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Meningitis
Specialty	Neurology, infectious diseases

Meningitis is a medical condition caused by inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. While some forms of meningitis are mild and resolve on their own, meningitis is a potentially life-threatening condition due to the proximity of the inflammation to the brain and spinal cord. It is a medical emergency. The inflammation is usually caused by infection with bacteria, viruses or other microorganisms but may also arise due to cancer, certain drugs, and other diseases.

The most common symptoms of meningitis are headache and neck stiffness, associated with fever, confusion or altered consciousness and inability to tolerate bright light (photophobia) or loud noises (phonophobia). Sometimes the only symptoms may be nonspecific, such as irritability and drowsiness, especially in small children. The presence of a rash may indicate particular causes, such as the non-blanching rash of meningitis caused by meningococcus bacteria. Meningitis is diagnosed by lumbar puncture, the removal with a needle of a sample of cerebrospinal fluid, the fluid that envelops the brain and the spinal cord.

Meningitis is best treated promptly with antibiotics and often antiviral drugs, and in some situations corticosteroid drugs can be used to prevent complications from overactive inflammation. Meningitis can lead to long-term complications such as deafness, epilepsy, hydrocephalus and cognitive deficit. Some forms of meningitis (such as those associated with meningococcus, Hemophilus influenzae type B, pneumococcus or mumps virus infections) may be prevented with immunization.

Signs and symptoms

Diagnostic features

In adults, severe headaches are the most common symptom of meningitis (87%) followed by nuchal rigidity ("neck stiffness", found in 83%). The classic triad of diagnostic signs consists of nuchal rigidity, sudden high fever and altered mental status. All three features are present in only 44-46% of all cases of bacterial meningitis. If none of the three signs are present, meningitis is extremely unlikely. Other signs commonly associated with meningitis are photophobia (inability to tolerate bright light), phonophobia (inability to tolerate loud noises), irritability and delirium (in small children). In infants up to 6 months, bulging of the fontanelle (soft spot) may be present. Other features that might distinguish meningitis from less severe illness in young children are leg pain, cold extremities, and abnormal skin color.

Nuchal rigidity is the inability to flex the neck forward passively due to increased tone in the neck muscles. It occurs in 70% of adult cases. Other signs of meningism include Kernig's sign and Brudzinski's sign. Kernig's sign is typically assessed with the patient lying supine, with both 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 knee and hip flexion. Although commonly tested, the sensitivity of Kernig's and Brudzinski's tests are limited. They are, however, very specific: they rarely occur in other diseases. The patient may assume the "tripod position" (extending the neck, arching the spine backward and flexing knees and hips). A test known as the "jolt accentuation maneuver" is helpful in excluding meningitis in people reporting fever and headache: if the headache is not worsened by rapidly (2-3 times per second) rotating the head horizontally, meningitis is unlikely.

In "meningococcal" meningitis (i.e. meningitis caused by the bacteria Neisseria meningitidis), a rapidly spreading petechial rash is typical, and may precede other symptoms. It is not necessarily present. The rash consists of numerous small, irregular purple or red spots on the trunk, lower extremities, mucous membranes, conjunctiva, and occasionally on the palms of hands and soles of feet. The same kind of rash is rarely seen in other forms of bacterial meningitis, but may occur in meningitis due to Haemophilus bacteria (see below). Other clues to the nature of the cause may be the skin signs of hand, foot and mouth disease and genital herpes, both of which may be associated with viral meningitis.

Most people with meningitis have no obvious source for the infection. In a small proportion, there has been previous infection in the head and neck area, such as middle ear infection, or a recent trauma to the skull during which bacteria from the nasal cavity have entered the meningeal space. Those with a previously inserted cerebral shunt (a device that drains off excessive cerebrospinal fluid) or related devices (such as an extraventricular drain or Ommaya reservoir) are at increased risk of bacterial infection of these devices.

Early complications

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 (DIC), the excessive activation of blood clotting, may lead both to the obstruction of blood flow to organs and a paradoxical increase of bleeding risk. In meningococcal disease, gangrene of limbs can occur.

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, amongst other functions. Visual symptoms and hearing loss may persist after an episode of meningitis (see below). Inflammation of the brain (encephalitis) or its blood vessels (cerebral vasculitis), as well as the formation of blood clots in the veins (cerebral venous thrombosis), may all lead to weakness, loss of sensation, or abnormal movement or function of the part of the body supplied by the affected area in the brain.

Seizures are common in children (30% of cases), but more unusual in adults, in whom it may indicate increasing intracranial pressure. 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.

Causes

Infection

Meningitis is usually caused by infection with microorganisms. Most cases are due to infection with viruses (enterovirus, herpes simplex virus 2, varicella zoster virus, mumps and HIV), followed by bacteria, fungi, or parasites.

The types of bacteria that cause bacterial meningitis vary by age group. In premature babies and newborn up to three months, common bacteria are Group B streptococcus (subtype III)–especially in the first week of life–and bacteria 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 areas without vaccination, see below). Adults, too, are predominantly affected by N. meningitidis and S. pneumoniae, with increased risk of L. monocytogenes in those over 50. In trauma, neurosurgery, or other contact between the skin and the meninges, staphylococci are more likely, as well as infections with pseudomonas and related Gram-negative bacilli. The same pathogens are also more common in those with an impaired immune system. 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.

The term aseptic meningitis 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 valves 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, the cause of 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.

Recurrent bacterial meningitis may be caused by 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, usually with leakage of cerebrospinal fluid (which can be gross or mild, depending upon the defect). Skull fractures are the most common cause of recurrent meningitis, particularly those which affect the base of the brain, or those extending towards the sinuses and petrous pyramids. Immune deficiency, such as caused by splenectomy (surgical removal of the spleen) may lead to recurrent infections. People with leukemia or lymphoma have a particularly high incidence of recurrent bacterial meningitis. When recurrent bacterial meningitis is caused by the same species of bacteria, it is likely to have been caused by inadequate therapy or resistance of the organism to previous treatment. A literature review of 363 reported cases of recurrent meningitis showed that 59% of cases occur due to anatomical abnormalities, 36% due to immune deficiencies, and 5% due to ongoing infectious in areas adjacent to the meninges.

Non-infectious

Meningitis may occur as the result of a number of non-infectious causes: spread of cancer to the meninges (malignant meningitis) and certain drugs (mainly non-steroidal anti-inflammatory drugs, antibiotics and intravenous immunoglobulins). It may also be encountered in 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. Mollaret's meningitis is a syndrome of recurring episodes of aseptic meningitis; it is now 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.

Mechanism

In most cases, meningitis follows invasion of the bloodstream by organisms which live upon mucous surfaces such as the nasal cavity. This is often preceded further by viral infections. This allows organisms to invade spaces in the blood-brain barrier that lead to the subarachnoid space—such as the choroid plexus—that have been left vulnerable from prior infections. It can also develop as a result of cerebrospinal fluid (CSF) contamination of bacteria, such as by severe head trauma involving skull fractures or by congenital dural defects.

Large-scale inflammation occurs within the subarachnoid space during meningitis; however, this is not a direct result of bacterial infection but rather of the host's inflammatory pathways caused by pro-inflammatory cytokines. Upon entry to the host's central nervous system, pathogens rapidly replicate in cell walls or membrane components. Subsequently, when using antibiotics that affect the cell walls of bacteria, products can leak into the CSF. This causes an increased permeability to the blood-brain barrier (due to vascular endothelium injury), meningeal inflammation and cerebral vasculitis. This, when large numbers of leukocytes enter the subarachnoid space, contributes to overall edema and eventually an increased intracranial pressure (ICP). It is the increased ICP that then leads to perfusion and eventually neuronal injury and apoptosis (automated cell death).

Recently, there has been move evidence to suggest that a complicated network of cytokines, chemokines, proteolytic enzymes and oxidants are responsible for the entire inflammatory process which leads to necrosis. Genetic targeting and/or pharmacological blockages of these pathways may help to prevent diffuse (widespread) brain injury and therefore decrease mortality of meningitis.

Diagnosis

In someone suspected of having meningitis, blood tests are performed for markers of inflammation (e.g. C-reactive protein), as well as blood cultures. The most important test in identifying or ruling out meningitis, however, is analysis of the cerebrospinal fluid through lumbar puncture (LP, spinal tap). If a person is at risk for a cerebral mass lesion or elevated intracranial pressure (recent head injury, a known immune system problem, localizing neurological signs, or evidence on examination of a raised ICP), a lumbar puncture may be contraindicated because of the possibility of fatal brain herniation. In such cases a CT or MRI scan is generally performed prior to the lumbar puncture to exclude these possibilities. 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 after the LP if not done previously to assess for complications of meningitis.

During the lumbar puncture procedure, the opening pressure is measured. A pressure between 200 and 500 mm H₂O (20-50 cm) is consistent with a diagnosis of bacterial meningitis, although lower values are encountered in children. 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 point at bacterial meningitis.

The cerebrospinal fluid (CSF) sample is examined for white blood cells (and which subtypes), red blood cells, 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; microbiological culture of the sample may still yield a causative organism. The type of white blood cell predominantly present predicts whether meningitis is due to bacterial or viral infection. Other tests sometimes performed on the CSF sample include the latex agglutination test, the limulus lysate test and polymerase chain reaction (PCR) for bacterial or viral DNA. Apart from PCR, which is a highly sensitive and specific technique, guidelines recommend the routine use of these tests only if Gram stain and culture have not yielded a causative organism; in other circumstances they rarely lead to changes in the treatment of the patient.

In bacterial meningitis, the CSF glucose to serum glucose ratio is =<0.4; in neonates the cutoff of 0.6 is used. High levels of lactate indicate a higher likelihood of bacterial meningitis, as does a higher white blood cell count. The Gram stain is positive in about 60% of cases; sensitivity of the Gram stain may be lower in particular infections, such as listeria. Its sensitivity is reduced by 20% if the CSF is obtained after antibiotics have already been commenced. Cultures are more sensitive, with a reported sensitivity of 70–85%, but may take up to 48 hours to become available. Latex agglutination may be positive in meningitis due to Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Escherichia coli and Group B streptococci. Limulus lysates may be positive in Gram-negative meningitis. The various causes of viral meningitis may be identified by performing PCR or serology on CSF or blood for common viral causes of meningitis (enterovirus, herpes simplex virus 2 and mumps in those not vaccinated for this). Diagnosis of cryptococcal meningitis requires an India ink stain of the CSF; alternatively, cryptococcal antigen may be detected in blood or CSF.

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).

Meningitis can be diagnosed after death has occurred. The findings from a post mortem are usually a diffuse (widespread) inflammation of the pia-arachnoid area. Neutrophil leucocytes 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.

Treatment

Initial treatment

Meningitis is a potentially life-threatening condition that has a high mortality rate if untreated; 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 benzylpenicillin is administered before transfer to hospital. High-flow oxygen should be administered as soon as possible, along with intravenous fluids if hypotensive or in shock. Given that meningitis can cause a number of early severe complications, regular medical review is recommended to identify these complications early.

Bacterial meningitis

Empiric antibiotics 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 in some situations. 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 there is a cerebral shunt 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, it may be possible to change the antibiotics to those likely to deal with the presumed pathogen.

Once the results of the CSF analysis are known, which generally takes longer, empiric therapy may be switched to specific antibiotic therapy targeted to the specific causative organism and its sensitivities. 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 patents in clinical trials. Rather, the relevant knowledge has mostly derived from laboratory studies in rabbits.

Adjuvant treatment with corticosteroids (usually dexamethasone) reduces rates of mortality, severe hearing loss and neurological damage in adults, specifically when the causative agent is Pneumococcus. The use of corticosteroids has been proven in adults as well as in children from high-income countries. Their use in children from low-income countries is not supported by evidence. In adults, professional guidelines recommend the commencement of dexamethasone or a similar corticosteroid just before the first dose of antibiotics are given, and continued for four days. Given that most of the benefit of the treatment is confined to those with pneumococcal meningitis, American guidelines suggest that dexamethasone is discontinued if another cause for meningitis is identified. In tuberculous meningitis, there is a strong evidence base for treatment with corticosteroids, although this evidence is restricted to those without AIDS.

Other infections

Viral meningitis typically requires supportive therapy only, and tends to run a more benign course than bacterial meningitis. Most viruses responsible for causing meningitis are not amenable to specific treatment. Herpes simplex virus and varicella zoster virus may respond to treatment with antiviral drugs such as acyclovir, but there are no clinical trials that have specifically addressed whether this treatment is effective. Fungal meningitis, such as cryptococcal meningitis, is treated with long courses of highly dosed antifungals, such as amphotericin B and flucytosine.

Prognosis

In children there are several potential disabilities which result from damage to the nervous system. These include sensorineural hearing loss, epilepsy, diffuse brain swelling, hydrocephalus, cerebral vein thrombosis, intra cerebral bleeding and cerebral palsy. Acute neurological complications may lead to adverse consequences. In childhood acute bacterial meningitis deafness is the most common serious complication. Sensorineural hearing loss often develops during the first few days of the illness as a result of inner ear dysfunction, but permanent deafness is rare and can be prevented by prompt treatment of meningitis.

Those who contract the disease during the neonatal period and those infected by S. pneumoniae and gram negative bacilli are at greater risk of developing neurological, auditory, or intellectual impairments or functionally important behaviour or learning disorders which can manifest as poor school performance.

In adults central nervous system complications include brain infarction, brain swelling, hydrocephalus, intracerebral bleeding; systemic complications are dominated by septic shock, adult respiratory distress syndrome and disseminated intravascular coagulation. Those who have underlying predisposing conditions e.g. head injury may develop recurrent meningitis. Case-fatality ratio is highest for gram-negative etiology and lowest for meningitis caused by H. influenzae (also a gram negative bacilli). Fatality for those over 60 years of age is more likely to be from systemic complications e.g. pneumonia, sepsis, cardio-respiratory failure; however in younger individuals it is usually associated with neurological complications. Age more than 60, low Glasgow coma scale at presentation and seizure within 24 hours increase the risk of death among community acquired meningitis.

Epidemiology

Exact rates of meningitis are not known, despite the fact that in many countries public health bodies need to be notified for every episode; studies have shown that bacterial meningitis occurs in about 3 people per 100,000 annually in Western countries. 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. In sub-Saharan Africa, large epidemics of meningococcal meningitis occur in the dry season, leading to it being labeled the "meningitis belt"; annual rates of 500 cases per 100,000 are encountered in this area, which is poorly served by medical care. These cases are predominantly caused by meningococcus. Meningococcal disease has also occurred in epidemics in areas where many people live together, such as army barracks (especially during mobilization), college campuses and the annual Hajj pilgrimage.

There are significant differences in the local distribution of causes for bacterial meningitis. For instance, N. meningitides groups B and C cause most disease episodes in Europe, while group A meningococci are more common in China and amongst Hajj pilgrims. In the "meningitis belt" of Africa, group A and C meningicocci cause most of the outbreaks. Group W135 meningococci have caused several recent epidemics in Africa and during the Hajj. These differences are expected to change further as vaccines against common strains are introduced.

Prevention

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 meningococus group C vaccine 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 meningococcus; some have shown good results and are used in local immunization schedules.

Pneumococcal polysaccharide vaccine against Streptococcus pneumoniae has the potential to prevent meningitis due to this pathogen. However, the vaccines only cover a particular group of subtypes, and the vaccine is expensive. 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.

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.

History

Some suggest that Hippocrates 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 credited to Edinburgh physician Sir Robert Whytt in a posthumous report that appeared in 1768. Still, it appears that epidemic meningitis is a relatively recent disease. 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 Simon Flexner and markedly decreased mortality from meningococcal disease. In 1944, penicillin was first reported to be effective in meningitis.

References

1. ^ Sáez-Llorens X, McCracken GH (2003). "Bacterial meningitis in children". Lancet. 361 (9375): 2139–48. doi:10.1016/S0140-6736(03)13693-8. PMID 12826449. {{cite journal}}: Unknown parameter |month= ignored (help)
2. ^ Ginsberg L (2004). "Difficult and recurrent meningitis". Journal of neurology, neurosurgery, and psychiatry. 75 Suppl 1: i16–21. doi:10.1136/jnnp.2003.034272. PMC 1765649. PMID 14978146. {{cite journal}}: Unknown parameter |month= ignored (help)
3. ^ Tunkel AR, Hartman BJ, Kaplan SL; et al. (2004). "Practice guidelines for the management of bacterial meningitis". Clinical Infectious Diseases. 39 (9): 1267–84. doi:10.1086/425368. PMID 15494903. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
4. van de Beek D, de Gans J, Spanjaard L, Weisfelt M, Reitsma JB, Vermeulen M (2004). "Clinical features and prognostic factors in adults with bacterial meningitis". The New England journal of medicine. 351 (18): 1849–59. doi:10.1056/NEJMoa040845. PMID 15509818. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
5. ^ Attia J, Hatala R, Cook DJ, Wong JG (1999). "The rational clinical examination. Does this adult patient have acute meningitis?". JAMA. 282 (2): 175–81. doi:10.1001/jama.282.2.175. PMID 10411200. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
6. ^ Theilen U, Wilson L, Wilson G, Beattie JO, Qureshi S, Simpson D (2008). "Management of invasive meningococcal disease in children and young people: summary of SIGN guidelines". BMJ (Clinical research ed.). 336 (7657): 1367–70. doi:10.1136/bmj.a129. PMC 2427067. PMID 18556318. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
7. Thomas KE, Hasbun R, Jekel J, Quagliarello VJ (2002). "The diagnostic accuracy of Kernig's sign, Brudzinski's sign, and nuchal rigidity in adults with suspected meningitis". Clinical infectious diseases. 35 (1): 46–52. doi:10.1086/340979. PMID 12060874. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
8. ^ Logan SA, MacMahon E (2008). "Viral meningitis". BMJ (Clinical research ed.). 336 (7634): 36–40. doi:10.1136/bmj.39409.673657.AE. PMC 2174764. PMID 18174598. {{cite journal}}: Unknown parameter |month= ignored (help)
9. Thwaites G, Chau TT, Mai NT, Drobniewski F, McAdam K, Farrar J (2000). "Tuberculous meningitis". Journal of neurology, neurosurgery, and psychiatry. 68 (3): 289–99. PMC 1736815. PMID 10675209. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
10. ^ Menkes, John H (1980). Textbook of Child Neurology. Henry Kimpton Publishers. ISBN 0-8121-0661-X.
11. Tebruegge M, Curtis N (2008). "Epidemiology, etiology, pathogenesis, and diagnosis of recurrent bacterial meningitis". Clinical microbiology reviews. 21 (3): 519–37. doi:10.1128/CMR.00009-08. PMID 18625686. {{cite journal}}: Unknown parameter |month= ignored (help)
12. Chamberlain MC (2005). "Neoplastic meningitis". Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 23 (15): 3605–13. doi:10.1200/JCO.2005.01.131. PMID 15908671. {{cite journal}}: Unknown parameter |month= ignored (help)
13. Moris G, Garcia-Monco JC (1999). "The Challenge of Drug-Induced Aseptic Meningitis". Archives of Internal Medicine. 159 (11): 1185–94. doi:10.1001/archinte.159.11.1185. PMID 10371226. {{cite journal}}: Unknown parameter |month= ignored (help)
14. Provan, Drew (2005). Oxford Handbook of clinical and laboratory investigation. Oxford: Oxford University Press. ISBN 0198566638. {{cite book}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
15. ^ Straus SE, Thorpe KE, Holroyd-Leduc J (2006). "How do I perform a lumbar puncture and analyze the results to diagnose bacterial meningitis?". JAMA : the journal of the American Medical Association. 296 (16): 2012–22. doi:10.1001/jama.296.16.2012. PMID 17062865. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
16. ^ Heyderman RS, Lambert HP, O'Sullivan I, Stuart JM, Taylor BL, Wall RA (2003). "Early management of suspected bacterial meningitis and meningococcal septicaemia in adults". The Journal of infection. 46 (2): 75–7. doi:10.1053/jinf.2002.1110. PMID 12634067. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link) - formal guideline at British Infection Society & UK Meningitis Research Trust (2004). "Early management of suspected meningitis and meningococcal septicaemia in immunocompetent adults" (PDF). British Infection Society Guidelines. Retrieved 2008-10-19. {{cite web}}: Unknown parameter |month= ignored (help)
17. ^ Bicanic T, Harrison TS (2004). "Cryptococcal meningitis". British medical bulletin. 72: 99–118. doi:10.1093/bmb/ldh043. PMID 15838017.
18. Warrell, David A (2003). Oxford Textbook of Medicine Volume One. Oxford. pp. 1115–1129. ISBN 0-19852787-X. {{cite book}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
19. van de Beek D, de Gans J, McIntyre P, Prasad K (2007). "Corticosteroids for acute bacterial meningitis". Cochrane database of systematic reviews (Online) (1): CD004405. doi:10.1002/14651858.CD004405.pub2. PMID 17253505.{{cite journal}}: CS1 maint: multiple names: authors list (link)
20. Prasad K, Singh MB (2008). "Corticosteroids for managing tuberculous meningitis". Cochrane database of systematic reviews (Online) (1): CD002244. doi:10.1002/14651858.CD002244.pub3. PMID 18254003.
21. Gottfredsson M, Perfect JR (2000). "Fungal meningitis". Seminars in neurology. 20 (3): 307–22. doi:10.1055/s-2000-9394. PMID 11051295.
22. Vasallo, G (January 2004). "Neurological complications of pneumococcal meningitis". Developmental Medicine and Child Neurology. Vol. 46: pg. 11. {{cite journal}}: |pages= has extra text (help); |volume= has extra text (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
23. Richardson MP, Reid A, Tarlow MJ, Rudd PT (1997). "Hearing loss during bacterial meningitis". Archives of disease in childhood. 76 (2): 134–8. PMC 1717058. PMID 9068303. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
24. Grimwood K (2001). "Legacy of bacterial meningitis in infancy. Many children continue to suffer functionally important deficits". BMJ (Clinical research ed.). 323 (7312): 523–4. doi:10.1136/bmj.323.7312.523. PMC 1121114. PMID 11546680. {{cite journal}}: Unknown parameter |month= ignored (help)
25. Pfister HW, Feiden W, Einhäupl KM (1993). "Spectrum of complications during bacterial meningitis in adults. Results of a prospective clinical study". Archives of neurology. 50 (6): 575–81. PMID 8503793. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
26. ^ Adriani KS, van de Beek D, Brouwer MC, Spanjaard L, de Gans J (2007). "Community-acquired recurrent bacterial meningitis in adults". Clinical infectious diseases. 45 (5): e46–51. doi:10.1086/520682. PMID 17682979. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
27. Durand ML, Calderwood SB, Weber DJ; et al. (1993). "Acute bacterial meningitis in adults. A review of 493 episodes". The New England journal of medicine. 328 (1): 21–8. doi:10.1056/NEJM199301073280104. PMID 8416268. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
28. ^ Wilder-Smith A (2007). "Meningococcal vaccine in travelers". Current opinion in infectious diseases. 20 (5): 454–60. doi:10.1097/QCO.0b013e3282a64700. PMID 17762777. {{cite journal}}: Unknown parameter |month= ignored (help)
29. ^ Segal S, Pollard AJ (2004). "Vaccines against bacterial meningitis". British medical bulletin. 72: 65–81. doi:10.1093/bmb/ldh041. PMID 15802609.
30. Peltola H (2000). "Worldwide Haemophilus influenzae type b disease at the beginning of the 21st century: global analysis of the disease burden 25 years after the use of the polysaccharide vaccine and a decade after the advent of conjugates". Clinical microbiology reviews. 13 (2): 302–17. doi:10.1128/CMR.13.2.302-317.2000. PMC 100154. PMID 10756001. {{cite journal}}: Unknown parameter |month= ignored (help)
31. ^ Harrison LH (2006). "Prospects for vaccine prevention of meningococcal infection". Clinical microbiology reviews. 19 (1): 142–64. doi:10.1128/CMR.19.1.142-164.2006. PMC 1360272. PMID 16418528. {{cite journal}}: Unknown parameter |month= ignored (help)
32. Fraser A, Gafter-Gvili A, Paul M, Leibovici L (2006). "Antibiotics for preventing meningococcal infections". Cochrane database of systematic reviews (Online) (4): CD004785. doi:10.1002/14651858.CD004785.pub3. PMID 17054214.{{cite journal}}: CS1 maint: multiple names: authors list (link)
33. ^ Arthur Earl Walker, Edward R. Laws, George B. Udvarhelyi (1998). "Infections and inflammatory involvement of the CNS". The Genesis of Neuroscience. Thieme. pp. 219–21. ISBN 1-879-28462-6.{{cite book}}: CS1 maint: multiple names: authors list (link)
34. Whytt R (1768). Observations on the Dropsy in the Brain. Edinburgh: J. Balfour.
35. ^ Greenwood B (2006). "Editorial: 100 years of epidemic meningitis in West Africa - has anything changed?". Tropical medicine & international health : TM & IH. 11 (6): 773–80. doi:10.1111/j.1365-3156.2006.01639.x. PMID 16771997. {{cite journal}}: Unknown parameter |month= ignored (help)
36. Vieusseux G (1806). "Memoire sur la maladie qui regnéà Geneve au printemps de 1805". Journal de Médecine, de Chirurgie et de Pharmacologie (Bruxelles). 11: 50–53.
37. Weichselbaum A (1887). "Ueber die Aetiologie der akuten Meningitis cerebro-spinalis". Fortschrift der Medizin. 5: 573–583.
38. ^ Swartz MN (2004). "Bacterial meningitis--a view of the past 90 years". The New England journal of medicine. 351 (18): 1826–8. doi:10.1056/NEJMp048246. PMID 15509815. {{cite journal}}: Unknown parameter |month= ignored (help)
39. Rosenberg DH, Arling PA (1944). "Penicillin in the treatment of meningitis". JAMA. 125: 1011–1017. reproduced in Rosenberg DH, Arling PA (1984). "Penicillin in the treatment of meningitis". JAMA. 251 (14): 1870–6. PMID 6366279. {{cite journal}}: Unknown parameter |month= ignored (help)

External links

• Template:Dmoz

• WHO: Meningococcal meningitis
• Merck Manual: Central nervous system infections
• CDC: Meningococcal disease

• Inflammations
• Medical emergencies
• Neurological disorders