Herpes simplex virus (HSV)-1 encephalitis is the most common infectious cause of sporadic encephalitis. Despite treatment with acyclovir, HSV encephalitis is still associated with severe morbidity characterized by persistent neurological deficits. HSV encephalitis usually follows a monophasic course, however, some patients might develop relapsing symptoms caused by the formation of auto-antibodies directed against the N-methyl-D-aspartate receptor (NMDAR). Here we present an 82-year-old male patient with HSV encephalitis who developed shortly after his hospital discharge a Post-HSV NMDAR encephalitis, characterized by recurrent epileptic seizures and deterioration of his residual aphasia. First-line immunotherapy with intravenous immunoglobulins (IgIV) was administered and the patient returned almost to his baseline residual deficits of HSV encephalitis. Subsequently, he presented with recurrent relapses of NMDAR encephalitis. Since periodic treatment with IgIV has been started the patient is seizure-free and his neuropsychiatric condition is stable. In conclusion, the recognition of Post-HSV NMDAR encephalitis is very important because neurological manifestations can markedly improve with immunotherapy. Interestingly, in some patients cerebral HSV infection seems to trigger a chronic inflammatory disorder with persistent autoimmune activation which requires chronic treatment.
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