Management of central nervous system tuberculosis in children: light and shade

Pediatric tuberculosis of the central nervous system (CNS-TB) is a severe form of extrapulmonary TB. It is most common in children between 6 months and 4 years of age. CNS-TB can present as meningitis and/or tuberculoma. In both situations, brain damage results from a cytokine-mediated inflammatory response, which causes vasculitis, obstructive hydrocephalus and cranial nerve palsy. Tumor necrosis factor alpha (TNF-alpha) is an important cytokine in this response. The prognosis of tuberculous meningitis (TBM) correlates most closely with the clinical stage of illness at the time treatment is started. Most patients in the 1st stage have a good outcome, whereas the management of patients in the 2nd and 3rd stage is still a clinical challenge, and the few patients who survive have permanent severe disabilities. Due to the important role of inflammation in CNS-TB pathogenesis, corticosteroids are routinely used in TBM or tuberculomas, in order to reduce death and disabling residual neurological deficits among survivors. Nevertheless, not all patients show a good response to standard anti-inflammatory treatment. Thalidomide is a drug with pleiotropic effects: it appears to downregulate production of TNF-alpha and other proinflammatory cytokines. Due to its anti-inflammatory effects, thalidomide has been evaluated as an adjunctive drug in the management of difficult-to-treat CNS-TB.

A literature review was carried out based on MEDLINE/pubmed database (1997/2010) searching for the following descriptors: corticosteroids and tuberculous meningitis (limits: review, all child); thalidomide and tuberculosis treatment; and tuberculous meningitis; and CNS-TB; and brain abscess; and TB clinical trial.

Literature review on the use of corticosteroids and thalidomide in the treatment of CNS-TB.

The Cochrane review for randomized-controlled trials evaluating the use of steroids in TBM showed significantly reduced overall mortality, reduced death and severe residual disability in children. Regarding the use of thalidomide, a randomized controlled trial published in 2004 do not support the use of adjunctive high-dose thalidomide therapy in the treatment of TBM in children, but results from four case reports, one clinical trial and one placebo-controlled trial suggest the use of thalidomide in CNS-TB not responding to standard therapy.

"Adjuvant" treatment with dexamethasone improves survival in patients with TBM but probably does not prevent disability. Thalidomide should not be used for the routine treatment, but it may be helpful as a "salvage therapy" in patients with TBM and tuberculomas not responding to anti-TB drugs and high dose corticosteroids. More studies should evaluate its not completely conclusive role.