What is the management approach for a patient with a history of ovarian cystic teratoma (cystic teratoma) presenting with bilateral arm cramps and suspected anti-N-methyl-D-aspartate (NMDA) receptor encephalitis?

Management of Ovarian Cystic Teratoma with Suspected Anti-NMDA Receptor Encephalitis

Immediately initiate first-line immunotherapy with pulse-dose methylprednisolone (1g IV daily for 3-5 days) plus either IVIG or plasma exchange as soon as infection is excluded by basic CSF analysis, and proceed urgently with surgical removal of the ovarian teratoma once the patient is medically stable. 1, 2

Immediate Diagnostic Confirmation

• Send serum and CSF for anti-NMDA receptor antibodies immediately, but do not wait for results before starting treatment 2
• The bilateral arm cramps (likely faciobrachial dystonic seizures or choreoathetosis) combined with psychiatric symptoms in a young woman with known ovarian teratoma is highly characteristic of NMDAR encephalitis 3
• Confirm the teratoma with transvaginal or transabdominal pelvic ultrasound if not already done; proceed to pelvic MRI if ultrasound findings are equivocal 4

First-Line Immunotherapy Protocol

Start immunotherapy immediately once infection is excluded based on CSF cell count, protein, and glucose—do not delay for antibody confirmation. 1, 2

Combination Therapy for Severe Presentation

• Use pulse-dose methylprednisolone (1g IV daily for 3-5 days) combined with either IVIG or plasma exchange from the outset 1
• Choose IVIG if the patient is agitated (easier to administer), has bleeding disorders, or when central line placement poses risks 1
• Choose plasma exchange (5-10 sessions every other day) if the patient has severe hyponatremia, high thromboembolic risk, or when corticosteroids are contraindicated 1
• Plasma exchange combined with corticosteroids shows superior modified Rankin score improvement compared to corticosteroids alone in NMDAR encephalitis 1

Surgical Management of Teratoma

Surgical removal of the ovarian teratoma is critical and should be performed as soon as the patient is medically stable, as the tumor triggers the autoimmune response. 1, 2

• In female patients with NMDAR encephalitis, 20-50% harbor an ovarian teratoma that requires surgical removal 4, 2
• Laparoscopic cystectomy or adnexectomy should be performed depending on the extent of disease 5, 6
• Tumor removal combined with immunotherapy results in rapid improvement in approximately half of patients 7
• Complete recovery after surgery emphasizes the need for early tumor removal to improve prognosis 6

Second-Line Therapy if Inadequate Response

If no meaningful clinical, radiological, or electrophysiological improvement occurs within 2-4 weeks after completing combined first-line therapy, initiate rituximab. 1, 2

• Rituximab is preferred for NMDAR encephalitis as it targets B-cells and indirectly suppresses T-cell activity 1
• Rituximab has a more favorable toxicity profile than cyclophosphamide, making it the first choice for most newly diagnosed cases 1
• Cyclophosphamide is reserved for suspected cell-mediated autoimmunity with intracellular antibodies 1

Monitoring and Relapse Prevention

• After acute treatment, initiate bridging therapy with gradual oral prednisone taper, monthly IVIG, or monthly IV methylprednisolone to prevent relapse 1
• Relapses occur in 20-25% of non-paraneoplastic patients and can be separated by months or years 3
• Critical pitfall: Tumor screening should be performed annually for several years, particularly if treatment response is poor or relapses occur, as even microscopic teratomas can contribute to treatment resistance 3, 4, 7

Clinical Context and Prognosis

• NMDAR encephalitis is the single most common cause of encephalitis in patients under 30 years, with a median age of 25 years and female-to-male ratio of 2:1 3, 1
• Treatment started within 4 weeks of symptom onset confers the best recovery 3
• With appropriate treatment including tumor removal and immunotherapy, 74% of patients achieve full or substantial recovery at 1 year 3
• Patients who had a teratoma and were treated with tumor removal and immunotherapy had more frequent full recovery 3