Anti-N-methyl-D-aspartate receptor encephalitis associated with reactivated Epstein-Barr virus infection in pediatric patients: Three case reports

Rationale: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most frequent autoimmune encephalitis in children, and its presentation is various. The disease can be triggered by various infections. Patient concerns: Case 1 was a 7-year-old female with the presentation of seizure, repeated fever, language disorder, and decreased muscle strength of the right limbs; Case 2 was a 7-year-old male with the manifestation of repeated emesis, headache, involuntary movement, altered personality, seizures, and cognitive impairment; Case 3 was a 2-year-old female with repeated fever, emesis, seizures, coma, and decreased muscle strength of limbs. Anti-NMDAR antibody was identified in cerebrospinal fluid (CSF) in the 3 cases, confirming the diagnosis of anti-NMDAR encephalitis. Pathogenic examinations revealed positive serum Epstein-Barr virus (EBV)-nuclear antigen and EBV-capsid antigen (CA)-IgG antibodies in the 3 cases, as well as positive EBV-early antigen (EA)-IgG antibody in CSF. Case 1 also had positive EBV-CA-IgA antibody; Case 3 also had positive EBV-CA-IgA and EBV-CA-IgG antibodies. Diagnoses: Anti-NMDAR antibody and EBV-EA-IgG antibody in CSF were tested positive in the 3 cases. Thus, they were diagnosed as anti-NMDAR encephalitis associated with reactivated EBV infection. Interventions: All of the 3 cases received immunoglobulin, corticosteroid, and ganciclovir treatment. Cases 2 and 3 also received antiepileptic drugs due to repeated seizures. In addition, Case 3 also received assistant respiration, plasma exchange, and rituximab. Outcomes: The 3 cases were substantially recovered after treatment. Repeat CSF analysis showed decreased titer of the anti-NMDAR antibody. Lessons: Reactivated EBV infection may trigger anti-NMDAR encephalitis in children, which has not been reported previously. Related possible virology tests should be completed while diagnosing the disease.