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PATHOGENESIS AND PATHOLOGY

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Development of bacterial meningitis progresses through the following five related steps: (1) bacterial colonization of the nasopharynx, (2) mucosal invasion and penetration into the blood stream, (3) intravascular multiplication and entrance through the blood-brain barrier (BBB), (4) generation of inflammation within the subarachnoid space, and (5) induction of neuronal and auditory cell damage.[4]
The three common meningeal pathogens colonize the nasopharyngeal mucosa in 5% to 40% of young children at any given time; for Hib and N. meningitidis, fimbriae mediate adherence to epithelial cells; for S. pneumoniae, specialized surface components have not been clearly identified. These encapsulated organisms are able to evade local host defenses and either invade between epithelial cells (Hib) or pass through epithelial cells ( N. meningitidis) to reach the subepithelial tissues, where the organisms apparently can invade small blood vessels to enter the blood stream.[4] A viral upper respiratory tract infection can facilitate this process. Intravascular replication leads to bacteremia and, with sufficient density of organisms, egress through the endothelium of the choroid plexus and cerebral capillaries into the ventricular fluid. A complex interplay between endothelial cells and microbial gene products appears to orchestrate the traversal of bacteria across the blood-brain barrier. The organisms quickly multiply and spread throughout the subarachnoid space because of the lack of host

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TABLE 41-1 -- Underlying Conditions and Organisms Commonly Associated with Bacterial Meningitis
Condition
Organism
Cerebrospinal fluid leak (otorrhea, rhinorrhea)
Streptococcus pneumoniae, Haemophilus influenzae
Dermal sinus tracts, meningomyelocele
Staphylococci, gram-negative enteric bacilli, intestinal bacteria (related to site of defect)
Terminal complement deficiencies
Neisseria meningitidis
Asplenia (anatomic or functional)
S. pneumoniae, N. meningitidis, Salmonella spp.
Renal transplantation, T-lymphocyte deficiency
Listeria monocytogenes
Otic fistula (stapes footplate, oval window)
S. pneumoniae
Ventriculoperitoneal shunt
Staphylococci, S. pneumoniae, H. influenzae, N. meningitidis (hematogenous), diphtheroids (e.g., contaminated shunt)
Antibody deficiency states (including HIV infection)
S. pneumoniae, N. meningitidis, H. influenzae type b
Penetrating trauma
Varies with nature and site of trauma (e.g., Pasteurella multocida after dog or cat bite, skin organisms after skull trauma, nasopharyngeal organisms after orbital or sinus trauma)
Surgery
Skin organisms, nosocomial pathogens
Abbreviation: HIV, human immunodeficiency virus.

defenses within the CSF. The host inflammatory response to organisms leads to many of the alterations in CNS function and in the CSF that are characteristic of meningitis.
Communications between mucosal surfaces or skin and CSF that result from trauma or congenital malformations can lead to direct invasion of the CNS by bacteria. A fracture through the cribriform plate (CSF rhinorrhea), paranasal sinuses, or temporal bone (CSF otorrhea) provides entrance for respiratory tract organisms into the CNS. Penetrating injuries of the skull by sharp objects (toys, teeth) in younger infants or children can precede bacterial meningitis. Bacteria also can reach the CNS through congenital defects, such as a dermoid sinus tract, meningomyelocele, or fistula through the stapes footplate, oval window, or cochlear aqueduct. These defects should be sought in patients with recurrent bacterial meningitis.[5] Bacterial meningitis also can be a complication of neurosurgery, spinal anesthesia, or ventriculostomy placement ( Table 41–1 ). [6]
The pathology of Hib meningitis has been described in detail.[7] [8] Increased brain weight and flattened convolutions are evidence of cerebral edema. Temporal lobe or cerebellar herniation can occur. The brain and spinal cord are covered with a purulent subarachnoid exudate that consists primarily of neutrophils, which also infiltrate the perivascular spaces of blood vessels in the outer layers of the cortex of the brain and connective tissue sheaths of cranial and spinal nerves. Endothelial cells of small subarachnoid arteries and veins are swollen, leading to narrowing of the lumen and microscopic changes within brain parenchyma consistent with infarction. The interstitial tissue of the plexus is infiltrated with neutrophils (choroid plexitis). Phlebitis, venous thrombosis, arteritis, and brain necrosis are pathologic changes noted at necropsy in children who had untreated bacterial meningitis for less than 3 weeks. The foramina of Magendie and Luschka can be obstructed by exudate, resulting in obstructive hydrocephalus; communicating hydrocephalus is more common. This exudate, rich in bacterial products and proinflammatory substances, also can traverse the cochlear duct to involve the auditory tissue, resulting in hearing deficit. Ongoing research is focusing on delineation of the complex molecular events taking place at the cellular level that can potentially explain the precise mechanisms of the brain damage resulting from bacterial meningitis.[4]