Exploring the coexistence of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and demyelinating disorders in a pediatric case

Abstract

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an immune-mediated disorder characterized by a complex neuropsychiatric syndrome and the presence of cerebrospinal fluid antibodies targeting the GluN1 subunit of the NMDAR. While well-documented, its association with demyelinating disorders—such as neuromyelitis optica, myelitis, and acute disseminated encephalomyelitis—remains rare, particularly in pediatric cases. Here, we present an unusual case of a 7-year-old female who initially exhibited area postrema syndrome, followed by acute brainstem syndrome and encephalopathy. Within 2 years, she experienced two relapses marked by longitudinally extensive transverse myelitis, seizures, and diencephalic syndrome. Neuroimaging revealed mild contrast-enhancing lesions in both infratentorial and supratentorial regions. Despite repeated testing, both antibodies to myelin-oligodendrocyte glycoprotein and aquaporin-4 remained negative. Subsequently, a comprehensive antibody testing protocol, including indirect immunohistochemistry on rat brain tissue and an extensive panel of both fixed and live cell-based assays was requested, confirming the presence of anti-NMDAR antibodies, along with superimposed reactivity to cerebellar granular cells. This report explores the diagnostic and therapeutic complexities of coexisting anti-NMDAR encephalitis and demyelinating disorders. The rarity of this overlap and its distinct clinical features underscore the need for further research into the immunological mechanisms underlying these conditions.