Anti-NMDA-receptor encephalitis
ICD-10 G04.8 · ICD-11 8E4A.0.3

Severe Anti-NMDA-Receptor Encephalitis in Children Under 18 — What to Do When First-Line Immunotherapy Has Not Worked

This protocol addresses children under 18 years with confirmed Anti-NMDA-receptor encephalitis classified as severe disease in whom first-line immunotherapy did not achieve sufficient clinical improvement.

Clinical Scenario

Children (age <18 years) with NMDA receptor antibody encephalitis are classified as severe disease when at least one severity marker affecting safety or function is present — including requirement for intensive care, airway support, dysautonomia threatening safety, being bed-bound, suicidal thoughts, or an adapted mRS score of 4–5.

Escalation Trigger — Previous Treatment Goal Not Met
First-line therapy — goal not reached

First-line immunotherapy (IV corticosteroids combined with TPE and/or IVIg) did not achieve significant gains in function assessed approximately one week after initiation. This protocol is the next step following that failure.

Next Step — Second-Line Immunotherapy (Partial Overview)

For children with severe Anti-NMDA-receptor encephalitis who have not improved sufficiently on first-line therapy, second-line immunotherapy with rituximab (RTX) as the agent of choice — or a defined alternative when rituximab cannot be used — is indicated, typically initiated around 2 weeks after first-line treatment began.

Full dosing, scheduling options, and selection criteria are specified in the complete protocol.

Treatment Goal

Adequate improvement assessed 1–3 months following initiation of the first second-line immunotherapy.

Instant Access to Structured Evidence-Based Regimens

References

DOI: 10.1212/NXI.0000000000001052

  • Severe is defined by issues affecting SAFETY and FUNCTION.
  • Any (≥1) of the severity markers present below (items a-i) scoring “severe” rather than “standard” would classify as severe disease.
  • Second-line immunotherapy should be offered to patients with severe disease.
  • Rituximab (RTX) is generally the second-line therapy of choice. Cyclophosphamide (CYC) may be considered if RTX is contraindicated or not available.
  • Another second-line therapy (i.e., CYC, if RTX was used first, or vice versa) can be used in any patient with severe disease who fails to improve adequately 1–3 mo following initiation of the first second-line immunotherapy.
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