What are the clinical features of viral encephalitis in infants?

Clinical Features of Viral Encephalitis in Infants

Infants with viral encephalitis present most commonly with fever, seizures, and altered consciousness, but critically, they often display non-specific symptoms such as feeding difficulties, respiratory distress, irritability, and fussiness that can easily be mistaken for other acute illnesses—making early recognition particularly challenging in this age group. 1

Core Clinical Presentation

Most Common Features (in order of frequency):

• Fever (67-80% of cases) - though notably can be low-grade rather than high fever 1
• Seizures (61-78%) - may be generalized, focal, or subtle motor seizures (mouth, digit, or eyelid twitching) 1
• Behavioral changes/Irritability/Confusion (76%) - manifests as fussiness or personality changes in infants 1
• Focal neurological signs (37-78%) 1
• Decreased consciousness (47%) 1
• Vomiting (57%) 1

Critical Infant-Specific Features:

The guideline explicitly warns that infants frequently present with non-specific symptoms that differ substantially from older children and adults 1:

• Feeding difficulties
• Respiratory difficulties
• Fussiness/irritability (may be the primary manifestation)
• Concomitant respiratory infection signs (54% of cases) 1
• Gastrointestinal symptoms (21% of cases) 1

Pathogen-Specific Presentations

Herpes Simplex Virus (HSV):

• More subtle presentations now recognized with CSF PCR availability 1
• Low-grade pyrexia rather than high fever
• Speech disturbances (dysphasia/aphasia) in older infants
• Behavioral changes
• Labial herpes may be noted in infants with primary HSV infection (unlike adults where it's non-specific) 1
• Can present as mild encephalitis with fever, single seizure, lethargy, and headache 1

Human Parechovirus (PeV):

• Characteristic triad: fever, rash, and fussiness (50% of cases) 2
• Sepsis-like syndrome (39% of cases) - critical mimicker 2
• Seizures (13%) 2
• Normal CSF parameters (absence of pleocytosis, normal protein/glucose) - major diagnostic pitfall 2
• MRI shows periventricular white matter changes with frontoparietal predominance, corpus callosum, thalami involvement 2

Varicella Zoster Virus (VZV):

• Most common identified viral agent in some series (26.9%) 3
• May present with acute or subacute onset 1
• Vesicular eruption may be mild or absent 1

Physical Examination Findings to Assess

1:

• Subtle motor seizures - mouth, digit, eyelid twitching (easily missed)
• Evidence of prior seizures - tongue biting, injury
• Meningism (22% of cases)
• Focal neurological signs
• Papilloedema
• Rash patterns:
  • Vesicular (VZV, hand-foot-mouth disease)
  • Purpuric (meningococcus)
• Movement disorders, including Parkinsonism

Critical Diagnostic Pitfalls

The "Classical Picture" is Outdated:

The most common reason for failure to diagnose HSV encephalitis is non-specific initial clinical presenting symptoms and signs 1. The concept of a "classical" picture of HSV encephalitis in children is now considered outdated 1.

Normal CSF Does Not Exclude Encephalitis:

• Parechovirus encephalitis characteristically has normal CSF parameters 2
• CSF may be devoid of cells in immunocompromised patients or early in infection 4
• CSF pleocytosis defined as ≥5 WBC/mm³ for diagnostic purposes 4

Seizure Considerations:

• Status epilepticus (including subtle motor status) associated with higher mortality (p = 0.0003) 1
• Non-convulsive status epilepticus rare as presenting feature 1
• Febrile seizures alone in young children do not mandate encephalitis evaluation unless altered mentation persists >24 hours 4

Severity Indicators and Outcomes

Poor Prognostic Features:

• Glasgow Coma Scale scores 5
• Presence of shock 5
• Need for mechanical ventilation 5
• Status epilepticus 1

Admission Patterns:

• 25-55% require PICU admission 1, 2
• Mortality ranges 1.7-11.4% 5, 3
• Neurological sequelae develop in 6-17% of survivors 5, 3

Diagnostic Approach for Infants

When evaluating an infant with fever and any combination of seizures, altered behavior/consciousness, feeding difficulties, or respiratory distress, maintain high suspicion for viral encephalitis even with normal CSF parameters, as this presentation is characteristic of parechovirus and early HSV infection 1, 2.

The threshold for empiric acyclovir treatment should be low given the devastating consequences of untreated HSV encephalitis and the relative safety of early antiviral therapy 1.