Viral meningitis, sometimes referred to as nonbacterial or aseptic meningitis, is milder and more common than bacterial forms. It can be caused by any of a number of viruses, including enteroviruses, the mumps virus, herpesviruses, HIV, and several mosquito-borne viruses (Bunyavirus and flavivirus) usually associated with encephalitis. Viral meningitis is usually seen only in individual cases rather than in outbreaks. Those not vector-borne are usually spread from person to person by the fecal-oral route. Symptoms include headache, fever, stiff neck, and tiredness, sometimes accompanied by a rash. There is no specific treatment.
A variety of organisms can cause bacterial meningitis, a serious form that can be fatal, especially in children. Symptoms include high fever, headache, chills, vomiting, stiff neck or back, and confusion, sometimes accompanied by a purplish rash. Serious cases can quickly lead to delirium, coma, or convulsions. It is spread by oral or nasal secretions.
The leading cause of bacterial meningitis is the ill-named bacterium Haemophilus influenzae b (Hib), originally thought to be an influenza virus. It commonly affects infants and children. The second most common bacterial cause of meningitis is Neisseria meningitidis (meningococcus). Meningococcal meningitis affects people of all ages and tends to occur in epidemics, especially among those who live in crowded conditions. An outbreak in the slums of Brazil in 1974-75 killed 11,000 people and left over 75,000 with permanent neurological complications. In 1996, an epidemic centered in the Sahel region of W Africa killed 16,000. In the United States it is seen most often in children and teens.
Strepococcus pneumoniae, also referred to as pneumococcus, is another cause of serious meningitis cases. It is the most common cause of meningitis in adults. It often accompanies pneumococcus infections in other parts of the body, such as the ear or sinuses. Other bacterial causes of meningitis include tuberculosis, leptospirosis, and Lyme disease.
Bacterial meningitis calls for emergency medical care and the administration of antibiotics. Close contacts of patients with bacterial meningitis may receive prophylactic antibiotics, such as rifampin. Definitive diagnosis can be made by laboratory tests of cerebrospinal fluid obtained by a lumbar puncture (spinal tap). Twenty to thirty percent of children who survive bacterial meningitis sustain permanent neurological damage such as deafness, mental retardation, or convulsions. Since the late 1980s, routine vaccination of young children against Hib has virtually eliminated Hib disease in the United States. Routine vaccination against meningococcal meningitis is recommended for pre-adolescents, and vaccination is also recommended for persons in the military or traveling to parts of Africa where the disease is endemic. The meningococcal vaccine does not provide protection against all meningococcus strains.
Fungal meningitis has been on the rise in the United States due to opportunistic infection with Cryptococcus neoformans in people weakened by AIDS. In these patients, it is often fatal. It can be treated with the antifungals amphotericin B and fluconazole. Other causes include coccidioidomycosis and histoplasmosis.
The most common symptoms of meningitis are headache and neck stiffness. There can also be fever, altered consciousness and inability to tolerate bright light (photophobia) or loud noises (phonophobia). In meningococcal meningitis (caused by a type of bacteria called meningococcus) there is a typical petechial rash consisting of small purple or red spots that do not blanch when compressed (which can be checked using a transparent object such as a glass). 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. The potential for serious neurological damage or even death necessitates prompt medical evaluation.
The inflammation is usually caused by an infection of the fluid surrounding the brain and spinal cord. Meningitis may develop in response to a number of causes, usually bacteria, viruses and other microbes, but also physical injury, cancer or certain drugs.
Meningitis is treated promptly with antibiotics or antiviral drugs. To prevent complications from overactive inflammation, corticosteroid drugs are given in some situations. Some forms of meningitis (such as those associated with meningococcus, mumps virus or pneumococcus infections) are contagious, but may be prevented with immunization. Meningitis can also lead to long-term complications such as deafness, epilepsy or hydrocephalus.
Severe headache is the most common symptom of meningitis (87 percent) 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% of all cases of infectious meningitis. 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) and seizures (in 20-40% of cases). In infants (0-6 months), swelling of the fontanelle (soft spot) may be present.
Nuchal rigidity is the inability to flex the neck forward passively due to increased tone in the neck muscles. 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 and specificity of Kernig's and Brudzinski's tests are limited.
In "meningococcal" meningitis (i.e. meningitis caused by the bacteria Neisseria meningitidis), a rapidly spreading petechial rash is typical, and may precede other symptoms. 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. 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.
|Acute bacterial meningitis||Low||high||high, often > 300/mm³|
|Acute viral meningitis||Normal||normal or high||mononuclear, < 300/mm³|
|Tuberculous meningitis||Low||high||pleocytosis, mixed < 300/mm³|
|Fungal meningitis||Low||high||< 300/mm³|
|Malignant meningitis||Low||high||usually mononuclear|
|Subarachnoid hemorrhage||Normal||normal, or high||Erythrocytes|
Investigations include blood tests (electrolytes, liver and kidney function, inflammatory markers and a complete blood count) and usually X-ray examination of the chest. The most important test in identifying or ruling out meningitis is analysis of the cerebrospinal fluid (fluid that envelops the brain and the spinal cord) through lumbar puncture (LP). However, 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. Otherwise, the CT or MRI should be performed after the LP, with MRI preferred over CT due to its superiority in demonstrating areas of cerebral edema, ischemia, and meningeal inflammation.
During the lumbar puncture procedure, the opening pressure is measured. A pressure of over 180 mm H2O is consistent with a diagnosis of 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 performed on the CSF sample include the latex agglutination test, the LAL test and polymerase chain reaction (PCR) for bacterial or viral DNA. If a person is immunocompromised, testing the CSF for toxoplasmosis, Epstein-Barr virus, cytomegalovirus, JC virus and fungal infection may be performed.
In bacterial meningitis, the CSF glucose to serum glucose ratio is < 0.4. The Gram stain is positive in >60% of cases, and culture in >80%. Latex agglutination may be positive in meningitis due to Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Escherichia coli, Group B Streptococci. Limulus lysates may be positive in Gram-negative meningitis.
Cultures are often negative if CSF is taken after the administration of antibiotics. If this happens, PCR can be helpful in arriving at a diagnosis. It has been suggested that CSF cortisol measurement may be helpful.
Aseptic meningitis refers to non-bacterial causes of meningitis and includes infective etiologies such as viruses and fungi, neoplastic etiologies such as carcinomatous and lymphomatous meningitis, inflammatory causes such as sarcoidosis (neurosarcoidosis)) and chemical causes such as meningitis secondary to the intrathecal introduction of contrast media.
Although the term "viral meningitis" is often used for someone with a mild meningeal illness with appropriate CSF findings, certain people will present with clinical and CSF features of viral meningitis, yet ultimately be diagnosed with one of the other conditions categorized as "aseptic meningitis". This may be prevented 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).
A related 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).
Meninigitis 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.
The Bacterial Meningitis Score predicts reliably whether a child (older than two months) may have infectious meningitis. In children with at least 1 risk factor (positive CSF Gram stain, CSF absolute neutrophil count ≥ 1000 cell/µL, CSF protein ≥ 80 mg/dL, peripheral blood absolute neutrophil count ≥ 10,000 cell/µL, history of seizure before or at presentation time) it had a sensitivity of 100%, specificity of 63.5%, and negative predictive value of 100%.
Most cases of meningitis are caused by microorganisms, such as viruses, bacteria, fungi, or parasites, that spread into the blood and into the cerebrospinal fluid (CSF). Non-infectious causes include cancers, systemic lupus erythematosus and certain drugs. The most common cause of meningitis is viral, and often runs its course within a few days. Bacterial meningitis is the second most frequent type and can be serious and life-threatening. Numerous microorganisms may cause bacterial meningitis, but Neisseria meningitidis ("meningococcus") and Streptococcus pneumoniae ("pneumococcus") are the most common pathogens in people without immune deficiency, with meningococcal disease being more common in children. Staphylococcus aureus may complicate neurosurgical operations, and Listeria monocytogenes is associated with poor nutritional state and alcoholism. Haemophilus influenzae (type b) incidence has been much reduced by immunization in many countries. Mycobacterium tuberculosis (the causative agent of tuberculosis) rarely causes meningitis in Western countries but is common and feared in countries where tuberculosis is endemic. A rare, usually fatal type of meningitis is primary amoebic meningoencephalitis, which is most notably caused by Naegleria fowleri, though it can also be a result of infection by Balamuthia mandrillaris or other amoebae.
Meningitis is a life-threatening condition and treatment with wide-spectrum antibiotics should not be delayed while confirmatory tests are being conducted. High-flow oxygen should be administered as soon as possible, along with intravenous fluids if hypotensive or in shock.
Bacterial meningitis is a medical emergency and has a high mortality rate if untreated. All suspected cases, however mild, need emergency medical attention. Empiric antibiotics must be started immediately, even before the results of the lumbar puncture and CSF analysis are known. Antibiotics started within 4 hours of lumbar puncture will not significantly affect lab results. Adjuvant treatment with corticosteroids reduces rates of mortality, severe hearing loss and neurological sequelae in adults, specifically when the causative agent is Pneumococcus.
|Neonates||Group B Streptococci, Escherichia coli, Listeria monocytogenes|
|Infants||Neisseria meningitidis, Haemophilus influenzae, Streptococcus pneumoniae|
|Children||N. meningitidis, S. pneumoniae|
|Adults||S. pneumoniae, N. meningitidis, Mycobacteria, Cryptococci|
The choice of antibiotic depends on local advice. In most of the developed world, the most common organisms involved are Streptococcus pneumoniae and Neisseria meningitidis: first line treatment in the UK is a third-generation cephalosporin (such as ceftriaxone or cefotaxime). In those under 3 years of age, over 50 years of age, or immunocompromised, ampicillin should be added to cover Listeria monocytogenes. In the U.S. and other countries with high levels of penicillin resistance, the first line choice of antibiotics is vancomycin and a carbapenem (such as meropenem). In sub-Saharan Africa, oily chloramphenicol or ceftriaxone are often used.
Staphylococci and gram-negative bacilli are common infective agents in individuals who have just had a neurosurgical procedure. Again, the choice of antibiotic depends on local patterns of infection: cefotaxime and ceftriaxone remain good choices in many situations, but ceftazidime is used when Pseudomonas aeruginosa is a problem, and intraventricular vancomycin is used for those with intraventricular shunts because of high rates of staphylococcal infection. For people with intracerebral prosthetic material (metal plates, electrodes or implants, etc.) then sometimes chloramphenicol is the only antibiotic that will adequately cover infection by Staphylococcus aureus (cephalosporins and carbapenems are inadequate under these circumstances).
Once the results of the CSF analysis are known along with the Gram-stain and culture, empiric therapy may be switched to therapy targeted to the specific causative organism and its sensitivities.
A person diagnosed with mild viral meningitis may improve quickly enough to not require admission to a hospital, while others may be hospitalized for many more days for observation and supportive care. Overall, the illness is usually much less severe than bacterial meningitis.
Unlike bacteria, viruses cannot be killed by antibiotics. Drugs such as acyclovir may be employed if herpes virus infection is either suspected or demonstrated.
This form of meningitis is rare in otherwise healthy people but is a higher risk in those who have AIDS, other forms of immunodeficiency (an immune system that does not respond adequately to infections) and immunosuppression (immune system malfunction as a result of medical treatment). In AIDS, Cryptococcus neoformans is the most common cause of fungal meningitis; it requires Indian ink staining of the CSF sample for identification of this capsulated yeast. Fungal meningitis is treated with long courses of highly dosed antifungals.
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.
Recurrent bacterial meninigitis may be caused by anatomical defects, either congenital or aquired, or by disorders in immune mechanisms. Anatomic defects are ususally those which allow continuity between the external environment and the nervous system, ususally 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. Neuroschisis may also be present in front of the pharynx as an encephalocele or defect in the cribriform or orbital plates.
Recurrent infections due to immune response may occur after a splenectomy, or in other conditions affecting the immune system. Leukemias and lymphomas have particularly high incidences of recurrent bacterial meningitis. When recurrent bacterial meningitis is caused by the same species of bacteria, it is likely to have been caused by inadequete therapy or resistence of the organism to previous treatment.
Vaccines against type A and C Neisseria meningitidis, the kind that causes most disease in preschool children and teenagers in the United States, have also been around for a while. Type A is also prevalent in sub-Sahara Africa and W135 outbreaks have affected those on the Hajj pilgrimage to Mecca. Immunisation with the ACW135Y vaccine against four strains is now a visa requirement for taking part in the Hajj.
Vaccines against type B Neisseria meningitidis are much harder to produce, as its capsule is very weakly immunogenic masking its antigenic proteins. There is also a risk of autoimmune response, and the porA and porB proteins on Type B resemble neuronal molecules. A vaccine called MeNZB for a specific strain of type B Neisseria meningitidis prevalent in New Zealand has completed trials and is being given to many people in the country under the age of 20 free of charge. There is also a vaccine, MenBVac, for the specific strain of type B meningococcal disease prevalent in Norway, and another specific vaccine for the strain prevalent in Cuba. Novartis has conducted preliminary clinical trials of a meningococcus type B vaccine in Britain with encouraging results.
Pneumococcal polysaccharide vaccine against Streptococcus pneumoniae is recommended for all people 65 years of age or older. Pneumococcal conjugate vaccine is recommended for all newborns starting at 6 weeks - 2 months, according to American Academy of Pediatrics (AAP) recommendations.
Mumps vaccination has led to a sharp decline in mumps virus associated meningitis, which prior to vaccination occurred in 15% of all cases of mumps.
Meningitis occurs in localised outbreaks, whose scale depends on several factors including amount of contact with other people and varies seasonally. People with weaker immune systems are more susceptable, but during large epidemics Meningitis can affect any age group. In temperate climates winter and spring increase the number of cases.
In the area in sub-Saharan Africa stretching from Senegal to Ethiopia (largely coinciding with the Sahel region), large epidemics of meningococcal meningitis occur in the dry season, leading to it being labelled the Meningitis Belt. These outbreaks occur in a cyclic fashion, due to herd immunity from vaccinations, and have localised infection rates of up to 1 in 100 people.
The largest epidemic outbreak was in 1996, when over 250,000 cases occurred and 25,000 people died as a consequence of the disease.
Meningitis was first described in Avicenna's 1025 medical encyclopedia, 'The Canon of Medicine, and again more accurately by Avenzoar of al-Andalus in the 12th century. Symptoms of the disease were also noted in 1805 by the Swiss Gabinetto Vieusseux (a scientific-literary association) during an outbreak in Geneva, Switzerland. In 1887, Dr. Anton Weichselbaum (1845-1920) of Vienna became the first to isolate the specific germ, meningococcus.
In the 19th century, meningitis was a scourge of the Japanese imperial family, playing the largest role in the horrendous pre-maturity mortality rate the family endured. In the mid-1800s, only the Emperor Kōmei and two of his siblings reached maturity out of fifteen total children surviving birth. Kōmei's son, the Emperor Meiji, was one of two survivors out of Kōmei's six children, including an elder brother of Meiji who would have taken the throne had he lived to maturity. Five of Meiji's 15 children survived, including only his third son, Emperor Taishō, who was feeble-minded, perhaps as a result of having contracted meningitis himself. By Emperor Hirohito's generation the family was receiving modern medical attention. As the focal point of tradition in Japan, during the Tokugawa Shogunate the family was denied modern "Dutch" medical treatment then in use among the upper caste; despite extensive modernization during the Meiji Restoration in the latter half of the 19th centrury, the Emperor insisted on traditional medical care for his children.