Meningitis

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 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.

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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.^[2]

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 mmH₂O 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 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.

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.^[4]

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". Not all patients with typical "viral meningitis" have PCR (polymerase chain reaction) studies on the CSF, and the diagnosis remains presumptive rather than definitive.^{[citation needed]}

A related diagnostic and therapeutic conundrum is the "partially treated meningitis", i.e. meningitis symptoms in patients who have already been receiving antibiotics (such as for presumptive sinusitis). In these patients, 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).^{[citation needed]}

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%.^[5]

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).^[6] 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 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.^[7] 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.^[8]

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.^{[citation needed]}

• 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

Patients diagnosed with mild viral meningitis may improve quickly enough to not require admission to a hospital, whilst others may be hospitalised for many more days for observation and supportive care.

Unlike bacteria, viruses cannot be killed by antibiotics although drugs such as acyclovir may be employed if meningoencephalitis due to herpes virus infection is suspected.

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.^[9]

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.^[10] 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.^[11]

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.^[12]

In adults central nervous system complications include cerebrovascular disease, brain swelling, hydrocephalus, intracerebral bleeding; systemic complications are dominated by septic shock, adult respiratory distress syndrome and disseminated intravascular coagulation.^[13] Those who have underlying predisposing conditions e.g. head injury may develop recurrent meningitis.^[14] 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.^[14] Age more than 60, low glasgow coma scale at presentation and seizure within 24 hours increase the risk of death among community acquired meningitis.^[15]

Prevention

Immunization

All current vaccines target only bacterial meningitis.

Vaccinations against Haemophilus influenzae (Hib) have decreased early childhood meningitis significantly.^[16]

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.^[17]

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,^[18] and again more accurately by Avenzoar of al-Andalus in the 12th century.^[19] 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.^[20]

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.

See also

• Encephalitis
• Maurice Hilleman

References