INTRODUCTION Granulomatous inflammation is a distinctive ...

neuroimaging characteristics. Evidence of extra-neural TB with appropriate microbiological,
radiological or histopathological findings will add to the confirmation of the diagnosis. A history
of recent TB contact is also an important supporting feature of tuberculous etiology.
Routine laboratory studies, such as erythrocyte sedimentation rate (ESR) or differential count of
peripheral white blood cells, follow no characteristic pattern. However, a definitive diagnosis of
TB etiology depends upon lumbar puncture and CSF examination, and detection of TB bacilli in
CSF either by microscopy or in culture (Muralidhar, 2004).
The CSF examination abnormalities found in CSF of untreated patients with tuberculous
meningitis are well described. Usually, a “cobweb” like appearance of the pellicle on the surface of
CSF when allowed to stand for a short time at room temperature is a characteristic feature but
not pathognomonic (Zuger and Lowry, 1997). Opening pressure at initial lumbar puncture is
significantly elevated in about 50% of patients. There is a predominant lymphocytic reaction (60–
400 white cells per ml) with raised protein levels (0.8–4 g/l). In the early stages of infection, a
significant number of polymorphonuclear cells may be observed, but over the course of several
days to weeks they are typically replaced by lymphocytes. There is a gradual decrease in the sugar
concentration of the CSF, which is usually less than 50% of serum glucose concentration, the
values may range between 18–45 mg/dl (Molavi and LeFrock.,1985; Leonard and Des Prez, 1990;
Ahuja,et al., 1994; Berger, 1994; Newton, 1994). Low chloride levels in CSF, considered earlier as
a specific marker for TBM, is actually a reflection of coexistent serum hypochloremia, and is not
helpful in distinguishing TB infection from other bacterial and viral infections (Ramkisson and
Coovadia, 1998).
Definitive diagnosis of tuberculous meningitis depends upon the detection of the tubercle bacilli in
the CSF, either by smear examination or by bacterial culture and both are still considered the
golden standard for diagnosis (Muralidhar, 2004). With repeated examinations of sequential CSF
examinations Kennedy and Fallon reported tubercle bacilli in 87% of patients (Kennedy and
Fallon,1979). In other series especially from developing countries bacteriological confirmation of
the diagnosis could be achieved in as few as 10% of the cases (Molavi and LeFrock.,1985).
Spinning of large volumes (10–20 ml) of CSF for 30 min and smear examination from the deposit
of as many as four serial CSF samples would enhance the detection rate of AFB (Muralidhar,
2004).
Culture of the CSF for tubercle bacilli are not invariably positive. Rates of positivity for clinically
diagnosed cases range from 25% to 70% (Kent et al.,1993). The solid media cultures such as
Lowenstein-Jensen may take up to 8 weeks to culture M. tuberculosis. Semiautomated
radiometric culture systems such as Bactec 460 and automated continuously monitored systems
have reduced culture time (Gillespie and McHugh.,1997). Although such systems do reduce the
time taken for culture the decision to treat the patient should not wait for culture results.
In cases of intracranial tuberculomas and tubercular abscesses, the CSF analyses are
unremarkable or show a mild, nonspecific increased protein content and usually negative
bacteriology. The “gold standard” remains histological. Approximately 60% of tissue specimens
from tuberculomas show AFB in smear and culture (Meyers et al.,1978).
Molecular diagnostic approaches (new approach)
Since the present conventional methods, namely microscopy and culture techniques, are,
respectively, less sensitive and time consuming, alternative diagnostic methods have become
necessary for the specific diagnosis of TB etiology in the CNS infections. An ideal molecular
diagnostic test should be rapid, cost-effective, sensitive, and specific in the diagnosis of TB
etiology. The newer diagnostic tests fall into three categories