Abstract

Bacterial meningitis remains an overwhelmingly serious disease worldwide, associated with a considerably high incidence of long term neurological morbidity or even death. Despite the institution of appropriate antibiotic therapy over recent years, these therapeutic advances have failed to produce a corresponding reduction in neurological complications. Amongst the long-term neurological sequelae in bacterial meningitis, the most important sequelae include cerebrovascular disease and brain edema with subsequent increases in intracranial pressure. Recent experimental evidence suggests that live meningeal organisms account for only a minor degree of neurological injury in models of bacterial meningitis. More importantly, bacterial derived products, including toxic cell wall fragments and endotoxins, persistent and accumulative in the subarachnoid space following bactericidal killing by antibiotics or a sustenance of bacterial invasion and subarachnoid inflammation represent highly active elements capable of initiating adverse neuronal injury. This, in conjunction with other pathophysiological alterations in the central nervous system augments cerebral edema formation, which begins to increase during the acute phase of infection and progressively continues to increase over the disease course to culminate in dangerously elevated intracranial pressure levels, secondarily accounting for a high incidence of morbidity and mortality.