To present a case of anti-NMDA receptor (NMDA-R) encephalitis with atypical demographics and subtle clinical symptoms nine months after herpes simplex virus (HSV) encephalitis.

 HSV encephalitis has been reported to be followed by anti-NMDA receptor encephalitis with the seroconversion rate up to 30 percent. Symptoms of NMDA-R encephalitis typically present within two months of initial onset of HSV infection and usually include mood disorder, psychosis and seizures.

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Case report.

a 74 year-old woman presented with confusion, fever and seizures in November 2017, diagnosed with HSV encephalitis. She was treated with 21-days of acyclovir, then discharged on levetiracetam, with apparent recovery. She re-presented in September 2018 with new-onset auditory hallucinations and mood changes, in the absence of prior psychiatric history.  Auditory hallucinations featured complex, well-formed sounds and voices rather than simple auditory phenomena. She had full insight into the unrealistic nature of her hallucinations. She exhibited depressed mood with no other psychotic symptoms. MRI showed stable post HSV encephalitic changes. V-EEG monitoring showed left temporal periodic lateralizing epileptiform discharges (PLEDs); no electrographic seizure activity correlated with the events of auditory hallucinations. Initial CSF analysis was unremarkable; an autoimmune CSF panel was pending at the time of discharge. Her discharge diagnosis was depression with psychotic features and levetiracetam had been changed to oxcarbazepine secondary to mood symptoms. The patient presented three weeks later, with persistent auditory hallucinations. In the interim, CSF had returned positive for NMDA-R antibody. Surveillance MRI ruled out possible underlying malignancy. She was readmitted and treated with intravenous methyl-prednisone for five days; her status as a Jehovah’s Witness precluded treatment with intravenous immunoglobulin or plasmapharesis. Nonetheless, she experienced significant resolution of her symptoms, sustained at outpatient follow-up two weeks after discharge.

Anti-NMDAR encephalitis following HSV encephalitis can present several months later in elderly with unusually mild psychotic symptoms.