervical disc with radicular pain, a close-fitting foam collar is sometimes beneficial. The collar should be fitted so that minimal flexion and extension of the neck are allowed, but it must remain comfortable enough to encourage consistent use. The patient is advised to wear the collar at all times during the day, especially while riding in a car, unless this becomes completely impractical. Although of uncertain value, traction with a halter around the occiput and chin may be of some benefit in cervical disc syndromes. Analgesic medication may be required for a few days.

In most instances the radicular pain subsides over a few weeks or less. Intractable cases may require surgery, especially if there is substantial weakness in the muscles corresponding to the affected root. Mild weakness alone is not recognized as an indication for surgery, and in those few cases where weakness alone has occurred, without pain, the same conservative measures outlined above should be implemented. Most often the surgeon tackles this problem through an anterior approach (transdiscally), which leaves the posterior elements intact and allows for remaining stability of the spine.

Cervical Spondylosis (See also Chap. 44)

This is basically a chronic degenerative disease of the midand lower cervical spine that narrows the spinal canal and intervertebral foramina, causing compressive injury of the spinal cord and roots. The problem of central disc protrusion, discussed above, often contributes as one component of the narrowing of the canal. Because the main effects of cervical spondylosis are on the cord, this process is discussed in detail in Chap. 44, but cervical spondylosis is also a common cause of neck and arm pain, as described earlier. If minor signs of spinal cord and root involvement are present, a collar to limit movement of the head and neck may halt the progression and lead to improvement. Decompressive laminectomy or anterior excision of single spondylotic spurs and fusion are reserved for instances of the disease with advancing neurologic symptoms or intractable pain as discussed in Chap. 44. As with lumbar stenosis, success is not assured with surgery, but almost invariably, progression of symptoms is prevented.

Cervical Spondylosis with Myelopathy (Spondylitic Myelopathy) (See also Chap. 11)

It has been stated, correctly in our opinion, that this is the most frequently observed myelopathy in general practice. It is a degenerative disease of the spine involving the lower and midcervical vertebrae that narrows the spinal canal and intervertebral foramina and causes progressive injury of the spinal cord, roots, or both.

Historical Note Key, in 1838, probably gave the first description of a spondylotic bar, or ossified protrusion into the spinal canal. In 2 cases of compressive myelopathy with paraplegia, he found a projection of the intervertebral substance and posterior ligament of the spine, which was thickened and presented as a firm ridge that had lessened the diameter of the canal by nearly a third.

The ligament, where it passes over the posterior surface of the intervertebral substance, was found to be ossified. In 1892, Horsley performed a cervical laminectomy on such a patient, removing a transverse ridge of bone compressing the spinal cord at the level of the sixth cervical vertebra. Thereafter, operations were performed in many cases of this sort, and the tissues removed at operation were repeatedly misidentified as benign cartilaginous tumors or chondromata. In 1928, Stookey described in detail the pathologic effects upon the spinal cord and roots of these ventral extradural chondromas. Peet and Echols, in 1934, were probably the first to suggest that the so-called chondromata represented protrusions of intervertebral disc material. But this idea never gained wide credence until the publication, in the same year, of the classic article on the ruptured intervertebral disc by Mixter and Barr. Although their names are usually associated with the lumbar disc syndrome, 4 of their original 19 cases were instances of cervical disc disease. It was C.S. Kubik who identified the nucleus pulposus from surgical specimens obtained by Mixter and Barrs cases.

Also of importance is Gowers account, in 1892, of vertebral exostoses, in which he described osteophytes that protrude from the posterior surfaces of the vertebral bodies and encroach upon the spinal canal, causing slow compression of the cord as well as bony overgrowth in the intervertebral foramina, giving rise to radicular pain. Gowers correctly predicted that these lesions would offer a more promising field for the surgeon than would other kinds of vertebral tumors. For some reason, there was little awareness of the frequency and importance of spondylotic myelopathy for many years after these early observations had been made.

All the interest was in the acute ruptured disc. Finally, it was Russell Brain who, in 1948, put cervical spondylosis on the neurologic map, so to speak. He drew a distinction between acute rupture and protrusion of the cervical disc (often traumatic and more likely to compress the nerve roots than the spinal cord) and chronic spinal cord and root compression consequent to disc degeneration and associated osteophytic outgrowths (hard disc), as well as changes in the surrounding joints and ligaments. In 1957, Payne and Spillane documented the importance of a developmentally smaller-than-normal spinal canal in the genesis of myelopathy in patients with cervical spondylosis.

These reports were followed by a spate of articles on the subject (see Wilkinson). Rowlands review of the natural history of cervical spondylosis and the results of surgical therapy is a useful modern reference, as is that by Uttley and Monro.

Symptomatology

The characteristic syndrome consists of varying combinations of the following: (1) painful, stiff neck or pain in the neck, shoulders, and upper arms (brachialgia) that may be aching or radicular (stabs of sharp and radiating pain evoked by movement), asymmetric or unilateral; (2) numbness and paresthesias of the hands; and (3) spastic leg weakness with Babinski signs, unsteadiness of gait, and a Romberg sign. The numbness and paresthesias are occasionally the earliest symptoms and typically involve the distal limbs, especially the hands. Variations of these symptoms are elaborated below. Each of the components may occur separately, or they may occur in combination and various sequences.

With reference to the most common of these symptoms, the neck and shoulder pain, in any sizable group of patients older than 50 years of age, approximately 40 percent will be found at times to have some clinical abnormality of the neck, usually crepitus or pain, with restriction of lateral flexion and rotation (less often of extension). Pallis and colleagues, in a survey of 50 patients, all of them older than 50 years of age and none with neurologic complaints, found that 75 percent showed radiologic evidence of narrowing of the cervical spinal canal as a result of osteophytosis of the posterior vertebral bodies or of narrowing of the intervertebral foramina because of osteoarthropathy at the apophyseal joints; thickening of the ligaments (both the ligamentum flavum posteriorly and the posterior longitudinal ligament anteriorly) adds to the narrowing of the canal. However, only half of the patients with radiologic abnormalities showed physical signs of root or cord involvement such as changes in the tendon reflexes in the arms, briskness of reflexes and impairment of vibratory sense in the legs, and sometimes Babinski signs. The occasional finding of a Babinski sign in older individuals who had never had a stroke or complained of neurologic symptoms is often explained by an otherwise inevident cervical osteophyte (Savitsky and Madonick).

The pain is usually centered at the base of the neck or higher, often radiating to an area above the scapula. When brachialgia is also present, it takes several forms: a sharp pain in the pre- or postaxial border of the limb, extending to the elbow, wrist, or fingers; or a persistent dull ache in the forearm or wrist, sometimes with a burning sensation.

Discomfort may be elicited by coughing, Valsalva maneuver, or neck extension, or neck flexion may induce electrical feelings down the spine (Lhermitte symptom). Rarely, the pain is referred substernally.As to the sensory disorders (which may occasionally be absent), numbness, tingling, and prickling of the hands and soles of the feet and around the ankles are the most frequent complaints. Some patients complain of numbness or paresthesias, most often in one or two digits, a part of the palm, or a longitudinal band along the forearm.

Slight clumsiness or weakness of a hand is another complaint. A feeling as if wearing gloves, swollen, or the hands coated with glue are common descriptions. Several of our patients have complained of paresthesias in the distal limbs and trunk for years before there was any indication of motor involvement. In advanced cases, there may be a vague sensory level at or just above the clavicles. Impaired vibratory sensation and diminished position sense in the toes and feet (all indicative of a lesion of the posterior columns), as well as the Romberg sign, are the most conspicuous sensory findings. This imparts a tabetic unsteadiness to the gait. Sensory defects tend to be asymmetrical. (It is noteworthy that symmetric sensory symptoms and signs of identical type are seen with subacute combined degeneration as a result of vitamin B12 deficiency.) Rarely, the sensorimotor pattern takes the form of a Brown-Squard syndrome. Less frequently, paresthesias and dysesthesias in the lower extremities and trunk may be the principal symptoms; even less often there are sensory complaints on the face, ostensibly corresponding to compression of the trigeminal sensory tract in the upper cervical cord.

The third part of the typical syndrome, spastic legs from a compressive myelopathy, most often manifests as a complaint of weakness of a leg and slight unsteadiness of gait. The whole leg or the quadriceps feels stiff and heavy and gives out quickly after exercise. Mobility of the ankle may be reduced, and the advancing toe of the shoe scrapes the floor. On examination, hypertonicity is more evident than weakness, and the tendon reflexes are increased (ankle jerks may not share in this change in the elderly). Although the patient may believe that only one leg is affected, it is commonly found that both plantar reflexes are extensor, the one on the side of the stiffer leg being more clearly so. Less often, both legs are equally affected. As the compression continues, walking becomes unsteady because of the addition of sensory ataxia.

The biceps and brachioradial reflexes on one or both sides may be depressed, sometimes in association with an increase in the triceps and finger reflexes. The hand or forearm muscles may undergo slight atrophy; in a few cases, the atrophy of hand muscles is severe. In such cases, the spondylotic compression, as judged by MRI or CT myelography, may be confined to the high cervical cord, well above the levels of the motor neurons that innervate these muscles. In patients with sensory loss, pain and thermal sensation often appear to be affected more than tactile sense. An unexpected Babinski sign has already been mentioned and a few fasciculations may be seen, especially in proximal muscles.As the myelopathy progresses, sometimes intermittently, both legs become weaker and more spastic. Sphincteric control may then be altered; slight hesitancy or precipitancy of micturition are the usual complaints; frank incontinence is infrequent. In the more advanced form of this condition, walking requires the aid of a cane or canes or a walker; in some cases, all locomotion ultimately becomes impossible, especially in the elderly patient. Abrupt worsening, even paraplegia or quadriplegia, may follow forceful traumatic flexion or extension injuries of the neck, as indicated later.

Pathologic Changes

The fundamental spinal lesion is generated initially by a fraying of the annulus fibrosus with extrusion of disc material into the spinal canal. The disc becomes covered with fibrous tissue or partly calcified, thereby forming a transverse osteophytic spondylitic bar or there may be simply central bulging of the annulus without extrusion of nuclear material. The latter, unlike ruptured discs that occur mainly at the C5-C6 or C6-C7 interspace, often involve higher interspaces and almost invariably occur at several adjacent levels. The dura may be thickened and adherent to the posterior longitudinal ligament at affected levels. The underlying pia-arachnoid is also thickened and the adjacent ligamentous hypertrophy contributes to compression of the cord or the nerve roots. This series of pathologic changes is often ascribed to a type of hypertrophic osteoarthritis. However, osteophyte formation and ridging are so frequently observed in patients who have no other signs of arthritic disease that this explanation is surely not totally correct. Subclinical trauma in persons who are structurally susceptible to spondylosis is more likely to be the cause of bar formation, in the authors opinion.

When a cervical nerve root is compressed by lateral osteophytic overgrowth, the dural sleeve is thickened and occluded and the root fibers are damaged. Usually the fifth, sixth, or seventh cervical roots are affected in this way, both the anterior and posterior or only the anterior, on one or both sides. A small neuroma may rarely appear proximal to the site of anterior root compression. The dura is ridged and the underlying spinal cord is flattened. The root lesions may lead to secondary wedgeshaped areas of degeneration in the lateral parts of the posterior columns at higher levels. The most marked changes in the spinal cord are at the level(s) of compression.

There are zones of demyelination or focal necrosis at the points of attachment of the dentate ligaments (which tether the spinal cord to the dura) and areas of rarefaction in the posterior and lateral columns, as well as loss of nerve cells. Ventral gray matter lesions, often asymmetrical, are attributed by Hughes to ischemia.

Pathogenesis

The particular vulnerability of the cervical spine to degenerative change has no ready explanation. Most likely it is related in some way to the high degree of mobility of the lower cervical vertebrae, which is accentuated by their location next to the relatively immobile thoracic spine. The mechanism of spinal cord injury would seem to be one of simple compression and ischemia. When the spinal canal is developmentally diminished in its anteroposterior dimension at one or several points, the space available for the spinal cord becomes insufficient. A small canal certainly makes an individual more subject to the compressive effects of spondylosis. The range acquired of narrowing of the canal that produces symptomatic cervical spondylosis is generally from 7 to 12 mm (normal canal diameter: 17 to 18 mm). Consequently, one must consider several additional mechanisms by which the cord might be damaged. The effects of the natural motions of the spinal cord during flexion and extension of the neck are probably important in this respect. Adams and Logue confirmed the observation of OConnell that, during full flexion and extension of the neck, the cervical cord and dura move up and down. The spinal cord is literally dragged over protruding osteophytes and hypertrophied ligaments; conceivably it is this type of intermittent trauma that causes progressive injury. It has also been shown that the spinal cord, displaced posteriorly by osteophytes, is compressed by the infolding of the posterolateral ligamentum flavum each time the neck is extended (Stoltmann and Blackwood). Segmental ischemic necrosis resulting from intermittent compression of spinal arteries or from compression of the anterior spinal artery has also been postulated. Most neuropathologists favor the idea of intermittent cord compression between osteophytes anteriorly and ligamentum flavum posteriorly, with an added vascular element accounting for the scattered lesions deep in the cord. Trauma from sudden extreme extension, as in a fall, severe whiplash injury, or chiropractic manipulation, or from a lesser degree of retraction of the head during myelography, tooth extraction, or a tonsillectomy may be operative in individual cases, particularly in patients with congenitally narrow canals. The lateral extension of the osteophyte and hypertrophy of the facet joint together compress the nerve root as it is entering its spinal foramen. Sometimes these are the main changes and cause only a radiculopathy, as discussed in Chap. 11.

Diagnosis

When pain and stiffness in the neck, brachialgia, either in the form of aching or a more distinctive radicular pain, and sensorimotor-reflex changes in the arms are combined with signs of myelopathy, there is little difficulty in diagnosis. When the neck and arm changes are inconspicuous or absent, the diagnosis becomes more difficult. The myelopathy must then be distinguished from the late, progressive form of spinal MS. Because posterior vertebral osteophytes and other bony alterations are frequent in the sixth and seventh decades of life, the question that must be answered in any given case is whether the vertebral changes are adequately severe to cause the neurologic abnormality. The finding of some degree of sensorimotor or reflex change corresponding only to the level of the spinal abnormalities is a point that always favors spondylotic myelopathy. A lack of such corresponding changes and the presence of oligoclonal bands and signs of lesions in the optic nerves and brain indicate demyelinating myelopathy.

The findings on both MRI and CT myelography become critical in such cases (Fig. 44-10). The MRI tends to overestimate the degree of cord compression by an osteophyte, but clear deformation of the cord into the shape of a kidney bean and obliteration of the surrounding CSF spaces in the transverse image support the diagnosis of spondylotic compression. To confidently attribute neurologic symptoms to spondylosis there should be considerable encroachment on the CSF space at that level, not simply an impingement or slight deformation of the normal oval shape of the cord.Signal changes within the body of the cord are seen in advanced cases and usually indicate a degree of irreversibility of at least the sensory symptoms. Curiously, these signal changes may be one or two levels above or below the site of main compression. However, serious symptoms may occur even without intrinsic changes in the MRI signal.

Contrast myelography with the patient supine and lateral views taken during flexion and extension of the neck are useful diagnostic procedures in uncertain cases. It has been said that spondylotic myelopathy may simulate amyotrophic lateral sclerosis (amyotrophy of arms and spastic weakness of the legs). This has seldom been a diagnostic problem. Although brachial and shoulder fasciculations with muscle atrophy may be combined with hyperreflexia in spondylosis, the widespread denervation and progressive course of ALS are not in evidence. We have observed only a few patients with spondylotic myelopathy who exhibited an absolutely pure motor syndrome, i.e., one in which there was no cervical or brachial pain and no sensory symptoms in the arms or impairment of vibratory or position sense in the legs. Likewise, a pure spastic paraparesis is more likely to be a manifestation of MS, hereditary spastic paraplegia, motor neuron disease (primary lateral sclerosis type), HTLV-I myelopathy, or the carrier state of adrenoleukodystrophy or other intrinsic myelopathy.

When imbalance, both perceived by the patient and observed in tests of walking, is a major symptom, spondylosis must be differentiated from a number of acquired large-fiber polyneuropathies, particularly inflammatory or immune types and the more benign sensory neuropathy of the aged (see discussion of this entity in Chap. 46).

Loss of tactile sensation in the feet and loss of tendon reflexes are characteristic of the latter; examination of the tendon reflexes distinguishes neuropathy from myelopathy. Subacute combined degeneration of the spinal cord because of vitamin B12 deficiency, combined system disease of the nonpernicious anemia type, AIDS and HTLV-I myelopathy, ossification of the posterior longitudinal ligament, and spinal cord tumor (discussed further on) are usually listed among the conditions that might be confused with spondylotic myelopathy. Adherence to the diagnostic criteria for each of these disorders and scrutiny of the radiologic studies eliminate the possibility of error in most instances. The gait abnormality produced by spondylotic myelopathy may also be mistaken for that of normal-pressure hydrocephalus; a marked increase of imbalance with removal of visual cues (Romberg sign) is a feature of spondylosis but not of hydrocephalus, and the short-stepped and magnetic quality of walking that is characteristic of hydrocephalus is not seen in cervical myelopathy. Incontinence occurs only in advanced cases of spondylotic myelopathy but usually follows soon after gait deterioration in hydrocephalus.The special problems of spondylotic radiculopathy, which may accompany or occur independently of themyelopathy, are discussed in Chap. 11.

Treatment

The slow, intermittently progressive course of cervical myelopathy with long periods of relatively unchanging symptomatology makes it difficult to evaluate the effects of therapy. Assuming that the prevailing opinion of the mechanism of the cord and root injury is correct, the use of a soft collar to restrict anteroposterior motions of the neck seems reasonable. This form of immobilization alone may be sufficient to control the discomfort in the neck and arms. Only exceptionally in our experience has arm and shoulder pain alone been sufficiently severe and persistent to require surgical decompression unless there is in addition a laterally protruded disc or osteophytic constriction of a root foramen. Many of our patients have been dissatisfied with this passive approach and are unable to wear a collar for prolonged periods. If osteophytes have narrowed the spinal canal at several interspaces, a posteriordecompressive laminectomy with severance of the dentate ligaments helps to prevent further injury.

The results of such a procedure are fairly satisfactory (Epstein and Epstein); in fully two-thirds of the patients, improvement in the function of the legs occurs, and in most of the others, progression of the myelopathy is halted. The operation carries some risk; rarely, an acute quadriplegiapresumably a result of manipulation of the spinal cord and damage to nutrient spinal arterieshas followed the surgical procedure. Newer techniques have been developed in which titanium cages are used to stabilize the adjacent vertebrae, thereby obviating the need for bone grafts to fuse adjacent bodies; the conventional process using bone grafts requires many weeks or longer and stabilization in a hard collar. When only one or two interspaces are the site of osteophytic overgrowths, their removal by an anterior approach has given better results and carries less risk. Braakman reviewed the surgical methods and their relative advantages.

The long-term results after surgical treatment are less than ideal. Ebersold and colleagues evaluated the out- Figure 44-10. MRI in a patient with symptomatic cervical spondylosis The spinal cord at C4-C5 and C5-C6 is flattened on its ventral surface by spondylotic bars and on its posterior surface by ligamentous hypertrophy. Axial images are required to confirm that the cord is truly compressed and that the subarachnoid space is nearly or completely obliterated. comes in 84 patients in whom the median duration of followup was 7 years. In the group of 33 patients who had undergone anterior decompressive procedures, 18 had improved, 9 were unchanged, and 6 had deteriorated. Of the 51 patients who underwent posterior decompression, 19 had improved, 13 were unchanged, and 19 were worse at their last followup examinations. These results, similar to those of most other series, indicate that the outcome varies and that a significant proportion, even after adequate decompression and initial improvement, have persistent symptoms or undergo some degree of later functional deterioration. Whether the new surgical appliances give more satisfactory results is unknown (see also Chap. 11).

Spinal Cord Compression and MyelopathiesWilliam F. Schmalstieg and Brian G. Weinshenker

Patients with signs and symptoms of acute myelopathy require urgent neurologic evaluation focused upon the identification and management of treatable disorders. MRI of the spine is the imaging modality of choice to evaluate for a compressive lesion. When cord compression is present, surgical treatment is usually indicated. When compression is not detected, an analysis of precise lesion localization, nonneurological clinical features, MRI findings, and serologic studies narrow the differential diagnosis. The key diagnostic considerations include demyelinating, vascular, inflammatory, infectious, and paraneoplastic disorders. Empiric high-dose corticosteroid treatment is often indicated in noncompressive myelopathy; additional investigations are important to identify patients with relapsing or progressive disorders who may benefit from preventive therapies.

Patients whose symptoms continue to progress after initial immunosuppressive treatment may benefit from plasmapheresis and occasionally from biopsy for definitive diagnosis.

KeywordsCNS Demyelinating autoimmune disease Magnetic resonance imaging Myelitis Spinal cord compression Spinal cord diseases Transverse

Acute myelopathies are potentially devastating conditions that may result in irreversible loss of mobility and control of bodily functions. Many etiologies of acute myelopathy are treatable, and rapid diagnosis and institution of appropriate treatment can prevent or reduce the extent of permanent damage to the spinal cord. Delays in the diagnosis and treatment of acute cord syndromes are frequent and may contribute to loss of neurologic function [ 1 ] . Furthermore, some inflammatory conditions that cause myelopathy may stabilize or remit but later relapse; patients with such conditions may benefit from maintenance prophylactic therapies, and therefore, consideration of the risk of relapse is important even when spontaneous or treatment-induced remission occurs.

This chapter considers the clinical presentation, evaluation, and management of acute and subacute spinal cord disorders and includes a diagnostic algorithm to distinguish compressive and noncompressive myelopathies and also to distinguish among the various noncompressive etiologies (Fig. 13.1 ). The key elements are high index of suspicion and confirmation, primarily with neuroimaging, but occasionally supported by other laboratory studies. This chapter concludes with treatment recommendations.

Pathophysiology

A review of spinal anatomy informs a discussion of the pathophysiology and clinical presentation of acute disorders of the cord. The spinal cord extends between the medulla and the conus medullaris, the terminus of which ends opposite the L1 vertebral body. Much of the substance of the cord is composed of large myelinated tracts, the most clinically relevant of which include:1. Lateral corticospinal tracts carrying ipsilateral motor fibers2. Spinothalamic tracts carrying contralateral pain and temperature sensation3. Dorsal columns carrying ipsilateral joint position and vibratory sensation

The arterial vascular supply of the spinal cord includes a single anterior spinal artery and two posterior spinal arteries, which originate from the vertebral arteries. The anterior spinal artery is also supplied by multiple segmental arteries arising from the thoracic and abdominal aorta. The anterior spinal artery supplies the lateral corticospinal and spinothalamic tracts, whereas the dorsal columns are supplied by the posterior spinal arteries. The venous drainage of the cord is through the epidural venous plexus.

The cord is surrounded by the meninges (pia, arachnoid, and dura mater), which are in turn encircled by the vertebrae. The vertebral bodies are anterior to the cord, the pedicles lateral, and the laminae and spinous processes posterior. In compressive lesions, such as epidural abscess or metastatic disease, obstruction of the epidural venous plexus initiates spinal cord injury. Impairment of venous drainage causes vasogenic edema, which is in turn followed by an inflammatory cascade mediated, in part, by prostaglandins and other inflammatory cytokines.

Simultaneously, the combination of external mechanical compression and internal swelling of the cord disrupts axonal conduction. Subsequent inflammation then leads to localized demyelinationand frank ischemia of the cord [ 2 ] .

Vascular occlusions or other vascular anomalies can cause acute cord injury. The portion of the cord supplied by the anterior spinal artery is particularly vulnerable. Restricted flow of the feeding vessels to this artery may produce watershed ischemia, particularly at the terminal regionssupplied by the dominant radicular artery of Adamkiewicz as may occur during surgical crossclamping of the aorta. Other potential causes of anterior spinal artery obstruction include aortic dissection, atherosclerosis, cardiac embolism, hypercoagulable states, and fibrocartilaginous embolism from intervertebral disk fragments.

Another uncommon but important vascular anomaly associated with myelopathy is the dural arteriovenous fistula. In this condition, an abnormal connection of a dural artery to a vein results in venous hypertension, resulting in damage to the cord and leading to the telltale distension of the epidural venous plexus that is an important radiologic sign of this entity.

As elaborated in the section on differential diagnosis, a wide variety of demyelinating, inflammatory, and infectious conditions can produce intrinsic damage to the substance of the spinal cord. A detailed description of the underlying pathophysiology of each of these conditions is beyond the scope of this text, and in many of these conditions the pathogenesis is poorly understood.

One recent noteworthy discovery is that the NMO-IgG antibody, a clinically validated biomarker of neuromyelitis optica (NMO), may be responsible for an important portion of what had been previously regarded as idiopathic transverse myelitis. NMO is an inflammatory demyelinating disease characterized by recurrent, severe attacks of optic neuritis and longitudinally extensive transverse myelitis [ 3 ] . The target of the NMO-IgG antibody is the aquaporin-4 (AQP4) water channel, which is highly expressed at the astrocytic end feet of the bloodbrain barrier.

Current evidence suggests that this antibody is pathogenic and not merely a marker of autoimmunity or disease severity. Brain MRI lesions in patients with NMO occur in regions known to express high levels of AQP4 [ 4 ]. Additionally, transfer of pooled IgG antibodies from NMO-IgG positive patients to rats reproduces lesions similar to those seen in human NMO [ 5, 6 ]. Antibodyand complement-mediated cytotoxicity to astrocytes occurs in vitro in the presence of AQP4 autoantibodies and active complement and may account for the tissue damage seen in pathologic samples from patients with NMO [ 7 ].

Additional mechanisms that may contribute to injury caused by AQP4 specific autoantibodies include disruption of potassium and glutamate homeostasis due to the physical association of AQP4 with an inward rectifying potassium channel and the excitatory amino acid transporter EAAT2.

Differential Diagnosis

The differential diagnosis of acute myelopathy is extensive, including structural, vascular, demyelinating, infectious, inflammatory, neoplastic, and paraneoplastic conditions (Table 13.1 ).

Structural

External compression of the spinal cord is an important and treatable cause of acute myelopathy. Recognition of these conditions with MR imaging is usually considered straightforward. A typical example of cord compression in the setting of vertebral metastasis from a primary lung carcinoma is displayed in Fig. 13.2 . It is essential to have a high index of suspicion for these disorders as few symptoms aside from pain may be present initially and neurologic deterioration can occur rapidly.

Spinal cord compression in the setting of congenital spinal canal stenosis and/or degenerative disk disease usually presents with subacute or chronic symptoms, although acute presentations can occur in the setting of trauma or acute disk herniation. Magnetic resonance imaging readily detects these abnormalities.

Occasionally, patients with myelopathy secondary to chronic stenosis, often due to a combination of congenital and acquired causes, will have dramatic longitudinally extensive cord signal abnormalities on MRI. These intrinsic cord abnormalities may cause the clinician to overlook an underlying spinal stenosis producing a subacute ischemic myelopathy due to compression, or the apparent cord compression may be attributed to cord edema from an intramedullary lesion rather than to the primary compressive process.

Erroneous diagnoses of neuromyelitis optica, transverse myelitis, or spinal cord tumor may be made in these circumstances. However, patients with myelopathy secondary to stenosis usually develop symptoms over a period of several months, whereas transverse myelitis (either idiopathic or related to NMO) worsens to the point of maximal severity over days to weeks. In addition, gadolinium enhancement associated with stenosis tends to be quite focal and localized to the area of maximal compression, whereas enhancement in longitudinally extensive myelitis or tumor often extends over several vertebral segments (Fig. 13.3 ) [ 8 ] .

Uncommon causes of extradural compression include extramedullary hematopoiesis, epidural lipomatosis, and atlantoaxial instability. Extramedullary hematopoiesis occurs in a number of hematologic disorders and in rare circumstances the epidural space may be involved. Reported causes include beta thalassemia, myelodysplastic syndromes, and polycythemia vera. Symptoms typically evolve over one to several months [ 9 ] . Epidural lipomatosis is a condition in which excess fat deposits form in the epidural space. Spinal cord compression can occur as a consequence, particularly in patients with preexisting spinal stenosis. Risk factors include endogenous or exogenous corticosteroid excess, obesity, and diabetes mellitus [ 10 ] . This condition often causes slowly progressive neurologic symptoms, but there are several reports of acute myelopathy related to epidural fat deposition [ 11 ] . Atlantoaxial instability is usually associated with an underlying condition and most commonly occurs in patients with rheumatoid arthritis or trisomy 21 [ 12, 13 ] . Patients with atlantoaxial dislocation may present with progressive myelopathy or acute spinal cord injury.

Spinal cord syrinx usually presents with a slowly progressive central cord syndrome. Characteristic findings include early occurrence of deep, poorly localized pain followed by loss of pain sensation at the level of the lesion, and progressive motor symptoms [ 14 ] . When a syrinx is present in the cervical cord, weakness appears initially in the upper limbs as the motor pathways to the arms are medial to those supplying the trunk and legs. Patients with this condition may present for acute evaluation when motor symptoms become bothersome or when painless injuries, especially burns, occur. Rarely, acute spinal cord damage due to syrinx occurs in the setting of trauma [ 15 ] or Valsalva maneuver [ 16 ] .

Vascular

In the absence of a compressive lesion, the sudden onset of severe impairment of motor and spinothalamic sensory functions with relative preservation of dorsal column sensory modalities suggests a stroke in the distribution of the anterior spinal artery. This is a feared complication of surgical manipulation of the thoracic or abdominal aorta, and in that context is readily identified.

However, cord infarction may occur spontaneously and occasionally without clearly identifiable risk factors that aid in the diagnosis. MRI findings suggestive of anterior spinal cord infarction include central T2 hyperintensity with sparing of the posterior cord and swelling of the cord. Gadolinium enhancement is variable, and absence of enhancement in the setting of a sudden-onset myelopathy is more suggestive of infarct than an inflammatory process. Figures 13.4 and 13.5 display the evolution of a typical cord infarct.

Intraspinal hematomas are uncommon. These conditions can occur as a rare but serious consequence of lumbar puncture, especially in patients treated with anticoagulant drugs. A study of 342 patients who were anticoagulated with heparin after lumbar puncture demonstrated a 2% risk of spinal hematoma, whereas there were no hematomas in a matched cohort of patients who were not anticoagulated [ 17 ] . Patients with a recent history of spinal surgery, epidural anesthesia, or coagulopathy are also at risk. Hemorrhage into the subarachnoid, subdural, or epidural spaces can occur, epidural hematoma being the most common [ 17 ]. Patients present with new, severe spinal pain and rapidly progressive neurologic deficits. These conditions can be readily identified with MR imaging.

A high index of suspicion for spinal arteriovenous fistula (AVF) is necessary as this is a treatable cause of progressive myelopathy. In the majority of cases, this condition produces a myelopathy that evolves over months. Some patients present with a stepwise course with repeated episodic deterioration related to upright posture or to minor exertion. Although this disorder is most common in men in the seventh decade of life, this potentially reversible process should be considered in all patients with an otherwise unexplained progressive or subacute myelopathy [ 18 ]. Abnormal high T2 signal in the cord extending into the conus and gadolinium enhancement are typical but nonspecific MRI findings of spinal dural AVF. The absence of any abnormal T2 signal is distinctly unusual in patients with dural AVF and suggests an alternate diagnosis. Presence of flow voids representing dilation of the epidural venous plexus is a more specific finding (Fig. 13.6 ), but may be seen in less than 50% of patients on standard MRI imaging.

Prone-supine myelography is highly sensitive for detection of dilated epidural veins; the invasive nature of the procedure and substantial false positive rate limit the usefulness of myelography as a screening tool [ 18 ] . In patients with a stepwise or progressive myelopathy and radiologic findings suggestive of dural AV fistula, comprehensive spinal angiography may be warranted. Fistulae producing a progressive myelopathy may be found as high as the brainstem, and accordingly one needs to be determined to detect the abnormality in cases where the clinical and screening radiologic features strongly suggest that a fistula is present.

Demyelinating Disease

Demyelinating diseases account for a substantial percentage of acute myelopathies. Distinguishing patients who have or are at risk to develop MS from those with less common demyelinating disorders such as NMO, acute disseminated encephalomyelitis (ADEM), and idiopathic transverse myelitis is important for the prognosis of the patient and for selection of appropriate therapy to prevent recurrence.

In a patient presenting with a new, incomplete myelopathy the following features on spinal MRI should suggest the possibility of an MS-related lesion (Fig. 13.7 ):1. Clearly circumscribed, focal T2 hyperintensity2. Affects only part of the cord in axial cross section, usually, but not exclusively in the periphery of the spinal cord3. Extends over less than two vertebral segments4. Minimal or no cord swelling is present [ 19 ]

In patients with spinal lesions meeting these criteria, a careful history regarding any previous episodic neurologic symptoms may reveal a history of past MS exacerbations that assist with the diagnosis. MRI scan of the brain may detect typical brain lesions of multiple sclerosis (focal, T2 hyperintense lesions that are periventricular, juxtacortical, or located in the brainstem). However, nonspecific brain lesions are common due to definable (e.g., migraine) and nondefinable causes and therefore such lesions should not be assumed to be pathognomonic of MS. Additionally, brain lesions are common in NMO and do not exclude that diagnosis [ 20 ] .

Cerebrospinal fluid (CSF) examination is often performed in this setting, although this testing may be unnecessary in patients with a high pretest probability of having MS based on clinical and radiographic evidence. Detection of oligoclonal bands in the CSF, preferably by isoelectric focusing on agarose gels followed by immunodetection, is predictive of eventual development of MS independent of MRI findings [ 21 ]. Nevertheless, as oligoclonal bands are not present in all patients with MS and occur in other inflammatory, infectious, and neoplastic conditions, presence of oligoclonal bands should not be regarded as diagnostic of MS and the result of this study should not be used to guide treatment decisions in isolation. Other CSF findings that should suggest a diagnosis other than MS include a nucl eated cell count greater than 50/ m L and an excess of neutrophils.

Longitudinally extensive cord signal change extending over three or more vertebral segments is unusual in multiple sclerosis. Some authors argue for the existence of an opticospinal variant of MS in Asian patients that is distinct from NMO, and longitudinally extensive spinal cord lesions may occur in patients with that condition [ 22 ]. Nevertheless, the occurrence of longitudinally extensive transverse myelitis (LETM) in the setting of a previous history of one or more attacks of severe optic neuritis is highly suspicious for NMO and should prompt the clinician to obtain a serum NMO-IgG antibody. The sensitivity and specificity of this immunofluorescent antibody test in classic NMO are approximately 75% and >90%, respectively [ 3, 23 ] .

Brain MRI is helpful in the evaluation of suspected NMO. Brain MRI lesions are common in NMO patients. In one series of 60 NMO patients, 60% had an abnormal brain MRI [ 20 ] . MRI lesions have been reported in NMO in regions of the brain known to express high levels of aquaporin- 4, including the hypothalamus and periventricular regions [ 4 ] . However, brain lesions in NMO patients usually differ from lesions that are characteristic of MS. CSF findings in NMO differ from those of MS; oligoclonal bands are infrequent in NMO and pleocytosis exceeding 50 WBC/ m L and neutrophilic pleocytosis occur in approximately 25% of cases in the context of an acute attack [ 24 ] .

Occasional patients have CSF NMO-IgG antibodies despite having negative results in serum [ 25 ] . Wingerchuk and colleagues have suggested the following diagnostic criteria for definiteNMO:1. History of optic neuritis2. History of acute myelitis3. At least two of three supportive criteria (a) MRI demonstrating contiguous spinal cord lesion extending over 3 vertebral segments (Fig. 13.8 )(b) Brain MRI at the onset of NMO symptoms that does not satisfy diagnostic criteria for MS(c) Seropositivity for NMO-IgG [ 23 ]

The absence of a history of optic neuritis does not exclude an NMO spectrum disorder. Some patients with an isolated LETM will subsequently develop classic findings of NMO. Others may have recurrent attacks of myelitis in the absence of optic neuritis, and may have a limited form of NMO. Presence of the NMO-IgG antibody in the setting of a single episode of LETM is strongly predictive of subsequent relapse; one series demonstrated a 55% risk of further episodes of myelitis and/or optic neuritis within one year in patients with a LETM [ 26 ] .

Acute myelopathy may occur in the setting of ADEM, a multifocal demyelinating disorder of the CNS that typically occurs after an infectious syndrome or recent vaccination; it is more common in children. In the classic presentation, MRI demonstrates multifocal gadolinium-enhancing CNS lesions. The most specific criterion that distinguishes ADEM from MS, and is required for the diagnosis, is encephalitis [27].

Patients with a symmetric, severe acute myelopathy (complete transverse myelitis) and/or isolated LETM with negative NMO-IgG may have an isolated inflammatory demyelinating transverse myelitis (i.e., idiopathic transverse myelitis) or another infectious, inflammatory, or neoplastic condition. As discussed below, serum and CSF testing may reveal evidence of a parainfectious cause in these patients; when such testing is unrevealing, clinical and radiographic follow-up is important. In patients in this group who display ongoing clinical deterioration beyond 3 weeks or have worsening findings on MRI, biopsy of the spinal cord should be considered to exclude tumor or another treatable inflamatory disorder, such as neurosarcoidosis.

Infectious

In addition to compression by an extrinsic infectious lesion such as an epidural abscess, some pathogens can produce acute or subacute myelopathies by direct infection of the cord or by inducing a parainfectious, presumably autoimmune process. Clinical features that should prompt an increased level of suspicion for an infectious process include current or recent presence of fever, meningismus, rash, symptoms of systemic illness, recent travel, or immunosuppression.

Although nonspecific, CSF pleocytosis (particularly if greater than 50 WBCs/ m L) suggests this possibility. However, patients with parainfectious myelopathy often do not recall or have symptoms of a recent illness. In a review of 23 patients with parainfectious myelopathy confirmed by serological or CSF studies, only nine (39%) recalled symptoms consistent with an infectious process in the previous month [28] .

Viruses are the most common cause of parainfectious myelopathy [ 28 ] . CSF PCR testing for herpes viruses (herpes simplex virus 1 and 2, EpsteinBarr virus, varicella zoster virus, cytomegalovirus, human herpesvirus-6) is appropriate in an unexplained myelopathy as these viruses are the most commonly identified causes of parainfectious myelopathy and may be treatable with specific antiviral therapies [ 28 ] . A multitude of other viruses have been implicated as causes of infectious or parainfectious myelitis, including adenoviruses, coxsackie B virus, enteroviruses, measles [ 28 ] , and dengue [ 29 ] .

Certain viral infections characteristically produce an acute flaccid paralysis with sparing of sensory function when involving the central nervous system. Poliomyelitis is the classic example of such a condition. This disorder is now extraordinarily rare in developed countries, although importation of this disease from endemic regions [ 30 ] and limited person to person spread in an undervaccinated community have been reported in recent years [ 31 ] . Similar clinical presentations have been associated with epidemics of enterovirus 70 (acute hemorrhagic conjunctivitis) and enterovirus 71 (hand, foot, and mouth disease) [ 32 ] , as well as West Nile virus [ 33 ] . In a minority of cases, rabies encephalomyelitis can also present as an ascending flaccid paralysis with spinal cord signal change [34].

Parainfectious myelitis may occur in association with recent bacterial infections, often with Chlamydia and Mycoplasma species [ 28 ]. Myelitis can occur in Mycobacterium tuberculosis infection either due to direct involvement of the cord or on a compressive basis in the setting of vertebral involvement (Pott disease). Bacterial myelitis can also occur with Treponema pallidum (syphilis) [ 35 ] or Borrelia burgdorferi (Lyme disease) infections [ 36 ] ; both of these presentations are uncommon.

Fungal and parasitic infections are rare causes of acute myelitis, but should be considered in patients at risk due to immunosuppression and/or travel exposures. Infections associated with acute myelopathies include schistosomiasis [ 37 ], strongylosis, candidiasis [ 28 ], and blastomycosis [ 38 ] .

Inflammatory In addition to inflammatory demyelinating diseases, other systemic inflammatory disorders can produce acute or subacute myelopathies. Myelopathy can occur as a complication of Sjgren syndrome or systemic lupus erythematosus. However, antibodies associated with these syndromes (e.g., ANA, SS-A) are encountered in patients with NMO and may occur in other inflammatory demyelinating diseases.

A serological survey of 153 patients with NMO spectrum disorders found positive ANA and SS-A antibodies in 44% and 16%, respectively [ 39 ] . Accordingly, diagnoses of lupus or Sjgren syndrome should not be made on the basis of antibody findings alone in cases of acute myelopathy unless specific diagnostic criteria for these diseases are met.

Behet disease is a chronic, relapsing inflamatory disorder characterized by recurrent oral aphthous ulcers and other systemic manifestations including recurrent genital ulcerations, eye, and skin lesions [ 40 ] . Spinal cord and other nervous system involvement occurs in a minority of patients with this condition, either due to direct formation of lesions in the CNS or secondary to infarct from involvement of major vascular structures [ 41 ] . Presence of a positive pathergy test (development of a nodule 2 mm in diameter 2448 h after subcutaneous insertion of a sterile needle) is accepted as a supportive criterion for diagnosis of this disease, but this test is insensitive and does not establish a diagnosis in isolation [ 40 ] . There are no other laboratory or imaging findings that are unique to this condition, andaccordingly the diagnosis requires presence of other characteristic systemic features.

Sarcoidosis is a nonnecrotizing granulomatous inflammatory process that can involve multiple organ systems. Neurological involvement occurs in approximately 5% of cases, and in those cases, neurologic symptoms are the initial manifestation in about half [ 42 ] . In the absence of systemic disease, the diagnosis of neurosarcoidosis is often difficult. Spinal imaging findings that may suggest this process include a nodular enhancing pattern in the parenchyma, meningeal enhancement, and nerve root enhancement. Oligoclonal bands in the CSF have been reported in 2751% of cases; the presence of oligoclonal bands should not automatically lead to a diagnosis of MS [ 43, 44 ] . Although neither sensitive nor specific, an elevated serum ACE level may suggest sarcoidosis as well. In patients with imaging findings suspicious for sarcoid and those with an otherwise unexplained myelopathy, it is helpful to search for evidence of systemic sarcoid in a lesion that could be biopsied (e.g., an enlarged lymph node). CT imaging of the chest may demonstrate evidence of hilar lymphadenopathy. Blind conjunctival biopsy occasionally demonstrates characteristic noncaseating granulomatous inflammation. In cases of isolated CNS involvement, such studies will be unrevealing and empiric corticosteroid treatment for both therapeutic and diagnostic purposes is often the best approach; dramatic and sustained improvement in the face of a syndrome suggestive of sarcoidosis is often the basis of a tentative but acceptable diagnosis.

Toxic/Metabolic

Metabolic disorders affecting the cord usually produce a chronic myelopathy, although many patients will not complain of symptoms until a certain level of impairment develops. In most, careful history reveals that the symptoms of myelopathy are long-standing. Nevertheless, given that the diagnosis and treatment of these disorders is associated with minimal risk, obtaining limited metabolic studies such as serum vitamin B12, methylmalonic acid, and copper levels is appropriate in the setting of unexplainedsubacute or chronic myelopathies.

Acute myelopathies have occurred secondary to toxic exposures from consumption of toxic dietary staples (e.g., cassava, Lathyrus sativus ) or recreational substance abuse (e.g., tricresyl phosphate toxicity from consumption of adulterated Jamaican ginger extract); many of these conditions are of limited historical or geographic relevance [ 45 ] . An exception is myelopathy secondary to nitrous oxide exposure. Nitrous oxide can produce myelopathy via irreversible oxidation of cobalamin, resulting in secondary vitamin B12 deficiency [ 45 ] . Individuals with preexisting subclinical vitamin B12 deficiency are particularly vulnerable. This condition continues to occur secondary to recreational abuse [ 46 ] and rarely in patients receiving nitrous oxide anesthesia [ 47 ] or dental professionals working in poorly ventilated offices [ 46 ] . In recreational users, specific questioning about use of nitrous oxide is important as users may be reluctant to admit this habit and unaware of its toxic potential.

Iatrogenic

Patients who have undergone radiation treatment for cancer can develop radiation myelitis when the spinal cord is included in the radiation field. This condition can present acutely during radiation treatment or in a delayed fashion. In a patient with a history of cancer, it is essential to exclude direct metastatic involvement of the cord prior to attributing any myelopathy to radiation effect. Autoimmune myelitis may occur after vaccinations. Classic descriptions of postvaccination encephalomyelitis occurred in individuals who received obsolete forms of rabies vaccination, but postvaccination myelitis has been reported after a host of other common vaccinations including influenza, pertussis, diphtheriatetanus,MMR, and hepatitis B [ 48 ] . However, the onset of myelopathy after vaccination may be purely coincidental and recent vaccination should not deter investigations to uncover othertreatable causes. Subacute myelopathy also may result from toxic effects of intrathecal chemotherapy with several agents including methotrexate, doxorubicin, vincristine, and cytarabine [ 45 ] .Neoplastic and Paraneoplastic

Intramedullary neoplasms, such as astrocytomas and ependymomas, and extramedullary, intradural tumors, such as meningiomas and neurofibromas, may become symptomatic with a subacute time course mimicking extradural tumors or transverse myelitis. These tumors are easily visualized on MRI, although they may sometimes be confused with inflammatory lesions. Biopsy is usually required to confirm the diagnosis.

Lymphoproliferative malignancies, such as lymphomatoid granulomatosis and intravascular lymphoma, can involve the spinal cord and evolve with a subacute time course. Confident diagnosis requires biopsy of the CNS or other involved site, although in the case of lymphomatoid granulomatosis the presence of oligoclonal bands and positive CSF PCR for Epstein-Barr virus increases the index of suspicion. Myelitis may occur as a paraneoplastic disease. The index of suspicion for a paraneoplastic process should be increased in patients with a known history of cancer and in smokers. A serum evaluation for paraneoplastic autoantibodies should be considered in these circumstances.

Certain imaging patterns may also be suspicious for a paraneoplastic etiology; we have encountered a number of patients with hyperintense T2 lesions that appear confined within individual spinal tracts in this circumstance, often symmetrically on both sides of the cord (Fig. 13.9 ) [ 49 ] .

Paraneoplastic syndromes may produce multifocal nervous system involvement mimicking other disorders such as NMO. In particular, collapsing response-mediator protein-5 (CRMP-5) IgG antibodiescan cause autoimmune myelitis and optic neuritis [ 50, 51 ] .

Alternate Localizations

When there is no spinal cord abnormality on neuroimaging in the context of an apparent acutemyelopathy, the responsible lesion may be elsewhere in the nervous system. The primary item on the differential diagnosis in patients with bilateral motor and sensory symptoms is an acute neuropathy such as GuillainBarr syndrome. In addition to ascending weakness, findings favoring this diagnosis include areflexia, absence of a defined sensory level, and elevated protein concentration in the CSF with a normal cell count. In patients with pure motor symptoms, myopathies and occasionally neuromuscular junction disorders can be mistaken for spinal cord disease.

Parafalcine space-occupying lesions (e.g., meningioma) and bilateral anterior cerebral artery distribution infarcts occasionally present with bilateral lower limb weakness mimicking myelopathyas well.

However, the absence of an MRI abnormality should not automatically lead to the conclusion that the problem does not localize to the spinal cord. Subtle imaging abnormalities such as swelling of the cord in the absence of signal change, as occasionally seen in early cord infarct, or symptomatic epidural lipomatosis may be missed on initial review. The possibility of an acute presentation of a chronic metabolic, degenerative, or infectious disorder (e.g., AIDS myelopathy, tropical spastic paraparesis due to HTLV-I) should also be considered, although these conditions rarely evolve during short-term neurologic follow-up. Occasionally, patients with chronic myelopathies do not seek medical attention despite long-standing symptoms until they become associated with functional impairment.

Epidemiology

Metastatic spinal cord compression is a common complication of advanced cancer, occurring in 2.5 6% of individuals with systemic malignancy ascertained in population-based studies [ 52, 53 ]. In approximately 20% of cases, cord compression is the presenting manifestation of cancer [ 54 ] .Metastases attributable to a specific cancer generally parallel the relative frequency of that cancer, with approximately half of cases attributable to carcinomas of the breast, prostate, and lung [ 52 ] .

However, certain malignancies including renal cell carcinoma [ 52 ] , multiple myeloma, and lymphoma [ 54 ] are disproportionately more likely to result in cord compression, whereas gastrointestinal cancers, including colorectal and pancreatic carcinoma, are disproportionately less likely to do so [ 53 ] . As MS is a relatively common disorder (prevalence estimated at 0.9 cases per 1,000 in the United States population [ 55 ] ) and the majority of patients have imaging evidence of spinal cord involvement even at the time of diagnosis [ 56 ] ,

MS is responsible for a substantial proportion of acute myelopathies. MS plaques in the cord often result in minimal symptoms, and are asymptomatic in up to two-thirds of cases [ 57 ] . Milder myelopathic presentations with asymmetric motor and sensory involvement (i.e., partial transverse myelitis) are the most common myelopathies that are manifestations of inaugural or established MS [ 58 ] .

Other individual causes of nontraumatic, acute myelopathy are uncommon. For instance, retrospective studies suggest that the incidence of acute transverse myelitis in patients without a previous history of neurologic disease ranges from 1.3 to 4.6 cases per million per year [ 59, 60 ] . Similarly, epidural abscess was diagnosed at a rate of only 2 of 10,000 hospital admissions per year at an urban referral center [ 61] . Collectively, however, these less common entities constitute an important group of disorders that may need very specific treatment.

The etiology of new-onset, noncompressive myelopathy is often unclear at the time of presentation. A recent French series reported that the etiology of acute myelopathy could not be determined in 101 of 170 patients at onset. Fifty-four percent of these patients were subsequently diagnosed with either multiple sclerosis (45 patients), neuromyelitis optica (5 patients), or a connective tissue disease (5 patients). Many patients with each of these disorders would likely benefit from maintenance therapies to prevent relapse. This result highlights the importance of diagnostic testing in cases of acute noncompressive myelopathy, as many patients with this type of presentation have treatable disorders with potential to result in serious future morbidity.

Demographics and Other Risk Factors

Age, gender, ethnicity, and race may suggest that a particular cause of acute myelopathy is more or less likely. Demographic features associated with selected causes of acute myelopathy are presented in Table 13.2 [ 18, 62 65 ] . Most causes of acute myelopathy are not restricted by demography, and age, gender, and ethnicity do not exclude any etiology from consideration in an individual patient.

Recognition of risk factors related to habits or other medical history is equally important. Risk factors associated with particular causes of myelopathy are listed in Table 13.3 .

Clinical Features

Syndromes

Presentations of spinal cord disease are often described in terms of clinical syndromes. Spinal cord syndromes associated with specific etiologies are listed in Table 13.4 . Although the type of clinical presentation seen may help to narrow the differential diagnosis, none of these syndromes are pathognomonic for any particular condition. Accordingly, recognition of other characteristic clinical features, imaging findings, and the results of other diagnostic studies are necessary for accuratediagnosis.

Brown-Squard Syndrome

Complete Brown-Squard syndrome refers to the clinical presentation seen with hemisection of the spinal cord. An affected patient has loss of motor function and dorsal column sensory modalities on the side of the lesion, with pain and temperature loss below the level of the lesion on the opposite side of the body due to disruption of the spinothalamic tract. The complete presentation is unusual; a partial Brown-Squard syndrome with preservation of dorsal column sensory function is more common. This type of asymmetric presentation is often seen in demyelinating diseases, particularly MS, but can also occur in the early stages of a compressive lesion.

Anterior Cord Syndrome

In this presentation, the corticospinal and spinothalamic tracts are injured bilaterally with preservation of dorsal column sensory functions. This syndrome is seen with infarction of the anterior spinal artery, but can also occur with compressive lesions.

Central Cord Syndrome

The characteristic evolution of a central cord syndrome in the setting of a syrinx was described earlier. Common features include deep, uncomfortable pain, loss of pain and temperature sensation at the level of the lesion due to disruption of the crossing fibers of the spinothalamic tracts, and impairment of motor function in the upper limbs prior to the lower limbs and trunk. In addition to syrinx and cord tumor, the features of central cord syndrome can occur with inflamatory demyelinating diseases, particularly neuromyelitis optica.

Posterior Cord Syndrome

Isolated involvement of the dorsal columns is most commonly seen in the setting of a chronic myelopathy; tabes dorsalis in the setting of tertiary syphilis is a classic example. This syndrome occasionally occurs due to infarction of the posterior spinal artery.

Conus Medullaris Syndrome

Myelopathy confined to the terminal portion of the spinal cord results in flaccid paralysis of the bladder and anal sphincters. The presentation may occur as a component of a more extensive cord lesion involving the conus or be quite isolated.

There are multiple causes including compression, dural arteriovenous fistula, neoplasm, and demyelination. One needs to distinguish this presentation from a cauda equina syndrome. Compression or inflammation of the cauda equine produces lower motor neuron findings including weakness and reflex loss in the lower limbs corresponding to the involved nerve roots as well as sensory changes in the dermatomes innervated by involved sensory roots. Pain is usual in cauda equina syndrome; bowel and bladder involvement is variable depending on the levels involved.

Complete Cord Syndrome

The clinical picture of complete transection of the spinal cord at the level of the lesion (absence of all sensory modalities and motor function below the lesion) is described as the complete cord syndrome. This type of presentation occurs with severe idiopathic transverse myelitis and is also a common presentation of an extradural compressive lesion producing severe cord compression.

Symptoms

Although many symptoms of acute cord injury are nonspecific, certain symptoms are characteristic and suggestive of particular conditions. Pain is not unique to cord compression, but is an important red flag. In the majority of cases of metastatic SCC, pain precedes the onset of other neurologic symptoms. Pain in the thoracic region is particularly concerning, not only because the majority of metastatic cord compressions occur in this region [ 66 ] , but also because benign musculoskeletal and radicular causes of pain in the thoracic spine are far less common than in the neck or low back. Pain that worsens at night or with recumbent position is also suggestive of cord compression.

A history of prior neurological symptoms is often informative in the diagnosis of inflamatory demyelinating diseases. A history of previous episodic visual, motor, urinary, or sensory disturbances lasting greater than 24 h may suggest previously unrecognized MS exacerbations.

A history of clear worsening of neurologic symptoms in response to heat or a reproducible shocklike sensation traveling down the spine with forward flexion of the neck (Lhermitte sign) is quite suggestive of demyelination. Paroxysmal tonic spasms (brief, involuntary muscle contractions typically lasting from 15 to 60 s at a time) are a less common but highly specific indicator of an inflammatory demyelinating disease. A history of episodes of intractable vomiting or hiccoughs is now recognized as a common harbinger of NMO spectrum disorders [ 67, 68 ].

Time Course

Myelopathies can develop suddenly, acutely (