Not applicable 

Patients with acute encephalitis typically present with rapidly progressive encephalopathy from infectious or autoimmune etiologies. West Nile Virus (WNV) is the most common cause of infectious encephalitis in the United States. However, neuroinvasive WNV occurs in <1% of documented cases. Meanwhile, Anti-N-methyl-D-aspartate receptor (Anti-NMDAR) encephalitis is classically known as a paraneoplastic autoimmune encephalitis affecting women with ovarian teratomas, but it has been increasingly diagnosed among children and men without any identifiable malignancy as well.

In July 2024, a 23-year-old immunocompetent male with no prior medical history presented to a community hospital for bilateral upper extremity shaking. After obtaining unremarkable CT and MRI brain imaging and labs, he was discharged home. 1 day later, he presented to our hospital with similar complaints, along with worsened headaches, lethargy, and occasional hallucinations. Imaging and electroencephalogram (EEG) monitoring were again unremarkable. After being discharged with presumptive migraines, he returned to the hospital within 3 days, now in a floridly psychotic state with frequent generalized convulsions. Cerebrospinal fluid (CSF) samples were sent out and the patient was empirically treated with methylprednisolone and IV immunoglobulin (IVIG) infusions for suspected autoimmune encephalitis. CSF labs eventually returned with Anti-NMDAR (1:65 titer) and WNV (both IgM and IgG) positivity and a negative paraneoplastic panel. Scrotal ultrasound and whole-body CT were negative for malignancy. EEG was notable for extreme delta brush. The patient’s psychosis, agitation, and dyskinetic movements improved after prolonged treatment with rituximab infusions and scheduled benzodiazepines.