Outcome from tuberculous meningitis is believed to be dependent on the severity of the intracerebral inflammatory immune response. However, elevated cerebrospinal fluid inflammatory cytokines at presentation were not associated with death or disability in our cohort of HIV negative TBM patients. Cerebrospinal fluid IL-6 concentrations at presentation were independently associated with severe disease presentation, suggesting an immunological correlate of neurological damage before treatment. MMP-9/CSF leucocyte concentrations are also significantly elevated in tuberculous meningitis patients presenting with severe disease. CSF concentrations of lactate, IL-8 and IFN-γ are raised at presentation and fall sharply upon initiation of antituberculous chemotherapy. However significant immune activation and blood-brain barrier dysfunction remains after 60 days of therapy. Death is associated with high lactate, low white blood cell count and low CSF glucose levels.
While HIV infection does not alter the neurological presentation of tuberculous meningitis, the outcomes are significantly worse, with <40% of HIV co-infected patients surviving to nine months. HIV attenuates multiple cerebrospinal fluid indices. Low cerebrospinal fluid IFN-γ concentrations were independently associated with death in HIV-positive TBM patients, confirming the classical view that IFN-γ contributes to immunity and survival.
Dexamethasone does not appear to improve survival from tuberculous meningitis by attenuating immunological mediators of inflammation in the subarachnoid space or by suppressing peripheral T-cell responses to mycobacterial antigens. These findings challenged previously held theories of corticosteroid action in this disease. An MRI study of patients enrolled into the steroid trial suggested dexamethasone may affect outcome from tuberculous meninigitis by reducing hydrocephalus and preventing infarction.
Together these studies suggest that classical dogma in our understanding of tuberculous meningitis is often flawed. Further studies are on-going in-vitro and in-vivo to improve our understanding of the pathogenesis of tuberculous meningitis, correlates of immunity and disease severity.