Meningitis is an infection of the meninges. Meningitis is usually due to viral (less
severe; can be resolved without specific treatment) or bacteria Infection (very
The meninges are membranes that envelop the CNS (brain and spinal cord), and it
includes the dura mater, arachnoid mater, and pia mater. Cerebrospinal fluid is
located between the arachnoid and pia maters (subarachnoid space).
The BBB is a protective cellular structure that restricts the passage of chemicals,
toxins, and microorganisms from the blood to the CNS not the same as the
meninges. If you inject a die into the CSF, the brain turns blue while the rest of the
body’s compartments did not, showing that there is a barrier that
compartmentalizes these two structures (BBB).
Due to the BBB, the CNS is an “immune privileged” site, meaning that if you put
something exogenous in, you wont get any infection. Astrocytes are located in the
brain and provide support for other cells of the CNS including the BBB. Endothelial
cells and associated astrocytes are stitched together by structures called “tight
junctions”, preventing things from entering the brain. Since white blood cells are not
present in the CNS, you wont have antibodies present in the CNS either.
Note: Microglia cells are the “tissue macrophages” of the CNS.
The disease: bacterial meningitis
The major pathogens that cause bacterial meningitis live in our nasopharynx.
1. Nasopharynx colonization
2. Invasion into the blood 3. Multiplication in the blood
4. Crossing of the BBB
5. Invasion of the meninges and the CNS
6. Increased permeability of the BBB
7. Increased inflammation
8. Edema, increased cranial pressure, leukocyte migration
9. Pro-inflammatory cytokines from WBC
Note: once the bacteria enters the CNS, there is no immune system to control them
The disease: bacterial meningitis
Is rare, but a very dangerous disease (can kill in days). Early signs may be non-
specific. In an outbreak, the first people to develop disease are the most likely to die,
but once the outbreak is known, people are more wary of the initial symptoms.
People who survive the disease may have irreversible neurological damage
(especially children), such as brain damage, blindness, hearing loss, and learning
The main symptoms in children and adults vary, but 95% of people infected will
have at least two of the following symptoms:
Symptoms in infants involve excessive crying as well as a bulge in the soft spot on
top of a baby’s head (fontanel).
There are also many risk factors that contribute to bacterial meningitis. These
include a lack of vaccination, being 15 months to 25 years, and living in a community
setting. Immunocompromised individuals are also at risk due to disease,
chemotherapy, or surgery (such as cranial).
Diagnosis of bacterial meningitis involves looking at the history and symptoms of
the individual, blood tests for inflammatory markers, CT/MRI imaging, and the most
important spirdl tapthlumbar puncture): spinal needle is inserted usually
between the 3 and 4 lumbar vertebrae. CSF is withdrawn and subject to gram
stain and culture. If there is white cells and low glucose (due to organisms using it
up), then you can confirm the disease.
Other methods involve: Nucal rigidity: inability to flex the head forward
Brudzinski’s sign: severe neck stiffness causes patients knees to flex when the head
Kernig’s sign: sever stiffness of the hamstrings causes an inability to straighten the
leg when the hip is flexed to 90 degrees
But, LUMBAR PUNCTURE IS THE MAIN TOOL FOR DIAGNOSIS
Treatment must be sought immediately:
IV antibiotics (prior to culture analysis)
Corticosteroids (dexamethasone) to redice swelling in the meninges
Supportive therapies (monitoring, oxygen, fluids, etc…)
Major causes of bacterial meningitis
Almost all bacteria has the potential to cause bacterial meningitis, The major causes
of bacterial meningitis are:
(Haemophilus influenza) – not influenze flu
In infants (0-2 months):
E. coli KI
Note: These diverse pathogens (except Listeria) produce a capsule as a major
A capsule is a loose, relatively unstructured network of polymers that cover the
surface of some bacteria. Most are composed of polysaccharides, and the main role
in meningitis is to protect bacteria from inflammatory responses (major way is by
preventing complement activation and phagocytic killing). Encapsulated bacteria
are less likely to be opsonized by C3b using the alternative complement cascade.
C3b is deposited on the bacterial surface, but what the capsule does it block the
complement receptors (of the phagocytic WBC) from getting access to C3b.