Pathogenesis and Pathophysiology

The primary pathogenesis of VO varies by patient age. In children, the intervertebral disc receives a direct blood supply through collateral vessels associated with the vertebral end plates. Thus, systemic bacteria are able to relatively easily affect and penetrate the vertebral body. By the third decade of life, the collateral vessels present in childhood often involute, such that there is no direct vascular connection between the systemic circulation and the vertebral body. Therefore, in adults, transient bacteremia seeding relatively avascular regions adjacent to subchondral bone, as well as urinary sepsis, become the more prominent means of initiating infection. As a result, spinal infection in adults more often involves the subchondral bone, with secondary involvement of the vertebral end plates and a relative ease of spread between adjacent vertebral bodies.

The pathogenesis of SEA has traditionally been thought to develop through direct extension from a VO primary site, by hematologic seeding, or from direct contamination, such as through surgical intervention. Most cases of SEA develop dorsally, as the spinal epidural space contains relatively loose areolar tissue and a rich venous supply; these factors make the dorsal region more prone to infection, at least to the S2 vertebral level, beyond which dura surrounds the epidural space circumferentially.

Microbiology of Vertebral Osteomyelitis and Spinal Epidural Abscess

Bacterial pathogens remain the primary infectious agents responsible for most cases of VO and SEA. Fungal agents occasionally cause disease, particularly in immunosuppressed patients, and some parasitic agents have been associated with VO and SEA in certain endemic geographic regions.

Among bacterial pathogens, Staphylococcus aureus, most often drawn from a primary skin or soft-tissue infection, is by far the most common etiologic agent responsible for VO and SEA. S. aureus accounts for more than one half of all cases of VO and more than three fourths of all SEA cases. Gram-negative bacteria-based infections are increasing as well, with Escherichia coli being responsible for more than one half of all Gram-negative bacteria-based infections, followed by Enterobacter and Proteus infections. Pseudomonal infections are particularly prominent in intravenous drug-using patients. Tuberculosis remains a relatively rare cause of infection in developed countries, but is often the most common source of VO in many endemic regions.

Laboratory Findings

Laboratory findings associated with VO and SEA reflect the underlying inflammatory nature of the disease and are not specific. The erythrocyte sedimentation rate (ESR) is the most consistently elevated laboratory value in spinal infection, with the ESR typically being greater than 40. In one meta-analysis, the average ESR was 77.^2,8 ESR has been shown to be greater than 20 in 95% of cases in some studies.^3,19 The ESR is also helpful in monitoring the disease process during therapy, with declining values of ESR to be expected with appropriate therapy. The C-reactive protein (CRP), an acute phase reactant, has also been found to be elevated in patients with spinal infections.^2,8 Obtaining CRP levels may be useful because CRP levels have been shown to rise more quickly during inflammation and to return to normal more quickly than ESR levels.²⁴ In addition, one study showed CRP values obtained over 2 weeks after surgery for SEAs can provide prognostic information regarding outcomes.²⁰

The peripheral white blood cell count may be elevated in patients with spinal infections, but many times may be normal. An elevation of the peripheral white blood cell count may be more indicative of a systemic infectious process. The average peripheral white blood cell count in one large meta-analysis of SEAs was 15,700/μL.¹¹

In patients with SEA, a cerebrospinal fluid (CSF) sample may show an elevated white blood cell count and protein level, which are indicative of a parameningeal process. In addition, the CSF values may be reflective of concomitant encephalitis or meningitis, which may present along with a spinal infection in a significant proportion of cases.² However, a lumbar puncture is often inadvisable in the setting of a SEA because of the risk of seeding bacteria into the thecal sac, especially in abscesses in the lumbar region that are located in the dorsal epidural space.

Blood cultures are often positive in the setting of a spinal infection. The organism grown on blood culture may be the same as the causative organism in a SEA or VO, especially if the spinal infection was caused by a hematogenous seeding. Blood cultures have been reported to be positive in approximately 50% of cases in some studies.¹⁵ Positive blood cultures can be useful for guiding antibiotic therapy in the setting in which direct cultures from the spinal infection cannot be obtained. Because blood cultures may become negative if obtained after the administration of antibiotics, it is important to obtain blood cultures prior to the initiation of antibiotics if possible.

Radiographic Studies

Imaging studies are essential for the diagnosis of both VO and SEA. Plain film examination of the spine should be performed as part of the initial workup. In cases of SEA, x-rays are usually normal unless they are associated with an adjacent vertebral body’s osteomyelitis.²⁵ In cases of VO, plain radiographs are usually helpful in localizing the spinal level and the extent of the lesion and in assessing the presence of deformity. Unfortunately, early in the course of VO, plain radiographs may be entirely normal and provide little or no clue to the diagnosis. Most of the time, radiographic changes lag well behind the clinical presentation and frequently are not helpful in establishing an early diagnosis. Plain x-ray changes usually take 2 to 8 weeks to develop from the onset of infection. The earliest changes are loss of the cortical end plate margins and loss of the disc’s space height.²⁵

Narrowing of the intervertebral disc space can be seen in plain films as early as 2 weeks from the onset of symptoms but usually appear at week 6 or 8.^15,26–28 As the infection progresses, there is an increase in vertebral body destruction followed, in some cases, by subsequent spinal deformity. Lytic lesions, demineralization, and scalloping of the end plates may occur.²⁵ As the infection resolves and healing takes place, new bone formation and subsequent fusion can occur, but this may not be evident for as long as 1 year.

For the above-described reasons, computed tomography (CT) has become an important diagnostic tool in the diagnosis of spinal infections, especially for VO. Among its benefits, CT provides excellent detail of the bony anatomy, and it clearly demonstrates the lytic lesions as well as gas within the disc space or soft tissues (Fig. 145-1). Although identification of SEA has been reported using CT alone, it is generally thought that plain CT is not particularly sensitive for visualizing SEA.²⁹ Indirect findings such as intraspinal gas have been described in the presence of SEA.²⁵

FIGURE 145-1 Axial computed tomographic scan of a patient with vertebral osteomyelitis (VO). Note the destructive changes of the vertebral body as well as the paravertebral soft-tissue reaction.

CT is the most valuable tool when performing image-guided percutaneous biopsies of the vertebral body and paravertebral tissues to obtain culture material, and CT is also effective in performing aspiration of paravertebral abscesses.³⁰ Image-guided CT biopsy has been shown to be safe and effective in obtaining diagnostic material at all levels of the spine; however, this technique yields a lower diagnostic rate than the previously reported biopsy of neoplastic vertebral lesions, especially if performed in patients who have undergone previous antibiotic treatment.³¹ Therefore, it is imperative to perform the biopsy prior to administration of antibiotics to maximize the yield of a positive culture.

MRI has lately become the single most important imaging modality in the evaluation of infectious and inflammatory diseases of the spine.^32–35 The advantages of MRI over other imaging modalities include the ability to perform multiplanar imaging and to directly visualize the paraspinal soft tissues and spinal cord as well as it being a noninvasive procedure. Additionally, MRI abnormalities seen in patients with VO are apparent long before the findings can be detected on plain radiographs. Classic MRI findings of VO described by Modic and colleagues^32,33 typically include the following. (1) The clinician can usually see confluent low signals from the vertebral bodies and intervertebral disc space on T1-weighted (T1W1) images, that is, decreased signal intensity in the affected vertebral body with loss of delineation of the end plates from the intervertebral disc. (2) The practitioner can see increased signal intensity from the involved vertebral body and disc space on T2W1 images (Fig. 145-2).

FIGURE 145-2 A, Midsagittal T1-weighted MRI scan of a 62-year-old woman who presented with midthoracic back pain and myelopathy. There is decreased signal intensity of the involved vertebral bodies. The spinal cord is draped over a ventral mass representing a combination of retropulsed bone and induration of the posterior longitudinal ligament. B, This T2-weighted sequence reveals increased signal intensity of the involved vertebral bodies, particularly of the intervertebral disc. C, After administration of gadolinium enhancement within the vertebral body is revealed and the ventral epidural abscess is more clearly defined.

Contrast-enhanced sequences obtained to visualize VO often show enhancement of the affected vertebral body and disc, and there is often little or no soft-tissue contrast between the involved bone, interspace, and paravertebral and epidural soft tissues. Additionally, in patients with a ventral abscess associated with VO, T1W1 images typically demonstrate a soft-tissue mass with tapering edges at the rostral and caudal poles that displaces the thecal sac away from the posterior aspect of the vertebral body. Occasionally, the abscess may appear to be indented by the confines of the posterior longitudinal ligament.

MRI is also the imaging modality of choice for SEA and is helpful in differentiating other conditions, such as spinal myelitis and spinal cord infarction. The following are typical findings. (1) T1W1 imaging is beneficial in detecting a hypo- or isointense epidural mass. (2) T2W1 imaging is useful for visualizing a hyperintense epidural mass, which often enhances with gadolinium. There are usually three patterns of enhancement: (1) dense homogeneous, (2) nonhomogeneous with scattered areas of no uptake, and (3) thin peripheral enhancement.³⁶ On the other hand, an unenhanced MRI scan can cause clinicians to miss some SEAs.³⁷

MRI is very helpful in differentiating an infectious from a neoplastic process. In most of the cases, the paravertebral soft-tissue swelling that accompanies osteomyelitis completely surrounds the spine ventrally. However, neoplastic processes usually have minimal to no soft-tissue reaction, and bony changes produced by tumors may often involve the posterior elements, whereas osteomyelitis seldom compromises the posterior elements unless the patient has had a prior surgical procedure.³⁸ It may also be possible to differentiate pus from granulation tissue with the use of MRI.³⁷ In such cases, more discrete areas of increased signal intensity on T2W1 images are believed to show liquid pus, and administration of gadolinium results in enhancement of chronic granulation tissue, though there is usually little to no enhancement of the abscess cavity itself.

Computed tomographic myelography is seldom used in the diagnosis of SEA and has been widely supplanted by MRI. Not only is MRI as sensitive as computed tomographic myelography but also the numerous advantages of MRI noted previously significantly expand the ability to differentiate SEA from other conditions included in the differential diagnosis, such as, but not limited to, neoplastic disease, disc herniation, intraspinal hematoma, spinal cord infarction, syringomyelia, and transverse myelitis.

Other diagnostic studies include radionuclide imaging with technetium, gallium-67, and indium-111, which may provide valuable adjunct to diagnosis, particularly for VO, especially before changes on plain radiographs become evident. In cases of VO, technetium scans generally show a diffuse uptake of tracer in the region of infection (Fig. 145-3). Technetium scans have fairly high sensitivity of approximately 90% but specificity of only 78% and accuracy of 86%.³² The probability of a positive study is increased with the duration of symptoms and, in long-standing cases, approaches 100%; however, false-positive increased uptake may be due to degenerative changes, recent surgery, or fracture. False-negative scans also occur, particularly in children and elderly patients.

FIGURE 145-3 Technetium radionuclide imaging in a patient with vertebral osteomyelitis (VO) shows focal uptake of the radiotracer at the involved level.

Gallium-67 scanning has sensitivity roughly equivalent to that of technetium (89%), specificity of 85%, and accuracy of 86% in the diagnosis of spinal infection. Diagnostic accuracy can be improved to approximately 94% by combining technetium and gallium imaging. Indium-111 leukocyte labeling has proven helpful in the evaluation of soft-tissue infections as well as infections involving the skeleton. Unfortunately, indium-111 scans have not been found to be particularly beneficial in rendering the diagnosis of spinal infection. This may be due to the fact that many cases of VO are chronic by the time they come to the attention of clinicians, and the inflammatory response may have a paucity of leukocytes. Overall, the sensitivity of indium-111 scans is only 17%, their specificity is approximately 100%, and their accuracy is 31%.

Antibiotic Therapy

Antibiotic therapy has remained a mainstay treatment for both VO and SEA. To tailor antibiotic therapy as narrowly as possible, the initiation of this therapy is traditionally withheld until cultures are obtained. However, in the event that a patient presents with signs of rapid neurologic decline or, less commonly, with signs of bacterial meningitis, broad-spectrum antibiotics may be initiated prior to obtaining cultures, despite the fact that this may commit the practitioner to providing a long-term course of broad-spectrum antibiotic coverage.

Empiric antibiotic therapy should include coverage of those organisms most likely to cause VO and SEA, namely, Gram-positive organisms such as Staphylococcus, as well as Gram-negative organisms such as E. coli and anaerobes.¹⁷ Such coverage may include vancomycin, a third-generation cephalosporin, and metronidazole given at bactericidal levels. Given that staphylococci and streptococcal species account for the vast majority of causative agents in VO and SEA, the addition of an aminoglycoside, fluoroquinolone, or rifampin may be considered for their potential synergistic effect, especially in cases of extensive bony involvement, where vancomycin and cephalosporins may have poor penetration into devascularized bone or the disc.²⁶

While there have been no prospective, randomized studies comparing the duration of various antiobiotic therapy regimens for the treatment of VO and SEA, most practitioners treat patients for at least 4 to 6 weeks with intravenous antiobiotic therapy with the goals of sterilizing infected vertebral levels, preventing neurologic decline, and preventing the formation of painful spinal deformities.³ In patients with prominent disease over multiple spinal levels or in immunocompromised patients, therapy extended to 8 weeks has been associated with more effective prevention of relapse of infection.¹⁰ Diminished pain, malaise, fever, and reduced ESR levels over the course of antibiotic therapy correlate well with radiographic evidence of resolution of the disease.^2,8

Role of Immobilization

Immobilization of the spine in patients with VO has traditionally been employed to achieve one of two goals: to reduce pain and to prevent postinfection spinal deformity. Given that the risk of postinfection spinal deformity is greatest in patients in whom the disease process causes more than a 50% reduction in vertebral body height or in which there is involvement of two or more adjacent vertebral bodies, patients presenting with these pathologies are most often immobilized. Although immobilization has played an important role in the treatment of VO patients with spinal instability, its importance in VO patients without spinal instability has remained less clear. Some authors have employed immobilization for all VO patients until pain is minimal or absent, with the type of orthotic used being dependent upon the region of the spine affected.³⁸

Surgery for Vertebral Osteomyelitis

Many authors believe that uncomplicated cases of VO, especially at early stages of the disease, will respond well to conservative treatment and can be effectively managed with antibiotics and immobilization with good outcomes and minimum morbidity.³⁹ Usually, surgical intervention is reserved for more complicated and advanced cases.³⁹

Major indications for surgery include the following:

Spinal deformity and instability usually occur in 2% to 28% of patients with VO. Spinal deformity in most cases begins with a loss of anterior column height and progresses to kyphosis. Bony involvement usually includes the anterior and middle columns; posterior column involvement is unusual in the absence of previous surgery. In very advanced cases, severe deformity and even complete dislocation may occur. Therefore, posterior decompressive procedures are usually contraindicated in this condition, unless they are combined with circumferential reconstruction of the spine.²⁸ Indeed, in such instances, an unstabilized laminectomy almost always exacerbates the problem (Fig. 145-4). The goal in such cases is to restore the integrity of the anterior column with a weight-bearing construct.²⁸

FIGURE 145-4 A, T1-weighted MRI scan of a 67-year-old woman who presented with fever, thoracic pain, and mild lower-extremity weakness. Note the extensive destruction of the vertebral body and the ventral epidural mass that displaces and deforms the cord. She underwent a laminectomy, after which a decline in neurologic function occurred. B, Postoperative MRI scan shows instability with retrolisthesis of the rostral vertebral body. She subsequently underwent further surgery for spinal stabilization which led to improvement in neurologic function.

If, in fact, the posterior column is intact and deformity is limited to kyphosis or loss of lordosis, then an anterior-only reconstruction should be sufficient. However, if the posterior column is deficient due to previous surgery, then both anterior and posterior reconstruction are necessary.

In most surgical cases, the involved vertebrae have little viable structure to support the reconstructive strut; therefore, multilevel corpectomies are required to expose end plates that are strong enough to support the construct.²⁸ Anterior column reconstruction can be performed using either an autologous iliac graft^26,28 or titanium cages packed with cancellous iliac autograft or allograft.²⁶ If there is absence or loss of posterior element integrity, posterior instrumentation should be added to the anterior construct.²⁶ In cases with posterior element integrity, the cages can be stabilized with a rigid anterior device.

Over the past several years, a large number of authors have reported the successful use of instrumentation in the presence of infection as long as all obviously infected material has been removed^39,40 (Fig. 145-5). Instrumentation is usually used in those cases (1) where the infectious process has destroyed bone and the spine has become unstable under physiologic loading and/or (2) when the surgical procedure itself has rendered the spine unstable. In most cases, the recurrence of the infectious process is not related to the implants themselves, but to the compromised general health of the patient.³⁹

FIGURE 145-5 Sagittal (A) and axial (B) T1-weighted MRI scans enhanced with gadolinium of a 54-year-old patient with diabetes who presented with a 2-week history of neck pain, fever, and quadriparesis. His erythrocyte sedimentation rate was 85 mm/hr. The images show involvement of several vertebral bodies with cord compression due to an associated ventral epidural abscess. At the time of surgery, the majority of the abscess consisted of granulation tissue with only a small amount of liquid pus that was completely removed. C, This patient was treated with a multilevel corpectomy and fusion using both anterior and posterior spinal instrumentation (C) without complications.

Surgery for Spinal Epidural Abscess

The majority of retrospective studies provide consensus which supports the traditional management of SEA: immediate surgical drainage followed by systemic antibiotic therapy of variable duration. Surgical management has clear advantages.

The type of surgical procedure chosen varies, depending upon different independent situations. As a general rule, the procedure level should be based on the site of maximal compression. For spontaneous abscesses that are located dorsally and not associated with VO, a laminectomy over the involved levels generally provides adequate decompression, and, if treated with appropriate antibiotic therapy, simple laminectomies are usually not followed by instability⁴¹ (Fig. 145-6). All purulent material should be removed by using both suction and irrigation. Patients with more chronic abscesses may have a significant amount of granulation tissue that is often adherent to the dura, but it can be carefully dissected in most cases. Once all purulent material has been removed, most practitioners prefer primary closure without a drain to prevent a possible source of infection.

FIGURE 145-6 Midsagittal T1-weighted MRI scan enhanced with gadolinium of a 22-year-old IV drug user who presented with fever, back pain, and paraparesis. This imaging study shows a spontaneous, dorsally located epidural abscess extending over multiple levels. Note the absence of any changes associated with osteomyelitis. The patient underwent decompressive laminectomy and evacuation of a mostly liquid epidural abscess that grew Pseudomonas aeruginosa. After being treated for 8 weeks with IV antibiotics, she recovered full neurologic function.

In most cases, abscesses do not extend over more than three or four segments of the spine; therefore, laminectomy can easily be performed over the entire area of involvement. Some patients occasionally develop a SEA that extends over many segments and, in rare situations, involves the entire spinal axis. For these cases, Schulz and colleagues⁴² have described a minimally invasive technique for decompression of abscesses that extend over a long distance. This technique involves performing a one-segment or two-segment laminectomy at the most rostral and caudal levels of the abscess and then advancing a Fogarty 5-French catheter (Edwards Lifesciences, Irvine, CA) through the epidural space from the caudal laminectomy to the rostral one. The balloon is then inflated with 1 to 1.5 mL of saline and slowly and gently withdrawn. The procedure is repeated until all purulent material has been adequately removed.

CT-guided percutaneous aspiration has also been used as a minimally invasive technique for drainage of SEA.^43,44 It is effective only for posterior abscesses that primarily contain pus and is contraindicated for ventral abscesses. The major reported complication associated with this procedure is dural penetration with subsequent contamination of the CSF and development of meningitis.

SEA has usually been considered a surgical disease. Lately, however, there has been an increasing tendency toward more conservative nonoperative treatment.^3,11,45 This approach is based mainly on early identification of the pathologic organism and subsequent specific antibiotic therapy. Usually, nonoperative therapy is reserved for the following patients:

Patients with cervical and or thoracic abscesses generally require surgical evacuation due to a smaller epidural space and the increased possibility of developing a neurologic deficit. All patients require strict monitoring. Neurologic deterioration can still occur despite appropriate antibiotic therapy, and, in such cases, emergent decompression should be advocated.