Outcomes in influenza and RANBP2 mutation-associated acute necrotizing encephalopathy of childhood

Aim To evaluate clinical and imaging features in patients with acute necrotizing encephalopathy of childhood (ANEC) to identify predictors of RANBP2 mutations, influenza association, and long-term outcomes. Method A retrospective chart review in patients with ANEC (2012-2020) seen at a tertiary pediatric center was performed. Children were included if they had acute inflammatory lesions in the basal ganglia and pons. Variables included presenting features, imaging characteristics, RANBP2 gene testing, nasopharyngeal swab findings, therapies, and long-term outcomes. Results Twenty patients were included (average age at presentation 3y 6mo, interquartile range 3y 7mo, SD 2y 8mo; 14 females, six males). Three of the 20 experienced recurrences; one of the 20 died. Ten patients were influenza positive. Seven patients were RANBP2 mutation positive. A higher likelihood of hemorrhage was observed in patients who were influenza positive compared to influenza negative (p=0.048). Patients with influenza had a higher degree of thalamic hemorrhage (2, p=0.035) and greater extent of diffusion restriction (3, p=0.035) in semiquantitive analysis. Interpretation Children with ANEC who are positive for influenza are more likely to have hemorrhage and greater thalamic swelling. RANBP2 status was predictive of relapse but not predictive of overall outcome.