What is the treatment for a patient with NMDA (N-methyl-D-aspartate) receptor encephalitis associated with a teratoma?

Treatment of NMDA Receptor Encephalitis with Teratoma

Patients with NMDA receptor encephalitis and teratoma require immediate tumor removal combined with aggressive immunotherapy, as early surgical resection of the teratoma followed by first-line immunotherapy (corticosteroids plus IVIG or plasma exchange) results in the best neurological outcomes and lowest relapse rates. 1, 2, 3

Immediate Surgical Management

Tumor removal is the cornerstone of treatment and should be performed urgently once the teratoma is identified. 1, 2

• Laparoscopic cystectomy should be performed during the acute phase of neurological symptoms, as early operative treatment is associated with reduced relapse risk (14.6% vs 33.3% in those without tumor removal) and complete recovery in 96.5% of patients 2

• The surgical approach should prioritize ovarian-sparing cystectomy when possible to preserve fertility, particularly in young women, as successful outcomes have been documented even with multiple surgeries 4

• Careful bilateral ovarian exploration is critical because teratomas can be as small as 1 cm and bilateral in 13.8% of cases 2

• Even microscopic teratomas can drive treatment resistance, so thorough surgical exploration is essential 4

First-Line Immunotherapy

Immunotherapy must be initiated immediately after infection is excluded by basic CSF studies, without waiting for antibody confirmation. 1

Severe Presentations Require Combination Therapy

For patients with decreased consciousness, dyskinetic movements, autonomic instability, or seizures (which characterize most teratoma-associated cases):

• Pulse-dose methylprednisolone (1g IV daily for 3-5 days) PLUS either IVIG or plasma exchange should be started from the outset 1

• Plasma exchange (5-10 sessions every other day) combined with corticosteroids is superior to corticosteroids alone for improving modified Rankin scores in NMDAR encephalitis 1

• Choose plasma exchange over IVIG for patients with severe hyponatremia, high thromboembolic risk, or when corticosteroids are contraindicated 1

• Choose IVIG over plasma exchange for agitated patients (easier administration), those with bleeding disorders, or when central line placement poses risks 1

Second-Line Immunotherapy

If no meaningful clinical, radiological, or electrophysiological improvement occurs within 2-4 weeks after completing combined first-line therapy, escalate to second-line agents. 1

• Rituximab is the preferred second-line agent for NMDAR encephalitis due to its favorable toxicity profile compared to cyclophosphamide 1

• Rituximab targets B-cells and indirectly suppresses T-cell activity 1

• Cyclophosphamide is reserved for suspected cell-mediated autoimmunity with intracellular antibodies 1

Critical Clinical Considerations

Severity in Teratoma-Associated Cases

Patients with ovarian teratomas present with significantly more severe disease compared to those without tumors:

• 75.9% develop fever, 65.5% have decreased consciousness, 55.2% require ventilator-assisted respiration, and 58.6% require ICU care 2

• The modified Rankin Scale at acute onset averages 4.11 in teratoma patients versus 3.58 in non-teratoma patients 2

Tumor Screening Protocol

All young and middle-aged adults with typical NMDAR encephalitis require specific teratoma screening: 5

• Transvaginal or transabdominal pelvic ultrasound is the primary screening tool for ovarian teratoma in females 5

• Testicular ultrasound should be performed in males 5

• If ultrasound is equivocal, obtain pelvic MRI 5

• Annual tumor screening should continue for several years, particularly if treatment response is poor or relapses occur 6, 5

Timing and Prognosis

Early tumor removal correlates with rapid neurological improvement - one case demonstrated prompt response and full recovery when teratoma was removed early, followed by plasma exchange and corticosteroids 3

Serial antibody monitoring shows serum titers decrease early after tumor removal, though CSF titers correlate better with clinical outcome 3

Refractory Cases

For patients showing no improvement with conventional therapies:

• Consider tocilizumab (IL-6 inhibitor) or bortezomib as third-line options 1

• Additional surgeries may be necessary for residual or recurrent teratomas in treatment-resistant cases 4

Maintenance Therapy

After acute treatment, initiate bridging therapy with gradual oral prednisone taper, monthly IVIG, or monthly IV methylprednisolone to prevent relapse 1