Uncommon Presentation of Anti-NMDA Receptor Encephalitis: A Case Report of Mediastinal Teratoma and Refractory Neurological Symptoms

Case Diagnosis: Anti-N-methyl-D-aspartate receptor (NMDA-R) encephalitis is a rare autoimmune disorder affecting young individuals, with symptoms like psychosis, seizures, movement disorders, and cognitive impairments.

Case Description or Program Description: It is often triggered by ovarian teratomas but can occur without a tumor. Early recognition and immunosuppressive treatment are crucial, as delays can lead to severe morbidity or death. This case highlights the need for a multidisciplinary approach, particularly when the condition presents with unusual features and an atypical cause.

Setting: A 16-year-old male presented after experiencing two witnessed seizures on 5/7/2024, with no prior seizure history. Initial imaging revealed an anterior mediastinal mass, suspected to be a mature teratoma which biopsy later confirmed. Further workup revealed encephalopathy with agitation and confusion, leading to transfer to the PICU.

Assessment/Results: A lumbar puncture confirmed autoimmune encephalitis secondary to NMDA receptor antibodies (NMDARE), a paraneoplastic syndrome rarely associated with mediastinal teratomas. Despite treatments with steroids, IVIG, and plasmapheresis, the patient's encephalopathy persisted, along with seizures, movement disorders, and dysautonomia. He underwent resection of the mass, but his condition remained critically unstable. A second dose of rituximab and tocilizumab was administered, and in January 2025, a ketamine infusion trial was attempted to enhance NMDA receptor trafficking. However, it did not improve his condition. By October 2024, his NMDA-R antibody titers remained high, and immunosuppressive therapy was escalated.

Discussion (relevance): While often triggered by ovarian teratomas, mediastinal teratomas can also cause the condition, a rare occurrence with only four documented cases by 2017. Initial treatments were ineffective, requiring escalation to rituximab, tocilizumab, and cyclophosphamide. A ketamine coma infusion trial was attempted to enhance NMDA receptor signaling. The delayed response underscores the need for early diagnosis and ongoing management, especially as NMDA receptor antibodies may persist after tumor resection, complicating treatment.

Conclusions: This case highlights the complexity of anti-NMDA receptor encephalitis and the challenges in treating refractory cases.