Cancer, Infection, Fracture

Home , Cancer pain

REVIEW KRZYSZTOF SIEMIONOW, MD MICHAEL STEINMETZ, MD GORDON BELL, MD Department of Orthopaedic Surgery, Department of Neurosurgery, and Cleveland Vice-Chairman, Department of Orthopaedic Cleveland Clinic Clinic Center for Spine Health, Surgery, and Associate Director, Cleveland Cleveland Clinic Clinic Center for Spine Health, Cleveland Clinic HAKAN ILASLAN, MD ROBERT F. McLAIN, MD Department of Radiology, Cleveland Clinic Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University; Director of Spine Fellowship Program, Depart- ment of Orthopaedic Surgery and Cleveland Clinic Center for Spine Health, Cleveland Clinic Identifying serious causes of back pain: Cancer, infection, fracture

■■ ABSTRACT ack pain is one of the most common com- B plaints that internists and primary care Most patients with back pain have a benign condition, physicians encounter.1 Although back pain is but tumors, infections, and fractures must be considered nonspecific, some hallmark signs and symp- during an initial evaluation because overlooking them toms indicate that a patient is more likely to can have serious consequences. This article discusses the have a serious disorder. This article contrasts presentation and diagnostic strategies of these serious the presentation of cancer, infections, and causes of back pain. fractures with the more common and benign conditions that cause back pain and provides ■■ KEY POINTS guidance for diagnosis. A primary tumor or metastasis to the spine tends to ■■ UNCOMMON, BUT MUST BE CONSIDERED cause unremitting back pain that worsens at night and is Although a variety of tissues can contribute accompanied by systemic disease and abnormal labora- to pain—intervertebral disks, vertebrae, liga- tory findings. ments, neural structures, muscles, and fascia— and many disorders can damage these tissues, Infection typically causes focal pain, an elevated eryth- most patients with back or neck pain have a rocyte sedimentation rate (the most sensitive laboratory benign condition. Back pain is typically caused test) and C-reactive protein level, and sometimes neuro- by age-related degenerative changes or by mi- nor repetitive trauma; with supportive care logic signs and symptoms. and physical therapy, up to 90% of patients with back pain of this nature improve substan- Fractures cause focal pain and should be suspected tially within 4 weeks.2 especially in older white women and patients who take Serious, destructive diseases are uncommon corticosteroids or who have ankylosing spondylitis. causes of back pain: malignancy, infection, ankylosing spondylitis, and epidural abscess to- Plain radiography can help detect fractures, but magnetic gether account for fewer than 1% of cases of resonance imaging is needed to evaluate spinal tumors, back pain in a typical primary care practice. But their clinical impact is out of proportion soft tissue infections, and epidural abscesses, and to to their prevalence. The fear of overlooking a further evaluate neural compression due to fractures. serious condition influences any practitioner’s approach to back pain and is a common rea- son for ordering multiple imaging studies and consultations.3 Therefore, the time, effort, and resources invested in ruling out these disorders is considerable. Whether a patient with back pain has an ominous disease can usually be determined with a careful history, physical examination,

CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 75 • NUMBER 8 AUGUST 2008 557 Downloaded from www.ccjm.org on September 28, 2021. For personal use only. All other uses require permission. BACK PAIN

Cancer pain is persistent and progressive table 1 Pain from spinal cancer is often different from Features associated with degenerative idiopathic back pain or degenerative disk dis- disk disease and with neoplastic disease ease (TABLE 1). Benign back pain often arises from a Degenerative disk disease known injury, is relieved by rest, and increases Pain that: with activities that load the disk (eg, sitting, Developed after known injury getting up from bed or a chair), lumbar flexion Increases with activity with or without rotation, lifting, vibration (eg, Is aching Subsides with rest, physical therapy, nonsteroidal riding in a car), coughing, sneezing, laughing, anti-inflammatory drugs and the Valsalva maneuver. It is most com- Laboratory studies are typically normal monly focal to the lumbosacral junction, the Patient may have a history of spine surgery lumbar muscles, and the buttocks. Pain due to injury or a flare-up of degenerative disease typ- Neoplastic disease ically begins to subside after 4 to 6 weeks and Age > 50 years responds to nonsteroidal anti-inflammatory Pain is not relieved by rest or recumbency 10 Anemia drugs and physical therapy. Elevated erythrocyte sedimentation rate, C-reactive protein level In contrast, pain caused by spinal neopla- Failure to improve with conservative therapy sia is typically persistent and progressive and is History of cancer not alleviated by rest. Often the pain is worse Pain worsens at night at night, waking the patient from sleep. Back pain is typically focal to the level of the lesion ADAPTED FROM INFORMATION PRESENTED IN DEYO RA, DIEHL AK. CANCER AS A CAUSE OF BACK PAIN: FREQUENCY, CLINICAL PRESENTATION, AND DIAGNOSTIC STRATEGIES. J GEN INTERN and may be associated with belt-like thoracic MED 1988; 3:230–238 AND PATEL RK, SLIPMAN CW. LUMBAR DEGENERATIVE DISK DISEASE. pain or radicular symptoms of pain or weakness EmEDICINE. WWW.EMEDICINE.COM/PMR/TOPIC67.HTM. in the legs. A spinal mass can cause neurologic signs or symptoms by directly compressing the and appropriate diagnostic studies. Once a se- spinal cord or nerve roots, mimicking disk The spine is rious diagnosis is ruled out, attention can be herniation or stenosis.11,12 one of the most focused on rehabilitation and back care. Pathologic fractures resulting from verte- Back pain can also be due to musculoskele- bral destruction may be the first—and unfor- common sites tal disorders, peptic ulcers, pancreatitis, pyelo- tunately a late—presentation of a tumor. of metastasis nephritis, aortic aneurysms, and other serious conditions, which we have discussed in other Ask about, look for, articles in this journal.4–6 signs and symptoms of cancer In taking the history, one should ask about ■■ SPINAL CANCER AND METASTASES possible signs and symptoms of systemic disease such as fatigue, weight loss, and changes Since back pain is the presenting symptom in bowel habits. Hemoptysis, lymphadenopa- in 90% of patients with spinal tumors,7 neo- thy, subcutaneous or breast masses, nipple plasia belongs in the differential diagnosis of discharge, atypical vaginal bleeding, or blood any patient with persistent, unremitting back in the stool suggest malignancy and should pain. However, it is also important to recog- direct the specific diagnostic approach.13 A nize atypical presentations of neoplasia, such history of cancer, even if remote, should raise as a painless neurologic deficit, which should suspicion, as should major risk factors such as prompt an urgent workup. smoking. The spine is one of the most common sites Because most spinal tumors are metastases, of metastasis: about 20,000 cases arise each a clinical examination of the breast, lungs, ab- year.8 Brihaye et al9 reviewed 1,477 cases of domen, thyroid, and prostate are appropriate spinal metastases with epidural involvement starting points.14 The spine should be exam- and found that 16.5% arose from primary tu- ined to identify sites of focal pain. A neuro- mors in the breast, 15.6% from the lung, 9.2% logic examination should be done to evaluate from the prostate, and 6.5% from the kidney. any signs of neurologic compromise or abnor-

558 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 75 • NUMBER 8 AUGUST 2008 Downloaded from www.ccjm.org on September 28, 2021. For personal use only. All other uses require permission. siemionow and colleagues

Spinal metastasis: CT study Spinal metastasis: MRI study

The ESR and

FIGURE 1. A 43-year-old man with a 2-week CRP are almost history of progressive back pain and an always elevated abdominal mass. Sagittal CT scan shows an FIGURE 2. A 63-year-old woman with osteolytic lesion of the L3 vertebral body history of hepatocellular carcinoma who with systemic (arrow). The primary tumor was renal. presented with bilateral leg weakness and neoplasia Fracture of the vertebral end plate (arrow- debilitating back pain. T2-weighted MRI heads) may cause first symptoms of pain. shows pathologic compression fracture of the L2 vertebral body with retropulsion of fracture fragments into the canal and mal reflexes. Signs or symptoms of spinal cord severe central canal stenosis (arrow). compression should be investigated immedi- ately. cell count and chemistry panel. If laboratory Cancer usually elevates the ESR, CRP studies reveal anemia, hypercalcemia, and If cancer is suspected, initial tests should in- elevated levels of alkaline phosphatase, con- clude a complete blood cell count, erythrocyte cern should increase. Chest radiography, ab- sedimentation rate, C-reactive protein level, dominal computed tomography (CT) (FIGURE urinalysis, prostate-specific antigen level, and 1), and mammography for women are needed fecal occult blood testing. Normal results can if laboratory results are abnormal. Plain radio- considerably relieve suspicion of cancer: the graphs are the first imaging study of the spine erythrocyte sedimentation rate and C-reactive to obtain. Compression fractures, soft tissue protein level are almost always elevated with calcifications, or focal loss of bone mineral- systemic neoplasia. ization suggests tumor. Abnormal results on Other initial tests include a complete blood serum and urine protein electrophoresis in-

CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 75 • NUMBER 8 AUGUST 2008 559 Downloaded from www.ccjm.org on September 28, 2021. For personal use only. All other uses require permission. BACK PAIN

crease the likelihood of multiple myeloma or 7% of all cases of osteomyelitis and is an un- plasmacytoma, but normal results do not rule common cause of back pain.22 Any source of out monoclonal gammopathy of uncertain sig- infection (eg, dental abscess, pneumonia) can nificance. seed the spine; urinary tract infection is the most common. Patients with immunocompro- Imaging tests mise or diabetes are most at risk.23 The onset Unfortunately, spinal tumors cannot be well is usually insidious with focal back pain at the visualized on radiographs until significant de- level of involvement. struction has occurred.15 A bone scan can usually detect tumors History and physical examination other than the purely lytic ones such as my- reveal localized pain eloma and has a sensitivity of 74%, a specific- Spinal infections typically cause pain that is ity of 81%, and a positive predictive value of worsened with weight-bearing and activity 64% for vertebral metastasis in patients with and is relieved only when lying down. Chron- back pain.16 ic infection is usually associated with weight Magnetic resonance imaging (MRI) is the loss, fatigue, fevers, and night sweats. best imaging study for evaluating spinal tumors Pain is usually well localized and repro- because it can show the status of the bone mar- duced by palpation or percussion over the row and has excellent contrast resolution in involved level. Severe pain can sometimes be 17,18 soft tissue (FIGURE 2). It can show vertebral elicited by sitting the patient up or by chang- bone marrow infiltration by tumor cells as well ing the patient’s position. Focal kyphosis may as soft tissue masses in and around the spinal be detectable if the vertebra has collapsed. column. Bone marrow invaded by a neoplasm In a series of 41 patients with pyogenic in- is characterized by increased cellularity, result- fectious spondylitis, 90% had localized back ing in a decreased signal on T1-weighted im- pain aggravated by percussion, 59% had radic- ages and a high signal on T2-weighted images. ular signs and symptoms, and 29% had neuro- Intravenous gadolinium further increases the logic signs of spinal cord compression, includ- Early infection contrast between a tumor and normal tissues ing hyperreflexia, clonus, the Babinski sign can be hard to and is important for characterizing and grad- (extension of the toes upward when the sole of ing tumors.19 the foot is stroked upwards), or the Hoffmann differentiate sign (flexion of the thumb elicited by flicking from idiopathic ■■ INFECTION CAN BE INDOLENT OR ACUTE the end of a middle finger).24 back pain Spinal infection is a serious condition that can ■■ Laboratory results take an indolent, smoldering course or, alter- typically indicate infection natively, can erupt into sepsis or rapidly progressive vertebral destruction. Although the The erythrocyte sedimentation rate is the latter conditions are hard to miss, early diskitis most sensitive test for infection, and an el- and osteomyelitis can be difficult to differenti- evated rate may be the only abnormal labora- ate from idiopathic back pain. In a series of tory finding: Digby and Kersley25 found that 101 patients with vertebral osteomyelitis, mis- the rate was increased in all of 30 patients diagnosis occurred in 33.7%, and the average with nontuberculous pyogenic osteomyelitis delay from the onset of clinical manifestations of the spine. The C-reactive protein level is to diagnosis was 2.6 months.20 Tuberculosis also usually elevated, but 40% of patients have can be even more elusive: in a series of 78 a normal white blood cell count.25 Results of patients diagnosed with definite or probable other laboratory tests are typically in the nor- tuberculous vertebral osteomyelitis, the mean mal range. Tuberculin skin testing should be delay to diagnosis was about 6 months.21 done for patients at high risk of the disease Acute spinal infections are most often (eg, immigrants from areas of endemic disease, pyogenic; chronic infections may be pyogenic, non-Hispanic blacks, immunocompromised fungal, or granulomatous. patients, and those with known exposure to Vertebral osteomyelitis accounts for 2% to tuberculosis). Patients with high fever, chills,

560 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 75 • NUMBER 8 AUGUST 2008 Downloaded from www.ccjm.org on September 28, 2021. For personal use only. All other uses require permission. siemionow and colleagues

or rigors should have cultures taken of blood, Vertebral osteomyelitis: MRI study urine, and sputum and from any intravenous lines.

Imaging changes may not appear for months Radiographic findings characteristic of osteomyelitis are not apparent for at least 4 to 8 weeks after the onset of infection.26 Narrowing of the disk space is the earliest and most consistent finding but is nonspecific.27 Pyogenic infection is often heralded by rapid disk destruction and L2 disk space narrowing. MRI is as accurate and sensitive as nuclear medicine scanning (sensitivity 96%, specificity 93%, accuracy 94%).28 MRI can help differentiate degenerative and L3 neoplastic disease from vertebral osteomyeli- tis29 and provides better imaging than CT for soft-tissue infections (FIGURE 3). CT, on the other hand, may be better for showing the extent of bone involvement. In cases of vertebral osteomyelitis and intervertebral disk space infection, simultaneous involvement of the adjacent vertebral end plates and the intervertebral disk are the major findings.30 Signs of infection using T1-weighted MRI include low-signal marrow or disk spaces with- Guided biopsy in the vertebral body, loss of definition of end may be needed plates (which appear hypointense compared with the bone marrow), and destruction of to differentiate the cortical margins of the involved vertebral abscess, bodies. T2-weighted MRI typically discloses FIGURE 3. A 32-year-old woman with hematoma, high signals of the affected areas of the verte- systemic lupus erythematosus who is on bral body and disk. Contrast should be used to chronic steroid therapy and who has a tumor, and increase specificity; enhancement may be the 6-week history of back pain. T2-weighted inflammation first sign of an acute inflammatory process.31 sagittal MRI shows a disk space infection at CT and MRI can help identify sequestra, L2–L3, with ventral paraspinal soft tissue perilesional sclerosis, and epidural or soft tis- enhancement consistent with early abscess sue abscesses. Guided biopsy may be needed formation (arrows). to differentiate between abscess, hematoma, tumor, and inflammation. tions, patients with tuberculous spondylitis had a significantly higher incidence of a well- MRI findings: defined paraspinal abnormal signal on MRI, a Pyogenic vs tuberculous spondylitis thin and smooth abscess wall, a paraspinal or MRI can help differentiate pyogenic verte- intraosseous abscess, subligamentous spread to bral osteomyelitis from tubercular disease, three or more vertebral levels, involvement of although findings may be similar (eg, both multiple vertebral bodies, thoracic spine in- conditions have a high signal on T2-weighted volvement, and a hyperintense signal on T2- images).32 Jung et al,33 in a retrospective study weighted images. Other MRI features charac- of 52 patients with spondylitis, found that teristically seen in patients with tuberculous compared with patients with pyogenic infec- spinal disease are anterior corner destruction,

CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 75 • NUMBER 8 AUGUST 2008 561 Downloaded from www.ccjm.org on September 28, 2021. For personal use only. All other uses require permission. BACK PAIN

a relative preservation of the intervertebral ment further increases sensitivity.39,40 Spinal disk, and large soft-tissue abscesses with cal- canal abscesses usually appear hypointense on cifications.34 T1-weighted images and hyperintense on T2- weighted images, with ring enhancement sur- Prompt diagnosis rounding the abscess area in contrast studies.41 and aggressive treatment needed MRI may give negative findings in the early Pigrau et al35 found that spinal osteomyelitis stages of a spinal canal infection and so may is highly associated with endocarditis: among need to be repeated.41 MRI may not help dis- 606 patients with infectious endocarditis, 28 tinguish an epidural from a subdural abscess. (4.6%) had pyogenic vertebral osteomyelitis, However, primary spinal epidural abscesses and among 91 patients with pyogenic verte- without concomitant vertebral osteomyelitis bral osteomyelitis, 28 (30.8%) had infectious are rare; therefore, the finding of associated endocarditis. vertebral osteomyelitis makes a spinal epidural McHenry et al36 retrospectively studied abscess more likely. outcomes of 253 patients with vertebral osteomyelitis after a median of 6.5 years (range 2 ■■ FRACTURES days to 38 years): 11% died, more than one- third of survivors had residual disability, and Fractures of the spine can be asymptomatic 14% had a relapse. Surgery resulted in recov- and may have no preceding trauma. They can ery or improvement in 86 (79%) of 109 pa- be due to osteoporosis, malignancy, infection, tients. Independent risk factors for adverse or metabolic disorders such as renal osteo- outcome (death or incomplete recovery) were dystrophy or hyperparathyroidism. Fractures neurologic compromise, increased time to di- in normal bone are almost always associated agnosis, and having a hospital-acquired infec- with trauma. Any suspicion of infection or tion (P ≤ .004). Relapse commonly developed malignancy should be investigated. in patients with severe vertebral destruction and abscesses, which appeared some time af- Corticosteroids increase risk Fractures in ter surgical drainage or debridement. Recur- Any patient with back pain who is receiving normal bone rent bacteremia, paravertebral abscesses, and corticosteroid therapy should be considered chronically draining sinuses were indepen- as having a compression fracture until proven are almost dently associated with relapse (P ≤ .001). MRI, otherwise.3 De Vries et al42 found that in a always done in 110 patients, was often performed late database of nearly 200,000 patients receiving associated with in the course of infection and did not signifi- glucocorticoids, risk increased substantially cantly affect outcome. The authors stressed with increasing cumulative exposure. Those trauma that an optimal outcome of vertebral osteo- who intermittently received high doses (≥ 15 myelitis requires heightened awareness, early mg/day) and those who had no or little pre- diagnosis, prompt identification of pathogens, vious exposure to corticosteroids (cumulative reversal of complications, and prolonged anti- exposure ≤ 1 g) had only a slightly increased microbial therapy. risk of osteoporotic fracture, and their risk of fracture of the hip and femur was not in- Epidural abscess may also be present creased. In contrast, patients who received a Epidural abscess occurs in 10% of spine infec- daily dose of at least 30 mg and whose cumula- tions. About half of patients with an epidu- tive exposure was more than 5 g had a relative ral abscess are misdiagnosed on their initial risk of osteoporotic vertebral fracture of 14.42 evaluation.37,38 Patients initially complain of (95% confidence interval 8.29–25.08). local spine pain, followed by radicular pain, weakness, and finally paralysis. Between Osteoporotic compression fractures 12% and 30% of patients report a history of are common in the elderly trauma, even as minor as a fall, preceding the Osteoporosis involves reduced bone den- infection.38,39 sity, disrupted trabecular architecture, and Radiologic findings are frequently equivo- increased susceptibility to fractures. About cal, and MRI is preferred; gadolinium enhance- 700,000 vertebral body compression fractures

562 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 75 • NUMBER 8 AUGUST 2008 Downloaded from www.ccjm.org on September 28, 2021. For personal use only. All other uses require permission. siemionow and colleagues

table 2 Imaging features of benign vs malignant compression fractures

BENIGN MALIGNANT

Solitary lesion with smooth margins Multiple lesions, heterogeneous enhancement in multiple vertebrae Superior end plate fracture Inferior end plate fracture with abnormal band-like signal or abnormal signal parallel to superior end plate only in lower portion of vertebral body Normal fatty marrow Normal fatty marrow absent No pedicle involvement Pedicle involvement Fracture line No fracture line No convex cortical contour Convex cortical contour No extraosseous soft tissue mass Extraosseous soft tissue mass Intravertebral fluid No intravertebral fluid Fragmentation No fragmentation

ADAPTED FROM TAHRANZADEH J, TAO C. ADVANCES IN MR IMAGING OF VERTEBRAL COLLAPSE. SEMIN ULTRASOUND CT MRI 2004; 25:440–460. WITH PERMISSION FROM ELSEVIER.

occur in the United States each year43: about History, physical examination 10% result in hospitalization, involving an Patients may present with a history of trauma average stay of 8 days.44 Osteoporotic com- with associated back pain or a neurologic pression fractures are highly associated with deficit. In osteoporotic patients, the trauma Fractures in age older than 65, female sex, and European may have been minimal, eg, a sneeze, a fall the upper descent.45,46 The estimated lifetime risk of a from a chair, or a slip and fall in the home. clinically evident vertebral fracture after age Pain tends to be worse when standing erect thoracic spine 50 years is 16% among postmenopausal white and occasionally when lying flat. may indicate 47 women and 5% among white men. The patient is commonly visibly uncom- an underlying A single osteoporotic vertebral compres- fortable and may be limited to a wheelchair sion fracture increases the risk of subsequent or stoop forward when standing. The spine tumor fractures by a factor of five, and up to 20% may show an absence of the midline crease of patients with a vertebral compression frac- or an exaggerated thoracic kyphosis. Pain is ture are likely to have another one within the typically reproduced by deep pressure over same year if osteoporosis remains untreated.48 the spinous process at the involved level. Population studies suggest that the death rate Compression fractures rarely cause neurologic among patients who have osteoporotic verte- deficits but should always be considered. bral compression fractures increases with the Fractures commonly occur in the thora- number of involved vertebrae.43 columbar region but may be anywhere in the Unfortunately, osteoporotic vertebral spine. Fractures in the upper thoracic spine compression fractures are not always easily may indicate an underlying malignant tumor, amenable to treatment: up to 30% of patients and a thorough search for a possible primary who are symptomatic and seek treatment lesion should always be carried out for frac- do not respond adequately to nonsurgical tures in this location. methods.49,50 However, new minimally inva- sive interventions such as vertebral augmen- Laboratory testing tation make timely evaluation clinically rel- Routine laboratory evaluation and thyroid evant. function tests should be done, as well as a 24-

CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 75 • NUMBER 8 AUGUST 2008 563 Downloaded from www.ccjm.org on September 28, 2021. For personal use only. All other uses require permission. BACK PAIN

table 3 Features of cauda equina compression vs spinal cord compression

FEATURES CAUDA EQUINA COMPRESSION SPINAL CORD COMPRESSION

Vertebral level L2-sacrum C1-L1 Spinal level Injury to lumbosacral nerve roots Injury to spinal cord Symmetry of Usually asymmetric Usually symmetric signs, symptoms Pain Prominent, asymmetric, and radicular Typically, bilateral extremity pain or painless Motor Weakness or flaccid paralysis Weakness or spastic paralysis Sensory Saddle anesthesia, may be asymmetric Loss of pinprick, temperature, position, and vibratory sensation may occur early Reflexes Areflexic lower extremities; Hyperreflexia, Babinski sign, clonus bulbocavernosus reflex is absent in low (sacral) lesion

reprinted with permission FROM QURESHI NH. CAUDA EQUINA. EMEDICINE. WWW.EMEDICINE.COM/MED/TOPIC2904.HTM. ACCESSED 2/20/2008.

hour urine specimen for collagen breakdown linear pattern is replaced by restoration of products, calcium, phosphate, and creatinine fatty marrow.51 levels. Serum and urine protein electropho- Sagittal short tau inversion recovery se- resis should be performed if myeloma is sus- quences, which use specifically timed pulse pected. A white blood-cell count, erythrocyte sequences to suppress fat signals, show high- Ankylosing sedimentation rate, and C-reactive protein intensity signal changes in areas of edema from spondylitis level help determine if an underlying infec- acute or healing fractures. They provide a sen- tion caused the fracture. sitive but nonspecific marker of abnormality. predisposes to Dual energy x-ray absorptiometry helps serious spinal MRI needed if plain films reveal fracture determine the extent of osteoporosis. injury or are equivocal Bone scans should only be used for patients Anteroposterior and lateral roentgenograms with suspected metastatic disease. should be taken first; they typically show os- teopenia. A fracture in the vertebral body is Patients with ankylosing spondylitis characterized by loss of height and by wedg- need thorough workup ing. Osseous fragments can occasionally be Ankylosing spondylitis predisposes to serious seen in the spinal canal. spinal injury. Even after only minor trauma, If a fracture is diagnosed or the radio- patients with ankylosing spondylitis and graphs are equivocal, MRI of the spine should acute, severe back pain should be thoroughly be done next, since it is probably best for evaluated for fracture with CT and MRI of determining fracture age, detecting a malig- the entire spine. Plain radiography should not nant tumor (TABLE 2), and helping select ap- be relied on for these patients because of the propriate treatment. Shortly after a vertebral risk of misinterpretation, delayed diagnosis, fracture, MRI shows a geographic pattern of and poorer outcomes.52,53 low-intensity signal changes on T1-weighted images and high-intensity signal changes on ■■ NEUROLOGIC COMPROMISE—A RED FLAG T2-weighted images. As a fracture becomes chronic, a linear area of low-intensity signal Neural compromise can result from spinal change replaces the geographic area on T1- cord or cauda equina compression (TABLE 3). weighted images. As healing continues, the Cauda equina compression usually results

564 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 75 • NUMBER 8 AUGUST 2008 Downloaded from www.ccjm.org on September 28, 2021. For personal use only. All other uses require permission. siemionow and colleagues

from a fracture, tumor, epidural hematoma, the first symptom to maximal neurologic defi- or abscess, and occasionally from massive disk cit ranged from a few minutes to 4 days, with herniation. Paraplegia, quadriplegia, or cauda the average interval being nearly 13 hours. equina deficit should trigger an aggressive Although painless onset has been search for the cause.54 reported,58 spinal epidural hematoma typi- Cauda equina compression classically pres- cally presents with acute pain at the level of ents with back pain, bilateral sciatica, saddle the lesion, which is often rapidly followed by anesthesia, and lower extremity weakness pro- paraplegia or quadriplegia, depending on the gressing to paraplegia, but in practice these location of the hemorrhage. Sometimes the symptoms are variably present and diagnosing onset of pain is preceded by a sudden increase the condition often requires a high degree of of venous pressure from coughing, sneezing, or suspicion. Hyporeflexia is typically a sign of straining at stool. Urinary retention often de- cauda equina compression, while hyperreflex- velops at an early stage. ia, clonus, and the Babinski sign suggest spinal Most lesions occur in the thoracic region cord compression, requiring an evaluation of and extend into the cervicothoracic or the the cervical and thoracic spine. Cauda equina thoracolumbar area. The pain distribution compression typically involves urinary reten- may be radicular, mimicking a ruptured inter- tion; in contrast, cord compression typically vertebral disk. causes incontinence.55 Evaluation should be with MRI. Acute hem- If either cauda equina or spinal cord com- orrhage is characterized by a marked decrease in pression is detected during an initial examina- signal intensity on T2-weighted images. Sub- tion, an immediate more extensive evaluation acute hematoma has increased signal intensity is warranted. MRI is the study of choice. on both T1- and T2-weighted images.56 Early recognition, MRI confirmation, and Spinal epidural hematoma treatment should be accomplished as soon as Spinal epidural hematoma is a rare but dra- possible.56 Recovery depends on the sever- matic cause of paralysis in elderly patients. ity of the neurologic deficit and the duration In most cases, there is no antecedent trauma. of symptoms before treatment. Lawton et al56 Lawton et al,56 in a series of 30 patients treated found that patients taken to surgery within 12 surgically for spinal epidural hematoma, found hours had better neurologic outcomes than pa- that 73% resulted from spine surgery, epidural tients with identical preoperative neurologic catheterization, or anticoagulation therapy. status whose surgery was delayed beyond 12 Other possible causes of epidural hematoma hours. Surgery should not be withheld because include vascular malformations, angiomas, an- of advanced age or poor health: in 10 reported eurysms, hypertension, and aspirin therapy.57 cases in which surgery was delayed, all patients The same study56 found that the time from died.59 ■

■■ REFERENCES 8. Black P. Spinal metastasis: current status and recommended guide- lines for management. Neurosurgery 1979; 5:726–746. 1. Deyo RA, Tsui-Wu YJ. Descriptive epidemiology of low-back pain 9. Brihaye J, Ectors P, Lemort M, Van Houtte P. The management and its related medical care in the United States. Spine 1987; of spinal epidural metastases. Adv Tech Stand Neurosurg 1988; 12:264–268. 16:121–176. 2. Pengel LH, Herbert RD, Maher CG, Refshauge KM. Acute back pain: 10. Patel RK, Slipman CW. Lumbar degenerative disk disease. Emedi- systematic review of its prognosis. BMJ 2003; 327:323–325. cine. Accessed March 25, 2008. http://www.emedicine.com/pmr/ 3. Deyo RA, Rainville J, Kent DL. What can the history and physical topic67.htm. examination tell us about back pain? JAMA 1992; 268:760–765. 11. Deyo RA, Diehl AK. Cancer as a cause of back pain: frequency, clini- 4. Pateder DB, Brems J, Lieberman I, Bell GR, McLain RF. Masquerade: cal presentation, and diagnostic strategies. J Gen Intern Med 1988; nonspinal musculoskeletal disorders that mimic spinal conditions. 3:230–238. Cleve Clin J Med 2008; 75:50–56. 12. Rosen P, Barkin RM, Danzl DF, et al. Emergency Medicine: Concepts 5. Klineberg E, Mazanec D, Orr D, Demicco R, Bell G, McLain R. and Clinical Practice. 4th ed. St Louis, MO: Mosby; 1998:2100–2102. Masquerade: medical causes of back pain. Cleve Clin J Med 2007; 13. Abbruzzese JL, Abbruzzese MC, Lenzi R, Hess KR, Raber MN. Analy- 74:905–913. sis of a diagnostic strategy for patients with suspected tumors of 6. McLain RF, Bell G, Montgomery W. Masquerade: systemic causes of unknown origin. J Clin Oncol 1995; 13:2094–2103. back pain. Cleve Clin J Med. In press. 14. McCarthy EF, Frassica FJ. Pathology of Bone and Joint Disorders: 7. Gilbert RW, Kim JH, Posner JB. Epidural spinal cord compression With Clinical and Radiographic Correlation. Philadelphia: WB Saun- from metastatic tumor: diagnosis and treatment. Ann Neurol 1978; ders; 1998. 3:40–51. 15. Edelstyn GA, Gillespie PJ, Grebbell FS. The radiological demonstra-

CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 75 • NUMBER 8 AUGUST 2008 565 Downloaded from www.ccjm.org on September 28, 2021. For personal use only. All other uses require permission. BACK PAIN

tion of osseous metastases. Experimental observations. Clin Radiol and review of the literature. Rev Infect Dis 1987; 9:265–274. 1967; 18:158–162. 38. Kaufman DM, Kaplan JG, Litman N. Infectious agents in spinal epi- 16. Han LJ, Au-Yong TK, Tong WC, Chu KS, Szeto LT, Wong CP. Com- dural abscesses. Neurology 1980; 30:844–850. parison of bone single-photon emission tomography and planar 39. Rezai AR, Woo HH, Errico TJ, Cooper PR. Contemporary manage- imaging in the detection of vertebral metastases in patients with ment of spinal osteomyelitis. Neurosurgery 1999; 44:1018–1026. back pain. Eur J Nucl Med 1998; 25:635–638. 40. Bertino RE, Porter BA, Stimac GK, Tepper SJ. Imaging spinal osteo- 17. Feun LG, Savaraj N. Detection of occult bone metastasis by MRI myelitis and epidural abscess with short TI inversion recovery (STIR). scan. J Fla Med Assoc 1990; 77:881–883. AJNR Am J Neuroradiol 1988; 9:563–564. 18. Citrin DL, Bessent RG, Greig WR. A comparison of the sensitiv- 41. Rigamonti D, Liem L, Sampath P, et al. Spinal epidural abscess: con- ity and accuracy of the 99TCm-phosphate bone scan and skeletal temporary trends in etiology, evaluation, and management. Surg radiograph in the diagnosis of bone metastases. Clin Radiol 1977; Neurol 1999; 52:189–197. 28:107–117. 42. De Vries F, Bracke M, Leufkens HG, Lammers JW, Cooper C, Van Staa 19. Runge VM, Lee C, Iten AL, Williams NM. Contrast-enhanced mag- TP. Fracture risk with intermittent high-dose oral glucocorticoid netic resonance imaging in a spinal epidural tumor model. Invest therapy. Arthritis Rheum 2007; 56:208–214. Radiol 1997; 32:589–595. 43. Cooper C, Atkinson EJ, O’Fallon WM, Melton LJ 3rd. Incidence of 20. Buranapanitkit B, Lim A, Geater A. Misdiagnosis in vertebral os- clinically diagnosed vertebral fractures: a population-based study in teomyelitis: problems and factors. J Med Assoc Thai 2001; 84:1743– Rochester, Minnesota, 1985–1989. J Bone Miner Res 1992; 7:221– 1750. 227. 21. Colmenero JD, Jiménez-Mejías ME, Reguera JM, et al. Tuberculous 44. Kim DH, Vaccaro AR. Osteoporotic compression fractures of the vertebral osteomyelitis in the new millennium: still a diagnostic spine; current options and considerations for treatment. Spine J and therapeutic challenge. Eur J Clin Microbiol Infect Dis 2004; 2006; 6:479–487. 23:477–483. 45. Cohn SH, Abesamis C, Yasumura S, Aloia JF, Zanzi I, Ellis KJ. Com- 22. Waldvogel FA, Medoff G, Swartz MN. Osteomyelitis: a review of parative skeletal mass and radial bone mineral content in black and clinical features, therapeutic considerations and unusual aspects. 3. white women. Metabolism 1977; 26:171–178. Osteomyelitis associated with vascular insufficiency. N Engl J Med 46. Tobias JH, Hutchinson AP, Hunt LP, et al. Use of clinical risk factors to 1970; 282:316–322. identify postmenopausal women with vertebral fractures. Osteopo- 23. Carragee EJ. Pyogenic vertebral osteomyelitis. J Bone Joint Surg Am ros Int 2007; 18:35–43. 1997; 79:874–880. 47. Melton LJ 3rd, Kallmes DF. Epidemiology of vertebral fractures: impli- 24. Kapeller P, Fazekas F, Krametter D, et al. Pyogenic infectious cations for vertebral augmentation. Acad Radiol 2006; 13:538–545. spondylitis: clinical, laboratory and MRI features. Eur Neurol 1997; 48. Silverman SL. The clinical consequences of vertebral compression 38:94–98. fracture. Bone 1992; 13:S27–S31. 25. Digby JM, Kersley JB. Pyogenic non-tuberculous spinal infection: an 49. Melton LJ 3rd, Kan SH, Frye MA, Wahner HW, O’Fallon WM, Riggs analysis of thirty cases. J Bone Joint Surg Br 1979; 61:47–55. BL. Epidemiology of vertebral fractures in women. Am J Epidemiol 26. Modic MT, Feiglin DH, Piraino DW, et al. Vertebral osteomyelitis: 1989; 129:1000–1011. assessment using MR. Radiology 1985; 157:157–166. 50. Wasnich RD. Vertebral fracture epidemiology. Bone 1996; 18:179S– 27. Szypryt EP, Hardy JG, Hinton CE, Worthington BS, Mulholland RC. A 183S. comparison between magnetic resonance imaging and scintigraphic 51. Yamato M, Nishimura G, Kuramochi E, Saiki N, Fujioka M. MR ap- bone imaging in the diagnosis of disk space infection in an animal pearance at different ages of osteoporotic compression fractures of model. Spine 1988; 13:1042–1048. the vertebrae. Radiat Med 1998; 16:329–334. 28. Küker W, Mull M, Mayfrank L, Töpper R, Thron A. Epidural spinal 52. Einsiedel T, Schmelz A, Arand M, et al. Injuries of the cervical spine infection. Variability of clinical and magnetic resonance imaging in patients with ankylosing spondylitis: experience at two trauma findings. Spine 1997; 22:544–551. centers. J Neurosurg Spine 2006; 5:33–45. 29. Tung GA, Yim JW, Mermel LA, Philip L, Rogg JM. Spinal epidural 53. Olerud C, Frost A, Bring J. Spinal fractures in patients with ankylos- abscess: correlation between MRI findings and outcome. Neuroradi- ing spondylitis. Eur Spine J 1996; 5:51–55. ology 1999; 41:904–909. 54. Spangfort EV. The lumbar disk herniation. A computer-aided analy- 30. Sapico FL, Montgomerie JZ. Vertebral osteomyelitis. Infect Dis Clin sis of 2,504 operations. Acta Orthop Scand Suppl 1972; 142:1–95. North Am 1990; 4:539–550. 55. Kostuik JP, Harrington I, Alexander D, Rand W, Evans D. Cauda 31. Tali ET. Spinal infections. Eur J Radiol 2004; 50:120–133. equina syndrome and lumbar disk herniation. J Bone Joint Surg Am 32. Smith AS, Weinstein MA, Mizushima A, et al. MR imaging character- 1986; 68:386–391. istics of tuberculous spondylitis vs vertebral osteomyelitis. AJR Am J 56. Lawton MT, Porter RW, Heiserman JE, Jacobowitz R, Sonntag VK, Roentgenol 1989; 153:399–405. Dickman CA. Surgical management of spinal epidural hematoma: 33. Jung NY, Jee WH, Ha KY, Park CK, Byun JY. Discrimination of relationship between surgical timing and neurological outcome. J tuberculous spondylitis from pyogenic spondylitis on MRI. AJR Am J Neurosurg 1995; 83:1–7. Roentgenol 2004; 182:1405–1410. 57. Simmons EH, Grobler LJ. Acute spinal epidural hematoma. J Bone 34. Joseffer SS, Cooper PR. Modern imaging of spinal tuberculosis. J Joint Surg Am 1978; 60:395–396. Neurosurg Spine 2005; 2:145–150. 58. Senelick RC, Norwood CW, Cohen GH. “Painless” spinal epidural he- 35. Pigrau C, Almirante B, Flores X, et al. Spontaneous pyogenic ver- matoma during anticoagulant therapy. Neurology 1976; 26:213–225. tebral osteomyelitis and endocarditis: incidence, risk factors, and 59. Watts C, Porto L. Recognizing spontaneous spinal epidural hema- outcome. Am J Med 2005; 118:1287. toma. Geriatrics 1976; 31:97–99. 36. McHenry MC, Easley KA, Locker GA. Vertebral osteomyelitis: long- term outcome for 253 patients from 7 Cleveland-area hospitals. Clin ADDRESS: Robert F. McLain, MD, Cleveland Clinic Center for Spine Infect Dis 2002; 34:1342–1350. Health, Department of Orthopaedic Surgery, A41, Cleveland Clinic, 9500 37. Danner RL, Hartman BJ. Update on spinal epidural abscess: 35 cases Euclid Avenue, Cleveland, OH 44195; e-mail [email protected].

566 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 75 • NUMBER 8 AUGUST 2008 Downloaded from www.ccjm.org on September 28, 2021. For personal use only. All other uses require permission.