Meningitis

Other symptoms include confusion or altered consciousness, nausea, and an inability to tolerate light or loud noises.^[1] Young children often exhibit only nonspecific symptoms, such as irritability, drowsiness, or poor feeding.^[1] A non-blanching rash (a rash that does not fade when a glass is rolled over it) may also be present.^[11]


The inflammation may be caused by infection with viruses, bacteria, fungi or parasites.^[12] Non-infectious causes include malignancy (cancer), subarachnoid hemorrhage, chronic inflammatory disease (sarcoidosis) and certain drugs.^[4] Meningitis can be life-threatening because of the inflammation's proximity to the brain and spinal cord; therefore, the condition is classified as a medical emergency.^[2][8] A lumbar puncture, in which a needle is inserted into the spinal canal to collect a sample of cerebrospinal fluid (CSF), can diagnose or exclude meningitis.^[1][8]


Some forms of meningitis are preventable by immunization with the meningococcal, mumps, pneumococcal, and Hib vaccines.^[2] Giving antibiotics to people with significant exposure to certain types of meningitis may also be useful.^[1] The first treatment in acute meningitis consists of promptly giving antibiotics and sometimes antiviral drugs.^[1][7] Corticosteroids can also be used to prevent complications from excessive inflammation.^[3][8] Meningitis can lead to serious long-term consequences such as deafness, epilepsy, hydrocephalus, or cognitive deficits, especially if not treated quickly.^[2][3]


In 2019, meningitis was diagnosed in about 7.7 million people worldwide,^[9] of whom 236,000 died, down from 433,000 deaths in 1990.^[9] With appropriate treatment, the risk of death in bacterial meningitis is less than 15%.^[1] Outbreaks of bacterial meningitis occur between December and June each year in an area of sub-Saharan Africa known as the meningitis belt.^[13] Smaller outbreaks may also occur in other areas of the world.^[13] The word meningitis comes from the Greek μῆνιγξ meninx, 'membrane', and the medical suffix -itis, 'inflammation'.^[14][15]

Mechanism[edit]

The meninges comprise three membranes that, together with the cerebrospinal fluid, enclose and protect the brain and spinal cord (the central nervous system). The pia mater is a delicate impermeable membrane that firmly adheres to the surface of the brain, following all the minor contours. The arachnoid mater (so named because of its spider-web-like appearance) is a loosely fitting sac on top of the pia mater. The subarachnoid space separates the arachnoid and pia mater membranes and is filled with cerebrospinal fluid. The outermost membrane, the dura mater, is a thick durable membrane, which is attached to both the arachnoid membrane and the skull.


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]

History[edit]

Some suggest that Hippocrates may have realized the existence of meningitis,^[17] and it seems that meningism was known to pre-Renaissance physicians such as Avicenna.^[92] The description of tuberculous meningitis, then called "dropsy in the brain", is often attributed to Edinburgh physician Sir Robert Whytt in a posthumous report that appeared in 1768, although the link with tuberculosis and its pathogen was not made until the next century.^[92][93]


It appears that epidemic meningitis is a relatively recent phenomenon.^[94] The first recorded major outbreak occurred in Geneva in 1805.^[94][95] Several other epidemics in Europe and the United States were described shortly afterward, and the first report of an epidemic in Africa appeared in 1840. African epidemics became much more common in the 20th century, starting with a major epidemic sweeping Nigeria and Ghana in 1905–1908.^[94]


The first report of bacterial infection underlying meningitis was by the Austrian bacteriologist Anton Weichselbaum, who in 1887 described the meningococcus.^[96] Mortality from meningitis was very high (over 90%) in early reports. In 1906, antiserum was produced in horses; this was developed further by the American scientist Simon Flexner and markedly decreased mortality from meningococcal disease.^[97][98] In 1944, penicillin was first reported to be effective in meningitis.^[99] The introduction in the late 20th century of Haemophilus vaccines led to a marked fall in cases of meningitis associated with this pathogen,^[60] and in 2002, evidence emerged that treatment with steroids could improve the prognosis of bacterial meningitis.^[75][78][98]