Everything about Meningitis totally explained
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| ICD9 = -
| MedlinePlus = 000680
| eMedicineSubj = med
| eMedicineTopic = 2613
| eMedicine_mult =
| MeshID = D008581
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Meningitis is
inflammation of the protective membranes covering the
brain and
spinal cord, known collectively as the
meninges. Meningitis may develop in response to a number of causes, most prominently
bacteria,
viruses and other infectious agents, but also physical injury,
cancer, or certain drugs. While some forms of meningitis are mild and resolve on their own, meningitis is a potentially serious 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 attention and evaluation. Infectious meningitis, the most common form, is typically treated with
antibiotics and requires close observation. Some forms of meningitis (such as those associated with
meningococcus,
mumps virus or
pneumococcus infections) may be prevented with
immunization.
Signs and symptoms
Severe 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), 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 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.
In "meningococcal" meningitis (for example 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.
Diagnosis
Investigations
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 (for example 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 mm H
2O is indicative 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 doesn't 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 different conditions>
| 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 hemorrhage | Normal |
normal, or high |
Erythrocytes
|
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.
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 in any patient with a mild meningeal illness with appropriate CSF findings, certain patients 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
polymerase chain reaction 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).
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). 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 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 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.
Treatment
Bacterial meningitis
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 won't 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.
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.
Viral meningitis
Patients 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 can't be killed by antibiotics although drugs such as
acyclovir may be employed, especially if herpes virus infection is either suspected or demonstrated.
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. 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 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 that 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 for example 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). Fatal outcome in patients over 60 years of age is more likely to be from systemic complications for example
pneumonia,
sepsis, cardio-respiratory failure; however in younger individuals it's 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.
Prevention
Immunization
Vaccinations against
Haemophilus influenzae (
Hib) have decreased early childhood meningitis significantly.
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 meningoccocal disease prevalent in
Norway, and another specific vaccine for the strain prevalent in
Cuba. According to reports released in May 2008,
Novartis is in the advanced stages of testing a general meningococcus type B vaccine.
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.
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.
Epidemiology
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 was first described in the 1020s in
Avicenna's
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 the Emperor insisted on
traditional medical care for his children.
Further Information
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