Original Paper Received: April 23, 2015 Accepted: July 5, 2015 Published online: August 22, 2015
Eur Neurol 2015;74:100–106 DOI: 10.1159/000437418
Stepwise Therapy for Treating Tuberculosis of the Upper Cervical Spine: A Retrospective Study of 11 Patients Kedong Hou a Huadong Yang b Lin Zhang c Xifeng Zhang d Songhua Xiao d Ning Lu d
a
Pinggu Hospital of Capital Medical University, b Medical Center of Tsinghua University, c Shanxi Medical University, and d Chinese PLA General Hospital, Beijing, China
Abstract Aims: Tuberculosis of the upper cervical spine is a rare occurrence with serious consequence, and its optimal treatment protocol remains inconclusive. This study aims at investigating the clinical characteristics and management outcomes of the stepwise therapy for different stages of tuberculosis of the upper cervical spine. Methods: We conducted a retrospective analysis of 11 patients with tuberculosis of the upper cervical spine who received anti-tuberculosis chemotherapy for 15 months. Two infants were treated by individualized chemotherapy, while 9 patients with retropharyngeal abscess were first treated with CT-guided percutaneous puncture, and the catheter was used to administer local chemotherapy. Two of these 9 patients continued to receive posterior instrumentation due to atlantoaxial subluxation. Patients were followed up clinically and radiologically for an average period of 60 months. Results: Two patients underwent catheter change due to catheter falling off and blockage, 2 patients had gastrointestinal side effects, and 2 patients had drug-induced hepatitis derived from the chemotherapy. Mean erythrocyte sedimentation rate was 10.27 mm/h (range 4–16 mm/h) and average visual analogue scale
© 2015 S. Karger AG, Basel 0014–3022/15/0742–0100$39.50/0 E-Mail [email protected] www.karger.com/ene
score was 2.55. A total of 11 cases underwent routine antituberculosis chemotherapy for 15 months. 9 of 11 cases received supplementary surgical therapy, and all patients were cured at the final follow-up. Conclusion: Standard antituberculosis chemotherapy is the cornerstone of stepwise therapy for tuberculosis of the upper cervical spine. Local chemotherapy is effective and minimally invasive for patients with severe local symptoms without spinal cord compression. Just as in patients with atlantoaxial instability, open fixation and bone grafting are necessary. © 2015 S. Karger AG, Basel
Introduction
Tuberculosis infections have a higher incidence rate in both developing and developed countries. Although tuberculosis of the spine (Pott’s disease) is a well-known manifestation of infection, tuberculosis of the upper cervical spine is uncommon and occurs rarely in approximately 1% of all spinal tuberculosis cases [1, 2]. This disease is potentially dangerous due to the severe neurological complications and the relatively small cross-sectional
Kedong Hou and Huadong Yang are co-first authors, they contributed equally to this paper.
Dr. Xifeng Zhang Chinese PLA General Hospital No. 28 Fuxing Road, Haidian District Beijing 100853 (China) E-Mail zhangxf00000 @ 163.com
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Key Words Spinal cord · Upper cervical vertebrae · Tuberculosis · Chemotherapy · Minimally invasive
Color version available online
Fig. 1. A 2-year-old boy with tuberculosis of the C1–C2 vertebrae. a CT axial view
showing destruction of the vertebral body. coronal reconstruction and destruction of the odontoid process and C2 vertebral body. d A patient was treated with oral anti-tuberculosis drugs and halo vest protection. e Lateral X-ray of the cervical spine at 2 years of follow-up. The prevertebral space was normal. The space between the odontoid process and anterior arch of the atlas was normal. f Anterior-posterior cervical open mouth view. The odontoid process was in the median position. g CT sagittal reconstruction. The C1–C2 vertebrae were free of tuberculosis lesions and bone destruction.
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d
diameter of the spinal canal relative to the diameter of the cervical cord. Anti-tuberculosis chemotherapy, brace, and improved nutrition have achieved excellent functional outcomes in patients diagnosed with early stages of tuberculosis of the upper cervical spine without presenting deformities, neurologic deficits, abscess and spinal instability [3]. Patients with tuberculous retropharyngeal abscess are usually secondary to tuberculous involvement of the cervical spine [4]; in such patients, anti-tuberculosis chemotherapy is merely limited. However, profound vertebral destruction and severe complications have occurred in radical debridement and bone grafts for cases without atlantoaxial instability [5]. Our earlier study has revealed that CT-guided percutaneous puncture and local chemotherapy for tuberculosis of the lumbar spine has achieved satisfactory results [6]. To the best of our knowledge, tuberculosis of the upper cervical spine combined with minimally invasive surgery has rarely been reported. We have treated tuberculosis of the upper cervical spine in different stages using drugs, minimally invasive surgery, and combination of posterior instrumentation and fusion surgery in a stepwise way, which achieved good clinical outcomes. In this study, we report our experience with 11 cases of tuberculosis of the upper cervical spine. Stepwise Therapy for Treating Tuberculosis of the Upper Cervical Spine
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Materials and Methods Study Population and Data Collection A total of 11 patients with clinically and histologically proven spinal tuberculosis underwent surgery at the Chinese PLA General Hospital between November 2005 and January 2012. Among these patients, 8 patients were males and 3 patients were females; and the mean age of all patients was 33.3 years (range 2–68 years). In 9 patients, the disease involved 2 adjacent segments: C1–C2 in 8 patients and C2–C3 in 1 patient, while in 2 patients, the disease involved 3 adjacent segments (C1–C3). Other comorbidities included renal tuberculosis in 1 patient, pulmonary tuberculosis in 2 patients, cerebral thrombosis in 1 patient, and rheumatic disease in 1 patient. Symptoms included cervical pain and restricted cervical movement, no signs of neurological defects were observed. 2 patients complained of foreign body sensation in the pharynx. Mycobacterium tuberculosis was cultured from specimens obtained from 9 of 11 patients (9/11), and 44% of specimens (4/9) produced positive cultures. All cultures were susceptible patterns. Medical records were reviewed for patient demographics and clinical characteristics, anti-tuberculosis treatment history, treatment modalities, and outcomes. Written informed consent was obtained from all patients. Imaging Study CT revealed that the bone destruction occurred in the anterior arch of the atlas and base of the odontoid process (fig. 1a–c, 2b, 3c, 3d), as well as increased retropharyngeal space (fig. 2b, 3b, 3c). No signs of spinal cord compression or kyphosis in the cervical spine were observed. One patient showed scoliosis in the cervical spine (fig. 3d). Magnetic resonance imaging (MRI) showed retro-
Eur Neurol 2015;74:100–106 DOI: 10.1159/000437418
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b CT sagittal reconstruction showing destruction of the odontoid process. c CT
Color version available online
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Fig. 2. A 42-year-old woman with tuberculosis of the C1–C2 vertebrae. a X-ray lateral view showing normal cervical curvature and increased retropharyngeal space. b CT axial view showing increased retropharyngeal space, abscess, and destruction of the C2 vertebra. c T1-weighted MRI showing the retropharyngeal abscess. d A cath-
eter was inserted through the right mastoid process and advanced into the retropharyngeal abscess under CT guidance. e A catheter was inserted through the right mastoid process. f 6 weeks after local chemotherapy, T1-weighted MRI showed no spinal cord compression and retropharyngeal abscess. C1–C2 vertebrae were normal.
pharyngeal abscess in 9 patients (fig. 2c, 3e, 3f). Lateral X-ray also revealed increased retropharyngeal space in all patients (fig. 2a, 3a).
withdrawn, and an epidural tube (disposable nerve block anesthesia kit I, Tuoren Medical Company, China) was inserted according to the depth of the puncture needle. The catheter was fixed with transparent dressing and the catheter length was recorded (fig. 2e). The following 4–8 weeks, 0.1 g of isoniazid was locally administered 1–2 times per day; and oral anti-tuberculosis medication continued.
Stepwise Therapy Step Ι: General Anti-Tuberculosis Chemotherapy Indications. (1) Clinical diagnosis of tuberculosis of the upper cervical spine in infant patients; (2) adult patients without abscess formation, vertebral destruction and neurologic deficits. Chemotherapy Regimen. All patients received a 4-drug anti-tuberculosis regimen daily for the first 3 months including 0.3 g of isoniazid, 0.45 g of rifampicin, 0.75 g of ethambutol, and 1.0 g of pyrazinamide. Doses for children were adjusted according to body weight. A 3-drug anti-tuberculosis regimen was administered daily for the following 12 months including 0.3 g of isoniazid, 0.45 g of rifampicin, and 0.75 g of ethambutol. A halo vest or Philadelphia collar was used to protect the cervical spine (fig. 1d). Step II: CT-Guided Catheter and Local Chemotherapy of Isoniazid Combined with Step I Indications. (1) Unresponsive to drug treatment; (2) in poor health status and could not tolerate open surgery; (3) retropharyngeal abscess or vertebral canal abscess; (4) there is no atlantoaxial dislocation. Surgical Technique. With the patient in the supine positionunder CT guidance, a puncture needle (18 G, 200 mm; Nihon Kohden Company, Japan) was advanced through the site anterior to the mastoid process to the lesion (fig. 2d, 3g). The needle core was
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Eur Neurol 2015;74:100–106 DOI: 10.1159/000437418
Step III: Posterior Pedicle Screw Internal Fixation Succeeded with Step II Indications. (1) Atlantoaxial dislocation or subluxation during the course of Step II; (2) progressive compression of the spinal cord during the course of Step II. After local chemotherapy, 2 patients still showed signs of atlantoaxial subluxation. Hence, internal fixation through a posterior approach was performed after 8 and 11 weeks of drug treatment, respectively. Oral anti-tuberculosis medication was continued. Surgical Technique. Under general anesthesia, the patient was placed in prone position with head immobilized using a Mayfield headholder in case of reducible C1–C2 subluxation. The head was fixed in a neutral position. A midline incision was made extending from the inion to the C4 spinous process; and the C1 posterior arch, C2 lateral mass and C2–C3 facet joint were exposed subperiosteally. The medial aspect of the C2 dorsal element was carefully exposed to confirm the entry point and trajectory of the C2 pars interarticularis or pedicle screw. The C1 lateral mass inferior to the C1 arch was exposed. The medial and lateral aspects of the C1 lateral mass were palpated for safe placement of the C1 screw. The C1
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lateral mass and C2 screws were connected tightly with a rod. The patient was immobilized on the first postoperative day and wore a Philadelphia collar for 3 months.
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liosis. e T2-weighted MRI showing soft tissue swelling of the retropharynx, abnormal signals of the odontoid process, and C1–C2 semi-dislocation. f T2-weighted MRI showing displacement of the odontoid process, suggesting atlantoaxial dislocation. g Under CT guidance, a catheter was inserted through the right mastoid process and advanced into the lesion anterior to the C1 vertebral body. h X-ray lateral view showing C1–C2 fusion fixation for atlantoaxial dislocation treatment.
Results
Postoperative Management A halo vest was used in 2 infant patients to protect the cervical spine. Collar protection was used in other 9 patients for 3–4 months. Patients were encouraged to start activity from the first postoperative day. All patients received a 4-drug anti-tuberculosis regimen for the first 3 months and a 3-drug anti-tuberculosis regimen for the following 12 months. The epidural tube was properly fixed to prevent it from accidentally falling off and pumping back necrotic tissue that could obstruct the tube before local administration of isoniazid.
Demographic and Clinical Characteristics Among the 11 patients, 3 were female and 8 were male; and median age was 33.3 years (range 2–68 years). 2 vertebral levels were involved in 8 patients, 1 vertebral level existed in 1 patient, and 3 vertebral levels occurred in 2 patients. Among these patients, 27.3% (3/11) coexisted with other tuberculosis symptoms. All patients were primary cases and no patient had neurological deficits or kyphotic deformities. None of the patients were co-infected with HIV (table 1).
Follow-Up Index The following indices were recorded preoperatively at 1, 2 and 6 months of follow-ups, and every 6 months thereafter: (1) clinical presentation; (2) X-ray, CT or MRI scans; (3) erythrocyte sedimentation rate (ESR), hepatic function and renal function. Visual analogue scale (VAS) was performed to assess cervical pain. Fusion assessment was determined by X-ray according to the criteria defined by Lee et al. [7]. Definitive and probable fusions were classified as spinal fusion in this study.
Treatment Outcomes All patients were followed-up for a mean period of 60 months (range 28–108 months). 2 infant patients with tuberculosis of the upper cervical spine received chemotherapy and all patients received minimally invasive surgery. 7 of them were completely cured, while 2 patients continued to receive open fixation and autologous bone
Stepwise Therapy for Treating Tuberculosis of the Upper Cervical Spine
Eur Neurol 2015;74:100–106 DOI: 10.1159/000437418
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Fig. 3. A 19-year-old man with tuberculosis of the C1–C2 vertebrae and atlantoaxial dislocation. a X-ray lateral view showing loss of cervical curvature, increased retropharyngeal space, and increased anterior atlantodens interval. b CT axial view showing the broken anterior arch of the atlas, displacement of the odontoid process, bone destruction, and increased retropharyngeal space. c CT sagittal reconstruction showing destruction of the odontoid process and increased retropharyngeal space. d CT coronal reconstruction showing destruction of the base of the odontoid process and sco-
d
ulation Characteristics
Value (n = 11)
Male/female Median age, years (range) Other sites of tuberculosis Pulmonary tuberculosis Nephrotuberculosis Paravertebral cold abscess Previous surgery for spinal tuberculosis HIV co-infection
8/11 33.3 (2–68) 3 (27.3) 2 (18.2) 1 (9.1) 9 (81.8) none none
Values given as n (%) unless otherwise noted.
Table 2. Surgery and follow-up data
Characteristics
Value (n = 11)
Step I Step II Step III ESR mm/h, median (range) Preoperative Postoperative Follow-up time, months Complication Chemotherapy Surgery
2/11 9/11 2/11# 50.45 (38–64) 10.27 (4–16) 60 (28–108) 4/11 2/9
# Atlantoaxial
subluxation occurred in patients treated with Step II, and these patients were treated with Step III.
grafting for atlantoaxial sublaxation. 2 cases underwent catheter change: catheter fall off occurred in 1 case and catheter blockage occurred in the other case. The mean ESR value was 6.24 mm/h (range 0–32 mm/h) at the final follow-up. 2 patients had gastrointestinal side effects derived from chemotherapy and 2 suffered drug hepatitis (table 2). Bone grafting achieved good fusion at a mean time of 3.5 months (range 3–4 months). Anti-tuberculosis drugs were stopped when patients met the following criteria: (1) normal body temperature with generally good health status; (2) no cervical pain and local symptoms; (3) normal ESR for 3 consecutive months; (4) imaging examination did not reveal any abscess. Mean VAS score significantly decreased from 8.36 (range 6–10) at baseline to 2.55 (range 0–4) at the last follow-up (P < 0.01). At the last follow-up, all patients were asymptomatic. All tuberculosis lesions were healed as shown by radiological ex104
Eur Neurol 2015;74:100–106 DOI: 10.1159/000437418
amination (fig. 1e–g, 3h). The upper cervical spine showed normal curvature. No significant complications, such as tuberculosis recurrence, fistula, bone graft dislodgement and pseudoarticulation, occurred.
Discussion
Tuberculosis of the upper cervical spine can cause spinal cord compression, resulting from atlantoaxial dislocation, abscess compression, and direct involvement of the tuberculosis lesion. Neurologic deficits are common in patients with tuberculosis of the upper cervical spine, which is associated with compression on the spinal cord or nerve roots [8]. Tuberculosis of the upper cervical spine has an insidious onset, and symptoms of vertebral destruction and neurologic deficits occur in late stages of the disease. However, in our patients, no symptoms of spinal cord compression were observed. Patients with pharyngeal abscess may have symptoms of dysphagia, dyspnea, and feeling of foreign body in the pharynx. In our study, 9 patients had retropharyngeal abscess and 2 of these patients had a feeling of foreign body in the pharynx. However, no symptoms of dysphagia and dyspnea were observed. These patients were initially referred to an otolaryngologist, suggesting a risk of misdiagnosis. Imaging examination is important for the accurate diagnosis and evaluation of tuberculosis of the upper cervical spine [9, 10]. However, inconsistencies between imaging results and clinical manifestations are common. MRI is capable of detecting tuberculosis lesions in the early stages; thus, it is useful in reducing the risks of bone destruction, upper cervical deformities and paraplegia. The aim of spinal tuberculosis treatment is to control active tuberculosis lesions, but not to remove dead bones. Medication remains as the cornerstone for treating tuberculosis of the upper cervical spine. First-line drugs include isoniazid, rifampicin, ethambutol, pyrazinamide and streptomycin. In our study, 2 infants were treated with anti-tuberculosis medications and halo vest protection. At the last follow-up, these 2 patients were free of tuberculosis symptoms and cervical spinal deformities. Retropharyngeal abscess has no impact on spinal stability; and therefore, it is not necessary to actively debride lesions using an anterior approach. A study performed by Jutte et al. [11] revealed that rifampin concentrations were below MIC values in tuberculosis cold abscess. Gumbo et al. [12] demonstrated that rifampin had concentration-dependent characteristics that enhanced riHou/Yang/Zhang/Zhang/Xiao/Lu
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Table 1. Demographic and clinical characteristics of the study pop-
fampin entry with higher concentrations in the bacillary milieu. Its mechanisms remain unclear, but findings suggest a role for saturable efflux transporter proteins. Piddock et al. [13] have demonstrated that rifampin accumulation in wild-type M. tuberculosis increases in the presence of reserpine, which is consistent with a low-level efflux pump. Higher concentrations in microenvironments may enable them to overcome the effects of the pump. Local infusion of rifampin may enhance rifampin concentration and overcome oral anti-tuberculosis regimen lower drug concentrations in cold abscess. Spinal tuberculosis treatment aims to control active tuberculosis lesions, but not to remove dead bones. Debridement is not capable of removing upper cervical tuberculosis lesions completely. Active debridement of tuberculosis lesions does not eliminate the risk of tuberculosis recurrence, but may cause diffusion of the disease or even death. Atlantoaxial vertebrae are adjacent to the medulla oblongata, which requires emergent surgery once dislocation occurs [10, 14]. The diameter of the cervical vertebral canal is relatively large. Patients without atlantoaxial dislocation would not develop compression symptoms in general; and therefore, can be treated with medications [15]. Based on the above researches and our preliminary study on minimally invasive surgery for tuberculosis of the lumbar spine, tuberculosis of the upper cervical spine with absess formation and without atlantoaxial sublaxation and remarkable spinal cord compression can be treated with CT-guided catheter and local chemotherapy of isoniazid. Local chemotherapy can increase drug concentration and cure lesions. Atlantoaxial dislocation and spinal cord lesions are absolute indications for open surgery of upper cervical tuberculosis. Allali et al. [16] performed debridement of retropharyngeal abscess through the submandibular approach and atlantoaxial fusion or occipito-cervical fusion through the posterior approach, which achieved
good surgical outcomes. Compared with the transoral approach, the submandibular approach is less invasive, it has a shortened operative time, less bleeding, and lower risks of postoperative infection. This approach is especially suitable for debridement of upper cervical tuberculosis lesions [16]. However, Zhang et al. [17] performed a 1-stage surgery of debridement and short-segment fusion through the posterior approach in 11 children with upper cervical tuberculosis. They thought that anterior debridement may disrupt the anterior column and compromise spinal stability. The novel characteristic of our study was that the initial systemic and local chemotherapy was able to control active tuberculosis lesions well and provided a solid basis for open surgery. In addition, 1-stage posterior surgery has many advantages over anterior surgery such as shorter anesthesia time, direct access to the lesion, less complications and stable fixation.
Conclusion
To summarize, tuberculosis of the upper cervical spine has the following characteristics: low incidence, difficult to diagnose, and lack of treatment experience. Oral drug treatment alone is effective for this disease at an early stage. Local chemotherapy through minimally invasive surgery can be considered a treatment option if medical treatment is not effective. Open surgery is needed when a patient has cervical spinal deformities or atlantoaxial dislocation. This stepwise therapy has successfully cured our 11 patients.
Disclosure Statement The authors declare no conflict of interest in this study.
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Stepwise Therapy for Treating Tuberculosis of the Upper Cervical Spine
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7 Lee CK, Vessa P, Lee JK: Chronic disabling low back pain syndrome caused by internal disc derangements. The results of disc excision and posterior lumbar interbody fusion. Spine (Phila Pa 1976) 1995;20:356–361. 8 Morantz RA, Devlin JF, George A, Budzilovich G: Pott’s disease as cause of atlanto-axial subluxation. N Y State J Med 1974;74:1634–1637. 9 Ansari S, Amanullah MF, Ahmad K, Rauniyar RK: Pott’s spine: diagnostic imaging modalities and technology advancements. N Am J Med Sci 2013;5:404–411.
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15 Tuli SM: Tuberculosis of the craniovertebral region. Clin Orthop Relat Res 1974;104:209– 212. 16 Allali F, Benomar A, El Yahyaoui M, Chkili T, Hajjaj-Hassouni N: Atlantoaxial tuberculosis: three cases. Joint Bone Spine 2000;67:481–484. 17 Zhang HQ, Lin MZ, Guo HB, Ge L, Wu JH, Liu JY: One-stage surgical management for tuberculosis of the upper cervical spine by posterior debridement, short-segment fusion, and posterior instrumentation in children. Eur Spine J 2013;22:72–78.
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10 Sharif HS, Morgan JL, al Shahed MS, al Thagafi MY: Role of CT and MR imaging in the management of tuberculous spondylitis. Radiol Clin North Am 1995; 33: 787– 804. 11 Jutte PC, Rutgers SR, Van Altena R, Uges DR, Van Horn JR: Penetration of isoniazid, rifampicin and pyrazinamide in tuberculous pleural effusion and psoas abscess. Int J Tuberc Lung Dis 2004;8:1368–1372.
Eur Neurol 2015;74:100–106 DOI: 10.1159/000437418
Stepwise Therapy for Treating Tuberculosis of the Upper Cervical Spine: A Retrospective Study of 11 Patients Kedong Hou a Huadong Yang b Lin Zhang c Xifeng Zhang d Songhua Xiao d Ning Lu d
a
Pinggu Hospital of Capital Medical University, b Medical Center of Tsinghua University, c Shanxi Medical University, and d Chinese PLA General Hospital, Beijing, China
Abstract Aims: Tuberculosis of the upper cervical spine is a rare occurrence with serious consequence, and its optimal treatment protocol remains inconclusive. This study aims at investigating the clinical characteristics and management outcomes of the stepwise therapy for different stages of tuberculosis of the upper cervical spine. Methods: We conducted a retrospective analysis of 11 patients with tuberculosis of the upper cervical spine who received anti-tuberculosis chemotherapy for 15 months. Two infants were treated by individualized chemotherapy, while 9 patients with retropharyngeal abscess were first treated with CT-guided percutaneous puncture, and the catheter was used to administer local chemotherapy. Two of these 9 patients continued to receive posterior instrumentation due to atlantoaxial subluxation. Patients were followed up clinically and radiologically for an average period of 60 months. Results: Two patients underwent catheter change due to catheter falling off and blockage, 2 patients had gastrointestinal side effects, and 2 patients had drug-induced hepatitis derived from the chemotherapy. Mean erythrocyte sedimentation rate was 10.27 mm/h (range 4–16 mm/h) and average visual analogue scale
© 2015 S. Karger AG, Basel 0014–3022/15/0742–0100$39.50/0 E-Mail [email protected] www.karger.com/ene
score was 2.55. A total of 11 cases underwent routine antituberculosis chemotherapy for 15 months. 9 of 11 cases received supplementary surgical therapy, and all patients were cured at the final follow-up. Conclusion: Standard antituberculosis chemotherapy is the cornerstone of stepwise therapy for tuberculosis of the upper cervical spine. Local chemotherapy is effective and minimally invasive for patients with severe local symptoms without spinal cord compression. Just as in patients with atlantoaxial instability, open fixation and bone grafting are necessary. © 2015 S. Karger AG, Basel
Introduction
Tuberculosis infections have a higher incidence rate in both developing and developed countries. Although tuberculosis of the spine (Pott’s disease) is a well-known manifestation of infection, tuberculosis of the upper cervical spine is uncommon and occurs rarely in approximately 1% of all spinal tuberculosis cases [1, 2]. This disease is potentially dangerous due to the severe neurological complications and the relatively small cross-sectional
Kedong Hou and Huadong Yang are co-first authors, they contributed equally to this paper.
Dr. Xifeng Zhang Chinese PLA General Hospital No. 28 Fuxing Road, Haidian District Beijing 100853 (China) E-Mail zhangxf00000 @ 163.com
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Key Words Spinal cord · Upper cervical vertebrae · Tuberculosis · Chemotherapy · Minimally invasive
Color version available online
Fig. 1. A 2-year-old boy with tuberculosis of the C1–C2 vertebrae. a CT axial view
showing destruction of the vertebral body. coronal reconstruction and destruction of the odontoid process and C2 vertebral body. d A patient was treated with oral anti-tuberculosis drugs and halo vest protection. e Lateral X-ray of the cervical spine at 2 years of follow-up. The prevertebral space was normal. The space between the odontoid process and anterior arch of the atlas was normal. f Anterior-posterior cervical open mouth view. The odontoid process was in the median position. g CT sagittal reconstruction. The C1–C2 vertebrae were free of tuberculosis lesions and bone destruction.
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diameter of the spinal canal relative to the diameter of the cervical cord. Anti-tuberculosis chemotherapy, brace, and improved nutrition have achieved excellent functional outcomes in patients diagnosed with early stages of tuberculosis of the upper cervical spine without presenting deformities, neurologic deficits, abscess and spinal instability [3]. Patients with tuberculous retropharyngeal abscess are usually secondary to tuberculous involvement of the cervical spine [4]; in such patients, anti-tuberculosis chemotherapy is merely limited. However, profound vertebral destruction and severe complications have occurred in radical debridement and bone grafts for cases without atlantoaxial instability [5]. Our earlier study has revealed that CT-guided percutaneous puncture and local chemotherapy for tuberculosis of the lumbar spine has achieved satisfactory results [6]. To the best of our knowledge, tuberculosis of the upper cervical spine combined with minimally invasive surgery has rarely been reported. We have treated tuberculosis of the upper cervical spine in different stages using drugs, minimally invasive surgery, and combination of posterior instrumentation and fusion surgery in a stepwise way, which achieved good clinical outcomes. In this study, we report our experience with 11 cases of tuberculosis of the upper cervical spine. Stepwise Therapy for Treating Tuberculosis of the Upper Cervical Spine
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Materials and Methods Study Population and Data Collection A total of 11 patients with clinically and histologically proven spinal tuberculosis underwent surgery at the Chinese PLA General Hospital between November 2005 and January 2012. Among these patients, 8 patients were males and 3 patients were females; and the mean age of all patients was 33.3 years (range 2–68 years). In 9 patients, the disease involved 2 adjacent segments: C1–C2 in 8 patients and C2–C3 in 1 patient, while in 2 patients, the disease involved 3 adjacent segments (C1–C3). Other comorbidities included renal tuberculosis in 1 patient, pulmonary tuberculosis in 2 patients, cerebral thrombosis in 1 patient, and rheumatic disease in 1 patient. Symptoms included cervical pain and restricted cervical movement, no signs of neurological defects were observed. 2 patients complained of foreign body sensation in the pharynx. Mycobacterium tuberculosis was cultured from specimens obtained from 9 of 11 patients (9/11), and 44% of specimens (4/9) produced positive cultures. All cultures were susceptible patterns. Medical records were reviewed for patient demographics and clinical characteristics, anti-tuberculosis treatment history, treatment modalities, and outcomes. Written informed consent was obtained from all patients. Imaging Study CT revealed that the bone destruction occurred in the anterior arch of the atlas and base of the odontoid process (fig. 1a–c, 2b, 3c, 3d), as well as increased retropharyngeal space (fig. 2b, 3b, 3c). No signs of spinal cord compression or kyphosis in the cervical spine were observed. One patient showed scoliosis in the cervical spine (fig. 3d). Magnetic resonance imaging (MRI) showed retro-
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b CT sagittal reconstruction showing destruction of the odontoid process. c CT
Color version available online
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Fig. 2. A 42-year-old woman with tuberculosis of the C1–C2 vertebrae. a X-ray lateral view showing normal cervical curvature and increased retropharyngeal space. b CT axial view showing increased retropharyngeal space, abscess, and destruction of the C2 vertebra. c T1-weighted MRI showing the retropharyngeal abscess. d A cath-
eter was inserted through the right mastoid process and advanced into the retropharyngeal abscess under CT guidance. e A catheter was inserted through the right mastoid process. f 6 weeks after local chemotherapy, T1-weighted MRI showed no spinal cord compression and retropharyngeal abscess. C1–C2 vertebrae were normal.
pharyngeal abscess in 9 patients (fig. 2c, 3e, 3f). Lateral X-ray also revealed increased retropharyngeal space in all patients (fig. 2a, 3a).
withdrawn, and an epidural tube (disposable nerve block anesthesia kit I, Tuoren Medical Company, China) was inserted according to the depth of the puncture needle. The catheter was fixed with transparent dressing and the catheter length was recorded (fig. 2e). The following 4–8 weeks, 0.1 g of isoniazid was locally administered 1–2 times per day; and oral anti-tuberculosis medication continued.
Stepwise Therapy Step Ι: General Anti-Tuberculosis Chemotherapy Indications. (1) Clinical diagnosis of tuberculosis of the upper cervical spine in infant patients; (2) adult patients without abscess formation, vertebral destruction and neurologic deficits. Chemotherapy Regimen. All patients received a 4-drug anti-tuberculosis regimen daily for the first 3 months including 0.3 g of isoniazid, 0.45 g of rifampicin, 0.75 g of ethambutol, and 1.0 g of pyrazinamide. Doses for children were adjusted according to body weight. A 3-drug anti-tuberculosis regimen was administered daily for the following 12 months including 0.3 g of isoniazid, 0.45 g of rifampicin, and 0.75 g of ethambutol. A halo vest or Philadelphia collar was used to protect the cervical spine (fig. 1d). Step II: CT-Guided Catheter and Local Chemotherapy of Isoniazid Combined with Step I Indications. (1) Unresponsive to drug treatment; (2) in poor health status and could not tolerate open surgery; (3) retropharyngeal abscess or vertebral canal abscess; (4) there is no atlantoaxial dislocation. Surgical Technique. With the patient in the supine positionunder CT guidance, a puncture needle (18 G, 200 mm; Nihon Kohden Company, Japan) was advanced through the site anterior to the mastoid process to the lesion (fig. 2d, 3g). The needle core was
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Step III: Posterior Pedicle Screw Internal Fixation Succeeded with Step II Indications. (1) Atlantoaxial dislocation or subluxation during the course of Step II; (2) progressive compression of the spinal cord during the course of Step II. After local chemotherapy, 2 patients still showed signs of atlantoaxial subluxation. Hence, internal fixation through a posterior approach was performed after 8 and 11 weeks of drug treatment, respectively. Oral anti-tuberculosis medication was continued. Surgical Technique. Under general anesthesia, the patient was placed in prone position with head immobilized using a Mayfield headholder in case of reducible C1–C2 subluxation. The head was fixed in a neutral position. A midline incision was made extending from the inion to the C4 spinous process; and the C1 posterior arch, C2 lateral mass and C2–C3 facet joint were exposed subperiosteally. The medial aspect of the C2 dorsal element was carefully exposed to confirm the entry point and trajectory of the C2 pars interarticularis or pedicle screw. The C1 lateral mass inferior to the C1 arch was exposed. The medial and lateral aspects of the C1 lateral mass were palpated for safe placement of the C1 screw. The C1
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a
a
b
c
e
f
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lateral mass and C2 screws were connected tightly with a rod. The patient was immobilized on the first postoperative day and wore a Philadelphia collar for 3 months.
h
liosis. e T2-weighted MRI showing soft tissue swelling of the retropharynx, abnormal signals of the odontoid process, and C1–C2 semi-dislocation. f T2-weighted MRI showing displacement of the odontoid process, suggesting atlantoaxial dislocation. g Under CT guidance, a catheter was inserted through the right mastoid process and advanced into the lesion anterior to the C1 vertebral body. h X-ray lateral view showing C1–C2 fusion fixation for atlantoaxial dislocation treatment.
Results
Postoperative Management A halo vest was used in 2 infant patients to protect the cervical spine. Collar protection was used in other 9 patients for 3–4 months. Patients were encouraged to start activity from the first postoperative day. All patients received a 4-drug anti-tuberculosis regimen for the first 3 months and a 3-drug anti-tuberculosis regimen for the following 12 months. The epidural tube was properly fixed to prevent it from accidentally falling off and pumping back necrotic tissue that could obstruct the tube before local administration of isoniazid.
Demographic and Clinical Characteristics Among the 11 patients, 3 were female and 8 were male; and median age was 33.3 years (range 2–68 years). 2 vertebral levels were involved in 8 patients, 1 vertebral level existed in 1 patient, and 3 vertebral levels occurred in 2 patients. Among these patients, 27.3% (3/11) coexisted with other tuberculosis symptoms. All patients were primary cases and no patient had neurological deficits or kyphotic deformities. None of the patients were co-infected with HIV (table 1).
Follow-Up Index The following indices were recorded preoperatively at 1, 2 and 6 months of follow-ups, and every 6 months thereafter: (1) clinical presentation; (2) X-ray, CT or MRI scans; (3) erythrocyte sedimentation rate (ESR), hepatic function and renal function. Visual analogue scale (VAS) was performed to assess cervical pain. Fusion assessment was determined by X-ray according to the criteria defined by Lee et al. [7]. Definitive and probable fusions were classified as spinal fusion in this study.
Treatment Outcomes All patients were followed-up for a mean period of 60 months (range 28–108 months). 2 infant patients with tuberculosis of the upper cervical spine received chemotherapy and all patients received minimally invasive surgery. 7 of them were completely cured, while 2 patients continued to receive open fixation and autologous bone
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Fig. 3. A 19-year-old man with tuberculosis of the C1–C2 vertebrae and atlantoaxial dislocation. a X-ray lateral view showing loss of cervical curvature, increased retropharyngeal space, and increased anterior atlantodens interval. b CT axial view showing the broken anterior arch of the atlas, displacement of the odontoid process, bone destruction, and increased retropharyngeal space. c CT sagittal reconstruction showing destruction of the odontoid process and increased retropharyngeal space. d CT coronal reconstruction showing destruction of the base of the odontoid process and sco-
d
ulation Characteristics
Value (n = 11)
Male/female Median age, years (range) Other sites of tuberculosis Pulmonary tuberculosis Nephrotuberculosis Paravertebral cold abscess Previous surgery for spinal tuberculosis HIV co-infection
8/11 33.3 (2–68) 3 (27.3) 2 (18.2) 1 (9.1) 9 (81.8) none none
Values given as n (%) unless otherwise noted.
Table 2. Surgery and follow-up data
Characteristics
Value (n = 11)
Step I Step II Step III ESR mm/h, median (range) Preoperative Postoperative Follow-up time, months Complication Chemotherapy Surgery
2/11 9/11 2/11# 50.45 (38–64) 10.27 (4–16) 60 (28–108) 4/11 2/9
# Atlantoaxial
subluxation occurred in patients treated with Step II, and these patients were treated with Step III.
grafting for atlantoaxial sublaxation. 2 cases underwent catheter change: catheter fall off occurred in 1 case and catheter blockage occurred in the other case. The mean ESR value was 6.24 mm/h (range 0–32 mm/h) at the final follow-up. 2 patients had gastrointestinal side effects derived from chemotherapy and 2 suffered drug hepatitis (table 2). Bone grafting achieved good fusion at a mean time of 3.5 months (range 3–4 months). Anti-tuberculosis drugs were stopped when patients met the following criteria: (1) normal body temperature with generally good health status; (2) no cervical pain and local symptoms; (3) normal ESR for 3 consecutive months; (4) imaging examination did not reveal any abscess. Mean VAS score significantly decreased from 8.36 (range 6–10) at baseline to 2.55 (range 0–4) at the last follow-up (P < 0.01). At the last follow-up, all patients were asymptomatic. All tuberculosis lesions were healed as shown by radiological ex104
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amination (fig. 1e–g, 3h). The upper cervical spine showed normal curvature. No significant complications, such as tuberculosis recurrence, fistula, bone graft dislodgement and pseudoarticulation, occurred.
Discussion
Tuberculosis of the upper cervical spine can cause spinal cord compression, resulting from atlantoaxial dislocation, abscess compression, and direct involvement of the tuberculosis lesion. Neurologic deficits are common in patients with tuberculosis of the upper cervical spine, which is associated with compression on the spinal cord or nerve roots [8]. Tuberculosis of the upper cervical spine has an insidious onset, and symptoms of vertebral destruction and neurologic deficits occur in late stages of the disease. However, in our patients, no symptoms of spinal cord compression were observed. Patients with pharyngeal abscess may have symptoms of dysphagia, dyspnea, and feeling of foreign body in the pharynx. In our study, 9 patients had retropharyngeal abscess and 2 of these patients had a feeling of foreign body in the pharynx. However, no symptoms of dysphagia and dyspnea were observed. These patients were initially referred to an otolaryngologist, suggesting a risk of misdiagnosis. Imaging examination is important for the accurate diagnosis and evaluation of tuberculosis of the upper cervical spine [9, 10]. However, inconsistencies between imaging results and clinical manifestations are common. MRI is capable of detecting tuberculosis lesions in the early stages; thus, it is useful in reducing the risks of bone destruction, upper cervical deformities and paraplegia. The aim of spinal tuberculosis treatment is to control active tuberculosis lesions, but not to remove dead bones. Medication remains as the cornerstone for treating tuberculosis of the upper cervical spine. First-line drugs include isoniazid, rifampicin, ethambutol, pyrazinamide and streptomycin. In our study, 2 infants were treated with anti-tuberculosis medications and halo vest protection. At the last follow-up, these 2 patients were free of tuberculosis symptoms and cervical spinal deformities. Retropharyngeal abscess has no impact on spinal stability; and therefore, it is not necessary to actively debride lesions using an anterior approach. A study performed by Jutte et al. [11] revealed that rifampin concentrations were below MIC values in tuberculosis cold abscess. Gumbo et al. [12] demonstrated that rifampin had concentration-dependent characteristics that enhanced riHou/Yang/Zhang/Zhang/Xiao/Lu
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Table 1. Demographic and clinical characteristics of the study pop-
fampin entry with higher concentrations in the bacillary milieu. Its mechanisms remain unclear, but findings suggest a role for saturable efflux transporter proteins. Piddock et al. [13] have demonstrated that rifampin accumulation in wild-type M. tuberculosis increases in the presence of reserpine, which is consistent with a low-level efflux pump. Higher concentrations in microenvironments may enable them to overcome the effects of the pump. Local infusion of rifampin may enhance rifampin concentration and overcome oral anti-tuberculosis regimen lower drug concentrations in cold abscess. Spinal tuberculosis treatment aims to control active tuberculosis lesions, but not to remove dead bones. Debridement is not capable of removing upper cervical tuberculosis lesions completely. Active debridement of tuberculosis lesions does not eliminate the risk of tuberculosis recurrence, but may cause diffusion of the disease or even death. Atlantoaxial vertebrae are adjacent to the medulla oblongata, which requires emergent surgery once dislocation occurs [10, 14]. The diameter of the cervical vertebral canal is relatively large. Patients without atlantoaxial dislocation would not develop compression symptoms in general; and therefore, can be treated with medications [15]. Based on the above researches and our preliminary study on minimally invasive surgery for tuberculosis of the lumbar spine, tuberculosis of the upper cervical spine with absess formation and without atlantoaxial sublaxation and remarkable spinal cord compression can be treated with CT-guided catheter and local chemotherapy of isoniazid. Local chemotherapy can increase drug concentration and cure lesions. Atlantoaxial dislocation and spinal cord lesions are absolute indications for open surgery of upper cervical tuberculosis. Allali et al. [16] performed debridement of retropharyngeal abscess through the submandibular approach and atlantoaxial fusion or occipito-cervical fusion through the posterior approach, which achieved
good surgical outcomes. Compared with the transoral approach, the submandibular approach is less invasive, it has a shortened operative time, less bleeding, and lower risks of postoperative infection. This approach is especially suitable for debridement of upper cervical tuberculosis lesions [16]. However, Zhang et al. [17] performed a 1-stage surgery of debridement and short-segment fusion through the posterior approach in 11 children with upper cervical tuberculosis. They thought that anterior debridement may disrupt the anterior column and compromise spinal stability. The novel characteristic of our study was that the initial systemic and local chemotherapy was able to control active tuberculosis lesions well and provided a solid basis for open surgery. In addition, 1-stage posterior surgery has many advantages over anterior surgery such as shorter anesthesia time, direct access to the lesion, less complications and stable fixation.
Conclusion
To summarize, tuberculosis of the upper cervical spine has the following characteristics: low incidence, difficult to diagnose, and lack of treatment experience. Oral drug treatment alone is effective for this disease at an early stage. Local chemotherapy through minimally invasive surgery can be considered a treatment option if medical treatment is not effective. Open surgery is needed when a patient has cervical spinal deformities or atlantoaxial dislocation. This stepwise therapy has successfully cured our 11 patients.
Disclosure Statement The authors declare no conflict of interest in this study.
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