Bacterial Meningitis II: Pathophysiology

Bacterial meningitis typically begins when pathogens such as Neisseria meningitidis and Streptococcus pneumoniae colonize the nasopharynx and invade the bloodstream. This process is facilitated by bacterial virulence factors, such as polysaccharide capsules, which resist phagocytosis and complement-mediated killing. Less commonly, bacteria reach the central nervous system via contiguous spread from infections like otitis media or sinusitis, through congenital or acquired dural defects, or following neurosurgical procedures.

Crossing the Blood–Brain Barrier
After entering the bloodstream, bacteria can cross into the central nervous system through the cerebral microvascular endothelium or the choroid plexus. These sites form the blood–brain and blood–cerebrospinal fluid barriers. The exact entry point varies among pathogens and may involve both structures.

Subarachnoid Invasion and Inflammatory Activation
Within the subarachnoid space, bacteria proliferate in cerebrospinal fluid, which has limited immune surveillance. Bacterial components such as lipopolysaccharides (in gram-negative bacteria) and teichoic acids (in gram-positive bacteria) trigger the activation of microglia and astrocytes. These cells, in turn, release pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Adhesion molecules such as ICAM-1 and selectins are also upregulated, promoting neutrophil migration into the CSF.

Cerebral Edema and Elevated Intracranial Pressure
Inflammation disrupts the blood–brain barrier and causes:

• Vasogenic edema: leakage of plasma into the extracellular space due to increased vascular permeability.
• Cytotoxic edema: intracellular swelling of neurons and glia caused by inflammatory injury.
• Interstitial edema: impaired cerebrospinal fluid reabsorption at the arachnoid villi due to inflammatory exudates, contributing to hydrocephalus.

These forms of edema lead to increased intracranial pressure, which can impair cerebral perfusion.

Vascular Injury and Ischemic Damage
Inflammatory processes can lead to vasculitis and the formation of microthrombi, resulting in reduced cerebral blood flow, ischemic injury, and neuronal damage.