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Meningitis, an infection of the subarachnoid space and leptomeninges caused by a variety of pathogenic organisms, continues to be an important source of mortality and morbidity. Despite the introduction of new vaccines that prevent the most severe causes, bacterial or purulent meningitis remains the most important form of meningitis in the United States in terms of incidence, sequelae, and ultimate loss of productive life. Aseptic meningitis, usually caused by viruses, especially enteroviruses, is more common; however, significant sequelae are uncommon, and the disease is usually self-limited. Granulomatous meningitis, caused either by Mycobacterium tuberculosis or fungi, is a major cause of neurologic injury and death in the developing world.


The most common progression of infection in children with bacterial meningitis is hematogenous spread from the nasopharynx followed by bacterial entry into the subarachnoid space where the cerebrospinal fluid (CSF) contains few fixed or circulating scavenger cells to remove bacteria. Different bacteria cross the blood-brain barrier using a variety of cell surface receptors. There is poor opsonic and bactericidal capability in the CSF, so there is not a rapid cellular or humoral immune response, and bacteria can grow to the level of 106 to 107 organisms per milliliter of CSF. Meningitis may also occur as a direct extension from a contiguous focus or as a result of congenital, traumatic, or surgical disruption of normal anatomic barriers. Examples of such disruption include congenital dermal sinuses along the craniospinal axis, basilar skull fractures, and placement of CSF shunts.

Many of the neurologic sequelae of bacterial meningitis are a consequence of altered physiology due to the host’s inflammatory response to the infecting organism (Fig. 226-1). In the subarachnoid space, components of the surface of the multiplying bacteria (lipopolysaccharide, lipo-oligosaccharide, teichoic acid) stimulate generation of proinflammatory cytokines (tumor necrosis factor [TNF]-α, interleukin [IL]-1β, IL-6, platelet activating factor [PAF], and others). These, in turn, increase adhesion of leukocytes to cerebral vascular endothelium, promoting increased blood-brain barrier permeability and migration of leukocytes into the subarachnoid space. White blood cell (WBC) and endothelium-derived reactive oxygen species, and perhaps nitric oxide, then participate in altering cerebrovascular reactivity. Cerebral edema associated with meningitis represents a combination of vasogenic, cytotoxic, and interstitial edema. Cerebral perfusion is reduced in meningitis in approximately 30% of children in whom brain blood-flow studies have been performed. Cerebral edema not only contributes to reduced cerebral perfusion, but may also cause cerebral herniation due to increased intracranial pressure.

Figure 226-1

Pathophysiologic changes that occur in the brain in response to invasion by bacteria in meningitis. Note that different regions of the brain may be hyperperfused or hypoperfused. LPS, lipopolysaccharide; TNF, tumor necrosis factor.

Direct cytotoxic neuronal injury, frequently found in postmortem studies, is likely caused by reactive oxygen and nitrogen species (oxygen radical, nitric ...

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