What could be the cause of a 6-month-old infant's cessation of smiling after a viral fever, with normal MRI (Magnetic Resonance Imaging) and normal blood counts?

Loss of Social Responsiveness Following Viral Illness in a 6-Month-Old

This infant requires urgent lumbar puncture and empiric acyclovir for presumed viral encephalitis, despite normal MRI and blood counts, as imaging can be normal early in disease and the behavioral change represents a critical neurological sign.

Immediate Clinical Concern

The cessation of smiling in a 6-month-old following viral fever represents a significant behavioral regression that warrants aggressive evaluation for post-infectious encephalitis, even with normal initial investigations 1.

Why Normal MRI Does Not Exclude Encephalitis

• MRI can be normal in up to 10% of viral encephalitis cases within the first 48 hours of presentation, particularly in HSV encephalitis where only 25% show abnormalities on initial CT scanning 1
• Normal blood counts do not exclude CNS infection, as viral encephalitis frequently presents with normal peripheral laboratory values 1
• The behavioral change (loss of smiling) represents altered mental status and personality change, which are hallmark features of encephalitis 1

Essential Next Steps

Lumbar Puncture is Critical

• Perform LP immediately unless contraindications exist (GCS <9, signs of raised intracranial pressure, coagulopathy with platelets <50-100 × 10⁹/L, or clinical instability) 1
• CSF analysis is essential as it provides diagnostic information that imaging cannot, particularly for viral encephalitis where MRI may be normal 1
• Send CSF for: cell count, protein, glucose (with paired serum glucose), HSV PCR, enterovirus PCR, VZV PCR, and bacterial/viral cultures 1
• Approximately 50% of HSV encephalitis cases show elevated CSF red cell count, though acellular CSF can occur with VZV, EBV, and CMV 1

Empiric Antiviral Therapy

• Start intravenous acyclovir immediately for suspected viral encephalitis, even before LP results return 1
• This is standard of care for any child with suspected encephalitis given the devastating consequences of untreated HSV encephalitis 1

Differential Diagnosis Beyond Encephalitis

While encephalitis is the primary concern, consider:

• Post-infectious encephalopathy from various viral pathogens (enterovirus, VZV, influenza) 1
• Mycoplasma pneumoniae CNS involvement (can show focal cortical lesions, white matter lesions, or demyelination on MRI) 1
• Evolving epilepsy syndrome following complex febrile seizure (if seizures occurred during the fever) - would require EEG and neurology consultation 2, 3
• HIV-related CNS infection if risk factors present (though less likely at 6 months without other symptoms) 1

Critical Pitfalls to Avoid

• Do not be falsely reassured by normal MRI - imaging sensitivity is only 90% even at 48 hours, and can be much lower in the first week 1
• Do not delay LP and acyclovir while waiting for additional imaging or specialist consultation 1
• Do not assume this is simple post-viral fatigue - loss of developmental milestones (social smiling) is a red flag for neurological injury 1
• At 6 months of age, if any seizures occurred during the fever, this would be atypical for simple febrile seizures and warrants EEG and neurology evaluation 2, 3

Specialist Involvement

• Immediate pediatric neurology consultation is indicated for behavioral regression following viral illness 3, 4
• Neurology consultation results in modification of diagnosis or treatment in 66% of pediatric neurological emergencies 4
• If no diagnosis is established after one week of evaluation and the child continues to deteriorate, consider brain biopsy (though this has no role in initial assessment) 1

Prognosis Considerations

The extent of early MRI abnormality in HSV encephalitis does not correlate well with clinical evolution, though correlation exists between number of seizures and subsequent brain atrophy 1. Early aggressive treatment with acyclovir significantly impacts morbidity and mortality outcomes 1.