What is the treatment approach for compound encephalitis in pediatric patients?

Understanding and Managing Encephalitis in Children

Definition and Classification

Encephalitis is inflammation of the brain parenchyma causing neurological dysfunction, and it represents a medical emergency requiring immediate recognition and systematic treatment. 1

Encephalitis in children can be broadly classified into:

• Infectious causes: Direct CNS infection by viruses (HSV, enteroviruses, flaviviruses), bacteria (especially intracellular organisms like Mycoplasma pneumoniae), parasites, and fungi 1
• Para-infectious/immune-mediated: Acute disseminated encephalomyelitis (ADEM), which occurs temporally related to prior infection or immunization 1
• Autoimmune/antibody-mediated: Including NMDA-receptor antibody encephalitis and voltage-gated potassium channel (VGKC)-complex antibody encephalitis, increasingly recognized in children 1

Clinical Presentation

The presenting features in children differ from adults and include:

• Altered mental status (confusion, irritability, behavior change): 76% of cases 1
• Fever: 67-80% of cases 1
• Seizures: 45-61% of cases 1
• Focal neurological signs: 29-37% of cases 1
• Vomiting: 57% of cases 1

Young children and infants present with non-specific symptoms including feeding difficulties and respiratory problems, making diagnosis particularly challenging. 1

Important Clinical Clues by Etiology

• Lower cranial nerve involvement: Enteroviruses, especially EV-71 1
• Myoclonus: Flaviviruses (West Nile virus, Japanese encephalitis) 1
• Autonomic dysfunction: Rabies 1
• Limbic encephalitis with speech/movement disorders: Antibody-mediated encephalitis 1

Treatment Approach

Immediate Management

All children with suspected encephalitis require urgent empiric aciclovir treatment while awaiting diagnostic results, as delays beyond 48 hours after hospital admission are associated with worse prognosis. 1

Patients with falling level of consciousness require urgent pediatric ICU assessment for airway protection, ventilatory support, management of raised intracranial pressure, optimization of cerebral perfusion pressure, and correction of electrolyte imbalances. 1

Specific Treatments by Etiology

HSV Encephalitis

• Aciclovir remains the cornerstone of treatment and dramatically improves outcomes when started early 1
• Immunocompromised patients may require prolonged treatment courses 1

Enterovirus Encephalitis

• No specific treatment is recommended for enterovirus encephalitis 1
• In severe disease, pleconaril (if available) or intravenous immunoglobulin may be considered, though no randomized trials support their use 1
• Pleconaril reduced symptoms in aseptic meningitis by approximately 2 days but is not widely available 1

Antibody-Mediated Encephalitis

Immunosuppressive strategies with high-dose intravenous corticosteroids, IVIG, and plasma exchange should be initiated promptly, as treatment started within 4 weeks of symptom onset confers the best recovery. 1

• VGKC-complex and NMDA-receptor antibody encephalitis require tumor screening, including imaging for ovarian teratomas 1
• Annual tumor screening should be conducted for several years, particularly in NMDA-receptor antibody cases 1
• 25-30% of patients with NMDA-receptor encephalitis relapse, requiring ongoing surveillance 1

Flavivirus Encephalitis (Including Dengue)

Corticosteroids, interferon alpha-2a, ribavirin, minocycline, or other antivirals should NOT be routinely used for flavivirus encephalitis, as controlled trials show no improvement in clinical outcomes. 2

• Early aggressive supportive management is crucial, as dengue encephalitis has a 20-30% case-fatality ratio 2

Critical Care Requirements

Patients with suspected acute encephalitis must have access to pediatric neurological specialist opinion within 24 hours of referral. 1

Access to neuroimaging (MRI preferred, CT if unavailable) under general anesthetic if needed is essential. 1

Diagnostic Evaluation

CSF Analysis

• CSF examination is critical, though in immunocompromised patients, CSF may be acellular despite active infection 1
• All CSF specimens should be tested for HSV PCR, enterovirus PCR, and increasingly for anti-NMDAR antibodies 3

Neuroimaging

• MRI is the imaging modality of choice, particularly in immunocompromised patients 1
• Specific patterns may suggest etiology (e.g., temporal lobe involvement in HSV, transient splenial lesions in HHV-7) 4

Additional Testing

The differential diagnosis requires consideration of:

• Para-infectious immune-mediated processes: Requiring MRI brain/spine, influenza PCR, CSF examination 1
• Autoimmune/inflammatory causes: Requiring extensive autoantibody panels including VGKC-complex and NMDA-receptor antibodies 1
• Metabolic, vascular, neoplastic, and toxic causes 1

Prognosis and Rehabilitation

All children require comprehensive rehabilitation assessment before discharge, as neurological sequelae may not be immediately apparent. 1

• 30-50% of survivors develop long-term neurological or psychiatric sequelae 2
• Common sequelae include anxiety, depression, behavioral problems (intrusive obsessive behavior, challenging behavior, hyperactivity/concentration difficulties) 1
• Refractory status epilepticus at presentation predicts worse neurological outcome (odds ratio 20.38) and longer ICU stay 5

At discharge, children must have either a definite or suspected diagnosis, with arrangements for outpatient follow-up and ongoing therapy/rehabilitation formulated at a discharge meeting. 1

Rehabilitation Services Required

A broad, comprehensive approach includes:

• Neuropsychology and child/adolescent mental health teams as central components 1
• Speech and language therapists 1
• Neuro-physiotherapists 1
• Occupational therapists 1
• Access to specialist brain injury rehabilitation services 1

Parents and older children should be informed about support from organizations like the Encephalitis Society, as information reduces isolation and helps family adjustment. 1

Common Pitfalls

• Failure to start empiric aciclovir promptly: The most common reason for missed HSV encephalitis diagnosis is dismissing non-specific initial symptoms 1
• Overlooking antibody-mediated encephalitis: These have poorer outcomes if untreated and require different management 1
• Inadequate follow-up: 33% of patients are discharged without outpatient follow-up despite 96% reporting ongoing complications 1
• Missing subtle seizures: Non-convulsive status epilepticus and subtle motor status can occur and worsen prognosis 1
• Delayed specialist consultation: Neurological opinion must be obtained within 24 hours 1