Phenotypic Diversity and Outcomes in Pediatric NMDA Receptor Encephalitis: A 15-Year Retrospective Study from the Largest Children's Hospital in the United States.

Abstract

Anti-NMDAR encephalitis (NMDARE) is an autoantibody-mediated disorder characterized by seizures, movement disorders, neurocognitive deficits, and psychosis, but the complete phenotypic heterogeneity, and outcomes are incompletely understood in children. This single-center retrospective analysis of NMDARE at the largest pediatric hospital in the United States between 2009 and 2024 screened 115 patients diagnosed with NMDARE. 103 had sufficient clinical data available for analyses. Two-thirds were Hispanic, disproportionate to the Houston metro area demographics, and Hispanic patients had a higher CSF white cell count and antibody titer. Approximately one-half of the patients with idiopathic NMDARE presented with a focal cortical phenotype that localized to the perisylvian region as initial symptomology, which we describe as a "perisylvian phenotype." Patients with teratomas had more severe early symptoms, earlier lumbar punctures, higher CSF white cell counts, earlier treatment, and longer hospital durations than HSVE and idiopathic patients. CSF antibody titers directly correlated to hospital length of stay and mRS at presentation through 12-month follow up, and normal routine CSF studies and brain MRI delayed initiation of first-line immunotherapy. These novel and corroborating observations serve as the foundation for future studies on early focal neurological deficits (i.e., perisylvian phenotype) that must be addressed by clinicians to prevent delay in care.