Test Diagnosis of Tuberculous Spondylitis – Treatment

Diagnosis of Tuberculous Spondylitis

The clinical presentation of spinal tuberculosis is variable. The manifestations depend upon the duration of illness, the severity of the disease, site of the lesion, and the presence of associated complications including deformity and neurological deficit.[rx] Rest pain is pathognomonic, and rarely, radicular pain can be the main presenting symptom. Constitutional symptoms including weight or appetite loss, fever, and malaise/ fatigue are less commonly associated with extrapulmonary tuberculosis than pulmonary disease.[rx][rx]

Cold Abscess

• These abscesses typically lack all the inflammatory signs obvious in abscesses; and hence the name. In the cervical spine, they can present in the retropharyngeal space, anterior or posterior triangles of the neck or axilla. In the thoracic spine, they may present as pre- or paravertebral abscesses; or over the chest wall. In the lumbar spine, they may track down along the psoas muscle, Petit’s triangle, Scarpa’s triangle, or the gluteal region.[rx]

Deformity

• The clinical appearance of kyphotic deformity has been classified as knuckle (one vertebral involvement), gibbous (two vertebrae), and rounded kyphosis (more than three vertebrae). Owing to the greater involvement of the anterior spinal column in TB, the spinal column progressively develops a kyphotic orientation; especially in the thoracic and thoracolumbar spine.[rx] Jain et al. observed that kyphotic deformity greater than 60 degrees leads to significant disability and can potentially inflict neurological deficits.[rx]

Neurological Deficit

• A neurological deficit can occur either at the active stage of the disease (secondary to compression from an abscess, inflammatory tissue, sequestrum, or spinal instability) or during the healed stage (usually secondary to mechanical traction over the internal gibbus or spinal instability).[rx][rx]
• The initial compression in TB is secondary to vertebral body collapse, leading to anterior spinal tract involvement (exaggerated deep tendon reflexes and Babinski sign, further progression on to UMN-type motor deficit).

There were five stages of Pott paraplegia

• Stage 1 – Deficit only evident, based on the clinical examination by the clinician (ankle clonus, exaggerated deep tendon reflexes and Babinski or plantar extensor)
• Stage 2 – The patient has UMN-type of a motor deficit with spasticity, however, is still ambulatory. The anticipated motor score in tetraparesis is 60 to 100 and in paraparesis is between 80 and 100; sensory deficit involves the lateral column
• Stage 3 – The patient is bedridden and spastic. The anticipated motor score in tetraparesis is 0 to 30, and in paraparesis is between 50 and 80; sensory deficit involves the lateral column
• Stage 4 – The patient is bedridden with severe sensory loss/ pressure sores. The Anticipated motor score in tetraplegia is 0, and in paraplegia is between 50; sensory deficit involves posterior and lateral columns
• Stage 5 – Similar to stage 4 +/- bladder/bowel involvement +/- flexor spasms/ flaccid tetraplegia/ paraplegia

Pediatric Spinal TB

Owing to the immaturity and increased flexibility of the spine in children, they are particularly prone to developing severe deformity progression. Such worsening of deformity in children can also occur after the disease has completely healed, and therefore the need to follow-up this patient population until skeletal maturity cannot be understated. Rajasekaran et al. described 4 signs of “spine at risk” in children, which include:

• Retropulsion of the posterior aspect of the involved vertebra
• Faceted subluxation (separation of facets on lateral radiographs)
• Lateral translation of vertebrae (as observed on anteroposterior radiographs)
• The toppling of one vertebra over the other (defined by a line along the anterior surface of caudal normal vertebra crossing the mid-point of the anterior surface of the cranial normal vertebral bone)

He proposed that children with two or more of these signs had posterior facet disruption and required surgical intervention. He also proposed a classification system for the progression of the deformity in children:

• Type 1 – curves where curvature increases until growth cessation or skeletal maturity and surgical intervention was required
• Type 2 – curves where the deformity decreased with growth progression
• Type 3 – curves where there was minimal change in the deformity either during the active or healed phases of the disease[rx][rx]

Atypical Presentations

• Some of the atypical clinical presentations may include intervertebral disc prolapse, isolated abscess without skeletal involvement, and pure intraspinal granulomas. Similarly, atypical radiological presentations may include skipping lesions, concentric vertebral collapse, circumferential vertebral involvement, isolated posterior arch involvement, ivory vertebra, isolated meningeal, neural or perineural involvement without any vertebral destruction and multifocal osseous lesions.[rx]

Imaging Modalities

• Plain radiographs (15% sensitivity) – Early stages (less than 30% vertebral destruction) – not much role; later stages (beyond 30% vertebral destruction) – can present with disc space reduction, endplate rarefaction, vertebral body destruction, instability, and spinal deformity. The chest x-ray is also an important investigation, as up to thirds of these patients with spinal TB can also have a concomitant pulmonary disease.
• The following are radiographic changes characteristic of spinal tuberculosis on plain radiography
  • Increased anterior wedging
  • Lytic destruction of the anterior portion of the vertebral body
  • Collapse of vertebral body
  • Reactive sclerosis on a progressive lytic process
  • Enlarged psoas shadow with or without calcification

• Additional radiographic findings may include the following
  • Vertebral endplates are osteoporotic.
  • Intervertebral disks may be shrunk or destroyed.
  • Vertebral bodies show variable degrees of destruction.
  • Fusiform paravertebral shadows suggest abscess formation.
  • Bone lesions may occur at more than one level.[rx]
• Computed tomography (CT) (100% sensitivity) – Can help in the diagnosis at a much earlier stage than plain x-rays. The types of vertebral destructive lesions by CT in spinal TB include fragmentary, osteolytic, subperiosteal, and localized sclerosis. CT scans can also aid in image-guided biopsy for establishing the diagnosis.[rx][rx][rx]
• Magnetic resonance imaging (MRI) (100% sensitivity and 80% specificity) – MRI is the most useful modality in the diagnosis of spinal TB. MRI best detects the extent of soft tissue enhancement, the location of the abscess, and spinal canal compromise. Gadolinium-enhanced MRI may provide additional information regarding the diagnosis. Screening sequences involving the whole spine can also help us in identifying non-contiguous vertebral involvement. MRI can also assess response to treatment.[rx][rx]
• Nuclear imaging – 18 F-fluorodeoxyglucose (18F-FDG) labeled positron emission tomography (PET) scan provides evidence of functional activity in the involved tissues, based on the rationale that 18F-FDG is known to accumulate in macrophages at the inflammation site.[rx] These modalities cannot help in distinguishing tubercular infections from malignancy or other pyogenic infections.

Laboratory Tests

• Blood tests
• CBC: leukocytosis
• Elevated erythrocyte sedimentation rate: >100 mm/h
• Erythrocyte sedimentation rate (ESR) (60% to 90% sensitivity) – is usually more than 20 mm/hour in TB and decreases with treatment response. Nevertheless, it is not a very sensitive test. C-reactive protein (CRP) (71% sensitivity) is more specific than ESR.[rx]
• Serological examination of IgG and IgM antibody levels against TB antigen – cannot effectively distinguish between active or healed disease; natural TB infection or vaccinated persons; and is raised in both active and chronic stages of infection.[rx][rx]
• Acid-fast bacilli (AFB) staining (25% to 75% sensitivity and 99% specificity) – Using the Ziehl-Neelsen technique, tubercle bacillus presents with a bright red stain. At least, a concentration of 1 to 10 bacteria/ ml is necessary for detection.
• TB culture – BACTEC radiometric culture assay (56% sensitivity and 100% specificity) takes 2 weeks of incubation time; while traditional culture on Lowenstein-Jenson (LJ) medium takes up to 6 weeks (47% sensitivity and 100% specificity).[rx] Growth on the LJ medium requires a concentration of at least 10 to 100 bacteria/ml.
• Molecular testing and polymerase chain reaction (PCR) (75% sensitivity and 97% specificity)[rx] –  This technique requires only a concentration of 1 to 10 bacilli/ ml. This is a very useful technique in paucibacillary, extrapulmonary TB infections.
• Gene Xpert MTB/RIF – This is a fully automated test, which yields results within 90 minutes (82.9% sensitivity and 98% specificity). This test also helps in diagnosing resistance to rifampicin. WHO, in March 2017 recommended Xpert MTB/RIF Ultra (87.8% sensitivity and 94.8% specificity) as an investigation with good yield in pediatric and extrapulmonary patients.[rx][rx]
• Histopathological evaluation – Characteristic findings including caseating necrosis, epithelioid cell granuloma, and Langhans giant cells can be found in 72% to 97% of patients.[rx][rx]

Tests to Detect Latent Tuberculosis

• Mantoux test (40% to 55% sensitivity and 75% specificity) – Skin hypersensitivity test (purified protein derivative [PPD]) has been recommended as a low-cost test in developing nations; nevertheless, it is not an accurate test in endemic countries or immunodeficient patients.
• Interferon-gamma release assay (50% to 65% sensitivity and 85% specificity) – Measuring interferons produced in response to tubercular antigens; not useful in endemic regions.[rx]
• Whole blood-based enzyme-linked immunosorbent assay (ELISA)[rx]

Clinico-Radiological Staging of Pott Spine (Prognostic Staging)[rx]

• I – Predestructive stage; straightening of curvature, perivertebral muscle spasm, hyperemia on scintiscan (Duration fewer than 3 months)
• II – Early destructive stage; disc space reduction and paradisiacal erosion, knuckle less than 10 degrees, MRI demonstrates marrow edema, and CT shows erosions or cavitations (Duration 2 to 4 months)
• III – Mild angular kyphosis; 2 to 3 vertebrae involved and kyphosis 10 – 30 degrees (Duration 3 to 9 months)
• IV – Moderate angular kyphosis; 2 to 3 vertebrae involved and kyphosis 30 to 60 degrees (Duration 6 to 24 months)
• V – Severe angular kyphosis; more than 3 vertebrae involved and kyphosis greater than 60 degrees (Duration more than 24 months)

Treatment of Tuberculous Spondylitis

It is essential to classify spinal TB disease into a complicated and uncomplicated disease, based on their presentation. While uncomplicated spinal TB is essentially a medical disease; complicated TB spine patients need surgical intervention in addition to chemotherapy.[rx][rx]

First Line

All first-line anti-tuberculous drug names have a standard three-letter and a single-letter abbreviation:

• ethambutol is EMB or E,
• isoniazid is INH or H,
• pyrazinamide is PZA or Z,
• rifampicin is RMP or R,
• streptomycin is SM or S.

First-line anti-tuberculous drug names are often remembered with the mnemonic “RIPE,” referring to the use of a rifamycin (like rifampin), isoniazid, pyrazinamide, and ethambutol. The US uses abbreviations and names that are not internationally recognized,  rifampicin is called rifampin and abbreviated RIF; streptomycin is abbreviated STM. In the US only, streptomycin is no longer considered a first-line drug by ATS/IDSA/CDC because of high rates of resistance. The WHO have made no such recommendation.

Second Line

The second-line drugs (WHO groups 2, 3, and 4) are only used to treat the disease that is resistant to first-line therapy (i.e., for extensively drug-resistant tuberculosis (XDR-TB) or multidrug-resistant tuberculosis (MDR-TB)). A drug may be classed as second-line instead of first-line for one of three possible reasons: it may be less effective than the first-line drugs (e.g., p-aminosalicylic acid); or, it may have toxic side-effects (e.g., cycloserine); or it may be effective, but unavailable in many developing countries (e.g., fluoroquinolones):

• aminoglycosides (WHO group 2): e.g., amikacin (AMK), kanamycin (KM);
• polypeptides (WHO group 2): e.g., capreomycin, viomycin, enviomycin;
• fluoroquinolones (WHO group 3): e.g., ciprofloxacin (CIP), levofloxacin, moxifloxacin (MXF);
• thioamides (WHO group 4): e.g. ethionamide, prothionamide
• cycloserine (WHO group 4)
• terizidone (WHO group 5)

Third Line

Third-line drugs (WHO group 5) include drugs that may be useful, but have doubtful or unproven efficacy:

• rifabutin
• macrolides: e.g., clarithromycin (CLR);
• linezolid (LZD);
• thioacetazone (T);
• thioridazine;
• arginine;
• vitamin D;
• bedaquiline.

These drugs are listed here either because they are not very effective (e.g., clarithromycin) or because their efficacy has not been proven (e.g., linezolid, R207910). Rifabutin is effective but is not included on the WHO list because for most developing countries, it is impractically expensive.

Chemotherapy

• The mainstay of treatment in spinal TB – is chemotherapy (antitubercular treatment [ATT]). Tubercle bacilli may exist as intracellular or extracellular forms or as dormant or rapidly multiplying forms.[rx] Therefore, multi-drug treatment is essential to attack the bacilli in various stages or forms and reduce the instance of drug resistance. The duration (6, 9, 12, or 18 months) and frequency (daily versus alternate-day regimen) of administration of ATT have been controversial.[rx]
• WHO recommends 6 months of multidrug anti-tubercular therapy – including 2 months of four- or five-drug treatment (isoniazid, rifampicin, pyrazinamide, ethambutol, and/ or streptomycin) constituting the initiation” phase, followed by 4 months of “continuation” phase therapy with a two-drug regimen including isoniazid and rifampicin.
• The American Thoracic Spine Society – recommends a regimen involving 9 months of treatment with the same drugs (“continuation” phase extending for a period of 7 months). The Canadian Thoracic Society recommends treatment for 9 to 12 months duration.[rx]
• Other second-line anti-tubercular drugs including –  kanamycin, capreomycin, pyrazinamide, amikacin, among others are typically indicated when there is resistance or poor tolerance to first-line medications. A recent meta-analysis has not demonstrated any difference between self-administered and directly observed treatment (directly observed therapy, short course); nevertheless WHO has continued to recommend DOTS therapy for optimum results.[rx][rx][rx]

Multidrug Resistance

• MDR-TB is defined as TB infection resistant to INH and rifampicin. Extensively drug-resistant TB (XDR-TB) is defined as infection resistant to INH and rifampicin, along with resistance to a fluoroquinolone and at least one injectable second-line medication. Velayati et al. described the term “totally drug-resistant” TB, where the tubercular strain is resistant to all first- and second-line drugs.[rx][rx][rx]

Surgical Management

Traditionally, TB was treated by radical debridement through an anterior approach.[rx][rx] However, following successful outcomes with multidrug chemotherapy and Medical Research Council observations,[rx]. Introduced the concept of “middle path regimen” in the treatment of tuberculosis.[rx] This regimen recommended medical management in all patients, along with surgical management necessitated in the following situations:

• Lack of response to chemotherapy
• Recurrent disease
• Severe neurological weakness
• Static or progressive neuro deficit despite a course of ATT
• Deformity
• Debilitating pain
• Instability

Anterior Approach

• As TB spine involves the anterior vertebral structures predominantly, debridement through anterior approach and fusion has been traditionally used to manage the diseased tissues directly. Nevertheless, the anterior approach has been reported to be associated with serious complications including graft-related complications (subsidence, slippage, fracture, absorption among others), approach-related complications (respiratory compromise) and even mortality. An ideal indication for anterior surgery includes patients without any posterior vertebral structure involvement, in other words, no prevertebral disease.[rx][rx][rx]

Posterior Approach

In modern spine surgery, posterior approaches are more preferred in TB spondylitis in view of the following reasons[rx][rx][rx][rx][rx]

• Ease and familiarity of the approach
• Availability of more robust pedicle screw system
• Less approach-related morbidity
• Ability to perform circumferential decompression through a transpedicular approach
• Ability to perform global reconstruction through transpedicular, transplacental, costotrans versectomy or intracavitary-extrapleural approaches

Combined (Anterior and Posterior) Approach

• Typically, this approach should be reserved for severe destructive lesions with severe deformities or inherently unstable spines only, as it is associated with significant morbidities and complications. The approaches can be performed in single or more than one stage.[rx][rx]

Minimally Invasive Surgery

• Recently, minimally invasive approaches including thoracoscopic debridement, minimally invasive fusion procedures and posterolateral endoscopic debridement have been demonstrated to provide an excellent outcome in TB spondylitis.[rx][rx][rx]

Surgery in Healed Tuberculosis

• Surgery may be indicated in healed disease with instability or kyphotic deformity more than 60 degrees.[rx][rx] The decision to perform surgery in such cases should be made after taking into consideration multiple factors including age, associated comorbidities, the severity of the deformity, the location of the spine involved, number of involved levels, and the surgeon’s preference.
• Anterior approach can be particularly difficult in thoracic and thoracolumbar levels at the apex of kyphosis. Posterior approaches are the most popular and include transpedicular decancellation, Ponte’s osteotomy, pedicle subtraction osteotomy/ closing wedge osteotomy, posterior vertebral column resection, and closing opening wedge osteotomy.[rx][rx] Combined anterior and posterior approaches may be required in more severe deformities, the disease involving two or three vertebrae or complex revision surgeries.[rx]

Differential Diagnosis

Radiological Differentials

• Pyogenic and fungal infections
• Neoplastic – Lytic benign, benign aggressive and malignant (primary tumors and spinal metastases): In general, spinal metastasis and primary spinal malignancies present with primary vertebral body involvement and disc space preservation as compared to TB and other infections. Tuberculosis also presents with soft tissue and perivertebral abscess, in comparison with malignant tumors.

Differentials Based on Pathological Appearance

• Other pathologies involving granulomatous infections and clinically mimic TB include

  • Atypical bacteria – Actinomyces israelii, Nocardia asteroids, Brucella
  • Fungi – Coccidioides immitis, Blastomyces dermatitidis, Cryptococcus neoformans, Aspergillosis
  • Spirochetes – Treponema pallidum
• Other pathologies – presenting with non-caseating granulomas include Sarcoidosis, Wegener’s granulomatosis, Crohn disease, and leprosy.

Poor Prognostic Factors in Pott Paraplegia

• Level of disease (junctional vertebral levels) pan-vertebral involvement, long duration of neuro deficit, rapidity of progression of neuro deficit, the severity of deficit, nature of compression (abscess versus granuloma) and presence of spinal cord changes

Poor Prognosis for Deformity Progression

• Age less than 10 years Kyphosis angle greater than 30 degrees, three or more vertebrae involved, greater than or equal to 1.5 vertebral body loss, pan-vertebral disease, and evidence of instability

Complications

• Failure of treatment: Depends on the presentation (complicated versus uncomplicated), clinical and radiological prognostic factors, patient compliance to chemotherapy, stage of the disease, drug resistance and other patient-related factors (socio-economic factors, general health, nourishment among others)
• Abscess
• Neuro deficit
• Spinal instability
• Spinal deformity (kyphosis)
• Systemic TB disease

References