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(i) Tuberculosis of the spine
MINI-SYMPOSIUM FROM THE ASIA PACIFIC REGION
(i) Tuberculosis of the spine
and subsequently the immune response is stimulated. A delayed hypersensitivity immune response produces cytokines which in turn leads to recruitment of monocytes, lymphocytes and macrophages. These infected inflammatory cells then form a granuloma and the macrophages differentiate into foam cells, giant cells and epithelioid cells. The centre of the granuloma then caseates and becomes necrotic. The infection can progress to destroy bone, cause pain and lead to collapse of the vertebral body(ies) and kyphosis. Tuberculosis abscesses containing necrotic debris expand following the path of least resistance and beneath the anterior and posterior longitudinal ligaments to the adjacent levels and skin sinuses may form and drain spontaneously. While nerve roots may be compressed causing pain or radiculopathy, more commonly spinal cord or cauda equina compression gives rise myelopathy or paraplegia. This may happen early in active disease due to spinal cord compression by inflammatory tissues, epidural abscess, protruded intervertebral discs, pachymeningitis or spinal subluxation. It may also happen years after the initial tuberculosis infection e late-onset paraplegia e due to severe kyphosis with chronic spinal cord compression and spinal cord atrophy, with or without reactivation of the infection. Late-onset paraplegia may also arise due to due to spinal stenosis above the healed kyphosis.5 To compensate for the kyphotic deformity as a result of the tuberculosis infection, patients hyper-extend their thoracic spine to achieve overall sagittal balance. Such hyper-extension of adjacent levels can lead to early degeneration, spinal stenosis and neurological deficits.
W Y Cheung Keith D K Luk
Abstract The incidence of spinal tuberculosis, which may lead to severe spinal deformity, early and late neurological complications, is increasing. This paper reviews its pathophysiology, clinical presentation, diagnosis and management.
Keywords
diagnosis;
management;
pathophysiology;
spine;
tuberculosis
Epidemiology Worldwide tuberculosis is the commonest infectious disease and about 95% of cases occur in developing countries. The World Health Organization estimates that in China alone there are 1.4 million new cases annually and 1.81 million deaths from tuberculosis in Asia each year. The US Center for Disease Control (CDC) has predicted that the number of new diagnoses of active tuberculosis worldwide will increase from 7.5 to 11.8 million per year. The prevalence will rise from 143 to 173 per 100 000 and deaths due to tuberculosis will climb from 2.5 to 3.5 million or more per year.1,2 This has been attributed partly to an increase in HIV infection because HIV disables and destroys the thymic lymphocytes and tissue macrophages that are the body’s main defence against tuberculosis making those who are HIV-positive extremely susceptible to the disease. In some African countries, the number of reported tuberculosis cases has doubled or even tripled from 2001 to 2003 because of the spread of HIV/AIDS.1,2 While tuberculosis most commonly infects the lungs, it affects the spine in three to five per cent of patients.3 Tuberculous spondylitis, although less common, is the most dangerous form of skeletal tuberculosis.4
Clinical presentation In the early stages of the disease, most commonly there are slowly progressive constitutional symptoms including generalized weakness, malaise, night sweats, fever, and weight loss. Pain is a late symptom associated with bone collapse. While patients may present with neurological symptoms and signs such as lower limb weakness and numbness (Pott’s paraplegia) due to spinal cord or cauda equina compression, with, in severe cases, loss of urinary and bowel control, usually neurological signs occur later in the disease; Jain et al. calculated that the spinal canal can accommodate 76% encroachment on CT scan without neurological abnormality.6 Rarely cervical involvement can cause hoarseness because of recurrent laryngeal nerve paralysis, dysphagia, and respiratory stridor (Millar asthma) due to anterior abscess formation in the neck (Figure 1). Sudden death due to erosion into the great vessels has also been reported in association with cervical disease.
Pathophysiology Tuberculosis of the spine is a potentially life threatening infection caused by Mycobacterium tuberculosis which is an aerobic, weakly Gram positive bacillus with a thick cell wall containing mycolic acid, which renders it acid fast. The bacteria commonly reach the spine by haematogenous spread, so it is the vertebral bodies that are usually affected. They are then phagocytosed by macrophages
Diagnosis Laboratory studies are suggestive of chronic infection, i.e. anaemia, hypoproteinemia, and an elevated ESR. Tuberculin skin testing may be helpful, but is not diagnostic especially in TB endemic areas where the population may have had subclinical exposures or have received BCG vaccination. Interferon gammarelease assays (IGRA) is a relatively new method for detecting T cells specific for Mycobacterium tuberculosis antigens. It has sensitivity about 80% and is more specific than the tuberculin skin test. Its sensitivity remains high in immune-compromised patients and is not confounded by BCG vaccination. The main
W Y Cheung FRCSEdOrth FHKAM Associate Consultant, The Department of Orthopedics & Traumatology, The University of Hong Kong, Pokfulam, Hong Kong SAR, China. Keith D K Luk MCh Orth FRCSEd FRACS FHKAM Tam Sai Kit Chair in Spine Surgery, Chair Professor and Head, The Department of Orthopedics & Traumatology, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
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evaluation of the bony destruction and possible instability while MRI permits further delineation of the soft-tissue components, activity of the disease and status of the spinal cord (Figure 2). Gupta et al. noted that abscess formation and the presence of bone fragments on MRI helped distinguish spinal tuberculosis from neoplasia. However definitive diagnosis is dependant on culture of the organism, requiring biopsy of the lesion. Percutaneous biopsies under radiographic or CT control usually suffice. Francis et al. reported 29 patients with suspected spinal tuberculosis. Epithelioid granulomata were seen in 89%, positive acid-fast bacilli cultures in 83% and positive acid-fast bacilli smears in 52%. Percutaneous thoracoscopic or laparoscopic biopsy has been reported by Dusmet et al. Nonetheless, open biopsy may be necessary if needle biopsy is unsuccessful or during a definitive open procedure. Because Mycobacterium tuberculosis is difficult to culture due to its fastidious growth requirements and slow growth rate, there is a need for techniques that permit more effective and earlier diagnosis. Polymerase chain reaction (PCR), a non-culture, molecular diagnostic test, amplifies the DNA of the Mycobacterium tuberculosis for identification. This utilizes a primer pair targeting a 123 base pair segment of the repetitive sequence IS6110 of the M. tuberculosis complex which covers M. tuberculosis, M. africanum, M. bovis, M. canetti and M. microti. The amplified segment of the tuberculosis DNA is subsequently detected with the Southern Blot hybridization technique. PCR is highly sensitive (95e98%) for diagnosing tuberculosis from smear-positive and culture-positive cases, but it has lower sensitivity (57e78%) for smear-negative and culture-positive cases. This is an exciting development, allowing quicker diagnosis and has also been used as a marker to monitor response to treatment. With different primers, it has also been shown to provide rapid information on drug resistance and clonality in epidemiological investigations of outbreaks.7
Figure 1 Marked soft-tissue swelling at the cervical or upper thoracic region may cause airway obstruction (Millar asthma).
limitation of the test is it cannot differentiate active from latent infection. Early radiographic findings include a subtle decrease in one or more disc spaces with localized osteopenia. Later findings include vertebral collapse, described by Seddon, as “concertina collapse” because of its resemblance to an accordion. Soft-tissue swelling and later calcification are highly predictable radiographic findings. CT scanning, with contrast, allows better
Figure 2 Contrast MRI shows enhancement at L4 and L5 vertebral body and a rim enhancement lesion at epidural space with cauda equina compression.
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Treatment
Surgical treatment Surgical treatment is an important component in the treatment of spinal tuberculosis. In the presence of active disease surgery is indicated if: there is significant neurological deficit due to spinal cord or cauda equina compression, there is severe deformity that requires surgical stabilization, the diagnosis is uncertain and open biopsy is required, and if conservative treatment has failed and there is significant back pain. As the disease is usually in the anterior aspect of the spine, surgery is commonly performed via the anterior approach. This was first described by Ito et al. in 19349 and subsequently popularized by Hodgson and Stock in 1956.10 It allows direct access to the anterior disease focus and permits complete clearance of the abscess, tissue biopsy for diagnosis and, more importantly, insertion of strut grafts under compression at the kyphus. Various studies have shown that patients with Pott’s paraplegia due to active disease had better neurological recovery if treated with surgery compared with conservative treatment alone. Martin et al. reported 60% of patients with Pott’s paraplegia treated with surgery had neurological recovery compared with 48% of patients treated conservatively.11 Guirguis et al. reported an even higher success rate with 93% patients treated surgically having neurological recovery versus 40% of patients treated conservatively.12 The role of surgery for patients without significant neurological deficit is less well defined. To study the relative merits of the conservative and surgical approach to the treatment of TB spine in this group of patients, the Medical Research Council of the United Kingdom initiated and coordinated a series of important clinical trials. These were carried out from 1965 in multiple centres in the world where the disease was prevalent. The patients were carefully selected, documented and followed up for as long as 15 years prospectively. The results were published in a series of reports that should be mandatory reading for every spinal surgeon.13e17 The efficacy of surgical treatment was compared with that of conservative drug treatment. In Rhodesia (now Zimbabwe), Korea and Hong Kong, patients were randomly allocated to the drug treatment group, debridement group or radical debridement plus anterior spinal fusion group. The inclusion criterion was clinical or radiological evidence of tuberculosis at any level except the cervical spine. Patients with significant neurological deficit such that they could not walk across the room, those had been given anti-tuberculous drugs for more than 1 year, those that had significant extra-spinal disease and, for the fusion group, those that had more than three levels of vertebral destruction were excluded from the study. All patients were given 18 months of two or three drug combination chemotherapy. In the debridement group, the abscess, the sequestrum and the loose disc fragments were removed to achieve spinal cord decompression and no fusion was performed. In Hong Kong, the radical surgery group underwent radical debridement of the necrotic tissue until healthy bleeding bone was reached. This was then followed by an anterior strut graft fusion using autologous rib, iliac or fibula grafts. The results reported at the 5-, 10- and 15-year reports indicated that all three groups achieved the same 87% favourable outcome, defined as
Tuberculosis is usually considered to be cured when there are no clinical signs of infection, the patient is neurologically intact, has regained their previous activity level and does not suffer relapse. However, spinal tuberculosis presents some additional problems, kyphosis and delayed neurological deficit. Therefore modern treatment is also directed at correcting the kyphosis thereby restoring the balance of the spine, achieving early bony fusion (healing), preventing local recurrence of spinal tuberculosis, and thus preventing late neurologic complications. Medical treatment The main stay of treatment is chemotherapy. Since the advent of specific anti-tuberculous chemotherapy, patients rarely die from the disease, the period of infectivity is considerably reduced, relapses are avoided and chronicity reduced. With the increasing prevalence of drug-resistant tuberculosis worldwide, it is very important to know the bacterial sensitivities before commencing chemotherapy. By culture of aspirate or tissue specimens, sensitivity tests of the cultured tubercle bacilli against each drug can be ascertained. There are currently five first line anti-tuberculous drugs, isoniazid, rifampicin, pyrazinamide, streptomycin and ethambutol. Various treatment regimens have been described and generally 6e12 months of chemotherapy is required2,8 (Table 1). In our centre, the standard regimen is ethambutol, pyrazinamide, rifampicin and isoniazid for 2 months, followed by rifampicin and isoniazid for 4 months. Longer treatment may be necessary for elderly or immune-compromised patients. Drug-resistant tuberculosis is defined as resistance to one or more of the primary anti-tuberculous drugs. Its management is very complex, necessitating treatment with secondary chemotherapeutic agents, which include amikacin, capreomycin, ciprofloxacin, cycloserine, ethionamide, kanamycin, ofloxacin, and para-aminosalicylic acid. It is better not to just add a single drug to a failing regimen because that creates an ideal condition for the development of resistance to the new medication. Instead, expert opinion from a microbiologist should be sought. The most common causes of development of drug resistance are inadequate treatment and/or patient non-compliance. Preventative measures including directly observed therapy to maximize compliance are essential.
Anti-tuberculosis regimes Three drug regimes (months) Davies PC (1996): HRZ (2) HR (10) Upadhyay et al (1999): HPaS(3)Hpa(3) Moon et al (1987, 1995, 1997, 2004): RHE(Z)(12) Four drug regimes (months) Medical research council (1993): RHEZ(2) RH(4) Yilmaz et al (1999): SRHZ(2) RH(7) Metha IS et al (2001): RHEZ(2) RHE(4) RH(6) Govender et al (2003): RHZE(12) H: isoniazid, R: rifampicin, Z: pyrazinamide, Pa: P-aminosalicylic acid, S: streptomycin.
Table 1
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no evidence of central nervous system involvement, no sinus or clinically evident abscess, no radiological evidence of disease activity and no restriction of normal physical activity. However, when these data were analyzed in greater detail, it was evident that the radical surgery group treated in Hong Kong had distinct advantages over the other two groups. There was much quicker relief of pain, earlier resolution of the sinus tracts and abscesses, and there was no neurologic involvement during treatment. There was a much higher rate of bony fusion of 85% at 5 years, which rose to 94% at 15 years. This compared with 46% at 5 years and 72% at 15 years for the group treated conservatively in Korea. The progression of the deformity was also different between the three groups. In the conservatively treated group, there was an increase of 21 at 5 years, which further increased to 25 at 15 years. The corresponding figures for the debridement group were 8 and 11 respectively. In contrast, the radical surgery group showed an improvement of 3 at 5 years, and this was maintained at the final 15-years follow-up assessment. It is also worth noting that in 5% of the conservative group, there was an alarming increase of kyphosis from 51 to 70 . Based on the results of this series of studies, the Medical Research Council concluded in its 13th report16 that: Conservative drug treatment, debridement alone and radical debridement and fusion all achieved similar favourable outcome in the majority of patients. The excellent results at 10 years are sustained at 15 years with no late relapse or late-onset paraplegia. The only advantage of radical operation is less late deformity compared with debridement. A question therefore comes, who will develop severe kyphosis that may benefit from early surgical stabilization and fusion? Rajasekaran et al. tried to answer this question by identifying some risk factors in patients who developed severe angular kyphosis.18,19 They retrospectively reviewed 90 adult patients who had suffered from tuberculosis of the spine. The vertebral body loss at the start of treatment had a good correlation with the severity of the deformity at the 5-year follow-up. It was reported that the deformity at 5 years could be predicted with a fair level of accuracy by the calculation of the pretreatment vertebral body loss and the application of the formula
While early surgical Intervention for prevention of deformity is relatively simple, producing good results, and preventing additional deformity, surgery for established severe deformity is difficult, and hazardous with a relatively high complication rate. However, gross kyphotic deformities in the thoracic and thoracolumbar region can result in severe cardio-respiratory embarrassment and in the lumbar region, the kyphosis can cause severe postural imbalance and frequently results in severe foreshortening of the trunk. There can also be increased back pain due to muscle fatigue and impingement of the rib cage on the iliac crest as well as self-image and psychological problems. Previously single stage correction of deformity had an unacceptable rate of neurologic complications and achieved negligible correction, which was dissatisfying both to the surgeon and the patient. Additionally there was a significant risk of paraplegia because of the need for meticulous debridement of the tissues all around the spinal cord before osteotomy. Side-slip deformity at the apex of the kyphosis made the procedure even more dangerous, because of the difficulty in actually locating the spinal canal. To minimize the complications, Yau et al. advocated a staged sequential procedure, first fitting halo-pelvic distraction apparatus, followed by anterior spinal osteotomy and decompression of the spinal cord, slow and gradual spinal distraction, posterior osteotomy and fusion, additional spinal distraction, and anterior spine fusion after achieving maximum correction.20 (Figure 3) Even with this technique of staged procedures, there was a 10% mortality rate and the average amount of correction obtained was only 28%. Therefore this is only recommended for patients with severe deformity, active disease and imminent paraplegia or death from chest complications. Instrumentation: Oga et al. have shown that Mycobacterium tuberculosis is not adhesive to implant surfaces and does not form biofilms which means it is safe to use implants in the presence of active tuberculosis infection, provided intensive anti-tuberculosis therapy is given. Various studies also confirmed that spinal instrumentation is safe and effective in active tuberculosis infections.21,22 Recent advances in spinal instrumentation in recent years and intra-operative spinal cord monitoring techniques have made more aggressive kyphosis correction surgery possible. Rajasekaran et al. recently described a single-stage closing/ opening wedge osteotomy to correct severe tuberculous kyphosis.23 The procedure is performed through a single posterior approach, performing wide laminectomies and a wedge of vertebral column is excised. The anterior column is reconstructed with a cage and the deformity correction achieved by posterior closing and anterior opening, fulcruming at the cage. The merits of this procedure are that the spinal column is not excessively shortened or lengthened during the procedure, so the risk of neurological complication should be low. They reported 17 cases with average kyphosis correction of 57% and only one patient had deterioration of neurological status after the procedure. However care has to be taken regarding the flexibility of the compensatory hyper-lordosis proximal and distal to the kyphus before proceeding with this surgical procedure. Particularly if the thoracic lordosis is not reversible, any overcorrection of the thoraco-lumbar kyphosis may result in stresses being thrown into the cervical segment. Thus, the best candidates for this procedure would be for children or young adults without neurological symptoms or signs and the
Y ¼ a þ bX where Y is the deformity at 5-year follow-up, X is the pretreatment vertebral body loss, and a and b are constant values of 5.5 and 30.5. There was an average kyphus angle of 30 to 35 for the complete destruction of each vertebral body in the dorsal and dorso-lumbar region and approximately 20 for the complete loss of each vertebral body in the lumbar region. They recommended surgery for patients with loss of 0.75 thoracic or thoraco-lumbar vertebrae, or the loss of one lumbar vertebra to produce final kyphosis of less than 30 . In another study, they also identified some risk factors for severe kyphosis in paediatric patients, namely separation of facet joints, posterior retropulsion, lateral translation and toppling. Patients with more than two of these signs had progression of kyphosis more than 30 and a final kyphosis of more than 60 . Surgical treatment is therefore also recommended for this group of patients.
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Figure 3 a Severe tuberculosis kyphosis. b Treated with halo-pelvic traction and combined anterior, posterior spinal fusion. c Sagittal profile after treatment.
compensatory curves are still flexible and can be reversed with the segmental instrumentation.
by blunt dissection. Anterior to the transverse processes are the pedicles and the intervertebral foramina. The spinal canal is entered by tracing the intercostal nerves and removing the surrounding bone. Crowded pedicles at the apex are removed and the dura is exposed posterior to the posterior longitudinal ligament. Then excision of the internal kyphus is performed to decompress the spinal cord and anterior fusion carried out with strut grafts. Hsu et al. reported 80% of patients with active disease and 50% of patients with healed disease had neurological improvement with this procedure, but 10% of patients had neurological deterioration after the surgery.24 We recently published our 5-year results for patients with lateonset Pott’s paraplegia of healed disease and severe kyphosis treated by this method.25 Forty per cent of patients had neurological improvement and none had neurological deterioration after the surgery. Solid bone fusion was demonstrated in all patients at 5 years after surgery. While this surgical procedure is technically less demanding, it does not correct the kyphosis and sagittal mal-alignment. Thus it is particularly indicated for older patients with fixed compensatory lordosis or patients with multiple co-morbidities and high surgical risks.
Late-onset paraplegia: late-onset paraplegia with residual spinal deformity is one of the most disastrous complications of Pott’s disease and the prognosis is generally poor. Chronic spinal cord compression as a result of the severe kyphotic deformity, with or without reactivation of the tuberculosis infection, leads to spinal cord dysfunction and progressive neurological deficits. In our centre, we prefer to use anterior decompression and strut bone grafting via a costo-transversectomy approach to treat this group of patients (Figure 4). A curved longitudinal incision 6e8 cm lateral to the midline is created, centred over the kyphus. The paraspinal muscles are stripped and retracted medially from the lateral side to expose the transverse processes and the adjacent 5e6 cm ribs subperiosteally. Two to three transverse processes and the corresponding posterior end of the ribs including the rib heads are excised. Segmental intercostal nerves are identified and held with slings. Great care is taken to remain extra-pleural and extra-peritoneal. Soft tissue, pleura, and peritoneum are mobilized from the pedicles and the collapsed vertebral bodies
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Figure 4 a Severe post-tubercular kyphosis. b Internal kyphectomy for spinal cord (arrow) compression and anterior fusion with strut graft. c Postoperative X-ray showed internal kyphectomy and bone graft in position (arrow).
Conclusion
5 Luk KD, Krishua M. Spinal stenosis above a healed tuberculosis kyphosis. A case report. Spine 1996; 21: 1098e101. 6 Jain AK, Aggarwal A, Mehrotra G. Correlation of canal encroachment with neurological deficit in tuberculosis of spine. Int Orthop (SICOT) 1999; 23: 85e6. 7 Rattan A. PCR for diagnosis of tuberculosis: where are we now? Indian J Tuberculosis 2000; 47: 79e82. 8 Medical Research Council Working Party on Tuberculosis of the Spine. Controlled trial of short-course regimens of chemotherapy in ambulatory treatment of spinal tuberculosis. J Bone Joint Surg 1993; 75: 240e8. 9 Ito H, Tsuchiya J, Asami G. A new radical operation for Pott’s disease. J Bone Joint Surg 1934; 16: 499. 10 Hodgson AR, Stock FE. Anterior spinal fusion. Br J Surg 1956; 44: 266e75. 11 Martin NS. Pott’s paraplegia. A report on 120 cases. J Bone Joint Surg Br 1971; 53: 596e608. 12 Guirguis AR. Pott’s paraplegia. J Bone Joint Surg Br 1967; 49: 658e67. 13 Medical Research Council Working Party on Tuberculosis of the Spine. Five-year assessments of controlled trials of ambulatory treatment, debridement and anterior spinal fusion in the management of tuberculosis of the spine: studies in Bulawayo (Rhodesia) and in Hong Kong. J Bone Joint Surg Br 1978; 60: 163e77. 14 Medical Research Council Working Party on Tuberculosis of the Spine. A ten-year assessment of a controlled trial comparing debridement and anterior spinal fusion in the management of tuberculosis of the spine in patients on standard chemotherapy in Hong Kong. J Bone Joint Surg Br 1982; 64: 393e8. 15 Medical Research Council Working Party on Tuberculosis of the Spine. A ten-year assessment of controlled trials of inpatient and outpatient treatment and of plaster-of-Paris jacket for tuberculosis of the spine in children on standard chemotherapy. Studies in Masan and Pusan, Korea. J Bone Joint Surg Br 1985; 67: 103e10. 16 Medical Research Council Working Party on Tuberculosis of the Spine. A 15-year assessment of controlled trials of the management of
Tuberculosis infection of the spine is a serious clinical condition which may lead to severe deformity, early or late neurological complications and even mortality. Its incidence is increasing worldwide. Advances in laboratory testing allow more effective and earlier diagnosis of this condition. The aims of treatment are to cure the infection, prevent or correct kyphotic deformity and preservation of neurology. Though most infections can be cured by anti-tuberculosis chemotherapy, surgery is indicated for selected groups of patients. The majority of patients with early onset paraplegia due to active disease have a good neurological recovery with surgical decompression. Surgery should also be considered for patients at high risk of developing significant kyphosis which may lead to sagittal imbalance and late-onset paraplegia. Late-onset Pott’s paraplegia with severe kyphotic deformity is notoriously difficult to treat. Surgical decompression with or without correction of the kyphosis are the main stays of treatment but is technically demanding with high operative risks and should therefore not be attempted by the inexperienced. A
REFERENCES 1 Moon MS. Tuberculosis of the spine; controversies and new challenges. Spine 1997; 22: 1791e7. 2 Moon MS. Tuberculosis of the spine e contemporary thoughts on current issues and perspective views. Curr Orthop 2007; 21: 364e79. 3 Jutte PC, Van Loenhout-Rooyackers JH. Routine surgery in addition to chemotherapy for treating spinal tuberculosis. Cochrane Database Syst Rev 2006; doi:10.1002/14651858.CD004532.pub2. Issue 1: Art. No.: CD004532. 4 Watts HG, Lifeso RM. Tuberculosis of bone and joints. J Bone Joint Surg 1996; 78-A: 288e98.
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18
19
20
21 Oga M, Arizono T, Takasita M, Sugioka Y. Evaluation of the risk of instrumentation as a foreign body in spinal tuberculosis. Spine 1993; 18: 1890e4. 22 Moon MS, Woo YK, Lee KS, Ha KY, Kim SS, Sun DH. Posterior instrumentation and anterior interbody fusion for tuberculous kyphosis of dorsal and lumbar spine. Spine 1995; 20: 1910e6. 23 Rajasekaran S, Vijay K, Shetty AP. Single-stage closingeopening wedge osteotomy of spine to correct severe post-tubercular kyphotic deformities of the spine: a 3-year follow-up of 17 patients. Eur Spine J 2010; 19: 583e92. 24 Hsu LCS, Cheng CL, Leong JCY. Pott’s paraplegia of late onset: the cause of compression and results after anterior decompression. J Bone Joint Surg Br 1988; 70: 534e8. 25 Wong YW, Leong JCY, Luk KDK. Direct internal kyphectomy for severe angular tuberculosis kyphosis. Clin Orthop Relat Res 2007; 460: 124e9.
tuberculosis of the spine in Korea and Hong Kong. J Bone Joint Surg Br 1998; 80: 456e62. Medical Research Council Working Party on Tuberculosis of the Spine. A controlled trial of anterior spinal fusion and debridement in the surgical management of tuberculosis of the spine in patients on standard chemotherapy: a study in Hong Kong. Br J Surg 1974; 61: 853e66. Rajasekaran S, Shanmugasundaram TK. Prediction of the angle of gibbus deformity in tuberculosis of the spine. J Bone Joint Surg Am 1987; 69: 503e9. Rajasekaran S. The natural history of post-tubercular kyphosis in children: radiology signs which predict late increase in deformity. J Bone Joint Surg Br 2001; 83: 954e62. Yau ACMC, Hsu LCS, O’Brien JP, Hodgson AR. Tuberculosis kyphosiscorrection with spinal osteotomy, halo-pelvic distraction and anterior and posterior fusion. J Bone Joint Surg 1974; 56A: 1419e34.
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(i) Tuberculosis of the spine
and subsequently the immune response is stimulated. A delayed hypersensitivity immune response produces cytokines which in turn leads to recruitment of monocytes, lymphocytes and macrophages. These infected inflammatory cells then form a granuloma and the macrophages differentiate into foam cells, giant cells and epithelioid cells. The centre of the granuloma then caseates and becomes necrotic. The infection can progress to destroy bone, cause pain and lead to collapse of the vertebral body(ies) and kyphosis. Tuberculosis abscesses containing necrotic debris expand following the path of least resistance and beneath the anterior and posterior longitudinal ligaments to the adjacent levels and skin sinuses may form and drain spontaneously. While nerve roots may be compressed causing pain or radiculopathy, more commonly spinal cord or cauda equina compression gives rise myelopathy or paraplegia. This may happen early in active disease due to spinal cord compression by inflammatory tissues, epidural abscess, protruded intervertebral discs, pachymeningitis or spinal subluxation. It may also happen years after the initial tuberculosis infection e late-onset paraplegia e due to severe kyphosis with chronic spinal cord compression and spinal cord atrophy, with or without reactivation of the infection. Late-onset paraplegia may also arise due to due to spinal stenosis above the healed kyphosis.5 To compensate for the kyphotic deformity as a result of the tuberculosis infection, patients hyper-extend their thoracic spine to achieve overall sagittal balance. Such hyper-extension of adjacent levels can lead to early degeneration, spinal stenosis and neurological deficits.
W Y Cheung Keith D K Luk
Abstract The incidence of spinal tuberculosis, which may lead to severe spinal deformity, early and late neurological complications, is increasing. This paper reviews its pathophysiology, clinical presentation, diagnosis and management.
Keywords
diagnosis;
management;
pathophysiology;
spine;
tuberculosis
Epidemiology Worldwide tuberculosis is the commonest infectious disease and about 95% of cases occur in developing countries. The World Health Organization estimates that in China alone there are 1.4 million new cases annually and 1.81 million deaths from tuberculosis in Asia each year. The US Center for Disease Control (CDC) has predicted that the number of new diagnoses of active tuberculosis worldwide will increase from 7.5 to 11.8 million per year. The prevalence will rise from 143 to 173 per 100 000 and deaths due to tuberculosis will climb from 2.5 to 3.5 million or more per year.1,2 This has been attributed partly to an increase in HIV infection because HIV disables and destroys the thymic lymphocytes and tissue macrophages that are the body’s main defence against tuberculosis making those who are HIV-positive extremely susceptible to the disease. In some African countries, the number of reported tuberculosis cases has doubled or even tripled from 2001 to 2003 because of the spread of HIV/AIDS.1,2 While tuberculosis most commonly infects the lungs, it affects the spine in three to five per cent of patients.3 Tuberculous spondylitis, although less common, is the most dangerous form of skeletal tuberculosis.4
Clinical presentation In the early stages of the disease, most commonly there are slowly progressive constitutional symptoms including generalized weakness, malaise, night sweats, fever, and weight loss. Pain is a late symptom associated with bone collapse. While patients may present with neurological symptoms and signs such as lower limb weakness and numbness (Pott’s paraplegia) due to spinal cord or cauda equina compression, with, in severe cases, loss of urinary and bowel control, usually neurological signs occur later in the disease; Jain et al. calculated that the spinal canal can accommodate 76% encroachment on CT scan without neurological abnormality.6 Rarely cervical involvement can cause hoarseness because of recurrent laryngeal nerve paralysis, dysphagia, and respiratory stridor (Millar asthma) due to anterior abscess formation in the neck (Figure 1). Sudden death due to erosion into the great vessels has also been reported in association with cervical disease.
Pathophysiology Tuberculosis of the spine is a potentially life threatening infection caused by Mycobacterium tuberculosis which is an aerobic, weakly Gram positive bacillus with a thick cell wall containing mycolic acid, which renders it acid fast. The bacteria commonly reach the spine by haematogenous spread, so it is the vertebral bodies that are usually affected. They are then phagocytosed by macrophages
Diagnosis Laboratory studies are suggestive of chronic infection, i.e. anaemia, hypoproteinemia, and an elevated ESR. Tuberculin skin testing may be helpful, but is not diagnostic especially in TB endemic areas where the population may have had subclinical exposures or have received BCG vaccination. Interferon gammarelease assays (IGRA) is a relatively new method for detecting T cells specific for Mycobacterium tuberculosis antigens. It has sensitivity about 80% and is more specific than the tuberculin skin test. Its sensitivity remains high in immune-compromised patients and is not confounded by BCG vaccination. The main
W Y Cheung FRCSEdOrth FHKAM Associate Consultant, The Department of Orthopedics & Traumatology, The University of Hong Kong, Pokfulam, Hong Kong SAR, China. Keith D K Luk MCh Orth FRCSEd FRACS FHKAM Tam Sai Kit Chair in Spine Surgery, Chair Professor and Head, The Department of Orthopedics & Traumatology, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
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evaluation of the bony destruction and possible instability while MRI permits further delineation of the soft-tissue components, activity of the disease and status of the spinal cord (Figure 2). Gupta et al. noted that abscess formation and the presence of bone fragments on MRI helped distinguish spinal tuberculosis from neoplasia. However definitive diagnosis is dependant on culture of the organism, requiring biopsy of the lesion. Percutaneous biopsies under radiographic or CT control usually suffice. Francis et al. reported 29 patients with suspected spinal tuberculosis. Epithelioid granulomata were seen in 89%, positive acid-fast bacilli cultures in 83% and positive acid-fast bacilli smears in 52%. Percutaneous thoracoscopic or laparoscopic biopsy has been reported by Dusmet et al. Nonetheless, open biopsy may be necessary if needle biopsy is unsuccessful or during a definitive open procedure. Because Mycobacterium tuberculosis is difficult to culture due to its fastidious growth requirements and slow growth rate, there is a need for techniques that permit more effective and earlier diagnosis. Polymerase chain reaction (PCR), a non-culture, molecular diagnostic test, amplifies the DNA of the Mycobacterium tuberculosis for identification. This utilizes a primer pair targeting a 123 base pair segment of the repetitive sequence IS6110 of the M. tuberculosis complex which covers M. tuberculosis, M. africanum, M. bovis, M. canetti and M. microti. The amplified segment of the tuberculosis DNA is subsequently detected with the Southern Blot hybridization technique. PCR is highly sensitive (95e98%) for diagnosing tuberculosis from smear-positive and culture-positive cases, but it has lower sensitivity (57e78%) for smear-negative and culture-positive cases. This is an exciting development, allowing quicker diagnosis and has also been used as a marker to monitor response to treatment. With different primers, it has also been shown to provide rapid information on drug resistance and clonality in epidemiological investigations of outbreaks.7
Figure 1 Marked soft-tissue swelling at the cervical or upper thoracic region may cause airway obstruction (Millar asthma).
limitation of the test is it cannot differentiate active from latent infection. Early radiographic findings include a subtle decrease in one or more disc spaces with localized osteopenia. Later findings include vertebral collapse, described by Seddon, as “concertina collapse” because of its resemblance to an accordion. Soft-tissue swelling and later calcification are highly predictable radiographic findings. CT scanning, with contrast, allows better
Figure 2 Contrast MRI shows enhancement at L4 and L5 vertebral body and a rim enhancement lesion at epidural space with cauda equina compression.
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Treatment
Surgical treatment Surgical treatment is an important component in the treatment of spinal tuberculosis. In the presence of active disease surgery is indicated if: there is significant neurological deficit due to spinal cord or cauda equina compression, there is severe deformity that requires surgical stabilization, the diagnosis is uncertain and open biopsy is required, and if conservative treatment has failed and there is significant back pain. As the disease is usually in the anterior aspect of the spine, surgery is commonly performed via the anterior approach. This was first described by Ito et al. in 19349 and subsequently popularized by Hodgson and Stock in 1956.10 It allows direct access to the anterior disease focus and permits complete clearance of the abscess, tissue biopsy for diagnosis and, more importantly, insertion of strut grafts under compression at the kyphus. Various studies have shown that patients with Pott’s paraplegia due to active disease had better neurological recovery if treated with surgery compared with conservative treatment alone. Martin et al. reported 60% of patients with Pott’s paraplegia treated with surgery had neurological recovery compared with 48% of patients treated conservatively.11 Guirguis et al. reported an even higher success rate with 93% patients treated surgically having neurological recovery versus 40% of patients treated conservatively.12 The role of surgery for patients without significant neurological deficit is less well defined. To study the relative merits of the conservative and surgical approach to the treatment of TB spine in this group of patients, the Medical Research Council of the United Kingdom initiated and coordinated a series of important clinical trials. These were carried out from 1965 in multiple centres in the world where the disease was prevalent. The patients were carefully selected, documented and followed up for as long as 15 years prospectively. The results were published in a series of reports that should be mandatory reading for every spinal surgeon.13e17 The efficacy of surgical treatment was compared with that of conservative drug treatment. In Rhodesia (now Zimbabwe), Korea and Hong Kong, patients were randomly allocated to the drug treatment group, debridement group or radical debridement plus anterior spinal fusion group. The inclusion criterion was clinical or radiological evidence of tuberculosis at any level except the cervical spine. Patients with significant neurological deficit such that they could not walk across the room, those had been given anti-tuberculous drugs for more than 1 year, those that had significant extra-spinal disease and, for the fusion group, those that had more than three levels of vertebral destruction were excluded from the study. All patients were given 18 months of two or three drug combination chemotherapy. In the debridement group, the abscess, the sequestrum and the loose disc fragments were removed to achieve spinal cord decompression and no fusion was performed. In Hong Kong, the radical surgery group underwent radical debridement of the necrotic tissue until healthy bleeding bone was reached. This was then followed by an anterior strut graft fusion using autologous rib, iliac or fibula grafts. The results reported at the 5-, 10- and 15-year reports indicated that all three groups achieved the same 87% favourable outcome, defined as
Tuberculosis is usually considered to be cured when there are no clinical signs of infection, the patient is neurologically intact, has regained their previous activity level and does not suffer relapse. However, spinal tuberculosis presents some additional problems, kyphosis and delayed neurological deficit. Therefore modern treatment is also directed at correcting the kyphosis thereby restoring the balance of the spine, achieving early bony fusion (healing), preventing local recurrence of spinal tuberculosis, and thus preventing late neurologic complications. Medical treatment The main stay of treatment is chemotherapy. Since the advent of specific anti-tuberculous chemotherapy, patients rarely die from the disease, the period of infectivity is considerably reduced, relapses are avoided and chronicity reduced. With the increasing prevalence of drug-resistant tuberculosis worldwide, it is very important to know the bacterial sensitivities before commencing chemotherapy. By culture of aspirate or tissue specimens, sensitivity tests of the cultured tubercle bacilli against each drug can be ascertained. There are currently five first line anti-tuberculous drugs, isoniazid, rifampicin, pyrazinamide, streptomycin and ethambutol. Various treatment regimens have been described and generally 6e12 months of chemotherapy is required2,8 (Table 1). In our centre, the standard regimen is ethambutol, pyrazinamide, rifampicin and isoniazid for 2 months, followed by rifampicin and isoniazid for 4 months. Longer treatment may be necessary for elderly or immune-compromised patients. Drug-resistant tuberculosis is defined as resistance to one or more of the primary anti-tuberculous drugs. Its management is very complex, necessitating treatment with secondary chemotherapeutic agents, which include amikacin, capreomycin, ciprofloxacin, cycloserine, ethionamide, kanamycin, ofloxacin, and para-aminosalicylic acid. It is better not to just add a single drug to a failing regimen because that creates an ideal condition for the development of resistance to the new medication. Instead, expert opinion from a microbiologist should be sought. The most common causes of development of drug resistance are inadequate treatment and/or patient non-compliance. Preventative measures including directly observed therapy to maximize compliance are essential.
Anti-tuberculosis regimes Three drug regimes (months) Davies PC (1996): HRZ (2) HR (10) Upadhyay et al (1999): HPaS(3)Hpa(3) Moon et al (1987, 1995, 1997, 2004): RHE(Z)(12) Four drug regimes (months) Medical research council (1993): RHEZ(2) RH(4) Yilmaz et al (1999): SRHZ(2) RH(7) Metha IS et al (2001): RHEZ(2) RHE(4) RH(6) Govender et al (2003): RHZE(12) H: isoniazid, R: rifampicin, Z: pyrazinamide, Pa: P-aminosalicylic acid, S: streptomycin.
Table 1
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no evidence of central nervous system involvement, no sinus or clinically evident abscess, no radiological evidence of disease activity and no restriction of normal physical activity. However, when these data were analyzed in greater detail, it was evident that the radical surgery group treated in Hong Kong had distinct advantages over the other two groups. There was much quicker relief of pain, earlier resolution of the sinus tracts and abscesses, and there was no neurologic involvement during treatment. There was a much higher rate of bony fusion of 85% at 5 years, which rose to 94% at 15 years. This compared with 46% at 5 years and 72% at 15 years for the group treated conservatively in Korea. The progression of the deformity was also different between the three groups. In the conservatively treated group, there was an increase of 21 at 5 years, which further increased to 25 at 15 years. The corresponding figures for the debridement group were 8 and 11 respectively. In contrast, the radical surgery group showed an improvement of 3 at 5 years, and this was maintained at the final 15-years follow-up assessment. It is also worth noting that in 5% of the conservative group, there was an alarming increase of kyphosis from 51 to 70 . Based on the results of this series of studies, the Medical Research Council concluded in its 13th report16 that: Conservative drug treatment, debridement alone and radical debridement and fusion all achieved similar favourable outcome in the majority of patients. The excellent results at 10 years are sustained at 15 years with no late relapse or late-onset paraplegia. The only advantage of radical operation is less late deformity compared with debridement. A question therefore comes, who will develop severe kyphosis that may benefit from early surgical stabilization and fusion? Rajasekaran et al. tried to answer this question by identifying some risk factors in patients who developed severe angular kyphosis.18,19 They retrospectively reviewed 90 adult patients who had suffered from tuberculosis of the spine. The vertebral body loss at the start of treatment had a good correlation with the severity of the deformity at the 5-year follow-up. It was reported that the deformity at 5 years could be predicted with a fair level of accuracy by the calculation of the pretreatment vertebral body loss and the application of the formula
While early surgical Intervention for prevention of deformity is relatively simple, producing good results, and preventing additional deformity, surgery for established severe deformity is difficult, and hazardous with a relatively high complication rate. However, gross kyphotic deformities in the thoracic and thoracolumbar region can result in severe cardio-respiratory embarrassment and in the lumbar region, the kyphosis can cause severe postural imbalance and frequently results in severe foreshortening of the trunk. There can also be increased back pain due to muscle fatigue and impingement of the rib cage on the iliac crest as well as self-image and psychological problems. Previously single stage correction of deformity had an unacceptable rate of neurologic complications and achieved negligible correction, which was dissatisfying both to the surgeon and the patient. Additionally there was a significant risk of paraplegia because of the need for meticulous debridement of the tissues all around the spinal cord before osteotomy. Side-slip deformity at the apex of the kyphosis made the procedure even more dangerous, because of the difficulty in actually locating the spinal canal. To minimize the complications, Yau et al. advocated a staged sequential procedure, first fitting halo-pelvic distraction apparatus, followed by anterior spinal osteotomy and decompression of the spinal cord, slow and gradual spinal distraction, posterior osteotomy and fusion, additional spinal distraction, and anterior spine fusion after achieving maximum correction.20 (Figure 3) Even with this technique of staged procedures, there was a 10% mortality rate and the average amount of correction obtained was only 28%. Therefore this is only recommended for patients with severe deformity, active disease and imminent paraplegia or death from chest complications. Instrumentation: Oga et al. have shown that Mycobacterium tuberculosis is not adhesive to implant surfaces and does not form biofilms which means it is safe to use implants in the presence of active tuberculosis infection, provided intensive anti-tuberculosis therapy is given. Various studies also confirmed that spinal instrumentation is safe and effective in active tuberculosis infections.21,22 Recent advances in spinal instrumentation in recent years and intra-operative spinal cord monitoring techniques have made more aggressive kyphosis correction surgery possible. Rajasekaran et al. recently described a single-stage closing/ opening wedge osteotomy to correct severe tuberculous kyphosis.23 The procedure is performed through a single posterior approach, performing wide laminectomies and a wedge of vertebral column is excised. The anterior column is reconstructed with a cage and the deformity correction achieved by posterior closing and anterior opening, fulcruming at the cage. The merits of this procedure are that the spinal column is not excessively shortened or lengthened during the procedure, so the risk of neurological complication should be low. They reported 17 cases with average kyphosis correction of 57% and only one patient had deterioration of neurological status after the procedure. However care has to be taken regarding the flexibility of the compensatory hyper-lordosis proximal and distal to the kyphus before proceeding with this surgical procedure. Particularly if the thoracic lordosis is not reversible, any overcorrection of the thoraco-lumbar kyphosis may result in stresses being thrown into the cervical segment. Thus, the best candidates for this procedure would be for children or young adults without neurological symptoms or signs and the
Y ¼ a þ bX where Y is the deformity at 5-year follow-up, X is the pretreatment vertebral body loss, and a and b are constant values of 5.5 and 30.5. There was an average kyphus angle of 30 to 35 for the complete destruction of each vertebral body in the dorsal and dorso-lumbar region and approximately 20 for the complete loss of each vertebral body in the lumbar region. They recommended surgery for patients with loss of 0.75 thoracic or thoraco-lumbar vertebrae, or the loss of one lumbar vertebra to produce final kyphosis of less than 30 . In another study, they also identified some risk factors for severe kyphosis in paediatric patients, namely separation of facet joints, posterior retropulsion, lateral translation and toppling. Patients with more than two of these signs had progression of kyphosis more than 30 and a final kyphosis of more than 60 . Surgical treatment is therefore also recommended for this group of patients.
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Figure 3 a Severe tuberculosis kyphosis. b Treated with halo-pelvic traction and combined anterior, posterior spinal fusion. c Sagittal profile after treatment.
compensatory curves are still flexible and can be reversed with the segmental instrumentation.
by blunt dissection. Anterior to the transverse processes are the pedicles and the intervertebral foramina. The spinal canal is entered by tracing the intercostal nerves and removing the surrounding bone. Crowded pedicles at the apex are removed and the dura is exposed posterior to the posterior longitudinal ligament. Then excision of the internal kyphus is performed to decompress the spinal cord and anterior fusion carried out with strut grafts. Hsu et al. reported 80% of patients with active disease and 50% of patients with healed disease had neurological improvement with this procedure, but 10% of patients had neurological deterioration after the surgery.24 We recently published our 5-year results for patients with lateonset Pott’s paraplegia of healed disease and severe kyphosis treated by this method.25 Forty per cent of patients had neurological improvement and none had neurological deterioration after the surgery. Solid bone fusion was demonstrated in all patients at 5 years after surgery. While this surgical procedure is technically less demanding, it does not correct the kyphosis and sagittal mal-alignment. Thus it is particularly indicated for older patients with fixed compensatory lordosis or patients with multiple co-morbidities and high surgical risks.
Late-onset paraplegia: late-onset paraplegia with residual spinal deformity is one of the most disastrous complications of Pott’s disease and the prognosis is generally poor. Chronic spinal cord compression as a result of the severe kyphotic deformity, with or without reactivation of the tuberculosis infection, leads to spinal cord dysfunction and progressive neurological deficits. In our centre, we prefer to use anterior decompression and strut bone grafting via a costo-transversectomy approach to treat this group of patients (Figure 4). A curved longitudinal incision 6e8 cm lateral to the midline is created, centred over the kyphus. The paraspinal muscles are stripped and retracted medially from the lateral side to expose the transverse processes and the adjacent 5e6 cm ribs subperiosteally. Two to three transverse processes and the corresponding posterior end of the ribs including the rib heads are excised. Segmental intercostal nerves are identified and held with slings. Great care is taken to remain extra-pleural and extra-peritoneal. Soft tissue, pleura, and peritoneum are mobilized from the pedicles and the collapsed vertebral bodies
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Figure 4 a Severe post-tubercular kyphosis. b Internal kyphectomy for spinal cord (arrow) compression and anterior fusion with strut graft. c Postoperative X-ray showed internal kyphectomy and bone graft in position (arrow).
Conclusion
5 Luk KD, Krishua M. Spinal stenosis above a healed tuberculosis kyphosis. A case report. Spine 1996; 21: 1098e101. 6 Jain AK, Aggarwal A, Mehrotra G. Correlation of canal encroachment with neurological deficit in tuberculosis of spine. Int Orthop (SICOT) 1999; 23: 85e6. 7 Rattan A. PCR for diagnosis of tuberculosis: where are we now? Indian J Tuberculosis 2000; 47: 79e82. 8 Medical Research Council Working Party on Tuberculosis of the Spine. Controlled trial of short-course regimens of chemotherapy in ambulatory treatment of spinal tuberculosis. J Bone Joint Surg 1993; 75: 240e8. 9 Ito H, Tsuchiya J, Asami G. A new radical operation for Pott’s disease. J Bone Joint Surg 1934; 16: 499. 10 Hodgson AR, Stock FE. Anterior spinal fusion. Br J Surg 1956; 44: 266e75. 11 Martin NS. Pott’s paraplegia. A report on 120 cases. J Bone Joint Surg Br 1971; 53: 596e608. 12 Guirguis AR. Pott’s paraplegia. J Bone Joint Surg Br 1967; 49: 658e67. 13 Medical Research Council Working Party on Tuberculosis of the Spine. Five-year assessments of controlled trials of ambulatory treatment, debridement and anterior spinal fusion in the management of tuberculosis of the spine: studies in Bulawayo (Rhodesia) and in Hong Kong. J Bone Joint Surg Br 1978; 60: 163e77. 14 Medical Research Council Working Party on Tuberculosis of the Spine. A ten-year assessment of a controlled trial comparing debridement and anterior spinal fusion in the management of tuberculosis of the spine in patients on standard chemotherapy in Hong Kong. J Bone Joint Surg Br 1982; 64: 393e8. 15 Medical Research Council Working Party on Tuberculosis of the Spine. A ten-year assessment of controlled trials of inpatient and outpatient treatment and of plaster-of-Paris jacket for tuberculosis of the spine in children on standard chemotherapy. Studies in Masan and Pusan, Korea. J Bone Joint Surg Br 1985; 67: 103e10. 16 Medical Research Council Working Party on Tuberculosis of the Spine. A 15-year assessment of controlled trials of the management of
Tuberculosis infection of the spine is a serious clinical condition which may lead to severe deformity, early or late neurological complications and even mortality. Its incidence is increasing worldwide. Advances in laboratory testing allow more effective and earlier diagnosis of this condition. The aims of treatment are to cure the infection, prevent or correct kyphotic deformity and preservation of neurology. Though most infections can be cured by anti-tuberculosis chemotherapy, surgery is indicated for selected groups of patients. The majority of patients with early onset paraplegia due to active disease have a good neurological recovery with surgical decompression. Surgery should also be considered for patients at high risk of developing significant kyphosis which may lead to sagittal imbalance and late-onset paraplegia. Late-onset Pott’s paraplegia with severe kyphotic deformity is notoriously difficult to treat. Surgical decompression with or without correction of the kyphosis are the main stays of treatment but is technically demanding with high operative risks and should therefore not be attempted by the inexperienced. A
REFERENCES 1 Moon MS. Tuberculosis of the spine; controversies and new challenges. Spine 1997; 22: 1791e7. 2 Moon MS. Tuberculosis of the spine e contemporary thoughts on current issues and perspective views. Curr Orthop 2007; 21: 364e79. 3 Jutte PC, Van Loenhout-Rooyackers JH. Routine surgery in addition to chemotherapy for treating spinal tuberculosis. Cochrane Database Syst Rev 2006; doi:10.1002/14651858.CD004532.pub2. Issue 1: Art. No.: CD004532. 4 Watts HG, Lifeso RM. Tuberculosis of bone and joints. J Bone Joint Surg 1996; 78-A: 288e98.
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21 Oga M, Arizono T, Takasita M, Sugioka Y. Evaluation of the risk of instrumentation as a foreign body in spinal tuberculosis. Spine 1993; 18: 1890e4. 22 Moon MS, Woo YK, Lee KS, Ha KY, Kim SS, Sun DH. Posterior instrumentation and anterior interbody fusion for tuberculous kyphosis of dorsal and lumbar spine. Spine 1995; 20: 1910e6. 23 Rajasekaran S, Vijay K, Shetty AP. Single-stage closingeopening wedge osteotomy of spine to correct severe post-tubercular kyphotic deformities of the spine: a 3-year follow-up of 17 patients. Eur Spine J 2010; 19: 583e92. 24 Hsu LCS, Cheng CL, Leong JCY. Pott’s paraplegia of late onset: the cause of compression and results after anterior decompression. J Bone Joint Surg Br 1988; 70: 534e8. 25 Wong YW, Leong JCY, Luk KDK. Direct internal kyphectomy for severe angular tuberculosis kyphosis. Clin Orthop Relat Res 2007; 460: 124e9.
tuberculosis of the spine in Korea and Hong Kong. J Bone Joint Surg Br 1998; 80: 456e62. Medical Research Council Working Party on Tuberculosis of the Spine. A controlled trial of anterior spinal fusion and debridement in the surgical management of tuberculosis of the spine in patients on standard chemotherapy: a study in Hong Kong. Br J Surg 1974; 61: 853e66. Rajasekaran S, Shanmugasundaram TK. Prediction of the angle of gibbus deformity in tuberculosis of the spine. J Bone Joint Surg Am 1987; 69: 503e9. Rajasekaran S. The natural history of post-tubercular kyphosis in children: radiology signs which predict late increase in deformity. J Bone Joint Surg Br 2001; 83: 954e62. Yau ACMC, Hsu LCS, O’Brien JP, Hodgson AR. Tuberculosis kyphosiscorrection with spinal osteotomy, halo-pelvic distraction and anterior and posterior fusion. J Bone Joint Surg 1974; 56A: 1419e34.
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