What is the epidemiology and management of neonatal and pediatric encephalitis?

Epidemiology of Neonatal and Pediatric Encephalitis

The incidence of encephalitis in children ranges from 10.5 to 13.8 per 100,000 children, with viral pathogens being the most common cause, particularly herpes simplex virus (HSV) which has an annual incidence of 1 in 250,000 to 500,000 people. 1

Epidemiological Overview

Incidence and Distribution

• Encephalitis affects children of all ages, with higher incidence in the pediatric population compared to adults 2
• In western settings, reported incidences range from 6.3 to 7.4 per 100,000 for all ages 1
• In the UK, this equates to approximately 1-2 children per year in a typical district general hospital and 8-10 in a large tertiary children's hospital 1
• Slight male predominance has been observed in most studies 2

Age-Specific Patterns

• Age-specific incidence of HSV encephalitis is bimodal, with peaks in childhood and the elderly 1, 3
• Neonatal encephalitis has distinct patterns, with HSV-2 accounting for about 10% of HSV encephalitis cases, occurring primarily in neonates and immunocompromised patients 1, 3

Etiological Distribution

Viral Causes (69% of confirmed/probable cases) 3

• Herpes simplex virus (HSV): Most commonly diagnosed cause in industrialized nations 1, 3
  • HSV-1: Accounts for approximately 90% of HSV encephalitis cases
  • HSV-2: Accounts for about 10% of cases, primarily in neonates and immunocompromised patients
• Varicella zoster virus (VZV): Relatively common cause, especially in immunocompromised patients 1, 3
• Enteroviruses: Common cause in children, accounting for 10% of cases 3, 4
• Parechovirus: Accounts for 10% of pediatric encephalitis cases 4
• Influenza viruses: Account for 6% of cases 4
• Other viral causes:
  • West Nile virus (common in the US)
  • Measles virus (can cause three distinct encephalitic syndromes)
  • Rotavirus
  • Human herpesvirus 6 4

Non-Viral Infectious Causes

• Bacterial causes (20% of confirmed/probable cases) 3:
  • Mycoplasma pneumoniae (6% of cases) 4
  • Bacterial meningoencephalitis (8% of cases) 4
  • Other bacteria: Listeria monocytogenes, Mycobacterium tuberculosis, Borrelia burgdorferi
• Parasitic causes: Account for approximately 3% of confirmed/probable cases 3
• Fungal causes: Account for approximately 1% of confirmed/probable cases 3

Immune-Mediated Causes

• Account for 25% of pediatric encephalitis cases 4
• Acute disseminated encephalomyelitis (ADEM): 18% of cases 4
• Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis: 6% of cases 4

Unknown Etiology

• Despite extensive evaluation, the cause remains unknown in 17-32% of cases 3, 4

Age-Related Patterns

Neonatal Encephalitis

• HSV-2 is a predominant cause in neonates 1, 3
• Typically presents at a mean age of 24 ± 20 days 5
• Common presentations include seizures (67%), lethargy (67%), temperature changes (56%), and apnea (33%) 5

Childhood Encephalitis

• Infectious encephalitis occurs in younger children (median age 1.7 years) compared to immune-mediated encephalitis (median age 7.6 years) 4
• Enterovirus and parechovirus are common causes in younger children 4
• Immune-mediated causes like ADEM and anti-NMDAR encephalitis are more common in older children 4

Mortality and Morbidity

• Overall mortality rate is approximately 5% in recent studies 4
• Most deaths are associated with infectious causes, including influenza, human herpesvirus 6, bacterial pathogens, HSV, parechovirus, and enterovirus 4
• Approximately 27% of children show moderate to severe neurological sequelae at discharge 4
• Delays in treatment, particularly beyond 48 hours after hospital admission, are associated with worse outcomes 1, 3

Geographic and Seasonal Variations

• Some etiologies have global distribution (herpesviruses) while others are geographically restricted (arboviruses) 2
• Seasonal patterns may exist for certain causes, such as enteroviruses (summer-fall predominance) and influenza (winter predominance) 1, 3

Risk Factors and Epidemiological Clues

Important epidemiological clues that may help direct investigation include:

• Season of the year
• Geographic location
• Prevalence of disease in the local community
• Travel history
• Recreational activities
• Occupational exposures
• Insect or animal contacts
• Vaccination history
• Immune status of the patient 1, 3

Understanding the epidemiology of pediatric encephalitis is crucial for early recognition, appropriate management, and improved outcomes in this potentially devastating condition.