Fixel-Based Analysis of Pretreatment MRI Identifies White Matter Abnormalities in Pediatric Anti-NMDAR Encephalitis

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune disorder in which conventional MRI often appears normal, leading to clinical–radiologic dissociation and hindering early diagnosis and monitoring. We retrospectively studied five pediatric patients with anti-NMDAR encephalitis and compared their pretreatment diffusion MRI to age- and sex-matched controls. Using fixel-based analysis (FBA), we quantified tract-specific white matter abnormalities at the individual level. All patients showed significantly reduced fiber density and cross-section, with patterns ranging from focal to widespread involvement. In two patients, FBA abnormalities corresponded to seizure lateralization on EEG despite normal MRI, emphasizing FBA's added value in detecting seizure-concordant injury. One patient, exhibiting the highest disease burden and marked CSF pleocytosis, demonstrated extensive white matter tract disruption. These findings indicate that FBA derived from pretreatment MRI can identify clinically significant white matter injury at disease onset in pediatric anti-NMDAR encephalitis. Future large-scale studies should explore its potential as an individualized biomarker, which may offer diagnostic and prognostic value beyond conventional imaging.