What is the treatment for Anti-NMDA (N-methyl-D-aspartate) encephalitis?

Treatment for Anti-NMDA Receptor Encephalitis

The treatment for Anti-NMDA receptor encephalitis requires prompt initiation of immunotherapy with first-line agents (corticosteroids, IVIG, or plasma exchange), followed by second-line therapy (rituximab and/or cyclophosphamide) if no improvement occurs within 4 weeks, along with tumor screening and removal if present. 1, 2

Diagnostic Confirmation

Before initiating treatment, confirm the diagnosis with:

• CSF analysis for anti-NMDAR antibodies
• Brain MRI with contrast
• EEG to assess for seizure activity
• Comprehensive tumor screening

Treatment Algorithm

First-Line Immunotherapy

1. Corticosteroids: Intravenous methylprednisolone 1g daily for 3-5 days, followed by oral prednisone taper 2
2. IVIG: 2g/kg divided over 2-5 days 2
3. Plasma Exchange: 5-7 exchanges over 10-14 days 2

Key Point: For severe presentations (status epilepticus, severe dysautonomia), combination therapy with steroids plus IVIG or steroids plus plasma exchange is recommended from the outset 2

Tumor Screening and Removal

• Thorough cancer screening with CT scans of chest, abdomen, and pelvis with contrast (or MRI when CT is contraindicated) 2
• Additional screening with mammography, pelvic ultrasound, and/or FDG-PET total body scan based on clinical presentation and risk factors 2
• If tumor is identified (particularly ovarian teratoma), surgical removal should be performed promptly 1

Second-Line Immunotherapy

If no improvement within 4 weeks of first-line treatment:

• Rituximab: 375 mg/m² weekly for 4 weeks or two 1000 mg doses 2 weeks apart 2
• Cyclophosphamide: 600-1000 mg/m² 2

Evidence Note: Patients who received second-line immunotherapy had significantly better outcomes (mRS 0-2) than those who did not (OR 2.69, CI 1.24-5.80; p=0.012) 3

Maintenance Therapy

After acute treatment:

• Gradual oral prednisone taper
• Monthly IVIG or monthly IV methylprednisolone 2
• Consider mycophenolate mofetil or azathioprine for steroid-responsive patients 2
• A 6-month course of IVIG during rituximab treatment period 2

Monitoring and Follow-up

• Regular assessment of clinical response using modified Rankin scale
• Monitor for seizures and provide appropriate antiepileptic treatment
• Monitor for autonomic instability (cardiac arrhythmias, blood pressure fluctuations)
• Track CD19+ B cell levels in patients receiving rituximab 2
• Continue follow-up for at least 24 months, as improvement can continue for up to 18 months after symptom onset 3

Special Considerations

Refractory Cases

For patients not responding to conventional second-line therapies:

• Consider tocilizumab (IL-6 inhibitor) or bortezomib (proteasome inhibitor) 2, 4
• Permanent cardiac pacemaker may be necessary for severe, refractory autonomic instability with bradycardia/asystole 5
• Management of increased intracranial pressure may be required in some cases 5

Relapse Prevention

• 12% risk of relapse within 2 years 3
• Subsequent relapses are typically less severe than initial episodes 3
• Extended immunosuppression may be necessary for patients with relapsing disease

Common Pitfalls to Avoid

1. Delayed diagnosis due to psychiatric presentation - maintain high index of suspicion for anti-NMDAR encephalitis in young patients with new-onset psychiatric symptoms 2
2. Underestimating disease severity - be prepared to escalate therapy quickly in deteriorating cases 2
3. Premature discontinuation of therapy - continue treatment as recovery may take up to 18 months 3
4. Missing associated malignancy - perform thorough tumor screening 2
5. Delayed initiation of second-line therapy - early treatment is a predictor of good outcome (OR 0.62,0.50-0.76; p<0.0001) 3

Early and aggressive immunotherapy is critical for improving outcomes in anti-NMDAR encephalitis, with predictors of good outcome being early treatment initiation and avoidance of ICU admission 3.