Cytokine/chemokine elevation during the transition phase from HSV encephalitis to autoimmune anti-NMDA receptor encephalitis

Abstract

A 3-year-old girl suffered from anti-N-methyl-d-aspartate (anti-NMDA) receptor encephalitis after resolution of herpes simplex virus encephalitis (HSE). Methylprednisolone pulse and immunoglobulin therapies showed little effect, but the patient completely recovered after six courses of monthly cyclophosphamide pulse therapy and successive maintenance on mycophenolate mofetil for one year. Anti-NMDA receptor antibody in the cerebrospinal fluid (CSF) was minimally detected during the prodromal febrile period and then was seen to be markedly elevated at the onset of second encephalopathy phase. CSF interleukin (IL)-6, and 10, tumor necrosis factor-α, interferon gamma, C-X-C motif ligands (CXCL)10 and 13, chemokine ligand 2, and migration inhibitory factor showed a second peak during the prodromal period and were reduced at the onset of anti-NMDA receptor encephalitis. These suggest the presence of cytokine/chemokine phase between the initial HSE and the secondary autoimmune encephalitis phases. Treatment strategy during the early stage of this entity should be further explored.

Keywords: Anti-NMDA receptor antibody; CXCL13; Cyclophosphamide; Herpes simplex virus; Monocyte/microglia.