In bacterial meningitis, bacteria reach the meninges by one of two main routes: through the bloodstream (hematogenous spread) or

through direct contact between the meninges and either the nasal cavity or the skin. In most cases, meningitis follows invasion of
the bloodstream by organisms that live on mucosal surfaces such as the nasal cavity. This is often in turn preceded by viral
infections, which break down the normal barrier provided by the mucosal surfaces. Once bacteria have entered the bloodstream,
they enter the subarachnoid space in places where the blood–brain barrier is vulnerable – such as the choroid plexus. Meningitis
occurs in 25% of newborns with bloodstream infections due to group B streptococci; this phenomenon is much less common in
adults.[2] Direct contamination of the cerebrospinal fluid may arise from indwelling devices, skull fractures, or infections of the
nasopharynx or the nasal sinuses that have formed a tract with the subarachnoid space (see above); occasionally, congenital
defects of the dura mater can be identified.[2]

The large-scale inflammation that occurs in the subarachnoid space during meningitis is not a direct result of bacterial infection but
can rather largely be attributed to the response of the immune system to the entry of bacteria into the central nervous system. When
components of the bacterial cell membrane are identified by the immune cells of the brain (astrocytes and microglia), they respond
by releasing large amounts of cytokines, hormone-like mediators that recruit other immune cells and stimulate other tissues to
participate in an immune response. The blood–brain barrier becomes more permeable, leading to "vasogenic" cerebral
edema (swelling of the brain due to fluid leakage from blood vessels). Large numbers of white blood cells enter the CSF, causing
inflammation of the meninges and leading to "interstitial" edema (swelling due to fluid between the cells). In addition, the walls of the
blood vessels themselves become inflamed (cerebral vasculitis), which leads to decreased blood flow and a third type of
edema, "cytotoxic" edema. The three forms of cerebral edema all lead to increased intracranial pressure; together with the lowered
blood pressure often encountered in sepsis, this means that it is harder for blood to enter the brain; consequently brain cells are
deprived of oxygen and undergo apoptosis (programmed cell death).[2]

Administration of antibiotics may initially worsen the process outlined above, by increasing the amount of bacterial cell membrane
products released through the destruction of bacteria. Particular treatments, such as the use of corticosteroids, are aimed at
dampening the immune system's response to this phenomenon.[2][3]

Diagnosis
[edit]

CSF findings in different forms of meningitis[46]

Type of
Glucose Protein Cells
meningitis

PMNs,
Acute bacterial low high
often > 300/mm3

normal or mononuclear,
Acute viral normal
high < 300/mm3

mononuclear and
Tuberculous low high
PMNs, < 300/mm3

Fungal low high < 300/mm3

usually
Malignant low high
mononuclear

Diagnosing meningitis as promptly as possible can improve outcomes.[47] There are no specific signs or symptoms that can indicate
meningitis, and a lumbar puncture (spinal tap) to examine the cerebrospinal fluid is recommended for diagnosis.[47] Lumbar puncture
is contraindicated if there is a mass in the brain (tumor or abscess) or the intracranial pressure (ICP) is elevated, as it may lead
to brain herniation. If someone is at risk for either a mass or raised ICP (recent head injury, a known immune system problem,
localizing neurological signs, or evidence on examination of a raised ICP), a CT or MRI scan is recommended prior to the lumbar
puncture.[8][48][49] This applies in 45% of all adult cases.[3]

There are no physical tests that can rule out or determine if a person has meningitis. [50] The jolt accentuation test is not specific or
sensitive enough to completely rule out meningitis.[50]

If someone is suspected of having meningitis, blood tests are performed for markers of inflammation (e.g. C-reactive
protein, complete blood count), as well as blood cultures.[8][48] If a CT or MRI is required before LP, or if LP proves difficult,
professional guidelines suggest that antibiotics should be administered first to prevent delay in treatment, [8] especially if this may be
longer than 30 minutes.[48][49] Often, CT or MRI scans are performed at a later stage to assess for complications of meningitis. [2]

In severe forms of meningitis, monitoring of blood electrolytes may be important; for example, hyponatremia is common in bacterial
meningitis.[51] The cause of hyponatremia, however, is controversial and may include dehydration, the inappropriate secretion of
the antidiuretic hormone (SIADH), or overly aggressive intravenous fluid administration.[3][51]

Lumbar puncture
[edit]

Cloudy CSF from a person with meningitis due to Streptococcus

Gram stain of meningococci from a culture showing Gram negative

A lumbar puncture is done by positioning the person, usually lying on the side, applying local anesthetic, and inserting a needle into
the dural sac (a sac around the spinal cord) to collect cerebrospinal fluid (CSF). When this has been achieved, the "opening
pressure" of the CSF is measured using a manometer. The pressure is normally between 6 and 18 cm water (cmH2O);[52] in bacterial
meningitis the pressure is usually elevated.[8][48] In cryptococcal meningitis, intracranial pressure is markedly elevated.[53] The initial
appearance of the fluid may prove an indication of the nature of the infection: cloudy CSF indicates higher levels of protein, white
and red blood cells and/or bacteria, and therefore may suggest bacterial meningitis. [8]

The CSF sample is examined for presence and types of white blood cells, red blood cells, protein content and glucose level.[8] Gram
staining of the sample may demonstrate bacteria in bacterial meningitis, but absence of bacteria does not exclude bacterial
meningitis as they are only seen in 60% of cases; this figure is reduced by a further 20% if antibiotics were administered before the
sample was taken. Gram staining is also less reliable in particular infections such as listeriosis. Microbiological culture of the sample
is more sensitive (it identifies the organism in 70–85% of cases) but results can take up to 48 hours to become available.[8] The type
of white blood cell predominantly present (see table) indicates whether meningitis is bacterial (usually neutrophil-predominant) or
viral (usually lymphocyte-predominant),[8] although at the beginning of the disease this is not always a reliable indicator. Less
commonly, eosinophils predominate, suggesting parasitic or fungal etiology, among others. [43]
The concentration of glucose in CSF is normally above 40% of that in blood. In bacterial meningitis it is typically lower; the CSF
glucose level is therefore divided by the blood glucose (CSF glucose to serum glucose ratio). A ratio ≤0.4 is indicative of bacterial
meningitis;[52] in the newborn, glucose levels in CSF are normally higher, and a ratio below 0.6 (60%) is therefore considered
abnormal.[8] High levels of lactate in CSF indicate a higher likelihood of bacterial meningitis, as does a higher white blood cell count.
[52]
If lactate levels are less than 35 mg/dl and the person has not previously received antibiotics then this may rule out bacterial
meningitis.[54]

Various other specialized tests may be used to distinguish bet