Japanese encephalitis-induced anti-N-methyl-d-aspartate receptor encephalitis: A hospital-based prospective study

Objectives: A hospital-based prospective study was performed to determine: 1) whether Japanese encephalitis (JE) normally triggers anti-N-methyl-d-aspartate receptor (NMDAR) immunoglobulin G (IgG) synthesis, especially in monophasic JE patients; and 2) the incidence of JE-induced anti-NMDAR encephalitis in pediatric patients with JE.

Methods: We detected the level of anti-NMDAR IgG in the serum and cerebral spinal fluid (CSF) of JE patients within one week of onset. If patients relapsed during the convalescence phase, we detected JE virus RNA in the CSF and anti-NMDAR IgG in both the serum and CSF. For patients who did not relapse during the convalescence phase, serum was collected and anti-NMDAR IgG was detected during the 30-60-day course of the disease.

Results: We enrolled 65 JE patients, who were negative for anti-NMDAR IgG in the serum and CSF during the acute phase, of which 63 patients were successfully followed up. Five patients relapsed during the convalescence phase, for whom JE virus RNA in the CSF was negative and excluded latent JE reactivation. The distinctive symptoms of four younger patients were choreoathetosis, whereas the psychiatric and behavioral manifestations were the distinctive symptoms experienced by the teenager. Anti-NMDAR IgG in the CSF of three patients was positive and they were diagnosed with anti-NMDAR encephalitis. The other two patients were negative for anti-NMDAR IgG in both the serum and CSF. For the 58 patients who did not relapse during the convalescence phase, anti-NMDAR IgG was negative in the serum of all patients at 30-60 days during the course of the disease.

Conclusions: JE does not typically trigger anti-NMDAR IgG synthesis. Besides anti-NMDAR IgG, other unknown autoantibodies can also cause autoimmune encephalitis in the convalescence phase of JE. The incidence of JE-induced autoimmune encephalitis in pediatric patients with JE was 7.9%, and the incidence of JE-induced anti-NMDAR encephalitis was 4.7%.