Meningitis in Children

Meningitis is inflammation of the meninges around the brain and spinal cord. The majority of cases occur during childhood and are predominantly viral or bacterial in etiology. Clinical presentation is influenced by the age of the child and the causative pathogen, but meningitis typically presents with signs of meningeal irritation, fever, and lethargy. Management varies depending on the pathogen and is isolated to the CSF. Prognosis is dependent on the causative pathogen and appropriate timely intervention. Bacterial meningitis can be life-threatening and has severe complications that may result in long-term sequelae.

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Overview

Definition

Meningitis is inflammation of the meninges surrounding the spinal cord and brain.

Epidemiology

  • 80% of meningitis cases occur in childhood.
  • Mostly in children < 10 years
  • Viral meningitis:
    • Approximately 75,000 cases per year in the United States
    • Most common type in children
    • Boys > girls
    • 2 peaks of incidence at ages 1 and 5 years 
    • During the autumn and winter months
    • Enteroviruses represent 85%–95% of cases.
  • Bacterial meningitis: 
    • Most common type in neonates
    • Untreated, mortality rate of 100% 
    • Neonates (< 28 days old) are at ↑ risk due to ↓ immune response.
    • Streptococcus pneumoniae is the leading cause of community-acquired meningitis in children (1.1 cases per 100,000 population).
    • Vaccination against causative agents (e.g., Haemophilus influenzae type B (Hib)) has ↓ the incidence in all age groups, except for nonimmunized infants < 1 month of age.

Risk factors

  • Neonates: 
    • Prematurity
    • ↓ Birth weight 
    • Delivery complications 
    • Maternal group B streptococcal colonization
    • Maternal infections such as HSV
  • Older children:
    • ↓ Family income
    • Daycare
    • Head trauma 
    • Splenectomy
    • Chronic disease, e.g., HIV
    • Other infections

Etiology

  • Viral (most common)
  • Bacterial
  • Fungal
  • Parasitic
  • Noninfectious
Table: Common causal agents of meningitis in children
BacteriaVirusesFungi
Newborns:
  • Group B Streptococcus
  • Escherichia coli
  • Listeria monocytogenes
Infants > 1 month and children:
  • S. pneumoniae
  • Neisseria meningitidis
  • H. influenzae type b
  • Mycobacterium tuberculosis
  • Borrelia burgdorferi
  • Enteroviruses
  • Arboviruses
  • Herpesviruses
  • Mumps virus
  • Adenovirus
  • Influenza virus
  • Rabies virus
  • Lymphocytic choriomeningitis virus (LCMV)
  • Cryptococcus neoformans
  • Coccioides immitis
  • Candida albicans

Pathophysiology

  • Microorganisms replicate to levels that are not contained by typical immune response and cross the blood–brain barrier (BBB) to cause meningeal infections. 
  • Pathogens undergo an incubation period before onset of symptoms:
    • 3–7 days in bacterial infections
    • 2–14 days in viral infections
  • Microorganisms cross the BBB through 1 of several mechanisms:
    • Hematogenous dissemination (most common) 
    • Direct spread from a contiguous site of infection
      • Otitis media
      • Sinusitis
      • Orbital cellulitis
    • Transplacental spread of bacteria (in neonates)
    • Head trauma or cranial surgery
    • Open neural tube defects
  • Meningeal inflammation and irritation → IL-1 and tumor necrosis factor α (TNF-α)  → platelet activating factor → phospholipase A₂ → prostaglandins + thromboxanes + leukotrienes
  • Leukocyte adhesion → release of proteolytic enzymes → increased permeability of BBB
  • Swelling and proliferation of endothelial cells → increased intracellular sodium and water → brain edema and ↓ cerebral circulation

Clinical Presentation

Clinical presentation in infants and newborns tends to be very nonspecific, and there is a high index of suspicion for all infants and newborns who appear ill.

Classic symptoms

  • Fever
  • Headache 
  • Meningeal signs (altered mental status, irritability, or confusion)
  • Neck stiffness (nuchal rigidity)

Infants

  • Fever (always prompts suspicion of meningitis)
  • Bulging fontanelle (20% of patients)
  • Irritability/lethargy
  • Excessive crying
  • Grunting 
  • ↑ or ↓ tone
  • Toxic appearance 
  • Hypothermia or hyperthermia

Older children

  • Fever
  • Vomiting
  • Headache
  • Photophobia
  • Confusion
  • Nuchal rigidity
  • Opisthotonus
  • Kernig and Brudzinksi signs
  • Petechiae and purpura (N. meningitidis)
Signs positive signs for meningitis

Positive clinical examination findings for meningitis

Image by Lecturio.

Diagnosis

A diagnosis of meningitis is based on clinical findings and confirmed with positive findings in the CSF.

CSF analysis

  • The likelihood of positive CSF findings is 80%–90% if the sample is taken before the initiation of antibiotics.
  • CSF is obtained by lumbar puncture (LP):
    • Contraindications to LP include:
      • ↑ Intracranial pressure caused by tumors or an intracranial mass
      • Active seizures 
      • Papilledema (optic disc swelling) 
    • CT scan is only indicated prior to LP if there is concern because of: 
      • ↑ Intracranial pressure
      • Recent CNS surgery 
      • Presence of a ventriculoperitoneal (VP) shunt
  • Findings:
    • ↑ WBCs
    • ↑ RBCs
    • ↑ or ↓ glucose and protein depending on etiology
    • CSF lactate has a high diagnostic yield for bacterial meningitis.
    • Gram stain and culture is used to identify the organism.
  • Nigrovic rules: a meningitis scale used to assess for bacterial meningitis
    • History of seizures before or at time of presentation
    • CSF proteins > 80 mg/dL
    • CSF neutrophils > 1000/µL
    • Total blood neutrophils or absolute neutrophil count (ANC) > 10,000/µL
    • + CSF Gram stain
Table: CSF studies in meningitis
CSF Gram stainHigh false-negatives, low false-positives
CSF proteinIn bacterial disease, usually > 80
CSF glucoseIn bacterial disease, usually < ⅔ serum glucose
CSF cell count
  • > 21: < 4 weeks
  • > 11: 4–8 weeks>
  • > 8: > 8 weeks

Supporting laboratory tests

  • CBC: WBCs > 10,000/µL
  • Metabolic panel: hyponatremia
  • ↑ BUN and creatinine 
  • Serum glucose level
  • C-reactive protein: an inflammatory marker 
  • Blood cultures prior to starting antibiotics
  • Urinalysis and urine culture

Special tests

  • Serum Lyme titers may be obtained in areas where Lyme disease is endemic.
  • Enterovirus PCR
  • Acid-fast stain and interferon gold in cases of suspected tuberculous meningitis
  • HSV PCR of CSF
Table: Differential diagnosis of meningitis according to the characteristics of the CSF
Cells/mm3Type of cellProteins (mg/dl)Glucose (mg/dl)
Normal CSF< 10Mononuclear (MN)< 4535–100
Bacterial meningitis> 1000PMC> 80↓ or < ⅔ of serum glucose
Viral meningitis< 300First PMC, later MNNormal or ↑Normal
MN: mononuclear
PMC: polymorphonuclear
Haemophilus influenzae meningitis

Inferior view of a brain infected with gram-negative Haemophilus influenzae bacteria

Image: “Haemophilus influenzae meningitis” by CDC. License: Public Domain

Management

Viral meningitis

  • Self-limiting
  • Supportive care
  • Drug therapy is not the standard of care.
  • Acyclovir is indicated in cases of HSV for a period of 14–21 days.

Bacterial meningitis

  • Monitor hydration status because SIADH may develop.
  • Empiric antibiotic treatment should be started prior to receiving culture results in suspected cases and discontinued if cultures are negative.
  • If positive, administer directed antibiotic therapy to specific pathogens per standard-of-care guidelines and discontinue when CSF clears on repeat LP and clinical improvement is achieved.

Empiric therapy by suspected bacteria

  • S. pneumoniae: 
    • Cefotaxime or ceftriaxone
    • Vancomycin
    • Rifampin 
  • N. meningitidis:
    • Ampicillin/penicillin G
    • Cefotaxime or ceftriaxone
  • Hib:
    • Ampicillin
    • Cefotaxime or ceftriaxone for beta-lactamase resistance
  • Staphylococcus aureus:
    • Cloxacillin +/– rifampin 
    • Vancomycin + rifampin or linezolid for MRSA

Empiric therapy by age

  • Infants < 4 weeks:
    • Ampicillin: 300–400 mg/kg/day divided into 4–6 doses
    • Gentamicin: 7.5 mg/kg/day divided into 3 doses
    • +/– Cefotaxime: 225–300 mg/kg/day divided into 3–4 doses
  • Infants 4–8 weeks:
    • Ampicillin: 300–400 mg/kg/day divided into 4–6 doses
    • Ceftriaxone: 100 mg/kg/day divided into 2 doses
  • Children > 8 weeks:
    • Vancomycin: 15 mg/kg/dose every 6 hours
    • Ceftriaxone: 100 mg/kg/day divided into 2 doses
Meningitis - Usual time of antibiotic therapy required for different pathogens

Usual time of antibiotic therapy required for different pathogens

Image by Lecturio.

Complications

  • Cerebral edema
  • SIADH
  • Seizures
  • Hydrocephalus
  • Hearing loss
  • Neurologic deficits
  • Vascular infarcts

Prevention

  • Routine childhood immunizations against the following is recommended:
    • Hib
    • S. pneumoniae
    • N. meningitidis
    • Varicella
    • Influenza virus
  • Chemoprophylaxis: Preventive therapy can ↓ morbidity and mortality in the contacts of index cases.
    • N. meningitidis: rifampin, ceftriaxone, ciprofloxacin
    • Hib: rifampin

Prognosis

  • Viral meningitis:
    • Full recovery in most cases, usually in 7–10 days
    • Morbidity and mortality data unclear
    • Minimal or no long-term effects noted
  •  Bacterial meningitis: 
    • Ranges from complete recovery to severe neurologic deficit or death
    • Overall mortality: 5%–10% 
    • In neonates: 15%–20% mortality
    • S. pneumoniae mortality: 10%–15%

Differential Diagnosis

  • Brain abscess: intracranial abscesses usually originating from contiguous spread from sinusitis, mastoiditis or dental infections, or due to skull trauma. Clinical presentation is similar to meningitis. Diagnosis by brain imaging modalities and management  involves broad spectrum antibiotics. Complications are related to pressure effects causing increased intracranial pressure and sepsis.
  • Hydrocephalus: a disturbance of the formation, flow and distribution of the cerebrospinal fluid leading to a build-up of CSF. It may be classified as communicating and non-communicating types. Infants present with difficulty feeding, irritability, reduced activity and lethargy. Older children have headaches, neck pain, vomiting, blurred vision and double vision. Management is by medication or surgery.
  • Brain tumors: the 2nd most common malignancy in pediatrics and a leading cause of mortality. Clinical symptoms may have a gradual onset and are related to increased intracranial pressure and include headaches, vomiting and neurological deficits. Diagnosis is via imaging, and management is specific to tumor type and location and may involve surgical resection, radiation therapy or chemotherapy.
  • Seizures: uncontrolled excessive synchronous neuronal activity in the brain causing sudden transient changes in motor function, sensation, behavior or mental status. They are classified primarily as generalized or focal. Diagnosis depends on history, exam and electroencephalography findings. Management is directed at the underlying trigger and medication as necessary.

References

  1. Levine, A. (2016). Meningitis in infants and children. In: Tintinalli, J. E., Stapczynski, J. S., Ma, O. J., Yealy, D. M., Meckler, G. D., Cline, D. M. (Eds.), Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8th ed. New York: McGraw-Hill Education. 
  2. Meningitis bacteriana. (2007). Anales de Pediatria Continuada 5(1):22_29. 
  3. Muller, M. L. (2020). Pediatric bacterial meningitis: practice essentials, background, pathophysiology. Medscape. Retrieved August 8, 2021, from https://emedicine.medscape.com/article/961497-overview
  4. Nasir, H., Afzal, M. F., Hamid, M.H., Laeeq, A. (2020). Diagnostic accuracy of cerebrospinal fluid lactate in confirmed cases of acute bacterial meningitis in children. Pak J Med Sci 36:1558–1561.
  5. Owens, B. D. M. (2021). Pediatric aseptic meningitis: background, pathophysiology, etiology. Medscape. Retrieved August 8, 2021, from https://emedicine.medscape.com/article/972179-overview

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