'Meningitis' is the
inflammation of the protective membranes covering the
central nervous system, known collectively as the
meninges. Meningitis may develop in response to a number of causes, including infectious agents, physical injury,
cancer, or certain drugs. While some forms of meningitis are mild and resolve on their own, meningitis is a potentially serious condition owing to the proximity of the inflammation to the brain and spinal cord. The potential for serious neurologic damage or even death necessitates prompt medical attention and evaluation. Infectious meningitis, the most common form, is typically treated with
antibiotics and close observation.
Signs and symptoms
Headache is the most common symptom of meningitis (87 percent) followed by
nuchal rigidity ("neck stiffness", 83 percent). The classic triad of diagnostic signs consists of nuchal rigidity (being unable to flex the neck forward),
fever and altered mental status. All three features are present in only 44% of all cases of infectious meningitis.
[1] 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 typically assessed with the patient lying
supine, and both hips and knees flexed. If pain is elicited when the knees are passively extended (
Kernig's sign), this indicates nuchal rigidity and meningitis. In infants, forward flexion of the neck may cause involuntary knee and hip flexion (
Brudzinski's sign). Although commonly tested, the sensitivity and specificity of Kernig's and Brudzinski's tests are uncertain.
[ The diagnostic accuracy of Kernig's sign, Brudzinski's sign, and nuchal rigidity in adults with suspected meningitis, Thomas KE, Hasbun R, Jekel J, Quagliarello VJ, , , Clin. Infect. Dis., 2002 ]
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.
Diagnosis
Investigations
The suspicion of meningitis is generally based on the nature of the symptoms and findings on
physical examination. Meningitis is a
medical emergency, and referral to hospital is indicated. If meningitis is suspected based on clinical examination, early administration of
antibiotics is recommended, as the condition may deteriorate rapidly. In the hospital setting, initial management consists of stabilization (e.g. securing the
airway in a depressed level of consciousness, administration of
intravenous fluids in
hypotension or
shock), followed by antibiotics if not already administered.
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 the patient 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 this possibility. 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 mmH
2O is indicative of bacterial meningitis.
The 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
latex agglutination test,
limulus lysates, or
polymerase chain reaction (PCR) for bacterial or viral DNA. If the patient is
immunocompromised, testing the CSF for
toxoplasmosis,
Epstein-Barr virus,
cytomegalovirus,
JC virus and
fungal infection may be performed.
'CSF finding in differrent conditions'[2]| Condition | Glucose | Protein | Cells |
|---|
| 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 haemorrhage | Normal | normal, or high | Erythrocytes |
|---|
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. In these patients,
PCR can be helpful in arriving at a diagnosis. It has been suggested that CSF
cortisol measurement may be helpful.
[3]
Prediction rules
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%.
[4]
Causes
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).
[ Sherris Medical Microbiology, Ryan KJ, Ray CG (editors), , , McGraw Hill, 2004, ] 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 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 patients 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 alcoholicism. ''
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.
Treatment
Bacterial meningitis
Bacterial meningitis is a
medical emergency and has a high mortality rate if untreated.
[ Initial Management of Acute Bacterial Meningitis in Adults: Summary of IDSA Guidelines, Beckham J, Tyler K, , , Rev Neurol Dis, 2006 ] 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.
[5]
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 because only a single dose is needed in most cases.
Staphylococci and gram-negative bacilli are common infective agents in patients 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 patients with intraventricular shunts because of high rates of
staphylococcal infection. In patients 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.
★ ''
Neisseria meningitidis'' (Meningococcus) can usually be treated with a 7-day course of IV antibiotics:
★
★ Penicillin-sensitive --
penicillin G or
ampicillin
★
★ Penicillin-resistant --
ceftriaxone or
cefotaxime
★
★ Prophylaxis for close contacts (contact with oral secretions) --
rifampin 600 mg bid for 2 days ''(adults)'' or 10 mg/kg bid ''(children)''. Rifampin is not recommended in pregnancy and as such, these patients should be treated with single doses of
ciprofloxacin,
azithromycin, or
ceftriaxone
★ ''
Streptococcus pneumoniae'' (Pneumococcus) can usually be treated with a 2-week course of IV antibiotics:
★
★ Penicillin-sensitive --
penicillin G
★
★ Penicillin-intermediate --
ceftriaxone or
cefotaxime
★
★ Penicillin-resistant --
ceftriaxone or
cefotaxime +
vancomycin
★ ''
Listeria monocytogenes'' is treated with a 3-week course of IV
ampicillin +
gentamicin.
★ Gram negative bacilli --
ceftriaxone or
cefotaxime
★ ''
Pseudomonas aeruginosa'' --
ceftazidime''
★ ''
Staphylococcus aureus''
★
★ Methicillin-sensitive --
nafcillin
★
★ Methicillin-resistant --
vancomycin
★ ''
Streptococcus agalactiae'' --
penicillin G or
ampicillin
★ ''
Haemophilus influenzae'' --
ceftriaxone or
cefotaxime
Viral meningitis
Unlike bacteria, viruses cannot be killed by antibiotics. Patients with very mild viral meningitis may only have to spend a few hours in a hospital, while those who have a more serious infection may be hospitalised for many more days for supportive care. Patients with mild cases, which often cause only flu-like symptoms, may be treated with fluids, bed rest (preferably in a quiet, dark room), and analgesics for pain and fever. Serious cases, especially in the case of young children or neonates, may require the use of antiviral drugs, such as
acyclovir. The physician may also prescribe
anticonvulsants such as
phenytoin to prevent
seizures and
corticosteroids to reduce brain inflammation. If inflammation is severe, pain medicine and sedatives may be prescribed to make the patient more comfortable.
Fungal meningitis
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.
[6]
Complications
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[7]. Acute neurological complications may lead to adverse consequences. Those contract the disease during
neonatal period and those infected by S pneumoniae and gram negative
bacilli are in greater risk of developing neurological, auditory, or intellectual impairments or functionally important behaviour or learning disorders which can manifest as poor school performance
[8]. Those who have underlying predisposing conditions e.g. head injury may develop recurrent meningitis
[9].
In adults
case-fatality ratio is highest for
gram-negative etiology and lowest for meningitis caused by
''H influenzae'' (also a gram negative bacili). Fatal outcome in patients over 60 years of age are 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
[9]. Age more than 60, low
glasgow coma scale at presentation and
seizure within 24 hours increase the risk of death among community acquired meningitis
[11].
A common complication is loss of hearing as a result from damages to the
hair cells in the
cochlea, making them unable to transmit fluid-borne sound vibrations into electrical signaling to the
auditory cortex. Hearing may be restored with the use of a
cochlear implant, with better prognosis for the patient if they receive it early. As time passes from the meningitis until the implantation, the liquid in the cochlea may become progressively stiffer, first like jelly and then already within two months it may become hard like bone, making the implantation impossible to perform. But if the implant is received quickly enough, the resulting artificial hearing may be very good. A one-year-old child completely losing all hearing and receiving implants within 4 weeks can get an artificial hearing that is good enough to understand spoken language as well as, or even better than average children of the same age.
Prevention
Immunization
All current vaccines target only bacterial meningitis.
Vaccinations against ''
Haemophilus influenzae'' (
Hib) have decreased early childhood meningitis significantly.
[12]
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.
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. There is also a vaccine, MenBVac, for the specific strain of type B meningoccocal disease prevalent in
Norway, and another specific vaccine for the strain prevalent in
Cuba.
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 Association of Pediatrics (AAP) recommendations.
Prophylaxis
In cases of meningococcal meningitis, prophylactic treatment of close relatives with antibiotics (e.g.
rifampicin,
ciprofloxacin or
ceftriaxone) may reduce the risk of further cases.
[13]
Epidemiology
Countries with reported cases of meningitis. Red: meningitis belt, orange: epidemic meningitis, grey: sporadic cases
Meningitis can affect anyone in any age group, from the newborn to the elderly.
The "Meningitis Belt" is an area in
sub-Saharan Africa which stretches from
Senegal in the west to
Ethiopia in the east in which large epidemics of meningococcal meningitis occur (this largely coincides with the
Sahel region). It contains an estimated total population of 300 million 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.
History
Meningitis may have been described in the
Middle Ages, but it was first accurately identified by the
Swiss Vieusseux (a scientific-literary association) during an outbreak in
Geneva,
Switzerland in 1805.
In the 19th century, meningitis was a scourge of the
Japanese imperial family, playing the largest role in the horrendous pre-maturity death 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 the Emperor insisted on
traditional medical care for his children.
See also
★
Encephalitis
★
Maurice Hilleman
References
1. Clinical features and prognostic factors in adults with bacterial meningitis, van de Beek D, de Gans J, Spanjaard L, Weisfelt M, Reitsma JB, Vermeulen M, , , N. Engl. J. Med., 2004
2. Oxford Handbook of clinical and laboratory investigation, , Drew, Provan, Oxford university press, 2005,
3. Cortisol levels in cerebrospinal fluid correlate with severity and bacterial origin of meningitis, Holub M, Beran O, Dzupova O, ''et al.'', , , Critical Care, 2007
4. Clinical prediction rule for identifying children with cerebrospinal fluid pleocytosis at very low risk of bacterial meningitis, Nigrovic LE, Kuppermann N, Macias CG, ''et al'', , , JAMA, 2007
5. Corticosteroids for acute bacterial meningitis, van de Beek D, de Gans J, McIntyre P, Prasad K, , , Cochrane database of systematic reviews (Online), 2007
6. Fungal meningitis, Gottfredsson M, Perfect JR, , , Seminars in neurology, 2000
7. Neurological complications of pneumococcal meningitis, , G, Vasallo, Developmental Medicine and Child Neurology,
8. Legacy of bacterial meningitis in infancy. Many children continue to suffer functionally important deficits, Grimwood K, , , BMJ, 2001
9. Community-acquired recurrent bacterial meningitis in adults, Adriani KS, van de Beek D, Brouwer MC, Spanjaard L, de Gans J, , , Clin. Infect. Dis., 2007
10. Community-acquired recurrent bacterial meningitis in adults, Adriani KS, van de Beek D, Brouwer MC, Spanjaard L, de Gans J, , , Clin. Infect. Dis., 2007
11. Acute bacterial meningitis in adults. A review of 493 episodes, Durand ML, Calderwood SB, Weber DJ, ''et al'', , , N. Engl. J. Med., 1993
12. 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, Peltola H, , , Clin. Microbiol. Rev., 2000
13. Antibiotics for preventing meningococcal infections, Fraser A, Gafter-Gvili A, Paul M, Leibovici L, , , Cochrane database of systematic reviews (Online), 2006
External links
★
★
WHO: Meningococcal meningitis
★
Merck Manual: Central nervous system infections
★
Vaccination information from the NHS, UK
★
CDC: Meningococcal disease
★
CNN Health Library, Meningitis
★
BBC News: French Kissing of Many Different Partners Can Quadruple a Teenager's Risk of Meningitis
★
Forum Dedicated to the sufferers of Meningitis
★
Information on Meningitis UK and the charity's search for a vaccine
★
Information from the Meningitis Trust
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