Clinical and MRI Outcome Predictors in Pediatric Anti-NMDA Receptor Encephalitis.

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.