Spinesurgery.co.za2SAOJ Autumn 2010 2/18/10 2:58 PM Page 37 SA ORTHOPAEDIC JOURNAL Autumn 2010 / Page 37
The medical management of spinal
R Dunn MBChB(UCT), MMed(UCT), FCS(SA)Orth
Consultant Orthopaedic and Spine Surgeon, Associate Professor University of Cape Town, Head
Orthopaedic Spine Services: Groote Schuur Hospital
Prof Robert Dunn
Tel: (021) 404-5387
Fax: (021) 404-5389
The overall prevalence of spinal tuberculosis (TB) in South Africa is currently 948 per 100 000. All trends are
upward, including incidence of sputa positive cases, relapses and retreatment rates, as well as new extra-pul-
monary cases. This is driven by the co-existent HIV endemic and the effect of HIV on TB re-activation.1
Autopsy studies confirm that 30-40% of HIV-positive patients die of TB and 44% of TB patients have HIV.2
Musculoskeletal manifestations of TB are more frequent in the HIV host, reported as high as 60% compared to
the normal 3-5% incidence.3
TB is largely a public health issue and will only be controlled when the problems of abject poverty such as malnutrition, overcrowding and early access to medical care is improved. To this end it is notifiable by law inan effort to allow preventative measures to be effected.
TB spine represents about 1% of overall cases but places a large demand on resources due to the costs of para- plegia and tertiary level care. Although surgery is indicated in selected cases, medical care remains the key com-ponent. Medical care involves both the diagnostic process and the medical intervention by means of supportivecare and anti-tuberculous chemotherapy. Diagnosis of TB spine
False negatives occur due to immunosuppression from The presenting complaints are usually axial back pain and HIV, cytotoxics or even overwhelming TB infection.
may be associated with neurological deficit. The presen-tation is typically delayed due to the insidious nature of the disease as well as the poor access to care in the com- Sputum is frequently used to diagnose pulmonary TB by munity it frequently affects.
the presence of acid-fast bacilli (AFB). The yield isdependent on the number of serial tests, whether direct Tuberculin skin tests
staining or concentrated methods are employed as well as Intra-dermal skin testing to elicit an inflammatory the method of collection (Table I).4 Expectorated sputum response has been widely used. These include the is positive in 55%, induced sputa 38% and lavage 26%.5 Mantoux, Heaf and Tine tests. They are relatively inex-pensive and technically easy to administer. Unfortunately they need to be read at a definite point following inocula- The white cell count is typically normal and the ESR tion. This may lead to inaccuracies if the patient does not markedly raised. It averages in the 80's but may often return at the prescribed time. There are false positive exceed 100 mm/hour.3 There may be anaemia of chronic results due to patients being sensitised by BCG vaccina- disorder or related to the malnutrition. Likewise the albu- tion or exposure to environmental mycobacterium. min is reduced.
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There is vertebral body destruction with a focal kyphosis Table I: Accumulative positive rates from
(Figures 2 and 3). Typically at least two bodies are sputa for acid-fast bacilli if the culture is involved, with juxta-discal endplate destruction and col-
lapse. There may be preservation of the disc space in theearly phase.
No. of daily samples CT and MRI are useful to further delineate bony destruction and soft tissue elements especially in the case of neurological abnormality (Figure 4). Non-contiguous infection is as high as 16% and a full length MRI scout isrecommended.8 If not possible, full spine X-rays should Newer tests
Selective immunological tests are being developed.6 TB Nuclear scintigraphy (bone scan) may be useful to detect antigens induce early secretive antigen 6. This can be test- other non-contiguous lesions, both in the spine and limbs. ed on blood in the laboratory. It is not influenced by BCGor other mycobacteria.
Nucleic acid amplification by polymerase chain reaction (PCR) is possible in a few hours but requires strong labo-ratory capacity and is relatively expensive. It is not possi-ble to distinguish between live and dead mycobacteria.
There is a high specificity but variable sensitivity and itshould therefore be used in conjunction with other data.
The PCR technique can be used to identify drug resist- ance rather than wait for the definitive culture and sensi-tivities.
Traditionally mycobacterium is cultured using the
Lowenstein-Jensen slope or broth media. This takes 2-4
weeks if microscopy is positive and up to 8 weeks if
microscopy is negative. Newer techniques (BACTEC)
may reduce culture times by earlier recognition of bacte-
Figure 1: Chart depicting the incidence of
positive results for each diagnostic modality
employed in the author's cohort (unpub-
The presence of caseous granuloma with AFBs is diag- lished data)
nostic. Granuloma on its own is suggestive and the diag-nosis is dependent on the clinical context.
Patients are frequently initiated on anti-TB medication prior to diagnostic confirmation by primary care physi-cians. Thus the presence of AFBs on staining and positiveculture results are reduced. In these cases the histologicalresults are often the only confirmation. It is important toutilise all diagnostic modalities available to confirm thediagnosis. Figure 1 depicts the incidence of positiveresults in the author's series (unpublished data). Overall ahigh level of diagnostic confirmation is achieved.
The typical features of apical radiographic changes on the
chest X-ray have a positive predictive value of 61% with
The features of spine TB are that of paraspinal shadow in the thoracic spine indicating the presence of an abscess.
Figures 2 and 3: AP and lateral thoracic spine
In the lumbar area the pus dissipates in the psoas muscle demonstrating paraspinal abscess and focal
and thus the discrete paraspinal collection is not seen.
kyphosis due to vertebral body destruction
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The lumbar spine can be biopsied via the posterolateralinsertion of the needle, 7 cm from the midline, directed at45° to reach the vertebral body. Cores are taken under lat-eral image guidance. The author prefers the lateral decu-bitus position, left side up, to reduce anaesthetic require-ments. Thoracic and thoracolumbar levels are bestapproached via the percutaneous transpedicular route.
Should there be an associated large abscess, a costotrans-versectomy is recommended and the pus/tissue removedfor biopsy. Likewise a large psoas abscess can bedrained/biopsied via a small intermuscular retroperitonealapproach. The author performs open cervical biopsies.
The TB spine patient is frequently malnourished and may
present with complications of paraparesis such as decubi-
tus ulcers and contractures. The albumin level should be
checked and appropriate nutritional support implemented.
Pressure care and physiotherapy are important to treat and
prevent these complications.
Isoniazid (INH) is the most effective bactericidal drug but
rifampicin (RIF) is also important in this regard. RIF and
pyrazinamide (PZA) are the most important sterilising
drugs. They are utilised to kill the ‘persisters' which are
mycobacterium that are sealed off by the inflammatory
process and remain latent for later reactivation. INH and
RIF are most effective at preventing resistance to other
drugs and this is why multiple drug therapy is important.
The drug regimen is administered on a daily basis. In SA,
Figure 4: MRI of the thoracic spine in a para-
the ‘directly observed treatment short-course' (DOTS) paretic patient demonstrating a pre-verte-
system is employed to improve compliance. Completion bral and epidural abscess, bony destruction
rates for pulmonary TB have been shown to be 61% when with kyphotic collapse and the spinal cord
not supervised, 86% with DOTS and 91% with an incen- draped over an internal gibbus with intrinsic
tivised DOTS system.10 In SA there is a financial incentive cord signal
as TB patients receive a financial grant while on the TBmedication.
This technology has largely been superseded by MRI, but The duration of drug therapy in spine TB is controver- with access problems in some hospitals, bone scan may sial. The typical management of pulmonary TB is 2 still have a role. Unfortunately it does not delineate the months' intensive phase with four drugs followed by a soft tissue extent of the disease. continuation phase of two drugs for 4 months. In spine TB TB is the current great mimicker. Spine pathology in a however there is dead bone and tissue with probably poor- known pulmonary TB patient should not be assumed to be er antibiotic penetration and thus the argument for longer due to TB. In high incidence areas such as ours, they are duration at higher doses. Shorter duration is tempting as frequently unrelated and should be investigated independ- one would expect better compliance, a lower incidence of ently. Other infections, eosinophilic granuloma and side effects and a lower burden on the health system. The metastatic disease can be confused with spinal TB with risk, of course, is higher recurrence rates.
dire consequences if not recognised and appropriately The literature is replete in terms of exact duration of treat- ment in musculoskeletal TB. The British Thoracic Society To this end biopsy is mandatory. CT-guided fine biopsy recommends 6 months' duration for spine unless there is has a poor yield as insufficient tissue is provided for his- central nervous system involvement. Should this be the case, tology and TB spine is a pauci-bacterial disease. Multiple they recommend RIF and INH for 12 months.11,12 The cores with a Jamsheedie or Harlow-Wood needle are rec- Canadian Thoracic Society13 recommends that bone and joint ommended. This requires a general anaesthetic in theatre.
TB should be treated for longer but are not prescriptive.
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The MRC study in Hong Kong reviewed TB spine man- Streptomycin and ethambutol may affect renal function.
agement with drugs and aggressive surgery. At 5 years' fol- Many of the agents are hepatotoxic. Although not rou- low-up, both the 6-month and 9-month groups using tinely tested, any concerns such as nausea should raise the INH/RIF/streptomycin, had favourable results. At 14 years, possibility of hepatitis. Should the transaminases the 6-, 9-, and 18-month groups had similar clinical (AST/ALT) be raised but less than 2x normal, re-testing in 2 weeks is indicated. If greater than 2x normal, retest The Madras study used medication alone with no surgery.
weekly for 2 weeks, then every second week until normal.
They reported on 6- versus 9-month duration with a respec- If ≥ 5x normal or increased bilirubin, the INH, RIF and tive 91% and 98% favourable status. At 10 years' follow-up, PZA should be stopped. If clinically unwell, one can con- there was no difference.16 tinue with streptomycin or ethambutol. Once the transam- Ge et al reported on the drug penetration of the spine with inases normalise, the drugs can then be serially re-intro- good results with only 4.5 months' treatment. The study was duced with an initial low dose escalating every few days.
not focused on duration but only mentioned in the method- Multi-drug resistance (MDR) is 1.8%1 overall but 5% in ology, and long-term recurrence rates are not available.17 the author's personal series. This usually manifests by NICE recommends daily dosing with combination agents failure of medical therapy and confirmed later by sensi- but does not mention duration.12 tivities. The availability of PCR sensitivities will reducethe wait time. Once MDR is recognised, the treatmentregimen should be changed to amikacin or kanamycin (6 The Groote Schuur experience is that of four-drug
months), ofloxacin, ethionamide, ethambutol (or ter- therapy daily throughout the course, i.e. no reduction
izidone but expensive), PZA. INH and RIF can be con- after the first two months as in pulmonary TB
sidered in addition as not all mycobacterium may beresistant. This is best discussed with the local infectious Wang compared three protocols of different drug combi- diseases team. The use of the MDR protocol is logistical- nations and duration combined with surgical debridement.
ly difficult as the aminoglycosides need to be adminis- The ultra-short group was 4.5 months (2 months tered parenterally. This may require inpatient care should INH/RIF/PZA followed by 2.5 months INH and bi-weekly the home circumstances not be conducive to good com- RIF/PZA), the short course 8 months (3 on strep/INH/RIF pliance. A subcutaneous port should be considered, espe- PZA followed by 5 months INH and bi-weekly cially in children, to avoid the daily painful intra-muscu- INH/RIF/PZA) and a 12 month (3 Strep/INH/RIF/PZA fol- lar injections.
lowed by 9 months INH and bi-weekly RIF/PZA). Theyfound similar clinical effect with higher frequency of drug Effect of HIV on TB
side effects the longer the duration of treatment. They did Not only does HIV potentiate TB spine by negatively not report disease recurrence and it is unclear how many affecting the immune system, but it also modifies the patients reached the planned 5-year follow-up period.18 course of the disease creating therapeutic challenges. The Groote Schuur experience is that of four-drug therapy In TB endemic areas such as sub-Saharan Africa, most daily throughout the course, i.e. no reduction after the first people have been exposed to TB. During this exposure a two months as in pulmonary TB. INH/RIF/ cellular immunity is established. In 85% the disease is ter- ethionamide/PZA are used in a combination tablet minated by the host's immune system, in 10-15% it is (Rifafour). The dose is weight-related. This is usually com- incompletely sterilised with residual bacteria lying dor- bined with surgery. Duration is for a minimum of 9 months.
mant, and in a few patients progressive active disease If the patient was on medication pre-operatively, the 9 months is calculated from the date of surgery irrespective of As HIV negatively impacts the cellular immunity, it the pre-operative medication period. At 9 months clinical, reduces the host's reaction to TB. This manifests in poor radiological and ESR is assessed and frequently the dura- control of the initial infection or poor ability to control the tion is extended to 12 months if there are any concerns.
residual TB foci with reactivation of disease.
Clinically there should be resolution of axial pain, the ESRshould be normal and the X-rays confirm bony healing.
Once the drugs are stopped the patient is reviewed 3 months Effect of TB on HIV
later to confirm the ESR remains normal. The ESR is less TB reactivation is not only a result of the HIV-reduced useful in the HIV patient and may well be overridden by the immune system but a driver of accelerated HIV disease.
TB increases activation of the immune system with During medical treatment the patient should be monitored increased secretion of pro-inflammatory mediators such for side effects from the anti-TB drugs. Visual acuity should as interleukin and TNF-α. These in turn increase HIV be monitored and ethionamide can result in irreversible replication with CD4 cell loss and a negative effect on the deterioration. This is why it should not be used in children mono- and lymphocytes with accelerated HIV-related dis- where visual testing is not easily performed.
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Immune restoration inflammatory
4. Peterson EM, Nakasone A, Platon-DeLeon JM, Jang Y.
Comparison of direct and concentrated acid-fast smearsto identify specimens culture positive for Mycobacterium This immunocological relationship causes management Journal of Clinical Microbiology challenges which can be life-threatening in their own right. There is a risk of the host with a severely depressed 5. Yajko DM, Nassos PS, Sanders CA, Madej JJ, Hadley immune state developing IRIS with the initiation of anti- WK. High predictive value of the acid-fast smear for retroviral treatment (ARVs). ARVs may dramatically Mycobacterium tuberculosis despite the high prevalence improve the cellular immune response and lead to an of Mycobacterium avium complex in respiratory speci- overwhelming reaction to the TB antigens with a danger- mens. Clinical Infectious Diseases 1994;19(2):334–6.
ous decline in patient health. This period often requires 6. Nahid P, Pai M, Hopewell P. Advances in the diagnosis steroids to dampen the acute associated inflammatory and treatment of tuberculosis. Proc Am Thorac Soc Vol 3.
response. Should the patient be both HIV-positive with a pp 103–110, 2006 DOI: 10.1513/pats.200511-119JH.
low CD4 count and infected with TB, advice should be 7. Wilcke JT, Kok-Jensen A. Diagnostic strategy for pul- sought from the local infectious diseases specialists as monary tuberculosis in a low-incidence country: results these patients can rapidly become increasingly ill with of chest X-ray and sputum cultured for Mycobacterium medical intervention. In this context, initiation of ARVs must be delayed until the anti-TB medication is effective. 8. Polley P, Dunn RN. Non-contiguous spinal tuberculosis – incidence and management. European Spinal Journal 9. Zondagh I, Dunn RN. Spinal tuberculosis: Diagnostic
While many patients are managed non-operatively and all biopsy in mandatory. SAMJ May 2008;98(5);360-2.
require the abovementioned management, the clinician 10. Chaulk CP, Kazandjian VA. Directly observed therapy should be vigilant to those who require additional surgi- for treatment completion of pulmonary tuberculosis: cal decompression and stabilisation. Instability with both Consensus Statement of the Public Health Tuberculosis anterior and posterior column involvement requires Guidelines Panel. JAMA 1998;279:943–8.
urgent intervention. The neurological indications are less 11. Joint Tuberculosis Committee of the British Thoracic clear as medical treatment alone can reverse paraparesis.
Society. Chemotherapy and management of tuberculosis Deteriorating neurological status requires surgical consid- in the United Kingdom: recommendations 1998. Thorax eration and neurological recovery may well be accelerat- ed with decompression, in the author's opinion.
12. National Collaborating Centre for Chronic Conditions.
Tuberculosis: clinical diagnosis and management oftuberculosis, and measures for its prevention and con- trol. London: Royal College of Physicians, 2006. ISBN 1 As TB continues to increase, so will TB spine. Many of 86016 277 0.
these cases do not require reconstruction surgery and 13. Canadian tuberculosis standards 6th edition. Published medical care remains the mainstay of management.
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Diagnostic confirmation, rather than presumption, is HP40-18/2007E-PDF. ISBN 978-0-662-45955-2. mandatory and requires a biopsy to differentiate it from 14. Darbyshire J. A 15-year assessment of controlled trials of the many other conditions that TB mimics. the management of tuberculosis of the spine in Korea and Due to the increasing incidence many patients may need Hong Kong J Bone Joint Surg [Br] 1998;80-B:456-62.
to be cared for outside the tertiary centres by generalists, 15. Upadhyay SS, Saji MJ, Yau AC. Duration of antitubercu- necessitating a general awareness of appropriate medical losis chemotherapy in conjunction with radical surgery in the management of spinal tuberculosis. Spine
16. Medical Research Council Working Party on tuberculo- No commercial benefits were or will be derived for this sis of the spine five-year assessment of controlled trials of short-course chemotherapy regimens of 6, 9 or 18months' duration for spinal tuberculosis in patients ambulatory from the start or undergoing radical surgery.
1. World Health Organisation. WHO REPORT 2009 Global Tuberculosis Control. Website http://www.who.int.
17. Ge Z, Wang Z, Wei M. Measurement of the concentration 2. Martin DJ. Epidemiology, pathology and clinical presen- of three antituberculosis drugs in the focus of spinal tation of HIV/TB. Medical Chronicle 2009; Feb: 79.
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3. Govender S, Parbhoo AH, Kumar KPS, Annamalai K.
18. Wang Z, Ge, Z, Jin, W, et al. Treatment of spinal tuber- Anterior spinal decompression in HIV-positive patients culosis with ultrashort-course chemotherapy in conjunc- with tuberculosis A prospective study. J Bone Joint Surg tion with partial excision of pathologic vertebrae. The
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