Tuberculous Meningitis

Background

• Tuberculous meningitis (also called meningeal tuberculosis) is caused by infection of the central nervous system with Mycobacterium tuberculosis.
• It is the most severe form of tuberculosis, with high morbidity and mortality, and neurologic complications are common with delayed diagnosis or treatment.
• It comprises about 3%-5% of extrapulmonary tuberculosis cases with about 100 cases reported in the United States during 2014.
• Those at highest risk for tuberculous meningitis include children and persons with HIV infection.
• Spread to the central nervous system occurs by hematogenous dissemination of organisms to the brain.
• Cranial nerve involvement may occur due to due to vascular damage, ischemia, or nerve entrapment.
• Obstruction of cerebrospinal fluid (CSF) in basal cisterns may lead to communicating hydrocephalus.

Evaluation

• Tuberculous meningitis is difficult to diagnose and a high index of suspicion is required.
• Diagnosis should be considered when a patient presents with consistent signs and symptoms combined with risk factors for tuberculosis (TB).
• Early clinical presentation may be nonspecific, and similar to other types of meningitis.
• Symptoms in children may include meningeal irritation, poor weight gain or weight loss, altered consciousness, and fever.
  • It often presents within 3 months of primary pulmonary TB.
  • It is closely associated with disseminated TB with more rapid progression of symptoms and neurological complications compared to adults.
• Symptoms in adults include stiff neck, headache, fever, and vomiting.
• About one-third of patients with tuberculous meningitis have cranial neuropathies, with involvement of the sixth nerve most common.
• Patients with HIV typically have a similar clinical presentation of tuberculous meningitis as patients without HIV.
• A careful neurologic exam should be performed looking for motor deficits, cranial nerve palsies, and photophobia.
• Diagnosis is typically based on detection of mycobacteria in cerebrospinal fluid (CSF) by smear microscopy, mycobacterial culture, or a nucleic acid amplification test.
• Abnormalities on imaging may include basal cistern enhancement, widening of subarachnoid space, hydrocephalus, changes to cranial nerves, and abnormalities on chest x-ray.
• HIV testing is recommended during evaluation of all patients with suspected extrapulmonary TB.
• CSF testing should include measurement of cell count, glucose and protein, smear microscopy, mycobacterial culture with drug susceptibility testing, and nucleic acid amplification testing.
  • Typical findings on CSF analysis include clear appearance, lymphocytic pleocytosis (5-1,000 cells/mcL), elevated protein (0.5-3 g/L), and hypoglycorrhachia.
  • Nucleic acid amplification testing (NAAT) of CSF may be useful for diagnosis of tuberculous meningitis, however due to low bacillary loads in CSF a negative Xpert test does not rule out tuberculous meningitis (Weak recommendation).

Management

• Prompt treatment is very important.
• Because of the paucibacillary nature of tuberculous meningitis, time required for culture results, and morbidity and mortality that may delay treatment of tuberculous meningitis, initial empiric treatment is necessary in most instances.
• All cases of suspected or confirmed cases of tuberculous meningitis should be promptly reported to appropriate public health authorities.
• Tuberculous meningitis should only be managed by, or in collaboration with an experienced provider and with local public health authorities.
• Treatment is based on the standard antituberculosis regimen but with a longer continuation phase, including:
  • initiation phase of isoniazid, rifampin, pyrazinamide, ethambutol for 2 months (Strong recommendation)
  • continuation phase of isoniazid plus rifampin for 7-10 months (Weak recommendation)
  • The CDC has issued guidance regarding use of rifampin and rifapentine for treatment of active and latent TB infection after some manufacturers detect nitrosamine impurities in their products.
• Although their role remains controversial, adjunctive corticosteroids are recommended in the context of tuberculous meningitis (Strong recommendation).
• Surgery may be indicated in patients with hydrocephalus, tuberculous cerebral abscess, or vertebral tuberculosis with paraparesis.