Tuberculosis Meningitis

Tuberculosis (TB) is a contagious airborne disease that typically affects the lungs. Tuberculosis is caused by a bacterium called Mycobacterium tuberculosis (M. tuberculosis), which travels through the blood stream and infects other organs and tissues in the body if tuberculosis is left untreated. Tuberculosis meningitis (TBM) or tubercular meningitis is a life-threatening central nervous system (CNS) infection that occurs when the “Rich foci” seeded during the bacillemia of primary infection, travel and rupture into the subarachanoid space. It not only affects the meninges, but also the brain parenchyma as well as the vasculature.

Symptoms of Tuberculosis Meningitis

The primary symptoms of tuberculosis meningitis are:

  • Chills
  • Low-grade fever
  • Malaise
  • Headache
  • Fatigue
  • Dizziness
  • Vomiting
  • Personality changes.

These symptoms may persist for a few weeks, after which patients develop more severe symptoms like:

  • Headache
  • Altered mental status
  • Stiff neck
  • Photophobia
  • Stroke
  • Hydrocephalus, and
  • Other cranial neuropathies.

What are the Early Warning Signs of Tuberculosis Meningitis?

Tuberculosis meningitis causes inflammation, which is concentrated towards the base of the brain. The inflammation in the brain stem subarachanoid area in turn affects the cranial nerve roots. Blood-borne spread certainly occurs, presumably by crossing the blood–brain barrier; but a proportion of patients may get Tuberculosis meningitis from rupture of a cortical focus in the brain, an even smaller proportion get it from rupture of a bony focus in the spine. Seizures are uncommon manifestations of Tuberculosis meningitis in adults, and when present should prompt the clinician to consider alternate diagnoses such as bacterial or viral meningitis or cerebral tuberculoma; in contrast, seizures are commonly seen in children with tuberculosis meningitis, occurring in up to 50% of pediatric cases. Increased pressure in the brain is also very common. When allowed to progress without treatment, coma and death almost always ensue.

Epidemiology of Tuberculosis Meningitis

At present, nearly 2 billion people across the world are carrier of tuberculosis amongst whom around 10% would develop the disease of tuberculosis. The number of people getting affected with tuberculosis meningitis greatly depends on the number of people affected with primary tuberculosis. Tuberculosis meningitis is rare in developed countries with about 100 to 150 cases occurring annually in the US, less than 3% of the estimated 4,100 annual cases of bacterial meningitis. The highest rates of occurrence of tuberculosis are in Southeastern Asia, Western Pacific and Africa. In developing countries, the incidences of tuberculosis meningitis would be higher owing to the higher number of cases affected with tuberculosis. In the year 2000, a study reported that the mortality rate in India due to tuberculosis meningitis was 1.5 per 1,00,000 population. In the presence of HIV infection, the complications and fatality increased.

Prognosis and Survival Rate of Tuberculosis Meningitis

Prognosis of Tuberculosis meningitis largely depends on neurologic status at the time of presentation, and time-to-treatment initiation. While the course of Tuberculosis meningitis is generally not as rapid or fulminant as meningitis due to pyogenic bacteria, empiric treatment should be initiated as soon as the diagnosis is suspected as any delay in treatment can worsen outcome. Various case series indicate a mortality rate of 7%–65% in developed countries, and up to 69% in underdeveloped areas. Mortality risk is highest in those with comorbidities, severe neurologic involvement on admission, rapid progression of disease, and advanced or very young age. Neurologic sequelae occur in up to 50% of survivors.

Individuals with increased risk for tuberculosis meningitis include young children with primary tuberculosis or lung tuberculosis and patients with immunodeficiency caused by aging, malnutrition or disorders such as HIV or cancer.

Causes of Tuberculosis Meningitis

Tuberculosis meningitis is caused by Mycobacterium tuberculosis (M. tuberculosis) and is the most common form of central nervous system tuberculosis (TB). Tuberculosis meningitis is associated with a high frequency of neurologic sequelae and mortality if not treated promptly.

Diagnosis for Tuberculosis Meningitis

The diagnosis of Tuberculosis meningitis can be difficult and may be based only on clinical and preliminary cerebrospinal fluid (CSF) findings without definitive microbiologic confirmation. Diagnosis is made by analyzing cerebrospinal fluid collected by lumbar puncture. The CSF usually has high protein content, low glucose and a raised number of lymphocytes. Characteristic CSF findings of Tuberculosis meningitis include the following:

  1. Total white cell counts are usually between 100 and 500 cells/μL. Very early in the disease, lower counts and neutrophil predominance may be present.
  2. Elevated protein levels, typically between 100 and 500 mg/dL
  3. Low glucose, usually less than 45 mg/dL
  4. The ratio of CSF: plasma ratio < 0.5

Other diagnostic tests for diagnosing Tuberculosis Meninigitis includes:

  • Gram Stain Test to Diagnose Tuberculosis Meningitis: Acid-fast bacilli are sometimes seen on a cerebrospinal fluid smear, but more commonly, tuberculosis is grown in culture.
  • Assays for Diagnosing Tuberculosis Meningitis: A spiderweb clot in the collected cerebrocpinal fluid is characteristic of Tuberculosis meningitis, but is a rare finding. ELISPOT testing is not useful for the diagnosis of acute Tuberculosis meningitis and is often false negative but may paradoxically become positive after treatment has started, which helps to confirm the diagnosis. Although ELISA assays have been developed to detect antibodies directed against specific mycobacterial antigens in the CSF with varying sensitivities, their limited availability precludes their use as point-of-care tests.
  • Diagnosing Tuberculosis Meningitis with Nucleic Acid Amplification Tests (NAAT): Polymerase chain reaction (PCR) is used to detect mycobacterial nucleic acid. These tests vary in their nucleic acid sequence they detect, and their accuracy. The two most common commercially available tests are the amplified mycobacterium tuberculosis direct test (MTD, Gen-Probe) and Amplicor.

Apart from the tests with cerebrospinal fluid mentioned above, biopsy of meninges, blood culture, chest x-ray, chest radiography, CT scan, MRI scan of the head and tuberculin skin test for Tuberculosis are most common diagnostic procedures for Tuberculosis meningitis.

Treatment for Tuberculosis Meningitis

The Tuberculosis meningitis treatment approach needs to consider treating the infection, related symptoms and associated complications.

  • Anti-Microbial Therapy for Tuberculosis Meningitis: It is given to treat tuberculosis infection which includes drugs like Rifampicin (RIF), Isoniazid (INH), Pyrizinamide (PZA) and Streptomycin (SM). These are of particular importance in treating Tuberculosis meningitis or TB meningitis because they can enter into the cerebrospinal fluid (CSF) and help in treating meningeal inflammation. Given that the newer generation fluoroquinolones (FQN), for example, levofloxacin and moxifloxacin, have strong activity against most strains of M. tuberculosis and have excellent CSF penetration and safety profiles, FQN would appear to have great potential as part of the first-line therapy for Tuberculosis meningitis.
  • Corticosteroids to Treat Tuberculosis Meningitis: These may also be used depending on the severity of the infection and associated problems like focal neurological findings, altered consciousness, increased intracranial pressure or tuberculous encephalopathy.
  • Ventriculoperitoneal Shunt Placement and Endoscopic Third Ventriculostomy Surgeries for Tuberculosis Meningitis: These are surgical techniques which have been demonstrated to relieve elevated intracranial pressure in Tuberculosis meningitis, leading to improved neurological outcomes.

In patients with Tuberculosis meningitis, there may be non-osmotic stimuli for anti-diuretic hormone (ADH) expression, resulting in Syndrome of Inappropriate ADH (SIADH) release. While ADH itself may not aggravate cerebral edema, acute development of significant hyposmotic hyponatremia may worsen cerebral edema due to water shifting from the intravascular compartment into the extravascular (intracellular and extracellular) space of the brain. While restriction of water intake is a mainstay of SIADH treatment, hypovolemia should be avoided, since it may decrease cerebral perfusion as well as serve as a stimulus for further ADH release.

Conclusion

Tuberculous meningitis or TB meningitis can be prevented by controlling tuberculosis infection. BCG vaccine can offer protection against some forms of tuberculosis and help in Tuberculosis meningitis. For children living in areas where this infection is more common, BCG vaccine is an important vaccine in the recommended immunization schedule. Another important factor in preventing tuberculosis meningitis or TB meningitis is to control the spread of tuberculosis from infected persons. As tuberculosis is contagious, the necessary preventive measures should be taken. Personal hygiene like covering nose and mouth should be followed; proper ventilation of rooms should be ensured and in some cases isolation of the infected person may be required. Treating persons with non-active tuberculosis infection is equally important. Such cases should be identified in time and appropriate treatment should be started in addition to other preventive measures. For all persons under treatment of tuberculosis, it is important to complete the prescribed course of treatment, for which patient education and awareness programs should be considered.

Note: This information is only for reference and is not a substitute of a medical care in any form. Kindly consult with a Healthcare Professional for detailed diagnosis, treatment and follow up.

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