Pott’s disease

Pott disease also known as tuberculous spondylitis, is a classic presentation of extrapulmonary tuberculosis (TB) ¹. In 1779, Sir Percival Pott described the tubercular disease of the spinal column presenting clinically with kyphotic deformity and neurological deficit in European patients ². Pott’s disease is the most dangerous form of musculoskeletal tuberculosis because it can cause bone destruction, deformity, and paraplegia.

Pott disease most commonly involves the thoracic and lumbosacral spine. However, published series have shown some variation ³. The lower thoracic vertebrae make up the most common area of involvement (40-50%), followed closely by the lumbar spine (35-45%). In other series, proportions are similar but favor lumbar spine involvement ⁴. Approximately 10% of Pott disease cases involve the cervical spine.

The diagnosis tends to be delayed because of a nonspecific initial early manifestations and/or low degree of suspicion. The diagnostic approach needs to be based on chronic pain or deformity, epidemiological considerations, imaging, and adequate procedures to obtain samples for bacteriological, pathological, or molecular confirmation.

Treatment requires several months of medical therapy according to current recommendations and consideration for surgical procedures, when indicated.

Pott’s disease causes

The pathogen underlying tuberculosis is Mycobacterium genus complex. There are around 60 species, among which Mycobacterium tuberculosis is the most common type. These organisms are fastidious, slow-growing and aerobic bacilli. Other non-tubercular mycobacterial species affecting humans include Mycobacterium avium, Mycobacterium bovis, Mycobacterium microti, and Mycobacterium africanum ⁵. The tuberculosis bacilli are capable of remaining dormant for a long time; however, when the favorable conditions return, they tend to multiply once in every 15 to 20 hours ⁶.

Spinal tuberculosis is usually secondary to hematogenous spread from a primary site of infection (most commonly the lungs). The paradiscal vessels typically supply the subchondral bone on either side of the disc space and therefore, the most common site of vertebral involvement is paradiscal. The other patterns of involvement include central (with predominant vertebral body involvement), posterior (involving the posterior structures primarily) and non-osseous involvement (presenting with the abscess) ⁷. Progressive vertebral destruction leads to spinal kyphotic deformity and instability.

The infection results in a granulomatous inflammatory reaction, which is typically characterized by caseating necrosis, lymphocytes, epithelioid cells, and Langhans-type giant cells ⁸.

Some known risk factors for tuberculosis include prolonged exposure to infected patients, immunodeficiencies (HIV, alcohol, drug abuse), overcrowding, malnutrition, poverty, and lower socio-economic situation.

Pott’s disease symptoms

The clinical presentation of spinal tuberculosis is variable. The manifestations depend upon the duration of illness, severity of disease, site of lesion, and presence of associated complications including deformity and neurological deficit ⁹. In uncomplicated disease, the patient typically presents with back pain; while the presentation associated with complicated tubercular spine disease involves deformity, instability, and neuro deficit. Back pain in tuberculosis can be related to the active disease itself (secondary to inflammation), bone destruction and instability. 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 ¹⁰.

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 ¹¹.

Deformity

The clinical appearance of kyphotic deformity has been classified as knuckle (one vertebral involvement), gibbus (two vertebrae) and rounded kyphus (more than three vertebrae). Owing to the greater involvement of the anterior spinal column in tuberculosis, the spinal column progressively develops a kyphotic orientation; especially in the thoracic and thoracolumbar spine. Rajasekaran et al. ¹² purported a formula to predict the final kyphosis in adult population afflicted with spinal tuberculosis: y = a + bx, where y is the final kyphosis, a and b are constants equal to 5.5 and 30.5, respectively, and x is the initial loss of vertebral body height. Jain et al. ¹³ observed that kyphotic deformity greater than 60 degrees leads to significant disability and can potentially inflict neurological deficit.

Neurological deficit

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) ¹⁴.

The initial compression in tuberculosis is secondary to vertebral body collapse, leading to anterior spinal tract involvement (exaggerated deep tendon reflexes and Babinski sign, further progression on to upper motor neuron-type motor deficit). Further on, the lateral spinal tracts are progressively involved (with loss of crude touch, pain, and temperature); followed by posterior column deficit (sphincter disturbances and complete sensory loss). The Frankel and ASIA scores, which were initially developed to classify neurological deficits in acute spinal injury may also be employed to classify the neuro deficiency in spinal tuberculosis ¹⁵. Modified Tuli classification ¹⁶ is the most useful classification of Pott’s paraplegia with spinal cord involvement.

There were five stages of Pott’s paraplegia ¹:

• 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: Patient has upper motor neuron-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 lateral column
• Stage 3: 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 lateral column
• Stage 4: 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

Although most of the neuro deficit would fit into this classification, neuro deficits in intraspinal granulomas, cauda equina, or conus medullaris syndromes or tuberculosis of other atypical locations may not correspond to any of the stages mentioned above.

Pediatric Spinal tuberculosis

Owing to the immaturity and increased flexibility of 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. ¹² described 4 signs of “spine at risk” in children, which include:

1. Retropulsion of the posterior aspect of the involved vertebra
2. Facetal subluxation (separation of facets on lateral radiographs)
3. Lateral translation of vertebrae (as observed on anteroposterior radiographs)
4. 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 deformity in children ¹²:

• 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 ¹⁷

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 skip 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 ¹⁸.

Pott’s disease complications

Pott’s disease complications include:

• 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
• Neurodeficit
• Spinal instability
• Spinal deformity (kyphosis)
• Systemic tuberculosis disease

Pott’s disease diagnosis

The gold standard in the diagnosis of tuberculosis is the culture of Mycobacterium; however, the tuberculosis bacillus is fastidious; and the sole reliance on positive cultures for diagnosis can be associated with poor sensitivity.

Alternate laboratory reference standards for diagnosis include a histopathological demonstration of classic caseating granulomas, staining of smears to identify acid-fast bacilli (AFB), serological inflammatory markers, immunological tests, and molecular diagnostic modalities. A typical clinical presentation with additional indirect evidence from radiological and laboratory tests are usually necessary to clinch the diagnosis in a significant proportion of patients.

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, end plate rarefaction, vertebral body destruction, instability, and spinal deformity. Chest x-ray is also an important investigation, as up to thirds of these patients with spinal tuberculosis can also have a concomitant pulmonary disease ¹⁹.

• 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 tuberculosis include fragmentary, osteolytic, subperiosteal, and localized sclerosis. CT scan can also aid in image-guided biopsy for establishing the diagnosis ²⁰.
• Magnetic resonance imaging (MRI) (100% sensitivity and 80% specificity): MRI is the most useful modality in the diagnosis of spinal tuberculosis. MRI best detects the extent of soft tissue enhancement, the location of 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 ²¹. The typical MRI findings including multi-segment sub-ligamentous collection, the occurrence of well-defined para/pre-vertebral mass or abscess with relatively thickened abscess walls, relatively spared disc space until the later stages of the disease and heterogeneous enhancement of vertebral body can help in distinguishing tubercular spondylodiscitis from other pyogenic infections ²².
• 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 ²³. These modalities cannot help in distinguishing tubercular infections from malignancy or other pyogenic infections.

Laboratory tests

Erythrocyte sedimentation rate (ESR) (60% to 90% sensitivity) is usually more than 20 mm/hour in tuberculosis and decreases with treatment response. Nevertheless, it is not a very sensitive test. C-reactive protein (CRP) (71% sensitivity) is more specific than ESR ²⁴.

Serological examination of IgG and IgM antibody levels against tuberculosis antigen cannot effectively distinguish between active or healed disease; natural tuberculosis infection or vaccinated persons; and is raised in both active and chronic stages of infection ²⁵.

Acid-fast bacilli (AFB) staining (25% to 75% sensitivity and 99% specificity): Using the Ziehl-Neelson technique, tubercle bacillus presents with a bright red stain. At least, a concentration of 1 to 10 bacteria/ ml is necessary for detection.

Tuberculosis 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) ²⁶. Growth on 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): This technique requires only a concentration of 1 to 10 bacilli/ ml. This is a very useful technique in paucibacillary, extrapulmonary tuberculosis infections ²⁷.

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 ²⁷.

Histopathological evaluation: Characteristic findings including caseating necrosis, epithelioid cell granuloma, and Langhans giant cells can be found in 72% to 97% of patients ²⁸.

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 ²⁹.

Whole blood-based enzyme-linked immunosorbent assay (ELISA) ³⁰.

Pott’s disease treatment

It is essential to classify spinal tuberculosis disease into a complicated and uncomplicated disease, based on their presentation. While uncomplicated spinal tuberculosis is essentially a medical disease; complicated tuberculosis spine patients need surgical intervention in addition to chemotherapy ³¹.

Medications

The mainstay of treatment in spinal tuberculosis is chemotherapy (antitubercular treatment). Tubercle bacilli may exist as intracellular or extracellular forms or as dormant or rapidly multiplying forms ³². 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 antitubercular treatmen have been controversial ³³. The World Health Organization (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 ⁶. 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 [DOTS]); nevertheless WHO has continued to recommend DOTS therapy for optimum results ³⁴.

Multidrug resistance

Multidrug resistant-tuberculosis is defined as tuberculosis infection resistant to isoniazid (INH) and rifampicin. Extensively drug-resistant tuberculosis (XDR-tuberculosis) is defined as infection resistant to isoniazid 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” tuberculosis, where the tubercular strain is resistant to all first- and second-line drugs ³⁵.

Surgical management

Traditionally, tuberculosis was treated by radical debridement through an anterior approach ³⁶. However, following successful outcomes with multidrug chemotherapy and Medical Research Council observations ³⁶, Tuli et al. introduced the concept of “middle path regimen” in the treatment of tuberculosis ³⁷. This regimen recommended medical management in all patients, along with surgical management necessitated in the following situations:

1. Lack of response to chemotherapy
2. Recurrent disease
3. Severe neurological weakness
4. Static or progressive neurodeficit despite a course of antitubercular treatment
5. Deformity
6. Debilitating pain
7. Instability

The objectives of surgical intervention include drainage of abscess, debridement of infected tissues, stabilization of vertebrae and deformity correction. Tubercle bacilli do not produce any biofilm and therefore, tubercular infections are amenable to stabilization with implants. The surgical procedure typically involves debridement and fusion (instrumented or non-instrumented) through anterior, posterior or combined approaches ²⁷. Abscesses can be drained through minimally invasive or open approaches.

Anterior approach

As tuberculosis 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 panvertebral disease ³⁸.

Posterior approach

In modern spine surgery, posterior approaches are more preferred in tuberculosis spondylitis in view of the following reasons ³⁹:

1. Ease and familiarity of the approach
2. Availability of more robust pedicle screw system
3. Less approach-related morbidity
4. Ability to perform circumferential decompression through transpedicular approach
5. Ability to perform global reconstruction through transpedicular, transfacetal, costotransversectomy or extracavitary-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 stages ⁴⁰.

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 tuberculosis spondylitis ⁴¹.

Surgery in healed tuberculosis

Surgery may be indicated in healed disease with instability or kyphotic deformity more than 60 degrees ⁴². The decision to perform surgery in such cases should be made after taking into consideration multiple factors including age, associated comorbidities, the severity of deformity, the location of the spine involved, number of involved levels, and 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 ⁴³. Combined anterior and posterior approaches may be required in more severe deformities, the disease involving two or three vertebrae or complex revision surgeries ⁴⁴.

Pott’s disease prognosis

Current treatment modalities are highly effective against Pott disease if the disorder is not complicated by severe deformity or established neurologic deficit ⁴⁵.

Deformity and motor deficit are the most serious consequences of Pott disease and continue to be a serious problem when diagnosis is delayed or presentation of the patient is in advanced stages of the disease ⁴⁶.

Therapy compliance and drug resistance are additional factors that significantly affect individual outcomes.

Paraplegia resulting from cord compression caused by the active disease usually responds well to chemotherapy. However, paraplegia can manifest or persist during healing because of permanent spinal cord damage.

Operative decompression can greatly increase the recovery rate, offering a means of treatment when medical therapy does not bring rapid improvement.

Careful long-term follow up is also recommended, since late-onset complications can still occur (disease reactivation, late instability or deformity) ⁴⁷.

Clinico-Radiological Staging of Pott’s Spine (Prognostic Staging) ⁴⁸

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

Early diagnosis and treatment are of utmost importance in ensuring a good outcome in Pott’s tuberculosis.

In general, complicated tubercular spine disease (with associated deformity, instability or neuro deficit) has a poorer prognosis as compared to an uncomplicated disease. Other important prognostic factors include age (poorer outcome in extremes of ages) ⁴⁹, immunodeficiencies (HIV, alcohol, drug abuse), overcrowding, malnutrition, poverty, and lower socio-economic situation. Poor compliance and poor tolerance to antitubercular treatment (including deranged liver functions) is a major factor for drug failure in tuberculosis.

Poor prognostic factors in Pott’s 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.

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