CHAPTER 272 Differential Diagnosis and Initial Management Spine Pathology
A refined and logical approach is essential for the appropriate investigation, evaluation, and management of patients with suspected spine pathology. Kuntz and colleagues previously provided a fundamental guide that allows the physician’s evaluation to proceed in a stepwise fashion based on the clinical presentation (Fig. 272-1). With this algorithm, patients with possible spine disease can be assessed on the basis of pain and its characteristics, the presence and form of neurological deficits, and associated systemic signs and symptoms. With this information, laboratory and radiologic evaluation can proceed, a diagnosis can be made, and appropriate surgical or medical management can be prescribed.1
In this chapter, the Kuntz algorithm is used to explore the universe of spine pathology (Table 272-1). Our approach begins with the characterization of pain, evaluation of neurological deficits, and search for systemic symptoms and signs. The first section of this chapter reviews disorders that manifest predominantly with pain; the second covers conditions that manifest primarily with neurological deficits; subsections are based on the characteristics of the pain or neurological deficits and the associated systemic components. The algorithm can help clinicians classify spine pathology based on clinical presentation, restrict the differential diagnoses, and proceed with the evaluation in a logical order.2
TABLE 272-1 Differential Diagnosis of Spinal Disorders
| Axial Skeletal Infections |
| Neoplastic Processes |
| Axial Skeletal Inflammatory Disorders |
| Degenerative Spinal Disorders |
| Axial Skeletal Fracture/Dislocation and Metabolic Disorders |
| Acute Vascular Event |
| Myelitis |
| Chronic Ischemia and Neuronal Degeneration |
Pain
Neck and low back pain is one of the most common reasons to miss work; however, most back or neck pain results from musculoligamentous strain that resolves with conservative therapy. Persistent axial skeletal pain or radicular pain is more likely to result from a surgical lesion and requires a more extensive diagnostic evaluation. Assessment begins with a history and physical examination, followed by appropriate laboratory investigations and diagnostic imaging.3
Classically, imaging begins with plain radiographs: anteroposterior, lateral, and flexion-extension views, as well as coned-down views of transitional areas. Magnetic resonance imaging (MRI) or computed tomography (CT) of the spine should follow to further define underlying pathology. MRI is better for imaging soft tissues and changes in tissue hydration, and CT is better for imaging bony detail. CT-myelography often better delineates the neural elements in relation to the bony anatomy. Bone scans and bone density determination are occasionally required. The laboratory work and radiologic imaging may provide a definitive diagnosis, or pathologic evaluation of abnormal tissue may be required. Once a definitive diagnosis has been obtained, medical or surgical treatment can proceed.3
Pain Associated with Fever and Weight Loss
Patients presenting with spine or radicular pain associated with fever and weight loss are at increased risk of having an infectious process (see Fig. 272-1). The presentation of neoplastic processes can be similar. The presence of fever with spine or radicular pain should lead the physician to look for an axial skeletal infection first. Vertebral osteomyelitis, diskitis, epidural abscess, and granulomatous processes are the most common potential infectious conditions. Neurological deficits can occur, but they usually present weeks to months after the onset of pain and systemic symptoms.
Vertebral Osteomyelitis
Vertebral osteomyelitis typically results from a pyogenic infection of the vertebral column. It is the most frequently encountered infection of the axial skeleton, accounting for 2% to 19% of all cases of osteomyelitis. Osteomyelitis may be the result of trauma, extension from adjacent structures, or hematogenous spread. A definitive source of infection is found in less than 50% of cases. The most common foci are genitourinary, soft tissue, and respiratory, or the infection may be traced to intravenous drug abuse. The most common organisms isolated are gram-positive cocci, constituting 60% to 70% of all cases. Staphylococcus aureus is the most prevalent, representing up to 60% of all positive cultures. Gram-negative rods are found predominantly in parenteral drug abusers or immunocompromised patients. The lumbar spine is most often involved, followed by the thoracic and cervical spine. The vertebral body is involved in more than 95% of cases. Less than 5% of cases involve the posterior elements.4
Management is based on biopsy results from percutaneous aspiration and bone biopsy using CT or fluoroscopic guidance. Treatment entails bed rest and broad-spectrum antibiotics, followed by definitive antimicrobial therapy based on culture results. Decompression with or without fixation may be required if there is extensive bony involvement or if neurological sequelae ensue from excessive bony destruction or abscess formation.4–6
Spinal Epidural Abscess
A spinal epidural abscess usually results from a pyogenic infection of the epidural space. Although uncommon (reported incidence: 0.2 to 1.2 cases per 10,000 hospital admissions), its clinical importance overshadows its rarity. Approximately 50% of spinal epidural abscesses result from hematogenous spread to the epidural space. Other causes include direct extension of a preexisting osteomyelitis or diskitis and direct inoculation from surgical manipulation or trauma. The organisms of spinal epidural abscesses mirror those found in vertebral osteomyelitis. Gram-positive cocci are the most prevalent, with S. aureus isolated in 60% to 65% of the positive cultures; other staphylococcal and streptococcal species are the next most common organisms isolated. Thoracic involvement is slightly more common than lumbar involvement, followed less frequently by cervical involvement. Posterior location predominates in about two thirds of cases. An anterior abscess often results from direct extension of a ventrally located diskitis or vertebral osteomyelitis.4–6
Primarily adults are affected, and there is no sex predominance; spinal epidural abscess is rare in children. Axial skeletal pain is a common initial complaint. The pain may develop a radicular component, and sensory or motor dysfunction of the affected nerve root can occur. If untreated, paraplegia or quadriplegia ensues. The incidence of fever, leukocytosis, and neurological compromise is higher than in vertebral osteomyelitis. Laboratory studies include ESR, CRP, and white blood cell count, which are elevated in most patients. MRI is the diagnostic procedure of choice. T1 images reveal a hypointense epidural mass that enhances with contrast. On T2 images, the mass is hyperintense. Early diagnosis is important because patients with spinal epidural abscess can deteriorate rapidly, even on intravenous antibiotics. Treatment for spinal epidural abscess is surgical evacuation and administration of the appropriate antibiotics.7
Diskitis
Diskitis represents two entirely different entities in adults and children. Pediatric diskitis classically presents spontaneously. Adult diskitis is most often encountered after diskectomy, although it can occur spontaneously. Less often, adult diskitis results from hematogenous spread secondary to intravenous drug abuse or debilitating disease. Early detection is important to prevent diskitis from progressing to vertebral osteomyelitis or epidural abscess.7
In children, diskitis is a relatively benign disease due to a chronic inflammatory disorder, viral infection, or low-grade bacterial infection. The vascular network throughout the cartilaginous end plate and disk predisposes children to diskitis. This network functions as a bacterial and disappears in late adolescence. Postoperative diskitis in adults results from bacterial contamination during surgical manipulation. Gram-positive cocci, staphylococcal and streptococcal species, predominate in both pediatric and adult cultures. Biopsies and blood cultures can be nondiagnostic in 20% to 50% of patients. The lumbar spine is affected more frequently than the thoracic or cervical spine in both children and adults.8
Patients present with back pain and painful ambulation. In adults, the onset of pain at the surgical level 1 to 3 weeks after surgery signals the possibility of an infection. Typically, ESR and CRP are elevated. MRI is the most sensitive and specific modality for detecting infection and determining the efficacy of treatment. MRI scans show evidence of the infection sooner than plain radiography does. ESR is a sensitive test for detecting the infection and following the progression of treatment. Management consists of CT- or fluoroscopy-guided biopsy and culture, bed rest, and a course of intravenous and then oral antibiotic therapy. The prognosis of uncomplicated cases is excellent.4,7
Granulomatous Infection
Although rare in developed countries, globally, tuberculous spondylitis is the most common granulomatous infection affecting the axial skeleton. Historically, tuberculous spondylitis (Pott’s disease) is usually caused by M. tuberculosis, but other mycobacteria can also infect the axial spine. Infection results from hematogenous spread of mycobacteria from a pulmonary or genitourinary source. The infection spreads across the disk space, along the posterior or anterior longitudinal ligament, and tends to spare the disk space. The skeleton is affected in about 1% of all cases; of those, 50% to 60% involve the axial skeleton. The thoracolumbar spine is affected most frequently; cervical and sacral involvement are rare.7
Currently, individuals infected with the human immunodeficiency virus (HIV) account for most tubercular infections in the United States, and drug-resistant strains are being seen more frequently. Clinical presentation involves bone pain over the affected spinal level with fever, malaise, and weight loss. Vertebral collapse, spine deformity, epidural abscess, and subarachnoid seeding after dural erosion are late sequelae. In the progressive stages of the disease, kyphosis and epidural abscesses are common. Neurological sequelae occur in 10% to 50% of patients with active disease. In 20% of cases, tuberculous spondylitis causes paraparesis.9
Plain radiography, MRI, and CT-myelography evaluate disease progression and guide surgical planning. MRI evaluates the involvement of soft tissue and abscess formation. CT provides bony detail. Treatment is based on positive biopsy or culture results, degree of kyphosis, extent of neurological compromise, and refractory disease. Decompression and débridement, combined with antibiotic therapy, are the accepted treatment modalities when a neurological deficit evolves. Prognosis relates to patient age, extent of systemic disease, and preoperative neurological status.10
Actinomyces israelii, an anaerobic gram-positive bacterium, can cause purulent abscesses, external draining sinuses, and characteristic sulfur granules on microscopic examination. Infection is seen mostly in the cervical spine, secondary to direct extension from a preexisting mandible or supraclavicular infection. Nocardia asteroides, a gram-positive bacterium, can represent a rare cause of back pain when the spinal column is involved. Nocardia spreads hematogenously from a pulmonary focus, and osteomyelitis has occasionally been reported.10,11
Fungal infections of the axial skeleton are rare and occur by spore inhalation, with resultant pulmonary seeding and systemic spread. Spinal osseous involvement in patients with disseminated coccidioidomycotic and blastomycotic infection occurs in 10% to 50% of cases. The incidence of axial skeletal involvement with candidiasis or aspergillosis is low. Both fungal infections tend to occur in immunocompromised hosts. Other rare granulomatous diseases of the axial skeleton include parasitic infections such as syphilis and echinococcosis.10–12
Pain Associated with Recumbency and Nighttime
Pain is the most common presenting symptom for tumors involving the axial skeleton and spinal cord (extramedullary and intramedullary). Localized spinal pain at night or with recumbency is a hallmark of neoplastic lesions of the spine (see Fig. 272-1). Spinal column tumors often present with diffuse spine or radicular pain unrelieved by rest. Axial skeletal pain usually begins before any radicular pain or neurological deficit. In contrast, intramedullary and extramedullary spinal cord tumors also manifest with pain; however, the pain can be insidious in onset or diffuse, vaguely localized to the level of the tumor. Radicular pain or neurological deficit is commonly present by the time the tumor is diagnosed.
Benign Tumors of the Axial Skeleton
Benign axial skeleton tumors are typically posterior in location and seen in patients between 20 and 30 years old. The more common benign lesions, osteochondromas, osteoid osteomas, and osteoblastomas, have a lower incidence of recurrence after resection compared with malignant bone tumors. Other benign tumors include giant cell tumors, aneurysmal bone cysts, hemangiomas, and eosinophilic granulomas.13,14
Osteochondromas are the most common of the benign bone tumors. They develop from an adjacent physis or a cartilaginous remnant of the physis and present as a cartilage-capped bony protuberance. More than 50% occur in the cervical region, and they almost always involve the posterior elements. Osteochondromas may present with a dull backache in the case of smaller tumors or with decreased motion or deformity in the case of larger tumors. Neurological compromise is rare; however, when present, the cervical spine is the most typical location, followed by the thoracic spine, and myelopathic symptoms result. Plain radiographs usually demonstrate a protruding lesion with well-demarcated borders in the posterior elements. Resection is rarely required, except in cases of uncontrollable pain, neurological deficit, or accelerated growth. Prognosis is usually excellent when the affected periosteum and surrounding cartilage are resected completely. Osteochondromas occasionally degenerate into malignant chondrosarcomas.13,14
Osteoid osteomas and osteoblastomas share a pathologic origin but differ in size and incidence of spinal involvement. These tumors are thought to be a chronic inflammatory reaction rather than true neoplasms. Osteoid osteomas account for 2.6% of all excised primary bone tumors and up to 18% of primary axial skeletal tumors. Osteoid osteomas are less than 2 cm in diameter; larger lesions are classified as osteoblastomas. Approximately 40% of spinal osteoid osteomas occur in the lumbar region, and most are seen in the posterior elements. Most patients are young and male, and half of all symptomatic lesions appear in the second decade of life. Patients report a dull ache that is worse at night. This nocturnal exacerbation is believed to result from prostaglandin production by the tumor, and classically, the pain is relieved by aspirin. Neurological deficits are rare, but osteoid osteomas are the most common lesions associated with painful scoliosis in adolescents. Radiographically, the lesion is characterized by a radiolucent area with a central nidus surrounded by sclerosis. Treatment is excision. Instrumentation and fusion may be required if scoliosis is severe, but minor deformities resolve with resection alone. Overall, the prognosis is excellent, and the rate of recurrence, which is related to inadequate excision of the nidus, is marginal.13–14
Osteoblastomas are larger than osteoid osteomas (>2 cm), histologically equivalent, and less common, representing less than 2% of primary benign bone tumors. Approximately 30% to 40% of osteoblastomas involve the axial skeleton. Of those in the axial skeleton, most involve the posterior elements and have a propensity to produce spine deformity. In 90% of cases, osteoblastomas are found in patients aged 30 years or younger. The male-to-female predominance is 2 : 1. Clinical presentation involves a high incidence of neurological deficit, related to the size of the lesion. Treatment is en bloc resection, which usually resolves the scoliotic deformity. With adequate removal, prognosis is favorable. Long-term recurrence rates approach 10%.14–16
Giant cell tumors are benign lesions; however, they are aggressive, carry some malignant potential, and are associated with a high incidence of local recurrence. They are responsible for 21% of all primary benign bone tumors and affect the spinal axis in 8% to 11% of cases. When the spinal column is involved, the tumors typically occur in the sacral region. Unlike most primary bone tumors, giant cell tumors tend to be found in individuals in the third and fourth decades of life. Their frequency decreases in later years. Women are affected slightly more often than men. Plain radiographs demonstrate cortical expansion with little reactive sclerosis or periosteal reaction. MRI reveals homogeneous signals. CT better delineates the degree of vertebral bony involvement and defines surgical margins. Because the histologic characteristics of giant cell tumors are nondistinct, a thorough evaluation is important to differentiate this condition from other primary bone tumors. Treatment is usually en bloc resection, but because of the high rate of recurrence (50%), the prognosis is relatively poor. These tumors have the potential for malignant transformation, especially after local radiation if surgical margins were inadequate.14–16
Aneurysmal bone cysts are benign, nonneoplastic, proliferative lesions. Although accounting for only 1% to 2% of all primary bone tumors, aneurysmal bone cysts affect the axial skeleton in 12% to 25% of reported cases. Their pathogenesis is unclear, but accepted theories include an underlying tumor or traumatic arteriovenous malformation (AVM), with subsequent cyst formation. Histologically, aneurysmal bone cysts contain fluid-filled spaces separated by fibrous septa. Their incidence is greatest in the thoracolumbar region. Similar to most benign osseous lesions, 60% of spinal aneurysmal bone cysts occur in the posterior elements. Aneurysmal bone cysts typically occur in young patients in the second decade of life, with a slight female predominance. MRI and CT demonstrate a multiloculated, expansile, highly vascular osteolytic lesion with a thin, well-demarcated, eggshell-like cortical rim. Multiple vertebral levels may be involved in as many as 40% of cases. Treatment involves preoperative embolization and surgical resection. Postoperative radiation may have a role if the surgical margins are inadequate. Recurrence rates vary from 6% to 70% and depend on the extent of resection and the administration of postoperative radiation.14–17
Hemangiomas are benign tumors of vascular origin and are probably the most common benign tumor of the spine. Autopsy studies report hemangiomas of the axial skeleton in 10% to 12% of cases. Characterized by slow growth and a female predominance, vertebral hemangiomas most often occur in the thoracolumbar spine, with a predilection for the vertebral body. Symptomatic vertebral hemangiomas are rare; however, the most common initial symptom is back pain with or without radicular pain. Symptomatic lesions are best diagnosed with MRI; asymptomatic lesions are discovered incidentally during other radiographic investigations. Treatment of symptomatic lesions involving the spine consists of a combination of embolization, surgical resection, and possibly radiotherapy.14–1618
Eosinophilic granulomas are solitary osseous lesions characterized by an abnormal proliferation of Langerhans cells and are associated with a continuum of disorders (histiocytosis X and Letterer-Siwe and Hand-Schüller-Christian diseases). Eosinophilic granulomas are rare lesions of the axial skeleton and occur most frequently in the vertebral body. Most occur in children, with a peak incidence between 5 and 10 years of age. MRI and CT are the investigative procedures of choice, but diagnosis requires biopsy. Treatment is controversial but commonly includes surgical curettage, with adjuvant radiotherapy or chemotherapy reserved for disseminated versions of this uncommon disease.14–1618
Malignant Tumors of the Axial Skeleton
Malignant axial skeleton tumors are either metastatic or primary. Metastasis results from direct extension or hematogenous spread; the most common metastatic spinal tumors are breast, lung, and prostate malignancies. Multiple myeloma, chordoma, chondrosarcoma, osteogenic sarcoma, and Ewing’s sarcoma are the most common primary malignant neoplasms of the axial skeleton. Both primary and metastatic neoplasms most often involve the vertebral body. Malignant tumors of the axial skeleton are 25 to 40 times more likely to be metastatic than primary.14–16
Autopsy studies indicate that 40% to 85% of individuals with malignancy have metastatic disease, and the spine is the most common site of skeletal metastasis. As noted, breast, lung, and prostate malignancies account for most spinal metastatic lesions, which are spread equally throughout the thoracic and lumbosacral spine. Thoracic metastases tend to become symptomatic most often, whereas cervical lesions are symptomatic in 6% to 8% of patients. The vertebral body is the structure most often involved. Patients with known malignancy and new neck or back pain may have metastatic disease. Diagnosis relies on laboratory investigation, radiographic studies, and tumor biopsy results. MRI and CT-myelography help determine the extent of neural compression and bone destruction at the affected site, as well as screen for other areas of spine involvement. Treatment options for metastatic disease of the spine include both radiation and surgical intervention. Surgery is usually reserved for neurological compromise, radiation failure, spine instability, or an uncertain diagnosis. The goals of surgery are pain control and preservation of function and stability. Preoperative functional status and level of activity correlate directly with postoperative outcome. Patients who suffer rapid, progressive neurological deficits within a 24-hour period have a higher chance of developing permanent paraplegia than those with slowly evolving deficits, who are more likely to regain ambulatory function. Overall, prognosis is directly related to neoplastic type, spinal location, and extent of systemic involvement.14–1619
Multiple myelomas and solitary plasmacytomas are two manifestations of B-cell lymphoproliferative disease. Multiple myelomas are the most common malignant neoplasms of bone in adults and affect the spine in 30% to 50% of reported cases. The thoracic spine is affected most commonly, followed by the lumbar spine and, rarely, the cervical spine (<10%). The vertebral body is usually the site of tumor involvement. Multiple myeloma is primarily a disease of the fifth, sixth, and seventh decades of life and occurs equally in men and women. However, approximately 75% of solitary plasmacytomas occur in men. Unlike the classic presentation of pain with recumbency, the pain of multiple myeloma is sometimes relieved by rest and aggravated by mechanical agitation, mimicking other degenerative sources of pain. The diagnosis of multiple myeloma is based on characteristic serum protein abnormalities and radiologic imaging. Plain radiography and CT can be diagnostic because of the characteristic osteolytic picture, with no sclerotic edges involving the vertebral body and sparing of the posterior elements. Treatment and prognosis depend on whether the diagnosis is solitary plasmacytoma or systemic multiple myeloma. Both conditions are exquisitely radiosensitive, but patients with solitary plasmacytomas have significantly longer survival times.14,19
Chordomas, originally described by Virchow, are tumors that originate from the primitive notochord. As tumors of the axial skeleton and skull base, chordomas constitute 1% to 2% of all skeletal sarcomas. Histologically, they are low-grade, locally invasive tumors, but metastases can occur in 5% to 43% of cases. More than 50% of these lesions are located in the lumbosacral region, 35% are in the clival area, and the remainder are spread throughout the vertebral column. Chordomas are the most common primary neoplasm of the sacrococcygeal region and occur predominantly in the fifth and sixth decades of life. Neurological deficits include bowel and bladder dysfunction. MRI is the imaging modality of choice because of its ability to delineate soft tissue involvement. CT delineates the extent of bony destruction. Diagnosis is based on CT- or fluoroscopy-guided biopsy, and treatment is en bloc resection when feasible. Radiation is reserved for local recurrence and surgically inaccessible disease. Age at presentation and en bloc resection are probably the best prognostic indicators for disease-free survival after surgery, with younger patients having better prognoses.20
Chondrosarcomas are rare, malignant, cartilage-forming neoplasms that arise from cartilaginous elements and affect primarily the adult appendicular skeleton. Spinal involvement is rare (6% of cases). Chondrosarcomas arise either primarily or from preexisting solitary osteochondromas, hereditary multiple exostosis, or Paget’s disease. There is an even distribution of tumor involvement among cervical, thoracic, and lumbosacral locations. Primary and secondary chondrosarcomas usually arise in middle-aged and older patients and show a predilection for men. Diagnostic characteristics on MRI and CT include bone destruction, associated soft tissue mass, and characteristic flocculent calcifications in the soft tissue mass. Diagnosis is based on tumor biopsy. Treatment is en bloc resection if feasible. Neither radiation nor chemotherapy is particularly useful. Prognosis correlates with tumor extension and grade; patients with unresectable chondrosarcomas have a 5-year survival rate of only 20%.21
Osteogenic sarcomas are primary malignant tumors of bone that rarely involve the axial skeleton. Only 2% of osteogenic sarcomas arise in the spine; they can arise primarily or secondarily but are more likely to be metastatic. These lesions are distributed evenly throughout the spine, but the vertebral body is involved in more than 95% of cases. Most primary osteogenic sarcomas manifest in the first 20 years of life; secondary sarcomas arise in the fifth to sixth decades from irradiated bone or preexisting Paget’s disease. This neoplastic disease has a slight predilection for men. Radiologically, osteogenic sarcomas typically exhibit lytic and sclerotic areas, with cortical destruction and ossification in the tumor mass. CT- or fluoroscopy-guided biopsy provides the diagnosis. Preoperative embolization, chemotherapy, and surgical extirpation with adjuvant radiotherapy are the current treatment modalities. Overall, prognosis is poor, with a life expectancy of 10 months to 1.5 years; there have been a few long-term survivors.20,
