Immunomodulating treatments for bacterial meningitis and viral encephalitis.

BACKGROUND: In central nervous system infections outcome is not only determined by pathogen-mediated injury but also by the host inflammatory response. Inhibition of the immune response has been suggested as an important means of reducing morbidity and mortality. OBJECTIVES: In this review, we summarize the current evidence for immunomodulating treatments in bacterial meningitis and viral encephalitis, discuss the biological rationale underlying these interventions, and identify key knowledge gaps and priorities for future research. SOURCES: For this narrative review Pubmed and Medline were searched using Search terms ((bacterial meningitis[Mesh] OR viral encephalitis[mesh]) AND (immunomodulating treatment OR adjunctive treatment OR corticosteroids) NOT (tubercul* OR cryptococc* OR vaccine)). CONTENT: For bacterial meningitis, data from randomized clinical trials and meta-analyses showed a beneficial effect of adjunctive corticosteroids on hearing loss, neurological sequelae and mortality. This led to the introduction of adjunctive dexamethasone in clinical practice, after which observational studies confirmed the beneficial effect. Studies on other immunomodulating treatments in bacterial meningitis showed no benefit on outcome of paracetamol, a harmful effect of therapeutic hypothermia and insufficient evidence for intravenous immunoglobulins. For viral encephalitis, a systematic review and randomized controlled trial showed no clear benefit of corticosteroids. However, as treatment with dexamethasone was generally started late, it remains an open question whether early corticosteroid treatment could be beneficial. For treatment of viral encephalitis with intravenous immunoglobulins insufficient evidence is available to guide clinical practice. IMPLICATIONS: Studies on the modulation of the inflammatory response in bacterial meningitis showed adjunctive dexamethasone should be routinely used in patients with community-acquired bacterial meningitis. Other immunomodulating treatments in bacterial meningitis are currently not advised. There is no convincing evidence for immunosuppressive treatment in patients with viral encephalitis. Whether early corticosteroid treatment is beneficial in HSV encephalitis should be evaluated in a new RCT.