Discitis

Pyogenic discitis is a bacterial infection of the intervertebral disc that is frequently associated with involvement of the adjacent vertebral end plates (spondylodiscitis). Incidence is estimated to be between 0.2 and 2.4/100,000 each year, with two peaks in age distribution: one in early childhood and another between ages 60 and 70 years.^62,63 The relatively high proportion of children with pyogenic discitis is likely related to the anatomy of the disc space during development. Children still have a vascular supply into the nucleus pulposus of the disc, which allows septic emboli to lodge with the disc. The vascular supply in adults only reaches the anulus fibrosus. In the adult population, more men are affected than women.⁶⁴ Risk factors for developing discitis include invasive procedures, diabetes (11–31%), malignancy, IV drug use (IVDU), immunosuppression, alcoholism, renal failure, and cirrhosis.^62,63,65

The majority of cases are caused by S. aureus, with gram-negative rods, Streptococcus, and Enterococcus being the next most frequently involved organisms.^63,64 Gram-negative organisms are more common when associated with diabetes, immunocompromise, infections of the genitourinary or gastrointestinal tracts, or IVDU.⁶⁵ Tuberculosis (TB) and brucellosis are atypical bacterial infections that can cause discitis in endemic regions and in at-risk populations. Fungal discitis is rare but should be considered in patients who are critically ill, immunosuppressed, taking multiple antibiotics, or have an indwelling catheter.⁶⁶ The most frequent location is the lumbar spine (60%), followed by the thoracic (30%) spine and the cervical spine (10%).^62,64

In 1936, Milward and Grout were the first to describe the clinical and radiographic characteristics of interspace infection after the inadvertent introduction of microorganisms into a disc space during a lumbar puncture.⁶⁷ More than 90% of patients complain of back or neck pain.⁶² This pain often is not relieved by medications or recumbency. Radicular pain symptoms are not uncommon. Guarding against movement and a positive straight-leg raise may be present. Fever is present in approximately 60% to 70%.⁶³ Neurologic deficits, especially weakness, should raise concern for more a extensive infection such as an epidural abscess. In children, discitis often presents as a refusal to bear weight or walk.⁶⁸ The time from onset to diagnosis is often months. ESR and CRP are elevated in most patients, but leukocytosis is present in less than half of cases.⁶⁹

The differential diagnosis for discitis includes other infections of the spine and adjacent structures, trauma, osteoporotic fracture, degenerative disc disease or acute herniation, metastatic disease, and inflammatory spondyloarthopathies. Discitis is often also associated with bacterial endocarditis (3.7–15%). Echocardiography is recommended for patients with spontaneous discitis. Back pain in the setting of endocarditis or bacteremia should lead to an evaluation for discitis.⁷⁰

MRI with contrast is the image modality of choice for diagnosing spontaneous discitis, with a sensitivity and specificity greater than 90%. If an MRI is not possible, the next most sensitive studies are radioisotope scans followed by CT with contrast. Radiographs also show typical changes such as disc space narrowing and end-plate erosion, but these changes usually take several weeks to develop.⁴⁹ CT is particularly helpful for guiding percutaneous biopsy.

If possible, antibiotics should be held until cultures can be obtained. Blood cultures are positive in approximately half of discitis cases.⁶⁴ To maximize yield, three culture specimens taken at different times and locations should be obtained, ideally when the patient is febrile. If after 48 hours there is no growth, a CT-guided percutaneous biopsy should be obtained, which increases the yield to between 60% and 70%.⁶⁴ Samples should be taken from both adjacent vertebral end plates and the disc itself, and the disc space should be rinsed and aspirated. Biopsy samples are sent for histopathologic studies, aerobic, anaerobic, fungal, and mycobacterial cultures, and stains.⁶² A second percutaneous biopsy has been shown to increase yield when the first biopsy is negative.⁶⁹ Occasionally open biopsy is required to obtain a diagnosis.

Approximately three-quarters of spontaneous pyogenic discitis cases can be treated nonoperatively with IV antibiotics tailored according to the results of the cultures and sensitivities.⁶² There are no good studies comparing various antibiotic regimens, duration of antibiotic therapy, or the role of oral antibiotics after administration of IV antibiotics. Traditionally 4 to 6 weeks of IV antibiotics was recommended, but recent reports suggest there is a decreased risk of recurrence if antibiotics are used for 12 weeks, often with a switch to oral antibiotics after 6 weeks.^62,65 Spinal immobilization for pain control, using bracing or short-term bed rest, is recommended by most surgeons.

Response to therapy is demonstrated by diminishing pain, resolution of fever, and progressive decrease in CRP levels.⁴⁸ Radiographs should be obtained at regular intervals after initiation of treatment and should show sclerosis and osteophyte formation by 3 months if healing is occurring.⁶⁵ Patients generally progress to fusion over 6 to 12 months. Repeat MRI is generally not helpful and often initially appears worse than pretreatment scans.⁷¹ MRI should usually be reserved for patients with new or worsening neurologic symptoms to rule out expanding abscess.

Surgery is reserved for patients with neurologic deficits, especially those with associated epidural abscess and spinal cord compression, for clinical failure after conservative treatment, for treatment of spinal instability or correction of deformities, for obtaining a diagnosis by open biopsy after failed percutaneous biopsy, and occasionally for persistent pain.⁷²

Recurrence rates after a course of antibiotics are generally around 10% (0–16%).^62,69 Chronic pain is the most common residual complication. Functional impairment and neurologic deficits occur in a minority.⁶⁴ Mortality is generally low and usually related to associated sepsis, endocarditis, or underlying disease.^63,69

Vertebral Osteomyelitis

Infection of the bones of the spinal column—vertebral osteomyelitis—can occur after trauma, as a result of direct manipulation during surgery, via contiguous spread from adjacent structures, or via hematogenous spread from distant sources.⁷³ Vertebral osteomyelitis is relatively rare, with an estimated incidence of 2.4/100,000 people. Older adults are more likely to be affected, with the incidence increasing from 0.3/100,000 for those younger than 20 years of age to 6.5/100,000 for those older than 70.⁷⁴ There is a male predominance that also increases with age.^74,75

Patients with vertebral osteomyelitis usually have predisposing factors, with the most common being diabetes mellitus, end-stage renal disease requiring dialysis, sepsis, endocarditis, cancer, HIV infection, immunosuppression, alcoholism, and IVDU.^73,75,76 Urinary tract infections followed by skin infections were the most common sources of infection.⁷⁵

A vast majority of cases of pyogenic spine osteomyelitis involve the vertebral body, with only 3% to 12% involving the dorsal elements of the spine.⁷⁷ Infection generally begins at the highly vascular end plates. Most cases involve two or more contiguous vertebral bodies and the intervening disc. Vertebral osteomyelitis occasionally manifests as the collapse of an isolated vertebral body. The lumbar spine is the most commonly involved (58%), followed by the thoracic spine (30%) and cervical spine (11%).⁷⁵ Associated epidural abscesses (17%), paravertebral abscesses (26%), and disc space abscesses (5%) are frequent.⁷³

The most common causative organism is S. aureus. Escherichia coli is the most commonly reported gram-negative organism and is especially associated in cases when genitourinary or gastrointestinal infections are the source.⁷⁵ S. aureus is the most frequent organism in IV drug users, but they also have an increased frequency of Pseudomonas aeruginosa⁷⁶ In many developing regions of the world TB is a frequent cause of chronic vertebral osteomyelitis.

There is often a substantial delay in the diagnosis of vertebral osteomyelitis due to the nonspecific nature of its presenting symptoms. In one large series the mean time to diagnosis was 1.8 months, with only a quarter of cases being diagnosed in less than a month. The same study revealed that on initial presentation only a quarter of the patients had vertebral osteomyelitis considered in the differential diagnosis. The majority of patients (86%) present with several weeks of worsening back or neck pain.⁷³ Fever has been reported in 35% to 60% of patients.^73,78 Neurologic deficits are present in approximately a third of cases, and only around one fifth of patients have localized tenderness.⁷⁸ Rapidly worsening neurologic deficits and paralysis should raise the concern for associated spinal epidural abscess. Acute worsening of pain is often associated with vertebral collapse. Back pain in the setting of bacteremia, such as with endocarditis, should always lead to an evaluation for vertebral osteomyelitis. The differential diagnosis for vertebral osteomyelitis includes other localized spine infections, osteoporotic or traumatic fractures, spondyloarthopathies, degenerative disc disease, herniated disc, metastasis, and infections such as pancreatitis and pyelonephritis.⁷⁹

Leukocytosis is present in approximately two thirds of cases, and there is an associated neutrophilia in about a third of cases.⁸⁰ ESR and CRP measurements are much more sensitive to the presence of inflammation and are elevated in almost all cases of vertebral osteomyelitis.^48,80 Serial CRP is more accurate than ESR for gauging response to therapy.⁴⁸ Blood cultures should be obtained in all patients with suspected vertebral osteomyelitis because 58% (range, 30–78%) of cultures will be positive.⁷⁵ Identifying the organism via blood cultures often obviates the need for more invasive procedures.

MRI is the best imaging modality for evaluating for vertebral osteomyelitis, with a sensitivity of nearly 100% and accuracy over 90%.⁸¹ Findings associated with osteomyelitis include a low intensity on T1-weighted images with loss of the usual hyperintense signal of fat in the bone marrow, hyperintensity on T2-weighted images in the bone or adjacent disc and soft tissues indicative of edema, and enhancement with contrast of the end plates and associated abscesses. There is usually a loss of the intranuclear cleft of involved discs. End-plate destruction is a late finding.⁸¹

Radiographs and CT are beneficial in the delineation of bony destruction. Radiographs often reveal narrowing of intervertebral disc spaces, rarefaction of the vertebral body, loss of trabeculations near the end plate, or frank vertebral body collapse. Besides providing more accurate anatomic details of the bony involvement for assessment of stability, CT with IV contrast can be used for guiding percutaneous biopsy.

Combined gallium/bone scintigraphy is the most useful radionuclide study for diagnosing vertebral osteoarthritis in patients unable to have MRI due to incompatible implants or in whom MRI imaging is nondiagnostic. 2-[¹⁸F] Flouro-2-deoxy-d-glucose positron emission tomography (FDG-PET) is a promising new modality that also has a high reported accuracy. In contrast, labeled leukocyte imaging is not considered useful in the diagnosis of vertebral osteomyelitis.^54,81

The overall goal of treatment of vertebral osteomyelitis is to eliminate the infection while maintaining neurologic function and spinal stability. A majority of patients are able to obtain this goal without surgical intervention with antibiotics and spine immobilization via bracing or bed rest. The overall rate of surgery has likely been rising, and a recent systematic review found that 42% of patients had some form of surgical intervention. The reasons for surgery include open biopsy, spine stabilization (23%), drainage of associated abscess (21%), decompression of the spinal cord (13%), and correction of deformity after infection had been cleared (2%).⁷⁵ The use of instrumentation for stabilization in patients with acute infection does not appear to increase the risk of relapse when the patient has an appropriate course of antibiotics.⁸²

Antibiotics are chosen based on the results of culturing a causative organism and should be withheld prior to obtaining the culture results if possible. If blood cultures are negative, CT-guided percutaneous biopsy or open biopsy should be obtained. Aerobic, anaerobic, fungal, and mycobacterial culture specimens should be sent. Histopathology is useful in identifying granulomas that might be indicative of tuberculosis or brucellosis.⁷⁹ Antibiotics are usually continued for at least 6 weeks, but recommended courses ranging from 4 weeks to 3 months have been reported.⁸³ Longer courses should be considered in patients with complicated infections or implanted hardware. Antibiotic courses of less than 4 weeks have a higher incidence of relapse.⁸⁴ In certain instances oral regimens have been used successfully after a course of IV antibiotics. One randomized trial found similar outcomes in patients treated with a combination of an oral fluoroquinolone and rifampin and in those treated with IV antibiotics.⁸⁵

Patients should be monitored closely for failure of therapy. Failure of symptoms to improve and persistent CRP elevations at 4 weeks indicate likely treatment failure.⁴⁸ MRI obtained after starting treatment is a poor predictor of treatment outcome and should be reserved for patients in whom a change in symptoms occurs that might suggest new or worsening abscess.⁷⁹ Relapse occurs in 1% to 22% of cases and is more likely in patients with recurrent bacteremia, a chronically draining sinus, or a paravertebral abscess.⁷³

The systematic review by Mylona et al. found a mortality rate of 6%, with most deaths attributable to associated sepsis. Approximately a quarter of patients had a significant decrease in quality of life. The most common complications reported were chronic pain (28%), weakness (16%), and dysfunction of the bowels or bladder (7%).⁷⁵ Predictors of worse outcome include motor weakness or paralysis at presentation, delayed diagnosis (>2 months), and acquisition of the infection in the hospital.⁷³

Spinal Epidural Abscess

Spinal epidural abscess (SEA) is a relatively rare but extremely important clinical condition involving supportive infection in the epidural space of the spinal canal. SEA is considered a neurosurgical emergency because severe neurologic decline or death may become unavoidable if diagnosis and treatment are delayed. The mortality rate from SEA has been reported to be between 4.6% and 31%.⁸⁶

Incidence reports from longer than 2 decades ago estimated that 0.18 to 1.96 cases of SEA occur per 10,000 hospital admissions.^87,88 However, evidence suggests that the incidence has increased as the number of susceptible patients with known risk factors, such as IVDU and HIV infection, has increased.^46,86,89 This apparent increase in incidence may in part be due to the fact that the diagnosis of SEA is also made easier due to the advances in medical imaging. The male-to-female ratio was previously reported to be approximately 1:1,^87,88 but a large meta-analysis in 2000 revealed a ratio of 1:0.56.⁹⁰ This predominance is likely related to the higher incidence of trauma, alcoholism, IVDU, and other risk factors in men. SEA is more common in adults, with the majority of cases occurring from ages 30 to 60, but it can occur with any age group, with the youngest reported case being a 10-day-old patient.⁹⁰ The most common location for SEA is the thoracic spine, followed by the lumbar and lumbosacral regions.

Most patients with SEA have an underlying predisposing condition such as diabetes, end-stage renal disease with dialysis,⁹¹ cirrhosis, medical immunosuppression for transplant, chronic steroid therapy, HIV, malignancy and related chemotherapy, alcoholism, or previous trauma or spine intervention.^86,88,90,92 Approximately half of SEA cases are caused by hematogenous spread from a focus of infection, which can be either arterial or via the paravertebral venous plexus.⁹³ The most common source of infection is skin abscesses.⁹⁰ Other commonly reported sources include IVDU, indwelling venous or arterial catheters, dental abscesses, bacterial endocarditis, urinary tract infections, and respiratory infections. Iatrogenic introduction of disease via surgery, epidural anesthesia, or corticosteroid injection, among other causes, is another important source for the introduction of bacteria. Finally, contiguous spread to the epidural space can occur and has been reported from such sources as adjacent psoas abscesses, decubitus ulcers, abdominal infections, pyelonephritis, mediastinitis, and pharyngeal abscesses.

The most common microbial agent in SEA is S. aureus, which causes two-thirds to three-quarters of all cases.^46,90,94 Of concern is the increasing prevalence of MRSA, which in some reports represents almost 40% of abscesses.⁹⁵ Overall, aerobic gram-positive organisms, such as S. epidermidis, Streptococcus viridans, Enterococcus, and Propionibacterium, among others, account for nearly 80% of SEA cases.

Coagulase-negative staphylococci, such as S. epidermidis, are more common in patients who have undergone invasive spine procedures or who have implanted foreign bodies. Gram-negative organisms, such as E. coli, Enterobacter, Salmonella, Proteus, Serratia, and Pseudomonas, among others, are more likely to be involved when the source of the infection is gastrointestinal infection or urinary tract infection. Pseudomonas is more likely in patients with IVDU.⁹⁶ Multiple organisms can be found in up to 10% of abscesses. Anaerobic cultures should always be obtained since anaerobic bacteria, such as Bacteroides and Peptostreptococcus species, also rarely cause SEA.^87,97 Other causes of SEA include atypical bacterial infections, such as TB, brucellosis, and actinomycosis, for which acid-fast bacillus staining and extended cultures may be necessary; fungal infections, such as aspergillosis, in patients who are immunocompromised; and even parasitic infections, such as echinococcosis and dracunculiasis.⁹⁰

SEA can present acutely over the course of days, with gross pus in the epidural space and signs of sepsis, or in a more chronic presentation of symptoms that develop over months, with granulation tissue in the epidural space. The organism responsible for the infection often determines the time course of presentation.

Diagnosis begins with recognition of the clinical presentation. Heusner’s classic description of the presentation of SEA in 1948 describes four stages: (1) severe back pain, local tenderness and fever; (2) signs of spinal irritation such as Kernig sign, neck stiffness, and radicular pain; (3) development of neurologic deficits such as weakness, fecal or urinary incontinence, and sensory deficits; and (4) progression of weakness to paralysis.⁹⁸ Most patients with SEA do not present with such a characteristic course and often initially present with only complaints of isolated back pain. For this reason it is very common for the diagnosis of SEA to be initially missed. The most common signs and symptoms are back pain (71%) and fever (66%),⁹⁰ and the combination should always raise the possibility of SEA. Atypical signs and symptoms such as localized tenderness to percussion, thoracic radicular pain, and pain with recumbency should also raise red flags. Symptoms of systemic infection such as chills, night sweats, or sepsis may be present.⁹⁹ New-onset neurologic deficits are more common with cervical and thoracic SEA and need to be rapidly evaluated due to the possibility of progression. Approximately one third of patients present with some degree of paralysis.⁹⁰

In a patient with back pain, the addition of laboratory tests to identify systemic signs of inflammation can greatly enhance screening for pyogenic spine infection. The leukocyte count, ESR, and CRP are often elevated, though a normal lab value by itself should never be used to rule out the possibility of SEA. The incidence of leukocytosis is approximately 68% to 78%.^100,101 Approximately 94% to 100% of patients have an elevated ESR.^90,100 Leukocytosis and an elevated ESR are relatively nonspecific symptoms and must be interpreted in the setting of the patient’s condition as a whole. All patients thought to have SEA should also have blood cultures drawn as this can help with the diagnosis of SEA as well as identifying the offending pathogen.

After the history, clinical examination, and laboratory markers have raised the possibility of SEA, the next step is to identify or rule out the diagnosis with radiologic imaging. The most sensitive and specific imaging modality is MRI with gadolinium contrast. Plain-film radiographs, CT, and CT-myelography may be useful as adjuncts or when MRI is not possible.

MRI findings in SEA reveal an epidural mass that is hypointense to isointense on T1-weighted images and hyperintense on T2-weighted images. The abscess usually enhances with contrast administration, often as a linear rim enhancement surrounding a nonenhancing core that represents purulent material.¹⁰² More heterogeneous enhancement may be present if the abscess has more of a phlegmon consistency as opposed to liquid pus.⁴⁴ MRI is also excellent for identifying other conditions that may mimic SEA, such as spinal tumors, transverse myelitis, spinal cord infarction, or intervertebral disc herniation.

Radiographs and CT are useful for evaluating for adjacent osteomyelitis. Bony erosion or destruction may be seen on radiographs after 4 to 6 weeks of infection; however, delineation of bone involvement is appreciated much better with CT imaging. CT may show evidence of inflammation, such as stranding in the paravertebral soft tissues. After contrast administration, SEA may be identified as an enhancing epidural mass. However, there are reports of CT imaging alone missing a relatively high proportion of SEAs.¹⁰³ CT imaging can be useful for surgical planning, especially in deciding whether fusion and instrumentation will be needed after surgical debridement.

If MRI is not possible, CT-myelography can be a very useful diagnostic substitute. Prior to widespread availability of MRI, myelography and then CT-myelography were the gold standards for radiologic diagnosis of SEA. With CT-myelography contrast is directly injected into the thecal sac and an epidural mass can be identified as blockage of flow from above or below, depending on where the puncture was performed. In a direct comparison study, MRI and CT-myelography were found to be equally sensitive (91% vs. 92%).¹⁰⁴ CT-myelography is less specific than MRI and provides less information about the characteristics of the epidural mass. Moreover, CT-myelography requires an invasive procedure that can introduce infection or spread an epidural infection to a subdural space, causing a subdural empyema or meningitis.¹⁰⁵ Since SEA in the upper cervical spine is relatively rare, a lateral C1-2 puncture is often recommended to limit the chance of traversing the epidural collection during the myelogram. A myelogram also allows for the evaluation of CSF, which reveals associated meningitis in up to 15% of patients. However, most authors recommend against lumbar puncture for the purpose of CSF examination alone in the evaluation of suspected SEA due to the low specificity and risk of seeding infection.^{51,90,104–106}

Many conditions can present with back pain and signs and symptoms of inflammation in a manner similar to SEA. A large percentage of SEA cases are still initially misdiagnosed, leading to a delay in treatment. In a large meta-analysis, the most common initial misdiagnosis was intervertebral disc herniation, followed by meningitis, vertebral osteomyelitis, sepsis, endocarditis, and spinal tumors.⁹⁰ The differential diagnosis for SEA should also include epidural metastasis, acute transverse myelitis, subdural empyema, intramedullary abscess, epidural hematoma, autoimmune spondylitis, discitis, infections of adjacent structures (pyelonephritis, psoas abscess, etc.), vascular malformations, subarachnoid hemorrhage, and lymphoma. Acute transverse myelitis is more common than SEA and typically presents with rapidly progressing neurologic deficits without significant back pain. A history of a recent viral illness would also make acute transverse myelitis more likely.

The next step in the diagnosis of SEA after obtaining radiologic imaging is to obtain a culture of the organism causing the infection. Obtaining cultures prior to starting antibiotics is imperative to ensure the highest yield; however, this is not always possible when the patient is frankly septic. Antibiotics given prior to culture or biopsy can result in a failure to isolate a bacterial source and lead to the patient being unnecessarily treated with broad-spectrum antibiotics. The easiest method for isolation of the bacterial source involves obtaining blood culture specimens, which should be obtained from multiple sites and at different time points. Ideally, at least three separate blood specimens are obtained while the patient has spiking fevers. The yield from blood samples in the setting of SEA is between 30% and 60%.⁴⁴

If blood cultures are negative, then percutaneous needle biopsy with either fluoroscopic or CT guidance should be performed.¹⁰⁷ If the biopsy is unrevealing, a repeat percutaneous biopsy or open biopsy may be necessary. Antibiotics should be withheld, even in a patient with rapidly progressing neurologic symptoms, until an adequate sample can be obtained at the time of surgery. All biopsy samples should be sent for aerobic, anaerobic, mycobacterial, and fungal stains and cultures. Occasionally extended periods of incubation are necessary for fastidious organisms.

All patients with SEA need antibacterial treatment. After obtaining appropriate cultures or biopsy specimens, the patient is usually started on broad-spectrum antibiotics that are tailored once the species and antibiotic sensitivities are known. The initial antibiotic regimen should have activity against S. aureus, the most common organism, should be tolerable for weeks of therapy, and should have good bone penetration due to the frequency of adjacent osteomyelitis.¹⁰⁸ Many regimens of empiric antibiotics have been reported in the literature.⁹⁰ The combination of a synthetic penicillin with activity against Staphylococcus, such as nafcillin, with a third- or fourth-generation cephalosporin for gram-negative rod coverage is one option. Vancomycin should be substituted for nafcillin in areas with a high prevalence of MRSA or if the patient is allergic to penicillin.¹⁰⁹ Antipseudomonal coverage should be considered in patients with a history of IVDU.⁹⁶ Duration of antibiotic treatment is usually at least 6 weeks and sometimes longer in patients with extensive bony involvement or immunocompromise. Consultation with an infectious disease specialist is highly recommended for determining the best antibiotic regimen and the length of treatment and for monitoring for adverse effects of the antibiotics selected.

Surgical decompression with debridement and drainage of infected material is the other cornerstone of treatment of SEA. Traditionally, the recommendation was that all patients with SEA should undergo urgent surgical decompression and drainage. The guiding principle was “ubi pus, ibi evacua.”¹¹⁰ There are numerous reports of deterioration when surgical decompression was delayed. This principle still holds for most patients; however, there have been a number of reports of good outcomes in carefully selected patients who have received antibiotics or antibiotics plus percutaneous drainage without surgical decompression. Rigomonti et al. described the use of nonoperative treatment in patients in whom the causative organism had been identified and who had minimal or no neurologic symptoms, medical comorbidities precluding surgery, extensive spine involvement, or stable paraplegia. Overall they found that two thirds of these patients had a good outcome without surgical intervention.⁴⁶ Since then, a number of other nonrandomized comparisons have been conducted of nonoperative versus operative management in similarly selected groups of patients that have found conflicting data, with some groups finding that nonoperative management can provide equivalent results as long as close monitoring is performed,^111–113 as opposed to a report by Curry et al. that indicated worse outcomes in patients treated conservatively.¹¹⁴ The most important determinant of the need for surgery is the presence of neurologic deficits, which if present, and not long standing, warrant urgent decompression. Any patient being treated nonoperatively needs to be monitored extremely closely for the development of neurologic deficits, which occur in approximately 20% of patients,¹¹⁵ that would require urgent surgical intervention.

Surgical approach is dictated by the location of the abscess either ventral or dorsal to the spinal cord. The majority of SEAs are located dorsally⁸⁸ and are managed with laminectomy, drainage of pus, debridement of infected material, and copious irrigation, with the option of postoperative drainage or suction-irrigation.¹¹⁶ Care must be taken not to cause instability by extending the laminectomy too far laterally. The possibility of concomitant subdural abscess should be considered if the dura appears tense and nonpulsatile after evacuation of the epidural pus.¹¹⁷ Laminotomy for the drainage of dorsal abscesses has also been described, which may be especially beneficial in children to minimize the risk of future spinal instability.^118,119 Monofilament suture is recommended for closure.

An SEA located ventrally to the thecal sac usually requires an anterior approach, especially since concomitant discitis or osteomyelitis is often present and requires debridement as well. A ventral liquid pus collection, as opposed to a more solid, granulomatous collection, can sometimes be drained via a dorsal approach, especially below the conus medullaris; however, the great majority of cases require an anterior approach to achieve adequate decompression and drainage. Anterior approaches require graft with or without placement of instrumentation. The risk of infection of graft material or instrumentation is minimized with adequate debridement of infected bone and tissue. Numerous studies have shown that infection does not preclude the use of autograft, allograft, or instrumentation when combined with adequate debridement and appropriate courses of antibiotics.^120–123

Cervical SEAs tend to become symptomatic more rapidly, have a higher risk of severe neurologic deficits, and an overall higher mortality rate.¹²⁴ The severity of presentation is due to the smaller epidural space in the cervical region. Cervical SEAs are more likely to be ventrally located and have associated discitis and osteomyelitis for which an anterior approach with resection of disc and bone and reconstruction with graft with or without instrumentation is warranted.

Thoracic epidural abscesses also often present with significant neurologic compromise and present a technical challenge due to the difficulty of approach to a ventral SEA. The region involved dictates the approach. The cervicothoracic junction is particularly difficult to access. Partial sternotomy or manubrial resection⁴⁴ and transpedicular, lateral extracavitary,^125,126 or parascapular extrapleural¹²⁷ approaches have all been used to access this region. Anterior approaches in this region often necessitate concurrent dorsal instrumentation and fusion to prevent instability.^122,128 Anterior approaches to the midthoracic spine include thoracotomy,⁴⁴ lateral extracavitary,^125,126 or the retropleural approach.¹²⁹ Anterior approaches to the lower thoracic spine can be accomplished via a thoracoabdominal approach.

Lumbar and lumbosacral epidural abscesses are more likely to present without neurologic deficits and are more likely to have a favorable outcome, due to the increased size of the subarachnoid space below the conus medullaris. Ventral abscesses in this region are more likely to be accessible from a dorsal approach, though a ventral approach, such as a retroperitoneal approach, should be used if there is significant bony involvement or the purulent material does not appear to be liquid.

Extremely large SEAs involving the entire length of the spine have been reported. Medical management is often recommended for multisegmental SEA; however, there are case reports of good outcomes with extended laminectomy and surgical debridement of cervicothoracolumbar SEAs.¹²⁷

All patients with SEAs should be followed closely for changes in clinical condition. Serial monitoring of white blood cell count and ESR can be beneficial in determining the response to therapy. Most patients benefit from use of an orthosis and a course of rehabilitation.

Outcomes for patients with SEA have been improving since Walter Dandy’s 1926 review, which reported an 81% mortality rate.¹³⁰ A comprehensive meta-analysis found that mortality has decreased from around 34% during the period of 1954 to 1960 to 15% between 1991 and 1997. Moreover, the number of patients experiencing complete recovery has improved from 28% to 41% in the same time periods.⁹⁰ Mortality from SEA is likely now closer to 5% to 10%, usually caused by sepsis, meningitis, or underlying disease.⁹⁵ The best predictors of outcome are neurologic status at presentation and duration of neurologic deficits.^{88,103,104,131} Patients with paralysis of more than 48 to 36 hours’ duration have very little chance of recovery. Permanent paralysis still occurs in approximately 4% to 22% of patients.⁹⁵ Location of the SEA in the cervical or thoracic region, older age, significant cord compression, and delay of diagnosis also negatively affect the overall prognosis.¹¹⁵ Unfortunately, an estimated one half of cases of SEA are still initially misdiagnosed, emphasizing the importance of clinical suspicion to aid in the early diagnosis of SEA prior to permanent neurologic injury.⁹⁵

Spinal Subdural Empyema

Spinal subdural abscesses are localized infections inside the dura surrounding the spinal cord with or without associated meningitis. No estimate of incidence is available, and the total number of patients presented in case reports is less than a hundred.^115,117,132 The vast majority of reported cases are caused by S. aureus, although a number of other gram-positive cocci, gram-negative rods, anaerobes, and tuberculosis microbes have been reported as causative agents. The lumbar region is the area most likely to be involved, followed by the thoracic and cervical regions.¹³² Cases of simultaneous spinal and cranial subdural empyemas have been reported.¹³³ The reported cases reveal an approximately equal distribution between men and women, with the most common age range being between 50 and 70, though all ages can be affected.¹³²

Patients with spinal subdural abscesses have many of the same predisposing factors as patients with SEA. The pathogenesis is thought to be most commonly hematogenous spread from a distant source, such as a skin abscess. Other sources include direct extension from infected CSF, introduction of infection during surgery, direct inoculation during lumbar puncture or spinal anesthesia, and occasionally via a dermal sinus tract.^134,135 Injury to the spinal cord can be caused by direct compression, associated meningitis, or inflammation of the vessels of the spinal cord, causing thrombosis or hemorrhagic infarction.

Clinical signs and symptoms, as well as progression of neurologic deficits, are similar to SEAs except that subdural abscesses are more likely to present with signs of meningeal irritation and are less likely to demonstrate localized tenderness. The most common symptoms are of back pain and fever, followed by neurologic deficits. Most reported cases presented with symptoms developing in a subacute fashion (1–8 weeks).¹¹⁷ Spinal subdural empyema is often initially misdiagnosed for one of the more common conditions on the differential diagnosis, including transverse myelitis, epidural hematoma or abscess, vertebral osteomyelitis, discitis, or intradural tumor.

As with SEA, patients with subdural empyemas often have a leukocytosis with a left shift as well as elevations of ESR and CRP; however, normal values do not rule out the condition. Blood cultures may be useful for identifying the causative organism faster if the abscess has a hematogenous origin.

The best radiologic tool for diagnosing a subdural empyema is MRI with contrast because of its sensitivity, noninvasiveness, and ability to clearly identify the location and extent of the abscess.¹³⁶ CT-myelography may be useful when the patient is unable to undergo an MRI, but there are reports of difficulty in differentiating a subdural abscess from an epidural abscess with a CT-myelogram.^137,138 There is often minimal or no involvement of bone, making radiographs and noncontrasted CT less useful.

The management of subdural empyemas involves urgent surgical drainage and IV antibiotics. The surgery usually involves laminectomy, durotomy, drainage of pus and debridement of infected tissue, and copious irrigation. The dura is often found to be tense and nonpulsatile. If an extended area is involved, multiple separate laminectomies might be used to minimize the risk of future instability. Aerobic, anaerobic, and mycobacterial cultures should be obtained to guide antibiotic treatment. Though spinal subdural empyemas caused by fungal infection have not been reported, fungal cultures should probably also be obtained. Antibiotics should only be started after obtaining cultures, unless the patient is frankly septic. Intraoperative ultrasound can aid in identifying the true extent of the abscess and ensuring complete drainage.¹³⁹ Associated epidural abscess or osteomyelitis should also be debrided, and, if such an infection is present, the dermal sinuses should be excised. Most patients are found to have frank pus at surgery, even if they presented with chronic symptoms (>8 weeks of symptoms).¹¹⁷

The importance of surgical drainage is illustrated in the review by Bartels et al. of 44 patients, in which only one of five patients treated conservatively survived, in contrast to the 81% survival rate of patients treated with surgery in addition to antibiotics. Moreover, in the surgical group, approximately 30% of patients made a complete recovery, with the remainder of survivors showing improvement.¹¹⁷ Broad-spectrum IV antibiotics, similar to the regimen used for SEA, are started once cultures are obtained and narrowed appropriately once species and sensitivities are known. Antibiotics are continued for at least 6 weeks. Spinal subdural empyemas have a high mortality rate if not properly managed, but with prompt diagnosis, surgical drainage, and appropriate IV antibiotics, a majority of patients should survive and have a good recovery.^117,140

Intramedullary Pyogenic Spinal Cord Abscess

Intramedullary spinal cord abscess (ISCA) is a rare lesion involving infection contained within the spinal cord parenchyma. Slightly more than a hundred cases have been reported in the literature.¹⁴¹ Only one case of ISCA was found in a series of 40,000 autopsies.¹⁴² The proportion of pediatric cases is much higher for ISCA than epidural or subdural spinal abscesses, with approximately 40% of all cases presenting prior to age 20 and 25% of cases occurring in children younger than age 10.¹⁴³ The increased preponderance of pediatric patients is a result of the role played by congenital spine lesions in the pathophysiology of the disease, especially dermal sinuses, which are responsible for approximately a quarter of infections.¹⁴⁴ Overall, the thoracolumbar and lumbrosacral regions are the most commonly involved, especially in patients with midline deformities. In ISCA patients without midline deformities, the cervical region was more likely to be involved.¹⁴¹ These patients were also more likely to be adults. Most cases of ISCA are solitary, but some have multiple foci of infection and a number of cases of holocord ISCA have been documented.^145–147

The majority of currently diagnosed ISCAs have a cryptogenic source, likely from transient bacteremia from breaks in the mucosa or skin. Other sources include contiguous spread from congenital defects, surgery, or trauma, and hematogenous spread from known sources including IVDU.¹⁴⁴ Many of the patients, especially in the adult population, have comorbid conditions that impair the immune response (e.g., HIV), similar to those seen in the SEA population.⁹²

Staphylococcus species are the most common causative organisms, followed by Streptococcus species. However, the proportion of ISCAs caused by S. aureus is much lower than in other types of spinal abscess. ISCAs caused by Listeria, Brucella, Actinomyces, gram-negative rods including Pseudomonas, anaerobes, Mycobacterium tuberculosis, Histoplasma, Toxoplasma, Candida, and parasites have been reported.^141,148 Unfortunately, around 30% of cases strongly suggestive of ISCA have negative cultures.¹⁴⁸

Clinically, ISCAs have been categorized by duration of symptoms as acute (<1 week), subacute (1–6 weeks), or chronic (>6 weeks).¹⁴⁹ Acute cases often present with pain, fever, leukocytosis, elevated ESR, and progressive neurologic defects similar to acute transverse myelitis, though, like SEAs, presentation can be quite varied. Chronic ISCA often presents in a fashion similar to intramedullary spinal cord tumors, with a predominance of neurologic deficits occurring in the absence of fever or systemic signs of inflammation.¹⁵⁰ Patients can also have concurrent meningitis or brain abscesses.

MRI with contrast is the most useful diagnostic test for identifying ISCA and delineating its location and extent. Most lesions are hypointense on T1-weighted imaging, hyperintense on T2-weighted imaging, and demonstrate nodular or rim enhancement on postcontrast T1 imaging. The areas of T2 signal abnormality are usually more extensive than that seen with the postcontrast T1 sequences and likely represent adjacent edema. The differential diagnosis for ISCA includes intramedullary spinal cord tumors, acute transverse myelitis, multiple sclerosis, Guillain-Barré syndrome, and spinal cord infarct.¹⁵¹ Increased diffusion restriction on diffusion-weighted imaging at the center of the lesion may help differentiate ISCA from intramedullary tumors. CT-myelography can be used to diagnose an intramedullary enlargement and is useful when MRI is not possible, but its specificity and ability to delineate anatomic details is limited.

Treatment entails surgical drainage and IV antibiotics. The surgical approach involves laminectomy, dorsal myelotomy centered at the site of maximal thickness of the abscess, drainage of the abscess with collection of specimen for cultures, and copious irrigation.¹⁵² The specimen should be sent for Gram stain and aerobic, anaerobic, mycobacterial, and fungal cultures. The use of a limited laminectomy and myelotomy to allow a drainage catheter to be passed rostrally has been described for holocord ICSAs.¹⁴⁶ Excision of any associated dermal sinus should also occur. The risk of ISCA in patients with dermal sinuses is one of the reasons children should be screened for midline back abnormalities and why dermal sinuses should be prophylactically excised at the earliest possible time.¹⁴⁶

Broad-spectrum IV antibiotics are started after obtaining cultures and are narrowed as speciation and specificities become available. The choice of empiric antibiotics is similar to those used for SEA except that high-dose ampicillin should be added because of the relative frequency of Listeria monocytogenes in reported cases of ISCA.¹⁴¹ The duration of IV antibiotics should be at least 4 to 6 weeks, with follow-up neurologic examinations, laboratory studies, and imaging to demonstrate successful response to therapy and resolution of the lesion.¹⁴⁴ A few case reports and reviews discuss successful treatment of ISCA with antibiotics alone, but the role of medical management alone has yet to be defined.¹⁴¹

ISCA mortality rates have been progressively improving from the reported 90% mortality rate in cases in the preantibiotic era (1830–1944).¹⁵³ A recent review of cases from 1977 to 1997 reported a mortality rate of 8%.¹⁴⁴ Rapidly progressive deficits increase the likelihood of a poor outcome.¹⁴⁹ Most survivors have an improvement in neurologic status after treatment with surgery and antibiotics, but a substantial proportion, approximately 70%, have persistent neurologic deficits.¹⁴⁴

Tuberculosis

Tuberculosis may involve the vertebral column, the epidural space, the dura mater, the arachnoid, or the spinal cord itself. Tuberculous spinal infection most commonly involves the vertebral body. However, in up to 10% of patients the neural arch, transverse processes, or spinous processes may be affected. Tuberculous spondylitis most commonly involves the lower thoracic and upper lumbar vertebrae and most commonly affects the vertebral body. It is usually confined to a single level. Tuberculous spondylitis, with subsequent spinal cord compression, continues to be a major public health problem throughout much of the world.

Neurologic complications occur in 10% to 25% of cases, particularly if the thoracic spine is involved. Neurologic impairment may be caused by direct spinal cord compression or may be secondary to collapse of infected vertebrae, with subsequent spinal cord compression.

No distinctive pattern of neurologic signs or symptoms exists with Pott paraplegia. However, pain and local spine tenderness occur in an overwhelming number of patients. Radicular pain is common.

Radiographically, early vertebral body decalcification is observed about the disc, with slight diminution of the height of the disc space. Later, frank vertebral erosion and collapse occur, and paravertebral or psoas abscesses may appear. Sclerotic changes also may be present because of concomitant bone regeneration and fusion of vertebral bodies. Caseation beneath the anterior longitudinal ligament causes scalloping of the ventral vertebral border.

CT shows the expected vertebral body involvement. However, CT can also depict paraspinal abscess and an epidural tuberculous collection. Contrast enhancement may be useful for further delineation.

Spinal tuberculosis can be treated either medically or surgically. Treatment objectives include healing the disease, preventing or minimizing neurologic dysfunction, and preventing any further gibbus deformity. Treatment with pharmacologic agents has been shown to be successful in multiple series. The current recommendations for the first-line antibiotic treatment of spinal tuberculosis involve 6 to 9 months of isoniazid and rifampin with ethambutol and pyrazinamide added for the first 2 months.¹⁵⁴ This shorter 6- to 9-month course was equivalent to longer 18-month regimens involving isoniazid and para-aminosalicylic acid or ethambutol in clinical trials.^155,156 M. tuberculosis isolates should be tested for drug susceptibilities to guide therapy.

When the spine is stable and neurologic signs are absent or minimal, initial therapy should be pharmacologic rather than surgical. More than 85% of patients with Pott paraplegia make an excellent recovery with pharmacotherapy. Routine focal debridement and abscess evacuation in addition to antibiotics has not been shown to provide major benefit over antibiotics alone.¹⁵⁶ In general, surgery should be reserved for diagnostic biopsy, spinal instability, severe deformity, significant abscesses, open draining sinuses, or myelopathy.¹⁵⁷ Surgery often requires ventral decompression and stabilization. These ventral procedures in the thoracic spine are extensive and are often dangerous, fraught with the potential for catastrophe. In addition, any deformity correction obtained with surgery may subsequently recede with time.

Brucellosis

The causative agents in brucellosis are small, nonmotile, non–spore-forming, aerobic gram-negative coccobacilli that are commonly found in domestic animals, including Brucella melitensis (goats), Brucella abortus (cattle), B. canis (dogs), and B. suis (swine). The organism is usually transmitted to humans by ingestion of contaminated products, skin wound contamination from infected animal tissues, and inhalation of aerosols. The disease affects approximately 500,000 people per year worldwide.¹⁵⁸ Increasing use of milk pasteurization has resulted in a decreasing incidence of brucellosis in the United States. Likewise, brucellosis is also uncommon in other developed countries because of milk pasteurization.

Brucella infections are often asymptomatic. Initial infection leads to immunity in more than 90% of cases. After an incubation period of 10 days to 3 weeks, the patient typically develops a low-grade fever, malaise, lymphadenopathy, hepatosplenomegaly, and diffuse arthralgias. The infection spreads through the lymphatic system, resulting in acute systemic infection and chronic relapsing disease (undulant fever). However, a classic undulant fever rarely occurs in patients.¹⁵⁹

Failure to provide adequate treatment at this stage can result in involvement of almost any organ system. After the initial illness, which may last for several days to weeks, relapse occurs in approximately 5% of patients. Relapses seldom occur in appropriately treated patients and often are the result of focal suppurative lesions. Musculoskeletal involvement is the most common complication of brucellosis. The spine is most commonly affected. Brucellar spondylitis typically develops secondary to chronic brucellosis and occurs in 10% to 50% of patients with brucellosis.¹⁶⁰ Brucellosis is one of the major causes of spondylitis in the Mediterranean basin. Of those patients with spinal brucellosis, approximately 12% have some degree of spinal cord compromise.

Brucellar spondylitis should be part of the differential diagnosis of any patient with back and radicular pain in a region where brucellosis is endemic. Lumbar involvement is most common. Localized back pain is the most common symptom. It may be present even at rest. In most cases, radiating pelvic and girdle pains are often noted, along with restriction of movement, muscle spasms, tenderness, and signs of nerve root involvement. Neurologic deficits occur in approximately 20% of patients. Formation of a paraspinal or epidural abscess is uncommon but can occur with severe infections.¹⁶¹

Pathologic studies suggest the infection originates within the body of the vertebra, particularly in the more vascularized ventral portion, and only later extends to the intervertebral disc. The infected disc then may become necrotic and subsequently degenerate. As it bulges, the disc may press on adjacent neural structures. Usually, only one or two vertebrae are involved in brucellar infections. Infective organisms can be recovered from the infected disc or bony material in approximately 20% of cases. Serologic tests may be required to diagnose a brucellar spine infection.

Involvement of the spine can be either focal or diffuse, with a predilection to the lumbar region. Hallmarks of focal brucellar spondylitis include vertebral end-plate erosion and sclerosis, inflammatory changes, and intact discs. Features of diffuse brucellar spondylitis include osteomyelitis of neighboring vertebrae, involvement of the intervening disc, and epidural extension.¹⁶² Radiographic changes occur relatively late in the course of the disease and are similar to but less severe than those observed with tuberculosis. Plain radiographs demonstrate disc space involvement with erosion of the adjacent cortical bone, preservation of relatively intact vertebral architecture despite the amount of infection present, and absence of gibbus formations. Plain radiographs demonstrate a thinning of the disc space and erosion of the vertebral body adjacent to the involved disc. This epiphysitis usually occurs in the ventral-rostral angle and may be the main sign of bone destruction. Osteophytic bridging occurs across the infected disc interspace. CT demonstrates destruction of both cortical and cancellous bone. MRI and CT findings are similar for tuberculosis and brucellosis, except that tuberculosis produces more kyphosis and paraspinal abscess formation.

The mainstay of treatment for brucellosis is antibiotic therapy. A recent systematic review recommends that the first-line treatment for brucellosis should be combination therapy with doxycycline for 6 weeks and gentamicin for the initial 2 weeks, with the optional addition of rifampin for a total of 6 weeks.¹⁶³ Spinal brucellosis appears to have a higher incidence of recurrence, which leads some authors to recommend an antibiotic course of 6 months.¹⁶⁴

Although surgery is rarely necessary, the indications for surgery for brucellar spondylitis are similar to those for tuberculosis. The role of stabilization of the spine, or decompression of the spinal cord with stabilization, is determined by the clinical condition. Disc excision may be required for an infected, bulging disc causing neurologic symptoms, and laminectomy may be indicated for an epidural infection producing neural decompensation. The use of a spine orthosis should be considered if there is spinal involvement, but surgical intervention is not warranted.

Brucellosis is a completely curable infection. The primary pitfall is a delay of more than 1 month in diagnosis and treatment, which can lead to multisystem involvement and severe sequelae. Many patients with brucellar spondylitis recover spontaneously, which differentiates this entity from spinal tuberculosis, which is progressive.

Actinomycosis

The actinomycetes are a heterogeneous group whose morphology suggests fungus; however, they are classified as bacteria because of their small size, primitive nuclear organization, and cell wall composition. The usual infective organism for most cases of actinomycosis is Actinomyces israelii. Once known as ray fungus, A. israelii is now recognized as a gram-positive, non-acid–fast anaerobic bacterium that is intermediate between classic bacteria and higher fungi. The bacteria are present in the oral cavity, both on carious teeth and on tonsillar crypts. Endogenous organisms gain entry to the body via breaks in mucous membranes.

Actinomycosis is a noncontagious, suppurative, bacterial infection characterized by chronic inflammatory induration, sinus tract formation, fever, and leukocytosis. The pathologic reaction of the body to actinomycetes is typically suppuration. Acute and chronic inflammatory tissue is reminiscent of staphylococcal infections. Areas of infection are most characteristic for their gross appearance of sulfur granules, which are actually collections of foamy macrophages.

The common sites of involvement are the face, thorax, and abdomen. Involvement of the spine is rare (<1% of all patients with actinomycosis) and is usually the result of contiguous spread from nearby structures (e.g., thoracic infection). Early in the disease there may be vertebral body destruction, with new bone formation leading to a honeycomb appearance that may involve the pedicles, transverse processes, and ribs. After treatment, increasing sclerosis occurs, along with bone bridging and fusion between involved vertebrae. Unlike tuberculosis, from which this infection must be differentiated, actinomycosis rarely destroys the intervertebral disc.

Involvement of the CNS occurs by hematogenous spread from a pulmonary focus or by direct spread from lesions involving the skull, face, and throat, possibly via the lymphatics. Diagnosis is generally made by percutaneous needle biopsy and culture.

Most patients can be treated nonoperatively with antibiotics and spinal immobilization. Before the advent of penicillin, approximately 75% of cases were diagnosed postmortem. The disease involves the vertebrae and ribs in less than 1% of patients who have actinomycosis. Isolated vertebral body infections can be adequately treated nonoperatively with aggressive antibiotic therapy, usually IV penicillin G for 6 weeks followed by 6 to 12 months of oral penicillin or amoxicillin.¹⁶⁵ Tetracycline, doxycycline, and clindamycin have all been used successfully in patients with penicillin allergies. Indications for operative intervention include epidural infection with spinal cord compression, large abscesses, and progressive spinal deformity.

Mortality is high in untreated or improperly treated cases. Thus it is important to distinguish actinomycosis from other vertebral infections, such as pyogenic osteomyelitis or tuberculosis. Even today, an accurate diagnosis often is not made until a late stage; therefore, assiduous efforts must be made to obtain bacterial specimens from the infected site.

Nocardiosis

Nocardia asteroides is the most common human pathogen in this family of aerobic, weakly gram-positive bacteria. It is a natural soil saprophyte, often found in decaying organic matter. Infection most often occurs through the respiratory tract, although other modes of infection may occur. The infection is most commonly observed in immunocompromised hosts.

Nocardiosis may imitate a chronic granulomatous response, but more commonly the histologic features are suppurative necrosis and abscess formation, which are typical of pyogenic infections.

The most common primary site is the pulmonary system, but dissemination to nearly any organ occurs in 45% of cases. Dissemination to the brain, meninges, and spinal cord occurs in 23% of patients, but hematogenous involvement of the vertebrae is uncommon. Epidural spinal cord compression from vertebral osteomyelitis has been reported.

If there is no spinal cord compression or large abscess, medical therapy alone is often sufficient. Sulfonamides, in conjunction with appropriate surgery, have been the mainstay of treatment since the 1940s. The use of trimethoprim-sulfamethoxazole (TMP-SMX) for 6 or more months has been described for the treatment of systemic nocardiosis.¹⁶⁶ Many other antibiotics have been used, either alone or in combination. The optimal duration of therapy is uncertain, but because of the possibility of relapse, treatment is often continued for many months after apparent cure. A poor response to treatment may be related to the presence of a second pathogen.

Syphilis

Syphilitic spinal involvement was common at the beginning of the 20th century but is now quite rare due to the availability of antibiotics. The spirochete Treponema pallidum is responsible for syphilis. Syphilis is often referred to as the great imitator, because it can present and resemble many other diseases. Spinal involvement typically occurs with tertiary syphilis and presents as either Charcot arthropathy or intraosseous gumma formation.

Neuropathic (Charcot) arthropathy of the axial skeleton occurs in approximately 10% to 20% of patients with tabes dorsalis. Charcot arthropathy is a neuropathic disorder producing spinal degenerative changes. Tabes dorsalis causes posterior column degeneration with consequent loss of protective proprioceptive sensation; consequently, there is subluxation and traumatization of the intervertebral joints, destruction of the discs, and fragmentation of the articular cartilage and the subchondral bone. This produces excessive bone formation within and around the joint, as well as reactive bony sclerosis and spinal deformity. These changes occur most commonly in the lumbar and thoracic spine and are identifiable on plain radiographs. Charcot arthropathy may be detected coincidentally or may produce low back pain or nerve root involvement if destruction and hypertrophic changes are severe. Characteristically, the radiographic changes are out of proportion to the severity of the patient’s complaints.

Charcot arthropathy affecting the spine is notoriously difficult to treat. Treatment includes an orthosis to limit excessive movement and to minimize further injury. The role of fusion is undetermined.

The syphilitic gumma lesion is composed of micro-organisms and the local tissue reaction to the organisms. Gummas are rare, destructive, and usually symptomatic, causing collapse and neurologic deficits. The clinical features of spinal gumma are often difficult to distinguish from those of coincident neuropathy, which is often present, and biopsy is necessary for the diagnosis of spinal gumma. The indications for surgically treating syphilitic gummas are similar to those for treating tuberculous spondylitis. The treatment of choice for syphilis is penicillin, though the dosing depends on the specific manifestation of the disease.¹⁶⁷

Aspergillosis

Aspergillus is a saprophytic mold that is ubiquitous in the environment. Although Aspergillus involvement of the CNS does occasionally occur in otherwise healthy individuals, it is more commonly associated with IV drug abusers and severely immunocompromised patients.

Infection typically is acquired by inhaling small spores (conidia). Although uncommon, spine involvement nearly always results from hematogenous spread from the lungs; though postoperative Aspergillus discitis has been reported after lumbar discectomy.¹⁷⁰ Vertebral involvement can also result from contiguous spread from the lungs to the vertebral bodies. Vascular invasion is common in immunocompromised patients, and it leads to tissue necrosis with abundant hyphal proliferation.¹⁷¹ In patients with chronic granulomatous disease, vascular invasion is uncommon and hyphae are sparse.

The radiographic findings of aspergillosis are similar to those for tuberculous spondylitis. Destruction of adjacent disc plates with subsequent collapse leads to severe pain and neurologic deficits. Disc space narrowing, involvement of adjacent vertebrae, and the presence of paraspinal abscesses are common. Dense new bone formation with small lytic lesions without sequestration may be observed. Spinal CT scans are extremely useful in delineating the extent of spinal involvement, but the radiographic picture is not specific for Aspergillus.

Clinically, sinus tract formation is characteristic, though often not present. The incidence of epidural abscess formation, in association with neurologic deficits, is high. Diagnosis is established by percutaneous or open biopsy. Voriconazole has been demonstrated to be superior to amphotericin B for the treatment of invasive aspergillosis. Liposomal amphotericin, posaconazole, itraconazole, caspofungin, or micofungin are all possibilities for salvage therapy in cases refractory to voriconazole therapy. Treatment duration is usually 6 to 8 weeks minimum for patients with normal immune systems. Immunocompromised patients likely require longer treatment and usually warrant chronic suppression therapy.¹⁷²

In addition to antibiotics, surgical debridement with resection of devitalized bone and cartilage is important to achieve cure in most cases. With Aspergillus discitis, early surgery with vigorous surgical debridement combined with antifungal treatment, yields a good outcome in most cases.^170,173 There are rare reports of successful treatment with antifungal agents alone.^174,175 The prognosis of patients with Aspergillus spondylitis overall is guarded, in large part due to the patient’s usually poor condition and numerous comorbities.

Blastomycosis

Blastomycosis is caused by Blastomyces dermatitidis, a dimorphic fungus that is endemic to the midwestern, southeastern, and south central United States. Primary infection in humans occurs by inhalation of conidia, which then convert to the yeast phase in the lung. The incubation period for acute pulmonary infection is 30 to 45 days. The symptoms are nonspecific, and acute pulmonary infection may occasionally be undetected. Extrapulmonary disease involving the skin, bones, genitourinary system, or CNS occurs in approximately 25% to 40% of cases and is much more common in immunocompromised patients. The organism spreads hematogenously from the lungs to the spine.¹⁷⁶ Men are affected nine times more commonly than women, particularly those with a history of alcohol abuse.

Thoracic and lumbar lesions are more common than cervical lesions. The radiographic findings resemble those of tuberculous spondylitis, with disc space narrowing, ventral vertebral body involvement, and the development of large paraspinal abscesses. Unlike lesions in tuberculosis, thoracic and lumbar lesions often invade adjacent ribs, involve the dorsal elements, and produce draining sinuses. Collapse and gibbus deformity are more common with blastomycosis than with any of the other fungal diseases. Diagnosis usually requires biopsy, unless blastomycosis has been reliably detected elsewhere in the body either via culture of respiratory secretions or antigen testing. Serologic testing generally has low sensitivity and specificity.

Before the availability of effective antimicrobial therapy, the mortality rate exceeded 60%.¹⁷⁷ CNS blastomycosis should be treated with IV liposomal amphotericin B for 4 to 6 weeks followed by oral azole therapy (fluconazole, itraconazole, or voriconazole) for at least 12 months. Though mild pulmonary blastomycosis often resolves without treatment, antibiotic therapy should be considered to prevent dissemination to extrapulmonary sites.¹⁷⁸ Surgery is generally reserved for patients with severe infections, such as epidural abscesses, that are causing neurologic deficits.

Coccidioidomycosis

Coccidioidomycosis is caused by Coccidioides immitis, a fungus that is endemic to the southwestern United States, Central America, South America, and central California, where the infection is often referred to as San Joaquin Valley fever.

The primary focus of disease is the lungs, but the disease becomes disseminated in 0.5% of cases, and the rate of extrapulmonary disease is much higher in immunocompromised hosts.¹⁷⁹ The organism enters the body when arthroconidia are inhaled into the lungs and can secondarily disseminate via hematogenous spread. Osseous lesions are found in 20% of those with disseminated disease. Vertebral lesions are most common in the thoracic and lumbar spine. Multicentric disease is common. Radiographic studies usually reveal that the intervertebral disc is relatively uninvolved compared with the vertebral body, pedicles, and transverse processes. Contiguous rib involvement is also common. Paraspinal abscesses and skin tracts are common.

Extrapulmonary coccidioidomycosis is usually treated with oral ketoconazole, itraconazole, or fluconazole. IV amphotericin B is indicated for rapidly progressive infections or with infections not responsive to initial therapy. Surgical debridement is indicated for large abscesses, neurologic compromise, spinal instability, or failure of medical therapy.¹⁸⁰

Cryptococcosis

Cryptococcosis is a subacute or chronic infection caused by a yeastlike fungus surrounded by a gelatinous capsule, Cryptococcus neoformans. Infection is acquired by inhalation of the aerosolized organism. Because many cases of cryptococcal osteomyelitis occur in normal hosts, it should be considered in the differential diagnosis even in a normal host.¹⁸¹ Osseous involvement occurs in less than 5% of all cases and resembles cold abscesses. Sinus tracts and abscess formation are rare.

The onset of cryptococcosis is usually insidious. The bone infection typically has an indolent course. Both serum and CSF agglutination tests are available. Testing for cryptococcal antigen in the serum should be done prior to invasive diagnostic procedures.¹⁸¹ Radiographic studies show lucent lesions of the vertebral bodies with sharply scalloped margins and little, if any, reactive sclerosis or periosteal new bone formation. The disc spaces are typically unaffected.

Treatment for cryptococcosis consists of a 4- to 6-week combined induction regimen of IV amphotericin B and oral flucytosine followed by an 8-week course of high-dose oral fluconazole for consolidation. A lower maintenance dose of fluconazole is then continued for 6 to 12 months. A high relapse rate is common, particularly in patients with AIDS, whose disease is usually controlled rather than cured. All patients with cryptococcosis should be screened for HIV.

Cysticercosis

Cysticercosis is caused by the pork tapeworm Taenia solium. This disease is rare in developed areas such as the United States and Western Europe; however, it remains a significant problem for many economically deprived regions, including Central and South America, Africa, India, and Asia. This disease should be considered when treating patients who have recently emigrated from these areas.

Humans usually become infected by ingesting infected undercooked pork. For disseminated disease to occur, gravid proglottids or eggs must be digested by gastric juices before they hatch and liberate oncospheres, which penetrate the intestinal wall and spread widely.

Spinal cysticercosis occurs in 2% to 5% of all neurocysticercosis cases, usually as a result of intracranial parasites migrating caudally into the subarachnoid space, where they may settle at any level within the spinal canal. The presentation is variable. Backache, radiculopathy, and slowly progressive paraparesis are all possible.

Cysticercosis is suggested by a history of infection with an adult worm, multiple subcutaneous nodules, typical symptoms, previous residence in highly endemic regions where undercooked pork may have been eaten, and eosinophilia. Indirect hemagglutination tests may be positive in the blood or spinal fluid; however, a negative result does not rule out cysticercosis.

MRI is superior to CT for recognition of the subarachnoid cyst, the contained lesion, and adjacent spinal cord edema. Intramedullary inflammatory changes associated with those cysts may also be demonstrated.

Both albendazole and praziquantel have proven effective in the treatment of both cerebral and spinal cysticercosis. Recent analysis favors albendazole over praziquantel.¹⁸² Because of the CNS’s inflammatory reaction to dying parasites, concomitant administration of steroids to minimize this inflammatory reaction has been recommended. Excision of the cyst has produced significant improvement in patients with neurologic deficits secondary to neural compression.

Echinococcosis

Echinococcosis (also known as hydatidosis) is a rare disease in developed countries. It is caused by either Echinococcus granulosus or E. multilocularis. It is more commonly seen in the sheep-rearing areas of South America, the southern and central parts of the former Soviet Union, Australia, and parts of Africa. Humans become infected after the ingestion of raw meat containing viable parasites. Under the action of gastric juices, the oncosphere is released and penetrates the intestinal wall, where it is transported to the liver and other organs. The skeleton is affected in approximately 2.4% of patients with echinococcosis. Of those cases, approximately 50% involve the spine.

Once the oncosphere reaches the vertebral body, it develops into its larval stage, commonly known as the hydatid cyst. The organism grows within the intratrabecular space, destroying the bone like a tumor. Unlike other organisms, it does not elicit a large inflammatory response. Adjacent bones such as ribs or the ilium may also be invaded. The organism spreads beneath the periosteum and ligaments. Spinal cord compression occurs once the bony center has been perforated.

The clinical manifestations and duration of symptoms vary considerably. Back and radicular pain is common. Paraparesis or paraplegia is a common symptom.

Plain radiographs demonstrate an expansile lytic mass that is poorly delineated and that appears multiloculated. A complete blockage of flow is a common finding with myelography. The disease is usually confined to a single vertebra with predilection to the thoracic spine. The cyst appears as a well-defined area in the vertebral body, which may be apparent only on tomography. The articular cartilage and the intervertebral disc are usually resistant to the cyst. However, in untreated and advanced cases, the articular surfaces and discs may be destroyed, vertebral collapse may occur, and the cyst may spread into the paravertebral tissues or beneath the psoas sheath, simulating an abscess caused by tuberculosis. In an endemic area, the findings suggestive of hydatid disease are ring-shaped calcification in the cyst wall, eosinophilia, and specific enzyme-linked immunosorbant assay (ELISA) or Western blot serology. CT of hydatid disease reveals more specific findings than does conventional radiography. It may show cysts within the paraspinal muscles. In addition to bone destruction, the presence of daughter cysts is pathognomonic. Arachnoiditis may be demonstrated on CT or myelography.

All patients with echinococcosis should undergo surgical debridement if possible, with complete excision of the cyst and affected bone and stabilization, as needed. Unfortunately the relatively high risk of cyst rupture (up to 44% in extradural cases) can cause anaphylaxis or seed the surgical site, leading to future recurrence.¹⁸³ A hyperosmolar saline solution washout is recommended intraoperatively to prevent cyst recurrence. Although its value remains to be established, presumably, the hypertonic saline solution disrupts any residual cysts osmotically. Albendazole and mebendazole have both been used to treat echinococcosis, with most evidence favoring albendazole as the primary agent. Treatment with albendazole should be continued for a minimum of 3 to 4 months, with one report suggesting 1 year of treatment after neural decompression.¹⁸⁴

Recent studies have observed an improved prognosis for what was once thought to be a uniformly fatal disease. However, for spinal echinococcosis, reports of recurrence rates range from 30% to 100%, and mortality rates range from 5% to 50%.¹⁸⁵ Response to therapy should be monitored with serial imaging, given the high incidence of recurrence.

Schistosomiasis

The parasitic flukes (trematodes) of the Schistosoma genus can rarely involve the CNS, including the spinal cord. Three species have been implicated in causing diseases of the spinal cord: Schistosoma mansoni, S. haematobium, and S. japonicum¹⁸⁶ The trematode larvae gain access to humans by piercing the skin of people exposed to infected waters. Once the larvae penetrate the skin, they gain access to the vascular system, develop into adults, and produce eggs, which are passed out of the urine (S. haematobium) or feces (S. mansoni and S. japonicum). Their natural hosts are freshwater snails.

Injury to the spinal cord in schistosomal infections is caused by an inflammatory response to the schistosomal eggs that have been deposited in the spinal cord parenchyma or subarachnoid space. These eggs reach the area either via direct deposition or by embolus from anastomosis of the pelvic veins with the paravertebral vascular plexus. The vertebrae and intervertebral discs are not usually involved in schistosomiasis.

The most typical clinical picture is that of transverse myelitis or myeloradiculopathy. The lumbosacral region is the most commonly affected region, though all regions of the spinal cord, including the cervical spine,¹⁸⁶ can be affected. In the acute stage of lumbosacral myeloradiculopathy the patient presents with lumbar pain, lower extremity sensory changes, and bladder dysfunction, followed by lower extremity weakness, sexual dysfunction, or bowel dysmotility.

Diagnosis is based largely on a high index of suspicion in patients with exposures to regions of the world, including South America, Asia, and Africa, where schistosomiasis is endemic. Diagnosis is aided by either positive parasitic stool examination or positive antischistosomal immune reaction in serum or CSF in the presence of MRI findings of inflammatory myelopathy, myeloradiculopathy, or intramedullary mass. Serum and CSF eosinophilia are also usually present. The gold standard of diagnosis is demonstration of Schistosoma eggs from biopsy, but the risk of biopsy often outweighs the benefits in a disease that is usually treated medically.

Treatment involves the use of schistosomicidal drugs, such as praziquantel, to kill the adult worms and stop the production of eggs. Treatment with corticosteroids has been recommended as an adjuvant to praziquantel to stop the inflammatory response to the eggs that have already been deposited, though length of treatment has not been defined, with some groups recommending up to 6 months of steroid treatment.¹⁸⁷ Surgical intervention is reserved for acute paraplegia or evidence of medullary compression, medically refractory cases, or biopsy when the diagnosis is unclear. Surgery usually involves laminectomy for decompression and possible release of spinal nerve roots with biopsy if diagnosis is uncertain.¹⁸⁸ Resection of focal lesions has also been described.¹⁸⁶