LAUSR

OBJECTIVE To evaluate disease symptoms, clinical and MRI findings and to perform longitudinal volumetric MRI analyses in a European multi-center cohort of pediatric anti-NMDAR encephalitis (NMDARE) patients. METHODS We studied 38 children with NMDARE (median age 12.9years, range:1-18) and a total of 82 MRI scans for volumetric MRI analyses compared to matched healthy controls. Mixed-effect models and brain volume z-scores were applied to estimate longitudinal brain volume development. Ordinal logistic regression and ordinal mixed models were used to predict disease outcome and severity. RESULTS Initial MRI scans showed abnormal findings in 15/38(39.5%) patients, mostly white matter T2/FLAIR hyperintensities. Volumetric MRI analyses revealed reductions of whole brain, grey matter as well as hippocampal and basal ganglia volumes in NMDARE children. Longitudinal mixed-effect models and z-score transformation showed failure of age-expected brain growth in patients. Importantly, patients with abnormal MRI findings at onset were more likely to have poor outcome (PCPC score>1, incidence rate ratio (IIR)[95%CI]: 3.50[1.31-9.31], p=0.012) compared to patients with normal MRI. Ordinal logistic regression models corrected for time from onset confirmed abnormal MRI at onset OR[95%CI]: 9.90[2.51, 17.28]; p=0.009), a presentation with sensorimotor deficits (13.71[2.68, 24.73]; p=0.015), and a treatment delay >4 weeks (5.15[0.47, 9.82]; p=0.031) as independent predictors of poor clinical outcome. INTERPRETATION Children with NMDARE exhibit significant brain volume loss and failure of age-expected brain growth. Abnormal MRI findings, a clinical presentation with sensorimotor deficits, and a treatment delay >4 weeks are associated with worse clinical outcome. These characteristics represent promising prognostic biomarkers in pediatric NMDARE. This article is protected by copyright. All rights reserved.