Meningitis

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Meningitis
Classification and external resources
Meninges of the central nervous system: dura mater, arachnoid, and pia mater.
ICD-10 G00.-G03.
ICD-9 320-322
DiseasesDB 22543
MedlinePlus 000680
eMedicine med/2613  emerg/309 emerg/390
MeSH D008581

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.

Contents

[edit] 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[1] and altered mental status. All three features are present in only 44% of all cases of infectious meningitis.[2] 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.[3]

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.[4]

[edit] Diagnosis

[edit] 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 (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 mm H2O 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.

CSF finding in different conditions[5]
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
An autopsy demonstrating signs of pneumococcal meningitis. The forceps (center) are retracting the dura mater (white). Underneath the dura mater are the leptomeninges, which are edematous and have multiple small hemorrhagic foci (red).
An autopsy demonstrating signs of pneumococcal meningitis. The forceps (center) are retracting the dura mater (white). Underneath the dura mater are the leptomeninges, which are edematous and have multiple small hemorrhagic foci (red).

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.[6]

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).[4]

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).[4]

[edit] 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%.[7]

[edit] 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).[8] 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.

[edit] Treatment

[edit] Bacterial meningitis

Bacterial meningitis is a medical emergency and has a high mortality rate if untreated.[9] 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.[10]

Age group Causes
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.[11] 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]

[edit] 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 cannot be killed by antibiotics. Drugs such as acyclovir may be employed if herpes virus infection is either suspected or demonstrated.[4]

[edit] 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.[12]

[edit] 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.[13] 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.[14]

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.[15]

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.[16] Those who have underlying predisposing conditions e.g. head injury may develop recurrent meningitis.[17] 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 e.g. pneumonia, sepsis, cardio-respiratory failure; however in younger individuals it is usually associated with neurological complications.[17] Age more than 60, low Glasgow coma scale at presentation and seizure within 24 hours increase the risk of death among community acquired meningitis.[18]

[edit] Prevention

[edit] Immunization

Vaccinations against Haemophilus influenzae (Hib) have decreased early childhood meningitis significantly.[19]

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.[citation needed]

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.[citation needed] According to reports released in May 2008, Novartis is in the advanced stages of testing a general meningococcus type B vaccine.[20]

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.[citation needed]

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.[4]

[edit] 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.[21]

[edit] Epidemiology

Demography of meningococcal meningitis. Red: meningitis belt, orange: epidemic meningitis, grey: sporadic cases
Demography of meningococcal 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.

[edit] History

Meningitis was first described in the 1020s in Avicenna's The Canon of Medicine,[22] and again more accurately by Avenzoar of al-Andalus in the 12th century.[23] 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.[24]

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.[citation needed]

[edit] See also

[edit] References

  1. ^ Meningitis Symptoms & Warning Signs
  2. ^ 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". N. Engl. J. Med. 351 (18): 1849-59. doi:10.1056/NEJMoa040845. PMID 15509818. 
  3. ^ 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". Clin. Infect. Dis. 35 (1): 46-52. doi:10.1086/340979. PMID 12060874. 
  4. ^ a b c d e Logan SA, MacMahon E (2008). "Viral meningitis". BMJ 336 (7634): 36–40. doi:10.1136/bmj.39409.673657.AE. PMID 18174598. 
  5. ^ Provan, Drew; Andrew Krentz (2005). Oxford Handbook of clinical and laboratory investigation. Oxford: Oxford university press. ISBN 0198566638. 
  6. ^ Holub M, Beran O, Dzupova O, et al. (2007). "Cortisol levels in cerebrospinal fluid correlate with severity and bacterial origin of meningitis". Critical Care 11: R41. doi:10.1186/cc5729. 
  7. ^ Nigrovic LE, Kuppermann N, Macias CG, et al (2007). "Clinical prediction rule for identifying children with cerebrospinal fluid pleocytosis at very low risk of bacterial meningitis". JAMA 297 (1): 52-60. doi:10.1001/jama.297.1.52. PMID 17200475. 
  8. ^ Ryan KJ, Ray CG (editors) (2004). Sherris Medical Microbiology, 4th ed., McGraw Hill, 876–9. ISBN 0838585299. 
  9. ^ Beckham J, Tyler K (2006). "Initial Management of Acute Bacterial Meningitis in Adults: Summary of IDSA Guidelines". Rev Neurol Dis 3 (2): 57-60. PMID 16819421. 
  10. ^ 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. 
  11. ^ Longmore, Murray; Ian Wilkinson, Tom Turmezei, Chee Kay Cheung (2007). Oxford Handbook of Clinicial Medicine. Oxford, 841. ISBN 0-19-856837-1. 
  12. ^ Gottfredsson M, Perfect JR (2000). "Fungal meningitis". Seminars in neurology 20 (3): 307-22. doi:10.1055/s-2000-9394. PMID 11051295. 
  13. ^ Vasallo, G; T R Martland (Jan 2004). "Neurological complications of pneumococcal meningitis". Developmental Medicine and Child Neurology Vol. 46: pg. 11. 
  14. ^ Richardson MP, Reid A, Tarlow MJ, Rudd PT (1997). "Hearing loss during bacterial meningitis". Arch. Dis. Child. 76 (2): 134-8. PMID 9068303. 
  15. ^ Grimwood K (2001). "Legacy of bacterial meningitis in infancy. Many children continue to suffer functionally important deficits". BMJ 323 (7312): 523-4. PMID 11546680. 
  16. ^ Pfister HW, Feiden W, Einhäupl KM (1993). "Spectrum of complications during bacterial meningitis in adults. Results of a prospective clinical study". Arch. Neurol. 50 (6): 575-81. PMID 8503793. 
  17. ^ a b Adriani KS, van de Beek D, Brouwer MC, Spanjaard L, de Gans J (2007). "Community-acquired recurrent bacterial meningitis in adults". Clin. Infect. Dis. 45 (5): e46-51. doi:10.1086/520682. PMID 17682979. 
  18. ^ Durand ML, Calderwood SB, Weber DJ, et al (1993). "Acute bacterial meningitis in adults. A review of 493 episodes". N. Engl. J. Med. 328 (1): 21-8. doi:10.1056/NEJM199301073280104. PMID 8416268. 
  19. ^ 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". Clin. Microbiol. Rev. 13 (2): 302-17. doi:10.1128/CMR.13.2.302-317.2000. PMID 10756001. 
  20. ^ BBC News Health. Meningitis B trials "encouraging". Retrieved on 2008-05-15.
  21. ^ 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. 
  22. ^ Patricia Skinner (2001), Unani-tibbi, Encyclopedia of Alternative Medicine
  23. ^ Martin-Araguz, A.; Bustamante-Martinez, C.; Fernandez-Armayor, Ajo V.; Moreno-Martinez, J. M. (2002). "Neuroscience in al-Andalus and its influence on medieval scholastic medicine", Revista de neurología 34 (9), p. 877-892.
  24. ^ Weichselbaum's meningococcus at Who Named It

[edit] External links

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