In the early stages of meningitis, very little change in the substance of the brain can be detected. Neutrophils appear in the Virchow-Robin perivascular spaces but enter the brain only if there is necrosis. After several days, microglia and astrocytes increase in number, at first in the outer zone and later in all layers of the cortex. The associated nerve cell changes may be very slight. Obviously some disorder of the cortical neurons must take place from the beginning of the infection to account for the stupor, coma, and convulsions that are sometimes observed, but several days must elapse before any change can be demonstrated microscopically. It is uncertain whether these cortical changes are a result of the diffusion of toxins from the infected meninges, of a circulatory disturbance, or of some other factor, such as increased intracranial pressure or cortical venous thrombosis. The early cortical changes are therefore not because of invasion of brain substance by bacteria and should therefore be regarded as a noninfectious encephalopathy as contrasted with a true infectious meningoencephalitis, which is discussed later in the chapter. When macrophages are exposed to endotoxins, they synthesize and release cytokines, among which are interleukin-1 and tumor necrosis factor. These cytokines are believed to stimulate and modulate the local immune response but may also affect neurons.
There is also little change initially in the ependyma and the subependymal tissues; but in later stages of meningitis, conspicuous changes are invariably found. The most prominent finding is infiltration of the subependymal perivascular spaces and often of the adjacent brain tissue with neutrophilic leukocytes and later with lymphocytes and plasma cells. Microglia and astrocytes proliferate, the latter sometimes overgrowing and burying remnants of the ependymal lining. The bacteria may pass through the ependymal lining and set up this inflammatory reaction in part because this sequence of events is favored by a developing hydrocephalus, which stretches and breaks the ependymal lining. Collections of subependymal astrocytes then begin to protrude into the ventricle, giving rise to a granular ependymitis, which, if prominent, may narrow and obstruct the aqueduct of Sylvius. As any meningitis becomes more chronic, the pia-arachnoid exudate tends to accumulate around the base of the brain (basilar meningitis), obstructing the flow of CSF and giving rise to hydrocephalus. In a survey of community-acquired bacterial meningitis, hydrocephalus occurred in only 5 percent, but it was associated with poor outcome (Kasanmoentalib et al).
The reader may question this digression into matters that are more pathologic than clinical, but knowledge of the morphologic features and their temporal sequence in meningitis enables one to understand the clinical state and its sequelae. The meningeal and ependymal reactions to bacterial infection and the clinical correlates of these reactions are summarized in Table 31-1.
Types of Bacterial Meningitis
Almost any bacterium gaining entrance to the body may produce meningitis but the most common are S. pneumoniae, N. meningitidis, group B streptococcus, H. influenzae,