Meningitis

Clinical features In adults, the most common symptom of meningitis is a severe headache, occurring in almost 90% of cases of bacterial meningitis, followed by neck stiffness (the inability to flex the neck forward passively due to increased neck muscle tone and stiffness). The classic triad of diagnostic signs consists of neck stiffness, sudden high fever, and altered mental status; however, all three features are present in only 44–46% of bacterial meningitis cases. If none of the three signs are present, acute meningitis is extremely unlikely. Neck stiffness occurs in 70% of adults with bacterial meningitis. They do, however, have excellent specificity for meningitis: the signs rarely occur in other diseases. Meningitis caused by the bacterium Neisseria meningitidis (known as "meningococcal meningitis") can be differentiated from meningitis with other causes by a rapidly spreading petechial rash, which may precede other symptoms. Early complications developed severe meningococcal meningitis as a young child; in her case, the petechial rash progressed to gangrene and required amputation of all limbs. She survived the disease and became a poster child for a meningitis vaccination campaign in New Zealand. Additional problems may occur in the early stage of the illness. These may require specific treatment, and sometimes indicate severe illness or a worse prognosis. The infection may trigger sepsis, a systemic inflammatory response syndrome of falling blood pressure, fast heart rate, high or abnormally low temperature, and rapid breathing. Very low blood pressure may occur at an early stage, especially but not exclusively in meningococcal meningitis; this may lead to insufficient blood supply to other organs. The brain tissue may swell, pressure inside the skull may increase, and the swollen brain may herniate through the skull base. This may be noticed by a decreasing level of consciousness, loss of the pupillary light reflex, and abnormal posturing. The inflammation of the brain tissue may also obstruct the normal flow of CSF around the brain (hydrocephalus). Seizures may occur for various reasons; in children, seizures are common in the early stages of meningitis (in 30% of cases) and do not necessarily indicate an underlying cause. Seizures may result from increased pressure and from areas of inflammation in the brain tissue. Focal seizures (seizures that involve one limb or part of the body), persistent seizures, late-onset seizures, and those that are difficult to control with medication indicate a poorer long-term outcome. Inflammation of the meninges may lead to abnormalities of the cranial nerves, a group of nerves arising from the brain stem that supply the head and neck area and which control, among other functions, eye movement, facial muscles, and hearing. Visual symptoms and hearing loss may persist after an episode of meningitis. Inflammation of the brain (encephalitis) or its blood vessels (cerebral vasculitis), as well as the formation of blood clots in the veins (cerebral venous thrombosis), may all lead to weakness, loss of sensation, or abnormal movement or function of the part of the body supplied by the affected area of the brain. ==Causes==

Meningitis is typically caused by an infection. Most infections are due to viruses, and others due to bacteria, fungi, and parasites. Meningitis may also result from various non-infectious causes. and may cause meningitis in the newborn. • Older children are more commonly affected by Neisseria meningitidis (meningococcus) and Streptococcus pneumoniae (serotypes 6, 9, 14, 18, and 23), and those under five by Haemophilus influenzae type B (in countries that do not offer vaccination). A head injury potentially allows nasal cavity bacteria to enter the meningeal space. Similarly, devices in the brain and meninges, such as cerebral shunts, extraventricular drains, or Ommaya reservoirs, carry an increased risk of meningitis. In these cases, people are more likely to be infected with Staphylococci, Pseudomonas, and other Gram-negative bacteria. In rare cases, Enterococcus spp. can be responsible for meningitis, both community and hospital-acquired, usually as a secondary result of trauma or surgery, or due to intestinal diseases (e.g., strongyloidiasis). Tuberculous meningitis, which is meningitis caused by Mycobacterium tuberculosis, is more common in people from countries in which tuberculosis is endemic, but is also encountered in people with immune problems, such as AIDS. Recurrent bacterial meningitis may be caused by persisting anatomical defects, either congenital or acquired, or by disorders of the immune system. Anatomical defects allow continuity between the external environment and the nervous system. The most common cause of recurrent meningitis is a skull fracture, Mollaret's meningitis is a chronic recurrent form of herpes meningitis; it is thought to be caused by herpes simplex virus type 2. Fungal There are a number of risk factors for fungal meningitis, including the use of immunosuppressants (such as after organ transplantation), HIV/AIDS, and the loss of immunity associated with aging. It is uncommon in those with a normal immune system but has occurred with medication contamination. Symptom onset is typically more gradual, with headaches and fever being present for at least a couple of weeks before diagnosis. In Africa, cryptococcal meningitis is now the most common cause of meningitis in multiple studies, and it accounts for 20–25% of AIDS-related deaths in Africa. Other less common pathogenic fungi which can cause meningitis include: Coccidioides immitis, Histoplasma capsulatum, Blastomyces dermatitidis, and Candida species. Rarely, free-living parasitic amoebae can cause naegleriasis, also called amebic meningitis, and certain drugs (mainly non-steroidal anti-inflammatory drugs, antibiotics and intravenous immunoglobulins). It may also be caused by several inflammatory conditions, such as sarcoidosis (which is then called neurosarcoidosis), connective tissue disorders such as systemic lupus erythematosus, and certain forms of vasculitis (inflammatory conditions of the blood vessel wall), such as Behçet's disease. Epidermoid cysts and dermoid cysts may cause meningitis by releasing irritant matter into the subarachnoid space. Rarely, migraine may cause meningitis, but this diagnosis is usually only made when other causes have been eliminated. ==Mechanism==

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

Diagnosing meningitis as promptly as possible can improve outcomes. 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. This applies in 45% of all adult cases. The jolt accentuation test is not specific or sensitive enough to completely rule out meningitis. 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, Lumbar puncture of meningococci from a culture showing Gram-negative (pink) bacteria, often in pairs 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); in bacterial meningitis the pressure is usually elevated. 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. Various other specialized tests may be used to distinguish between different types of meningitis. A latex agglutination test may be positive in meningitis caused by Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Escherichia coli and group B streptococci; its routine use is not encouraged as it rarely leads to changes in treatment, but it may be used if other tests are not diagnostic. Similarly, the limulus lysate test may be positive in meningitis caused by Gram-negative bacteria, but it is of limited use unless other tests have been unhelpful. A diagnostic and therapeutic difficulty is "partially treated meningitis", where there are meningitis symptoms after receiving antibiotics (such as for presumptive sinusitis). When this happens, CSF findings may resemble those of viral meningitis, but antibiotic treatment may need to be continued until there is definitive positive evidence of a viral cause (e.g., a positive enterovirus PCR). ==Prevention==

For some causes of meningitis, protection can be provided in the long term through vaccination, or in the short term with antibiotics. Some behavioral measures may also be effective. Bacterial Bacterial and viral meningitis are contagious, but neither is as contagious as the common cold or flu. Both can be transmitted through droplets of respiratory secretions during close contact such as kissing, sneezing or coughing on someone, Similarly, immunization against mumps has led to a sharp fall in the number of cases of mumps meningitis, which before vaccination occurred in 15% of all cases of mumps. In countries where the vaccine for meningococcus group C was introduced, cases caused by this pathogen have decreased substantially. though the introduction of MenAfriVac (meningococcus group A vaccine) has demonstrated effectiveness in young people and has been described as a model for product development partnerships in resource-limited settings. Routine vaccination against Streptococcus pneumoniae with the pneumococcal conjugate vaccine (PCV), which is active against seven common serotypes of this pathogen, significantly reduces the incidence of pneumococcal meningitis. The pneumococcal polysaccharide vaccine, which covers 23 strains, is only administered to certain groups (e.g. those who have had a splenectomy, the surgical removal of the spleen); it does not elicit a significant immune response in all recipients, e.g. small children. Resistance to rifampicin has been noted to increase after use, which has caused some to recommend considering other agents. This applies to those with or without a CSF leak. ==Management==

Meningitis is potentially life-threatening and has a high mortality rate if untreated; Given that meningitis can cause many early severe complications, regular medical review is recommended to identify these complications early Bacterial meningitis Antibiotics Empiric antibiotics (treatment without exact diagnosis) should be started immediately, even before the results of the lumbar puncture and CSF analysis are known. The choice of initial treatment depends largely on the kind of bacteria that cause meningitis in a particular place and population. For instance, in the United Kingdom, empirical treatment consists of a third-generation cefalosporin such as cefotaxime or ceftriaxone. Empirical therapy may be chosen based on the person's age, whether the infection was preceded by a head injury, whether the person has undergone recent neurosurgery, and whether or not a cerebral shunt is present. Steroids Additional treatment with corticosteroids (usually dexamethasone) has shown some benefits, such as a reduction of hearing loss, and better short term neurological outcomes in adolescents and adults from high-income countries with low rates of HIV. Some research has found reduced rates of death Professional guidelines therefore recommend the commencement of dexamethasone or a similar corticosteroid just before the first dose of antibiotics is given, and continued for four days. Additional treatment with corticosteroids has a different role in children than in adults. Although the benefit of corticosteroids has been demonstrated in adults and children from high-income countries, their use in children from low-income countries is not supported by the evidence; the reason for this discrepancy is not clear. the incidence of which has decreased dramatically since the introduction of the Hib vaccine. Thus, corticosteroids are recommended for the treatment of pediatric meningitis if the cause is H. influenzae, and only if given before the first dose of antibiotics; other uses are controversial. It is not clear if any of these therapies are helpful or worsen outcomes in people with acute bacterial meningitis. Fungal meningitis Fungal meningitis, such as cryptococcal meningitis, is treated with long courses of high dose antifungals, such as amphotericin B and flucytosine. Raised intracranial pressure is common in fungal meningitis, and frequent (ideally daily) lumbar punctures to relieve the pressure are recommended, or a lumbar drain. ==Prognosis==

for meningitis per 100,000 inhabitants in 2004 Untreated, bacterial meningitis is almost always fatal. According to the WHO, bacterial meningitis has an overall mortality rate of 16.7% (with treatment). Viral meningitis, in contrast, tends to resolve spontaneously and is rarely fatal. With treatment, mortality (risk of death) from bacterial meningitis depends on the person's age and the underlying cause. Of newborns, 20–30% may die from an episode of bacterial meningitis. This risk is much lower in older children, whose mortality is about 2%, but rises again to about 19–37% in adults. In adults, 66% of all cases emerge without disability. The main problems are deafness (in 14%) and cognitive impairment (in 10%). ==Epidemiology==

Although meningitis is a notifiable disease in many countries, the exact incidence rate is unknown. In 2010 it was estimated that meningitis resulted in 420,000 deaths, excluding cryptococcal meningitis. leading to it being labeled the "meningitis belt". Epidemics typically occur in the dry season (December to June), and an epidemic wave can last two to three years, dying out during the intervening rainy seasons. Attack rates of 100–800 cases per 100,000 are encountered in this area, which is poorly served by medical care. Meningococci are the primary cause of these cases. Meningococcal disease occurs in epidemics in areas where many people live together for the first time, such as army barracks during mobilization, university and college campuses Although the pattern of epidemic cycles in Africa is not well understood, several factors have been associated with the development of epidemics in the meningitis belt. They include: medical conditions (immunological susceptibility of the population), demographic conditions (travel and large population displacements), socioeconomic conditions (overcrowding and poor living conditions), climatic conditions (drought and dust storms), and concurrent infections (acute respiratory infections). There are significant differences in the local distribution of causes for bacterial meningitis. For instance, while N. meningitides groups B and C cause most disease episodes in Europe, group A is found in Asia and continues to predominate in Africa, where it causes most of the major epidemics in the meningitis belt, accounting for about 80% to 85% of documented meningococcal meningitis cases. ==History==

Some suggest that Hippocrates may have realized the existence of meningitis, 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. It appears that epidemic meningitis is a relatively recent phenomenon. The first recorded major outbreak occurred in Geneva in 1805. Several other epidemics in Europe and the United States were described shortly afterward. The first report of an epidemic in Africa appeared in 1840. African epidemics became much more common in the 20th century, beginning with a major epidemic sweeping Nigeria and Ghana in 1905–1908. 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. In 1944, penicillin was first reported to be effective in meningitis. The introduction in the late 20th century of Haemophilus vaccines led to a marked fall in cases of meningitis associated with this pathogen, and in 2002, evidence emerged that treatment with steroids could improve the prognosis of bacterial meningitis. == See also ==