Early Gray Matter Volume Changes in Pediatric Anti–NMDA Receptor Encephalitis: A Voxel-Based Morphometry Analysis

Introduction Pediatric anti– N -methyl- d -aspartate (anti-NMDAR) encephalitis often shows normal or nonspecific findings on conventional magnetic resonance imaging (MRI) at clinical review despite substantial neurologic and psychiatric morbidity. Although adult neuroimaging studies suggest widespread structural brain involvement, comparable pediatric data remain limited. Objective To characterize regional gray matter volume (GMV) abnormalities in pediatric anti-NMDAR encephalitis using whole-brain voxel-based morphometry (VBM) and examine associations between GMV and clinical markers of disease burden and outcome. Methods We performed a retrospective cross-sectional study of 12 pediatric patients with anti-NMDAR encephalitis and 36 age- and sex-matched healthy controls. Pretreatment structural MRI was analyzed using whole-brain VBM (SPM25 with DARTEL normalization). Voxel-wise group comparisons were adjusted for age, sex, scanner batch and total intracranial volume, with cluster-level family-wise error correction at P < .05. Mean GMV from significant clusters was correlated with symptom-onset-to-MRI interval, cerebrospinal fluid white blood cell count, and 1-year modified Rankin Scale (mRS) outcome. Results Patients showed significant regional GMV reductions vs controls, with the largest cluster in the left calcarine fissure and surrounding cortex. Additional reductions involved the left precentral gyrus, left fusiform gyrus, left middle frontal gyrus, right medial orbital/superior frontal gyrus, and right postcentral gyrus. Symptom-onset-to-MRI interval was not associated with regional GMV. Left middle frontal gyrus GMV correlated with cerebrospinal fluid white blood cell count and worse 1-year mRS, although these associations may have been influenced by outliers. Conclusions VBM identified early regional GMV abnormalities on pretreatment MRI in children with anti-NMDAR encephalitis. These findings are hypothesis-generating and require validation in larger prospective cohorts.