Neurologic manifestations of infection with tuberculosis (TB) are diverse and can be challenging to diagnose given the limitations of available diagnostic tests. Suspicion for TB should be heightened in patients with a history of travel to areas with high prevalence (such as India and Africa), known exposure to an individual infected with TB, or an immunocompromised state. All patients suspected of having TB should be tested for human immunodeficiency virus, as this may affect response to and type of treatment.
Tuberculous meningitis typically presents with a subacute course developing over weeks, and can cause cranial neuropathies, communicating hydrocephalus through impaired absorption of cerebrospinal fluid (CSF), and an infectious vasculitis leading to cerebral infarction, which is usually subcortical and often bilateral affecting the caudate, internal capsule, and anterior thalamus. Initial examination with brain magnetic resonance imaging (MRI) with contrast is indicated when any of these manifestations are suspected, particularly if a patient exhibits signs of progressive alteration of mental status. In that case, hydrocephalus is a major concern, and prompt neurosurgical intervention for placement of a ventricular drain may be necessary, at which time CSF can be obtained.
Tuberculoma, a conglomeration of tuberculous nodules following hematogenous spread of the organism, can lead to focal neurologic deficits or be a seizure focus.
Spinal cord involvement may be indirect with bony invasion of the vertebral bodies leading to fracture (Pott’s disease) with resulting cord compression or direct due to spinal cord tuberculoma or arachnoiditis. The latter represents an inflammatory process along the arachnoid membrane, which leads to gradual encasement of the spinal cord with exudate. In the setting of acute paraparesis, computed tomography (CT) of the spine should be performed to assess for bony involvement; if acute fracture is present, urgent surgical consultation is indicated. Otherwise, and particularly with a more subacute course, MRI of the spine with contrast should be performed.
If hydrocephalus and mass effect are absent, CSF should be analyzed. A lymphocytic or mononuclear pleocytosis (white blood cells > 100/mm 3 ), highly elevated protein (> 100 mg/dL), and low glucose (45 mg/dL) are commonly seen with neurologic involvement of TB, although absence of these findings does not rule out the disease.
Interferon-gamma release assays, which measure the release of interferon gamma by memory T-cells following stimulation with Mycobacterium tuberculosis –specific antigens, can provide evidence of exposure to this organism, even in individuals who have previously been inoculated with Bacille Calmette-Guérin (BCG) vaccine. Tuberculin skin tests, which involve intradermal injection of mycobacterial purified protein derivatives to stimulate a delayed hypersensitivity response, may also be used, although prior BCG receipt may provide cross-reactive false positivity. Neither test reliably distinguishes between active and latent infection, nor is either sufficiently sensitive to rule out TB infection. Chest radiographs or CT scanning can identify infiltrates, consolidations, or cavities (especially in the upper lungs), as well as hilar lymphadenopathy, to provide evidence of pulmonary involvement (most common). Sputum smears and culture for acid-fast bacilli can confirm a diagnosis of mycobacterial disease. If there is no pulmonary disease, look for lymphadenopathy, pleuritis, involvement of the liver/spleen on abdominal CT, choroidal tubercles on ophthalmologic examination, and/or osseous involvement on skeletal survey. Any of these may provide evidence of active extraneural TB, in which case treatment is indicated.
Empiric therapy with a combination of rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE regimen) is standard initial therapy. Consider alternative regimens if disease may have been acquired from an area with high endemic levels of resistance to one or more of these drugs. All four medications are given for 2 months. Assuming a susceptible strain, isoniazid and rifampin are continued for an additional 7–10 months. Steroids have been shown to reduce mortality in TB meningitis and should also be administered; intravenous dexamethasone 0.3–0.4 mg/kg per day for 2 weeks followed by a taper over 6–8 weeks is a standard regimen.
If suspicion for TB remains high but the diagnosis remains unclear, serial lumbar punctures should be performed daily for 3 days. CSF acid-fast bacilli stains as well as culture should be sent. Yield is improved with large-volume CSF sampling. CSF nucleic acid amplification (NAA) can be confirmatory in the setting of negative cultures and should be sent, while CSF adenosine deaminase can support a diagnosis of CNS TB but cannot differentiate between TB and other types of bacterial meningitis.
Therapy should not be withheld in the setting of a strong clinical suspicion of CNS TB, as the sensitivity of CSF acid-fast bacilli staining with culture is only ~ 80%. CSF NAA has even poorer sensitivity (~ 60%) but very high specificity (nearly 100%), such that a positive result can be considered confirmatory of the diagnosis.