Abstract Anti-N-methyl-D-aspartate (NMDA) receptor antibody encephalitis is a rare autoimmune disorder targeting the GluN1 subunit of the NMDA receptor. It classically presents with acute psychiatric and neurological symptoms and is most often associated with ovarian teratomas, vaccines, or post-viral immune activation1. While it predominantly affects young women, cases in males and older adults are increasingly recognized2. Approximately 58% of cases are paraneoplastic, but an important subset follows Herpes Simplex Virus (HSV) encephalitis, suggesting post-infectious autoimmunity through molecular mimicry3. A 21-year-old male with no significant past medical history presented with acute onset of behavioral disturbance, disorganized speech, and rapidly progressive cognitive decline, ultimately developing catatonia and autonomic instability requiring ICU admission. Initial neuroimaging and CSF analyses were unremarkable, without evidence of infection, inflammation, or structural pathology. Eleven days after presentation, serum and CSF testing returned positive for anti-NMDA receptor (GluN1) antibodies, confirming the diagnosis. He received high-dose corticosteroids and intravenous immunoglobulin, followed by rituximab due to persistent neuropsychiatric symptoms and inadequate initial clinical response. With comprehensive neurocritical care and immunotherapy, he demonstrated gradual yet substantial improvement in neurological function and cognition, highlighting the need for prompt immunomodulatory intervention in atypical and tumor-negative presentations. Anti-NMDA receptor encephalitis is a rare autoimmune encephalitis, representing only ∼4% of all encephalitis cases2. Pathophysiologically, antibodies cross the blood-brain barrier and cause internalization of NMDA receptors, disrupting glutamatergic neurotransmission and leading to the characteristic neuropsychiatric syndrome1. The illness typically progresses through distinct phases—psychiatric disturbance, memory loss, seizures, dysautonomia, and movement disorders—often resulting in ICU admission for airway or hemodynamic instability. The differential diagnosis includes viral encephalitis, toxic/metabolic encephalopathy, and primary psychiatric disease. Clues suggesting an autoimmune etiology include fluctuating symptoms, resistance to antipsychotics, oropharyngeal dyskinesias, and autonomic dysfunction. Although teratoma-associated cases are well established, up to 40% of patients—particularly males—lack detectable tumors4. Post-HSV cases illustrate an evolving concept of “secondary autoimmune encephalitis,” where viral destruction exposes neuronal antigens that trigger antibody formation3. Early initiation of immunotherapy significantly improves prognosis. First-line therapy includes corticosteroids, IVIG, or plasma exchange, with escalation to rituximab or cyclophosphamide for refractory disease4. Most survivors achieve substantial neurological recovery, though relapses occur in approximately 12% within two years. Notably, NMDA receptor encephalitis is significantly less common in males, who represent a minority of cases, often without an underlying neoplasm. This highlights the atypical nature of presentations in men. This abstract is funded by: None
George et al. (Fri,) studied this question.