Investigators at University of Texas Southwestern Medical Center, Dallas, TX, report 2 male patients, an infant and adult, with confirmed herpes simplex encephalitis (HSE) and anti-NMDA receptor antibody encephalitis. Testing for anti-NMDA receptor antibodies and autoimmune disorder is recommended in patients with persistent encephalopathy, regression after initial improvement, or persistent movement disorders. Neuronal infections such as HSV may trigger subsequent anti-NMDA receptor antibody formation. Concomitant treatment or testing for immune-mediated encephalitis is indicated when treating viral encephalitis. 
COMMENTARY. The association of herpes simplex and anti-NMDA receptor antibody encephalitides is reported in 5 prospectively diagnosed patients (2 female) with relapsing post-herpes simplex encephalitis . In 3 further retrospectively studied patients with HSE and NMDAR antibodies the frequency of autoantibodies increased over time, suggesting that HSE triggers NMDAR antibodies and brain autoimmunity . All prospectively identified patients were treated with a second course of IV acyclovir, and 4 received immunotherapy with improvement in 3.