뇌수막염 (Meningitis)
Meningitis
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Meningitis
Classification & external resources
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Meninges of the central nervous system: dura mater, arachnoid, and pia mater. |
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Meningitis is the inflammation of the protective membranes covering the central nervous system, known collectively as the meninges. It may develop due to a variety of causes, including infective agents, physical injury, cancer, or certain drugs. Meningitis is a serious condition owing to the proximity of the location to the brain and spinal cord. The potential for serious damage to motor control, thought processes, or even death warrants prompt medical attention.
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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).[1] Non-infectious causes include cancers, systemic lupus erythematosus and certain drugs. Although the most common cause of meningitis is viral, bacterial, or Meningococcal meningitis -- the second most frequent cause -- can be serious and life-threatening. Anyone suspected of having meningitis should have prompt medical evaluation.
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Epidemiology
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Age group |
Causes |
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Group B Streptococci, Escherichia coli, Listeria monocytogenes |
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Infants |
Neisseria meningitidis, Haemophilus influenzae, Streptococcus pneumoniae |
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Children |
N. meningitidis, S. pneumoniae |
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Adults |
S. pneumoniae, N. meningitidis, Mycobacteria, Cryptococci |
Meningitis can affect anyone in any age group, from the newborn to the elderly.
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The African Meningitis Belt
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.
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Clinical symptoms
Meningitis usually presents with one or more of the following symptoms.
- High fever, sometimes with chills
- Severe headache
- Nausea or vomiting
- Light sensitivity (photophobia)
- Sound sensitivity
- Neurological signs such as drowsiness or confusion
- Twitching
- Sleepiness
- Opisthotonus
- Irritability
- Sore throat
- Delirium (particularly in children[1])
- Seizures (occurs in about 20 to 40 percent of patients).
- Nuchal rigidity (stiff neck, occurs in less than 50 percent of cases, but if seen, it is considered pathognomonic).
- Swelling of "soft spot" (in infants)
One large prospective study demonstrated that the classic triad of nuchal rigidity, fever, and mental status change was present in only 44 percent of confirmed cases of community acquired bacterial meningitis.[2] Headache was the most common reported symptom (87 percent) followed by neck stiffness (83 percent).
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]
Neck stiffness may prevent the head from bending forwards. If the child can touch the chest with the chin by bending the head forwards the physical sign of neck stiffness is probably not present. Neck stiffness in a child with a fever is a medical emergency.
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.
Symptoms in infants under 12 months include high fever, fretfulness, irritability - particularly when handled, difficulty awakening, drowsiness, difficulty feeding, and/or a stiff neck, or bulging fontanelle (soft spot on top of head).
In a recent validation study published in the Journal of the American Medical Association (JAMA), a Bacterial Meningitis Score in children over the age of 2 months 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) has a sensitivity of 100% (95% CI, 96.9%-100%), specificity of 63.5% (95% CI, 61.4%-65.6%), and negative predictive value of 100% (95% CI, 99.8%-100%) in predicting bacterial meningitis based on data collected from 20 academic medical centers as part of the Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics.[4]
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Diagnosis
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Laboratory tests
If meningitis is suspected based on clinical examination, the patient should be given antibiotics. The next step is to perform laboratory tests on the blood and cerebrospinal fluid (CSF).
CSF is obtained by means of a lumbar puncture (LP). However, if the patient is at risk for elevated intracranial pressure, a lumbar puncture may be contraindicated because of the possibility of fatal brain herniation. In such cases a CT or MRI scan should be performed prior to the lumbar puncture in order to make sure there are no large masses compressing the brain. Patients at risk for elevated intracranial pressure include those with recent head trauma, the immunocompromised, those with a known CNS neoplasm, or focal neurologic deficits such as papilledema or altered consciousness. 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.
The opening pressure is noted during the LP and the CSF sent for examination of white blood cell, red blood cell, glucose, and protein, and may have different tests performed, such as gram staining, culture, and possibly latex agglutination test, limulus lysates, or polymerase chain reaction (PCR) for bacterial or viral DNA. If the patient is immunocompromised, the doctor may also consider testing the CSF for toxoplasmosis, Epstein-Barr virus, cytomegalovirus, JC virus and fungal infection.
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CSF analysis in bacterial meningitis
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).
- Opening pressure: > 180 mm H2O
- White Blood Cells: 10-10,000/uL with neutrophil predominance
- Glucose: < 40 mg/dL
- CSF glucose to serum glucose ratio: < 0.4
- Protein: > 4.5 mg/dL
- Gram stain: positive in >60%
- Culture: positive in >80%
- Latex agglutination: may be positive in meningitis due to Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Escherichia coli, Group B Streptococci
- Limulus lysates: 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.[5]
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CSF analysis in viral meningitis
- Appearance is clear
- Will contain lymphocytes (lymphocytosis)
- Normal level of protein
- Normal or increased level of glucose
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Treatment
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Bacterial meningitis
Bacterial meningitis is a medical emergency and has a high mortality rate if untreated.[6] 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.
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 organisms. Because antibiotic-resistance is a prevalent problem, information from drug susceptibility testing should also be gathered.
- 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
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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.
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Fungal meningitis
This form of meningitis is rare in healthy people, but is a higher risk in those who have AIDS. Antifungals to combat the infection are usually administered, as well as fluids and medicine to control pain and fever. Often the pathogen in these cases is Cryptococcus Sp.[1] [2]
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Complications
There are several potential disabilities resulting from damage to the nervous system. These include seizures (with its concommitant brain damage), sensorineural hearing loss, hydrocephalus, and cerebral palsy.[citation needed]
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.[citation needed] 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.
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Vaccination
All current vaccines target only bacterial meningitis.
Vaccinations against Haemophilus influenzae (Hib) have decreased early childhood meningitis significantly[citation needed].
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.
Pneumovax (also known as Prevenar) against Streptococcus pneumoniae is recommended for all people 65 years of age or older, and for all newborns starting at 6 weeks - 2 months, according to American Association of Pediatrics (AAP) recommendations.
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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.
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See also
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References
- ^ a b Ryan KJ, Ray CG (editors) (2004). Sherris Medical Microbiology, 4th ed., McGraw Hill, 876–9. ISBN 0838585299.
- ^ 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.
- ^ 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. PMID 12060874.
- ^ 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.
- ^ 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.
- ^ 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.