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.