Meningitis pathophysiology

Meningitis Main Page
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]

Pathophysiology

The clinical picture of meningitis largely arises from the host response to the inciting organism in the CSF.

• It seems that the subcapsular components (the cell wall and lipopolysaccharide) of bacteria are more important in determining inflammation than the surface components (pili and polysaccharide capsule).
• The primary site of breakdown of the blood-brain barrier is the cerebral microvascular endothelium.

  • Electron microscope (EM) studies have shown complete separation of the intercellular tight junctions

• It appears that there is a final common pathway, mediated by TNF-alpha, IL-1 and IL-6, that results in meningeal inflammation and loss of the blood-brain barrier.

  • One of the major roles of these cytokines is to facilitate the migration of neutrophils across the vascular endothelium into the CSF.
  • A key initial step in this process is obviously adhesion of the PMN to the endothelial surface.

    • This is mediated by the expression of specific transmembrane glycoproteins expressed on the endothelial surface that interact with specific counterparts on the neutrophils.
    • These adhesion molecules fall into three large categories: the immunoglobin superfamily (including the antigen-specific T and B cell receptors, ICAM-1 and ICAM-2), the integrin family (beta-1, beta-2, and beta-3) and the selectin family (including ELAM-1).

  • The interaction of beta-2 integrin (CD18) and ICAM-1 is largely responsible for PMN diapedesis.

• Additionally, patients get cerebral edema that is mediated by an increase in capillary permeability, the inflammatory response from the neutrophils, and CSF outflow resistance.
• The above pathophysiologic processes are not only important in producing the symptoms associated with meningitis, but the understanding of the underlying disease process is necessary to guide therapy.

Mechanism

• In order to gain access to the CNS, the pathogen needs to colonize mucosal epithelium, invade and survive in the intravascular space, cross the blood-brain barrier and survive in the CSF.
• Colonization of the nasopharynx is usually asymptomatic, and during peak seasons, approximately 20% of the population are colonized with N. meningitidis.

Gross Pathology

Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission. © PEIR, University of Alabama at Birmingham, Department of Pathology

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  Meningitis: Gross, purulent leptomeningitis due to pneumococcus infection, an excellent example.

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  Bacterial Meningitis: Gross, basilar view

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  Bacterial Meningitis: Gross close-up

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  Meningitis: Gross base of frontal lobes well shown meningitis burn case with Pseudomonas sepsis

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  Meningitis: Gross natural color excellent demonstration of greenish pus in subarachnoid space

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  Tuberculous Meningitis: Gross fixed tissue close-up of large areas of necrosis in frontal parasagittal cortex secondary to tuberculous vasculitis. An excellent example

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  Tuberculous Meningitis: Micro low mag H&E. An excellent example with giant cells.

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  Purulent Meningitis: Gross natural color excellent photo lateral aspect of brain with easily seen purulent exudate due to Pneumococcus infection.

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  Purulent Meningitis: Gross natural color close-up view outstanding example of purulent exudate adjacent to blood vessels

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  Purulent Meningitis: Gross natural color Staphylococcal meningitis.

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  Ependymitis Granular Neoplastic: Gross fixed tissue close-up view and a spectacular one of this lesion case also has carcinomatous meningitis primary is lung oat cell.

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  Purulent Meningitis: Gross natural color brain in situ with removed calvarium very good illustration of exudate in meninges over convexities pneumococcus.

Microscopic Pathology

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References

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