A Mysterious Case of Encephalitis: Diagnostic Challenge and Our Clinical Reasoning

Acute psychotic symptoms in young patients are frequently attributed to toxic or infectious causes. After ruling out the most common causes, obtaining a firm diagnosis becomes challenging. In this case report, we present the case of a young woman who presented with acute psychosis after returning from a five-day vacation in Mexico. We treated this as a case of cerebral spinal fluid (CSF)-negative anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, as testing for CSF-NMDA receptor IgG antibodies was negative, and the absence of anti-NMDAR IgG antibodies does not rule out this autoimmune encephalitis. Moreover, IV methylprednisolone remarkably improved our patient’s mental status and behavior. Anti-NMDAR encephalitis manifests itself in a variety of ways. As a result, providers must maintain a high level of suspicion based on their clinical assessment, as delays in labs or failure to diagnose early based on the clinical presentation can lead to delays in treatment with which this severe immune-mediated paraneoplastic condition can quickly escalate and have worse consequences. We describe our thought process behind our clinical judgment toward this atypical scenario to contribute to identifying this condition early on in the complex clinical presentation.