Diagnosis of Tuberculous Meningitis

      Diagnosis or suspected TB meningitis symptoms and signs of meningitis requires that accompanied the drive to clinical tuberculous infection and the results of X-ray photograph and cerebrospinal fluid showed infection by Mycobacterium tuberculosis. Tuberculous meningitis can occur through two stages.

The first stage is when the bacillus Mycobacterium tuberculosis inhaled droplets that cause localized infections in the lungs with dissemination to the regional lymph nodes. Bacilli can be entered into the meninges or brain parenchyma tissue to form caseating focisub-ependimal metastatic lesions, which called rich foci. The second phase is rich foci increase in size until it ruptures into the subarachnoid space and cause meningitis. Tuberculous meningitis is the most fatal form of tuberculosis and cause permanent sequelae, therefore, needs immediate diagnosis and treatment. This disease is the fifth extrapulmonary tuberculosis is common and it is estimated that approximately 5.2% of all cases of extrapulmonary tuberculosis and 0.7% of all cases of tuberculosis. When clinical symptoms are acute cranial nerve deficits, headache, meningismus, and altered mental status. Prodromal symptoms that can be found are headache, vomiting, photophobia, and fever.

        Based on the table above, the possible diagnosis of TB meningitis (probable) is obtained when the scores between 10 and 12. Diagnosis of tuberculous meningitis may be (possible) if score above 6 under 10. Assessment cerebrospinal fluid in patients with TB meningitis can show colors clear, moderate pleocytosis with an increase in lymphocytes, increased protein content and glucose concentrations were very low. This discovery is very different when compared to other bacterial meningitis discovery, namely the discovery of typical bacterial meningitis in cerebrospinal fluid was cloudy white color, very high pleocytosis and with an increase in neutrophils.

       In TB meningitis, often found in the cerebrospinal fluid glucose below 5 mg / dl with a clear color, white blood cell count showed an increase in lymphocytes by 50% or more in the 50 to 500 per mL of white blood cells in the cerebrospinal fluid. Protein content above 1 g / L and glucose less than 2.2 mmol / L. But in some cases can be found different laboratory findings. To assure the diagnosis of tuberculous meningitis, cerebrospinal fluid tests another recently been developed. One is the evaluation of adenosine deaminase activity (ADA), the measurement of interferon-gamma (IFN-ɣ) released by lymphocytes, detection of M. tuberculosis bacterial antigens and antibodies and immunocytochemical staining of mycobacterial antigens (ISMA) in the cytoplasm of CSF macrophages.

       ADA activity test is a rapid test that displays the proliferation and differentiation of lymphocytes as a result of the activation of cell-mediated immunity (cell-mediated immunity) against M. tuberculosis bacterial infection (23,24). ADA activity can not distinguish TB meningitis with other bacterial meningitis, but the activity of NO may be a useful additional information to rule out the diagnosis of bacterial meningitis caused aside. ADA value of 1 to 4 U / L (sensitivity> 93% and a specificity of <80%) can help exclusion diagnosis of TB meningitis. Values​​> 8 U / L (sensitivity 59% and specificity> 96%) can help establish the diagnosis of TB meningitis (p <0.001). However, values ​​between 4 and 8 U / L insufisien to confirm or exclude the diagnosis of tuberculous meningitis (p = 0:07). False-positive results can also be found in patients with HIV infection.

       Measurement of IFN-ɣ released by lymphocytes stimulated by M. tuberculosis bacterial antigens has been recognized more accurately than the skin-testing for the diagnosis of latent TB infection and is very useful for the diagnosis of extrapulmonary tuberculosis. However, the sensitivity and specificity of the tests vary according to the origin or source of primary infection. It has been reported the failure of IFN-ɣ test measurement is caused by the rapid death of lymphocytes when stimulated ex vivo with M. tuberculosis antigens that can be found a negative test result even though there actually has TB infection.

       Use of ISMA test on CSF macrophage cytoplasm under the assumption that the initial infection occurs stase phagocytosis by macrophages and TB bacilli in the next stase the TB bacilli thrive and grow within macrophages. A positive test result indicates that there are TB bacteria isolates in the CSF. In a recent study in get 73.5% sensitivity and 90.7% specificity with a positive and a negative predictive value of 52.9% and 96% respectively.

      Definitive diagnosis of TB meningitis can be made only after a lumbar puncture in patients with symptoms and signs of disease in the central nervous system (neurologic deficits), and positive acid-fast bacilli or M. tuberculosis or detected using molecular methods and or or after CSF culture (CSF). However, all the methods to make a diagnosis of TB meningitis is at risk of slowing down the initiation of the therapy. Culture requires 2 to 3 weeks to get results. Microscopic detection of acid-fast bacilli and culture isolation has low sensitivity. The most recent molecular methods also have low sensitivity and specificity, but can be used to determine the concentration of bacteria residing in the CSF so that it can be considered to evaluate the therapeutic response.