Anti-NMDA receptor encephalitis in the setting of inherited chromosomally integrated human herpesvirus 6B (iciHHV-6B): A case report

Abstract

Human herpesvirus 6 (HHV-6) is a ubiquitous DNA virus most frequently associated with roseola infantum and implicated in encephalitis among immunocompromised patients. Notably, it can integrate into human telomeres, contributing to diagnostic complexities. Although herpes simplex virus is a recognized trigger of autoimmune encephalitis, a comparable relationship for HHV-6 remains unconfirmed. We present a case of a previously healthy 19-year-old woman who presented with altered mental status. Lumbar puncture revealed HHV-6 by polymerase chain reaction (PCR) in the cerebrospinal fluid (CSF), and brain magnetic resonance imaging (MRI) findings were normal. Further testing confirmed anti- N-methyl-D-aspartate (NMDA) receptor antibodies in the serum and CSF. HHV-6 serum viral load testing resulted in over 2 million copies/mL, and chromosomal integration of HHV-6 was later confirmed. Four months after diagnosis, the patient’s cognition was approaching their prior baseline. This case underscores the importance of investigating alternative etiologies of encephalitis in immunocompetent patients with detectable HHV-6 DNA in the CSF. Our report further highlights a potential association between HHV-6B and anti-NMDA receptor encephalitis, even under chromosomal integration.