Meningitis - Mechanism

Mechanism

The meninges comprise three membranes that, together with the cerebrospinal fluid, enclose and protect the brain and spinal cord (the central nervous system). The pia mater is a very delicate impermeable membrane that firmly adheres to the surface of the brain, following all the minor contours. The arachnoid mater (so named because of its spider-web-like appearance) is a loosely fitting sac on top of the pia mater. The subarachnoid space separates the arachnoid and pia mater membranes and is filled with cerebrospinal fluid. The outermost membrane, the dura mater, is a thick durable membrane, which is attached to both the arachnoid membrane and the skull.

In bacterial meningitis, bacteria reach the meninges by one of two main routes: through the bloodstream or through direct contact between the meninges and either the nasal cavity or the skin. In most cases, meningitis follows invasion of the bloodstream by organisms that live upon mucous surfaces such as the nasal cavity. This is often in turn preceded by viral infections, which break down the normal barrier provided by the mucous surfaces. Once bacteria have entered the bloodstream, they enter the subarachnoid space in places where the blood–brain barrier is vulnerable—such as the choroid plexus. Meningitis occurs in 25% of newborns with bloodstream infections due to group B streptococci; this phenomenon is less common in adults. Direct contamination of the cerebrospinal fluid may arise from indwelling devices, skull fractures, or infections of the nasopharynx or the nasal sinuses that have formed a tract with the subarachnoid space (see above); occasionally, congenital defects of the dura mater can be identified.

The large-scale inflammation that occurs in the subarachnoid space during meningitis is not a direct result of bacterial infection but can rather largely be attributed to the response of the immune system to the entry of bacteria into the central nervous system. When components of the bacterial cell membrane are identified by the immune cells of the brain (astrocytes and microglia), they respond by releasing large amounts of cytokines, hormone-like mediators that recruit other immune cells and stimulate other tissues to participate in an immune response. The blood–brain barrier becomes more permeable, leading to "vasogenic" cerebral edema (swelling of the brain due to fluid leakage from blood vessels). Large numbers of white blood cells enter the CSF, causing inflammation of the meninges and leading to "interstitial" edema (swelling due to fluid between the cells). In addition, the walls of the blood vessels themselves become inflamed (cerebral vasculitis), which leads to decreased blood flow and a third type of edema, "cytotoxic" edema. The three forms of cerebral edema all lead to increased intracranial pressure; together with the lowered blood pressure often encountered in acute infection, this means that it is harder for blood to enter the brain, consequently brain cells are deprived of oxygen and undergo apoptosis (automated cell death).

It is recognized that administration of antibiotics may initially worsen the process outlined above, by increasing the amount of bacterial cell membrane products released through the destruction of bacteria. Particular treatments, such as the use of corticosteroids, are aimed at dampening the immune system's response to this phenomenon.