Meningitis
Encyclopedia
Meningitis is inflammation
of the protective membranes covering the brain
and spinal cord
, known collectively as the meninges
. The inflammation may be caused by infection with virus
es, bacteria
, or other microorganism
s, and less commonly by certain drugs
. 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
.
The most common symptoms of meningitis are headache
and neck stiffness associated with fever
, confusion
or altered consciousness
, vomiting, and an inability to tolerate light (photophobia
) or loud noises (phonophobia). Sometimes, especially in small children, only nonspecific symptoms may be present, such as irritability and drowsiness. If a rash
is present, it may indicate a particular cause of meningitis; for instance, meningitis caused by meningococcal bacteria may be accompanied by a characteristic rash.
A lumbar puncture
may be used to diagnose or exclude meningitis. This involves inserting a needle into the spinal canal
to extract a sample of cerebrospinal fluid
(CSF), the fluid that envelops the brain and spinal cord. The CSF is then examined in a medical laboratory. The usual treatment for meningitis is the prompt application of antibiotic
s and sometimes antiviral drug
s. In some situations, corticosteroid
drugs can also be used to prevent complications from overactive inflammation. Meningitis can lead to serious long-term consequences such as deafness, epilepsy
, hydrocephalus
and cognitive deficit
s, especially if not treated quickly. Some forms of meningitis (such as those associated with meningococci
, Haemophilus influenzae type B, pneumococci
or mumps virus
infections) may be prevented by immunization
.
and stiffness). The classic triad of diagnostic signs consists of nuchal rigidity, sudden high fever, and altered mental status; however, all three features are present in only 44–46% of all cases of bacterial meningitis. If none of the three signs is present, meningitis is extremely unlikely. Other signs commonly associated with meningitis include photophobia
(intolerance to bright light) and phonophobia (intolerance to loud noises). Small children often do not exhibit the aforementioned symptoms, and may only be irritable
and look unwell. In infants up to 6 months of age, bulging of the fontanelle
(the soft spot on top of a baby's head) may be present. Other features that might distinguish meningitis from less severe illnesses in young children are leg pain, cold extremities, and an abnormal skin color
.
Nuchal rigidity occurs in 70% of adult cases of bacterial meningitis. Other signs of meningism
include the presence of positive Kernig's sign or Brudzinski's sign. Kernig's sign is assessed with the patient lying supine
, with the hip and knee flexed to 90 degrees. In a patient with a positive Kernig's sign, pain limits passive extension of the knee. A positive Brudzinski's sign occurs when flexion of the neck causes involuntary flexion of the knee and hip. Although Kernig's and Brudzinski's signs are both commonly used to screen for meningitis, the sensitivity
of these tests is limited. They do, however, have very good specificity
for meningitis: the signs rarely occur in other diseases. Another test, known as the "jolt accentuation maneuver" helps determine whether meningitis is present in patients reporting fever and headache. The patient is told to rapidly rotate his or her head horizontally; if this does not make the headache worse, meningitis is unlikely.
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. The rash consists of numerous small, irregular purple or red spots ("petechiae") on the trunk, lower extremities
, mucous membranes, conjuctiva, and (occasionally) the palms of the hands or soles of the feet. The rash is typically non-blanching: the redness does not disappear when pressed with a finger or a glass tumbler. Although this rash is not necessarily present in meningococcal meningitis, it is relatively specific for the disease; it does, however, occasionally occur in meningitis due to other bacteria. Other clues as to the nature of the cause of meningitis may be the skin signs of hand, foot and mouth disease
and genital herpes, both of which are associated with various forms of viral meningitis.
People with meningitis may develop additional problems in the early stages of their illness. These may require specific treatment, and sometimes indicate severe illness or 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 early, especially but not exclusively in meningococcal illness; this may lead to insufficient blood supply to other organs. Disseminated intravascular coagulation
, the excessive activation of blood clotting
, may cause both the obstruction of blood flow
to organs and a paradoxical increase of bleeding risk. In meningococcal disease, gangrene
of limbs can occur. Severe meningococcal and pneumococcal infections may result in hemorrhaging of the adrenal gland
s, leading to Waterhouse-Friderichsen syndrome
, which is often lethal.
The brain tissue may swell
, with increasing pressure inside the skull
and a risk of swollen brain tissue causing herniation
. This may be noticed by a decreasing level of consciousness, loss of the pupillary light reflex, and abnormal posturing
. Inflammation of the brain tissue may also obstruct the normal flow of CSF around the brain (hydrocephalus
). Seizure
s may occur for various reasons; in children, seizures are common in the early stages of meningitis (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 are indicators of a poorer long-term outcome.
The 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 control eye movement, facial muscles and hearing, among other functions. Visual symptoms and hearing loss may persist after an episode of meningitis (see below). Inflammation of the brain (encephalitis
) or its blood vessel
s (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 in the brain.
from virus
es or microorganisms. Most cases are due to infection with viruses, with bacteria
, fungi, and parasites being the next most common causes. It may also result from various non-infectious causes.
that cause bacterial meningitis vary by age group. In premature babies
and newborns
up to three months old, common causes are group B streptococci
(subtypes III which normally inhabit the vagina
and are mainly a cause during the first week of life) and those that normally inhabit the digestive tract
such as Escherichia coli
(carrying K1 antigen). Listeria monocytogenes (serotype IVb) may affect the newborn and occurs in epidemics. Older children are more commonly affected by Neisseria meningitidis
(meningococcus), 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, see below). In adults, N. meningitidis and S. pneumoniae together cause 80% of all cases of bacterial meningitis, with increased risk of L. monocytogenes in those over 50 years old. Since the pneumococcal vaccine was introduced, however, rates of pneumococcal meningitis have declined in children and adults.
Recent trauma
to the skull gives bacteria in the nasal cavity the potential to enter the meningeal space. Similarly, individuals with a cerebral shunt
or related device (such as an extraventricular drain
or Ommaya reservoir
) are at increased risk of infection through those devices. In these cases, infections with staphylococci are more likely, as well as infections by pseudomonas
and other Gram-negative
bacilli. The same pathogens are also more common in those with an impaired immune system
. In a small proportion of people, an infection in the head and neck area, such as otitis media
or mastoiditis
, can lead to meningitis. Recipients of cochlear implant
s for hearing loss are at an increased risk of pneumococcal meningitis.
Tuberculous meningitis
, meningitis due to infection with Mycobacterium tuberculosis
, is more common in those from countries where tuberculosis
is common, but is also encountered in those 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 skull fracture
, particularly fractures that affect the base of the skull or extend towards the sinuses and petrous pyramids. A literature review of 363 reported cases of recurrent meningitis showed that 59% of cases are due to such anatomical abnormalities, 36% due to immune deficiencies (such as complement deficiency
, which predisposes especially to recurrent meningococcal meningitis), and 5% due to ongoing infections in areas adjacent to the meninges.
refers loosely to all cases of meningitis in which no bacterial infection can be demonstrated. This is usually due to viruses, but it may be due to bacterial infection that has already been partially treated, with disappearance of the bacteria from the meninges, or by infection in a space adjacent to the meninges (e.g. sinusitis
). Endocarditis
(infection of the heart valve
s with spread of small clusters of bacteria through the bloodstream) may cause aseptic meningitis. Aseptic meningitis may also result from infection with spirochetes, a type of bacteria that includes Treponema pallidum
(the cause of syphilis
) and Borrelia burgdorferi
(known for causing Lyme disease
). Meningitis may be encountered in cerebral malaria (malaria infecting the brain). Fungal meningitis
, e.g. due to Cryptococcus neoformans
, is typically seen in people with immune deficiency such as AIDS. Amoebic meningitis, meningitis due to infection with amoebae such as Naegleria fowleri
, is contracted from freshwater sources.
es, herpes simplex virus type 2
(and less commonly type 1), varicella zoster virus
(known for causing chickenpox
and shingles
), mumps virus
, HIV
, and LCMV
.
(a type of white blood cell) in the CSF. The most common parasites implicated are Angiostrongylus cantonensis, Gnathostoma spinigerum
, Schistosoma
, as well as the conditions cysticercosis
, toxocariasis
, baylisascariasis
, paragonimiasis
, and a number of rarer infections and noninfective conditions.
to the meninges (malignant meningitis
) and certain drugs
(mainly non-steroidal anti-inflammatory drug
s, antibiotic
s and intravenous immunoglobulin
s). 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 cyst
s and dermoid cyst
s may cause meningitis by releasing irritant matter into the subarachnoid space. Mollaret's meningitis
is a syndrome of recurring episodes of aseptic meningitis; it is thought to be caused by herpes simplex virus type 2
. Rarely, migraine
may cause meningitis, but this diagnosis is usually only made when other causes have been eliminated.
, enclose and protect the brain
and spinal cord
(the central nervous system
). The pia mater
is a very 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 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 upon mucous surfaces
such as the nasal cavity
. This is often in turn preceded by viral infections, which break down the normal barrier provided by the mucous 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 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 entrance of bacteria into the central nervous system
. When components of the bacterial cell membrane
are identified by the immune cells of the brain (astrocyte
s and microglia
), they respond by releasing large amounts of cytokine
s, 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 cell
s 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 a decreased blood flow and a third type of edema, "cytotoxic" edema. The three forms of cerebral edema all lead to an increased intracranial pressure
; together with the lowered blood pressure often encountered in acute infection, this means that it is harder for blood to enter the brain, and brain cell
s are deprived of oxygen and undergo apoptosis
(automated cell death
).
It is recognized that 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.
s are performed for markers of inflammation (e.g. C-reactive protein
, complete blood count
), as well as blood culture
s.
The most important test in identifying or ruling out meningitis is analysis of the cerebrospinal fluid through lumbar puncture
(LP, spinal tap). However, 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. This applies in 45% of all adult cases. 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, especially if this may be longer than 30 minutes. Often, CT or MRI scans are performed at a later stage to assess for complications of meningitis.
In severe forms of meningitis, monitoring of blood electrolytes may be important; for example, hyponatremia
is common in bacterial meningitis, due to a combination of factors including dehydration, the inappropriate excretion of the antidiuretic hormone (SIADH), or overly aggressive intravenous fluid administration
.
, 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 typically 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.
The CSF sample is examined for presence and types of white blood cell
s, red blood cell
s, protein
content and glucose
level. 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, and 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. The type of white blood cell predominantly present (see table) indicates whether meningitis is bacterial (usually neutrophil-predominant) or viral (usually lymphocyte-predominant), although in the beginning of the disease this is not always a reliable indicator. Less commonly, eosinophils predominate, suggesting parasitic or fungal etiology, among others.
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; in the newborn, glucose levels in CSF are normally higher, and a ratio below 0.6 (60%) is therefore considered abnormal. High levels of lactate
in CSF indicate a higher likelihood of bacterial meningitis, as does a higher white blood cell count.
Various more specialized tests may be used to distinguish between various 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. Polymerase chain reaction
(PCR) is a technique used to amplify small traces of bacterial DNA in order to detect the presence of bacterial or viral DNA in cerebrospinal fluid; it is a highly sensitive and specific test since only trace amounts of the infecting agent's DNA is required. It may identify bacteria in bacterial meningitis and may assist in distinguishing the various causes of viral meningitis (enterovirus
, herpes simplex virus 2
and mumps
in those not vaccinated for this). Serology
(identification of antibodies to viruses) may be useful in viral meningitis. If tuberculous meningitis is suspected, the sample is processed for Ziehl-Neelsen stain
, which has a low sensitivity, and tuberculosis culture, which takes a long time to process; PCR is being used increasingly. Diagnosis of cryptococcal meningitis can be made at low cost using an India ink
stain of the CSF; however, testing for cryptococcal antigen in blood or CSF is more sensitive, particularly in persons with AIDS.
A diagnostic and therapeutic conundrum is the "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).
and arachnoid
layers of the meninges covering the brain and spinal cord. Neutrophil granulocyte
s tend to have migrated to the cerebrospinal fluid and the base of the brain, along with cranial nerves and the spinal cord
, may be surrounded with pus
—as may the meningeal vessels
.
or flu. Both can be transmitted through droplets of respiratory secretions during close contact such as kissing, sneezing or coughing on someone, but cannot be spread by only breathing the air where a person with meningitis has been. Viral meningitis is typically caused by Enteroviruses, and is most commonly spread through fecal contamination. By changing behavior to prevent the causes of transmission, infection by viruses and bacteria can be prevented.
, or in the short term with antibiotic
s.
Since the 1980s, many countries have included immunization against Haemophilus influenzae type B
in their routine childhood vaccination schemes. This has practically eliminated this pathogen as a cause of meningitis in young children in those countries. In the countries where the disease burden is highest, however, the vaccine is still too expensive. Similarly, immunization against mumps has led to a sharp fall in the number of cases of mumps meningitis, which prior to vaccination occurred in 15% of all cases of mumps.
Meningococcus vaccines
exist against groups A, C, W135 and Y. In countries where the vaccine for meningococcus group C was introduced, cases caused by this pathogen have decreased substantially. A quadrivalent vaccine now exists, which combines all four vaccines. Immunization with the ACW135Y vaccine against four strains is now a visa requirement for taking part in the Hajj. Development of a vaccine against group B meningococci has proved much more difficult, as its surface proteins (which would normally be used to make a vaccine) only elicit a weak response from the immune system
, or cross-react with normal human proteins. Still, some countries (New Zealand
, Cuba
, Norway
and Chile
) have developed vaccines against local strains of group B meningococci; some have shown good results and are used in local immunization schedules. In Africa, until recently, the approach for prevention and control of meningococcal epidemics was based on early detection of the disease and emergency reactive mass vaccination of the at-risk population with bivalent A/C or trivalent A/C/W135 polysaccharide vaccines, though the introduction of MenAfriVac
(meningiococcus 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 in 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.
Childhood vaccination with Bacillus Calmette-Guérin
has been reported to significantly reduce the rate of tuberculous meningitis, but its waning effectiveness in adulthood has prompted a search for a better vaccine.
Short-term antibiotic prophylaxis is also a method of prevention, particularly of meningococcal meningitis. In cases of meningococcal meningitis, prophylactic treatment of close contacts with antibiotics (e.g. rifampicin
, ciprofloxacin
or ceftriaxone
) can reduce their risk of contracting the condition, but does not protect against future infections.
be administered before transfer to hospital. Intravenous fluids should be administered if hypotension
(low blood pressure) or shock are present. Given that meningitis can cause a number of early severe complications, regular medical review is recommended to identify these complications early, as well as admission to an intensive care unit
if deemed necessary.
Mechanical ventilation
may be needed if the level of consciousness is very low, or if there is evidence of respiratory failure
. If there are signs of raised intracranial pressure, measures to monitor the pressure may be taken; this would allow the optimization of the cerebral perfusion pressure
and various treatments to decrease the intracranial pressure with medication (e.g. mannitol
). Seizures are treated with anticonvulsant
s. Hydrocephalus (obstructed flow of CSF) may require insertion of a temporary or long-term drainage device, such as a cerebral shunt
.
Empiric antibiotics (treatment without exact diagnosis) must 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. For instance, in the United Kingdom
empirical treatment
consists of a third-generation cefalosporin such as cefotaxime
or ceftriaxone
. In the USA, where resistance to cefalosporins is increasingly found in streptococci, addition of vancomycin
to the initial treatment is recommended. Empirical therapy may be chosen on the basis of the age of the patient, whether the infection was preceded by head injury
, whether the patient has undergone neurosurgery
and whether or not a cerebral shunt is present. For instance, in young children and those over 50 years of age, as well as those who are immunocompromised, addition of ampicillin
is recommended to cover Listeria monocytogenes. Once the Gram stain results become available, and the broad type of bacterial cause is known, it may be possible to change the antibiotics to those likely to deal with the presumed group of pathogens.
The results of the CSF culture
generally take longer to become available (24–48 hours). Once they do, empiric therapy may be switched to specific antibiotic therapy targeted to the specific causative organism and its sensitivities to antibiotics. For an antibiotic to be effective in meningitis, it must not only be active against the pathogenic bacterium, but also reach the meninges in adequate quantities; some antibiotics have inadequate penetrance and therefore have little use in meningitis. Most of the antibiotics used in meningitis have not been tested directly on meningitis patients in clinical trial
s. Rather, the relevant knowledge has mostly derived from laboratory studies in rabbit
s.
Tuberculous meningitis requires prolonged treatment with antibiotics. While tuberculosis of the lungs is typically treated for six months, those with tuberculous meningitis are typically treated for a year or longer. In tuberculous meningitis there is a strong evidence base for treatment with corticosteroids, although this evidence is restricted to those without AIDS.
treatment with corticosteroids (usually dexamethasone
) has been shown in some studies to reduce rates of mortality, severe hearing loss and neurological damage in adolescents and adults from high income countries which have low rates of HIV. The likely mechanism is suppression of overactive inflammation. 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. Given that most of the benefit of the treatment is confined to those with pneumococcal meningitis, some guidelines suggest that dexamethasone be discontinued if another cause for meningitis is identified.
Adjuvant corticosteroids have a different role in children than in adults. Though the benefit of corticosteroids has been demonstrated in adults as well as in children from high-income countries, their use in children from low-income
countries is not supported by evidence; the reason for this discrepancy is not clear. Even in high-income countries, the benefit of corticosteroids is only seen when they are given prior to the first dose of antibiotics, and is greatest in cases of H. influenzae meningitis, the incidence of which has decreased dramatically since the introduction of the Hib vaccine
. Thus, corticosteroids are recommended in the treatment of pediatric meningitis if the cause is H. influenzae and only if given prior to the first dose of antibiotics, whereas other uses are controversial.
A 2010 analysis of previous studies has shown that the benefit from steroids may not be as significant as previously found. The one possible significant benefit is reduction of hearing loss in survivors, and adverse neurological outcomes.
typically requires supportive therapy only; most viruses responsible for causing meningitis are not amenable to specific treatment. Viral meningitis tends to run a more benign course than bacterial meningitis. Herpes simplex virus
and varicella zoster virus
may respond to treatment with antiviral drugs such as aciclovir
, but there are no clinical trials that have specifically addressed whether this treatment is effective. Mild cases of viral meningitis can be treated at home with conservative measures such as fluid, bedrest, and analgesics.
, 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 alternatively a lumbar drain.
(risk of death) from bacterial meningitis depends on the age of the patient and the underlying cause. Of the newborn patients, 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. Risk of death is predicted by various factors apart from age, such as the pathogen and the time it takes for the pathogen to be cleared from the cerebrospinal fluid, the severity of the generalized illness, decreased level of consciousness or abnormally low count of white blood cells in the CSF. Meningitis caused by H. influenzae and meningococci has a better prognosis compared to cases caused by group B streptococci, coliforms and S. pneumonia. In adults, too, meningococcal meningitis has a lower mortality (3–7%) than pneumococcal disease.
In children there are several potential disabilities which result from damage to the nervous system. Sensorineural hearing loss
, epilepsy
, learning
and behavioral difficulties, as well as decreased intelligence, occur in about 15% of survivors. Some of the hearing loss may be reversible. In adults, 66% of all cases emerge without disability. The main problems are deafness (in 14%) and cognitive impairment
(in 10%).
Although meningitis is a notifiable disease
in many countries, the exact incidence
rate is unknown. Bacterial meningitis occurs in about 3 people per 100,000 annually in Western countries
. Population-wide studies have shown that viral meningitis is more common, at 10.9 per 100,000, and occurs more often in the summer. In Brazil, the rate of bacterial meningitis is higher, at 45.8 per 100,000 annually. Sub-Saharan Africa
has been plagued by large epidemics of meningococcal meningitis for over a century, 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
. These cases are predominantly caused by meningococci. The largest epidemic ever recorded in history swept across the entire region in 1996–1997, causing over 250,000 cases and 25,000 deaths.
Meningococcal disease occurs in epidemics in areas where many people live together for the first time, such as army barracks during mobilization, college campuses and the annual Hajj
pilgrimage. 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.
may have realized the existence of meningitis, and it seems that meningism was known to pre-Renaissance physicians such as Avicenna
. 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, 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.
The first report of bacterial infection underlying meningitis was by the Austrian bacteriologist Anton Weichselbaum
, who in 1887 described the meningococcus. 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.
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
of the protective membranes covering the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
and spinal cord
Spinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...
, known collectively as the meninges
Meninges
The meninges is the system of membranes which envelopes the central nervous system. The meninges consist of three layers: the dura mater, the arachnoid mater, and the pia mater. The primary function of the meninges and of the cerebrospinal fluid is to protect the central nervous system.-Dura...
. The inflammation may be caused by infection with virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
es, bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
, or other microorganism
Microorganism
A microorganism or microbe is a microscopic organism that comprises either a single cell , cell clusters, or no cell at all...
s, and less commonly by certain drugs
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
. 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
Medical emergency
A medical emergency is an injury or illness that is acute and poses an immediate risk to a person's life or long term health. These emergencies may require assistance from another person, who should ideally be suitably qualified to do so, although some of these emergencies can be dealt with by the...
.
The most common symptoms of meningitis are headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
and neck stiffness associated with fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
, confusion
Mental confusion
Confusion of a pathological degree usually refers to loss of orientation sometimes accompanied by disordered consciousness and often memory Confusion (from Latin confusĭo, -ōnis, noun of action from confundere "to pour together", also "to confuse") of a pathological degree usually refers to loss...
or altered consciousness
Consciousness
Consciousness is a term that refers to the relationship between the mind and the world with which it interacts. It has been defined as: subjectivity, awareness, the ability to experience or to feel, wakefulness, having a sense of selfhood, and the executive control system of the mind...
, vomiting, and an inability to tolerate light (photophobia
Photophobia
Photophobia is a symptom of abnormal intolerance to visual perception of light. As a medical symptom photophobia is not a morbid fear or phobia, but an experience of discomfort or pain to the eyes due to light exposure or by presence of actual physical photosensitivity of the eyes, though the term...
) or loud noises (phonophobia). Sometimes, especially in small children, only nonspecific symptoms may be present, such as irritability and drowsiness. If a rash
Rash
A rash is a change of the skin which affects its color, appearance or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracked or blistered, swell and may be painful. The causes, and...
is present, it may indicate a particular cause of meningitis; for instance, meningitis caused by meningococcal bacteria may be accompanied by a characteristic rash.
A lumbar puncture
Lumbar puncture
A lumbar puncture is a diagnostic and at times therapeutic procedure that is performed in order to collect a sample of cerebrospinal fluid for biochemical, microbiological, and cytological analysis, or very rarely as a treatment to relieve increased intracranial pressure.-Indications:The...
may be used to diagnose or exclude meningitis. This involves inserting a needle into the spinal canal
Spinal canal
The spinal canal is the space in vertebrae through which the spinal cord passes. It is a process of the dorsal human body cavity. This canal is enclosed within the vertebral foramen of the vertebrae...
to extract a sample of cerebrospinal fluid
Cerebrospinal fluid
Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...
(CSF), the fluid that envelops the brain and spinal cord. The CSF is then examined in a medical laboratory. The usual treatment for meningitis is the prompt application of antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
s and sometimes antiviral drug
Antiviral drug
Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses...
s. In some situations, corticosteroid
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...
drugs can also be used to prevent complications from overactive inflammation. Meningitis can lead to serious long-term consequences such as deafness, epilepsy
Epilepsy
Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...
, hydrocephalus
Hydrocephalus
Hydrocephalus , also known as "water in the brain," is a medical condition in which there is an abnormal accumulation of cerebrospinal fluid in the ventricles, or cavities, of the brain. This may cause increased intracranial pressure inside the skull and progressive enlargement of the head,...
and cognitive deficit
Cognitive deficit
Cognitive deficit, also known as cognitive impairment is an inclusive term to describe any characteristic that acts as a barrier to cognitive performance...
s, especially if not treated quickly. Some forms of meningitis (such as those associated with meningococci
Neisseria meningitidis
Neisseria meningitidis, often referred to as meningococcus, is a bacterium that can cause meningitis and other forms of meningococcal disease such as meningococcemia, a life threatening sepsis. N. meningitidis is a major cause of morbidity and mortality during childhood in industrialized countries...
, Haemophilus influenzae type B, pneumococci
Streptococcus pneumoniae
Streptococcus pneumoniae, or pneumococcus, is Gram-positive, alpha-hemolytic, aerotolerant anaerobic member of the genus Streptococcus. A significant human pathogenic bacterium, S...
or mumps virus
Mumps virus
Mumps virus is the causative agent of mumps, a well-known common childhood disease characterised by swelling of the parotid glands and other epithelial tissues, causing high morbidity and in some cases more serious complications such as deafness...
infections) may be prevented by immunization
Immunization
Immunization, or immunisation, is the process by which an individual's immune system becomes fortified against an agent ....
.
Clinical features
In adults, a severe headache is the most common symptom of meningitis – occurring in almost 90% of cases of bacterial meningitis, followed by nuchal rigidity (inability to flex the neck forward passively due to increased neck muscle toneMuscle tone
In physiology, medicine, and anatomy, muscle tone is the continuous and passive partial contraction of the muscles, or the muscle’s resistance to passive stretch during resting state. It helps maintain posture, and it declines during REM sleep.-Purpose:Unconscious nerve impulses maintain the...
and stiffness). The classic triad of diagnostic signs consists of nuchal rigidity, sudden high fever, and altered mental status; however, all three features are present in only 44–46% of all cases of bacterial meningitis. If none of the three signs is present, meningitis is extremely unlikely. Other signs commonly associated with meningitis include photophobia
Photophobia
Photophobia is a symptom of abnormal intolerance to visual perception of light. As a medical symptom photophobia is not a morbid fear or phobia, but an experience of discomfort or pain to the eyes due to light exposure or by presence of actual physical photosensitivity of the eyes, though the term...
(intolerance to bright light) and phonophobia (intolerance to loud noises). Small children often do not exhibit the aforementioned symptoms, and may only be irritable
Irritability
Irritability is an excessive response to stimuli. The term is used for both the physiological reaction to stimuli and for the pathological, abnormal or excessive sensitivity to stimuli; It is usually used to refer to anger or frustration....
and look unwell. In infants up to 6 months of age, bulging of the fontanelle
Fontanelle
A fontanelle is an anatomical feature on an infant's skull.-Anatomy:Fontanelles are soft spots on a baby's head which, during birth, enable the bony plates of the skull to flex, allowing the child's head to pass through the birth canal. The ossification of the bones of the skull causes the...
(the soft spot on top of a baby's head) may be present. Other features that might distinguish meningitis from less severe illnesses in young children are leg pain, cold extremities, and an abnormal skin color
Human skin color
Human skin color is primarily due to the presence of melanin in the skin. Skin color ranges from almost black to white with a pinkish tinge due to blood vessels underneath. Variation in natural skin color is mainly due to genetics, although the evolutionary causes are not completely certain...
.
Nuchal rigidity occurs in 70% of adult cases of bacterial meningitis. Other signs of meningism
Meningism
Meningism is the triad of nuchal rigidity , photophobia and headache. It is a sign of irritation of the meninges, such as seen in meningitis, subarachnoid hemorrhages and various other diseases...
include the presence of positive Kernig's sign or Brudzinski's sign. Kernig's sign is assessed with the patient lying supine
Supine position
The supine position is a position of the body: lying down with the face up, as opposed to the prone position, which is face down, sometimes with the hands behind the head or neck. When used in surgical procedures, it allows access to the peritoneal, thoracic and pericardial regions; as well as the...
, with the hip and knee flexed to 90 degrees. In a patient with a positive Kernig's sign, pain limits passive extension of the knee. A positive Brudzinski's sign occurs when flexion of the neck causes involuntary flexion of the knee and hip. Although Kernig's and Brudzinski's signs are both commonly used to screen for meningitis, the sensitivity
Sensitivity and specificity
Sensitivity and specificity are statistical measures of the performance of a binary classification test, also known in statistics as classification function. Sensitivity measures the proportion of actual positives which are correctly identified as such Sensitivity and specificity are statistical...
of these tests is limited. They do, however, have very good specificity
Sensitivity and specificity
Sensitivity and specificity are statistical measures of the performance of a binary classification test, also known in statistics as classification function. Sensitivity measures the proportion of actual positives which are correctly identified as such Sensitivity and specificity are statistical...
for meningitis: the signs rarely occur in other diseases. Another test, known as the "jolt accentuation maneuver" helps determine whether meningitis is present in patients reporting fever and headache. The patient is told to rapidly rotate his or her head horizontally; if this does not make the headache worse, meningitis is unlikely.
Meningitis caused by the bacterium Neisseria meningitidis
Neisseria meningitidis
Neisseria meningitidis, often referred to as meningococcus, is a bacterium that can cause meningitis and other forms of meningococcal disease such as meningococcemia, a life threatening sepsis. N. meningitidis is a major cause of morbidity and mortality during childhood in industrialized countries...
(known as "meningococcal meningitis") can be differentiated from meningitis with other causes by a rapidly spreading petechial rash which may precede other symptoms. The rash consists of numerous small, irregular purple or red spots ("petechiae") on the trunk, lower extremities
Human leg
The human leg is the entire lower extremity or limb of the human body, including the foot, thigh and even the hip or gluteal region; however, the precise definition in human anatomy refers only to the section of the lower limb extending from the knee to the ankle.Legs are used for standing,...
, mucous membranes, conjuctiva, and (occasionally) the palms of the hands or soles of the feet. The rash is typically non-blanching: the redness does not disappear when pressed with a finger or a glass tumbler. Although this rash is not necessarily present in meningococcal meningitis, it is relatively specific for the disease; it does, however, occasionally occur in meningitis due to other bacteria. Other clues as to the nature of the cause of meningitis may be the skin signs of hand, foot and mouth disease
Hand, foot and mouth disease
Hand, foot and mouth disease is a human syndrome caused by intestinal viruses of the Picornaviridae family. The most common strains causing HFMD are Coxsackie A virus and Enterovirus 71 ....
and genital herpes, both of which are associated with various forms of viral meningitis.
Early complications
Sepsis
Sepsis is a potentially deadly medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues...
, a systemic inflammatory response syndrome
Systemic inflammatory response syndrome
Systemic inflammatory response syndrome is an inflammatory state affecting the whole body, frequently a response of the immune system to infection, but not necessarily so...
of falling blood pressure
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
, fast heart rate
Tachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...
, high or abnormally low temperature and rapid breathing
Tachypnea
Tachypnea means rapid breathing. Any rate between 12-20 breaths per minute is normal. Tachypnea is a respiration rate greater than 20 breaths per minute. - Distinction from other breathing terms :...
. Very low blood pressure may occur early, especially but not exclusively in meningococcal illness; this may lead to insufficient blood supply to other organs. Disseminated intravascular coagulation
Disseminated intravascular coagulation
Disseminated intravascular coagulation , also known as disseminated intravascular coagulopathy or consumptive coagulopathy, is a pathological activation of coagulation mechanisms that happens in response to a variety of diseases. DIC leads to the formation of small blood clots inside the blood...
, the excessive activation of blood clotting
Coagulation
Coagulation is a complex process by which blood forms clots. It is an important part of hemostasis, the cessation of blood loss from a damaged vessel, wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel...
, may cause both the obstruction of blood flow
Blood flow
Blood flow is the continuous running of blood in the cardiovascular system.The human body is made up of several processes all carrying out various functions. We have the gastrointestinal system which aids the digestion and the absorption of food...
to organs and a paradoxical increase of bleeding risk. In meningococcal disease, gangrene
Gangrene
Gangrene is a serious and potentially life-threatening condition that arises when a considerable mass of body tissue dies . This may occur after an injury or infection, or in people suffering from any chronic health problem affecting blood circulation. The primary cause of gangrene is reduced blood...
of limbs can occur. Severe meningococcal and pneumococcal infections may result in hemorrhaging of the adrenal gland
Adrenal gland
In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...
s, leading to Waterhouse-Friderichsen syndrome
Waterhouse-Friderichsen syndrome
Waterhouse-Friderichsen syndrome or hemorrhagic adrenalitis or Fulminant meningococcemia, is a disease of the adrenal glands most commonly caused by the bacterium Neisseria meningitidis. The infection leads to massive hemorrhage into one or both adrenal glands...
, which is often lethal.
The brain tissue may swell
Cerebral edema
Cerebral edema or cerebral œdema is an excess accumulation of water in the intracellular or extracellular spaces of the brain.-Vasogenic:Due to a breakdown of tight endothelial junctions which make up the blood-brain barrier...
, with increasing pressure inside the skull
Intracranial pressure
Intracranial pressure is the pressure inside the skull and thus in the brain tissue and cerebrospinal fluid . The body has various mechanisms by which it keeps the ICP stable, with CSF pressures varying by about 1 mmHg in normal adults through shifts in production and absorption of CSF...
and a risk of swollen brain tissue causing herniation
Brain herniation
Brain herniation, also known as cistern obliteration, is a deadly side effect of very high intracranial pressure that occurs when the brain shifts across structures within the skull...
. This may be noticed by a decreasing level of consciousness, loss of the pupillary light reflex, and abnormal posturing
Abnormal posturing
Abnormal posturing is an involuntary flexion or extension of the arms and legs, indicating severe brain injury. It occurs when one set of muscles becomes incapacitated while the opposing set is not, and an external stimulus such as pain causes the working set of muscles to contract. The posturing...
. Inflammation of the brain tissue may also obstruct the normal flow of CSF around the brain (hydrocephalus
Hydrocephalus
Hydrocephalus , also known as "water in the brain," is a medical condition in which there is an abnormal accumulation of cerebrospinal fluid in the ventricles, or cavities, of the brain. This may cause increased intracranial pressure inside the skull and progressive enlargement of the head,...
). Seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...
s may occur for various reasons; in children, seizures are common in the early stages of meningitis (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
Focal seizures
Partial seizures are seizures which affect only a part of the brain at onset. The brain is divided into two hemispheres, each consisting of four lobes - the frontal, temporal, parietal and occipital lobes...
(seizures that involve one limb or part of the body), persistent seizures, late-onset seizures and those that are difficult to control with medication are indicators of a poorer long-term outcome.
The inflammation of the meninges may lead to abnormalities of the cranial nerves
Cranial nerves
Cranial nerves are nerves that emerge directly from the brain, in contrast to spinal nerves, which emerge from segments of the spinal cord. In humans, there are traditionally twelve pairs of cranial nerves...
, a group of nerves arising from the brain stem
Brain stem
In vertebrate anatomy the brainstem is the posterior part of the brain, adjoining and structurally continuous with the spinal cord. The brain stem provides the main motor and sensory innervation to the face and neck via the cranial nerves...
that supply the head and neck area and control eye movement, facial muscles and hearing, among other functions. Visual symptoms and hearing loss may persist after an episode of meningitis (see below). Inflammation of the brain (encephalitis
Encephalitis
Encephalitis is an acute inflammation of the brain. Encephalitis with meningitis is known as meningoencephalitis. Symptoms include headache, fever, confusion, drowsiness, and fatigue...
) or its blood vessel
Blood vessel
The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...
s (cerebral vasculitis
Cerebral vasculitis
Cerebral vasculitis or central nervous system vasculitis is vasculitis involving the brain and occasionally the spinal cord...
), as well as the formation of blood clots
Thrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...
in the veins (cerebral venous thrombosis
Cerebral venous sinus thrombosis
Cerebral venous sinus thrombosis is a rare form of stroke that results from thrombosis of the dural venous sinuses, which drain blood from the brain. Symptoms may include headache, abnormal vision, any of the symptoms of stroke such as weakness of the face and limbs on one side of the body, and...
), may all lead to weakness, loss of sensation, or abnormal movement or function of the part of the body supplied by the affected area in the brain.
Causes
Meningitis is usually caused by infectionInfection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
from virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
es or microorganisms. Most cases are due to infection with viruses, with bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
, fungi, and parasites being the next most common causes. It may also result from various non-infectious causes.
Bacterial
The types of bacteriaBacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
that cause bacterial meningitis vary by age group. In premature babies
Premature birth
In humans preterm birth refers to the birth of a baby of less than 37 weeks gestational age. The cause for preterm birth is in many situations elusive and unknown; many factors appear to be associated with the development of preterm birth, making the reduction of preterm birth a challenging...
and newborns
Infant
A newborn or baby is the very young offspring of a human or other mammal. A newborn is an infant who is within hours, days, or up to a few weeks from birth. In medical contexts, newborn or neonate refers to an infant in the first 28 days after birth...
up to three months old, common causes are group B streptococci
Group B Streptococcus
Infection with Group B Streptococcus , also known as 'Streptococcus agalactiae' and more colloquially as Strep B and group B Strep, can cause serious illness and sometimes death, especially in newborn infants, the elderly, and patients with compromised immune systems...
(subtypes III which normally inhabit the vagina
Vagina
The vagina is a fibromuscular tubular tract leading from the uterus to the exterior of the body in female placental mammals and marsupials, or to the cloaca in female birds, monotremes, and some reptiles. Female insects and other invertebrates also have a vagina, which is the terminal part of the...
and are mainly a cause during the first week of life) and those that normally inhabit the digestive tract
Gastrointestinal tract
The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
such as Escherichia coli
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
(carrying K1 antigen). Listeria monocytogenes (serotype IVb) may affect the newborn and occurs in epidemics. Older children are more commonly affected by Neisseria meningitidis
Neisseria meningitidis
Neisseria meningitidis, often referred to as meningococcus, is a bacterium that can cause meningitis and other forms of meningococcal disease such as meningococcemia, a life threatening sepsis. N. meningitidis is a major cause of morbidity and mortality during childhood in industrialized countries...
(meningococcus), Streptococcus pneumoniae
Streptococcus pneumoniae
Streptococcus pneumoniae, or pneumococcus, is Gram-positive, alpha-hemolytic, aerotolerant anaerobic member of the genus Streptococcus. A significant human pathogenic bacterium, S...
(serotypes 6, 9, 14, 18 and 23) and those under five by Haemophilus influenzae type B
Haemophilus influenzae
Haemophilus influenzae, formerly called Pfeiffer's bacillus or Bacillus influenzae, Gram-negative, rod-shaped bacterium first described in 1892 by Richard Pfeiffer during an influenza pandemic. A member of the Pasteurellaceae family, it is generally aerobic, but can grow as a facultative anaerobe. H...
(in countries that do not offer vaccination, see below). In adults, N. meningitidis and S. pneumoniae together cause 80% of all cases of bacterial meningitis, with increased risk of L. monocytogenes in those over 50 years old. Since the pneumococcal vaccine was introduced, however, rates of pneumococcal meningitis have declined in children and adults.
Recent trauma
Physical trauma
Trauma refers to "a body wound or shock produced by sudden physical injury, as from violence or accident." It can also be described as "a physical wound or injury, such as a fracture or blow." Major trauma can result in secondary complications such as circulatory shock, respiratory failure and death...
to the skull gives bacteria in the nasal cavity the potential to enter the meningeal space. Similarly, individuals with a cerebral shunt
Cerebral shunt
Cerebral shunts are commonly used to treat hydrocephalus, the swelling of the brain due to excess buildup of cerebrospinal fluid . If left unchecked, the cerebral spinal fluid can build up leading to an increase in intracranial pressure which can lead to intracranial hematoma, cerebral edema,...
or related device (such as an extraventricular drain
Extraventricular drain
An external ventricular drain , also known as a ventriculostomy, is a device used in neurosurgery that relieves raised intracranial pressure and hydrocephalus when the normal flow of cerebrospinal fluid around the brain is obstructed...
or Ommaya reservoir
Ommaya reservoir
An Ommaya reservoir is an intraventricular catheter system that can be used for the aspiration of cerebrospinal fluid or for the delivery of drugs into the cerebrospinal fluid. It consists of a catheter in one lateral ventricle attached to a reservoir implanted under the scalp...
) are at increased risk of infection through those devices. In these cases, infections with staphylococci are more likely, as well as infections by pseudomonas
Pseudomonas
Pseudomonas is a genus of gammaproteobacteria, belonging to the family Pseudomonadaceae containing 191 validly described species.Recently, 16S rRNA sequence analysis has redefined the taxonomy of many bacterial species. As a result, the genus Pseudomonas includes strains formerly classified in the...
and other Gram-negative
Gram-negative
Gram-negative bacteria are bacteria that do not retain crystal violet dye in the Gram staining protocol. In a Gram stain test, a counterstain is added after the crystal violet, coloring all Gram-negative bacteria with a red or pink color...
bacilli. The same pathogens are also more common in those with an impaired immune system
Immunodeficiency
Immunodeficiency is a state in which the immune system's ability to fight infectious disease is compromised or entirely absent. Immunodeficiency may also decrease cancer immunosurveillance. Most cases of immunodeficiency are acquired but some people are born with defects in their immune system,...
. In a small proportion of people, an infection in the head and neck area, such as otitis media
Otitis media
Otitis media is inflammation of the middle ear, or a middle ear infection.It occurs in the area between the tympanic membrane and the inner ear, including a duct known as the eustachian tube. It is one of the two categories of ear inflammation that can underlie what is commonly called an earache,...
or mastoiditis
Mastoiditis
Mastoiditis is an infection of mastoid process, the portion of the temporal bone of the skull that is behind the ear which contains open, air-containing spaces. It is usually caused by untreated acute otitis media and used to be a leading cause of child mortality. With the development of...
, can lead to meningitis. Recipients of cochlear implant
Cochlear implant
A cochlear implant is a surgically implanted electronic device that provides a sense of sound to a person who is profoundly deaf or severely hard of hearing...
s for hearing loss are at an increased risk of pneumococcal meningitis.
Tuberculous meningitis
Tuberculous meningitis
Tuberculous meningitis is also known as TB meningitis or tubercular meningitis.Tuberculous meningitis is Mycobacterium tuberculosis infection of the meninges—the system of membranes which envelops the central nervous system. It is the most common form of CNS tuberculosis.-Clinical features:Fever...
, meningitis due to infection with Mycobacterium tuberculosis
Mycobacterium tuberculosis
Mycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...
, is more common in those from countries where tuberculosis
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
is common, but is also encountered in those with immune problems, such as AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
.
Recurrent bacterial meningitis may be caused by persisting anatomical defects, either congenital or acquired, or by disorders of the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
. Anatomical defects allow continuity between the external environment and the nervous system
Nervous system
The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...
. The most common cause of recurrent meningitis is skull fracture
Skull fracture
A skull fracture is a break in one or more of the bones in the skull usually occurring as a result of blunt force trauma. If the force of the impact is excessive the bone may fracture at or near the site of the impact...
, particularly fractures that affect the base of the skull or extend towards the sinuses and petrous pyramids. A literature review of 363 reported cases of recurrent meningitis showed that 59% of cases are due to such anatomical abnormalities, 36% due to immune deficiencies (such as complement deficiency
Complement deficiency
Complement deficiency is an immunodeficiency of absent or suboptimal functioning of one of the complement system proteins.The disorders can be divided into two categories:...
, which predisposes especially to recurrent meningococcal meningitis), and 5% due to ongoing infections in areas adjacent to the meninges.
Aseptic
The term aseptic meningitisAseptic meningitis
Aseptic meningitis, or sterile meningitis, is a condition in which the layers lining the brain, meninges, become inflamed and a pyogenic bacterial source is not to blame. Meningitis is diagnosed on a history of characteristic symptoms and certain examination findings...
refers loosely to all cases of meningitis in which no bacterial infection can be demonstrated. This is usually due to viruses, but it may be due to bacterial infection that has already been partially treated, with disappearance of the bacteria from the meninges, or by infection in a space adjacent to the meninges (e.g. sinusitis
Sinusitis
Sinusitis is inflammation of the paranasal sinuses, which may be due to infection, allergy, or autoimmune issues. Most cases are due to a viral infection and resolve over the course of 10 days...
). Endocarditis
Endocarditis
Endocarditis is an inflammation of the inner layer of the heart, the endocardium. It usually involves the heart valves . Other structures that may be involved include the interventricular septum, the chordae tendineae, the mural endocardium, or even on intracardiac devices...
(infection of the heart valve
Heart valve
A heart valve normally allows blood flow in only one direction through the heart. The four valves commonly represented in a mammalian heart determine the pathway of blood flow through the heart...
s with spread of small clusters of bacteria through the bloodstream) may cause aseptic meningitis. Aseptic meningitis may also result from infection with spirochetes, a type of bacteria that includes Treponema pallidum
Treponema pallidum
Treponema pallidum is a species of spirochaete bacterium with subspecies that cause treponemal diseases such as syphilis, bejel, pinta and yaws. The treponemes have a cytoplasmic and outer membrane...
(the cause of syphilis
Syphilis
Syphilis is a sexually transmitted infection caused by the spirochete bacterium Treponema pallidum subspecies pallidum. The primary route of transmission is through sexual contact; however, it may also be transmitted from mother to fetus during pregnancy or at birth, resulting in congenital syphilis...
) and Borrelia burgdorferi
Borrelia burgdorferi
Borrelia burgdorferi is a species of Gram negative bacteria of the spirochete class of the genus Borrelia. B. burgdorferi is predominant in North America, but also exists in Europe, and is the agent of Lyme disease....
(known for causing Lyme disease
Lyme disease
Lyme disease, or Lyme borreliosis, is an emerging infectious disease caused by at least three species of bacteria belonging to the genus Borrelia. Borrelia burgdorferi sensu stricto is the main cause of Lyme disease in the United States, whereas Borrelia afzelii and Borrelia garinii cause most...
). Meningitis may be encountered in cerebral malaria (malaria infecting the brain). Fungal meningitis
Fungal meningitis
Fungal meningitis refers to meningitis caused by a fungal infection.One form of fungal meningitis is cryptococcal meningitis.Many cases of fungal meningitis are associated with immune deficiencies....
, e.g. due to Cryptococcus neoformans
Cryptococcus neoformans
Cryptococcus neoformans is an encapsulated yeast that can live in both plants and animals. Its teleomorph is Filobasidiella neoformans, a filamentous fungus belonging to the class Tremellomycetes. It is often found in pigeon excrement....
, is typically seen in people with immune deficiency such as AIDS. Amoebic meningitis, meningitis due to infection with amoebae such as Naegleria fowleri
Naegleria fowleri
Naegleria fowleri is a free-living excavate form of protist typically found in warm bodies of fresh water, such as ponds, lakes, rivers, and hot springs. It is also found in soil, near warm-water discharges of industrial plants, and unchlorinated swimming pools in an amoeboid or temporary...
, is contracted from freshwater sources.
Viral
Viruses that can cause meningitis include enterovirusEnterovirus
Enteroviruses are a genus of ssRNA viruses associated with several human and mammalian diseases. Serologic studies have distinguished 66 human enterovirus serotypes on the basis of antibody neutralization tests. Additional antigenic variants have been defined within several of the serotypes on the...
es, herpes simplex virus type 2
Herpes simplex virus
Herpes simplex virus 1 and 2 , also known as Human herpes virus 1 and 2 , are two members of the herpes virus family, Herpesviridae, that infect humans. Both HSV-1 and HSV-2 are ubiquitous and contagious...
(and less commonly type 1), varicella zoster virus
Varicella zoster virus
Varicella zoster virus is one of eight herpes viruses known to infect humans . It commonly causes chicken-pox in children and Herpes zoster in adults and rarely in children.-Nomenclature:...
(known for causing chickenpox
Chickenpox
Chickenpox or chicken pox is a highly contagious illness caused by primary infection with varicella zoster virus . It usually starts with vesicular skin rash mainly on the body and head rather than at the periphery and becomes itchy, raw pockmarks, which mostly heal without scarring...
and shingles
Herpes zoster
Herpes zoster , commonly known as shingles and also known as zona, is a viral disease characterized by a painful skin rash with blisters in a limited area on one side of the body, often in a stripe...
), mumps virus
Mumps
Mumps is a viral disease of the human species, caused by the mumps virus. Before the development of vaccination and the introduction of a vaccine, it was a common childhood disease worldwide...
, HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
, and LCMV
Lymphocytic choriomeningitis
Lymphocytic choriomeningitis , is a rodent-borne viral infectious disease that presents as aseptic meningitis, encephalitis or meningoencephalitis. Its causative agent is the Lymphocytic Choriomeningitis Virus , a member of the family Arenaviridae...
.
Parasitic
A parasitic cause is often assumed when there is a predominance of eosinophilsEosinophil granulocyte
Eosinophil granulocytes, usually called eosinophils or eosinophiles , are white blood cells that are one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. Along with mast cells, they also control mechanisms associated with...
(a type of white blood cell) in the CSF. The most common parasites implicated are Angiostrongylus cantonensis, Gnathostoma spinigerum
Gnathostoma spinigerum
Gnathostoma spinigerum is a parasitic nematode that causes gnathostomiasis in humans, also known as its clinical manifestations are creeping eruption, larva migrans, Yangtze edema, Choko-Fuschu Tua chid and wandering swelling. Gnathostomiasis in animals can be serious, and even fatal...
, Schistosoma
Schistosoma
A genus of trematodes, Schistosoma, commonly known as blood-flukes and bilharzia, includes flatworms which are responsible for a highly significant parasitic infection of humans by causing the disease schistosomiasis, and are considered by the World Health Organization as the second most...
, as well as the conditions cysticercosis
Cysticercosis
Cysticercosis refers to tissue infection after exposure to eggs of Taenia solium, the pork tapeworm. The disease is spread via the fecal-oral route through contaminated food and water, and is primarily a food borne disease. After ingestion the eggs pass through the lumen of the intestine into the...
, toxocariasis
Toxocariasis
-History of discovery:Werner described a parasitic nematode in dogs in 1782 which he named Ascaris canis. Johnston determined that what Werner had described was actually a member of the genus Toxocara established by Stiles in 1905. Fữlleborn speculated that T canis larvae might cause granulomatous...
, baylisascariasis
Baylisascaris procyonis
Baylisascaris procyonis is a roundworm nematode, found ubiquitously in raccoons, its larvae migrating in the intermediate hosts causing visceral larva migrans . Baylisascariasis as the zoonotic infection of humans is rare, though extremely dangerous due to the ability of the parasite's larvae to...
, paragonimiasis
Paragonimiasis
Paragonimiasis is a food-borne parasitic infection caused by the lung fluke, most commonly Paragonimus westermani. It infects an estimated 22 million people worldwide. It is particularly common in East Asia. More than 30 species of trematodes of the genus Paragonimus have been reported which...
, and a number of rarer infections and noninfective conditions.
Non-infectious
Meningitis may occur as the result of several non-infectious causes: spread of cancerCancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
to the meninges (malignant meningitis
Neoplastic meningitis
Neoplastic or malignant meningitis, also described with the older term meningitis carcinomatosa is the development of meningitis due to the infiltration of the subarachnoid space with cancer cells...
) and certain drugs
DRUGS
Destroy Rebuild Until God Shows are an American post-hardcore band formed in 2010. They released their debut self-titled album on February 22, 2011.- Formation :...
(mainly non-steroidal anti-inflammatory drug
Non-steroidal anti-inflammatory drug
Nonsteroidal anti-inflammatory drugs, usually abbreviated to NSAIDs or NAIDs, but also referred to as nonsteroidal anti-inflammatory agents/analgesics or nonsteroidal Anti-inflammatory medicines , are drugs with analgesic and antipyretic effects and which have, in higher doses, anti-inflammatory...
s, antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
s and intravenous immunoglobulin
Intravenous immunoglobulin
Intravenous immunoglobulin is a blood product administered intravenously. It contains the pooled IgG extracted from the plasma of over one thousand blood donors. IVIG's effects last between 2 weeks and 3 months...
s). It may also be caused by several inflammatory conditions such as sarcoidosis
Sarcoidosis
Sarcoidosis , also called sarcoid, Besnier-Boeck disease or Besnier-Boeck-Schaumann disease, is a disease in which abnormal collections of chronic inflammatory cells form as nodules in multiple organs. The cause of sarcoidosis is unknown...
(which is then called neurosarcoidosis
Neurosarcoidosis
Neurosarcoidosis refers to sarcoidosis, a condition of unknown cause featuring granulomas in various tissues, involving the central nervous system . It can have many manifestations, but abnormalities of the cranial nerves are the most common...
), connective tissue disorders such as systemic lupus erythematosus
Systemic lupus erythematosus
Systemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage...
, and certain forms of vasculitis
Vasculitis
Vasculitis refers to a heterogeneous group of disorders that are characterized by inflammatory destruction of blood vessels. Both arteries and veins are affected. Lymphangitis is sometimes considered a type of vasculitis...
(inflammatory conditions of the blood vessel wall) such as Behçet's disease
Behçet's disease
Behçet's disease is a rare immune-mediated systemic vasculitis that often presents with mucous membrane ulceration and ocular involvements...
. Epidermoid cyst
Epidermoid cyst
An epidermoid cyst is a benign cyst usually found on the skin. The cyst develops out of ectodermal tissue. Histologically, it is made of a thin layer of squamous epithelium.-Terminology:...
s and dermoid cyst
Dermoid cyst
A dermoid cyst is a cystic teratoma that contains developmentally mature skin complete with hair follicles and sweat glands, sometimes clumps of long hair, and often pockets of sebum, blood, fat, bone, nails, teeth, eyes, cartilage, and thyroid tissue. Because it contains mature tissue, a dermoid...
s may cause meningitis by releasing irritant matter into the subarachnoid space. Mollaret's meningitis
Mollaret's meningitis
Mollaret's meningitis is a recurrent inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges...
is a syndrome of recurring episodes of aseptic meningitis; it is thought to be caused by herpes simplex virus type 2
Herpes simplex virus
Herpes simplex virus 1 and 2 , also known as Human herpes virus 1 and 2 , are two members of the herpes virus family, Herpesviridae, that infect humans. Both HSV-1 and HSV-2 are ubiquitous and contagious...
. Rarely, migraine
Migraine
Migraine is a chronic neurological disorder characterized by moderate to severe headaches, and nausea...
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 fluidCerebrospinal fluid
Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...
, enclose and protect the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
and spinal cord
Spinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...
(the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
). The pia mater
Pia mater
Pia mater often referred to as simply the pia, is the delicate innermost layer of the meninges, the membranes surrounding the brain and spinal cord. The word finds its roots in Latin, meaning literally "tender mother." The other two meningeal membranes are the dura mater and the arachnoid mater....
is a very delicate impermeable membrane that firmly adheres to the surface of the brain, following all the minor contours. The arachnoid mater
Arachnoid mater
The arachnoid mater, literally from Latin "spider -like mother", is one of the three meninges, the membranes that cover the brain and spinal cord...
(so named because of its spider-web-like appearance) is a loosely fitting sac on top of the pia mater. The subarachnoid space
Subarachnoid space
In the central nervous system, the subarachnoid cavity is the interval between the arachnoid membrane and pia mater....
separates the arachnoid and pia mater membranes, and is filled with cerebrospinal fluid. The outermost membrane, the dura mater
Dura mater
The dura mater , or dura, is the outermost of the three layers of the meninges surrounding the brain and spinal cord. It is derived from Mesoderm. The other two meningeal layers are the pia mater and the arachnoid mater. The dura surrounds the brain and the spinal cord and is responsible for...
, 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 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 upon mucous surfaces
Mucous membrane
The mucous membranes are linings of mostly endodermal origin, covered in epithelium, which are involved in absorption and secretion. They line cavities that are exposed to the external environment and internal organs...
such as the nasal cavity
Nasal cavity
The nasal cavity is a large air filled space above and behind the nose in the middle of the face.- Function :The nasal cavity conditions the air to be received by the other areas of the respiratory tract...
. This is often in turn preceded by viral infections, which break down the normal barrier provided by the mucous surfaces. Once bacteria have entered the bloodstream, they enter the subarachnoid space
Subarachnoid space
In the central nervous system, the subarachnoid cavity is the interval between the arachnoid membrane and pia mater....
in places where the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
is vulnerable—such as the choroid plexus
Choroid plexus
The choroid plexus is a structure in the ventricles of the brain where cerebrospinal fluid is produced...
. Meningitis occurs in 25% of newborns with bloodstream infections due to group B streptococci; this phenomenon is 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
Congenital disorder
A congenital disorder, or congenital disease, is a condition existing at birth and often before birth, or that develops during the first month of life , regardless of causation...
of the dura mater
Dura mater
The dura mater , or dura, is the outermost of the three layers of the meninges surrounding the brain and spinal cord. It is derived from Mesoderm. The other two meningeal layers are the pia mater and the arachnoid mater. The dura surrounds the brain and the spinal cord and is responsible for...
can be identified.
The large-scale inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
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
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
to the entrance of bacteria into the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
. When components of the bacterial cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
are identified by the immune cells of the brain (astrocyte
Astrocyte
Astrocytes , also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord...
s and microglia
Microglia
Microglia are a type of glial cell that are the resident macrophages of the brain and spinal cord, and thus act as the first and main form of active immune defense in the central nervous system . Microglia constitute 20% of the total glial cell population within the brain...
), they respond by releasing large amounts of cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
s, 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 cell
White blood cell
White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...
s 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 a decreased blood flow and a third type of edema, "cytotoxic" edema. The three forms of cerebral edema all lead to an increased intracranial pressure
Intracranial pressure
Intracranial pressure is the pressure inside the skull and thus in the brain tissue and cerebrospinal fluid . The body has various mechanisms by which it keeps the ICP stable, with CSF pressures varying by about 1 mmHg in normal adults through shifts in production and absorption of CSF...
; together with the lowered blood pressure often encountered in acute infection, this means that it is harder for blood to enter the brain, and brain cell
Brain Cell
Brain Cell is a mail art project begun by Ryosuke Cohen in June 1985. The project is basically a networked art project where individual artists create their own 30x42cm work of art with stamps, drawings, stickers and so forth. This is sent to Cohen, who prints each cell - 150 copies each - with a...
s are deprived of oxygen and undergo apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
(automated cell death
Programmed cell death
Programmed cell-death is death of a cell in any form, mediated by an intracellular program. PCD is carried out in a regulated process which generally confers advantage during an organism's life-cycle...
).
It is recognized that 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
Glucocorticoid
Glucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor , which is present in almost every vertebrate animal cell...
, are aimed at dampening the immune system's response to this phenomenon.
Diagnosis
| Type of meningitis | Glucose CSF glucose CSF glucose or glycorrhachia is a measurement used to determine the levels of glucose in cerebrospinal fluid.It can be useful in distinguishing among causes of meningitis. It is more likely to be decreased in bacterial meningitis than in viral meningitis.Normal CSF glucose is between 45 and... |
Protein CSF total protein CSF albumin is a measurement used to determine the levels of albumin in cerebrospinal fluid.A closely related test, CSF total protein is a measurement used to determine the levels of protein in cerebrospinal fluid. It combines the albumin, IgG, and other proteins.It can be useful in distinguishing... |
Cells |
|---|---|---|---|
| Acute bacterial | low | high | PMNs, often > 300/mm³ |
| Acute viral | normal | normal or high | mononuclear Lymphocyte A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells... , < 300/mm³ |
| Tuberculous | low | high | mononuclear and PMNs, < 300/mm³ |
| Fungal | low | high | < 300/mm³ |
| Malignant | low | high | usually mononuclear |
Blood tests and imaging
In someone suspected of having meningitis, blood testBlood test
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....
s are performed for markers of inflammation (e.g. C-reactive protein
C-reactive protein
C-reactive protein is a protein found in the blood, the levels of which rise in response to inflammation...
, complete blood count
Complete blood count
A complete blood count , also known as full blood count or full blood exam or blood panel, is a test panel requested by a doctor or other medical professional that gives information about the cells in a patient's blood...
), as well as blood culture
Blood culture
Blood culture is a microbiological culture of blood. It is employed to detect infections that are spreading through the bloodstream...
s.
The most important test in identifying or ruling out meningitis is analysis of the cerebrospinal fluid through lumbar puncture
Lumbar puncture
A lumbar puncture is a diagnostic and at times therapeutic procedure that is performed in order to collect a sample of cerebrospinal fluid for biochemical, microbiological, and cytological analysis, or very rarely as a treatment to relieve increased intracranial pressure.-Indications:The...
(LP, spinal tap). However, lumbar puncture is contraindicated if there is a mass in the brain (tumor or abscess) or the intracranial pressure
Intracranial pressure
Intracranial pressure is the pressure inside the skull and thus in the brain tissue and cerebrospinal fluid . The body has various mechanisms by which it keeps the ICP stable, with CSF pressures varying by about 1 mmHg in normal adults through shifts in production and absorption of CSF...
(ICP) is elevated, as it may lead to brain herniation
Brain herniation
Brain herniation, also known as cistern obliteration, is a deadly side effect of very high intracranial pressure that occurs when the brain shifts across structures within the skull...
. 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
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...
or MRI
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
scan is recommended prior to the lumbar puncture. This applies in 45% of all adult cases. 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, especially if this may be longer than 30 minutes. Often, CT or MRI scans are performed at a later stage to assess for complications of meningitis.
In severe forms of meningitis, monitoring of blood electrolytes may be important; for example, hyponatremia
Hyponatremia
Hyponatremia is an electrolyte disturbance in which the sodium concentration in the serum is lower than normal. In the vast majority of cases, hyponatremia occurs as a result of excess body water diluting the serum sodium and is not due to sodium deficiency. Sodium is the dominant extracellular...
is common in bacterial meningitis, due to a combination of factors including dehydration, the inappropriate excretion of the antidiuretic hormone (SIADH), or overly aggressive intravenous fluid administration
Intravenous therapy
Intravenous therapy or IV therapy is the infusion of liquid substances directly into a vein. The word intravenous simply means "within a vein". Therapies administered intravenously are often called specialty pharmaceuticals...
.
Lumbar puncture
A lumbar puncture is done by positioning the patient, usually lying on the side, applying local anestheticLocal anesthetic
A local anesthetic is a drug that causes reversible local anesthesia, generally for the aim of having local analgesic effect, that is, inducing absence of pain sensation, although other local senses are often affected as well...
, 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 typically 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.
White blood cell
White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...
s, red blood cell
Red blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
s, protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
content and glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
level. Gram staining
Gram staining
Gram staining is a method of differentiating bacterial species into two large groups ....
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, and Gram staining is also less reliable in particular infections such as listeriosis. Microbiological culture
Microbiological culture
A microbiological culture, or microbial culture, is a method of multiplying microbial organisms by letting them reproduce in predetermined culture media under controlled laboratory conditions. Microbial cultures are used to determine the type of organism, its abundance in the sample being tested,...
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. The type of white blood cell predominantly present (see table) indicates whether meningitis is bacterial (usually neutrophil-predominant) or viral (usually lymphocyte-predominant), although in the beginning of the disease this is not always a reliable indicator. Less commonly, eosinophils predominate, suggesting parasitic or fungal etiology, among others.
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
Blood sugar
The blood sugar concentration or blood glucose level is the amount of glucose present in the blood of a human or animal. Normally in mammals, the body maintains the blood glucose level at a reference range between about 3.6 and 5.8 mM , or 64.8 and 104.4 mg/dL...
(CSF glucose to serum glucose ratio). A ratio ≤0.4 is indicative of bacterial meningitis; in the newborn, glucose levels in CSF are normally higher, and a ratio below 0.6 (60%) is therefore considered abnormal. High levels of lactate
Lactic acid
Lactic acid, also known as milk acid, is a chemical compound that plays a role in various biochemical processes and was first isolated in 1780 by the Swedish chemist Carl Wilhelm Scheele. Lactic acid is a carboxylic acid with the chemical formula C3H6O3...
in CSF indicate a higher likelihood of bacterial meningitis, as does a higher white blood cell count.
Various more specialized tests may be used to distinguish between various types of meningitis. A latex agglutination test may be positive in meningitis caused by Streptococcus pneumoniae
Streptococcus pneumoniae
Streptococcus pneumoniae, or pneumococcus, is Gram-positive, alpha-hemolytic, aerotolerant anaerobic member of the genus Streptococcus. A significant human pathogenic bacterium, S...
, Neisseria meningitidis
Neisseria meningitidis
Neisseria meningitidis, often referred to as meningococcus, is a bacterium that can cause meningitis and other forms of meningococcal disease such as meningococcemia, a life threatening sepsis. N. meningitidis is a major cause of morbidity and mortality during childhood in industrialized countries...
, Haemophilus influenzae
Haemophilus influenzae
Haemophilus influenzae, formerly called Pfeiffer's bacillus or Bacillus influenzae, Gram-negative, rod-shaped bacterium first described in 1892 by Richard Pfeiffer during an influenza pandemic. A member of the Pasteurellaceae family, it is generally aerobic, but can grow as a facultative anaerobe. H...
, Escherichia coli
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
and group B streptococci
Streptococcus agalactiae
Streptococcus agalactiae is a beta-hemolytic Gram-positive streptococcus.- Identification :The CAMP test is an important test for identification...
; 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
Limulus Amebocyte Lysate
Limulus amebocyte lysate is an aqueous extract of blood cells from the horseshoe crab, Limulus polyphemus. LAL reacts with bacterial endotoxin or lipopolysaccharide , which is a membrane component of Gram negative bacteria...
may be positive in meningitis caused by Gram-negative bacteria, but it is of limited use unless other tests have been unhelpful. Polymerase chain reaction
Polymerase chain reaction
The polymerase chain reaction is a scientific technique in molecular biology to amplify a single or a few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence....
(PCR) is a technique used to amplify small traces of bacterial DNA in order to detect the presence of bacterial or viral DNA in cerebrospinal fluid; it is a highly sensitive and specific test since only trace amounts of the infecting agent's DNA is required. It may identify bacteria in bacterial meningitis and may assist in distinguishing the various causes of viral meningitis (enterovirus
Enterovirus
Enteroviruses are a genus of ssRNA viruses associated with several human and mammalian diseases. Serologic studies have distinguished 66 human enterovirus serotypes on the basis of antibody neutralization tests. Additional antigenic variants have been defined within several of the serotypes on the...
, herpes simplex virus 2
Herpes simplex virus
Herpes simplex virus 1 and 2 , also known as Human herpes virus 1 and 2 , are two members of the herpes virus family, Herpesviridae, that infect humans. Both HSV-1 and HSV-2 are ubiquitous and contagious...
and mumps
Mumps
Mumps is a viral disease of the human species, caused by the mumps virus. Before the development of vaccination and the introduction of a vaccine, it was a common childhood disease worldwide...
in those not vaccinated for this). Serology
Serology
Serology is the scientific study of blood serum and other bodily fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum...
(identification of antibodies to viruses) may be useful in viral meningitis. If tuberculous meningitis is suspected, the sample is processed for Ziehl-Neelsen stain
Ziehl-Neelsen stain
The Ziehl–Neelsen stain, also known as the acid-fast stain, was first described by two German doctors; Franz Ziehl , a bacteriologist and Friedrich Neelsen , a pathologist. It is a special bacteriological stain used to identify acid-fast organisms, mainly Mycobacteria...
, which has a low sensitivity, and tuberculosis culture, which takes a long time to process; PCR is being used increasingly. Diagnosis of cryptococcal meningitis can be made at low cost using an India ink
India ink
India ink is a simple black ink once widely used for writing and printing and now more commonly used for drawing, especially when inking comic books and comic strips.-Composition:...
stain of the CSF; however, testing for cryptococcal antigen in blood or CSF is more sensitive, particularly in persons with AIDS.
A diagnostic and therapeutic conundrum is the "partially treated meningitis", where there are meningitis symptoms after receiving antibiotics (such as for presumptive sinusitis
Sinusitis
Sinusitis is inflammation of the paranasal sinuses, which may be due to infection, allergy, or autoimmune issues. Most cases are due to a viral infection and resolve over the course of 10 days...
). 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).
Postmortem
Meningitis can be diagnosed after death has occurred. The findings from a post mortem are usually a widespread inflammation of the pia materPia mater
Pia mater often referred to as simply the pia, is the delicate innermost layer of the meninges, the membranes surrounding the brain and spinal cord. The word finds its roots in Latin, meaning literally "tender mother." The other two meningeal membranes are the dura mater and the arachnoid mater....
and arachnoid
Arachnoid mater
The arachnoid mater, literally from Latin "spider -like mother", is one of the three meninges, the membranes that cover the brain and spinal cord...
layers of the meninges covering the brain and spinal cord. Neutrophil granulocyte
Neutrophil granulocyte
Neutrophil granulocytes are the most abundant type of white blood cells in mammals and form an essential part of the innate immune system. They are generally referred to as either neutrophils or polymorphonuclear neutrophils , and are subdivided into segmented neutrophils and banded neutrophils...
s tend to have migrated to the cerebrospinal fluid and the base of the brain, along with cranial nerves and the spinal cord
Spinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...
, may be surrounded with pus
Pus
Pus is a viscous exudate, typically whitish-yellow, yellow, or yellow-brown, formed at the site of inflammatory during infection. An accumulation of pus in an enclosed tissue space is known as an abscess, whereas a visible collection of pus within or beneath the epidermis is known as a pustule or...
—as may the meningeal vessels
Meningeal arteries
Meningeal arteries can refer to:* Middle meningeal artery* Posterior meningeal artery* Anterior meningeal artery...
.
Behavioral
Bacterial and viral meningitis are contagious. Neither are as contagious as the common coldCommon cold
The common cold is a viral infectious disease of the upper respiratory system, caused primarily by rhinoviruses and coronaviruses. Common symptoms include a cough, sore throat, runny nose, and fever...
or flu. Both can be transmitted through droplets of respiratory secretions during close contact such as kissing, sneezing or coughing on someone, but cannot be spread by only breathing the air where a person with meningitis has been. Viral meningitis is typically caused by Enteroviruses, and is most commonly spread through fecal contamination. By changing behavior to prevent the causes of transmission, infection by viruses and bacteria can be prevented.
Pharmaceutical
For some causes of meningitis, prophylaxis can be provided in the long term with vaccineVaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...
, or in the short term with antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
s.
Since the 1980s, many countries have included immunization against Haemophilus influenzae type B
Hib vaccine
Haemophilus influenzae type B vaccine is a conjugate vaccine developed for the prevention of invasive disease caused by Haemophilus influenzae type b bacteria. The Centers for Disease Control and Prevention has recommended the use of the Hib vaccine. Due to routine use of the Hib vaccine in...
in their routine childhood vaccination schemes. This has practically eliminated this pathogen as a cause of meningitis in young children in those countries. In the countries where the disease burden is highest, however, the vaccine is still too expensive. Similarly, immunization against mumps has led to a sharp fall in the number of cases of mumps meningitis, which prior to vaccination occurred in 15% of all cases of mumps.
Meningococcus vaccines
Meningococcal vaccine
Meningococcal vaccine is a vaccine used against Meningococcus, a bacterium that causes meningitis, meningococcemia, septicemia, and rarely carditis, septic arthritis, or pneumonia.-Types:...
exist against groups A, C, W135 and Y. In countries where the vaccine for meningococcus group C was introduced, cases caused by this pathogen have decreased substantially. A quadrivalent vaccine now exists, which combines all four vaccines. Immunization with the ACW135Y vaccine against four strains is now a visa requirement for taking part in the Hajj. Development of a vaccine against group B meningococci has proved much more difficult, as its surface proteins (which would normally be used to make a vaccine) only elicit a weak response from the immune system
Immunogenicity
Immunogenicity is the ability of a particular substance, such as an antigen or epitope, to provoke an immune response in the body of a human or animal.- Immunogenicity :The ability to induce humoral and/or cell-mediated immune responses....
, or cross-react with normal human proteins. Still, some countries (New Zealand
New Zealand
New Zealand is an island country in the south-western Pacific Ocean comprising two main landmasses and numerous smaller islands. The country is situated some east of Australia across the Tasman Sea, and roughly south of the Pacific island nations of New Caledonia, Fiji, and Tonga...
, Cuba
Cuba
The Republic of Cuba is an island nation in the Caribbean. The nation of Cuba consists of the main island of Cuba, the Isla de la Juventud, and several archipelagos. Havana is the largest city in Cuba and the country's capital. Santiago de Cuba is the second largest city...
, Norway
Norway
Norway , officially the Kingdom of Norway, is a Nordic unitary constitutional monarchy whose territory comprises the western portion of the Scandinavian Peninsula, Jan Mayen, and the Arctic archipelago of Svalbard and Bouvet Island. Norway has a total area of and a population of about 4.9 million...
and Chile
Chile
Chile ,officially the Republic of Chile , is a country in South America occupying a long, narrow coastal strip between the Andes mountains to the east and the Pacific Ocean to the west. It borders Peru to the north, Bolivia to the northeast, Argentina to the east, and the Drake Passage in the far...
) have developed vaccines against local strains of group B meningococci; some have shown good results and are used in local immunization schedules. In Africa, until recently, the approach for prevention and control of meningococcal epidemics was based on early detection of the disease and emergency reactive mass vaccination of the at-risk population with bivalent A/C or trivalent A/C/W135 polysaccharide vaccines, though the introduction of MenAfriVac
MenAfriVac
MenAfriVac is a vaccine developed for use in sub-Saharan Africa that protects people 1 to 29 years of age against meningococcal bacterium Neisseria meningitidis group A. MenAfriVac costs under US$.50 per dose and reduces carriage of the bacteria from one person to another...
(meningiococcus 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
Pneumococcal polysaccharide vaccine
Pneumococcal polysaccharide vaccine — the latest version is known as Pneumovax 23 — is the first pneumococcal vaccine, the first vaccine derived from a capsular polysaccharide, and an important landmark in medical history...
, which covers 23 strains, is only administered in certain groups (e.g. those who have had a splenectomy
Splenectomy
A splenectomy is a surgical procedure that partially or completely removes the spleen.-Indications:The spleen, similar in structure to a large lymph node, acts as a blood filter. Current knowledge of its purpose includes the removal of old red blood cells and platelets, and the detection and fight...
, the surgical removal of the spleen); it does not elicit a significant immune response in all recipients, e.g. small children.
Childhood vaccination with Bacillus Calmette-Guérin
Bacillus Calmette-Guérin
Bacillus Calmette-Guérin is a vaccine against tuberculosis that is prepared from a strain of the attenuated live bovine tuberculosis bacillus, Mycobacterium bovis, that has lost its virulence in humans by being specially subcultured in an artificial medium for 13 years, and also prepared from...
has been reported to significantly reduce the rate of tuberculous meningitis, but its waning effectiveness in adulthood has prompted a search for a better vaccine.
Short-term antibiotic prophylaxis is also a method of prevention, particularly of meningococcal meningitis. In cases of meningococcal meningitis, prophylactic treatment of close contacts with antibiotics (e.g. rifampicin
Rifampicin
Rifampicin or rifampin is a bactericidal antibiotic drug of the rifamycin group. It is a semisynthetic compound derived from Amycolatopsis rifamycinica ...
, ciprofloxacin
Ciprofloxacin
Ciprofloxacin is a synthetic chemotherapeutic antibiotic of the fluoroquinolone drug class.It is a second-generation fluoroquinolone antibacterial. It kills bacteria by interfering with the enzymes that cause DNA to rewind after being copied, which stops synthesis of DNA and of...
or ceftriaxone
Ceftriaxone
Ceftriaxone is a third-generation cephalosporin antibiotic. Like other third-generation cephalosporins, it has broad spectrum activity against Gram-positive and Gram-negative bacteria. In most cases, it is considered to be equivalent to cefotaxime in terms of safety and efficacy...
) can reduce their risk of contracting the condition, but does not protect against future infections.
Initial treatment
Meningitis is potentially life-threatening and has a high mortality rate if untreated; delay in treatment has been associated with a poorer outcome. Thus treatment with wide-spectrum antibiotics should not be delayed while confirmatory tests are being conducted. If meningococcal disease is suspected in primary care, guidelines recommend that benzylpenicillinBenzylpenicillin
Benzylpenicillin, commonly known as penicillin G, is the gold standard type of penicillin. 'G' in the name 'Penicillin G' refers to 'Gold Standard'. Penicillin G is typically given by a parenteral route of administration because it is unstable in the hydrochloric acid of the stomach...
be administered before transfer to hospital. Intravenous fluids should be administered if hypotension
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
(low blood pressure) or shock are present. Given that meningitis can cause a number of early severe complications, regular medical review is recommended to identify these complications early, as well as admission to an intensive care unit
Intensive Care Unit
thumb|220px|ICU roomAn intensive-care unit , critical-care unit , intensive-therapy unit/intensive-treatment unit is a specialized department in a hospital that provides intensive-care medicine...
if deemed necessary.
Mechanical ventilation
Mechanical ventilation
In medicine, mechanical ventilation is a method to mechanically assist or replace spontaneous breathing. This may involve a machine called a ventilator or the breathing may be assisted by a physician, respiratory therapist or other suitable person compressing a bag or set of bellows...
may be needed if the level of consciousness is very low, or if there is evidence of respiratory failure
Respiratory failure
The term respiratory failure, in medicine, is used to describe inadequate gas exchange by the respiratory system, with the result that arterial oxygen and/or carbon dioxide levels cannot be maintained within their normal ranges. A drop in blood oxygenation is known as hypoxemia; a rise in arterial...
. If there are signs of raised intracranial pressure, measures to monitor the pressure may be taken; this would allow the optimization of the cerebral perfusion pressure
Cerebral perfusion pressure
Cerebral perfusion pressure, or CPP, is the net pressure gradient causing blood flow to the brain . It must be maintained within narrow limits because too little pressure could cause brain tissue to become ischemic , and too much could raise intracranial pressure .-From resistance:CPP can be...
and various treatments to decrease the intracranial pressure with medication (e.g. mannitol
Mannitol
Mannitol is a white, crystalline organic compound with the formula . This polyol is used as an osmotic diuretic agent and a weak renal vasodilator...
). Seizures are treated with anticonvulsant
Anticonvulsant
The anticonvulsants are a diverse group of pharmaceuticals used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder, since many seem to act as mood stabilizers, and in the treatment of neuropathic pain. The goal of an...
s. Hydrocephalus (obstructed flow of CSF) may require insertion of a temporary or long-term drainage device, such as a cerebral shunt
Cerebral shunt
Cerebral shunts are commonly used to treat hydrocephalus, the swelling of the brain due to excess buildup of cerebrospinal fluid . If left unchecked, the cerebral spinal fluid can build up leading to an increase in intracranial pressure which can lead to intracranial hematoma, cerebral edema,...
.
Antibiotics
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
empirical treatment
Empirical treatment
Empirical treatment is a medical treatment not derived from the scientific method, but derived from observation, survey or common use.In the medical profession, the term is also used when treatment is started before a diagnosis is confirmed The most common reason is that investigations are...
consists of a third-generation cefalosporin such as cefotaxime
Cefotaxime
Cefotaxime is a third-generation cephalosporin antibiotic. Like other third-generation cephalosporins, it has broad spectrum activity against Gram positive and Gram negative bacteria...
or ceftriaxone
Ceftriaxone
Ceftriaxone is a third-generation cephalosporin antibiotic. Like other third-generation cephalosporins, it has broad spectrum activity against Gram-positive and Gram-negative bacteria. In most cases, it is considered to be equivalent to cefotaxime in terms of safety and efficacy...
. In the USA, where resistance to cefalosporins is increasingly found in streptococci, addition of vancomycin
Vancomycin
Vancomycin INN is a glycopeptide antibiotic used in the prophylaxis and treatment of infections caused by Gram-positive bacteria. It has traditionally been reserved as a drug of "last resort", used only after treatment with other antibiotics had failed, although the emergence of...
to the initial treatment is recommended. Empirical therapy may be chosen on the basis of the age of the patient, whether the infection was preceded by head injury
Head injury
Head injury refers to trauma of the head. This may or may not include injury to the brain. However, the terms traumatic brain injury and head injury are often used interchangeably in medical literature....
, whether the patient has undergone neurosurgery
Neurosurgery
Neurosurgery is the medical specialty concerned with the prevention, diagnosis, treatment, and rehabilitation of disorders which affect any portion of the nervous system including the brain, spine, spinal cord, peripheral nerves, and extra-cranial cerebrovascular system.-In the United States:In...
and whether or not a cerebral shunt is present. For instance, in young children and those over 50 years of age, as well as those who are immunocompromised, addition of ampicillin
Ampicillin
Ampicillin is a beta-lactam antibiotic that has been used extensively to treat bacterial infections since 1961. Until the introduction of ampicillin by the British company Beecham, penicillin therapies had only been effective against Gram-positive organisms such as staphylococci and streptococci...
is recommended to cover Listeria monocytogenes. Once the Gram stain results become available, and the broad type of bacterial cause is known, it may be possible to change the antibiotics to those likely to deal with the presumed group of pathogens.
The results of the CSF culture
Microbiological culture
A microbiological culture, or microbial culture, is a method of multiplying microbial organisms by letting them reproduce in predetermined culture media under controlled laboratory conditions. Microbial cultures are used to determine the type of organism, its abundance in the sample being tested,...
generally take longer to become available (24–48 hours). Once they do, empiric therapy may be switched to specific antibiotic therapy targeted to the specific causative organism and its sensitivities to antibiotics. For an antibiotic to be effective in meningitis, it must not only be active against the pathogenic bacterium, but also reach the meninges in adequate quantities; some antibiotics have inadequate penetrance and therefore have little use in meningitis. Most of the antibiotics used in meningitis have not been tested directly on meningitis patients in clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
s. Rather, the relevant knowledge has mostly derived from laboratory studies in rabbit
Rabbit
Rabbits are small mammals in the family Leporidae of the order Lagomorpha, found in several parts of the world...
s.
Tuberculous meningitis requires prolonged treatment with antibiotics. While tuberculosis of the lungs is typically treated for six months, those with tuberculous meningitis are typically treated for a year or longer. In tuberculous meningitis there is a strong evidence base for treatment with corticosteroids, although this evidence is restricted to those without AIDS.
Steroids
AdjuvantAdjuvant
An adjuvant is a pharmacological or immunological agent that modifies the effect of other agents, such as a drug or vaccine, while having few if any direct effects when given by itself...
treatment with corticosteroids (usually dexamethasone
Dexamethasone
Dexamethasone is a potent synthetic member of the glucocorticoid class of steroid drugs. It acts as an anti-inflammatory and immunosuppressant...
) has been shown in some studies to reduce rates of mortality, severe hearing loss and neurological damage in adolescents and adults from high income countries which have low rates of HIV. The likely mechanism is suppression of overactive inflammation. 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. Given that most of the benefit of the treatment is confined to those with pneumococcal meningitis, some guidelines suggest that dexamethasone be discontinued if another cause for meningitis is identified.
Adjuvant corticosteroids have a different role in children than in adults. Though the benefit of corticosteroids has been demonstrated in adults as well as in children from high-income countries, their use in children from low-income
Poverty
Poverty is the lack of a certain amount of material possessions or money. Absolute poverty or destitution is inability to afford basic human needs, which commonly includes clean and fresh water, nutrition, health care, education, clothing and shelter. About 1.7 billion people are estimated to live...
countries is not supported by evidence; the reason for this discrepancy is not clear. Even in high-income countries, the benefit of corticosteroids is only seen when they are given prior to the first dose of antibiotics, and is greatest in cases of H. influenzae meningitis, the incidence of which has decreased dramatically since the introduction of the Hib vaccine
Hib vaccine
Haemophilus influenzae type B vaccine is a conjugate vaccine developed for the prevention of invasive disease caused by Haemophilus influenzae type b bacteria. The Centers for Disease Control and Prevention has recommended the use of the Hib vaccine. Due to routine use of the Hib vaccine in...
. Thus, corticosteroids are recommended in the treatment of pediatric meningitis if the cause is H. influenzae and only if given prior to the first dose of antibiotics, whereas other uses are controversial.
A 2010 analysis of previous studies has shown that the benefit from steroids may not be as significant as previously found. The one possible significant benefit is reduction of hearing loss in survivors, and adverse neurological outcomes.
Viral meningitis
Viral meningitisViral meningitis
Viral meningitis refers to meningitis caused by a viral infection. It is sometimes referred to as "aseptic meningitis" in contrast to meningitis caused by bacteria.An example is lymphocytic choriomeningitis....
typically requires supportive therapy only; most viruses responsible for causing meningitis are not amenable to specific treatment. Viral meningitis tends to run a more benign course than bacterial meningitis. Herpes simplex virus
Herpes simplex virus
Herpes simplex virus 1 and 2 , also known as Human herpes virus 1 and 2 , are two members of the herpes virus family, Herpesviridae, that infect humans. Both HSV-1 and HSV-2 are ubiquitous and contagious...
and varicella zoster virus
Varicella zoster virus
Varicella zoster virus is one of eight herpes viruses known to infect humans . It commonly causes chicken-pox in children and Herpes zoster in adults and rarely in children.-Nomenclature:...
may respond to treatment with antiviral drugs such as aciclovir
Aciclovir
Aciclovir or acyclovir , chemical name acycloguanosine, abbreviated as ACV,is a guanosine analogue antiviral drug, marketed under trade names such as Cyclovir, Herpex, Acivir, Acivirax, Zovirax, and Zovir...
, but there are no clinical trials that have specifically addressed whether this treatment is effective. Mild cases of viral meningitis can be treated at home with conservative measures such as fluid, bedrest, and analgesics.
Fungal meningitis
Fungal meningitis, such as cryptococcal meningitis, is treated with long courses of highly dosed antifungalsAntifungal drug
An antifungal medication is a medication used to treat fungal infections such as athlete's foot, ringworm, candidiasis , serious systemic infections such as cryptococcal meningitis, and others...
, such as amphotericin B
Amphotericin B
Amphotericin B is a polyene antifungal drug, often used intravenously for systemic fungal infections...
and flucytosine
Flucytosine
Flucytosine, or 5-fluorocytosine, a fluorinated pyrimidine analogue, is a synthetic antimycotic drug.It is structurally related to the cytostatic fluorouracil and to floxuridine. It is available in oral and in some countries also in injectable form. A common brand name is Ancobon. Flucytosine was...
. Raised intracranial pressure is common in fungal meningitis, and frequent (ideally daily) lumbar punctures to relieve the pressure are recommended, or alternatively a lumbar drain.
Prognosis
Untreated, bacterial meningitis is almost always fatal. Viral meningitis, in contrast, tends to resolve spontaneously and is rarely fatal. With treatment, mortalityMortality rate
Mortality rate is a measure of the number of deaths in a population, scaled to the size of that population, per unit time...
(risk of death) from bacterial meningitis depends on the age of the patient and the underlying cause. Of the newborn patients, 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. Risk of death is predicted by various factors apart from age, such as the pathogen and the time it takes for the pathogen to be cleared from the cerebrospinal fluid, the severity of the generalized illness, decreased level of consciousness or abnormally low count of white blood cells in the CSF. Meningitis caused by H. influenzae and meningococci has a better prognosis compared to cases caused by group B streptococci, coliforms and S. pneumonia. In adults, too, meningococcal meningitis has a lower mortality (3–7%) than pneumococcal disease.
In children there are several potential disabilities which result from damage to the nervous system. Sensorineural hearing loss
Sensorineural hearing loss
Sensorineural hearing loss is a type of hearing loss in which the root cause lies in the vestibulocochlear nerve , the inner ear, or central processing centers of the brain....
, epilepsy
Epilepsy
Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...
, learning
Learning disability
Learning disability is a classification including several disorders in which a person has difficulty learning in a typical manner, usually caused by an unknown factor or factors...
and behavioral difficulties, as well as decreased intelligence, occur in about 15% of survivors. Some of the hearing loss may be reversible. In adults, 66% of all cases emerge without disability. The main problems are deafness (in 14%) and cognitive impairment
Developmental disability
Developmental disability is a term used in the United States and Canada to describe lifelong disabilities attributable to mental or physical impairments, manifested prior to age 18. It is not synonymous with "developmental delay" which is often a consequence of a temporary illness or trauma during...
(in 10%).
Epidemiology
Notifiable disease
A notifiable disease is any disease that is required by law to be reported to government authorities. The collation of information allows the authorities to monitor the disease, and provides early warning of possible outbreaks. Many governments have enacted regulations for reporting of both human...
in many countries, the exact incidence
Incidence (epidemiology)
Incidence is a measure of the risk of developing some new condition within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time period, it is better expressed as a proportion or a rate with a denominator.Incidence proportion is the...
rate is unknown. Bacterial meningitis occurs in about 3 people per 100,000 annually in Western countries
Western world
The Western world, also known as the West and the Occident , is a term referring to the countries of Western Europe , the countries of the Americas, as well all countries of Northern and Central Europe, Australia and New Zealand...
. Population-wide studies have shown that viral meningitis is more common, at 10.9 per 100,000, and occurs more often in the summer. In Brazil, the rate of bacterial meningitis is higher, at 45.8 per 100,000 annually. Sub-Saharan Africa
Sub-Saharan Africa
Sub-Saharan Africa as a geographical term refers to the area of the African continent which lies south of the Sahara. A political definition of Sub-Saharan Africa, instead, covers all African countries which are fully or partially located south of the Sahara...
has been plagued by large epidemics of meningococcal meningitis for over a century, 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
Health care
Health care is the diagnosis, treatment, and prevention of disease, illness, injury, and other physical and mental impairments in humans. Health care is delivered by practitioners in medicine, chiropractic, dentistry, nursing, pharmacy, allied health, and other care providers...
. These cases are predominantly caused by meningococci. The largest epidemic ever recorded in history swept across the entire region in 1996–1997, causing over 250,000 cases and 25,000 deaths.
Meningococcal disease occurs in epidemics in areas where many people live together for the first time, such as army barracks during mobilization, college campuses and the annual Hajj
Hajj
The Hajj is the pilgrimage to Mecca, Saudi Arabia. It is one of the largest pilgrimages in the world, and is the fifth pillar of Islam, a religious duty that must be carried out at least once in their lifetime by every able-bodied Muslim who can afford to do so...
pilgrimage. 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 HippocratesHippocrates
Hippocrates of Cos or Hippokrates of Kos was an ancient Greek physician of the Age of Pericles , and is considered one of the most outstanding figures in the history of medicine...
may have realized the existence of meningitis, and it seems that meningism was known to pre-Renaissance physicians such as Avicenna
Avicenna
Abū ʿAlī al-Ḥusayn ibn ʿAbd Allāh ibn Sīnā , commonly known as Ibn Sīnā or by his Latinized name Avicenna, was a Persian polymath, who wrote almost 450 treatises on a wide range of subjects, of which around 240 have survived...
. The description of tuberculous meningitis, then called "dropsy in the brain", is often attributed to Edinburgh physician Sir Robert Whytt
Robert Whytt
Robert Whytt was a Scottish physician. His work, on unconscious reflexes, tubercular meningitis, urinary bladder stones, and hysteria, is remembered now most for his book on diseases of the nervous system...
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
Geneva
Geneva In the national languages of Switzerland the city is known as Genf , Ginevra and Genevra is the second-most-populous city in Switzerland and is the most populous city of Romandie, the French-speaking part of Switzerland...
in 1805. 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
Nigeria
Nigeria , officially the Federal Republic of Nigeria, is a federal constitutional republic comprising 36 states and its Federal Capital Territory, Abuja. The country is located in West Africa and shares land borders with the Republic of Benin in the west, Chad and Cameroon in the east, and Niger in...
and Ghana
Ghana
Ghana , officially the Republic of Ghana, is a country located in West Africa. It is bordered by Côte d'Ivoire to the west, Burkina Faso to the north, Togo to the east, and the Gulf of Guinea to the south...
in 1905–1908.
The first report of bacterial infection underlying meningitis was by the Austrian bacteriologist Anton Weichselbaum
Anton Weichselbaum
Anton Weichselbaum was an Austrian pathologist and bacteriologist who was a native of Schiltern....
, who in 1887 described the meningococcus. Mortality from meningitis was very high (over 90%) in early reports. In 1906, antiserum
Antiserum
Antiserum is blood serum containing polyclonal antibodies. Antiserum is used to pass on passive immunity to many diseases. Passive antibody transfusion from a previous human survivor is the only known effective treatment for Ebola infection .The most common use of antiserum in humans is as...
was produced in horses; this was developed further by the American scientist Simon Flexner
Simon Flexner
Simon Flexner, M.D. was a physician, scientist, administrator, and professor of experimental pathology at the University of Pennsylvania . He was the first director of the Rockefeller Institute for Medical Research and a trustee of the Rockefeller Foundation...
and markedly decreased mortality from meningococcal disease. In 1944, penicillin
Penicillin
Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....
was first reported to be effective in meningitis. The introduction in the late 20th century of Haemophilus
Haemophilus
Not to be confused with Haemophilia.Haemophilus is a genus of Gram-negative, pleomorphic, coccobacilli bacteria belonging to the Pasteurellaceae family. While Haemophilus bacteria are typically small coccobacilli, they are categorized as pleomorphic bacteria because of the wide range of shapes they...
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.