Meningitis – causes, symptoms, diagnosis, treatment, pathology

With meningitis, mening- refers to the meninges
which are three protective membranes that cover the brain and spinal cord, and -itis
refers to inflammation; so meningitis is an inflammation of the meninges. More specifically, it refers to the inflammation
of the two inner layers which are called the leptomeninges. The outer layer of the meninges is the dura
mater, the middle layer is the arachnoid mater, and the inner layer is the pia mater. These last two, the arachnoid and pia maters,
are the leptomeninges. Between the leptomeninges there’s the subarachnoid
space, which houses cerebrospinal fluid, or CSF. CSF is a clear, watery liquid which is pumped
around the spinal cord and brain, cushioning them from impact and bathing them in nutrients. In one microliter or cubic millimeter, there
are normally a few white blood cells, up to 5. If we look at a bigger sample, like say a
decilitre, then around 70% of those will be lymphocytes, 30% monocytes, and just a few
polymorphonuclear cells — PMNs — like neutrophils. That same volume will contain some proteins,
as well, about 15-50 mg as well as some glucose, about 45-100 mg, which is close to two thirds
of the glucose we’d find in the same volume of blood. The CSF is held under a little bit of pressure,
below 200 mm of H2O, which is just under 15 mm of mercury — which is less than a fifth
of the mean arterial pressure. Now at any given moment, there’s about 150
ml of CSF in the body. This is constantly replenished, with around
500 ml of new CSF produced everyday and the excess, or 500 minus 150 mL or 350 mL, is
absorbed into the blood. But for any nutrients to enter and leave the
CSF, and the brain itself for the matter, they have to go through the tightly regulated
by the blood-brain barrier. The blood brain barrier is the special name
given to the blood vessels in the brain. That’s because the endothelial cells in
the blood vessels are so tightly-bound to one another that they prevent leakage and
only allow certain molecules to slip through them. Meningitis is the inflammation of the leptomeninges,
which remember are the inner two membranes around the brain and spinal cord. It is not the inflammation of the brain itself,
that’s encephalitis; but sometimes they can occur together and when that happens it’s
called meningoencephalitis. So meningitis needs some kind of trigger for
the inflammation, and could be an autoimmune disease, where the body attacks itself, like
lupus, or the body having an adverse reaction to some medication, which can happen with
intrathecal therapy, when medication is injected directly into the CSF. But, by far, infection is the most common
trigger for meningitis across all age groups, like with the Neisseria meningitidis bacteria
or herpes simplex virus for example. Now there are two routes that an infection
take to reach the CSF and leptomeninges. The first way is direct spread, which is when
a pathogen gets inside the skull or spinal column, and then penetrates the meninges,
eventually ending up in the CSF. Sometimes the pathogen will have come through
the overlying skin or up through the nose, but it’s more likely that there’s an anatomical
defect to blame. For example, it could be a congenital defect
like spina bifida, or an acquired one like a skull fracture, where there might be CSF
leaking through the sinuses. The second way is hematogenous spread, which
is when a pathogen enters the bloodstream and moves through the endothelial cells in
the blood vessels making up the blood-brain barrier and gets into the CSF. To do this, the pathogens typically have to
bind to surface receptors on the endothelial cells in order to get across. Otherwise, they have to find areas of damage
or more vulnerable spots like the choroid plexus. Once the pathogen finds a way into the CSF
it can start multiplying. Soon enough, the handful of white blood cells
surveilling the CSF identify the pathogen and release cytokines to recruit additional
immune cells. Over time, a microliter of CSF might go on
to contain up to thousands of white blood cells, but any more than five usually defines
meningitis. In most bacterial cases, there’ll be above
100 white blood cells per microliter, and more than 90% PMNs. In most viral cases, there’ll be 10 to 1000
white blood cells; over 50% lymphocytes and under 20% PMNs. In most fungal cases, there’ll be 10-500
white blood cells, with over being 50% lymphocytes. In most cases of tuberculous meningitis there’ll
be 50-500 white blood cells with over 80% being lymphocytes. The additional immune cells attract more fluid
to the area and start causing local destruction as they try to control the infection. As a result the CSF pressure typically rises
above 200 mm of H2O. The immune reaction also causes the glucose
concentration in the CSF to fall, to below two thirds of the concentration in the blood,
and makes the protein levels increase to over 50 mg per decilitre. When it comes to the causes of meningitis,
viruses and bacteria usually cause acute meningitis, whereas fungi usually cause chronic meningitis. Now for bacteria there are a lot of possibilities. In newborns, the most common causes are Group
B streptococci, E coli, and Listeria monocytogenes. In children and teens, the most common causes
are Neisseria meningitidis and Streptococcus pneumoniae. In adults and the elderly, the most common
causes are Streptococcus pneumoniae and Listeria monocytogenes. There are also tick-borne causes of meningitis
like Borrelia burgdorferi bacteria – which the cause of Lyme disease. As for viruses, the main culprits are enteroviruses,
especially coxsackie virus, and herpes simplex virus. HIV is usually contracted through body fluids
and can also cause viral meningitis. Less common causes include mumps virus, varicella
zoster virus, and lymphocytic choriomeningitis virus. There’s also the fungi, like those from
the Cryptococcus and Coccidioides genuses, which mainly affect immunocompromised individuals. And then of course there’s tubercular meningitis
is caused by the Mycobacterium tuberculosis bacteria, and finally parasitic causes of
meningitis like P. falciparum which is the main cause of malaria. Now, the classic triad of meningitis symptoms
are headaches, fevers, and nuchal rigidity, or neck stiffness. It can also cause photophobia which is discomfort
with bright lights, or phonophobia, which is discomfort with loud noises. Meningoencephalitis can cause an altered mental
state or seizures. The diagnosis of meningitis starts with a
physical exam. One maneuver is when a person lies flat on
their back facing upwards, and one of their legs is raised with the knee flexed to a 90
degree angle. Then, the leg is supported and slowly straightened
at the knee. If this causes back pain, then it’s called
the Kernig’s sign. Another maneuver, is when a person lies flat
on their back facing upwards, and has their neck supported and flexed. If this causes them to automatically flex
their knees or hips, then it’s called the Brudzinski’s sign. If meningitis is suspected, a lumbar puncture
can be done. This is when a needle goes through the lower
lumbar vertebral levels of the spinal cord, between L3 and L4 for example. The needle penetrates into the subarachnoid
space and a few milliliters of CSF is taken. The opening pressure can be measured, and
the CSF can be analyzed for white blood cells, protein, and glucose. Polymerase chain reaction, or PCR, might be
used to find Specific causes like HIV, enterovirus, HSV, or tuberculosis. If a particular infection seems like an obvious
cause, then a test for that might be used, like the Western blot for Borrelia burgdorferi
bacteria, or a thin blood smear for malaria. The treatment of meningitis depends on the
underlying cause. For bacterial meningitis, It’s common is
to administer steroids and then antibiotics, to prevent massive injury to the leptomeninges
from the inflammation caused as the antibiotics destroy the bacteria. In general the treatment – antivirals, antibacterials,
antifungals, or antiparasitic drugs are aimed at the specific cause of meningitis. Prevention with a vaccine, is appropriate
for some causes like Neisseria meningitidis, but also for mumps and for disseminated tuberculosis. Prophylactic antibiotics can also be administered,
to avoid outbreaks of bacterial meningitis like in households where individuals haven’t
been vaccinated against Neisseria meningitidis. All right, as a quick recap… meningitis
is an inflammation of the leptomeninges, the inner two membranes that surround and protect
both the brain and spinal cord. It normally starts when a foreign substance,
oftentimes bacteria, makes its way inside the leptomeninges, either by by direct contact
or hematogenous spread through the blood brain barrier. The immune system responds to the antigen
by flooding the subarachnoid space with white blood cells, which, release chemokines – and
create inflammation and this results in the classic triad of symptoms: headaches, fevers,
and neck stiffness.


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