Triple antibody-associated autoimmune encephalitis overlap: a case report of co-existing MOG-IgG, anti-NMDAR, and anti-mGluR5 positivity

Background Autoimmune encephalitis (AE) refers to a group of inflammatory brain disorders mediated by autoantibodies against neuronal surface antigens, synaptic receptors, or glial proteins. The co-occurrence of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease in a single patient is rare. Cases with concurrent anti-mGluR5 antibodies are even rarer, with only one previously reported globally in 2022. Case presentation A 20-year-old Chinese man presented with fever, headache, progressive cognitive impairment, and psychiatric symptoms, but no seizures. Cell-based assays (CBA) showed positive anti-NMDAR IgG in both serum (1:30) and cerebrospinal fluid (CSF, 1:100), positive MOG antibodies (serum 1:100, CSF 1:100), and low-titer anti-mGluR5 IgG positivity (serum and CSF both 1:10). He received intensive multimodal immunotherapy, including high-dose methylprednisolone, intravenous immunoglobulin, plasma exchange, and rituximab. The patient achieved complete clinical recovery within three months. At the four-month follow-up, mGluR5 antibodies had become negative, while MOG and NMDAR antibody titers were markedly reduced (both from 1:100 to 1:10). Tumor screening was negative. Conclusions This is the first report of a seizure-free, triple-positive autoimmune encephalitis subtype presenting with prominent cognitive impairment, thereby expanding the clinical spectrum of recently described overlapping autoimmune encephalitis syndromes. The low titer and rapid seroreversion of mGluR5 antibodies suggest a possible bystander phenomenon secondary to blood-brain barrier disruption.