We describe a clinical algorithm, based on decades of front-line experience of diagnosis and surgical treatment of human Brucellar spondylodiscitis in the largest medical center of the China's Xinjiang Pastoral Area.
Brucellar spondylodiscitis (BS) is the most prevalent and significant osteoarticular presentation of human Brucellosis, which is commonly manifested in pastoral communities. It is difficult to differentially diagnose and usually leads to irreversible neurologic deficits and spinal deformities. The initial diagnosis of BS is based on clinical findings and radiographic assessments, and the confirmed diagnosis should be established by the isolation of Brucella species from the blood and/or the standard tube agglutination test. Differential diagnosis of multifocal BS from either degenerative disc diseases or tuberculosis is especially highlighted. The surgical approach, either endoscopic or open, is demonstrated in detail, accompanied by radiographic evidence of structural compression or severe instability. Further, the crucial surgical steps, including single-stage transforaminal decompression, debridement, interbody fusion, and internal fixation, are explained. Moreover, perioperative care and postoperative rehabilitation are also addressed. Taken together, this clinical algorithm presents a practical guide that has yielded substantially satisfactory outcomes in the past decades, which can also be introduced for large-scale application to manage human BS, especially in endemic regions.
With more than half a million new cases annually, human Brucellosis has become a public health concern and remains an enormous burden worldwide1,2,3,4. BS, as the most common and severe osteoarticular manifestation of human Brucellosis, involves multiple structures including vertebral bodies, intervertebral disc, and paraspinal structures5,6. It occurs frequently in the lumbosacral zone and needs to be differentiated from other infectious diseases because of its nonspecific clinical characteristics7,8. Despite the significant advances in research over the past decades, accurate and timely diagnosis of BS is still a challenge for clinicians due to its late-onset radiological findings, slow growth rate in blood cultures, and the complexity of its serodiagnosis9. Therefore, human BS remains clinically underdiagnosed and underreported. Although the past decades have seen increasingly rapid advances in the introduction and popularization of several therapeutic guidelines, there is still no consensus for an optimal management modality10. Frequent relapses, treatment failure, and sequelae are reported constantly11.
Of note, BS can be severely debilitating and disabling even if it is rarely fatal. If it is not treated appropriately, possible serious sequelae might be induced including persistent back pain, neurological deficiency, and even kyphotic deformity12,13. Antibiotic therapy is the core in the treatment of BS and yields generally promising outcomes9. However, certain patients may require surgical treatment if neurological dysfunction, spinal instability, abscess formation, intractable pain, or a previous unsatisfactory response to conservative treatments are observed. Surgical intervention remains controversial. Different surgical procedures for debridement and fusion have been described for infectious diseases of the lumbar spine including anterior-only, posterior-only, and combined approaches14,15,16. Here, diagnostic guidelines have been presented for human BS and for the single-stage surgical treatment with transforaminal decompression, debridement, interbody fusion, and internal fixation via a posterior-only approach. A detailed protocol of this method is given below.
The study was approved by the ethical committee of the First Affiliated Hospital of Xinjiang Medical University, China17.
1. Informed Consent
- Obtain the patient's informed consent after explaining the details of the surgical procedure, postoperative prognosis, and possible complications (infection, epidural hematoma, spinal cord injury, failure of internal fixation, and cerebrospinal fluid leakage).
- Explain the other risks generally associated with using an implant (e.g., internal fixation system) such as allergic or immune system responses to the implanted materials.
- Rule out any contraindications of the patients.
2. Patient selection
- Diagnosis of BS
- Base the initial diagnosis of BS on the clinical manifestations and radiographic assessments8.
- Look for clinical manifestations and symptoms such as back pain, undulant fever, malaise, profuse night sweating, weight loss, polyarthralgia, and generalized myalgias8,18.
- In plain radiographs, look for osteophytes, sclerosis, osteoporosis of the vertebral body, and narrowing of the intervertebral disc space, with posterior elements being mostly preserved.
NOTE: Central necrosis is mostly not present, and the vertebral body is mostly morphologically intact (Figure 1)18.
- In computed tomography (CT), look for small bone destruction lesions at vertebral edges that occur in multiple areas, and for hyperplastic and sclerotic lesions that are more prominent and often admixed (Figure 1)18.
NOTE: CT features are divided into those of vertebral osteolysis and vertebral hyperplastic sclerosis stages19.
- As magnetic resonance imaging (MRI) is the best imaging tool for BS diagnosis (Figure 1)20,21,22, look for characteristic MRI findings that can be classified into five subsets: discitis, spondylitis, paraspinal/psoas abscess, appendicitis, and compound (Table 1).
- Confirm the diagnosis according to the presence of the following three criteria23:
- Ensure that the clinical picture is compatible with that of BS.
- Confirm the absence of any etiology other than Brucellosis that can explain spinal involvement.
- Confirm that the results of the standard tube agglutination test reveal a titer of antibodies to Brucella of ≥ 1/16024.
- Base the initial diagnosis of BS on the clinical manifestations and radiographic assessments8.
- Indications for surgery23
- Look for persistent pain due to spinal instability, which is caused by severe disc or/and vertebral destruction.
- Confirm severe or progressive neurologic dysfunction that can be attributed to nerve root compression by inflammatory granuloma or epidural abscesses.
- Confirm that there is no response to oral antibiotic therapy (e.g., doxycycline, rifampicin, streptomycin).
3. Preoperative procedure
- Administer a chemotherapy regimen (oral doxycycline 200 mg/day plus oral rifampicin 600-900 mg/day)25 to all patients.
- Offer surgical interventions to patients who have surgical indications after two weeks of antibiotic treatment.
4. Operative procedures for single-stage transforaminal decompression, debridement, interbody fusion, and internal fixation via posterior-only approach
- Place the patient on a four-poster frame in the prone position after administration of general anesthesia with endotracheal intubation.
- Disinfect the surgical area with 1% iodophor, and then cover with standard surgical towels (see Table of Materials).
- Make a midline longitudinal incision over the spinous process of the infected vertebra.
- Expose the posterior spinal structures including lamina, facet joints, and transverse processes.
- Place the pedicle screws (diameter: 5-7 mm, length: 20-65 mm) into both sides of the affected vertebra with the assistance of C-arm fluoroscopy26,27,28 (see Table of Materials).
NOTE: To achieve adequate debridement, place the pedicle screws closest to the superior or inferior endplate and away from the infection lesions. Fix the screws to a temporary rod (diameter: 5.5 mm) on the less involved side (see Table of Materials).
- Perform the facetectomy at the involved level on the side where neurologic and radiological manifestations are more severe29.
- Debride the epidural abscess, granulation tissues, infected disc with curettes, and scrape the vertebral endplates. Meanwhile, protect the nerve root with a nerve retractor (see Table of Materials).
NOTE: Perform a blunt dissention to adequately drain the psoas abscess from the posterolateral as thoroughly as possible. Analyze the tissues and abscess histopathologically30,31. Noncaseating granulomatous inflammation with predominant lymphocyte and monocytes infiltration is the typical histopathologic finding of BS32. If the result of decompression and debridement is not satisfactory after a unilateral facetectomy, perform the same procedure on the opposite side.
- After adequately removing the lesions and decompressing the neural elements, use 1000-2000 mL of 0.9% sodium chloride solution for surgical area irrigation to clear the residual Brucellar lesion (see Table of Materials).
- Saturate an absorbable gelatin sponge (60 mm x 20 mm x 5 mm) with 0.75-1.5 g of streptomycin, and use it for both hemostasis and local antibiotic treatment within the surgical area (see Table of Materials).
- Implant the locally harvested autogenous bone into the defected space for interbody fusion with a bone graft funnel and bone pusher (see Table of Materials).
- Fix pedicle screws (diameter: 5-7 mm, length: 20-65 mm) on both sides to the pre-contoured rods (diameter: 5.5 mm) under a slight compression33,34 (see Table of Materials).
- Drain and close the lesion35 (see Table of Materials).
5. Postoperative management
- Administer intravenous antibiotic (cefuroxime sodium, 1.5 g, q12h) for 1-3 days postoperatively.
- Remove the drainage tube when the drainage volume is less than 30 mL per day.
- Administer the aforementioned antibiotic therapies with doxycycline (200 mg/day) and rifampicin (600-900 mg/day) for at least 3 months (range 3-12 months) after surgery.
- Ensure the patient remains in bed for 3-5 days postoperatively, and allow for mobilization by providing effective support with a lumbosacral brace.
- Perform plain radiography before the patient's discharge to evaluate the location of the graft and instrumentation.
- Ensure at least 2-3 months of brace protection.
6. Follow-up evaluation
- Follow up with the patients at 1, 3, and 6 months postoperatively and then annually.
- Monitor the infection by measuring erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP).
- Evaluate interbody fusion by radiography at the last follow-up.
NOTE: Assess graft fusion with the radiologic criteria of Bridwell36. Perform CT scans if there is any uncertainty regarding plain radiographs.
- Utilize the visual analogue scale (VAS) to assess back pain.
- Evaluate pain-related dysfunction with the Oswestry Disability Index (ODI).
- Use the Japanese Orthopedic Association (JOA) scale to evaluate the functional outcomes.
This paper describes a prospective, non-randomized, controlled study of 32 consecutive BS patients who were treated by a single-stage transforaminal decompression, debridement, interbody fusion, and internal fixation via a posterior-only approach in the Department of Spine Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China. Figure 1 shows a typical case in this study.
The clinical symptoms are summarized in Table 2. Patients generally complained of chronic back pain with signs of neurological impairment. Brucella agglutination level was ≥1/160 in all patients; positive blood culture results were observed in 8 cases (25%). According to the aforementioned diagnostic criteria, all patients were indicated as candidates for a single-stage surgical treatment. The mean duration of surgery was 133.1 ± 36.6 min, and the mean blood loss was 378.1 ± 187.9 ml (range 120-800 mL). Histopathologic examinations on biopsy samples obtained from the paravertebral tissue indicated noncaseating granulomatous lesions infiltrated by inflammatory cells (lymphocyte and monocytes) with various spatial extents (Figure 2). Patients were followed up for over 12 months (24.9 ± 8.2 months). Postoperative complications, including superficial wound infection, was seen in 1 patient at postoperative day 10 and treated successfully with intravenous antibiotics. Deep wound infection and sinus formation were perceived in 2 patients with a history of diabetes and treated by a revision surgery and extended intravenous antibiotics. No clinical or radiological relapses were observed throughout the entire follow-up phase.
Radiating pain were immediately relieved after surgery, and significant decrease in constitutional symptoms was achieved within the first postoperative month. ESR and CRP levels returned to normal levels by the third postoperative month. The preoperative levels of ESR (46.03 ± 12.73) and CRP (41.47 ± 41.74) declined to 8.86 ± 3.05 and 4.56 ± 1.75, respectively, in postoperative month 3. The significant improvement in VAS, ODI, and JOA scores between the preoperative assessment and final follow-up are shown in Table 3.
The interbody fusion rate was 93.8% at 12 months postoperatively according to the Bridwell criteria. Grade I and II fusion was seen in 30 (93.75%) and 2 patients (6.25%), respectively. These two patients with grade II fusion were evaluated with lateral flexion/extension radiography and CT examinations; no noticeable movement or gap was detected within the interbody area.
Figure 1: A 69-year-old male presented with L3-L4 Brucellar spondylodiscitis. (A) Anteroposterior view shows hyperplastic changes on the lateral edge of the L3-L4 vertebral body and formation of osteophytes (arrow). (B) Lateral view shows disc space narrowing and anterior osteophyte formation (parrot's beak). (C, D) Sagittal T1- and T2-weighted MRI shows lesions involved in L3-L4 vertebral bodies and intervertebral disc, accompanied by epidural abscess and inflammatory granuloma formation. (E, F) Transverse MRI and CT demonstrate spinal canal stenosis. (G, H) Postoperative plain radiograph shows intervertebral bone grafting and instrumentation. (I) Twelve-month postoperative X-ray showed a firm fixation and interbody fusion. This figure has been modified from Abulizi et al.37. Abbreviations: MRI = magnetic resonance imaging; CT = computed tomography. Please click here to view a larger version of this figure.
Figure 2: Histological analysis of lesion biopsies. Hematoxylin and eosin staining shows lymphocyte and monocyte infiltration in the samples biopsied from affected paravertebral tissue. Yellow arrows indicate lymphocytes, and red arrows indicate monocytes. Scale bar = 50 µm. Please click here to view a larger version of this figure.
|Discitis||Regional inflammation involving intervertebral disc|
|Disc space narrowing|
|Low signal on T1-weighted image mixing high signal on T2-weighted image|
|Spondylitis||Regional inflammation involving adjacent vertebrae|
|Vertebrae diffuse marrow edema|
|Homogeneous or uneven low signal on T1-weighted image of vertebrae|
|Paraspinal/psoas abscess||Regional inflammation involving paraspinal or psoas|
|Appendicitis||Regional inflammation involving appendicitis|
|Low signal on T1-weighted image|
|High signal on T2-weighted image|
|Compound||Endemic inflammation involving two or more parts of vertebral and paravertebral structures|
|T1-weighted image reveals incomplete heterogeneous hypointensity|
|T2-weighted image reveals hyperintensity|
|This table has been modified from Bai et al.22.|
Table 1. Classification of Brucellar spondylodiscitis for MRI.
|Symptoms||Number of patients (%)|
|-Back pain||31 (96.9%)|
|-Weakness of fatigue||14 (43.8%)|
|-Weight loss||9 (28.1%)|
|This table has been modified from Abulizi et al.37.|
Table 2. Clinical characteristics of 32 patients.
|Parameters||Preoperative||Last follow-up||Improvement rate (%)||P value|
|VAS||5.19 ± 1.47||0.47 ± 0.67||90.9||<0.05|
|ODI||55.31 ± 9.16||10.72 ± 3.23||80.7||<0.05|
|JOA||12.38 ± 2.98||26.13 ± 2.58||82.7||<0.05|
|Scores were demonstrated as Mean ± Standard deviation. Abbreviations: VAS = visual|
|analogue scale; ODI = Oswestry Disability Index; JOA = Japanese Orthopaedic Association.|
|This table has been modified from Abulizi et al.37.|
Table 3. Comparison of preoperative and last follow-up VAS, ODI, JOA scores.
The present guideline of diagnosis and surgical treatment of human BS with a detailed protocol and satisfactory clinical evidence from representative cohorts shows clinical efficacy and is proposed for large-scale application to manage human BS, especially in endemic regions. The first critical step in the treatment of BS is to make the correct diagnosis. The diagnosis of BS needs to be differentiated from spinal tuberculosis compared to which BS is relatively less bone-destructive and usually responds effectively to antibiotic treatment38. In addition, noticeable neurological deficits, persistent pain, spinal instability, and paravertebral abscesses can be observed in BS patients in the later stages. Surgical treatment should be considered as the last resort for patients who do not respond well to antibiotic therapy39.
Surgical outcomes of BS are rarely elucidated in the literature, and the role of surgery treatment remains controversial. BS typically occurs in the lumbosacral region, particularly at the L4-L5 and L5-S1 levels8,20,40. Surgical debridement, decompression, and fusion via multiple approaches have been proposed14,16,41. As the gold standard, the anterior-only approach ensures a direct access with adequate exposure to the spinal lesion. However, anterior instrumentation at L4-L5 and L5-S1 is potentially dangerous and insubstantial due to the complicated regional anatomy16,41,42. Furthermore, most patients displayed bilateral nerve root compression, epidural abscess formation, and spinal stenosis. Therefore, it may not be possible to achieve complete decompression of the contralateral nerve root via the anterior approach.
The second critical step is to utilize transforaminal lumbar interbody fusion (TLIF) technology during surgery in the form of a modification of posterior lumbar interbody fusion. This can minimize traction force on the dura and nerve root during surgery and therefore, decrease the risk of postoperative complications43. Posterior-only approaches are reported increasingly as alternative surgical therapy for selective spinal tuberculosis41. Single-stage transforaminal decompression, debridement, interbody fusion, and internal fixation via posterior-only approach is generally reported in the treatment of spinal tuberculosis. However, obtaining adequate debridement and reconstruction of anterior column defects has been considered insufficient. Furthermore, this strategy is also considered unsuitable for patients with severe vertebral collapse and apparent paravertebral abscess formation44,45.
Unlike spinal tuberculosis, destruction in BS occurs mainly around and within the intervertebral disc, and vertebral collapse and local kyphosis are less likely to occur. Therefore, debridement and intervertebral bone graft fusion via a posterior approach is an effective and safe procedure for BS46. Brucellosis can affect the facets, which may be the reason for severe back pain in these patients. Accordingly, a facetectomy followed by intervertebral debridement and fusion may be more effective than traditional posterior approaches. In this study, no intraoperative complications were observed, and chronic back pain and radiating pain were relieved significantly in the present cohorts after surgery. Besides, no recurrence was reported during the follow-up period. Therefore, this single-stage surgical intervention with transforaminal decompression, debridement, interbody fusion, and internal fixation via the posterior-only approach is clinically effective for surgical candidates of human BS.
The third critical step is to plant the pedicle screw into the affected vertebra to achieve a shorter segmental fixation. The BS lesion mainly involves the structures within the intervertebral space and causes less bony destruction compared to other infectious diseases that occur in the same region. Therefore, the posterior approach has been suggested to be more convenient and minimally invasive during the process to access the involved structures, allowing for a possibly thorough removal of the lesion and complete decompression of bilateral nerve roots. Posterior bone graft implantation can also be straightforwardly performed via the far-lateral portion of vertebral foramen. As BS-related destruction of vertebral body is commonly not severe, the transpedicular screws can still be implanted in the affected vertebra with a minimal surgical exposure and shorter segmental fixation47. In conclusion, application of the aforementioned protocol for timely diagnosis and treatment of BS patients can achieve satisfactory short-term clinical outcomes. Further popularization of this single-stage surgery on a large-scale for surgical candidates, especially in endemic regions, might be helpful to reduce its global burden.
The authors have nothing to disclose.
Dr. Xiaoyu Cai acknowledges the financial support from the China Scholarship Council. This work was funded by the Natural Science Foundation of Xinjiang Province, P. R. China (no. 2016B03047-3).
|Absorbable gelatin sponge||Chuhe Medical Devices Co., Ltd.||AWZ-035-XSMJHM-AD.||60 mm x 20 mm x 5 mm|
|Box curette||Rudischhauser GmbH||R16-BD2310-ST||Width: 7.5 mm; height: 5.9 mm; shaft: 6.0 mm (diameter); working length: 223 mm|
|Bone graft funnel||Rudischhauser GmbH||R19-K00000-FU||Working length: 246.5 mm; End diameter: 42 mm; shaft: 6.4 mm (diameter)|
|Bone pusher||Rudischhauser GmbH||R19-EK4110-00||Working length: 220 mm; shaft: 6.0 mm (diameter)|
|Bone rongeur||Vet Direct & VETisco||EC-RG-BO-180||Length: 180 mm|
|Iodophor (1%)||Beijing SanYao Science & Technology Development Co.||14975I||Volume: 500 mL|
|Nerve retractor||Rudischhauser GmbH||R16-HD1710-00||Width: 10 mm; length: 145 mm; shaft: 5.0 mm (diameter)|
|Osteotome 1||Rudischhauser GmbH||R16-CD2310-08||Width: 8 mm; height: 3 mm; shaft: 6.0 mm (diameter); working length: 223 mm|
|Osteotome 2||Rudischhauser GmbH||R16-CD2310-10||Width: 10 mm; height: 3 mm; shaft: 6.0 mm (diameter); working length: 223 mm|
|Pedicle screw||DePuy Synthes Companies||199723540||Length: 40 mm; diameter: 5.0 mm|
|DePuy Synthes Companies||199723545||Length: 45 mm; diameter: 5.0 mm|
|DePuy Synthes Companies||199723550||Length: 50 mm; diameter: 5.0 mm|
|DePuy Synthes Companies||199723640||Length: 40 mm; diameter: 6.0 mm|
|DePuy Synthes Companies||199723645||Length: 45 mm; diameter: 6.0 mm|
|DePuy Synthes Companies||199723650||Length: 50 mm; diameter: 6.0 mm|
|DePuy Synthes Companies||199723740||Length: 40 mm; diameter: 7.0 mm|
|DePuy Synthes Companies||199723745||Length: 45 mm; diameter: 7.0 mm|
|DePuy Synthes Companies||199723750||Length: 50 mm; diameter: 7.0 mm|
|Securo Drain||Dispomedica GmbH||1.33578||Size: 7 mm; Length of perforation: 15 cm; Total length: 80 cm; Reservior size: 150 ml|
|Sterile 0.9% Sodium Chloride Solution||Beijing SanYao Science & Technology Development Co.||15935S||Volume: 500 mL|
|Straight rod||DePuy Synthes Companies||1797-62-480||Length: 480 mm; diameter: 5.5 mm|
|Streptomycin sulfate, Powder||Beijing SanYao Science & Technology Development Co.||P06-11025P||Size: 1 g|
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