A 52-year-old woman presents with acute onset of severe headache, confusion, and seizures. MRI brain shows limbic encephalitis. Anti-NMDA receptor antibodies are detected. Which is the most common malignancy associated with this paraneoplastic syndrome?

Explanation

## Anti-NMDA Receptor Encephalitis ### Clinical Presentation The patient exhibits the classic triad of anti-NMDA receptor encephalitis: - **Psychiatric phase:** Behavioral changes, paranoia, hallucinations - **Movement disorder phase:** Dystonia, choreoathetosis, rigidity - **Autonomic/seizure phase:** Seizures, autonomic instability, hypoventilation - **Imaging:** Limbic encephalitis pattern on MRI (T2/FLAIR hyperintensities in medial temporal lobes) ### Antibody-Malignancy Association | Antibody | Most Common Malignancy | Frequency | Demographics | |---|---|---|---| | Anti-NMDA receptor | Ovarian teratoma | 40–50% (young women) | Females <50 years | | Anti-NMDA receptor | Breast cancer | 10–15% | Older women | | Anti-NMDA receptor | Lung cancer | 5–10% | Smokers | | Anti-NMDA receptor | Gastric cancer | <5% | Rare | **High-Yield:** In young women with anti-NMDA receptor encephalitis, **ovarian teratoma** is the most common underlying malignancy (40–50% of cases). These are often immature teratomas containing neural tissue that expresses NMDA receptors. ### Pathophysiology Anti-NMDA receptor antibodies bind to the NR1 subunit of NMDA receptors on neuronal membranes. This causes: 1. Antibody-mediated internalization of NMDA receptors 2. Reduced synaptic transmission 3. Excitotoxic neuronal death 4. Limbic encephalitis and seizures ### Clinical Pearl **Key Point:** Anti-NMDA receptor encephalitis is one of the most common autoimmune encephalitis syndromes. In a young woman with this diagnosis, pelvic imaging (ultrasound or CT) to screen for ovarian teratoma is mandatory. **Warning:** Ovarian teratomas in this context are often **immature** and may be difficult to detect on imaging. Repeat imaging or even diagnostic laparoscopy may be needed. ### Diagnostic Approach 1. **Serology:** Anti-NMDA receptor (IgG) in serum and CSF 2. **CSF:** Lymphocytic pleocytosis, elevated protein, oligoclonal bands 3. **Brain MRI:** Limbic encephalitis (medial temporal lobe involvement) 4. **Pelvic imaging:** Transvaginal ultrasound, pelvic CT/MRI (teratoma screening) 5. **Pathology:** Ovarian biopsy if imaging inconclusive ### Management 1. **Immunotherapy:** First-line = IVIg + plasmapheresis ± corticosteroids 2. **Tumor removal:** Surgical resection of ovarian teratoma (definitive treatment) 3. **Seizure control:** Antiepileptic drugs 4. **Second-line:** Rituximab, cyclophosphamide if inadequate response **Mnemonic:** **NMDA-OT** = NMDA receptor antibodies + Ovarian Teratoma in young women.