The most important diagnostic test is lumbar puncture, which preferably should be performed before the administration of antibiotics. The CSF is usually under increased pressure and contains between 50 and 500 white cells per cubic millimeter, rarely more. Early in the disease there may be a more-or-less-equal number of polymorphonuclear leukocytes and lymphocytes, but after several days lymphocytes predominate in the majority of cases. In some cases, however, M. tuberculosis causes a persistent polymorphonuclear pleocytosis, the other usual causes of this CSF formula being Nocardia, Aspergillus, and Actinomyces (Peacock). The protein content of the CSF is always elevated, between 100 and 200 mg/dL in most cases, but much higher if the flow of CSF is blocked around the spinal cord. Glucose is reduced to levels below 40 mg/dL, but rarely to the very low values observed in conventional bacterial meningitis; the glucose falls slowly and a reduction may become manifest only several days after the patient has been admitted to the hospital. The serum sodium is often reduced, in most instances because of inappropriate ADH secretion or an addisonian state due to tuberculosis of the adrenals. In the past, much was made of a low concentration of CSF chloride.
Most children with tuberculous meningitis have positive tuberculin skin tests (85 percent) but the rate is far lower in adults with or without HIV: 40 to 60 percent in most series. In the current era, interferon-gamma-release assay is used to document previous or current tuberculosis infection. The blood test appears to be highly, but not perfectly, sensitive and about 90 percent specific for active tuberculous infection in patients with meningitis as indicated by Sali and coworkers but caution must be observed in endemic areas where there are high rates of positivity. The test has been used in CSF with similar results but it is not clear if this is valuable as a routine test.
The previously used conventional methods of demonstrating tubercle bacilli in the spinal fluid are inconsistent and often too slow for immediate therapeutic decisions. Success with the traditional identification of tubercle bacilli in smears of CSF sediment stained by the Ziehl-Neelsen method is a function not only of their number but also of the persistence with which they are sought. There are effective means of culturing the tubercle bacilli; because their the quantity of bacteria is usually small, however, attention must be paid to proper technique. The amount of CSF submitted to the laboratory is critical; the more that is cultured, the greater the chances of recovering the organism. Unless one of the newer techniques is used, growth in culture media is not seen for 3 to 4 weeks.
Now widely used is polymerase chain reaction amplification from the CSF, which rapidly permits the detection of small amounts of tubercle bacilli. The sensitivity of this test is stated to be close to 80 percent but there is a 10 percent false-positive rate. There is also a rapid culture technique that allows identification of the organisms in less than 1 week. However, even these new diagnostic methods may give uncertain results or take several days to demonstrate the organism and they cannot be counted on to exclude the diagnosis. For these reasons, if a presumptive diagnosis of tuberculous meningitis has been made and cryptococcosis and other fungal infections and meningeal neoplasia have been reasonably excluded, treatment can be instituted without waiting for the results of bacteriologic study.
Imaging procedures are informative in patients who present with or develop raised intracranial pressure, hydrocephalus, or focal neurologic deficits. One or more tuberculomas may be visualized (Figs. 31-3 and 31-4) or there may be deep cerebral infarction from occlusion of vessels of the circle of Willis or one of its primary branches. MR or CT angiography may demonstrate vascular occlusive disease from granulomatous infiltration of the walls of arteries.
Other Forms of Central Nervous System Tuberculosis