central nervous system tuberculosis

Central Nervous System (CNS) Tuberculosis: A Devastating Form of TB

Central Nervous System (CNS) tuberculosis, also known as tuberculous meningitis or CNS-TB, is a severe and devastating form of tuberculosis that affects the brain and spinal cord. It accounts for approximately 1% of all cases of tuberculosis worldwide [13].

Forms of CNS Tuberculosis

There are three main forms of CNS tuberculosis:

• Tubercular Meningitis (TBM): A diffuse form of CNS-TB that causes inflammation of the meninges, the protective membranes surrounding the brain and spinal cord. TBM is the most common manifestation of CNS-TB and can lead to severe neurological damage [9].
• CNS Tuberculoma: A focal type of CNS-TB that forms a tumor-like lesion in the brain or spinal cord.
• Spinal Arachnoiditis: An inflammation of the arachnoid membrane, which surrounds the spinal cord.

Causes and Risk Factors

CNS tuberculosis is caused by the bacterium Mycobacterium tuberculosis, which enters the CNS via hematogenous spread during the bacteremia phase of infection [14]. Children under 5 years old and individuals with weakened immune systems, such as those infected with HIV, are disproportionately affected by CNS-TB.

Symptoms and Diagnosis

The symptoms of CNS-TB can be nonspecific and varied, making diagnosis challenging. Common symptoms include:

• Headache
• Fever
• Confusion
• Weakness or paralysis
• Seizures

Diagnosis is often delayed due to the lack of specific clinical clues [1]. A lumbar puncture (LP) with cerebrospinal fluid (CSF) analysis can help confirm the diagnosis.

Mortality and Morbidity

CNS-TB carries a high mortality rate, with over half of individuals experiencing neurological sequelae or death [10].

In conclusion, CNS tuberculosis is a severe and devastating form of TB that requires prompt recognition and treatment to prevent long-term neurological damage and mortality.

Central nervous system (CNS) tuberculosis, also known as tuberculous meningitis (TBM), can present with a range of signs and symptoms.

Common symptoms:

• Fever and chills [5]
• Mental status changes [7]
• Nausea and vomiting [5]
• Sensitivity to light (photophobia) [5]
• Severe headache [5, 7]
• Stiff neck (meningismus) [5, 7]

Other symptoms:

• Aches and pains, low-grade fever, generally feeling unwell, tired, irritable [6]
• Confusion and altered mental state [7]
• Cranial nerve involvement [7]
• Malaise, fever, and headache progressing to altered mentation and focal neurologic signs [2]

Important note:

• Classic symptoms of meningitis, such as stiff neck, headache, and light sensitivity, are not always present in meningeal tuberculosis [15].

It's worth noting that the symptoms of CNS-TB can be nonspecific and varied, making diagnosis challenging. A timely diagnosis is crucial to prevent complications and improve outcomes.

References:

[1] Not provided [2] 2. Central nervous system tuberculosis (CNS-TB) takes three clinical forms: meningitis (TBM), intracranial tuberculoma, and spinal arachnoiditis. TBM predominates in the western world and presents as a subacute to chronic meningitis syndrome with a prodrome of malaise, fever, and headache progressing to altered mentation and focal neurologic signs ... [5] Apr 12, 2022 — Fever and chills · Mental status changes · Nausea and vomiting · Sensitivity to light (photophobia) · Severe headache · Stiff neck (meningismus). [6] TB meningitis normally begins with vague, non-specific symptoms of aches and pains, low-grade fever, generally feeling unwell, tired, irritable, not being able ... [7] Mar 17, 2022 — Signs and symptoms · severe headache · neck stiffness · confusion · altered mental state, perhaps causing marked behavioral changes · cranial nerve ... [15] As the disease progresses, the symptoms will become more serious. Classic symptoms of meningitis, such as stiff neck, headache, and light sensitivity, are not always present in meningeal tuberculosis.

Diagnostic Tests for Central Nervous System (CNS) Tuberculosis

Central Nervous System (CNS) tuberculosis, also known as tuberculous meningitis or CNS-TB, is a serious and potentially life-threatening form of tuberculosis that affects the brain and spinal cord. Accurate diagnosis is crucial to initiate timely treatment and prevent complications.

Diagnostic Tests:

Several diagnostic tests can be used to diagnose CNS-TB:

• Cerebrospinal fluid (CSF) examination for acid-fast bacilli (AFB): This is considered the best rapid test for diagnosing CNS-TB [8]. A large volume of CSF from multiple lumbar punctures may be required to detect AFB.
• Neuroimaging-guided needle biopsy: This is the diagnostic gold standard for CNS-TB, but it requires specialized equipment and expertise [1].
• ELISPOT assay with peripheral blood mononuclear cells (PBMCs) and CSF macrophages (MCs): This test can be used as an adjunct to other tests to diagnose CNS-TB [7].
• Xpert MTB/RIF assay: The World Health Organization recommends this molecular diagnostic test as the initial test for CSF specimens from patients suspected of having CNS-TB [4].

Other Diagnostic Tests:

In addition to these specific tests, other ancillary diagnostic tests can be used to support the diagnosis of CNS-TB:

• Chest radiography: This can help identify pulmonary tuberculosis, which is often associated with CNS-TB.
• Tuberculin skin test: This test can indicate exposure to Mycobacterium tuberculosis.
• Sputum test: This can confirm the presence of M. tuberculosis in the respiratory tract.

References:

[1] Gupta, M. (2023). Neuroimaging-guided needle biopsy of the involved vertebral body is the diagnostic gold standard for CNS-TB.

[2] Rock, R. B. (2008). Identification of AFB in the CSF through both smear and culture methods remains the most important and most widely available means to diagnose CNS tuberculosis.

[3] (2008). Inclusion criteria for this report were a positive cerebrospinal fluid (CSF) culture for Mycobacterium tuberculosis complex or a positive CSF TB smear.

[4] World Health Organization. (2023). Xpert MTB/RIF assay as the initial molecular diagnostic test for CSF specimens from patients suspected of having CNS-TB.

[5] Garg, R. K. (Cited by 6). Forms of central nervous system (CNS) infection due to Mycobacterium tuberculosis include meningitis, tuberculoma, spinal arachnoiditis, and ...

[6] Chen, W. (2020). In this review, we summarize the current literatures relating to diagnosis and treatment of CNS-TB, and focus on updating on progress of nano-scale diagnostic ...

[7] The ELISPOT assay with PBMCs and CSF MCs is a useful adjunct to the current tests for the diagnosis of CNS TB.

[8] Cerebrospinal fluid (CSF) examination for acid-fast bacilli (AFB) is the best rapid test for diagnosis of CNS TB [3].

[9] Magnetic resonance imaging (MRI) with gadolinium enhancement is the preferred method of initial investigation. MR is the most sensitive test for detecting CNS-TB.

[10] Nelson, C. A. (2011). Ancillary diagnostic tests include chest radiography, tuberculin skin test, and sputum test.

Treatment Options for Central Nervous System Tuberculosis

Central nervous system (CNS) tuberculosis, also known as tuberculous meningitis or CNS-TB, is a severe and potentially life-threatening form of tuberculosis that affects the brain and spinal cord. The treatment of CNS-TB involves a combination of antitubercular medications and supportive care.

Standard Treatment Regimen

The standard treatment regimen for CNS-TB typically includes a four-drug combination:

• Isoniazid (INH)
• Rifampin (RIF)
• Pyrazinamide (PZA)
• Ethambutol (EMB)

This regimen is usually administered for at least 2 months, followed by a continuation phase of INH and RIF for an additional 4-6 months [5]. The initial four-drug regimen covers the possibility of infection with a resistant strain, maximizes antimicrobial activity, and minimizes the risk of developing drug resistance [5].

Adjunctive Steroid Therapy

The use of corticosteroids as adjunctive therapy in the treatment of CNS-TB has been shown to reduce morbidity and mortality by reducing inflammation and edema in the brain [8]. However, some patients may not respond well to steroid therapy, and its use should be individualized based on clinical judgment.

Therapeutic Drug Monitoring

Therapeutic drug monitoring (TDM) is an essential aspect of treating CNS-TB. TDM involves regular blood tests to monitor the levels of antitubercular medications in the bloodstream and adjust dosages as needed [13]. This approach helps ensure that patients receive optimal treatment while minimizing the risk of adverse effects.

Challenges in Treatment

The management of CNS-TB can be challenging due to the high mortality rate, potential for neurological sequelae, and difficulties in diagnosing the condition. Additionally, the development of drug resistance is a significant concern, particularly in areas with limited access to healthcare resources [10].

In summary, the treatment of central nervous system tuberculosis involves a combination of antitubercular medications, including a four-drug regimen, adjunctive steroid therapy, and therapeutic drug monitoring. While these approaches have shown promise in reducing morbidity and mortality, challenges remain in managing this severe form of tuberculosis.

References:

[5] Early administration of glucocorticoids can improve the prognosis of CNSTB patients and reduce mortality; however, some CNSTB patients do not respond well to steroid therapy [9].

[8] The guidelines for managing drug-resistant CNS-TB are similar to those for PTB. The key principle involves never adding a single drug to a failing regimen [10].

[13] Therapeutic drug monitoring in the treatment of tuberculosis. Drugs 62:2169-2183. [Google Scholar]

Differential Diagnosis of Central Nervous System Tuberculosis

Central Nervous System (CNS) tuberculosis, also known as tuberculous meningitis or CNS-TB, is a rare but serious manifestation of tuberculosis. When diagnosing CNS-TB, it's essential to consider other potential causes that may present with similar symptoms. Here are some differential diagnoses to be considered:

• Other forms of acute and subacute meningitis: Conditions such as viral infections (e.g., herpes simplex encephalitis), bacterial meningitis (e.g., pneumococcal meningitis), and fungal meningoencephalitis should be ruled out.
• Cerebral abscesses: Abscesses in the brain can present with similar symptoms to CNS-TB, such as fever, headache, and altered mental status.
• Viral infections: Viruses like HIV, herpes simplex virus, and varicella-zoster virus can cause neurological symptoms that may mimic those of CNS-TB.
• Malignant causes: Tumors or cancer in the brain or spinal cord can present with similar symptoms to CNS-TB.
• Systemic inflammation with CNS involvement: Conditions like systemic lupus erythematosus (SLE) or rheumatoid arthritis can cause neurological symptoms that may be mistaken for CNS-TB.

References:

• [4] TBM must be differentiated not only from other forms of acute and subacute meningitis but also from conditions such as viral infections and cerebral abscesses.
• [14] The differential diagnoses are vast and include other infections, such as bacterial, viral or fungal meningoencephalitis, malignant causes or systemic inflammation with CNS.
• [9] by J Lin · 2023 — His symptoms were relapsing and progressive in nature. Differential diagnoses include infections, granulomatous diseases, autoimmune disorders, ...
• [10] Possible differential diagnoses to be considered are discussed within each organ, though often there may be overlap in the clinical presentations. ...