The Spectrum of Influenza-Associated Acute Necrotizing Encephalopathy of Childhood: A Case Series

BACKGROUND: Acute necrotizing encephalopathy of childhood (ANEC) is a rare inflammatory neurological disease with characteristic neuroimaging findings commonly leading to disability or death. It is associated with a variety of infectious agents, most commonly influenza. METHODS: This study is a retrospective case series describing three children presenting with ANEC during the 2023-2024 influenza season. RESULTS: All patients were influenza A positive with a variable duration of prodromal infectious symptoms. Each presented with witnessed or suspected seizures and persistent encephalopathy. Initial computed tomography (CT) was unremarkable in two patients; however, on follow-up neuroimaging all evolved multifocal brain lesions, including symmetric bilateral thalamic involvement consistent with ANEC. All patients received intravenous pulse methylprednisolone, but the timing and selection of additional immunomodulatory interventions differed between patients. Outcomes spanned from slight disability to death. CONCLUSIONS: These patients illustrate the spectrum of ANEC presentations and outcomes and underscore the importance of prompt investigations in children with persistent encephalopathy and prodromal infectious symptoms, even with unremarkable findings on initial CT. The variability in treatment and outcomes within a single center emphasizes the need for further research to establish a better pathophysiologic understanding of ANEC and optimal treatment protocols.