10
Back Pain in Spinal Infections
Rishi Mugesh Kanna, Ajoy Prasad Shetty, Emiliano Vialle, and Shanmuganathan Rajasekaran
■ Introduction: Pyogenic Spondylodiskitis
The spine is a common site of infection in pyogenic spondylodiskitis. Within the spine, the anterior structures (i.e., the vertebral body and the discs) are affected in more than 95% of patients.1 The incidence of pyogenic vertebral infection is reported to be 3 to 16% of all bone and joint infections, with a small increase in its incidence each year.2,3 The incidence is higher in less developed and developing nations due to malnutrition, immune deficiency states such as human immunodeficiency virus (HIV), delayed diagnosis, and lack of access to medical facilities. In developed nations, the increase is probably due to increased awareness, increased numbers of spinal surgeries, better diagnostic modalities, and the expanding at-risk group. Diabetes mellitus, malnutrition, intravenous substance abuse, HIV infection, malignancy, long-term steroid use, chronic renal failure, liver cirrhosis, septicemia, and previous spine surgery are the common predisposing factors identified. Protein malnutrition, defective cellular and antibody-mediated immunity, and steroid-mediated immunosuppression are also important. With the increase in the number of spinal surgeries, postoperative iatrogenic diskitis accounts for up to 30% of all cases of pyogenic spondylodiskitis.4
A bimodal age distribution has been observed, with the first peak occurring in young children and a second peak at approximately the fifth to sixth decades of life. Males are twice as commonly affected as females, for reasons that are not clear.5 Because of its rarity and vague presentation, diagnosis is often delayed, which can result in abscess formation and severe compression of the neural structures, leading to neurologic deficit and rarely septicemia and mortality in 2 to 4% of cases.6
Etiology
Most infections occur due to bacterial spread from a distant site to the spinal column through the bloodstream. The skin, the respiratory tract, and the genitourinary tract are the common primary foci. But in 30 to 70% of patients, a primary focus of infection cannot be detected.7 Earlier, tubercular bacilli accounted for most infections of the spine, and recent studies have found that pyogenic organisms are the common isolates. Among these, Staphylococcus aureus and Streptococcus species account for more than 50% of cases. Gram-negative organisms such as Escherichia coli and Proteus are causative in patients with urinary tract infections and intravenous drug abusers. Klebsiella pneumoniae and Pseudomonas are common isolates in patients with hospital-acquired infections. Anaerobic organisms and organisms of low virulence are common in patients with diabetes mellitus and those with penetrating spine trauma. Despite the best investigative efforts, including blood, urine, and tissue cultures to isolate the organism, in one third of cases, the infective organisms are never identified.8
Pathophysiology
The arterial route is the common route of bacterial spread to a vertebra following bacteremia. About 90 to 95% of pyogenic spinal infections affect the vertebral body or disk, and the posterior elements of the spine are infrequently involved. This is due to the increased blood supply of the cancellous bone of the vertebral body and its rich, cellular marrow. The circulating bacteria readily colonize in the subchondral end plates when the blood flow stagnates in the metaphyseal arterial loops just beneath the vertebral end plates. Due to the avascularity of the disk and the peculiar arterial anatomy of the vertebral subchondral region on either side of the disk, the subchondral region of the disk is infected first and the disk is secondarily invaded by bacteria from the end-plate region. Communicating vascular plexus of the paravertebral and epidural region enable the spread of infection from one metaphysis to the other. Vertebral body infections commonly occur in the lumbar spine because of the high blood flow to this region of the spine. In children, the intervertebral disk has penetrating arteries, and hence direct invasion of the disk can occur, resulting in primary diskitis, followed by vertebral body involvement.
Retrograde seeding of venous blood via the Batson’s venous plexus can also play a role. Whenever intra-abdominal or intrathoracic pressure increases, venous blood is shunted from the abdominal and pelvic organs toward the valveless paravertebral venous plexus. Thus, infections from pelvic and abdominal organs can reach the spine through retrograde veins. Rarely, contiguous spread of infection from a nearby infected focus such as a renal abscess, aortic vascular implants, or paravertebral nodes can infect the vertebra and disk, producing infective spondylitis.
In pyogenic spondylitis, the involvement is usually focal, but multiple-site involvement can infrequently occur in immune-deficient patients. As destruction proceeds, the vertebral canal can be invaded by pus and granulation tissue, which can cause cord compression, neurologic deficit, and systemic dissemination of bacilli, resulting in sepsis. Continued destruction of the vertebral body results in pathological collapse, kyphosis, and spinal instability. Unlike tubercular infection, where the spread of abscess is slow, in pyogenic spondylitis the abscess formation is rapid, associated with intense inflammation, resulting in early neurological deficit.
Clinical Presentation
A precipitous onset with signs of acute pyogenic infection is rare, and the usual presentation is one of insidious onset, with back pain being the most common symptom, developing in 1 or 2 weeks. The pain is initially localized to the level of infection, but vague distribution to the paraspinal areas is common. With progression, the pain is quite severe even at rest, being aggravated by the least spinal movement. Onset of severe pain can indicate severe instability, due to either gross destruction of the vertebral bodies or involvement of posterior structures, especially the facet joints. Radicular pain along the distribution of a nerve root can occur when the abscess and granulation tissue presses the corresponding nerve root.
Because low back pain is a common and nonspecific symptom, a high degree of suspicion is needed to make an early diagnosis of pyogenic spondylitis. The presence of clinical “red flags,” such as pediatric age or age > 65 years, chronic steroid intake, cancer chemotherapy, renal disease, diabetes mellitus, HIV infection, and high fever, must prompt a laboratory investigation and radiological workup.
Although fever is present in less than one third of adult patients, children with vertebral osteomyelitis can present with an abrupt onset of malaise and fever. Young children may not directly complain of back pain but rather present with refusal to eat, stiffness of the back with restricted spinal movements, and guarded walking.
Neurologic involvement occurs due to vertebral body collapse with kyphosis or with the development of large epidural abscess. It is manifested as numbness and weakness in one or both lower limbs and bladder or bowel disturbances. Where neurologic involvement is suspected, a meticulous neurologic examination must be performed, including a rectal examination to detect early cauda equina compression. This is important, as early surgical intervention in such cases would be beneficial.
Investigations
Laboratory Studies
The total and differential white cell counts, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) are the common blood tests performed to aid in the diagnosis of diskitis. Other tests including a complete hemogram and renal and liver function tests are mainly indicated for initiating antimicrobial chemotherapy and anesthetic purposes if surgical treatment is considered.
Leukocytosis (> 10,000 cells/mm3) is common in patients with pyogenic spondylitis but nonspecific. Elevation of the ESR, although nonspecific, is the most common laboratory abnormality. Elevated ESR is positive in more than 90% of patients with spinal infections.9 The average ESR in patients with pyogenic spondylitis ranges from 43 to 87 mm per hour in different studies.10,11 Unexplained back pain associated with spinal stiffness and an increased ESR should lead the clinician to suspect infective spondylitis.
The CRP is also an excellent indicator of acute inflammation. It is elevated in more than 90% of patients with spinal infection and is more specific than ESR.12 Because both ESR and CRP are sensitive markers but not specific for spinal infection, they assume more significance in combination with clinical features and imaging findings. Also, rather than single values, serial ESR and CRP values help in predicting infection in postoperative spondylodiskitis13,14 and in assessing the response to treatment.
In evaluating the treatment response to spinal infections, both ESR and CRP have significant roles. Carragee et al15 found that a 25% reduction of the initial value of the ESR after 1 month of treatment was a good prognosis marker in the treatment for spondylodiskitis. However, 50% of those with no change in the ESR values during the treatment period also had good outcome. Thus, in patients clinically responding to therapy, a raised ESR should not be a cause for concern and should not lead to unnecessary interventions or prolonged therapy.
Urine cultures are advised in situations where the genitourinary tract is considered the primary focus. Blood cultures should always be obtained in all patients, preferably during a febrile episode and prior to administration of antibiotics. But they are not sensitive and are positive in only 60% of patients.
Histopathology
A computed tomography (CT)-guided or image intensifier-guided percutaneous biopsy of the infected vertebra or disk is advised to acquire tissue for microbiological studies. This is especially useful in patients without significant neural compression, where tissue biopsy is required to initiate appropriate therapy. Trocar biopsies are better than fine needle aspiration because a larger amount of material from the infected area is available for examination. The acquired tissue is sent for aerobic cultures, Gram’s stain, tubercular polymerase chain reaction gene assay, culture for tubercular bacilli, and histopathological assessment. Although tissue aerobic cultures are positive in only 50 to 60% of patients, histological findings are helpful to identify the infective process and to differentiate diskitis from tuberculosis, tumors, and pathological fractures. The presence of infiltration of neutrophils, necrosis, and inflammatory changes are diagnostic of acute infective diskitis. In tubercular infections, epithelioid granulomas, lymphocytic infiltrates, and multinucleated giant cells are the typical findings. If blood cultures and percutaneous biopsy techniques fail to identify the infecting organism and the patient does not respond to empirical therapy, then open surgical biopsy during spinal debridement and stabilization is indicated.
Plain radiographs are not helpful initially, as they are normal in the early stages of the disease. The earliest findings are observed by 2 to 3 weeks and include loss of delineation of the trabeculae of the subchondral bone and destruction of the end plates with narrowing of the disk space (Fig. 10.1). In advanced disease, complete collapse of the disk space, destruction of vertebral bodies, asymmetrical kyphosis, and spinal instability due to subluxation may be evident (Fig. 10.2). CT is useful in assessing the degree of bone destruction, detecting cavities within the bone, and examining the surrounding soft tissues (Fig. 10.3). Hence, it is mainly useful if surgical treatment is planned. It is also used as a guide for accurate placement of the biopsy needle while performing a percutaneous biopsy.
Magnetic resonance imaging (MRI) is now the investigation of choice due to its ability to depict changes even in the early stages of the disease. MRI has been shown to have a sensitivity of 96%, a specificity of 92%, and an accuracy of 94% in patients with spinal infections.16 In fact, MRI has such high sensitivity that the marrow changes observed on MRI look more extensive than the actual extent of vertebral destruction. The standard sequences performed are T1- and T2-weighted images, short tau inversion recovery (STIR) sequences, and contrast studies (Fig. 10.4). T1-weighted images show decreased signal intensity changes in the vertebral bodies and disk spaces due to the presence of edema. In T2-weighted images, the signal intensity is increased in the vertebral disk and the body. The extension of infection in the adjoining tissue is better delineated by fat-suppression STIR sequences and contrast studies. MRI also clearly documents the location and size of the epidural abscess, the presence of sequestrum, the extent of compromise of the spinal canal, the degree of compression of the spinal cord, and any signal intensity changes in the cord (Fig. 10.5). Asymptomatic multilevel skip lesions can be present in other vertebral segments, and hence MRI must evaluate the whole spine.
Fig. 10.2 Anteroposterior (a) and lateral (b) radiographs of the lumbar spine showing extensive vertebral destruction with loss of disk space, scoliosis, bony irregularities, and vertebral erosions. Sagittal (c) and coronal (d) MRI of the same patient showing multilevel diskitis and spondylitis with epidural and paravertebral abscess formation.
Fig. 10.5 MRI features of advanced diskitis. (a) Axial T2 image shows extensive perivertebral and epidural abscess formation with spinal canal obliteration. Sagittal T1 (b), T2 (c), and STIR (d) sequences show extensive diskitis at L4-L5 with disk erosion, subchondral damage, and epidural and paravertebral abscess formation.
Also, MRI aids in differentiating pyogenic spondylitis from Modic changes, tubercular infections, benign osteoporotic fractures, and tumorous conditions (Table 10.1 and Fig. 10.6). The presence of disk space involvement favors infection as compared with neoplasm. Usually type 2 Modic changes are painful and can mimic infections but show hyperintense signals on both T1 and T2 sequences. Type 1 Modic changes may mimic pyogenic diskitis but do not enhance with contrast, and typically the disk is not affected. Tuberculous spondylitis has an extensive bone destruction pattern with relative sparing of the intervertebral disk in the early stages, heterogeneous enhancement of the vertebral body, subligamentous spread of abscess, and large paravertebral abscesses with thin smooth walls.
Furthermore, MRI is also useful in assessing the healing response to treatment. The healing of the vertebral lesion is diagnosed on follow-up MRI based on typical features of resolution of marrow edema, replacement of marrow by fat seen as a bright signal on T1- and T2-weighted images, and complete resolution of paravertebral collections (Fig. 10.7). However, Kowalski et al17 suggested that despite the clinical improvement, MRI findings of healing may lag clinical resolution and should not lead the surgeon to unnecessary invasive treatments.
A radionuclear scan with technetium (Tc) 99m is very sensitive (> 90%) for an early diagnosis of pyogenic vertebral osteomyelitis, but it has lower specificity (< 80%).18 Any inflammation or degenerative changes in the spine can also result in increased tracer uptake, and hence the radionuclear changes are nonspecific. Radioactive gallium scan and indium 111-labeled leukocyte scintigraphy are more specific, with 80 to 85% specificity rates, but they have very low sensitivity. Owing to the high rate of falsenegative results, they are not used routinely in diagnosing spinal infections.
Table 10.1 Typical MRI Features of Pyogenic Spondylitis and Its Mimics
Diagnosis | MRI features |
Pyogenic spondylitis | Early disk space involvement with hypointensity on T1 and hyperintense signals on T2 sequences |
Tubercular spondylitis | Extensive involvement of subchondral region and adjacent vertebral body; huge, multiple, thin-walled abscesses |
Modic changes | Signal changes are confined to the subchondral region; disk is spared; nonenhancing; no abscess |
Pathological fractures (metastasis) | Multilevel noncontiguous affliction; disk is spared; no abscess formation |
Fig. 10.6 Diskitis and its common differential diagnosis. (a) Diskitis. Sagittal MRI sequences show typical hypointense signals in T1 sections at L5-S1 and hyperintense changes in T2 sequences. (b) Tubercular spondylitis. Note the extensive abscess formation in the prevertebral and epidural regions, and the abscess wall is thin. (c) Metastasis involves multiple vertebral segments, heterogeneous signal changes, and no abscess formation. (d) Modic end-plate changes mirroring signal changes on either side of the disk. The disk signal is intact and no abscess formation is seen.
Differential Diagnosis
A high degree of suspicion is required for an early diagnosis of spinal infection, especially in patients with risk factors, as the presenting symptoms may be vague. Often initial investigations are normal, and imaging may need to be treated within short intervals if clinical suspicion is very high (Fig. 10.8). The important differential diagnoses are metastasis, osteoporotic fractures, and degenerative vertebral changes. In postoperative diskitis, the clinical picture and blood investigations are more important than radiological investigations, as normal signal intensity changes seen in the immediate postoperative period may mimic infection.
Fig. 10.7 Successful resolution of spinal infection at completion of treatment. (a) Sagittal MRI in the pretreatment phase shows abscess (arrow) in the epidural space with hyperintense signals within the disk and bone suggestive of infection. (b) Sagittal MRI after the completion of treatment shows resolution of the abscess and healing of the bone infection characterized by fatty replacement of the marrow.
Conservative treatment is usually successful in the early stages of the disease, when the diagnosis is certain, the infective organism is identified, and appropriate antibiotics can be instituted before the development of severe destruction or neurologic complications. Even in situations where the organism could not be isolated, conservative treatment with empirical antibiotics provides good results (Fig. 10.9). Bed rest, bracing, and antibiotics are the key features of conservative therapy. Management of comorbid factors such as diabetes mellitus, anemia, malnutrition, and associated diseases is also important. Immobilization of the affected region of the spine with a rigid thoracolumbar brace and bed rest is essential for conservative treatment.
Isolation of the organism either from blood/ urine culture or through a trocar biopsy of the lesion is important before the start of antibiotics. After the harvest of the material, it is prudent to start a first-generation cephalosporin empirically, as S. aureus is the most common organism. In patients with methicillin-resistant S. aureus (MRSA), vancomycin is the drug of choice. For immunocompromised patients and intravenous drug abusers, a third-generation cephalosporin along with coverage for gram-negative bacteria is advised. Recent studies show that rifampicin provides good results in pyogenic spondylitis because it is active against biofilm-embedded bacteria and has synergistic effects with other β-lactam antibiotics.19 It is an excellent oral antibiotic to prescribe after initial intravenous therapy in infections with gram-positive organisms.
There is no clear consensus on the exact duration of antibiotic therapy, but generally intravenous antibiotics are given for a period of 3 to 4 weeks followed by 6 weeks of oral antibiotic therapy. Although several studies have recommended 6 to 8 weeks of intravenous therapy, others recommend only 4 weeks.20–22 Antibiotic therapy for less than 4 weeks may result in an unacceptably high recurrence rate. Roblot et al23 found no difference in the risk of relapse among patients treated for 6 weeks or longer in a retrospective analysis of 120 patients. Serial monitoring with ESR and CRP levels and clinical improvement are important parameters to judge control of infection, and it is advisable to continue antibiotics for at least a month after the ESR and clinical symptoms have returned to normal. Failure of resolution of clinical symptoms, persistently high inflammatory parameters like ESR and CRP, progressive destruction in radiographs, and epidural abscess formation on the MRI indicate failure of conservative therapy. Nonoperative treatment has a success rate of 75%, and at the end of 1 to 2 years spontaneous interbody fusion can be observed as radiological evidence of complete healing.
