PT - JOURNAL ARTICLE AU - Salovin, Amy AU - Glanzman, Jason AU - Roslin, Kylie AU - Armangue, Thais AU - Lynch, David R. AU - Panzer, Jessica A. TI - Anti-NMDA receptor encephalitis and nonencephalitic HSV-1 infection AID - 10.1212/NXI.0000000000000458 DP - 2018 Jul 01 TA - Neurology - Neuroimmunology Neuroinflammation PG - e458 VI - 5 IP - 4 4099 - http://nn.neurology.org/content/5/4/e458.short 4100 - http://nn.neurology.org/content/5/4/e458.full SO - Neurol Neuroimmunol Neuroinflamm2018 Jul 01; 5 AB - Objective To determine whether there is an association between nonencephalitic herpes simplex virus 1 (HSV-1) infection and anti-NMDA receptor encephalitis (anti-NMDARE).Methods Antibody testing was performed using samples from 2 cohorts in a case-control observational study. The cohort “Philadelphia” included 16 serum samples of pediatric anti-NMDARE cases and 42 age-matched controls with other neuroinflammatory disorders studied at the Children's Hospital of Philadelphia and University of Pennsylvania. The cohort “Barcelona” contained 23 anti-NMDARE patient samples and 26 age-matched participants with other neuroinflammatory disorders studied at IDIBAPS-Hospital Clinic, University of Barcelona. The presence of HSV-1 IgG antibodies was examined by ELISA. As an additional control, IgG antibodies to cytomegalovirus (CMV) and Epstein-Barr virus viral capsid antigen (EBV-VCA) were determined.Results In each cohort, more participants with anti-NMDARE than controls had anti-HSV-1 IgG antibodies. In the Philadelphia cohort (58 participants), 44% of anti-NMDARE cases had antibodies to HSV-1 compared with 14% controls (OR 4.67, 95% CI 1.3–17.3, p = 0.031). In the Barcelona cohort (49 participants), 52% of participants with anti-NMDARE had antibodies to HSV-1 compared with 31% of controls (OR 2.45, 95% CI 0.7–7.9, p = 0.155). Overall, 49% of anti-NMDARE cases have antibodies to HSV-1 in these 2 combined cohorts compared with 21% of controls (Mantel-Haenszel OR 3.21, 95% CI 1.3–7.7, p = 0.007).Conclusion Past HSV-1 infection was found in significantly more anti-NMDARE cases than controls. This suggests a meaningful association between nonencephalitic HSV-1 infection and development of anti-NMDARE.CHOP=Children's Hospital of Philadelphia; CMV=cytomegalovirus; EBV=Epstein-Barr virus; HSV=herpes simplex virus 1; NMDAR=NMDA receptor; NMDARE=NMDA receptor encephalitis; UPenn=University of Pennsylvania