Imaging

Back pain is one of the most common complaints that internists and primary care physicians encounter.¹ Although back pain is nonspecific, some hallmark signs and symptoms indicate that a patient is more likely to have a serious disorder. This article contrasts the presentation of cancer, infections, and fractures with the more common and benign conditions that cause back pain and provides guidance for diagnosis.

UNCOMMON, BUT MUST BE CONSIDERED

Although a variety of tissues can contribute to pain—intervertebral disks, vertebrae, ligaments, neural structures, muscles, and fascia—and many disorders can damage these tissues, most patients with back or neck pain have a benign condition. Back pain is typically caused by age-related degenerative changes or by minor repetitive trauma; with supportive care and physical therapy, up to 90% of patients with back pain of this nature improve substantially within 4 weeks.²

Serious, destructive diseases are uncommon causes of back pain: malignancy, infection, ankylosing spondylitis, and epidural abscess together account for fewer than 1% of cases of back pain in a typical primary care practice. But their clinical impact is out of proportion to their prevalence. The fear of overlooking a serious condition influences any practitioner’s approach to back pain and is a common reason 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, and appropriate diagnostic studies. Once a serious diagnosis is ruled out, attention can be focused on rehabilitation and back care.

Back pain can also be due to musculoskeletal disorders, peptic ulcers, pancreatitis, pyelonephritis, aortic aneurysms, and other serious conditions, which we have discussed in other articles in this journal.^4–6

SPINAL CANCER AND METASTASES

Since back pain is the presenting symptom in 90% of patients with spinal tumors,⁷ neoplasia belongs in the differential diagnosis of any patient with persistent, unremitting back pain. However, it is also important to recognize atypical presentations of neoplasia, such as a painless neurologic deficit, which should prompt an urgent workup.

The spine is one of the most common sites of metastasis: about 20,000 cases arise each year.⁸ Brihaye et al⁹ reviewed 1,477 cases of spinal metastases with epidural involvement and found that 16.5% arose from primary tumors in the breast, 15.6% from the lung, 9.2% from the prostate, and 6.5% from the kidney.

Cancer pain is persistent and progressive

Pain from spinal cancer is often different from idiopathic back pain or degenerative disk disease (Table 1).

Benign back pain often arises from a known injury, is relieved by rest, and increases with activities that load the disk (eg, sitting, getting up from bed or a chair), lumbar flexion with or without rotation, lifting, vibration (eg, riding in a car), coughing, sneezing, laughing, and the Valsalva maneuver. It is most commonly focal to the lumbosacral junction, the lumbar muscles, and the buttocks. Pain due to injury or a flare-up of degenerative disease typically begins to subside after 4 to 6 weeks and responds to nonsteroidal anti-inflammatory drugs and physical therapy.¹⁰

In contrast, pain caused by spinal neoplasia is typically persistent and progressive and is not alleviated by rest. Often the pain is worse at night, waking the patient from sleep. Back pain is typically focal to the level of the lesion and may be associated with belt-like thoracic pain or radicular symptoms of pain or weakness in the legs. A spinal mass can cause neurologic signs or symptoms by directly compressing the spinal cord or nerve roots, mimicking disk herniation or stenosis.¹¹,¹²

Pathologic fractures resulting from vertebral destruction may be the first—and unfortunately a late—presentation of a tumor.

Ask about, look for, signs and symptoms of cancer

In taking the history, one should ask about possible signs and symptoms of systemic disease such as fatigue, weight loss, and changes in bowel habits. Hemoptysis, lymphadenopathy, subcutaneous or breast masses, nipple discharge, atypical vaginal bleeding, or blood in the stool suggest malignancy and should direct the specific diagnostic approach.¹³ A history of cancer, even if remote, should raise suspicion, as should major risk factors such as smoking.

Because most spinal tumors are metastases, a clinical examination of the breast, lungs, abdomen, thyroid, and prostate are appropriate starting points.¹⁴ The spine should be examined to identify sites of focal pain. A neurologic examination should be done to evaluate any signs of neurologic compromise or abnormal reflexes. Signs or symptoms of spinal cord compression should be investigated immediately.

 

Cancer usually elevates the ESR, CRP

If cancer is suspected, initial tests should include a complete blood cell count, erythrocyte sedimentation rate, C-reactive protein level, urinalysis, prostate-specific antigen level, and fecal occult blood testing. Normal results can considerably relieve suspicion of cancer: the erythrocyte sedimentation rate and C-reactive protein level are almost always elevated with systemic neoplasia.

Other initial tests include a complete blood cell count and chemistry panel. If laboratory studies reveal anemia, hypercalcemia, and elevated levels of alkaline phosphatase, concern should increase. Chest radiography, abdominal computed tomography (CT) (Figure 1), and mammography for women are needed if laboratory results are abnormal. Plain radiographs are the first imaging study of the spine to obtain. Compression fractures, soft tissue calcifications, or focal loss of bone mineralization suggests tumor. Abnormal results on serum and urine protein electrophoresis increase the likelihood of multiple myeloma or plasmacytoma, but normal results do not rule out monoclonal gammopathy of uncertain significance.

Imaging tests

Unfortunately, spinal tumors cannot be well visualized on radiographs until significant destruction has occurred.¹⁵

A bone scan can usually detect tumors other than the purely lytic ones such as myeloma and has a sensitivity of 74%, a specificity of 81%, and a positive predictive value of 64% for vertebral metastasis in patients with back pain.¹⁶

Magnetic resonance imaging (MRI) is the best imaging study for evaluating spinal tumors because it can show the status of the bone marrow and has excellent contrast resolution in soft tissue (Figure 2).¹⁷,¹⁸ It can show vertebral bone marrow infiltration by tumor cells as well as soft tissue masses in and around the spinal column. Bone marrow invaded by a neoplasm is characterized by increased cellularity, resulting in a decreased signal on T1-weighted images and a high signal on T2-weighted images. Intravenous gadolinium further increases the contrast between a tumor and normal tissues and is important for characterizing and grading tumors.¹⁹

INFECTION CAN BE INDOLENT OR ACUTE

Spinal infection is a serious condition that can take an indolent, smoldering course or, alternatively, can erupt into sepsis or rapidly progressive vertebral destruction. Although the latter conditions are hard to miss, early diskitis and osteomyelitis can be difficult to differentiate from idiopathic back pain. In a series of 101 patients with vertebral osteomyelitis, misdiagnosis occurred in 33.7%, and the average delay from the onset of clinical manifestations to diagnosis was 2.6 months.²⁰ Tuberculosis can be even more elusive: in a series of 78 patients diagnosed with definite or probable tuberculous vertebral osteomyelitis, the mean delay to diagnosis was about 6 months.²¹

Acute spinal infections are most often pyogenic; chronic infections may be pyogenic, fungal, or granulomatous.

Vertebral osteomyelitis accounts for 2% to 7% of all cases of osteomyelitis and is an uncommon cause of back pain.²² Any source of infection (eg, dental abscess, pneumonia) can seed the spine; urinary tract infection is the most common. Patients with immunocompromise or diabetes are most at risk.²³ The onset is usually insidious with focal back pain at the level of involvement.

History and physical examination reveal localized pain

Spinal infections typically cause pain that is worsened with weight-bearing and activity and is relieved only when lying down. Chronic infection is usually associated with weight loss, fatigue, fevers, and night sweats.

Pain is usually well localized and reproduced by palpation or percussion over the involved level. Severe pain can sometimes be elicited by sitting the patient up or by changing the patient’s position. Focal kyphosis may be detectable if the vertebra has collapsed.

In a series of 41 patients with pyogenic infectious spondylitis, 90% had localized back pain aggravated by percussion, 59% had radicular signs and symptoms, and 29% had neurologic signs of spinal cord compression, including hyperreflexia, clonus, the Babinski sign (extension of the toes upward when the sole of the foot is stroked upwards), or the Hoffmann sign (flexion of the thumb elicited by flicking the end of a middle finger).²⁴

LABORATORY RESULTS TYPICALLY INDICATE INFECTION

The erythrocyte sedimentation rate is the most sensitive test for infection, and an elevated rate may be the only abnormal laboratory finding: Digby and Kersley²⁵ found that the rate was increased in all of 30 patients with nontuberculous pyogenic osteomyelitis of the spine. The C-reactive protein level is also usually elevated, but 40% of patients have a normal white blood cell count.²⁵ Results of other laboratory tests are typically in the normal range. Tuberculin skin testing should be done for patients at high risk of the disease (eg, immigrants from areas of endemic disease, non-Hispanic blacks, immunocompromised patients, and those with known exposure to tuberculosis). Patients with high fever, chills, or rigors should have cultures taken of blood, 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 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 neoplastic disease from vertebral osteomyelitis²⁹ 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 within the vertebral body, loss of definition of end plates (which appear hypointense compared with the bone marrow), and destruction of the cortical margins of the involved vertebral bodies. T2-weighted MRI typically discloses high signals of the affected areas of the vertebral body and disk. Contrast should be used to increase specificity; enhancement may be the first sign of an acute inflammatory process.³¹

CT and MRI can help identify sequestra, perilesional sclerosis, and epidural or soft tissue abscesses. Guided biopsy may be needed to differentiate between abscess, hematoma, tumor, and inflammation.

 

 

MRI findings: Pyogenic vs tuberculous spondylitis

MRI can help differentiate pyogenic vertebral osteomyelitis from tubercular disease, although findings may be similar (eg, both conditions have a high signal on T2-weighted images).³² Jung et al,³³ in a retrospective study of 52 patients with spondylitis, found that compared with patients with pyogenic infections, patients with tuberculous spondylitis had a significantly higher incidence of a well-defined paraspinal abnormal signal on MRI, a thin and smooth abscess wall, a paraspinal or intraosseous abscess, subligamentous spread to three or more vertebral levels, involvement of multiple vertebral bodies, thoracic spine involvement, and a hyperintense signal on T2-weighted images. Other MRI features characteristically seen in patients with tuberculous spinal disease are anterior corner destruction, a relative preservation of the intervertebral disk, and large soft-tissue abscesses with calcifications.³⁴

Prompt diagnosis and aggressive treatment needed

Pigrau et al³⁵ found that spinal osteomyelitis is highly associated with endocarditis: among 606 patients with infectious endocarditis, 28 (4.6%) had pyogenic vertebral osteomyelitis, and among 91 patients with pyogenic vertebral osteomyelitis, 28 (30.8%) had infectious endocarditis.

McHenry et al³⁶ retrospectively studied outcomes of 253 patients with vertebral osteomyelitis after a median of 6.5 years (range 2 days to 38 years): 11% died, more than one-third of survivors had residual disability, and 14% had a relapse. Surgery resulted in recovery or improvement in 86 (79%) of 109 patients. Independent risk factors for adverse outcome (death or incomplete recovery) were neurologic compromise, increased time to diagnosis, and having a hospital-acquired infection (P = .004). Relapse commonly developed in patients with severe vertebral destruction and abscesses, which appeared some time after surgical drainage or debridement. Recurrent bacteremia, paravertebral abscesses, and chronically draining sinuses were independently associated with relapse (P = .001). MRI, done in 110 patients, was often performed late in the course of infection and did not significantly affect outcome. The authors stressed that an optimal outcome of vertebral osteomyelitis requires heightened awareness, early diagnosis, prompt identification of pathogens, reversal of complications, and prolonged antimicrobial therapy.

Epidural abscess may also be present

Epidural abscess occurs in 10% of spine infections. About half of patients with an epidural abscess are misdiagnosed on their initial evaluation.³⁷,³⁸ Patients initially complain of local spine pain, followed by radicular pain, weakness, and finally paralysis. Between 12% and 30% of patients report a history of trauma, even as minor as a fall, preceding the infection.³⁸,³⁹

Radiologic findings are frequently equivocal, and MRI is preferred; gadolinium enhancement further increases sensitivity.³⁹,⁴⁰ Spinal canal abscesses usually appear hypointense on T1-weighted images and hyperintense on T2-weighted images, with ring enhancement surrounding the abscess area in contrast studies.⁴¹ MRI may give negative findings in the early stages of a spinal canal infection and so may need to be repeated.⁴¹ MRI may not help distinguish an epidural from a subdural abscess. However, primary spinal epidural abscesses without concomitant vertebral osteomyelitis are rare; therefore, the finding of associated vertebral osteomyelitis makes a spinal epidural abscess more likely.

FRACTURES

Fractures of the spine can be asymptomatic and may have no preceding trauma. They can be due to osteoporosis, malignancy, infection, or metabolic disorders such as renal osteodystrophy or hyperparathyroidism. Fractures in normal bone are almost always associated with trauma. Any suspicion of infection or malignancy should be investigated.

Corticosteroids increase risk

Any patient with back pain who is receiving corticosteroid therapy should be considered as having a compression fracture until proven otherwise.³ De Vries et al⁴² found that in a database of nearly 200,000 patients receiving glucocorticoids, risk increased substantially with increasing cumulative exposure. Those who intermittently received high doses (= 15 mg/day) and those who had no or little previous exposure to corticosteroids (cumulative exposure = 1 g) had only a slightly increased risk of osteoporotic fracture, and their risk of fracture of the hip and femur was not increased. In contrast, patients who received a daily dose of at least 30 mg and whose cumulative exposure was more than 5 g had a relative risk of osteoporotic vertebral fracture of 14.42 (95% confidence interval 8.29–25.08).

Osteoporotic compression fractures are common in the elderly

Osteoporosis involves reduced bone density, disrupted trabecular architecture, and increased susceptibility to fractures. About 700,000 vertebral body compression fractures occur in the United States each year⁴³: about 10% result in hospitalization, involving an average stay of 8 days.⁴⁴ Osteoporotic compression fractures are highly associated with age older than 65, female sex, and European descent.⁴⁵,⁴⁶ The estimated lifetime risk of a clinically evident vertebral fracture after age 50 years is 16% among postmenopausal white women and 5% among white men.⁴⁷

A single osteoporotic vertebral compression fracture increases the risk of subsequent fractures by a factor of five, and up to 20% of patients with a vertebral compression fracture are likely to have another one within the same year if osteoporosis remains untreated.⁴⁸ Population studies suggest that the death rate among patients who have osteoporotic vertebral compression fractures increases with the number of involved vertebrae.⁴³

Unfortunately, osteoporotic vertebral compression fractures are not always easily amenable to treatment: up to 30% of patients who are symptomatic and seek treatment do not respond adequately to nonsurgical methods.⁴⁹,⁵⁰ However, new minimally invasive interventions such as vertebral augmentation make timely evaluation clinically relevant.

 

 

History, physical examination

Patients may present with a history of trauma with associated back pain or a neurologic deficit. In osteoporotic patients, the trauma may have been minimal, eg, a sneeze, a fall from a chair, or a slip and fall in the home. Pain tends to be worse when standing erect and occasionally when lying flat.

The patient is commonly visibly uncomfortable and may be limited to a wheelchair or stoop forward when standing. The spine may show an absence of the midline crease or an exaggerated thoracic kyphosis. Pain is typically reproduced by deep pressure over the spinous process at the involved level. Compression fractures rarely cause neurologic deficits but should always be considered.

Fractures commonly occur in the thoracolumbar region but may be anywhere in the spine. Fractures in the upper thoracic spine may indicate an underlying malignant tumor, and a thorough search for a possible primary lesion should always be carried out for fractures in this location.

Laboratory testing

Routine laboratory evaluation and thyroid function tests should be done, as well as a 24-hour urine specimen for collagen breakdown products, calcium, phosphate, and creatinine levels. Serum and urine protein electrophoresis should be performed if myeloma is suspected. A white blood-cell count, erythrocyte sedimentation rate, and C-reactive protein level help determine if an underlying infection caused the fracture.

MRI needed if plain films reveal fracture or are equivocal

Anteroposterior and lateral roentgenograms should be taken first; they typically show osteopenia. A fracture in the vertebral body is characterized by loss of height and by wedging. Osseous fragments can occasionally be seen in the spinal canal.

If a fracture is diagnosed or the radiographs are equivocal, MRI of the spine should be done next, since it is probably best for determining fracture age, detecting a malignant tumor (Table 2), and helping select appropriate treatment. Shortly after a vertebral fracture, MRI shows a geographic pattern of low-intensity signal changes on T1-weighted images and high-intensity signal changes on T2-weighted images. As a fracture becomes chronic, a linear area of low-intensity signal change replaces the geographic area on T1-weighted images. As healing continues, the linear pattern is replaced by restoration of fatty marrow.⁵¹

Sagittal short tau inversion recovery sequences, which use specifically timed pulse sequences to suppress fat signals, show high-intensity signal changes in areas of edema from acute or healing fractures. They provide a sensitive but nonspecific marker of abnormality.

Dual energy x-ray absorptiometry helps determine the extent of osteoporosis.

Bone scans should only be used for patients with suspected metastatic disease.

Patients with ankylosing spondylitis need thorough workup

Ankylosing spondylitis predisposes to serious spinal injury. Even after only minor trauma, patients with ankylosing spondylitis and acute, severe back pain should be thoroughly evaluated for fracture with CT and MRI of the entire spine. Plain radiography should not be relied on for these patients because of the risk of misinterpretation, delayed diagnosis, and poorer outcomes.⁵²,⁵³

NEUROLOGIC COMPROMISE—A RED FLAG

Neural compromise can result from spinal cord or cauda equina compression (Table 3). Cauda equina compression usually results from a fracture, tumor, epidural hematoma, or abscess, and occasionally from massive disk herniation. Paraplegia, quadriplegia, or cauda equina deficit should trigger an aggressive search for the cause.⁵⁴

Cauda equina compression classically presents with back pain, bilateral sciatica, saddle anesthesia, and lower extremity weakness progressing to paraplegia, but in practice these symptoms are variably present and diagnosing the condition often requires a high degree of suspicion. Hyporeflexia is typically a sign of cauda equina compression, while hyperreflexia, clonus, and the Babinski sign suggest spinal cord compression, requiring an evaluation of the cervical and thoracic spine. Cauda equina compression typically involves urinary retention; in contrast, cord compression typically causes incontinence.⁵⁵

If either cauda equina or spinal cord compression is detected during an initial examination, an immediate more extensive evaluation is warranted. MRI is the study of choice.

Spinal epidural hematoma

Spinal epidural hematoma is a rare but dramatic cause of paralysis in elderly patients. In most cases, there is no antecedent trauma. Lawton et al,⁵⁶ in a series of 30 patients treated surgically for spinal epidural hematoma, found that 73% resulted from spine surgery, epidural catheterization, or anticoagulation therapy. Other possible causes of epidural hematoma include vascular malformations, angiomas, aneurysms, hypertension, and aspirin therapy.⁵⁷

The same study⁵⁶ found that the time from the first symptom to maximal neurologic deficit ranged from a few minutes to 4 days, with the average interval being nearly 13 hours.

Although painless onset has been reported,⁵⁸ spinal epidural hematoma typically presents with acute pain at the level of the lesion, which is often rapidly followed by paraplegia or quadriplegia, depending on the location of the hemorrhage. Sometimes the onset of pain is preceded by a sudden increase of venous pressure from coughing, sneezing, or straining at stool. Urinary retention often develops at an early stage.

Most lesions occur in the thoracic region and extend into the cervicothoracic or the thoracolumbar area. The pain distribution may be radicular, mimicking a ruptured intervertebral disk.

Evaluation should be with MRI. Acute hemorrhage is characterized by a marked decrease in signal intensity on T2-weighted images. Subacute hematoma has increased signal intensity on both T1- and T2-weighted images.⁵⁶

Early recognition, MRI confirmation, and treatment should be accomplished as soon as possible.⁵⁶ Recovery depends on the severity of the neurologic deficit and the duration of symptoms before treatment. Lawton et al⁵⁶ found that patients taken to surgery within 12 hours had better neurologic outcomes than patients with identical preoperative neurologic status whose surgery was delayed beyond 12 hours. Surgery should not be withheld because of advanced age or poor health: in 10 reported cases in which surgery was delayed, all patients died.⁵⁹

Back pain is one of the most common complaints that internists and primary care physicians encounter.¹ Although back pain is nonspecific, some hallmark signs and symptoms indicate that a patient is more likely to have a serious disorder. This article contrasts the presentation of cancer, infections, and fractures with the more common and benign conditions that cause back pain and provides guidance for diagnosis.

UNCOMMON, BUT MUST BE CONSIDERED

Although a variety of tissues can contribute to pain—intervertebral disks, vertebrae, ligaments, neural structures, muscles, and fascia—and many disorders can damage these tissues, most patients with back or neck pain have a benign condition. Back pain is typically caused by age-related degenerative changes or by minor repetitive trauma; with supportive care and physical therapy, up to 90% of patients with back pain of this nature improve substantially within 4 weeks.²

Serious, destructive diseases are uncommon causes of back pain: malignancy, infection, ankylosing spondylitis, and epidural abscess together account for fewer than 1% of cases of back pain in a typical primary care practice. But their clinical impact is out of proportion to their prevalence. The fear of overlooking a serious condition influences any practitioner’s approach to back pain and is a common reason 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, and appropriate diagnostic studies. Once a serious diagnosis is ruled out, attention can be focused on rehabilitation and back care.

Back pain can also be due to musculoskeletal disorders, peptic ulcers, pancreatitis, pyelonephritis, aortic aneurysms, and other serious conditions, which we have discussed in other articles in this journal.^4–6

SPINAL CANCER AND METASTASES

Since back pain is the presenting symptom in 90% of patients with spinal tumors,⁷ neoplasia belongs in the differential diagnosis of any patient with persistent, unremitting back pain. However, it is also important to recognize atypical presentations of neoplasia, such as a painless neurologic deficit, which should prompt an urgent workup.

The spine is one of the most common sites of metastasis: about 20,000 cases arise each year.⁸ Brihaye et al⁹ reviewed 1,477 cases of spinal metastases with epidural involvement and found that 16.5% arose from primary tumors in the breast, 15.6% from the lung, 9.2% from the prostate, and 6.5% from the kidney.

Cancer pain is persistent and progressive

Pain from spinal cancer is often different from idiopathic back pain or degenerative disk disease (Table 1).

Benign back pain often arises from a known injury, is relieved by rest, and increases with activities that load the disk (eg, sitting, getting up from bed or a chair), lumbar flexion with or without rotation, lifting, vibration (eg, riding in a car), coughing, sneezing, laughing, and the Valsalva maneuver. It is most commonly focal to the lumbosacral junction, the lumbar muscles, and the buttocks. Pain due to injury or a flare-up of degenerative disease typically begins to subside after 4 to 6 weeks and responds to nonsteroidal anti-inflammatory drugs and physical therapy.¹⁰

In contrast, pain caused by spinal neoplasia is typically persistent and progressive and is not alleviated by rest. Often the pain is worse at night, waking the patient from sleep. Back pain is typically focal to the level of the lesion and may be associated with belt-like thoracic pain or radicular symptoms of pain or weakness in the legs. A spinal mass can cause neurologic signs or symptoms by directly compressing the spinal cord or nerve roots, mimicking disk herniation or stenosis.¹¹,¹²

Pathologic fractures resulting from vertebral destruction may be the first—and unfortunately a late—presentation of a tumor.

Ask about, look for, signs and symptoms of cancer

In taking the history, one should ask about possible signs and symptoms of systemic disease such as fatigue, weight loss, and changes in bowel habits. Hemoptysis, lymphadenopathy, subcutaneous or breast masses, nipple discharge, atypical vaginal bleeding, or blood in the stool suggest malignancy and should direct the specific diagnostic approach.¹³ A history of cancer, even if remote, should raise suspicion, as should major risk factors such as smoking.

Because most spinal tumors are metastases, a clinical examination of the breast, lungs, abdomen, thyroid, and prostate are appropriate starting points.¹⁴ The spine should be examined to identify sites of focal pain. A neurologic examination should be done to evaluate any signs of neurologic compromise or abnormal reflexes. Signs or symptoms of spinal cord compression should be investigated immediately.

 

Cancer usually elevates the ESR, CRP

If cancer is suspected, initial tests should include a complete blood cell count, erythrocyte sedimentation rate, C-reactive protein level, urinalysis, prostate-specific antigen level, and fecal occult blood testing. Normal results can considerably relieve suspicion of cancer: the erythrocyte sedimentation rate and C-reactive protein level are almost always elevated with systemic neoplasia.

Other initial tests include a complete blood cell count and chemistry panel. If laboratory studies reveal anemia, hypercalcemia, and elevated levels of alkaline phosphatase, concern should increase. Chest radiography, abdominal computed tomography (CT) (Figure 1), and mammography for women are needed if laboratory results are abnormal. Plain radiographs are the first imaging study of the spine to obtain. Compression fractures, soft tissue calcifications, or focal loss of bone mineralization suggests tumor. Abnormal results on serum and urine protein electrophoresis increase the likelihood of multiple myeloma or plasmacytoma, but normal results do not rule out monoclonal gammopathy of uncertain significance.

Imaging tests

Unfortunately, spinal tumors cannot be well visualized on radiographs until significant destruction has occurred.¹⁵

A bone scan can usually detect tumors other than the purely lytic ones such as myeloma and has a sensitivity of 74%, a specificity of 81%, and a positive predictive value of 64% for vertebral metastasis in patients with back pain.¹⁶

Magnetic resonance imaging (MRI) is the best imaging study for evaluating spinal tumors because it can show the status of the bone marrow and has excellent contrast resolution in soft tissue (Figure 2).¹⁷,¹⁸ It can show vertebral bone marrow infiltration by tumor cells as well as soft tissue masses in and around the spinal column. Bone marrow invaded by a neoplasm is characterized by increased cellularity, resulting in a decreased signal on T1-weighted images and a high signal on T2-weighted images. Intravenous gadolinium further increases the contrast between a tumor and normal tissues and is important for characterizing and grading tumors.¹⁹

INFECTION CAN BE INDOLENT OR ACUTE

Spinal infection is a serious condition that can take an indolent, smoldering course or, alternatively, can erupt into sepsis or rapidly progressive vertebral destruction. Although the latter conditions are hard to miss, early diskitis and osteomyelitis can be difficult to differentiate from idiopathic back pain. In a series of 101 patients with vertebral osteomyelitis, misdiagnosis occurred in 33.7%, and the average delay from the onset of clinical manifestations to diagnosis was 2.6 months.²⁰ Tuberculosis can be even more elusive: in a series of 78 patients diagnosed with definite or probable tuberculous vertebral osteomyelitis, the mean delay to diagnosis was about 6 months.²¹

Acute spinal infections are most often pyogenic; chronic infections may be pyogenic, fungal, or granulomatous.

Vertebral osteomyelitis accounts for 2% to 7% of all cases of osteomyelitis and is an uncommon cause of back pain.²² Any source of infection (eg, dental abscess, pneumonia) can seed the spine; urinary tract infection is the most common. Patients with immunocompromise or diabetes are most at risk.²³ The onset is usually insidious with focal back pain at the level of involvement.

History and physical examination reveal localized pain

Spinal infections typically cause pain that is worsened with weight-bearing and activity and is relieved only when lying down. Chronic infection is usually associated with weight loss, fatigue, fevers, and night sweats.

Pain is usually well localized and reproduced by palpation or percussion over the involved level. Severe pain can sometimes be elicited by sitting the patient up or by changing the patient’s position. Focal kyphosis may be detectable if the vertebra has collapsed.

In a series of 41 patients with pyogenic infectious spondylitis, 90% had localized back pain aggravated by percussion, 59% had radicular signs and symptoms, and 29% had neurologic signs of spinal cord compression, including hyperreflexia, clonus, the Babinski sign (extension of the toes upward when the sole of the foot is stroked upwards), or the Hoffmann sign (flexion of the thumb elicited by flicking the end of a middle finger).²⁴

LABORATORY RESULTS TYPICALLY INDICATE INFECTION

The erythrocyte sedimentation rate is the most sensitive test for infection, and an elevated rate may be the only abnormal laboratory finding: Digby and Kersley²⁵ found that the rate was increased in all of 30 patients with nontuberculous pyogenic osteomyelitis of the spine. The C-reactive protein level is also usually elevated, but 40% of patients have a normal white blood cell count.²⁵ Results of other laboratory tests are typically in the normal range. Tuberculin skin testing should be done for patients at high risk of the disease (eg, immigrants from areas of endemic disease, non-Hispanic blacks, immunocompromised patients, and those with known exposure to tuberculosis). Patients with high fever, chills, or rigors should have cultures taken of blood, 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 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 neoplastic disease from vertebral osteomyelitis²⁹ 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 within the vertebral body, loss of definition of end plates (which appear hypointense compared with the bone marrow), and destruction of the cortical margins of the involved vertebral bodies. T2-weighted MRI typically discloses high signals of the affected areas of the vertebral body and disk. Contrast should be used to increase specificity; enhancement may be the first sign of an acute inflammatory process.³¹

CT and MRI can help identify sequestra, perilesional sclerosis, and epidural or soft tissue abscesses. Guided biopsy may be needed to differentiate between abscess, hematoma, tumor, and inflammation.

 

 

MRI findings: Pyogenic vs tuberculous spondylitis

MRI can help differentiate pyogenic vertebral osteomyelitis from tubercular disease, although findings may be similar (eg, both conditions have a high signal on T2-weighted images).³² Jung et al,³³ in a retrospective study of 52 patients with spondylitis, found that compared with patients with pyogenic infections, patients with tuberculous spondylitis had a significantly higher incidence of a well-defined paraspinal abnormal signal on MRI, a thin and smooth abscess wall, a paraspinal or intraosseous abscess, subligamentous spread to three or more vertebral levels, involvement of multiple vertebral bodies, thoracic spine involvement, and a hyperintense signal on T2-weighted images. Other MRI features characteristically seen in patients with tuberculous spinal disease are anterior corner destruction, a relative preservation of the intervertebral disk, and large soft-tissue abscesses with calcifications.³⁴

Prompt diagnosis and aggressive treatment needed

Pigrau et al³⁵ found that spinal osteomyelitis is highly associated with endocarditis: among 606 patients with infectious endocarditis, 28 (4.6%) had pyogenic vertebral osteomyelitis, and among 91 patients with pyogenic vertebral osteomyelitis, 28 (30.8%) had infectious endocarditis.

McHenry et al³⁶ retrospectively studied outcomes of 253 patients with vertebral osteomyelitis after a median of 6.5 years (range 2 days to 38 years): 11% died, more than one-third of survivors had residual disability, and 14% had a relapse. Surgery resulted in recovery or improvement in 86 (79%) of 109 patients. Independent risk factors for adverse outcome (death or incomplete recovery) were neurologic compromise, increased time to diagnosis, and having a hospital-acquired infection (P = .004). Relapse commonly developed in patients with severe vertebral destruction and abscesses, which appeared some time after surgical drainage or debridement. Recurrent bacteremia, paravertebral abscesses, and chronically draining sinuses were independently associated with relapse (P = .001). MRI, done in 110 patients, was often performed late in the course of infection and did not significantly affect outcome. The authors stressed that an optimal outcome of vertebral osteomyelitis requires heightened awareness, early diagnosis, prompt identification of pathogens, reversal of complications, and prolonged antimicrobial therapy.

Epidural abscess may also be present

Epidural abscess occurs in 10% of spine infections. About half of patients with an epidural abscess are misdiagnosed on their initial evaluation.³⁷,³⁸ Patients initially complain of local spine pain, followed by radicular pain, weakness, and finally paralysis. Between 12% and 30% of patients report a history of trauma, even as minor as a fall, preceding the infection.³⁸,³⁹

Radiologic findings are frequently equivocal, and MRI is preferred; gadolinium enhancement further increases sensitivity.³⁹,⁴⁰ Spinal canal abscesses usually appear hypointense on T1-weighted images and hyperintense on T2-weighted images, with ring enhancement surrounding the abscess area in contrast studies.⁴¹ MRI may give negative findings in the early stages of a spinal canal infection and so may need to be repeated.⁴¹ MRI may not help distinguish an epidural from a subdural abscess. However, primary spinal epidural abscesses without concomitant vertebral osteomyelitis are rare; therefore, the finding of associated vertebral osteomyelitis makes a spinal epidural abscess more likely.

FRACTURES

Fractures of the spine can be asymptomatic and may have no preceding trauma. They can be due to osteoporosis, malignancy, infection, or metabolic disorders such as renal osteodystrophy or hyperparathyroidism. Fractures in normal bone are almost always associated with trauma. Any suspicion of infection or malignancy should be investigated.

Corticosteroids increase risk

Any patient with back pain who is receiving corticosteroid therapy should be considered as having a compression fracture until proven otherwise.³ De Vries et al⁴² found that in a database of nearly 200,000 patients receiving glucocorticoids, risk increased substantially with increasing cumulative exposure. Those who intermittently received high doses (= 15 mg/day) and those who had no or little previous exposure to corticosteroids (cumulative exposure = 1 g) had only a slightly increased risk of osteoporotic fracture, and their risk of fracture of the hip and femur was not increased. In contrast, patients who received a daily dose of at least 30 mg and whose cumulative exposure was more than 5 g had a relative risk of osteoporotic vertebral fracture of 14.42 (95% confidence interval 8.29–25.08).

Osteoporotic compression fractures are common in the elderly

Osteoporosis involves reduced bone density, disrupted trabecular architecture, and increased susceptibility to fractures. About 700,000 vertebral body compression fractures occur in the United States each year⁴³: about 10% result in hospitalization, involving an average stay of 8 days.⁴⁴ Osteoporotic compression fractures are highly associated with age older than 65, female sex, and European descent.⁴⁵,⁴⁶ The estimated lifetime risk of a clinically evident vertebral fracture after age 50 years is 16% among postmenopausal white women and 5% among white men.⁴⁷

A single osteoporotic vertebral compression fracture increases the risk of subsequent fractures by a factor of five, and up to 20% of patients with a vertebral compression fracture are likely to have another one within the same year if osteoporosis remains untreated.⁴⁸ Population studies suggest that the death rate among patients who have osteoporotic vertebral compression fractures increases with the number of involved vertebrae.⁴³

Unfortunately, osteoporotic vertebral compression fractures are not always easily amenable to treatment: up to 30% of patients who are symptomatic and seek treatment do not respond adequately to nonsurgical methods.⁴⁹,⁵⁰ However, new minimally invasive interventions such as vertebral augmentation make timely evaluation clinically relevant.

 

 

History, physical examination

Patients may present with a history of trauma with associated back pain or a neurologic deficit. In osteoporotic patients, the trauma may have been minimal, eg, a sneeze, a fall from a chair, or a slip and fall in the home. Pain tends to be worse when standing erect and occasionally when lying flat.

The patient is commonly visibly uncomfortable and may be limited to a wheelchair or stoop forward when standing. The spine may show an absence of the midline crease or an exaggerated thoracic kyphosis. Pain is typically reproduced by deep pressure over the spinous process at the involved level. Compression fractures rarely cause neurologic deficits but should always be considered.

Fractures commonly occur in the thoracolumbar region but may be anywhere in the spine. Fractures in the upper thoracic spine may indicate an underlying malignant tumor, and a thorough search for a possible primary lesion should always be carried out for fractures in this location.

Laboratory testing

Routine laboratory evaluation and thyroid function tests should be done, as well as a 24-hour urine specimen for collagen breakdown products, calcium, phosphate, and creatinine levels. Serum and urine protein electrophoresis should be performed if myeloma is suspected. A white blood-cell count, erythrocyte sedimentation rate, and C-reactive protein level help determine if an underlying infection caused the fracture.

MRI needed if plain films reveal fracture or are equivocal

Anteroposterior and lateral roentgenograms should be taken first; they typically show osteopenia. A fracture in the vertebral body is characterized by loss of height and by wedging. Osseous fragments can occasionally be seen in the spinal canal.

If a fracture is diagnosed or the radiographs are equivocal, MRI of the spine should be done next, since it is probably best for determining fracture age, detecting a malignant tumor (Table 2), and helping select appropriate treatment. Shortly after a vertebral fracture, MRI shows a geographic pattern of low-intensity signal changes on T1-weighted images and high-intensity signal changes on T2-weighted images. As a fracture becomes chronic, a linear area of low-intensity signal change replaces the geographic area on T1-weighted images. As healing continues, the linear pattern is replaced by restoration of fatty marrow.⁵¹

Sagittal short tau inversion recovery sequences, which use specifically timed pulse sequences to suppress fat signals, show high-intensity signal changes in areas of edema from acute or healing fractures. They provide a sensitive but nonspecific marker of abnormality.

Dual energy x-ray absorptiometry helps determine the extent of osteoporosis.

Bone scans should only be used for patients with suspected metastatic disease.

Patients with ankylosing spondylitis need thorough workup

Ankylosing spondylitis predisposes to serious spinal injury. Even after only minor trauma, patients with ankylosing spondylitis and acute, severe back pain should be thoroughly evaluated for fracture with CT and MRI of the entire spine. Plain radiography should not be relied on for these patients because of the risk of misinterpretation, delayed diagnosis, and poorer outcomes.⁵²,⁵³

NEUROLOGIC COMPROMISE—A RED FLAG

Neural compromise can result from spinal cord or cauda equina compression (Table 3). Cauda equina compression usually results from a fracture, tumor, epidural hematoma, or abscess, and occasionally from massive disk herniation. Paraplegia, quadriplegia, or cauda equina deficit should trigger an aggressive search for the cause.⁵⁴

Cauda equina compression classically presents with back pain, bilateral sciatica, saddle anesthesia, and lower extremity weakness progressing to paraplegia, but in practice these symptoms are variably present and diagnosing the condition often requires a high degree of suspicion. Hyporeflexia is typically a sign of cauda equina compression, while hyperreflexia, clonus, and the Babinski sign suggest spinal cord compression, requiring an evaluation of the cervical and thoracic spine. Cauda equina compression typically involves urinary retention; in contrast, cord compression typically causes incontinence.⁵⁵

If either cauda equina or spinal cord compression is detected during an initial examination, an immediate more extensive evaluation is warranted. MRI is the study of choice.

Spinal epidural hematoma

Spinal epidural hematoma is a rare but dramatic cause of paralysis in elderly patients. In most cases, there is no antecedent trauma. Lawton et al,⁵⁶ in a series of 30 patients treated surgically for spinal epidural hematoma, found that 73% resulted from spine surgery, epidural catheterization, or anticoagulation therapy. Other possible causes of epidural hematoma include vascular malformations, angiomas, aneurysms, hypertension, and aspirin therapy.⁵⁷

The same study⁵⁶ found that the time from the first symptom to maximal neurologic deficit ranged from a few minutes to 4 days, with the average interval being nearly 13 hours.

Although painless onset has been reported,⁵⁸ spinal epidural hematoma typically presents with acute pain at the level of the lesion, which is often rapidly followed by paraplegia or quadriplegia, depending on the location of the hemorrhage. Sometimes the onset of pain is preceded by a sudden increase of venous pressure from coughing, sneezing, or straining at stool. Urinary retention often develops at an early stage.

Most lesions occur in the thoracic region and extend into the cervicothoracic or the thoracolumbar area. The pain distribution may be radicular, mimicking a ruptured intervertebral disk.

Evaluation should be with MRI. Acute hemorrhage is characterized by a marked decrease in signal intensity on T2-weighted images. Subacute hematoma has increased signal intensity on both T1- and T2-weighted images.⁵⁶

Early recognition, MRI confirmation, and treatment should be accomplished as soon as possible.⁵⁶ Recovery depends on the severity of the neurologic deficit and the duration of symptoms before treatment. Lawton et al⁵⁶ found that patients taken to surgery within 12 hours had better neurologic outcomes than patients with identical preoperative neurologic status whose surgery was delayed beyond 12 hours. Surgery should not be withheld because of advanced age or poor health: in 10 reported cases in which surgery was delayed, all patients died.⁵⁹

Back pain is one of the most common complaints that internists and primary care physicians encounter.¹ Although back pain is nonspecific, some hallmark signs and symptoms indicate that a patient is more likely to have a serious disorder. This article contrasts the presentation of cancer, infections, and fractures with the more common and benign conditions that cause back pain and provides guidance for diagnosis.

UNCOMMON, BUT MUST BE CONSIDERED

Although a variety of tissues can contribute to pain—intervertebral disks, vertebrae, ligaments, neural structures, muscles, and fascia—and many disorders can damage these tissues, most patients with back or neck pain have a benign condition. Back pain is typically caused by age-related degenerative changes or by minor repetitive trauma; with supportive care and physical therapy, up to 90% of patients with back pain of this nature improve substantially within 4 weeks.²

Serious, destructive diseases are uncommon causes of back pain: malignancy, infection, ankylosing spondylitis, and epidural abscess together account for fewer than 1% of cases of back pain in a typical primary care practice. But their clinical impact is out of proportion to their prevalence. The fear of overlooking a serious condition influences any practitioner’s approach to back pain and is a common reason 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, and appropriate diagnostic studies. Once a serious diagnosis is ruled out, attention can be focused on rehabilitation and back care.

Back pain can also be due to musculoskeletal disorders, peptic ulcers, pancreatitis, pyelonephritis, aortic aneurysms, and other serious conditions, which we have discussed in other articles in this journal.^4–6

SPINAL CANCER AND METASTASES

Since back pain is the presenting symptom in 90% of patients with spinal tumors,⁷ neoplasia belongs in the differential diagnosis of any patient with persistent, unremitting back pain. However, it is also important to recognize atypical presentations of neoplasia, such as a painless neurologic deficit, which should prompt an urgent workup.

The spine is one of the most common sites of metastasis: about 20,000 cases arise each year.⁸ Brihaye et al⁹ reviewed 1,477 cases of spinal metastases with epidural involvement and found that 16.5% arose from primary tumors in the breast, 15.6% from the lung, 9.2% from the prostate, and 6.5% from the kidney.

Cancer pain is persistent and progressive

Pain from spinal cancer is often different from idiopathic back pain or degenerative disk disease (Table 1).

Benign back pain often arises from a known injury, is relieved by rest, and increases with activities that load the disk (eg, sitting, getting up from bed or a chair), lumbar flexion with or without rotation, lifting, vibration (eg, riding in a car), coughing, sneezing, laughing, and the Valsalva maneuver. It is most commonly focal to the lumbosacral junction, the lumbar muscles, and the buttocks. Pain due to injury or a flare-up of degenerative disease typically begins to subside after 4 to 6 weeks and responds to nonsteroidal anti-inflammatory drugs and physical therapy.¹⁰

In contrast, pain caused by spinal neoplasia is typically persistent and progressive and is not alleviated by rest. Often the pain is worse at night, waking the patient from sleep. Back pain is typically focal to the level of the lesion and may be associated with belt-like thoracic pain or radicular symptoms of pain or weakness in the legs. A spinal mass can cause neurologic signs or symptoms by directly compressing the spinal cord or nerve roots, mimicking disk herniation or stenosis.¹¹,¹²

Pathologic fractures resulting from vertebral destruction may be the first—and unfortunately a late—presentation of a tumor.

Ask about, look for, signs and symptoms of cancer

In taking the history, one should ask about possible signs and symptoms of systemic disease such as fatigue, weight loss, and changes in bowel habits. Hemoptysis, lymphadenopathy, subcutaneous or breast masses, nipple discharge, atypical vaginal bleeding, or blood in the stool suggest malignancy and should direct the specific diagnostic approach.¹³ A history of cancer, even if remote, should raise suspicion, as should major risk factors such as smoking.

Because most spinal tumors are metastases, a clinical examination of the breast, lungs, abdomen, thyroid, and prostate are appropriate starting points.¹⁴ The spine should be examined to identify sites of focal pain. A neurologic examination should be done to evaluate any signs of neurologic compromise or abnormal reflexes. Signs or symptoms of spinal cord compression should be investigated immediately.

 

Cancer usually elevates the ESR, CRP

If cancer is suspected, initial tests should include a complete blood cell count, erythrocyte sedimentation rate, C-reactive protein level, urinalysis, prostate-specific antigen level, and fecal occult blood testing. Normal results can considerably relieve suspicion of cancer: the erythrocyte sedimentation rate and C-reactive protein level are almost always elevated with systemic neoplasia.

Other initial tests include a complete blood cell count and chemistry panel. If laboratory studies reveal anemia, hypercalcemia, and elevated levels of alkaline phosphatase, concern should increase. Chest radiography, abdominal computed tomography (CT) (Figure 1), and mammography for women are needed if laboratory results are abnormal. Plain radiographs are the first imaging study of the spine to obtain. Compression fractures, soft tissue calcifications, or focal loss of bone mineralization suggests tumor. Abnormal results on serum and urine protein electrophoresis increase the likelihood of multiple myeloma or plasmacytoma, but normal results do not rule out monoclonal gammopathy of uncertain significance.

Imaging tests

Unfortunately, spinal tumors cannot be well visualized on radiographs until significant destruction has occurred.¹⁵

A bone scan can usually detect tumors other than the purely lytic ones such as myeloma and has a sensitivity of 74%, a specificity of 81%, and a positive predictive value of 64% for vertebral metastasis in patients with back pain.¹⁶

Magnetic resonance imaging (MRI) is the best imaging study for evaluating spinal tumors because it can show the status of the bone marrow and has excellent contrast resolution in soft tissue (Figure 2).¹⁷,¹⁸ It can show vertebral bone marrow infiltration by tumor cells as well as soft tissue masses in and around the spinal column. Bone marrow invaded by a neoplasm is characterized by increased cellularity, resulting in a decreased signal on T1-weighted images and a high signal on T2-weighted images. Intravenous gadolinium further increases the contrast between a tumor and normal tissues and is important for characterizing and grading tumors.¹⁹

INFECTION CAN BE INDOLENT OR ACUTE

Spinal infection is a serious condition that can take an indolent, smoldering course or, alternatively, can erupt into sepsis or rapidly progressive vertebral destruction. Although the latter conditions are hard to miss, early diskitis and osteomyelitis can be difficult to differentiate from idiopathic back pain. In a series of 101 patients with vertebral osteomyelitis, misdiagnosis occurred in 33.7%, and the average delay from the onset of clinical manifestations to diagnosis was 2.6 months.²⁰ Tuberculosis can be even more elusive: in a series of 78 patients diagnosed with definite or probable tuberculous vertebral osteomyelitis, the mean delay to diagnosis was about 6 months.²¹

Acute spinal infections are most often pyogenic; chronic infections may be pyogenic, fungal, or granulomatous.

Vertebral osteomyelitis accounts for 2% to 7% of all cases of osteomyelitis and is an uncommon cause of back pain.²² Any source of infection (eg, dental abscess, pneumonia) can seed the spine; urinary tract infection is the most common. Patients with immunocompromise or diabetes are most at risk.²³ The onset is usually insidious with focal back pain at the level of involvement.

History and physical examination reveal localized pain

Spinal infections typically cause pain that is worsened with weight-bearing and activity and is relieved only when lying down. Chronic infection is usually associated with weight loss, fatigue, fevers, and night sweats.

Pain is usually well localized and reproduced by palpation or percussion over the involved level. Severe pain can sometimes be elicited by sitting the patient up or by changing the patient’s position. Focal kyphosis may be detectable if the vertebra has collapsed.

In a series of 41 patients with pyogenic infectious spondylitis, 90% had localized back pain aggravated by percussion, 59% had radicular signs and symptoms, and 29% had neurologic signs of spinal cord compression, including hyperreflexia, clonus, the Babinski sign (extension of the toes upward when the sole of the foot is stroked upwards), or the Hoffmann sign (flexion of the thumb elicited by flicking the end of a middle finger).²⁴

LABORATORY RESULTS TYPICALLY INDICATE INFECTION

The erythrocyte sedimentation rate is the most sensitive test for infection, and an elevated rate may be the only abnormal laboratory finding: Digby and Kersley²⁵ found that the rate was increased in all of 30 patients with nontuberculous pyogenic osteomyelitis of the spine. The C-reactive protein level is also usually elevated, but 40% of patients have a normal white blood cell count.²⁵ Results of other laboratory tests are typically in the normal range. Tuberculin skin testing should be done for patients at high risk of the disease (eg, immigrants from areas of endemic disease, non-Hispanic blacks, immunocompromised patients, and those with known exposure to tuberculosis). Patients with high fever, chills, or rigors should have cultures taken of blood, 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 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 neoplastic disease from vertebral osteomyelitis²⁹ 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 within the vertebral body, loss of definition of end plates (which appear hypointense compared with the bone marrow), and destruction of the cortical margins of the involved vertebral bodies. T2-weighted MRI typically discloses high signals of the affected areas of the vertebral body and disk. Contrast should be used to increase specificity; enhancement may be the first sign of an acute inflammatory process.³¹

CT and MRI can help identify sequestra, perilesional sclerosis, and epidural or soft tissue abscesses. Guided biopsy may be needed to differentiate between abscess, hematoma, tumor, and inflammation.

 

 

MRI findings: Pyogenic vs tuberculous spondylitis

MRI can help differentiate pyogenic vertebral osteomyelitis from tubercular disease, although findings may be similar (eg, both conditions have a high signal on T2-weighted images).³² Jung et al,³³ in a retrospective study of 52 patients with spondylitis, found that compared with patients with pyogenic infections, patients with tuberculous spondylitis had a significantly higher incidence of a well-defined paraspinal abnormal signal on MRI, a thin and smooth abscess wall, a paraspinal or intraosseous abscess, subligamentous spread to three or more vertebral levels, involvement of multiple vertebral bodies, thoracic spine involvement, and a hyperintense signal on T2-weighted images. Other MRI features characteristically seen in patients with tuberculous spinal disease are anterior corner destruction, a relative preservation of the intervertebral disk, and large soft-tissue abscesses with calcifications.³⁴

Prompt diagnosis and aggressive treatment needed

Pigrau et al³⁵ found that spinal osteomyelitis is highly associated with endocarditis: among 606 patients with infectious endocarditis, 28 (4.6%) had pyogenic vertebral osteomyelitis, and among 91 patients with pyogenic vertebral osteomyelitis, 28 (30.8%) had infectious endocarditis.

McHenry et al³⁶ retrospectively studied outcomes of 253 patients with vertebral osteomyelitis after a median of 6.5 years (range 2 days to 38 years): 11% died, more than one-third of survivors had residual disability, and 14% had a relapse. Surgery resulted in recovery or improvement in 86 (79%) of 109 patients. Independent risk factors for adverse outcome (death or incomplete recovery) were neurologic compromise, increased time to diagnosis, and having a hospital-acquired infection (P = .004). Relapse commonly developed in patients with severe vertebral destruction and abscesses, which appeared some time after surgical drainage or debridement. Recurrent bacteremia, paravertebral abscesses, and chronically draining sinuses were independently associated with relapse (P = .001). MRI, done in 110 patients, was often performed late in the course of infection and did not significantly affect outcome. The authors stressed that an optimal outcome of vertebral osteomyelitis requires heightened awareness, early diagnosis, prompt identification of pathogens, reversal of complications, and prolonged antimicrobial therapy.

Epidural abscess may also be present

Epidural abscess occurs in 10% of spine infections. About half of patients with an epidural abscess are misdiagnosed on their initial evaluation.³⁷,³⁸ Patients initially complain of local spine pain, followed by radicular pain, weakness, and finally paralysis. Between 12% and 30% of patients report a history of trauma, even as minor as a fall, preceding the infection.³⁸,³⁹

Radiologic findings are frequently equivocal, and MRI is preferred; gadolinium enhancement further increases sensitivity.³⁹,⁴⁰ Spinal canal abscesses usually appear hypointense on T1-weighted images and hyperintense on T2-weighted images, with ring enhancement surrounding the abscess area in contrast studies.⁴¹ MRI may give negative findings in the early stages of a spinal canal infection and so may need to be repeated.⁴¹ MRI may not help distinguish an epidural from a subdural abscess. However, primary spinal epidural abscesses without concomitant vertebral osteomyelitis are rare; therefore, the finding of associated vertebral osteomyelitis makes a spinal epidural abscess more likely.

FRACTURES

Fractures of the spine can be asymptomatic and may have no preceding trauma. They can be due to osteoporosis, malignancy, infection, or metabolic disorders such as renal osteodystrophy or hyperparathyroidism. Fractures in normal bone are almost always associated with trauma. Any suspicion of infection or malignancy should be investigated.

Corticosteroids increase risk

Any patient with back pain who is receiving corticosteroid therapy should be considered as having a compression fracture until proven otherwise.³ De Vries et al⁴² found that in a database of nearly 200,000 patients receiving glucocorticoids, risk increased substantially with increasing cumulative exposure. Those who intermittently received high doses (= 15 mg/day) and those who had no or little previous exposure to corticosteroids (cumulative exposure = 1 g) had only a slightly increased risk of osteoporotic fracture, and their risk of fracture of the hip and femur was not increased. In contrast, patients who received a daily dose of at least 30 mg and whose cumulative exposure was more than 5 g had a relative risk of osteoporotic vertebral fracture of 14.42 (95% confidence interval 8.29–25.08).

Osteoporotic compression fractures are common in the elderly

Osteoporosis involves reduced bone density, disrupted trabecular architecture, and increased susceptibility to fractures. About 700,000 vertebral body compression fractures occur in the United States each year⁴³: about 10% result in hospitalization, involving an average stay of 8 days.⁴⁴ Osteoporotic compression fractures are highly associated with age older than 65, female sex, and European descent.⁴⁵,⁴⁶ The estimated lifetime risk of a clinically evident vertebral fracture after age 50 years is 16% among postmenopausal white women and 5% among white men.⁴⁷

A single osteoporotic vertebral compression fracture increases the risk of subsequent fractures by a factor of five, and up to 20% of patients with a vertebral compression fracture are likely to have another one within the same year if osteoporosis remains untreated.⁴⁸ Population studies suggest that the death rate among patients who have osteoporotic vertebral compression fractures increases with the number of involved vertebrae.⁴³

Unfortunately, osteoporotic vertebral compression fractures are not always easily amenable to treatment: up to 30% of patients who are symptomatic and seek treatment do not respond adequately to nonsurgical methods.⁴⁹,⁵⁰ However, new minimally invasive interventions such as vertebral augmentation make timely evaluation clinically relevant.

 

 

History, physical examination

Patients may present with a history of trauma with associated back pain or a neurologic deficit. In osteoporotic patients, the trauma may have been minimal, eg, a sneeze, a fall from a chair, or a slip and fall in the home. Pain tends to be worse when standing erect and occasionally when lying flat.

The patient is commonly visibly uncomfortable and may be limited to a wheelchair or stoop forward when standing. The spine may show an absence of the midline crease or an exaggerated thoracic kyphosis. Pain is typically reproduced by deep pressure over the spinous process at the involved level. Compression fractures rarely cause neurologic deficits but should always be considered.

Fractures commonly occur in the thoracolumbar region but may be anywhere in the spine. Fractures in the upper thoracic spine may indicate an underlying malignant tumor, and a thorough search for a possible primary lesion should always be carried out for fractures in this location.

Laboratory testing

Routine laboratory evaluation and thyroid function tests should be done, as well as a 24-hour urine specimen for collagen breakdown products, calcium, phosphate, and creatinine levels. Serum and urine protein electrophoresis should be performed if myeloma is suspected. A white blood-cell count, erythrocyte sedimentation rate, and C-reactive protein level help determine if an underlying infection caused the fracture.

MRI needed if plain films reveal fracture or are equivocal

Anteroposterior and lateral roentgenograms should be taken first; they typically show osteopenia. A fracture in the vertebral body is characterized by loss of height and by wedging. Osseous fragments can occasionally be seen in the spinal canal.

If a fracture is diagnosed or the radiographs are equivocal, MRI of the spine should be done next, since it is probably best for determining fracture age, detecting a malignant tumor (Table 2), and helping select appropriate treatment. Shortly after a vertebral fracture, MRI shows a geographic pattern of low-intensity signal changes on T1-weighted images and high-intensity signal changes on T2-weighted images. As a fracture becomes chronic, a linear area of low-intensity signal change replaces the geographic area on T1-weighted images. As healing continues, the linear pattern is replaced by restoration of fatty marrow.⁵¹

Sagittal short tau inversion recovery sequences, which use specifically timed pulse sequences to suppress fat signals, show high-intensity signal changes in areas of edema from acute or healing fractures. They provide a sensitive but nonspecific marker of abnormality.

Dual energy x-ray absorptiometry helps determine the extent of osteoporosis.

Bone scans should only be used for patients with suspected metastatic disease.

Patients with ankylosing spondylitis need thorough workup

Ankylosing spondylitis predisposes to serious spinal injury. Even after only minor trauma, patients with ankylosing spondylitis and acute, severe back pain should be thoroughly evaluated for fracture with CT and MRI of the entire spine. Plain radiography should not be relied on for these patients because of the risk of misinterpretation, delayed diagnosis, and poorer outcomes.⁵²,⁵³

NEUROLOGIC COMPROMISE—A RED FLAG

Neural compromise can result from spinal cord or cauda equina compression (Table 3). Cauda equina compression usually results from a fracture, tumor, epidural hematoma, or abscess, and occasionally from massive disk herniation. Paraplegia, quadriplegia, or cauda equina deficit should trigger an aggressive search for the cause.⁵⁴

Cauda equina compression classically presents with back pain, bilateral sciatica, saddle anesthesia, and lower extremity weakness progressing to paraplegia, but in practice these symptoms are variably present and diagnosing the condition often requires a high degree of suspicion. Hyporeflexia is typically a sign of cauda equina compression, while hyperreflexia, clonus, and the Babinski sign suggest spinal cord compression, requiring an evaluation of the cervical and thoracic spine. Cauda equina compression typically involves urinary retention; in contrast, cord compression typically causes incontinence.⁵⁵

If either cauda equina or spinal cord compression is detected during an initial examination, an immediate more extensive evaluation is warranted. MRI is the study of choice.

Spinal epidural hematoma

Spinal epidural hematoma is a rare but dramatic cause of paralysis in elderly patients. In most cases, there is no antecedent trauma. Lawton et al,⁵⁶ in a series of 30 patients treated surgically for spinal epidural hematoma, found that 73% resulted from spine surgery, epidural catheterization, or anticoagulation therapy. Other possible causes of epidural hematoma include vascular malformations, angiomas, aneurysms, hypertension, and aspirin therapy.⁵⁷

The same study⁵⁶ found that the time from the first symptom to maximal neurologic deficit ranged from a few minutes to 4 days, with the average interval being nearly 13 hours.

Although painless onset has been reported,⁵⁸ spinal epidural hematoma typically presents with acute pain at the level of the lesion, which is often rapidly followed by paraplegia or quadriplegia, depending on the location of the hemorrhage. Sometimes the onset of pain is preceded by a sudden increase of venous pressure from coughing, sneezing, or straining at stool. Urinary retention often develops at an early stage.

Most lesions occur in the thoracic region and extend into the cervicothoracic or the thoracolumbar area. The pain distribution may be radicular, mimicking a ruptured intervertebral disk.

Evaluation should be with MRI. Acute hemorrhage is characterized by a marked decrease in signal intensity on T2-weighted images. Subacute hematoma has increased signal intensity on both T1- and T2-weighted images.⁵⁶

Early recognition, MRI confirmation, and treatment should be accomplished as soon as possible.⁵⁶ Recovery depends on the severity of the neurologic deficit and the duration of symptoms before treatment. Lawton et al⁵⁶ found that patients taken to surgery within 12 hours had better neurologic outcomes than patients with identical preoperative neurologic status whose surgery was delayed beyond 12 hours. Surgery should not be withheld because of advanced age or poor health: in 10 reported cases in which surgery was delayed, all patients died.⁵⁹

CHICAGO — A selective adenosine receptor agonist was as effective as conventional adenosine for cardiac stress imaging and produced fewer adverse events in results from two pivotal, controlled trials with a total of about 800 patients.

Treating patients with binodenoson “provides similar clinical information on the extent and severity of ischemia as adenosine and is associated with a significant reduction in the incidence and intensity of many side effects,” Dr. James E. Udelson said at the annual meeting of the American College of Cardiology. A major feature of the improved safety profile was that treatment with binodenoson led to no episodes of second- or third-degree atrioventricular block in about 800 treated patients, compared with about a 2% rate of this complication when the same patients were treated with adenosine, reported Dr. Udelson, professor and acting chief of cardiology at Tufts Medical Center in Boston.

Binodenoson is being developed as CorVue by King Pharmaceuticals Inc. Dr. Udelson said that he received research grants and consulting honoraria from the company, as did several of his collaborators.

Results from the two studies reported by Dr. Udelson showed that the diagnostic accuracy of stress perfusion imaging with single-photon emission CT was comparable in binodenoson- and adenosine-treated patients, with binodenoson causing fewer adverse events and having easier, bolus dosing, commented Dr. Jagat Narula, professor and chief of cardiology at the University of California, Irvine. “It will all boil down to dollars. If we can reduce or contain the cost then [binodenoson] will become the preferred agent,” he said.

Dr. Udelson reported data from two separate arms of the Vasodilator Induced Stress in Concordance with Adenosine (VISION) study, conducted at 79 U.S. centers. Both studies enrolled patients aged 30 years or older who were scheduled to undergo pharmacologic stress imaging of their hearts because of typical or atypical angina and suspected ischemia. The study excluded patients with a very low pretest likelihood of disease, a contraindication for adenosine, or severe left-ventricular dysfunction. The two studies enrolled a total of 842 patients, with an average age of 63 years and an average BMI of 31 kg/m

In both studies, patients were randomized to initial imaging with either binodenoson or adenosine and also received a placebo dose in place of the other agent. Imaging was repeated 2–7 days later with the same protocol, but the active and placebo agents were reversed. Binodenoson (and its matched placebo) was administered at a dose of 1.5 mcg/kg as a bolus injection that lasted 30 seconds; adenosine (and its matching placebo) was given at a dose of 140 mcg/kg per minute administered as an intravenous infusion for 6 minutes. The imaging aspect of the study was done identically both times each patient was tested.

Efficacy was assessed by comparing the extent of myocardial ischemia diagnosed by blinded readers using the two stress methods. The study's prespecified criteria said that the two stress agents would be considered identical in performance if the average summed difference in stress ischemia between the two methods was less than 1.5 U, and if fewer than 10% of all tested patients had highly discordant findings.

The average summed difference in stress scores was 0.09 in one study and 0.68 in the other, which meant that the results from both trials fulfilled the criterion that the average difference between the summed stress scores was less than 1.5.

The safety analysis showed that binodenoson consistently produced fewer adverse events in both studies. In addition to causing no episodes of atrioventricular block, treatment with binodenoson was associated with significantly fewer and less intense episodes of flushing, chest pain, and dyspnea, Dr. Udelson said.

Document

70257_fx1.sml

Binodenoson provides similar clinical information to adenosine, with a significant reduction in many side effects. DR. UDELSON

CHICAGO — A selective adenosine receptor agonist was as effective as conventional adenosine for cardiac stress imaging and produced fewer adverse events in results from two pivotal, controlled trials with a total of about 800 patients.

Treating patients with binodenoson “provides similar clinical information on the extent and severity of ischemia as adenosine and is associated with a significant reduction in the incidence and intensity of many side effects,” Dr. James E. Udelson said at the annual meeting of the American College of Cardiology. A major feature of the improved safety profile was that treatment with binodenoson led to no episodes of second- or third-degree atrioventricular block in about 800 treated patients, compared with about a 2% rate of this complication when the same patients were treated with adenosine, reported Dr. Udelson, professor and acting chief of cardiology at Tufts Medical Center in Boston.

Binodenoson is being developed as CorVue by King Pharmaceuticals Inc. Dr. Udelson said that he received research grants and consulting honoraria from the company, as did several of his collaborators.

Results from the two studies reported by Dr. Udelson showed that the diagnostic accuracy of stress perfusion imaging with single-photon emission CT was comparable in binodenoson- and adenosine-treated patients, with binodenoson causing fewer adverse events and having easier, bolus dosing, commented Dr. Jagat Narula, professor and chief of cardiology at the University of California, Irvine. “It will all boil down to dollars. If we can reduce or contain the cost then [binodenoson] will become the preferred agent,” he said.

Dr. Udelson reported data from two separate arms of the Vasodilator Induced Stress in Concordance with Adenosine (VISION) study, conducted at 79 U.S. centers. Both studies enrolled patients aged 30 years or older who were scheduled to undergo pharmacologic stress imaging of their hearts because of typical or atypical angina and suspected ischemia. The study excluded patients with a very low pretest likelihood of disease, a contraindication for adenosine, or severe left-ventricular dysfunction. The two studies enrolled a total of 842 patients, with an average age of 63 years and an average BMI of 31 kg/m

In both studies, patients were randomized to initial imaging with either binodenoson or adenosine and also received a placebo dose in place of the other agent. Imaging was repeated 2–7 days later with the same protocol, but the active and placebo agents were reversed. Binodenoson (and its matched placebo) was administered at a dose of 1.5 mcg/kg as a bolus injection that lasted 30 seconds; adenosine (and its matching placebo) was given at a dose of 140 mcg/kg per minute administered as an intravenous infusion for 6 minutes. The imaging aspect of the study was done identically both times each patient was tested.

Efficacy was assessed by comparing the extent of myocardial ischemia diagnosed by blinded readers using the two stress methods. The study's prespecified criteria said that the two stress agents would be considered identical in performance if the average summed difference in stress ischemia between the two methods was less than 1.5 U, and if fewer than 10% of all tested patients had highly discordant findings.

The average summed difference in stress scores was 0.09 in one study and 0.68 in the other, which meant that the results from both trials fulfilled the criterion that the average difference between the summed stress scores was less than 1.5.

The safety analysis showed that binodenoson consistently produced fewer adverse events in both studies. In addition to causing no episodes of atrioventricular block, treatment with binodenoson was associated with significantly fewer and less intense episodes of flushing, chest pain, and dyspnea, Dr. Udelson said.

Document

70257_fx1.sml

Binodenoson provides similar clinical information to adenosine, with a significant reduction in many side effects. DR. UDELSON

CHICAGO — A selective adenosine receptor agonist was as effective as conventional adenosine for cardiac stress imaging and produced fewer adverse events in results from two pivotal, controlled trials with a total of about 800 patients.

Treating patients with binodenoson “provides similar clinical information on the extent and severity of ischemia as adenosine and is associated with a significant reduction in the incidence and intensity of many side effects,” Dr. James E. Udelson said at the annual meeting of the American College of Cardiology. A major feature of the improved safety profile was that treatment with binodenoson led to no episodes of second- or third-degree atrioventricular block in about 800 treated patients, compared with about a 2% rate of this complication when the same patients were treated with adenosine, reported Dr. Udelson, professor and acting chief of cardiology at Tufts Medical Center in Boston.

Binodenoson is being developed as CorVue by King Pharmaceuticals Inc. Dr. Udelson said that he received research grants and consulting honoraria from the company, as did several of his collaborators.

Results from the two studies reported by Dr. Udelson showed that the diagnostic accuracy of stress perfusion imaging with single-photon emission CT was comparable in binodenoson- and adenosine-treated patients, with binodenoson causing fewer adverse events and having easier, bolus dosing, commented Dr. Jagat Narula, professor and chief of cardiology at the University of California, Irvine. “It will all boil down to dollars. If we can reduce or contain the cost then [binodenoson] will become the preferred agent,” he said.

Dr. Udelson reported data from two separate arms of the Vasodilator Induced Stress in Concordance with Adenosine (VISION) study, conducted at 79 U.S. centers. Both studies enrolled patients aged 30 years or older who were scheduled to undergo pharmacologic stress imaging of their hearts because of typical or atypical angina and suspected ischemia. The study excluded patients with a very low pretest likelihood of disease, a contraindication for adenosine, or severe left-ventricular dysfunction. The two studies enrolled a total of 842 patients, with an average age of 63 years and an average BMI of 31 kg/m

In both studies, patients were randomized to initial imaging with either binodenoson or adenosine and also received a placebo dose in place of the other agent. Imaging was repeated 2–7 days later with the same protocol, but the active and placebo agents were reversed. Binodenoson (and its matched placebo) was administered at a dose of 1.5 mcg/kg as a bolus injection that lasted 30 seconds; adenosine (and its matching placebo) was given at a dose of 140 mcg/kg per minute administered as an intravenous infusion for 6 minutes. The imaging aspect of the study was done identically both times each patient was tested.

Efficacy was assessed by comparing the extent of myocardial ischemia diagnosed by blinded readers using the two stress methods. The study's prespecified criteria said that the two stress agents would be considered identical in performance if the average summed difference in stress ischemia between the two methods was less than 1.5 U, and if fewer than 10% of all tested patients had highly discordant findings.

The average summed difference in stress scores was 0.09 in one study and 0.68 in the other, which meant that the results from both trials fulfilled the criterion that the average difference between the summed stress scores was less than 1.5.

The safety analysis showed that binodenoson consistently produced fewer adverse events in both studies. In addition to causing no episodes of atrioventricular block, treatment with binodenoson was associated with significantly fewer and less intense episodes of flushing, chest pain, and dyspnea, Dr. Udelson said.

Document

70257_fx1.sml

Binodenoson provides similar clinical information to adenosine, with a significant reduction in many side effects. DR. UDELSON

The presence of infection at the time of magnetic resonance imaging using gadolinium contrast may predispose patients with renal failure to nephrogenic systemic fibrosis, according to a hospital analysis.

The estimated NSF development rate for infected patients with renal failure was 6.7%, compared with 0.3% for uninfected patients with renal failure—a 33-fold difference that was highly significant.

“If the presence of infection indeed proves to be a risk factor for the development of NSF, then some renal failure patients presently judged to be acceptable risks for MR contrast administration on the basis of the degree of renal failure might be reconsidered as high-risk patients,” wrote Dr. Lauren Goldberg of Moses H. Cone Memorial Hospital, Greensboro, N.C., and Dr. James Provenzale, a radiologist at Duke University, Durham, N.C. (Am. J. Roentgenol. 2008;190:1069–75).

Eight patients with symptoms consistent with NSF between 2002 and 2006 were prospectively identified by the nephrology group. Seven biopsy-proven cases were identified, along with another case involving strong clinical signs and symptoms of NSF without biopsy confirmation.

Seven patients had MRI contrast with gadodiamide (Omniscan, GE Healthcare), at a dose from 0.1 mmol/kg to 0.3 mmol/kg. NSF symptoms began 2 days to 5 months after contrast administration. The sole patient not exposed to gadolinium contrast had end-stage renal disease, breast carcinoma, and calciphylaxis.

All eight patients with NSF noted stiffening and thickening of the hands and lower extremities—often described as woody changes of the skin. Five patients had severe chronic pain, the authors reported.

No single medication was common to all patients with NSF. None had vascular thrombosis. Only one patient had undergone major surgery. Five of the patients had documented infection, including catheter infection, urinary tract infection, bacteremia, pneumonia, cellulitis, and osteomyelitis. Two patients who received gadolinium contrast did not have proinflammatory conditions. The one patient who did not receive gadolinium contrast was also considered not to have a proinflammatory condition.

The researchers estimated that 750 renal-failure patients without documented infection and 75 renal-failure patients with documented infection underwent contrast-enhanced MRI between 2002 and 2006.

“All six patients who were hemodialysis dependent at the time of contrast-enhanced MRI were dialyzed 1 day after gadodiamide administration, suggesting that prompt hemodialysis may not be protective against the development of NSF,” the authors wrote.

The investigators disclosed no conflicts of interest.

The presence of infection at the time of magnetic resonance imaging using gadolinium contrast may predispose patients with renal failure to nephrogenic systemic fibrosis, according to a hospital analysis.

The estimated NSF development rate for infected patients with renal failure was 6.7%, compared with 0.3% for uninfected patients with renal failure—a 33-fold difference that was highly significant.

“If the presence of infection indeed proves to be a risk factor for the development of NSF, then some renal failure patients presently judged to be acceptable risks for MR contrast administration on the basis of the degree of renal failure might be reconsidered as high-risk patients,” wrote Dr. Lauren Goldberg of Moses H. Cone Memorial Hospital, Greensboro, N.C., and Dr. James Provenzale, a radiologist at Duke University, Durham, N.C. (Am. J. Roentgenol. 2008;190:1069–75).

Eight patients with symptoms consistent with NSF between 2002 and 2006 were prospectively identified by the nephrology group. Seven biopsy-proven cases were identified, along with another case involving strong clinical signs and symptoms of NSF without biopsy confirmation.

Seven patients had MRI contrast with gadodiamide (Omniscan, GE Healthcare), at a dose from 0.1 mmol/kg to 0.3 mmol/kg. NSF symptoms began 2 days to 5 months after contrast administration. The sole patient not exposed to gadolinium contrast had end-stage renal disease, breast carcinoma, and calciphylaxis.

All eight patients with NSF noted stiffening and thickening of the hands and lower extremities—often described as woody changes of the skin. Five patients had severe chronic pain, the authors reported.

No single medication was common to all patients with NSF. None had vascular thrombosis. Only one patient had undergone major surgery. Five of the patients had documented infection, including catheter infection, urinary tract infection, bacteremia, pneumonia, cellulitis, and osteomyelitis. Two patients who received gadolinium contrast did not have proinflammatory conditions. The one patient who did not receive gadolinium contrast was also considered not to have a proinflammatory condition.

The researchers estimated that 750 renal-failure patients without documented infection and 75 renal-failure patients with documented infection underwent contrast-enhanced MRI between 2002 and 2006.

“All six patients who were hemodialysis dependent at the time of contrast-enhanced MRI were dialyzed 1 day after gadodiamide administration, suggesting that prompt hemodialysis may not be protective against the development of NSF,” the authors wrote.

The investigators disclosed no conflicts of interest.

The presence of infection at the time of magnetic resonance imaging using gadolinium contrast may predispose patients with renal failure to nephrogenic systemic fibrosis, according to a hospital analysis.

The estimated NSF development rate for infected patients with renal failure was 6.7%, compared with 0.3% for uninfected patients with renal failure—a 33-fold difference that was highly significant.

“If the presence of infection indeed proves to be a risk factor for the development of NSF, then some renal failure patients presently judged to be acceptable risks for MR contrast administration on the basis of the degree of renal failure might be reconsidered as high-risk patients,” wrote Dr. Lauren Goldberg of Moses H. Cone Memorial Hospital, Greensboro, N.C., and Dr. James Provenzale, a radiologist at Duke University, Durham, N.C. (Am. J. Roentgenol. 2008;190:1069–75).

Eight patients with symptoms consistent with NSF between 2002 and 2006 were prospectively identified by the nephrology group. Seven biopsy-proven cases were identified, along with another case involving strong clinical signs and symptoms of NSF without biopsy confirmation.

Seven patients had MRI contrast with gadodiamide (Omniscan, GE Healthcare), at a dose from 0.1 mmol/kg to 0.3 mmol/kg. NSF symptoms began 2 days to 5 months after contrast administration. The sole patient not exposed to gadolinium contrast had end-stage renal disease, breast carcinoma, and calciphylaxis.

All eight patients with NSF noted stiffening and thickening of the hands and lower extremities—often described as woody changes of the skin. Five patients had severe chronic pain, the authors reported.

No single medication was common to all patients with NSF. None had vascular thrombosis. Only one patient had undergone major surgery. Five of the patients had documented infection, including catheter infection, urinary tract infection, bacteremia, pneumonia, cellulitis, and osteomyelitis. Two patients who received gadolinium contrast did not have proinflammatory conditions. The one patient who did not receive gadolinium contrast was also considered not to have a proinflammatory condition.

The researchers estimated that 750 renal-failure patients without documented infection and 75 renal-failure patients with documented infection underwent contrast-enhanced MRI between 2002 and 2006.

“All six patients who were hemodialysis dependent at the time of contrast-enhanced MRI were dialyzed 1 day after gadodiamide administration, suggesting that prompt hemodialysis may not be protective against the development of NSF,” the authors wrote.

The investigators disclosed no conflicts of interest.

SAN DIEGO — Postendovascular aneurysm repair surveillance, with color flow duplex ultrasound only, is a safe alternative to the current standard practice of follow-up CT with contrast, results from a single-center study showed.

After endovascular aneurysm repair (EVAR), “CT follow-up is associated with significant risk, including increased cost, contrast nephropathy, contrast allergy, and radiation exposure,” Dr. Rabih A. Chaer said at the Vascular Annual Meeting. “Alternative follow-up methods have been proposed, including color flow duplex ultrasound, MRI, and contrast-enhanced ultrasound. Of all these modalities, it's clear that simple color flow duplex ultrasound is the most readily available, the cheapest, and the least invasive.”

He and his associates in the division of vascular surgery at the University of Pittsburgh Medical Center studied 184 patients who were switched to color flow duplex ultrasound (CDU) surveillance in 2003 as an alternative to CT. Selective CT scanning was used only for new endoleaks or for patients who presented with an enlarging abdominal aortic aneurysm (AAA) sac. Only patients with at least 1 year of follow-up were included.

Criteria for switch to CDU included patients with a residual AAA sac of 4 cm or less anytime after the first year of follow-up, patients with a stable AAA sac size for 2 years, or patients with a stable type II endoleak for 2 years. The average CDU study duration was 20 minutes. The researchers used a GE Logiq 9 machine with a 3.5-MHz curve probe.

Of the 184 patients, 13 had an active stable type II endoleak, 23 had a prior endoleak that was treated or that resolved spontaneously. The mean follow-up on CDU was 24 months. Of the 184 grafts, 76 were Ancure, 58 were Zenith, 39 were Excluder, 7 were AneuRx, and 4 were Lifepath.

Dr. Chaer reported that there were three new endoleaks detected on CDU follow-up, all in patients who received an Ancure graft. Only one patient presented with sac enlargement. “One type II endoleak was detected, but this spontaneously resolved at 3 months,” he said. “There were two distal type I endoleaks that were treated with limb extension.”

CDU identified two patients (one with an Ancure and one with an AneruRx graft) who had an increase in their AAA sac size, yet no endoleak was detected. No endoleak was seen on CT scan, but when both patients underwent angiograms, a distal type I endoleak was detected in one patient.

There were no ruptures or graft occlusions observed during the follow-up period. Eight patients died. One was an aneurysm-related death following an Ancure explantation for infection that occurred 4 years post EVAR; two were related to malignancy, and five were related to acute myocardial infarctions.

The cumulative freedom from secondary intervention after the switch to CDU was 98% at 4 years.

In order to determine the applicability of the switch criteria for a full cohort of EVAR patients, the researchers examined 196 consecutive EVAR patients in 2004. Of these, 86 (44%) had been switched to CDU surveillance, whereas the remaining 110 were still followed with CT scan. At the 6-month follow-up, only 1.5% of patients followed with CT scan met the current criteria for the switch to CDU-only surveillance. But the proportion at 1, 2, and 3 years was 55%, 86%, and 97%, respectively.

“CDU-only surveillance is safe and can be initiated early after treatment on patients with a shrinking or a stable AAA sac,” he concluded. “Most patients treated with EVAR are eligible for this modality. After the 1 year follow-up, we do recommend that CT scanning should only be selectively utilized in patients treated with EVAR. This policy should result in cost-saving advantages and avoid the complications associated with CT.”

Dr. Chaer disclosed he had no relevant conflicts.

SAN DIEGO — Postendovascular aneurysm repair surveillance, with color flow duplex ultrasound only, is a safe alternative to the current standard practice of follow-up CT with contrast, results from a single-center study showed.

After endovascular aneurysm repair (EVAR), “CT follow-up is associated with significant risk, including increased cost, contrast nephropathy, contrast allergy, and radiation exposure,” Dr. Rabih A. Chaer said at the Vascular Annual Meeting. “Alternative follow-up methods have been proposed, including color flow duplex ultrasound, MRI, and contrast-enhanced ultrasound. Of all these modalities, it's clear that simple color flow duplex ultrasound is the most readily available, the cheapest, and the least invasive.”

He and his associates in the division of vascular surgery at the University of Pittsburgh Medical Center studied 184 patients who were switched to color flow duplex ultrasound (CDU) surveillance in 2003 as an alternative to CT. Selective CT scanning was used only for new endoleaks or for patients who presented with an enlarging abdominal aortic aneurysm (AAA) sac. Only patients with at least 1 year of follow-up were included.

Criteria for switch to CDU included patients with a residual AAA sac of 4 cm or less anytime after the first year of follow-up, patients with a stable AAA sac size for 2 years, or patients with a stable type II endoleak for 2 years. The average CDU study duration was 20 minutes. The researchers used a GE Logiq 9 machine with a 3.5-MHz curve probe.

Of the 184 patients, 13 had an active stable type II endoleak, 23 had a prior endoleak that was treated or that resolved spontaneously. The mean follow-up on CDU was 24 months. Of the 184 grafts, 76 were Ancure, 58 were Zenith, 39 were Excluder, 7 were AneuRx, and 4 were Lifepath.

Dr. Chaer reported that there were three new endoleaks detected on CDU follow-up, all in patients who received an Ancure graft. Only one patient presented with sac enlargement. “One type II endoleak was detected, but this spontaneously resolved at 3 months,” he said. “There were two distal type I endoleaks that were treated with limb extension.”

CDU identified two patients (one with an Ancure and one with an AneruRx graft) who had an increase in their AAA sac size, yet no endoleak was detected. No endoleak was seen on CT scan, but when both patients underwent angiograms, a distal type I endoleak was detected in one patient.

There were no ruptures or graft occlusions observed during the follow-up period. Eight patients died. One was an aneurysm-related death following an Ancure explantation for infection that occurred 4 years post EVAR; two were related to malignancy, and five were related to acute myocardial infarctions.

The cumulative freedom from secondary intervention after the switch to CDU was 98% at 4 years.

In order to determine the applicability of the switch criteria for a full cohort of EVAR patients, the researchers examined 196 consecutive EVAR patients in 2004. Of these, 86 (44%) had been switched to CDU surveillance, whereas the remaining 110 were still followed with CT scan. At the 6-month follow-up, only 1.5% of patients followed with CT scan met the current criteria for the switch to CDU-only surveillance. But the proportion at 1, 2, and 3 years was 55%, 86%, and 97%, respectively.

“CDU-only surveillance is safe and can be initiated early after treatment on patients with a shrinking or a stable AAA sac,” he concluded. “Most patients treated with EVAR are eligible for this modality. After the 1 year follow-up, we do recommend that CT scanning should only be selectively utilized in patients treated with EVAR. This policy should result in cost-saving advantages and avoid the complications associated with CT.”

Dr. Chaer disclosed he had no relevant conflicts.

SAN DIEGO — Postendovascular aneurysm repair surveillance, with color flow duplex ultrasound only, is a safe alternative to the current standard practice of follow-up CT with contrast, results from a single-center study showed.

After endovascular aneurysm repair (EVAR), “CT follow-up is associated with significant risk, including increased cost, contrast nephropathy, contrast allergy, and radiation exposure,” Dr. Rabih A. Chaer said at the Vascular Annual Meeting. “Alternative follow-up methods have been proposed, including color flow duplex ultrasound, MRI, and contrast-enhanced ultrasound. Of all these modalities, it's clear that simple color flow duplex ultrasound is the most readily available, the cheapest, and the least invasive.”

He and his associates in the division of vascular surgery at the University of Pittsburgh Medical Center studied 184 patients who were switched to color flow duplex ultrasound (CDU) surveillance in 2003 as an alternative to CT. Selective CT scanning was used only for new endoleaks or for patients who presented with an enlarging abdominal aortic aneurysm (AAA) sac. Only patients with at least 1 year of follow-up were included.

Criteria for switch to CDU included patients with a residual AAA sac of 4 cm or less anytime after the first year of follow-up, patients with a stable AAA sac size for 2 years, or patients with a stable type II endoleak for 2 years. The average CDU study duration was 20 minutes. The researchers used a GE Logiq 9 machine with a 3.5-MHz curve probe.

Of the 184 patients, 13 had an active stable type II endoleak, 23 had a prior endoleak that was treated or that resolved spontaneously. The mean follow-up on CDU was 24 months. Of the 184 grafts, 76 were Ancure, 58 were Zenith, 39 were Excluder, 7 were AneuRx, and 4 were Lifepath.

Dr. Chaer reported that there were three new endoleaks detected on CDU follow-up, all in patients who received an Ancure graft. Only one patient presented with sac enlargement. “One type II endoleak was detected, but this spontaneously resolved at 3 months,” he said. “There were two distal type I endoleaks that were treated with limb extension.”

CDU identified two patients (one with an Ancure and one with an AneruRx graft) who had an increase in their AAA sac size, yet no endoleak was detected. No endoleak was seen on CT scan, but when both patients underwent angiograms, a distal type I endoleak was detected in one patient.

There were no ruptures or graft occlusions observed during the follow-up period. Eight patients died. One was an aneurysm-related death following an Ancure explantation for infection that occurred 4 years post EVAR; two were related to malignancy, and five were related to acute myocardial infarctions.

The cumulative freedom from secondary intervention after the switch to CDU was 98% at 4 years.

In order to determine the applicability of the switch criteria for a full cohort of EVAR patients, the researchers examined 196 consecutive EVAR patients in 2004. Of these, 86 (44%) had been switched to CDU surveillance, whereas the remaining 110 were still followed with CT scan. At the 6-month follow-up, only 1.5% of patients followed with CT scan met the current criteria for the switch to CDU-only surveillance. But the proportion at 1, 2, and 3 years was 55%, 86%, and 97%, respectively.

“CDU-only surveillance is safe and can be initiated early after treatment on patients with a shrinking or a stable AAA sac,” he concluded. “Most patients treated with EVAR are eligible for this modality. After the 1 year follow-up, we do recommend that CT scanning should only be selectively utilized in patients treated with EVAR. This policy should result in cost-saving advantages and avoid the complications associated with CT.”

Dr. Chaer disclosed he had no relevant conflicts.