Herpes simplex virus 1 infection is a common cause of encephalitis (HSVE) in the United States. Post-HSVE development of N-methyl-D-aspartate receptor (NMDAR) antibodies resulting in autoimmune encephalitis is a rare complication, primarily affecting children and young adults. Anti-NMDAR develops 1–4 weeks after HSVE, manifesting as choreoathetosis and/or orofacial dyskinesia in children and psychiatric symptoms in young adults. We describe a case of a 61-year-old male who presented with agitation, behavioral changes, and confusion eight months after being treated for HSVE. Extensive investigation was unrevealing except for cerebrospinal fluid lymphocytic pleocytosis, a positive anti-NMDAR Ab titer 1 : 64, and imaging changes consistent with postviral encephalitis suggestive of HSV-induced anti-NMDAR encephalitis. Aggressive therapy resulted in limited success and persistent neurologic deficits. The unique features of this case are the old age of the patient and preceding HSVE which triggered this autoimmune process. Physicians should consider anti-NMDAR encephalitis in the differentials for relapsing patients after HSVE.
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