Discussion
Disseminated tuberculosis (TB) resulting from lymphohematogenous
dissemination of Mycobacterium tuberculosis during primary infection or
reactivation of latent disease is rare among young immunocompetent
patients.8,9 Central nervous system TB (CNS TB) is one
of the most challenging clinical diagnoses, with a prevalence of 4.55%
of all cases of TB. The spectrum of CNS TB includes TB meningitis,
tuberculoma, and spinal arachnoiditis, where TB meningitis is the most
predominant form.10 Small tuberculous lesions known as
Rich’s foci, formed in the cerebral cortex, cerebral parenchyma, or
spinal cord, may remain dormant for several years. Rupture of these foci
leads to the spread of the bacilli into the subarachnoid space,
resulting in tuberculous meningitis.11 Risk factors of
miliary TB and extrapulmonary TB include HIV, diabetes mellitus,
smoking, alcohol abuse, malnutrition, and overcrowding, which were
absent in our patient. 8,12 Recent research has
suggested that this disease form may be predisposed by a genetic
abnormality in the interleukin-12 (IL-12) and interferon-gamma pathways.
The pathophysiology and genetic components driving immunocompetent
hosts’ susceptibility to Mycobacterium TB infection are yet
unclear.13
Due to the variable and non-specific presentation of the disease, CNS TB
is difficult and challenging to diagnose. The clinical course is
typically subacute or chronic.14 About one-third of
patients on presentation have underlying miliary TB. Careful fundoscopy
may reveal choroidal tubercles, offering a valuable clue to the
etiology.15
A definitive diagnosis of tuberculous meningitis may be established with
detection of AFB either by positive smear, culture, or with a positive
nucleic acid amplification test (NAAT).16 The poor
sensitivity and specificity of diagnostic tests, however, can make it
difficult to make a definitive diagnosis. Typically, the CSF in
tuberculous meningitis shows an elevated protein level, predominant
lymphocytosis, and a decreased glucose concentration.
Adenosine deaminase (ADA) testing has not been helpful in diagnosing TB
meningitis, as an ADA cut-off value that optimizes both sensitivity and
specificity has been difficult to establish. In 2013, WHO recommended
Xpert MTB/Rif assay, a commercial NAAT, preferentially over conventional
microscopy and culture for initial TB meningitis testing in
resource-limited settings, which is highly specific for TB meningitis
but is variable in specificity. Brain imaging in TB meningitis commonly
shows basilar meningeal enhancement, hydrocephalus, basal ganglion
enhancement, cerebral parenchymal tuberculomas, and infarcts. MRI is
superior to CT for detecting TB meningitis.17Pulmonary tuberculosis (PTB) gives clues to suspect bacillary etiology
of CNS infection. Therefore, this patient’s CNS diagnosis was made based
on specific CSF findings, CT/MRI findings, ophthalmologic, and
simultaneous pulmonary TB diagnosis.
The current WHO recommendations for treating TB meningitis are based on
those made to treat PTB and recommend that all patients receive therapy
with two months of rifampicin (RMP), isoniazid (INH), pyrazinamide
(PZE), and ethambutol (ETB), followed by up to 10 months of RMP and INH.
This regimen ignores the many anti-tuberculosis medications’ varying
capacities for brain penetration. Dexamethasone lowers mortality in
HIV-negative TB meningitis; however, there is not enough data to support
its usage in HIV co-infection.18 This patient was
started on two months of HRZE, two months of dexamethasone, and
continued with HR. Timely diagnosis and treatment are essential since
prognosis largely depends on neurological status at presentation,
time-to-treatment initiation, HIV co-infection, and drug resistance.
Therefore, empiric treatment should be initiated as soon as the
diagnosis is suspected. This patient, with no immunocompromised
conditions and drug resistance, received timely treatment for TB
meningitis and, thus, showed total recovery.
Disseminated TB involving CNS in immunocompetent adults is challenging
to diagnose and often delayed or missed. As there is little evidence on
the pathophysiology of disseminated TB in the immunocompetent host,
further research is essential.