The initial symptoms of disease that evolve over days or weeks are focal neck or back pain, followed by various combinations of paresthesias, sensory loss, motor weakness, and sphincter disturbance evolving over hours to several days. There may be only mild sensory symptoms or a devastating functional transection of the cord. Partial lesions selectively involve the posterior columns or anterior spinothalamic tracts or are limited to one side of the cord. Paresthesias or numbness typically begins in the feet and ascends symmetrically or asymmetrically. These symptoms initially simulate Guillain-Barré syndrome, but involvement of the trunk with a sharply demarcated spinal cord level indicates the myelopathic nature of the process. In severe and abrupt cases, areflexia reflecting spinal shock may be present, but hyperreflexia supervenes over days or weeks; persistent areflexic paralysis with a sensory level indicates necrosis over multiple segments of the spinal cord.
Approach the the Patient: Compressive and Noncompressive Myelopathy
Distinguishing Compressive from Noncompressive Myelopathy
The first priority is to exclude a treatable compression of the cord by a mass. The common causes are tumor, epidural abscess or hematoma, herniated disk, or vertebral pathology. Epidural compression due to malignancy or abscess often causes warning signs of neck or back pain, bladder disturbances, and sensory symptoms that precede the development of paralysis. Spinal subluxation, hemorrhage, and noncompressive etiologies such as infarction are more likely to produce myelopathy without antecedent symptoms. MRI with gadolinium infusion, centered on the clinically suspected level, is the initial diagnostic procedure; in some cases it is appropriate to image the entire spine (cervical through sacral regions) to search for additional clinically silent lesions. Once compressive lesions have been excluded, noncompressive causes of acute myelopathy that are intrinsic to the cord are considered, primarily vascular, inflammatory, and infectious etiologies.
Neoplastic Spinal Cord Compression
In adults, most neoplasms are epidural in origin, resulting from metastases to the adjacent spinal bones. The propensity of solid tumors to metastasize to the vertebral column probably reflects the high proportion of bone marrow located in the axial skeleton. Almost any malignant tumor can metastasize to the spinal column, with breast, lung, prostate, kidney, lymphoma, and plasma cell dyscrasia being particularly frequent. The thoracic spinal column is most commonly involved; exceptions are metastases from prostate and ovarian cancer, which occur disproportionately in the sacral and lumbar vertebrae, probably resulting from spread through Batson's plexus, a network of veins along the anterior epidural space. Retroperitoneal neoplasms (especially lymphomas or sarcomas) enter the spinal canal through the intervertebral foramens and produce radicular pain with signs of root weakness prior to cord compression.
Pain is usually the initial symptom of spinal metastasis; it may be aching and localized or sharp and radiating in quality and typically worsens with movement, coughing, or sneezing and characteristically awakens patients at night. A recent onset of persistent back pain, particularly if in the thoracic spine (which is uncommonly involved by spondylosis), should prompt consideration of vertebral metastasis. Rarely, pain is mild or absent. Plain radiographs of the spine and radionuclide bone scans have only a limited role in diagnosis because they do not identify 15–20% of metastatic vertebral lesions and fail to detect paravertebral masses that reach the epidural space through the intervertebral foramens. MRI provides excellent anatomic resolution of the extent of spinal tumors (Fig. 377-2) and is able to distinguish between malignant lesions and other masses—epidural abscess, tuberculoma, or epidural hemorrhage, among others—that present in a similar fashion. Vertebral metastases are usually hypointense relative to a normal bone marrow signal on T1-weighted MRI scans; after the administration of gadolinium, contrast enhancement may deceptively “normalize” the appearance of the tumor by increasing its intensity to that of normal bone marrow. Infections of the spinal column (osteomyelitis and related disorders) are distinctive in that, unlike tumor, they may cross the disk space to involve the adjacent vertebral body.
Epidural spinal cord compression due to breast carcinoma. Sagittal T1-weighted (A) and T2-weighted (B) MRI scans through the cervicothoracic junction reveal an infiltrated and collapsed second thoracic vertebral body with posterior displacement and compression of the upper thoracic spinal cord. The low-intensity bone marrow signal in A signifies replacement by tumor.
If spinal cord compression is suspected, imaging should be obtained promptly. If there are radicular symptoms but no evidence of myelopathy, it is usually safe to defer imaging for 24–48 h. Up to 40% of patients who present with cord compression at one level are found to have asymptomatic epidural metastases elsewhere; thus, the length of the spine should be imaged when epidural malignancy is in question.
Treatment: Neoplastic Spinal Cord Compression
Management of cord compression includes glucocorticoids to reduce cord edema, local radiotherapy (initiated as early as possible) to the symptomatic lesion, and specific therapy for the underlying tumor type. Glucocorticoids (dexamethasone, up to 40 mg daily) can be administered before the imaging study if the clinical suspicion is strong and continued at a lower dose until radiotherapy (generally 3000 cGy administered in 15 daily fractions) is completed. Radiotherapy appears to be effective even for most classically radioresistant metastases. A good response to radiotherapy can be expected in individuals who are ambulatory at presentation. Treatment usually prevents new weakness, and some recovery of motor function occurs in up to one-third of treated patients. Motor deficits (paraplegia or quadriplegia), once established for >12 h, do not usually improve, and beyond 48 h the prognosis for substantial motor recovery is poor. Although most patients do not experience recurrences in the months following radiotherapy, with survival beyond 2 years, recurrence becomes increasingly likely and can be managed with additional radiotherapy. New techniques, including intensity-modulated radiotherapy (IMRT), can deliver high doses of focused radiation with extreme precision, and preliminary data suggest that these methods produce similar rates of response compared to traditional radiotherapy. Biopsy of the epidural mass is unnecessary in patients with known primary cancer, but it is indicated if a history of underlying cancer is lacking. Surgery, either decompression by laminectomy or vertebral body resection, is usually considered when signs of cord compression worsen despite radiotherapy, when the maximum tolerated dose of radiotherapy has been delivered previously to the site, or when a vertebral compression fracture or spinal instability contributes to cord compression. The routine use of radiotherapy as first-line treatment for most cases of malignant spinal cord compression has recently been called into question by a randomized clinical trial indicating that surgery followed by radiotherapy is more effective than radiotherapy alone for patients with a single area of spinal cord compression by extradural tumor; patients with recurrent cord compression, brain metastases, radiosensitive tumors, or severe motor symptoms of >48 hours duration were excluded from this study.
In contrast to tumors of the epidural space, most intradural mass lesions are slow-growing and benign. Meningiomas and neurofibromas account for most of these, with occasional cases caused by chordoma, lipoma, dermoid, or sarcoma. Meningiomas (Fig. 377-3) are often located posterior to the thoracic cord or near the foramen magnum, although they can arise from the meninges anywhere along the spinal canal. Neurofibromas are benign tumors of the nerve sheath that typically arise near the posterior root; when multiple, neurofibromatosis is the likely etiology. Symptoms usually begin with radicular sensory symptoms followed by an asymmetric, progressive spinal cord syndrome. Therapy is by surgical resection.
MRI of a thoracic meningioma. Coronal T1-weighted postcontrast image through the thoracic spinal cord demonstrates intense and uniform enhancement of a well-circumscribed extramedullary mass (arrows), which displaces the spinal cord to the left.
Primary intramedullary tumors of the spinal cord are uncommon. They present as central cord or hemicord syndromes, often in the cervical region; there may be poorly localized burning pain in the extremities and sparing of sacral sensation. In adults, these lesions are ependymomas, hemangioblastomas, or low-grade astrocytomas (Fig. 377-4). Complete resection of an intramedullary ependymoma is often possible with microsurgical techniques. Debulking of an intramedullary astrocytoma can also be helpful, as these are often slowly growing lesions; the value of adjunctive radiotherapy and chemotherapy is uncertain. Secondary (metastatic) intramedullary tumors also occur, especially in patients with advanced metastatic disease (Chap. 379), although these are not nearly as frequent as brain metastases.
MRI of an intramedullary astrocytoma. Sagittal T1-weighted postcontrast image through the cervical spine demonstrates expansion of the upper cervical spine by a mass lesion emanating from within the spinal cord at the cervicomedullary junction. Irregular peripheral enhancement occurs within the mass (arrows).
Spinal epidural abscess presents as a clinical triad of midline dorsal pain, fever, and progressive limb weakness. Prompt recognition of this distinctive process will in most cases prevent permanent sequelae. Aching pain is almost always present, either over the spine or in a radicular pattern. The duration of pain prior to presentation is generally ≤2 weeks but may on occasion be several months or longer. Fever is usual, accompanied by elevated white blood cell count, sedimentation rate, and C-reactive protein. As the abscess expands, further spinal cord damage results from venous congestion and thrombosis. Once weakness and other signs of myelopathy appear, progression may be rapid. A more chronic sterile granulomatous form of abscess is also known, usually after treatment of an acute epidural infection.
Risk factors include an impaired immune status (diabetes mellitus, renal failure, alcoholism, malignancy), intravenous drug abuse, and infections of the skin or other tissues. Two-thirds of epidural infections result from hematogenous spread of bacteria from the skin (furunculosis), soft tissue (pharyngeal or dental abscesses), or deep viscera (bacterial endocarditis). The remainder arise from direct extension of a local infection to the subdural space; examples of local predisposing conditions are vertebral osteomyelitis, decubitus ulcers, lumbar puncture, epidural anesthesia, or spinal surgery. Most cases are due to Staphylococcus aureus; gram-negative bacilli, Streptococcus, anaerobes, and fungi can also cause epidural abscesses. Tuberculosis from an adjacent vertebral source (Pott's disease) remains an important cause in the underdeveloped world (Fig. 377-5).
MRI of a spinal epidural abscess due to tuberculosis. A. Sagittal T2-weighted free spin-echo MR sequence. A hypointense mass replaces the posterior elements of C3 and extends epidurally to compress the spinal cord (arrows). B.Sagittal T1-weighted image after contrast administration reveals a diffuse enhancement of the epidural process (arrows) with extension into the epidural space.
MRI scans localize the abscess and exclude other causes of myelopathy. Lumbar puncture is only required if encephalopathy or other clinical signs raise the question of associated meningitis, a feature that is found in <25% of cases. The level of the puncture should be planned to minimize the risk of meningitis due to passage of the needle through infected tissue. A high cervical tap is sometimes the safest approach. CSF abnormalities in subdural abscess consist of pleocytosis with a preponderance of polymorphonuclear cells, an elevated protein level, and a reduced glucose level, but the responsible organism is not cultured unless there is associated meningitis. Blood cultures are positive in <25% of cases.
Treatment: Spinal Epidural Abscess
Treatment is by decompressive laminectomy with debridement combined with long-term antibiotic treatment. Surgical evacuation prevents development of paralysis and may improve or reverse paralysis in evolution, but it is unlikely to improve deficits of more than several days duration. Broad-spectrum antibiotics should be started empirically before surgery and then modified on the basis of culture results; medication is continued for at least 4 weeks. If surgery is contraindicated or if there is a fixed paraplegia or quadriplegia that is unlikely to improve following surgery, long-term administration of systemic and oral antibiotics can be used; in such cases, the choice of antibiotics may be guided by results of blood cultures. However, paralysis may develop or progress during antibiotic therapy; thus, initial surgical management remains the treatment of choice unless the abscess is limited in size and causes few or no neurologic signs.
With prompt diagnosis and treatment of spinal epidural abscess, up to two-thirds of patients experience significant recovery.
Hemorrhage into the epidural (or subdural) space causes acute focal or radicular pain followed by variable signs of a spinal cord or conus medullaris disorder. Therapeutic anticoagulation, trauma, tumor, or blood dyscrasias are predisposing conditions. Rare cases complicate lumbar puncture or epidural anesthesia. MRI and CT confirm the clinical suspicion and can delineate the extent of the bleeding. Treatment consists of prompt reversal of any underlying clotting disorder and surgical decompression. Surgery may be followed by substantial recovery, especially in patients with some preservation of motor function preoperatively. Because of the risk of hemorrhage, lumbar puncture should be avoided whenever possible in patients with severe thrombocytopenia or other coagulopathies.
Hemorrhage into the substance of the spinal cord is a rare result of trauma, intraparenchymal vascular malformation (see below), vasculitis due to polyarteritis nodosa or systemic lupus erythematosus (SLE), bleeding disorders, or a spinal cord neoplasm. Hematomyelia presents as an acute painful transverse myelopathy. With large lesions, extension into the subarachnoid space results in subarachnoid hemorrhage (Chap. 275). Diagnosis is by MRI or CT. Therapy is supportive, and surgical intervention is generally not useful. An exception is hematomyelia due to an underlying vascular malformation, for which selective spinal angiography may be indicated, followed by surgery to evacuate the clot and remove the underlying vascular lesion.
The most frequent causes of noncompressive acute transverse myelopathy (ATM) are spinal cord infarction; systemic inflammatory disorders, including SLE and sarcoidosis; demyelinating diseases, including multiple sclerosis (MS); neuromyelitis optica (NMO); postinfectious or idiopathictransverse myelitis, which is presumed to be an immune condition related to acute disseminated encephalomyelitis (Chap. 380); and infectious (primarily viral) causes. After spinal cord compression is excluded, the evaluation generally requires a lumbar puncture and a search for underlying systemic disease (Table 377-3).
Table 377-3 Evaluation of Acute Transverse Myelopathy |Favorite Table|Download (.pdf)
Table 377-3 Evaluation of Acute Transverse Myelopathy
MRI of spinal cord with and without contrast (exclude compressive causes).
CSF studies: Cell count, protein, glucose, IgG index/synthesis rate, oligoclonal bands, VDRL; Gram's stain, acid-fast bacilli, and India ink stains; PCR for VZV, HSV-2, HSV-1, EBV, CMV, HHV-6, enteroviruses, HIV; antibody for HTLV-I, Borrelia burgdorferi, Mycoplasma pneumoniae, and Chlamydia pneumoniae; viral, bacterial, mycobacterial, and fungal cultures.
Blood studies for infection: HIV; RPR; IgG and IgM enterovirus antibody; IgM mumps, measles, rubella, group B arbovirus, Brucella melitensis, Chlamydia psittaci, Bartonella henselae, schistosomal antibody; cultures for B. melitensis. Also consider nasal/pharyngeal/anal cultures for enteroviruses; stool O&P for Schistosoma ova.
Immune-mediated disorders: ESR; ANA; ENA; dsDNA; rheumatoid factor; anti-SSA; anti-SSB, complement levels; antiphospholipid and anticardiolipin antibodies; p-ANCA; antimicrosomal and antithyroglobulin antibodies; if Sjögren syndrome suspected, Schirmer test, salivary gland scintography, and salivary/lacrimal gland biopsy.
Sarcoidosis: Serum angiotensin-converting enzyme; serum Ca; 24-hour urine Ca; chest x-ray; chest CT; total body gallium scan; lymph node biopsy.
Demyelinating disease: Brain MRI scan, evoked potentials, CSF oligoclonal bands, neuromyelitis optica antibody (anti-aquaporin-4 [NMO] antibody).
Vascular causes: CT myelogram; spinal angiogram.
The cord is supplied by three arteries that course vertically over its surface: a single anterior spinal artery and paired posterior spinal arteries. In addition to the vertebral arteries, the anterior spinal artery is fed by radicular vessels that arise at C6, at an upper thoracic level, and, most consistently, at T11-L2 (artery of Adamkiewicz). At each segment, paired penetrating vessels branch from the anterior spinal artery to supply the anterior two-thirds of the spinal cord; the posterior spinal arteries, which often become less distinct below the midthoracic level, supply the posterior columns.
Spinal cord ischemia can occur at any level; however, the presence of the artery of Adamkiewicz creates a watershed of marginal blood flow in the upper thoracic segments. With systemic hypotension or cross-clamping of the aorta, cord infarction occurs at the level of greatest ischemic risk, usually T3-T4, and also at boundary zones between the anterior and posterior spinal artery territories which may result in a rapidly progressive syndrome (over hours) of weakness and spasticity with little sensory change.
Acute infarction in the territory of the anterior spinal artery produces paraplegia or quadriplegia, dissociated sensory loss affecting pain and temperature sense but sparing vibration and position sense, and loss of sphincter control (“anterior cord syndrome”). Onset may be sudden and dramatic but more typically is progressive over minutes or a few hours, quite unlike stroke in the cerebral hemispheres. Sharp midline or radiating back pain localized to the area of ischemia is frequent. Areflexia due to spinal shock is often present initially; with time, hyperreflexia and spasticity appear. Less common is infarction in the territory of the posterior spinal arteries, resulting in loss of posterior column function.
Spinal cord infarction results from aortic atherosclerosis, dissecting aortic aneurysm (manifest as chest or back pain with diminished pulses in legs), vertebral artery occlusion or dissection in the neck, aortic surgery, or profound hypotension from any cause. Cardiogenic emboli and vasculitis related to collagen vascular disease [particularly SLE, Sjögren's syndrome, and the antiphospholipid antibody syndrome (see below)] are other causative conditions. Occasional cases develop from embolism of nucleus pulposus material into spinal vessels, usually from local spine trauma. In a substantial number of cases no cause can be found, and thromboembolism in arterial feeders is suspected. The MRI may fail to demonstrate limited infarctions of the cord, especially in the first day, but as often it becomes abnormal at the affected level.
In cord infarction due to presumed thromboembolism, acute anticoagulation is probably not indicated, with the exception of the unusual transient ischemic attack or incomplete infarction with a stuttering or progressive course. The antiphospholipid antibody syndrome is treated with anticoagulation. Drainage of spinal fluid has reportedly been successful in some cases of cord infarction but has not been studied systematically.
Inflammatory and Immune Myelopathies (Myelitis)
This broad category includes the demyelinating conditions MS, NMO, and postinfectious myelitis, as well as sarcoidosis and connective tissue disease. In approximately one-quarter of cases of myelitis, no underlying cause can be identified. Some will later manifest additional symptoms of an immune-mediated disease. Recurrent episodes of myelitis are usually due to one of the immune-mediated diseases or to infection with herpes simplex virus (HSV) type 2 (below).
MS (Chap. 380) may present with acute myelitis, particularly in individuals of Asian or African ancestry. In whites, MS rarely causes a complete transverse myelopathy (i.e., acute bilateral signs), but it is among the most common causes of a partial syndrome. MRI findings in MS-associated myelitis typically consist of mild swelling and edema of the cord and diffuse or multifocal areas of abnormal signal on T2-weighted sequences. Contrast enhancement, indicating disruption in the blood-brain barrier associated with inflammation, is present in many acute cases. A brain MRI is most helpful in gauging the likelihood that a case of myelitis represents an initial attack of MS. A normal scan indicates that the risk of evolution to MS is low, ˜10–15% over 5 years; in contrast, the finding of multiple periventricular T2-bright lesions indicates a much higher risk, >50% over 5 years and >90% by 14 years. The CSF may be normal, but more often there is a mild mononuclear cell pleocytosis, with normal or mildly elevated CSF protein levels; oligoclonal bands are variable, but when bands are present, a diagnosis of MS is more likely.
There are no adequate trials of therapy for MS-associated transverse myelitis. Intravenous methylprednisolone (500 mg qd for 3 days) followed by oral prednisone (1 mg/kg per day for several weeks, then gradual taper) has been used as initial treatment. A course of plasma exchange is indicated for severe cases if glucocorticoids are ineffective.
NMO is an immune-mediated demyelinating disorder consisting of a severe myelopathy that is typically longitudinally extensive, meaning that the lesion spans three or more vertebral segments. NMO is associated with optic neuritis that is often bilateral and may precede or follow myelitis by weeks or months, and also by brainstem and in some cases hypothalamic involvement. However, isolated recurrent myelitis without optic nerve involvemement can occur in NMO; affected individuals are usually female, and often of Asian ancestry. CSF studies reveal a variable mononuclear pleocytosis of up to several hundred cells per microliter; unlike MS, oligoclonal bands are generally absent. Diagnostic serum autoantibodies against the water channel protein aquaporin-4 are present in 60–70% of patients with NMO. NMO has also been associated with SLE and antiphospholipid antibodies (see below) as well as with other connective tissue diseases; rare cases are paraneoplastic in origin. Treatment is with glucocorticoids and, for refractory cases, plasma exchange (as for MS, above). Preliminary data suggest that treatment with azathioprine, mycophenolate, or anti-CD20 (anti–B cell) monoclonal antibody may protect against subsequent relapses; treatment for 5 years or longer is generally recommended. NMO is discussed in Chap. 380.
Systemic Immune-Mediated Disorders
Myelitis occurs in a small number of patients with SLE, many cases of which are associated with antiphospholipid antibodies. The CSF is usually normal or shows a mild lymphocytic pleocytosis; oligoclonal bands are a variable finding. Responses to glucocorticoids and/or cyclophosphamide have been reported, but there is no systematic evidence of their benefit. Other immune-mediated myelitides include cases associated with Sjögren's syndrome, mixed connective tissue disease, Behçet's syndrome, vasculitis with perinuclear antineutrophilic cytoplasmic antibodies (p-ANCA), and primary CNS vasculitis.
Another important consideration in this group is sarcoid mye-lopathy that may present as a slowly progressive or relapsing disorder. MRI reveals an edematous swelling of the spinal cord that may mimic tumor; there is almost always gadolinium enhancement of active lesions and in some cases of the adjacent surface of the cord; lesions may be single or multiple, and on axial images, enhancement of the central cord is usually present. The typical CSF profile consists of a variable lymphocytic pleocytosis and mildly elevated protein level; in a minority of cases reduced glucose and oligoclonal bands are found. The diagnosis is particularly difficult when systemic manifestations of sarcoid are minor or absent (nearly 50% of cases) or when other typical neurologic manifestations of the disease—such as cranial neuropathy, hypothalamic involvement, or meningeal enhancement visualized by MRI—are lacking. A slit-lamp examination of the eye to search for uveitis; chest x-ray and CT to assess pulmonary involvement; and mediastinal lymphadenopathy, serum or CSF angiotensin-converting enzyme (ACE; present in only a minority of cases), serum calcium, and a gallium scan may assist in the diagnosis. The usefulness of spinal fluid ACE is uncertain. Initial treatment is with oral glucocorticoids; immunosuppressant drugs are used for resistant cases. Sarcoidosis is discussed in Chap. 329.
Many cases of myelitis, termed postinfectious or postvaccinal, follow an infection or vaccination. Numerous organisms have been implicated, including Epstein-Barr virus (EBV), cytomegalovirus (CMV), mycoplasma, influenza, measles, varicella, rubeola, and mumps. As in the related disorder acute disseminated encephalomyelitis (Chap. 380), postinfectious myelitis often begins as the patient appears to be recovering from an acute febrile infection, or in the subsequent days or weeks, but an infectious agent cannot be isolated from the nervous system or spinal fluid. The presumption is that the myelitis represents an autoimmune disorder triggered by infection and is not due to direct infection of the spinal cord. No randomized controlled trials of therapy exist; treatment is usually with glucocorticoids or, in fulminant cases, plasma exchange.
Acute Infectious Myelitis
Many viruses have been associated with an acute myelitis that is infectious in nature rather than postinfectious. Nonetheless, the two processes are often difficult to distinguish. Herpes zoster is the best characterized viral myelitis, but herpes simplex virus (HSV) types 1 and 2, EBV, CMV, and rabies virus are other well-described causes. HSV-2 (and less commonly HSV-1) produces a distinctive syndrome of recurrent sacral myelitis in association with outbreaks of genital herpes mimicking MS. Poliomyelitis is the prototypic viral myelitis, but it is more or less restricted to the gray matter of the cord. Chronic viral myelitic infections, such as that due to HIV, are discussed below.
Bacterial and mycobacterial myelitis (most are essentially abscesses) are far less common than viral causes and much less frequent than cerebral bacterial abscess. Almost any pathogenic species may be responsible, including Listeria monocytogenes, Borrelia burgdorferi (Lyme disease), and Treponema pallidum (syphilis). Mycoplasma pneumoniae may be a cause of myelitis, but its status is uncertain since many cases are more properly classified as postinfectious.
Schistosomiasis is an important cause of parasitic myelitis in endemic areas. The process is intensely inflammatory and granulomatous, caused by a local response to tissue-digesting enzymes from the ova of the parasite, typically S. mansoni. Toxoplasmosis can occasionally cause a focal myelopathy, and this diagnosis should be considered in patients with AIDS (Chap. 214).
In cases of suspected viral myelitis, it may be appropriate to begin specific therapy pending laboratory confirmation. Herpes zoster, HSV, and EBV myelitis are treated with intravenous acyclovir (10 mg/kg q8h) or oral valacyclovir (2 g tid) for 10–14 days; CMV with ganciclovir (5 mg/kg IV bid) plus foscarnet (60 mg/kg IV tid), or cidofovir (5 mg/kg per week for 2 weeks).