Basics
Description
Inflammation of the membranes of the brain or spinal cord, usually caused by viruses or bacteria and, rarely, fungi or parasites
Epidemiology
- Bacterial meningitis
- Most common agents in children of all ages include Streptococcus pneumoniae and Neisseria meningitidis.
- Underlying host factors, age, exposure, and geographic location alter incidence and pathogen.
- Viral meningitis
- Most common agent in all age groups
- Most common isolated virus are enteroviruses that tend to occur in outbreaks in summer and early fall.
- Fungal meningitis
- Cryptococcus neoformans is a budding encapsulated yeast-like organism found in soil and avian excreta; associated with immunocompromised patients (especially AIDS), rare cases in healthy children
- Candida species occurs in immunocompromised patients and ill premature infants.
- Tuberculous meningitis
- Mycobacterium tuberculosis (TB) meningitis occurs in 0.5% of untreated primary TB infections.
- Most common in children aged 6 months to 4 years
- In ’ Ό50% of cases, miliary TB is accompanied by meningitis.
General Prevention
- Haemophilus influenzae type b (Hib) vaccine has significantly reduced the incidence of meningitis and other invasive Hib infections by up to 99%.
- 13-valent S. pneumoniae protein conjugate vaccine (PCV13) for use in all infants given at 2, 4, 6, and 12 " 15 months of age
- A tetravalent meningococcal vaccine (MCV4) is recommended for all patients ≥11 years of age and select at-risk populations <11 years. A booster dose is recommended for all patients who receive the first dose of the vaccine between 11 and 15 years of age.
Etiology
- Bacterial
- Cause differs depending on age:
- <1 month old: group B Streptococcus, gram-negative pathogens (Escherichia coli, Citrobacter koseri, Cronobacter sakazakii, Serratia marcescens, and Salmonella species), Listeria monocytogenes, S. pneumoniae
- 1 " 3 months old: group B Streptococcus, E. coli, S. pneumoniae, Hib
- 3 months to 5 years old: S. pneumoniae, N. meningitidis, Hib
- >5 years old: S. pneumoniae, N. meningitidis
- Consider Hib in unvaccinated patients of any age.
- Viral
- Herpes simplex virus (HSV) in the neonatal population
- Enteroviruses: ’ Ό70 different strains that include polioviruses, coxsackie A, coxsackie B, and echoviruses. Recently discovered enteroviruses are not placed in these 4 groups but are numbered (e.g., enterovirus 68).
- Other, less common: arboviruses (e.g., West Nile virus), mumps
- Fungal
- Fungi most commonly isolated include Candida species, Coccidioides immitis, Cryptococcus neoformans, and Aspergillus species.
- Aseptic meningitis
- Agents not easily cultured in the viral or microbiology laboratory can cause meningitis and include Borrelia burgdorferi (Lyme disease) and Treponema pallidum (syphilis).
- Tuberculous meningitis
- Unusual pathogens more likely in immunocompromised patients
Diagnosis
- Age-specific
- Pain
- Fever
- Nausea and/or vomiting
History
- Bacterial meningitis
- Older children may complain of classic meningeal inflammation signs including neck pain, headache, or back pain as well as photophobia, anorexia, and myalgias.
- Nausea and vomiting are common.
- In younger children, symptoms are often nonspecific, including fever, hypothermia, irritability, and poor feeding as well as signs of increased intracranial pressure, including seizures and apnea.
- Attention should be noted to the patient 's immunization status, birth history, travel history, trauma, health status, geographic location, and exposure to high-risk contacts.
- Common chief complaints by the infants ' caregivers include the following:
- Irritable or "sleeping all the time "
- "Won 't take to bottle "
- "Not acting right "
- "Cries when moved or picked up "
- Viral meningitis
- Headache and fever may precede signs of meningitis, such as stiff neck, vomiting, and photophobia.
- Duration 2 " 6 days
- Fungal meningitis
- Cryptococcal meningitis is often indolent, with complaints of worsening headaches and vomiting for days to weeks.
- Exposure to pigeon or other bird droppings can be a valuable clue.
- Tuberculous meningitis
- Symptoms are often nonspecific initially, with personality changes, fever, nausea, and vomiting progressing to anorexia, irritability, and lethargy (stage I disease).
- Stage II disease is characterized by focal neurologic signs (most often involving the cranial nerves III, VI, and VII).
- Stage III disease is characterized by coma and papilledema.
Physical Exam
- Stiff neck in older children. Infants have poor neck muscle tone and this finding is commonly absent.
- Brudzinski and Kernig signs may be present.
- Brudzinski sign: With the patient supine, flexion of the neck elicits involuntary flexion of the hips or knees.
- Kernig sign: With the patient supine, the legs are flexed 90 degrees at the hip, extensions of the lower legs are unable to be accomplished beyond 135 degrees.
- Negative Brudzinski or Kernig sign does not rule out meningitis.
- Younger children may not have nuchal rigidity and Kernig and/or Brudzinski signs.
- Any infant presenting with a sepsis-like picture needs to have meningitis as a consideration.
- Classically, there may be "paradoxical " crying " crying that increases when child is picked up.
- Signs of increased intracranial pressure, including papilledema, asymmetric pupils, bulging fontanelle, diplopia
- Skin exam for erythema migrans from borreliosis (Lyme disease), petechiae, or purpura with invasive meningococcal disease or vesicles in an infant <6 weeks old with HSV
Diagnostic Tests & Interpretation
Lab
- CSF analysis (cell count with differential, protein measurement, glucose concentration, and measurement of pressure)
- CSF gram stain and culture
- Blood culture
- CBC, platelet count, electrolytes, BUN, creatinine, serum glucose,
- Consider prothrombin time (PT), partial thromboplastin time (PTT), liver function tests, arterial blood gas
Diagnostic Procedures/Other
- Lumbar puncture
- Contraindicated with cardiopulmonary compromise, uncorrected coagulopathy, signs of increased intracranial pressure, or focal neurologic findings until head imaging can be obtained
- If no etiology is discovered after the first lumbar puncture and the child is not responding to therapy, repeat lumbar puncture at 36 " 48 hours.
- Opening pressure: normal is <200 mm H2O in lateral recumbent position
- Depending on the presentation, age, history, and physical exam findings, some or all of the following tests should be requested for CSF analysis:
- Cell count with differential and Gram stain
- Bacterial meningitis is characterized by CSF pleocytosis (>1.0 103/ ΌL) with predominance of neutrophils. Culture is the gold standard for diagnosis.
- Viral meningitis typically has a lower CSF cell count (0.05 " 0.5 103/ ΌL) compared to bacterial meningitis with a predominance of lymphocytes.
- Glucose: Compare with serum glucose; normal is >40 mg/dL or 1/2 " 2/3 of the serum glucose.
- Protein: normal is 5 " 40 mg/dL except in newborns, who may have protein levels of 150 " 200 mg/dL
- >1.0 g/dL in bacterial meningitis and normal to slightly elevated in viral meningitis
- Cultures for bacteria, fungi, virus, and mycobacteria
- 80% of blood cultures are positive in children with bacterial meningitis.
- Polymerase chain reaction (PCR) analysis for enterovirus, TB, HSV, Epstein-Barr virus
- B. burgdorferi PCR for CSF samples has a diagnostic yield as low as 17%. Antibody studies for neuroborreliosis are recommended.
Differential Diagnosis
- Encephalitis
- Toxic encephalopathy
- Epidural abscess
- Cerebral abscess
Treatment
General Measures
- Ensure adequate ventilation and cardiac function.
- Circulation, airway, breathing (CABs)
- Initiate hemodynamic monitoring and support by achieving venous access and treat shock syndrome, if present.
- Prompt initiation of appropriate antimicrobials
- If a lumbar puncture cannot be obtained or is contraindicated, a blood culture should be obtained and antimicrobials initiated immediately.
- Monitor serum sodium concentrations because syndrome of inappropriate ADH secretion (SIADH) is a frequent complication during the first 3 days of treatment.
- Steroids should be used in the initial therapy of TB meningitis along with anti-TB medication.
- Steroids are indicated for Hib meningitis and can be considered in S. pneumoniae meningitis; has been shown to decrease hearing loss and neurologic sequelae but not overall mortality. Consult ID expert for use.
- If giving steroids, use dexamethasone 0.6 mg/kg/24 h divided into 4 doses and given for 4 days. The first dose should be given before or with the first dose of antibiotic.
Medication
- Antimicrobial agents
- <1 month of age: ampicillin IV 200 " 300 mg/kg/24 h divided q6 " 12h based on postnatal age and weight. If <7 days of age, 200 mg/kg/24 h divided q8h; if >7 days of age, ampicillin 300 mg/kg/24 h divided q6h and cefotaxime IV 200 " 300 mg/kg/24 h divided q6h
- >1 month of age: vancomycin IV 60 " 80 mg/kg/24 h divided q6h; cefotaxime IV 300 mg/kg/24 h divided q6h or ceftriaxone 100 mg/kg/24 h divided q12h (should not be used in infants <2 months of age)
- Vancomycin IV 60 " 80 mg/kg/24 h divided q6h should be considered in a patient of any age suspected of S. pneumoniae.
- Alternative therapy for penicillin- or cephalosporin-allergic patients can include carbapenem or a quinolone in addition to vancomycin. Infectious disease specialist input should be considered.
- Fungal meningitis
- Amphotericin B with or without 5-flucytosine
- Tuberculous meningitis
- Treatment is generally with 4 drugs for 2 months followed by 2 drugs for 10 months.
- Initially, treat with isoniazid, rifampin, pyrazinamide, and streptomycin.
- Viral meningitis
- Enterovirus: supportive care
- HSV: acyclovir 60 mg/kg/24 h IV divided q8h
Alert
- Remember that in tuberculous meningitis, up to 50% of children will not react to the 5-tuberculin unit Mantoux tests. Therapy should be started if suspicious; do not rely on the skin testing.
- With the potential for resistant S. pneumoniae, vancomycin and cefotaxime or ceftriaxone should be used until antibiotic susceptibility data are available.
Ongoing Care
Follow-up Recommendations
- Neonatal HSV meningitis should be evaluated with a repeat CSF HSV DNA PCR at day 21 and therapy extended if the PCR remains positive.
- Prophylaxis in Hib:
- Oral rifampin (20 mg/kg/dose, maximum 600 mg/24 h for 4 days) should be given to all household contacts if 1 member is <4 years of age and is unvaccinated.
- Prophylaxis in N. meningitidis:
- Oral rifampin (10 mg/kg/dose, maximum 600 mg b.i.d. for 2 days) for all household contacts, day care contacts, and other persons with close contact 7 days prior to onset of illness
Patient Monitoring
- Most children with bacterial meningitis become afebrile by 7 " 10 days after starting therapy, with gradual improvement in activity with less irritability.
- Evaluation for neurologic sequelae, such as hearing and vision testing, is essential.
Prognosis
- Bacterial meningitis
- Fatality approaches 100% if untreated.
- ’ Ό500 " 1,000 deaths each year, or 5 " 10% of cases
- Hearing deficits and neurologic damage may occur in up to 30% of children.
- Viral meningitis
- Prognosis for enteroviral meningitis is good.
- Aseptic meningitis
- Lyme disease: Prognosis with diagnosis and treatment is good.
- Tuberculous meningitis
- The long-term prognosis in children with tuberculous meningitis depends on the stage of disease in which treatment is begun.
- Complete recovery occurs in 94% of those whose treatment was started in stage I but only 51% and 18% for those whose treatment began in stage II or stage III, respectively.
Complications
- Bacterial meningitis
- Acute complications: SIADH and seizures occur in up to 1/3 of patients, focal neurologic signs occur in 10 " 15%.
- Long-term complications: neurocognitive defects, hearing defects (most common morbidity among survivors)
- Viral meningitis
- Acute complications: SIADH in 10%
- Long-term complications: Complications from viral meningitis are rare. However, neonates (<1 month of age) may develop severe enterovirus disease and older agammaglobulinemic children may develop chronic enterovirus meningoencephalitis.
- Tuberculous meningitis
- Acute complications: most common are cranial nerve findings, especially 6th cranial nerve palsy affecting the eyes; hydrocephalus
- Long-term complications: many, including blindness, deafness, and mental retardation
Additional Reading
- Brouwer MC, McIntyre P, Prasad K, et al. Corticosteroids for acute bacterial meningitis. Cochrane Database Syst Rev. 2013;6:CD004405. [View Abstract]
- Kestenbaum LA, Ebberson J, Zorc JJ, et al. Defining cerebrospinal fluid white blood cell count reference values in neonates and young infants. Pediatrics. 2010;125(2):257 " 264. [View Abstract]
- Maconochie I, Baumer H, Stewart ME. Fluid therapy for acute bacterial meningitis. Cochrane Database Syst Rev. 2008;(1):CD004786. [View Abstract]
- Mann K, Jackson MA. Meningitis. Pediatr Rev. 2008;29(12):417 " 430. [View Abstract]
Codes
ICD09
- 322.9 Meningitis, unspecified
- 320.9 Meningitis due to unspecified bacterium
- 047.9 Unspecified viral meningitis
- 320.2 Streptococcal meningitis
- 321.0 Cryptococcal meningitis
- 036.0 Meningococcal meningitis
ICD10
- G03.9 Meningitis, unspecified
- G00.9 Bacterial meningitis, unspecified
- A87.9 Viral meningitis, unspecified
- G00.2 Streptococcal meningitis
- B45.1 Cerebral cryptococcosis
SNOMED
- 7180009 Meningitis (disorder)
- 95883001 Bacterial meningitis (disorder)
- 58170007 Viral meningitis (disorder)
- 4510004 Streptococcal meningitis (disorder)
- 192644005 Meningococcal meningitis (disorder)
- 14232007 Cryptococcal meningitis (disorder)
FAQ
- Q: Is a lumbar puncture required before starting antibiotics in the patient with suspected meningitis with unstable vital signs requiring resuscitation?
- A: No. In the unstable patient, it is contraindicated to perform a lumbar puncture. Appropriate IV antibiotics should be started. When resuscitated, a lumbar puncture should be performed.