What is the most likely cause of new‑onset hallucinations, seizures, and personality changes in a woman with an ovarian teratoma?

Anti-NMDA Receptor Encephalitis

The most likely cause of hallucinations, seizures, and personality changes in a woman with an ovarian teratoma is anti-NMDA receptor encephalitis, a paraneoplastic autoimmune disorder where antibodies produced against the teratoma cross-react with NMDA receptors in the brain.

Pathophysiology and Clinical Presentation

Anti-NMDA receptor encephalitis occurs when antibodies target the GluN1 subunit of NMDA receptors, leading to internalization of these synaptic receptors 1. This mechanism directly explains the neuropsychiatric syndrome you're observing. The classic presentation includes:

• Neuropsychiatric symptoms (hallucinations, personality changes, psychosis) - often the initial manifestation in 80-100% of patients 2
• Seizures (both focal and generalized)
• Movement disorders (dyskinesias, myoclonus)
• Autonomic instability in severe cases
• Decreased level of consciousness as disease progresses

The guideline evidence explicitly states that ovarian teratoma is strongly associated with NMDAR-antibody encephalitis, particularly in young and middle-aged women with this typical clinical picture 3.

Diagnostic Approach

Immediate workup should include:

• CSF analysis with autoimmune encephalopathy panel - testing for anti-NMDA receptor antibodies in both CSF and serum (CSF is more sensitive for NMDAR antibodies) 3
• Transvaginal or transabdominal pelvic ultrasound to confirm the teratoma 3
• Brain MRI - may show temporal lobe hyperintensities 4 though can be normal
• CSF studies typically show mild-to-moderate lymphocytic pleocytosis (20-200 cells), elevated protein, and sometimes oligoclonal bands 3

A critical caveat: Don't wait for antibody confirmation to initiate treatment if clinical suspicion is high. Recent case evidence demonstrates that early surgical resection within 72 hours before antibody confirmation, combined with immunotherapy, leads to sustained neurological recovery 1.

Treatment Algorithm

The treatment requires both tumor removal and immunosuppression:

1. First-line therapy (initiate immediately upon suspicion):

   • High-dose methylprednisolone
   • IVIG
   • Plasma exchange
   • Surgical resection of the ovarian teratoma - this is essential and should not be delayed 1, 4, 5

2. Second-line therapy (if refractory to first-line after 10-14 days):

   • Rituximab
   • Consider cyclophosphamide

The key principle: Immunotherapy alone frequently fails without tumor removal 5. The teratoma is the source of the antigenic stimulus, so surgical excision is not optional—it's a cornerstone of treatment alongside immunosuppression.

Prognosis and Pitfalls

The mechanism of NMDA receptor internalization is potentially reversible, meaning timely treatment can lead to complete neurological recovery 1. Multiple recent cases demonstrate full recovery with appropriate multidisciplinary management 1, 4, 5.

Common diagnostic pitfalls to avoid:

• Misdiagnosis as primary psychiatric illness - this is extremely common and delays appropriate treatment 4. Any young woman with new-onset psychosis, hallucinations, or personality changes should trigger consideration of anti-NMDA receptor encephalitis
• Waiting for antibody results - clinical suspicion should drive early treatment initiation 1
• Failing to screen for teratoma - pelvic imaging is mandatory even without gynecologic symptoms 4
• Seronegative cases exist - absence of detectable antibodies doesn't exclude the diagnosis if clinical picture is consistent 6

The clinical course can be severe with complications including status epilepticus, autonomic instability, and prolonged ICU stays 2, but early recognition and aggressive treatment combining tumor resection with immunotherapy offers the best chance for complete recovery.